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Current treatment strategies to stratify exacerbation risk rely on history of ≥2 events in the previous year.,To understand year-to-year variability and factors associated with consistent exacerbations over time, we present a prospective analysis of the SPIROMICS cohort.,We analyzed SPIROMICS participants with COPD and three years of prospective data (n=1,105).,We classified participants according to yearly exacerbation frequency.,Stepwise logistic regression compared factors associated with individuals experiencing ≥1 AECOPD in every year for three years versus none.,During three years follow-up, 48·7% of participants experienced at least one AECOPD, while the majority (51·3%) experienced none.,Only 2·1% had ≥2 AECOPD in each year.,An inconsistent pattern (both years with and years without AECOPD) was common (41·3% of the group), particularly among GOLD stages 3 and 4 subjects (56·1%).,In logistic regression, consistent AECOPD (≥1 event per year for three years) as compared to no AECOPD were associated with higher baseline symptom burden assessed with the COPD Assessment Test, previous exacerbations, greater evidence of small airway abnormality by computed tomography, lower Interleukin-15 (IL-15) and elevated Interleukin-8 (IL-8).,Although AECOPD are common, the exacerbation status of most individuals varies markedly from year to year.,Among participants who experienced any AECOPD over three years, very few repeatedly experienced ≥2 events/year.,In addition to symptoms and history of exacerbations in the prior year, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, IL-15 and IL-8.

COPD is a multifactorial disease caused by environmental determinants as well as genetic risk factors.,The prevalence and mortality of COPD continue to increase, and underdiagnosis of COPD remains a critical issue.,Previous reports investigated promising microRNAs (miRNAs) to reveal the molecular mechanism for the development of COPD; however, diagnostic and therapeutic markers for COPD have not yet been found.,For this study, 20 representative COPD patients were separated into four groups based on increasing severity (A, B, C, and D) and compared to six healthy controls.,Small RNA profiles of peripheral leukocytes were differentially expressed miRNAs (analyzed via next-generation sequencing) were validated via quantitative reverse transcriptase-polymerase chain reaction.,Compared to healthy controls, 19 differentially expressed miRNAs were found in COPD patients.,For all COPD groups, miR-3177-3p was downregulated, while 17 miRNAs were upregulated.,Furthermore, the results revealed 21 differentially expressed miRNAs, of which miR-183-5p was continually downregulated from A to B to D.,Between respective bronchodilator reversibility positive and negative groups of COPD different groups (A, B, C, and D), 10 miRNAs were differentially expressed, while miR-100-5p was upregulated in the negative groups.,In conclusion, miR-106b-5p, miR-125a-5p, miR-183-5p, and miR-100-5p are central for the development of COPD.,The severity of COPD was attenuated by miR-106b-5p, thus suggesting this miRNA as potential target for disease treatment.

Early morning respiratory symptoms impact quality of life and are often the most troublesome for patients with COPD.,Reduction in symptoms and their impact are important treatment outcomes for COPD.,The Early Morning Symptoms of COPD Instrument (EMSCI) is a daily diary designed to collect patients’ report of the occurrence, severity, and impact of morning COPD symptoms.,To assess the psychometric properties of the EMSCI, a split-half sample of data from a COPD clinical trial where participants completed the EMSCI daily was used for conducting descriptive statistics, factor analyses, and Rasch model analyses to examine item performance and inform scoring.,Once the final scoring algorithm was determined, data from the second split-half sample were used to examine the properties of the EMSCI.,Test-retest reliability was assessed using intraclass correlation coefficient (ICC).,Correlations with other study assessments were used to evaluate convergent and known-groups validity.,Data from 1,663 patients with COPD aged 40-93 years were analyzed.,Factor analysis and Rasch analysis confirmed a one-factor structure for the 6 individual symptom items.,Item analyses supported the generation of 4 scores.,All scores demonstrated good test-retest reliability: 6-item symptom severity (ICC, 0.84); overall morning symptom severity (ICC, 0.84); activity limitation (ICC, 0.85); and rescue medication (ICC, 0.62).,Significant correlations between EMSCI scores, St George’s Respiratory Questionnaire scores, and EXAcerbations of Chronic pulmonary disease Tool (EXACT)-Respiratory Symptoms scores supported the tool’s convergent validity.,Significant differences (p<0.0001) in all EMSCI domain scores were found between known-groups based on median split St George’s Respiratory Questionnaire and EXACT-Respiratory Symptoms scores.,The EMSCI consists of 4 scores: 6-item symptom severity, overall symptom severity, activity limitation, and rescue medication.,The EMSCI is a reliable and valid instrument for evaluating patients’ experience of early morning COPD symptoms.

Nighttime symptoms can negatively impact the quality of life of patients with chronic obstructive pulmonary disease (COPD).,The Nighttime Symptoms of COPD Instrument (NiSCI) was designed to measure the occurrence and severity of nighttime symptoms in patients with COPD, the impact of symptoms on nighttime awakenings, and rescue medication use.,The objective of this study was to explore item reduction, inform scoring recommendations, and evaluate the psychometric properties of the NiSCI.,COPD patients participating in a Phase III clinical trial completed the NiSCI daily.,Item analyses were conducted using weekly mean and single day scores.,Descriptive statistics (including percentage of respondents at floor/ceiling and inter-item correlations), factor analyses, and Rasch model analyses were conducted to examine item performance and scoring.,Test-retest reliability was assessed for the final instrument using the intraclass correlation coefficient (ICC).,Correlations with assessments conducted during study visits were used to evaluate convergent and known-groups validity.,Data from 1,663 COPD patients aged 40-93 years were analyzed.,Item analyses supported the generation of four scores.,A one-factor structure was confirmed with factor analysis and Rasch analysis for the symptom severity score.,Test-retest reliability was confirmed for the six-item symptom severity (ICC, 0.85), number of nighttime awakenings (ICC, 0.82), and rescue medication (ICC, 0.68) scores.,Convergent validity was supported by significant correlations between the NiSCI, St George’s Respiratory Questionnaire, and Exacerbations of Chronic Obstructive Pulmonary Disease Tool-Respiratory Symptoms scores.,The results suggest that the NiSCI can be used to determine the severity of nighttime COPD symptoms, the number of nighttime awakenings due to COPD symptoms, and the nighttime use of rescue medication.,The NiSCI is a reliable and valid instrument to evaluate these concepts in COPD patients in clinical trials and clinical practice.,Scoring recommendations and steps for further research are discussed.

To quantify the relationship between severity of chronic obstructive pulmonary disease (COPD) as expressed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and the annual exacerbation frequency in patients with COPD.,We performed a systematic literature review to identify randomized controlled trials and cohort studies reporting the exacerbation frequency in COPD patients receiving usual care or placebo.,Annual frequencies were determined for total exacerbations defined by an increased use of health care (event-based), total exacerbations defined by an increase of symptoms, and severe exacerbations defined by a hospitalization.,The association between the mean forced expiratory volume in one second (FEV1)% predicted of study populations and the exacerbation frequencies was estimated using weighted log linear regression with random effects.,The regression equations were applied to the mean FEV1% predicted for each GOLD stage to estimate the frequency per stage.,Thirty-seven relevant studies were found, with 43 reports of total exacerbation frequency (event-based, n = 19; symptom-based, n = 24) and 14 reports of frequency of severe exacerbations.,Annual event-based exacerbation frequencies per GOLD stage were estimated at 0.82 (95% confidence interval 0.46-1.49) for mild, 1.17 (0.93-1.50) for moderate, 1.61 (1.51-1.74) for severe, and 2.10 (1.51-2.94) for very severe COPD.,Annual symptom-based frequencies were 1.15 (95% confidence interval 0.67-2.07), 1.44 (1.14-1.87), 1.76 (1.70-1.88), and 2.09 (1.57-2.82), respectively.,For severe exacerbations, annual frequencies were 0.11 (95% confidence interval 0.02-0.56), 0.16 (0.07-0.33), 0.22 (0.20-0.23), and 0.28 (0.14-0.63), respectively.,Study duration or type of study (cohort versus trial) did not significantly affect the outcomes.,This study provides an estimate of the exacerbation frequency per GOLD stage, which can be used for health economic and modeling purposes.

COPD exacerbations are responsible for the morbidity and mortality of this disease.,The relationship between exacerbations and patient-related clinical outcomes is not clearly understood.,A retrospective analysis of two 1-year, placebo-controlled clinical trials with tiotropium 18 μg daily was conducted to examine relationships between exacerbations and other clinical outcomes.,The relationship between FEV1, St.,George’s Respiratory Questionnaire (SGRQ), and the transition dyspnea index (TDI) were examined based on the frequency of exacerbations (0, 1, 2, >2).,921 patients participated in the trials (mean age 65 years, mean FEV1 = 1.02 L (39% predicted).,The percent change from baseline in FEV1 in the tiotropium group was +12.6%, +12.0%, +2.1% and +8.9%; and in the placebo group was −3.4%, −3.4%, −5.7% and −6.7% for exacerbation frequencies of 0, 1, 2, >2, respectively.,Compared with baseline, the largest improvement in SGRQ occurred in patients with no exacerbations.,In the placebo group, there was a significant association between an increased frequency of exacerbations and worsening SGRQ scores.,A reduction in exacerbation rates of 4.4% to 42.0% such as that shown in this study cohort was associated with meaningful changes in questionnaire based instruments.,In the placebo-treated patients increased frequency of exacerbations was associated with larger decrements in FEV1, TDI, and SGRQ.,A reduction in the frequency of exacerbations is associated with changes that are considered meaningful in these clinical outcomes.

Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.,For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler.,Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).,295 and 291 patients were treated in MORACTO 1 and 2, respectively.,Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001).,Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).,Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies.,Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.,T/O reduces lung hyperinflation in COPD versus T, O or placebo and increases exercise endurance versus placebohttp://ow.ly/ml3G307XW6a

Exercise tolerance can be assessed by the cycle endurance test (CET) and six-minute walk test (6MWT) in patients with Chronic Obstructive Pulmonary Disease (COPD).,We sought to investigate the characteristics of functional exercise performance and determinants of the CET and 6MWT in a large clinical cohort of COPD patients.,A dataset of 2053 COPD patients (43% female, age: 66.9 ± 9.5 years, FEV1% predicted: 48.2 ± 23.2) was analyzed retrospectively.,Patients underwent, amongst others, respiratory function evaluation; medical tests and questionnaires, one maximal incremental cycle test where peak work rate was determined and two functional exercise tests: a CET at 75% of peak work rate and 6MWT.,A stepwise multiple linear regression was used to assess determinants.,On average, patients had impaired exercise tolerance (peak work rate: 56 ± 27% predicted, 6MWT: 69 ± 17% predicted).,A total of 2002 patients had CET time of duration (CET-Tend) less than 20 min while only 51 (2.5%) of the patients achieved 20 min of CET-Tend .,In former patients, the percent of predicted peak work rate achieved differed significantly between men (48 ± 21% predicted) and women (67 ± 31% predicted).,In contrast, CET-Tend was longer in men (286 ± 174 s vs 250 ± 153 s, p < 0.001).,Also, six minute walking distance (6MWD) was higher in men compared to women, both in absolute terms as in percent of predicted (443 m, 67%predicted vs 431 m, 72%predicted, p < 0.05).,Gender was associated with the CET-Tend but BMI, FEV1 and FRC were related to the 6MWD highlighting the different determinants of exercise performance between CET and 6MWT.,CET-Tend is a valuable outcome of CET as it is related to multiple clinical aspects of disease severity in COPD.,Gender difference should temper the interpretation of CET.

Bronchodilators are central in the symptomatic management of chronic obstructive pulmonary disease (COPD).,Long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) are the main classes of long-acting bronchodilators.,To date, tiotropium is the only once-daily LAMA available for the treatment of COPD.,Glycopyrronium is a novel LAMA, currently in development for COPD.,Phase II studies have shown that glycopyrronium 50 μg once daily provides clinically significant 24-hour bronchodilation with a rapid onset of action, which is faster than that of tiotropium, and a favorable safety and tolerability profile.,The Phase III GLycopyrronium bromide in COPD airWays (GLOW) program has now confirmed the long-term efficacy and tolerability of glycopyrronium 50 μg once daily.,The three studies included in this program have further shown that the effect of glycopyrronium versus placebo is similar to that of tiotropium in reducing dyspnea and the risk of exacerbations, as well as improving lung function, exercise tolerance, and health status in patients with COPD.,The safety profile of glycopyrronium is also similar to that of tiotropium in terms of overall incidence of adverse events and muscarinic side effects.,Glycopyrronium could be an alternative choice to tiotropium, and like tiotropium, has the potential to be used as a monotherapy or combination therapy.,Phase II studies have shown that a fixed-dose combination of glycopyrronium and the 24-hour LABA indacaterol, produces rapid and sustained bronchodilation compared with indacaterol monotherapy in patients with COPD.,Phase III studies are currently ongoing to assess the long-term efficacy and safety of this combination.

NVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease (COPD).,The glycopyrronium bromide in COPD airways clinical study 1 (GLOW1) evaluated the efficacy, safety and tolerability of NVA237 in patients with moderate-to-severe COPD.,Patients with COPD with a smoking history of ≥ 10 pack-years, post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% predicted normal and FEV1/forced vital capacity < 0.70 were enrolled.,Patients were randomized to double-blind treatment with NVA237 50 μg once daily or placebo for 26 weeks with inhaled/intranasal corticosteroids or H1 antagonists permitted in patients stabilized on them prior to study entry.,The primary outcome measure was trough FEV1 at Week 12.,A total of 822 patients were randomized to NVA237 (n = 552) or placebo (n = 270).,Least squares mean (± standard error) trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 (1.408 ± 0.0105 L), versus placebo (1.301 ± 0.0137 L; treatment difference 108 ± 14.8 mL, p < 0.001).,Significant improvements in trough FEV1 were apparent at the end of Day 1 and sustained through Week 26.,FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26, and at all other visits and timepoints.,Transition dyspnoea index focal scores and St.,George's Respiratory Questionnaire scores were significantly improved with NVA237 versus placebo at Week 26, with treatment differences of 1.04 (p < 0.001) and-2.81 (p = 0.004), respectively.,NVA237 significantly reduced the risk of first moderate/severe COPD exacerbation by 31% (p = 0.023) and use of rescue medication by 0.46 puffs per day (p = 0.005), versus placebo.,NVA237 was well tolerated and had an acceptable safety profile, with a low frequency of cardiac and typical antimuscarinic adverse effects.,Once-daily NVA237 was safe and well tolerated and provided rapid, sustained improvements in lung function, improvements in dyspnoea, and health-related quality of life, and reduced the risk of exacerbations and the use of rescue medication.,ClinicalTrials.gov: NCT01005901

Patient-reported outcome (PRO) measures that quantify disease impact have become important measures of outcome in COPD research and treatment.,The objective of this literature review was to comprehensively evaluate psychometric properties of available PRO instruments and the ability of each of them to characterize pharmaceutical treatment effects from published clinical trial evidence.,Identified in this study were several PRO measures, both those that have been used extensively in COPD clinical trials (St George’s Respiratory Questionnaire and Chronic Respiratory Questionnaire) and new instruments whose full value is still to be determined.,This suggests a great need for more information about the patient experience of treatment benefit, but this also may pose challenges to researchers, clinicians, and other important stakeholders (eg, regulatory agencies, pharmaceutical companies) who develop new treatment entities and payers (including but not limited to health technology assessment agencies such as the National Institute for Health and Care Excellence and the Canadian Agency for Drugs and Technologies in Health).,The purpose of this review is to enable researchers and clinicians to gain a broad overview of PRO measures in COPD by summarizing the value and purpose of these measures and by providing sufficient detail for interested audiences to determine which instrument may be the most suitable for evaluating a particular research purpose.

High frequency chest wall oscillation (HFCWO) is used for airway mucus clearance.,The objective of this study was to evaluate the use of HFCWO early in the treatment of adults hospitalized for acute asthma or chronic obstructive pulmonary disease (COPD).,Randomized, multi-center, double-masked phase II clinical trial of active or sham treatment initiated within 24 hours of hospital admission for acute asthma or COPD at four academic medical centers.,Patients received active or sham treatment for 15 minutes three times a day for four treatments.,Medical management was standardized across groups.,The primary outcomes were patient adherence to therapy after four treatments (minutes used/60 minutes prescribed) and satisfaction.,Secondary outcomes included change in Borg dyspnea score (≥ 1 unit indicates a clinically significant change), spontaneously expectorated sputum volume, and forced expired volume in 1 second.,Fifty-two participants were randomized to active (n = 25) or sham (n = 27) treatment.,Patient adherence was similarly high in both groups (91% vs. 93%; p = 0.70).,Patient satisfaction was also similarly high in both groups.,After four treatments, a higher proportion of patients in the active treatment group had a clinically significant improvement in dyspnea (70.8% vs.,42.3%, p = 0.04).,There were no significant differences in other secondary outcomes.,HFCWO is well tolerated in adults hospitalized for acute asthma or COPD and significantly improves dyspnea.,The high levels of patient satisfaction in both treatment groups justify the need for sham controls when evaluating the use of HFCWO on patient-reported outcomes.,Additional studies are needed to more fully evaluate the role of HFCWO in improving in-hospital and post-discharge outcomes in this population.,ClinicalTrials.gov: NCT00181285

Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.,For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler.,Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).,295 and 291 patients were treated in MORACTO 1 and 2, respectively.,Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001).,Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).,Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies.,Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.,T/O reduces lung hyperinflation in COPD versus T, O or placebo and increases exercise endurance versus placebohttp://ow.ly/ml3G307XW6a

Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY

Patients with chronic obstructive pulmonary disease (COPD) fall frequently, although the risk of falls may seem less important than the respiratory consequences of the disease.,Nevertheless, falls are associated to increased mortality, decreased independence and physical activity levels, and worsening of quality of life.,The aims of this systematic review was to evaluate information in the literature with regard to whether impaired postural control is more prevalent in COPD patients than in healthy age-matched subjects, and to assess the main characteristics these patients present that contribute to impaired postural control.,Five databases were searched with no dates or language limits.,The MEDLINE, PubMed, EMBASE, Web of Science, and PEDro databases were searched using “balance”, “postural control”, and “COPD” as keywords.,The search strategies were oriented and guided by a health science librarian and were performed on March 27, 2014.,The studies included were those that evaluated postural control in COPD patients as their main outcome and scored more than five points on the PEDro scale.,Studies supplied by the database search strategy were assessed independently by two blinded researchers.,A total of 484 manuscripts were found using the “balance in COPD or postural control in COPD” keywords.,Forty-three manuscripts appeared more than once, and 397 did not evaluate postural control in COPD patients as the primary outcome.,Thus, only 14 studies had postural control as their primary outcome.,Our study examiners found only seven studies that had a PEDro score higher than five points.,The examiners’ interrater agreement was 76.4%.,Six of those studies were accomplished with a control group and one study used their patients as their own controls.,The studies were published between 2004 and 2013.,Patients with COPD present postural control impairment when compared with age-matched healthy controls.,Associated factors contributing to impaired postural control were muscle weakness, physical inactivity, elderly age, need for supplemental oxygen, and limited mobility.

To evaluate an entirely outpatient-based program of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease COPD, using St.George’s Respiratory questionnaire (SGRQ), the 6-minutes walking test (6-MWT) and BODE index as the primary outcome measures.,A prospective, parallel-group controlled study of an outpatient rehabilitation program in 80 patients with COPD (67 men and 13 women; mean age 64.8 ± 10.6 years; FEV1, 42.8% ± 7.6% of the predicted value.,The active group (n = 40) took part in a 14-week rehabilitation program [3 h/wk, 1.5 h of education and exercise and 1.5 h of cycling].,The control group (n = 40) was reviewed routinely as medical outpatients.,The following evaluations were carried out at study entry and after14 weeks: (1) pulmonary function studies; (2) 6-minutes walking test 6MWT; (3) quality of life; and (4) BODE index.,The following patients completed the study: 35 patients (87.5%) from the active group (mean age, 63.7 ± 11.9 years; mean forced expiratory volume in one second (FEV1), 41.9 ± 2.6% of the predicted value); and 36 patients (88%) from the control group (mean age, 65.9 ± 10.3 years; mean FEV1, 43.33 ± 3.6% of the predicted value).,We found no changes in pulmonary function parameters in the active group and the control one at 14weeks.,On the other hand, there were significant changes within the components of the SGRQ (12.3 for the score total) for the patients of the active group but not for the patients of the control one (only 1.5 for the score total), we observed also a significant increase in the distance of the 6-MWT in the patients of the active group but not for the patients of the control one, and finally a decrease of two points (from 6 to 4) was noted in the score of the active group’s BODE index without any change in the control group’s one.,An outpatient-based of 14-week rehabilitation program significantly improved the quality of life and exercise tolerance without any change in the pulmonary function in patients with moderate COPD, and there was also a large decrease in the risk of death in rehabilitated patients as measured using the BODE index.

‘Clinically important deterioration’ (CID) is a composite endpoint measuring worsening of the key clinical features of chronic obstructive pulmonary disease (COPD), namely lung function, patient-reported outcomes, and exacerbations.,ACLIFORM and AUGMENT were two 24-week, randomized, double-blind, phase III studies assessing twice-daily (BID) aclidinium bromide (AB) 400 μg/formoterol fumarate (FF) 12 μg.,This pooled post-hoc analysis assessed the effects of AB/FF 400/12 μg on both first and sustained CID events versus placebo and monotherapies in patients with moderate to severe COPD.,A first CID event was defined as the occurrence of a moderate/severe exacerbation or the worsening from baseline in ≥1 of the following: trough forced expiratory volume in 1 second (FEV1; ≥100 mL), Transition Dyspnea Index (TDI) focal score (≥1 unit), or St George’s Respiratory Questionnaire (SGRQ) total score (≥4 units).,A ‘sustained’ CID was defined as a worsening maintained at all subsequent visits from appearance to week 24 or a moderate/severe exacerbation at any time.,CID events were assessed at three visits (weeks 4, 12, and 24); trough FEV1 was also measured at weeks 1 and 18.,AB/FF 400/12 μg reduced the risk of a first CID event by 45% versus placebo (hazard ratio [HR] 0.55, p < 0.001), 18% versus FF 12 μg (HR 0.82, p < 0.01), and 15% versus AB 400 μg (HR 0.85, p < 0.05).,Similarly, AB/FF 400/12 μg reduced the risk of a sustained CID event by 48% versus placebo (HR 0.52, p < 0.001) and 22% versus FF 12 μg (HR 0.78, p < 0.01).,AB/FF 400/12 μg reduced the risk of a first or sustained CID event for all four components versus placebo (trough FEV1 and TDI, first and sustained CID, all p < 0.001; SGRQ first CID p < 0.001; SGRQ sustained CID, p < 0.01; exacerbations first and sustained CID, both p < 0.05) and TDI and SGRQ versus FF 12 μg (TDI, first and sustained CID both p < 0.05; SGRQ first CID p < 0.01), and SGRQ versus AB 400 μg (first CID, p < 0.05).,AB/FF 400/12 μg BID may provide greater airway stability and fewer exacerbations or deteriorations in lung function, health status, or dyspnea compared with placebo or monotherapies.,Clinicaltrials.gov NCT01462942 (ACLIFORM); registered 26 October 2011.,Clinicaltrials.gov NCT01437397 (AUGMENT); registered 19 September 2011.,The online version of this article (doi:10.1186/s12931-017-0583-0) contains supplementary material, which is available to authorized users.

Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively.,We examined whether changes in trough forced expiratory volume in 1 second (FEV1) are correlated with changes in patient-reported outcomes.,Pooled data from three indacaterol studies (n = 3313) were analysed.,Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St.,George's Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV1.,Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use.,With increasing positive ΔFEV1, TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001).,Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95.,At 26 weeks, a 100 ml increase in FEV1 was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease).,Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV1 and outcomes.,These results suggest that larger improvements in FEV1 are likely to be associated with larger patient-reported benefits across a range of clinical outcomes.,ClinicalTrials.gov NCT00393458, NCT00463567, and NCT00624286

In light of the growing burden of COPD, there is increasing focus on the role of self-management for this population.,Currently, self-management varies widely.,Little is known either about nurses’ and allied health professionals’ (AHPs’) understanding and provision of self-management in clinical practice.,This study explores nurses’ and AHPs’ understanding and implementation of supported COPD self-management within routine clinical practice.,Nurses and AHPs participated in face-to-face semistructured interviews to explore their understanding and provision of COPD self-management, as well as their perceptions of the challenges to providing such care.,Purposive sampling was used to select participants from a range of professions working within primary, community, and secondary care settings.,Three researchers independently analyzed each transcript using a thematic approach.,A total of 14 participants were interviewed.,Nurses and AHPs viewed self-management as an important aspect of COPD care, but often misunderstood what it involved, leading to variation in practice.,A number of challenges to supporting self-management were identified, which related to lack of time, lack of insight regarding training needs, and assumptions regarding patients’ perceived self-management abilities.,Nurses and AHPs delivering self-management require clear guidance, training in the use of effective self-management skills, and education that challenges their preconceptions regarding patients.,The design of health care services also needs to consider the practical barriers to COPD self-management support for the implementation of such interventions to be successful.

Chronic Obstructive Pulmonary Disease (COPD) is a chronic disease with repeated exacerbations resulting in gradual debilitation.,The quality of life has been shown to be poor in patients with COPD despite efforts to improve self-management.,However, the evidence on the benefit of self-management in COPD is conflicting.,Whether this could be due to other unmet needs of patients have not been investigated.,Therefore, we aimed to explore unmet needs of patients from both patients and doctors managing COPD.,We conducted a qualitative study with doctors and patients in Malaysia.,We used convenience sampling to recruit patients until data saturation.,Eighteen patients and eighteen doctors consented and were interviewed using a semi-structured interview guide.,The interviews were audio-recorded, transcribed verbatim and checked by the interviewers.,Data were analysed using a thematic approach.,The themes were similar for both the patients and doctors.,Three main themes emerged: knowledge and awareness of COPD, psychosocial and physical impact of COPD and the utility of self-management.,Knowledge about COPD was generally poor.,Patients were not familiar with the term chronic obstructive pulmonary disease or COPD.,The word ‘asthma’ was used synonymously with COPD by both patients and doctors.,Most patients experienced difficulties in their psychosocial and physical functions such as breathlessness, fear and helplessness.,Most patients were not confident in self-managing their illness and prefer a more passive role with doctors directing their care.,In conclusion, our study showed that knowledge of COPD is generally poor.,There was mislabelling of COPD as asthma by both patients and physicians.,This could have resulted in the lack of understanding of treatment options, outcomes, and prognosis of COPD.,The misconception that cough due to COPD was contagious, and breathlessness that resulted from COPD, had important physical and psychosocial impact, and could lead to social isolation.,Most patients and physicians did not favour self-management approaches, suggesting innovations based on self-management may be of limited benefit.

The objective of this pilot study was to investigate the use of and satisfaction with a chronic obstructive pulmonary disease (COPD) telehealth program applied in both primary and secondary care.,The program consisted of four modules: 1) activity coach for ambulant activity monitoring and real-time coaching of daily activity behavior, 2) web-based exercise program for home exercising, 3) self-management of COPD exacerbations via a triage diary on the web portal, including self-treatment of exacerbations, and 4) teleconsultation.,Twenty-nine COPD patients were randomly assigned to either the intervention group (telehealth program for 9 months) or the control group (usual care).,Page hits on the web portal showed the use of the program, and the Client Satisfaction Questionnaire showed satisfaction with received care.,The telehealth program with decision support showed good satisfaction (mean 26.4, maximum score 32).,The program was accessed on 86% of the treatment days, especially the diary.,Patient adherence with the exercise scheme was low (21%).,Health care providers seem to play an important role in patients’ adherence to telehealth in usual care.,Future research should focus on full-scale implementation in daily care and investigating technological advances, like gaming, to increase adherence.

To estimate the potential cost savings by following the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline recommendations in patients being treated for chronic obstructive pulmonary disease (COPD) with the combination of long-acting β2-agonist (LABA), long-acting muscarinic antagonist (LAMA) or inhaled corticosteroids (ICS).,The Geisinger Health System (GHS) database was utilized to identify subjects between January 1, 2004 to March 12, 2007.,The index date was based on the first prescription of a LAMA plus LABA, LAMA plus LABA/ICS, or LABA plus ICS.,Patients were included in the study if they: had a COPD diagnosis; had data representative of treatment 12 months prior to and 12 months post index date; were 40 years of age or over; had no prior diagnosis for asthma; and had pulmonary function test (PFT) data.,We examined the baseline characteristics of these patients along with their healthcare resource utilization.,Based on PFT data within 30 days of the index date, a subgroup was classified as adhering or non-adhering to GOLD guidelines.,A total of 364 subjects could be classified as adhering or non-adherent to current GOLD guidelines based on their PFT results.,The adherent subgroup received COPD medications consistent with current GOLD guidelines.,Of the LAMA plus LABA cohort, 25 patients adhered and 39 patients were non-adherent to current GOLD guidelines.,In the cohort of LABA plus ICS, 74 patients were adherent and 180 patients non-adherent to current GOLD guidelines.,In the cohort of LAMA plus LABA/ICS, 21 patients were adherent and 25 patients non-adherent to current GOLD guidelines.,GOLD adherence was associated with mean total cost of all services savings of $5,889 for LAMA plus LABA, $3,330 for LABA + ICS, and $10,217 for LAMA plus LABA/ICS cohorts.,Staging of COPD with a PFT and adherence to current GOLD guidelines was associated with lower costs in subjects with moderate to severe COPD.,Appropriate use of LAMA plus LABA, LABA plus ICS, and LAMA plus LABA/ICS has economic as well as clinical benefits for patients and payers.

Addition of a second bronchodilator from a different pharmacological class may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) whose symptoms are insufficiently controlled by bronchodilator monotherapy.,GLOW6 evaluated the efficacy and safety of once-daily coadministration of the long-acting β2-agonist indacaterol (IND) and the long-acting muscarinic antagonist glycopyrronium (GLY) versus IND alone in patients with moderate-to-severe COPD.,In this randomized, double-blind, parallel group, placebo-controlled, 12-week study, patients were randomized 1:1 to IND 150 μg and GLY 50 μg daily (IND + GLY) or IND 150 μg daily and placebo (IND + PBO) (all delivered via separate Breezhaler® devices).,The primary objective was to demonstrate the superiority of IND + GLY versus IND + PBO for trough forced expiratory volume in 1 second (FEV1) at week 12.,Other end points included trough FEV1 at day 1, FEV1 area under the curve from 30 minutes to 4 hours (AUC30min-4h), peak FEV1, inspiratory capacity and trough forced vital capacity (FVC) at day 1 and week 12, and transition dyspnea index (TDI) focal score, COPD symptoms, and rescue medication use over 12 weeks.,A total of 449 patients were randomized (IND + GLY, 226; IND + PBO, 223); 94% completed the study.,On day 1 and at week 12, IND + GLY significantly improved trough FEV1 versus IND + PBO, with treatment differences of 74 mL (95% CI 46-101 mL) and 64 mL (95% CI 28-99 mL), respectively (both P<0.001).,IND + GLY significantly improved postdose peak FEV1, FEV1 AUC30min-4h, and trough FVC at day 1 and week 12 versus IND + PBO (all P<0.01).,TDI focal score and COPD symptoms (percentage of days able to perform usual daily activities and change from baseline in mean daytime respiratory score) were significantly improved with IND + GLY versus IND + PBO (P<0.05).,The incidence of adverse events was similar for the two treatment groups.,In patients with moderate-to-severe COPD, once-daily coadministration of IND and GLY provides significant and sustained improvement in bronchodilation versus IND alone from day 1, with significant improvements in patient-centered outcomes.

NVA237 (glycopyrronium bromide) is a once-daily long-acting muscarinic antagonist (LAMA) in development for chronic obstructive pulmonary disease (COPD).,The GLycopyrronium bromide in COPD airWays clinical Study 2 (GLOW2) evaluated the efficacy and safety of NVA237 in moderate-to-severe COPD over 52 weeks.,Patients were randomised 2:1:1 to NVA237 50 μg, placebo or open-label tiotropium 18 μg for 52 weeks.,Primary end-point was trough forced expiratory volume in 1 s (FEV1) at 12 weeks.,1,066 patients were randomised, 810 completed the study.,At week 12, trough FEV1 increased significantly by 97 mL with NVA237 (95% CI 64.6-130.2; p<0.001) and 83 mL with tiotropium (95% CI 45.6-121.4; p<0.001).,Compared with placebo, NVA237 produced significant improvements in dyspnoea (Transition Dyspnoea Index at week 26; p=0.002) and health status (St George's Respiratory Questionnaire at week 52; p<0.001).,NVA237 significantly reduced the risk of moderate-to-severe COPD exacerbations by 34% (p=0.001) and the use of rescue medication (p=0.039), versus placebo.,NVA237-placebo and tiotropium-placebo differences were comparable for all outcomes.,Safety profiles were similar across groups.,NVA237 50 μg provided significant improvements in lung function, dyspnoea, health status, exacerbations and rescue medication use, versus placebo, and was comparable to tiotropium.,NVA237 can potentially be an alternative choice of LAMA for COPD patients.

Background and objective: Viruses are important aetiological agents of acute exacerbation of COPD (AECOPD).,Their reported prevalence varies from region to region.,This systematic review calculated the prevalence of respiratory viral infections in AECOPD.,Methods: A systematic search was performed using Medline, and references of relevant articles and conference proceedings were hand searched.,Articles for review were selected based on the following criteria: (i) prospective or cross‐sectional study, (ii) original research, (iii) viral detection used the highly sensitive techniques of PCR and/or Reverse Transcriptase PCR (RT‐PCR), (iv) viral prevalence in AECOPD defined, and (v) full paper available in English.,We assessed the study quality and extracted data independently and in duplicate using a pre‐defined data extraction form.,Weighted mean prevalence (WMP) was calculated and a forest plot was constructed to show the dispersion.,Results: Eight studies met the inclusion criteria.,The WMP of respiratory viral infection in AECOPD was 34.1% (95% CI: 23.9-44.4). picornavirus was the most commonly detected virus with WMP 17.3% (95% CI: 7.2-27.3), followed by influenza; 7.4% (95% CI: 2.9-12.0), respiratory syncytial virus; 5.3% (95% CI: 1.6-9.0), corona viruses; 3.1% (95% CI: 0.4-5.8), parainfluenza; 2.6% (95% CI: 0.4-4.8), adenovirus; 1.1% (95% CI: −1.1 to 3.3), and human metapneumovirus; 0.7% (95% CI: −0.3 to 1.8).,Maximum WMP was observed in studies from Europe followed by the USA, Australia and Asia.,Picorna was the most common virus detected in Western countries whereas influenza was most common in Asia.,Conclusions: This systematic review demonstrated that viruses are strongly associated with AECOPD, with the highest detection rates of viruses being in Europe.,The geographical epidemiology of viruses may have important therapeutic implications for management of AECOPD.,Viruses are an important cause of acute exacerbation of COPD (AECOPD).,This systematic review calculated the weighted mean prevalence (WMP) of respiratory viruses detected in patients with AECOPD.,The overall WMP was 34.1% (95% CI: 23.9‐44.4), and picornavirus was the most commonly detected virus with WMP 17.3% (95% CI: 7.2‐27.3).

Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality.,COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation.,They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation.,Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations.,Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations.,Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials.,The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD.

Observational studies have suggested a beneficial effect of taking statins on frequency of chronic obstructive pulmonary disease (COPD) exacerbations.,However, clinical trials of statins in people with COPD did not confirm those results.,This study aimed to investigate this association using a methodological approach, which reduces the biases associated with some previous observational study designs.,Retrospective cohort study comparing new-users of statins with non-users.,General practices in England contributing to the Clinical Practice Research Datalink in 2007-2017, with linkage to data on Hospital Episode Statistics inpatient episodes.,48 124 people with COPD, aged over 40 years, who had not been prescribed statin in the previous year.,Participants became new-users of statins at their first prescription for a statin during follow-up.,They were then assumed to remain statin users.,Statin users were compared with non-users.,Primary outcomes were COPD exacerbation, or severe exacerbation requiring hospitalisation.,Secondary outcomes were death from any cause (for comparison with other studies) and urinary tract infection (negative-control).,Maximum follow-up was 3 years.,Adjusted HR were calculated using time-dependent Cox regression.,The Andersen-Gill model was used for recurrent exacerbations.,Covariates included demographic variables, variables related to COPD severity, cardiovascular comorbidities as time-dependent variables, and other comorbidities at baseline.,7266 participants became new-users of statins over an average 2.5 years of follow-up.,In total, 30 961 people developed an exacerbation, 8110 severe exacerbation, 3650 urinary tract infection and 5355 died.,Adjusted HR (95% CI) in statin users compared with non-users were first exacerbation 1.01 (0.96-1.06), severe exacerbation 0.92 (0.84-0.99), number of exacerbations 1.00 (0.97-1.04), urinary tract infection 1.10 (0.98-1.23) and death 0.63 (0.57-0.70).,In this study of health records from a Primary Care database, statin use in people with COPD was not associated with a lower risk of COPD exacerbation.

The objective of this study is to assess whether statin use is associated with beneficial effects on COPD outcomes.,We conducted a systematic review and meta-analysis of all available studies describing the association between statin use and COPD mortality, exacerbations and cardiovascular events.,Medline, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched, with no restrictions.,The hazard ratio (HR) with 95% confidence interval (CI) was estimated.,Fifteen studies with a total of 238,459 patients were included.,Nine articles provided data on all-cause mortality (124,543 participants), and they gave a HR of 0.62 (95% CI 0.52 to 0.73).,Three studies provided data on cancer mortality (90,077 participants), HR 0.83 (0.65 to 1.08); four studies on COPD mortality (88,767 participants), HR 0.48 (0.23 to 0.99); and three studies on cardiovascular mortality (90,041 participants), HR 0.93 (0.50 to 1.72).,Six articles provided data on COPD exacerbation with or without hospitalization (129,796 participants), HR 0.64 (0.55 to 0.75).,Additionally, the use of statins was associated with a significant reduction risk of myocardial infarction, but not for stroke.,Our systematic review showed a clear benefit of statins in patients with COPD.

Blood eosinophil count has been proposed as a predictor of response to inhaled corticosteroid (ICS) in the prevention of acute exacerbations of COPD.,An optimal threshold of blood eosinophil count for prescribing ICS has not been agreed.,Doubt has been cast on the role by observational studies.,The role of inhaled corticosteroids in this relationship, independent of long-acting bronchodilators, has not been examined.,We conducted a systematic review of post-hoc analyses of randomised controlled trials (RCTs) and observational studies examining three blood eosinophil thresholds and the independent role of ICS.,Included studies were categorised by the form (relative or absolute count) and cut point of eosinophil threshold used.,Thresholds assessed were relative eosinophil count of 2%, and absolute counts of 150 cells/μL and 300 cells/μL.,Three meta-analyses of the effect of ICS use in post-hoc analyses of RCTs based on these counts were carried out.,Initial analysis included all studies of ICS vs. any non-ICS regimen.,Further analysis examined the effect of ICS, independent of the effect of long-acting bronchodilators.,Sixteen studies examined the association between blood eosinophil count and response of exacerbation risk to ICS, in COPD patients.,Eleven studies (25,881 patients) were post-hoc analyses of RCTs.,Five studies (109,704 patients) were retrospective observational studies.,The independent effect of ICS on the reduction of exacerbation risk was 20% at ≥2% blood eosinophil threshold (RR, 0.80; 95% CI, 0.74-0.85), 35% at ≥150 cells/μL blood eosinophil threshold (RR, 0.65; 0.52-0.79), and 39% at ≥300 cells/μL blood eosinophil threshold (RR, 0.61; 0.44-0.78).,No association was found in four out of five observational studies.,This is the first systematic review to assess, in post-hoc analyses of RCTs, the independent effect of ICS in reducing the risk of COPD exacerbation across a range of blood eosinophil thresholds.,Association between ICS prescription and reduced exacerbation risk at these thresholds was confirmed.,The lack of association found in the observational studies questions the relevance of these observations to a “real world” COPD population.,To clarify the clinical utility of this biomarker, the association should be tested in prospective effectiveness studies.

Eosinophils in blood and sputum in chronic obstructive pulmonary disease (COPD) have been associated with more frequent exacerbations, lower lung function, and corticosteroid responsiveness.,We hypothesized increased eosinophils are associated with a severe COPD phenotype, including exacerbation frequency, and tested whether blood eosinophils reliably predict sputum eosinophils.,Comprehensive baseline data on SPIROMICS subjects, recruited for a range of COPD severity for smokers with ≥20 pack year history, included demographics, questionnaires, clinical assessments, quantitative computed tomography (QCT), blood and induced sputum.,Significantly, stratification by mean sputum eosinophils ≥1·25% (N=827) was associated with reduced FEV1 % predicted (differences: 10% pre-bronchodilator, 4·7% post-bronchodilator), QCT density measures for emphysema and air trapping, and exacerbations treated with corticosteroids (p=0·002).,In contrast, stratification by mean blood eosinophils ≥200/µL (N=2499) showed that FEV1 % predicted was significant between low and high blood subgroups, but less than observed between sputum subgroups (blood eosinophil group differences: 4·2% pre-bronchodilator, 2·7% post-bronchodilator), slightly increased airway wall thickness (0·02 mm, p=0·032), greater symptoms (p=0·037), and wheezing (p=0·018), but no evidence of association with COPD exacerbations or other indices of severity.,Blood eosinophils showed weak although significant association with sputum eosinophils (ROC AUC=0·64, p<0·001), but with a high false discovery rate (72%).,Elevated sputum eosinophils, with or without blood eosinophils, were associated with lower lung function.,Elevated blood eosinophils only in combination with elevated sputum eosinophils were associated with COPD exacerbations.,Stratification of SPIROMICS subjects by blood eosinophils alone showed minimal clinical differences and no association with exacerbations, whereas stratification by sputum eosinophils was associated with larger phenotypic differences and COPD exacerbations.,Importantly, increased blood eosinophils did not reliably predict airway eosinophils in induced sputum.

Reports have suggested a reduction in exacerbations of chronic obstructive pulmonary disease (COPD) during the coronavirus disease 2019 (COVID-19) pandemic, particularly hospital admissions for severe exacerbations.,However, the magnitude of this reduction varies between studies.,Electronic databases were searched from January 2020 to May 2021.,Two independent reviewers screened titles and abstracts and, when necessary, full text to determine if studies met inclusion criteria.,A modified version of the Newcastle-Ottawa Scale was used to assess study quality.,A narrative summary of eligible studies was synthesised, and meta-analysis was conducted using a random effect model to pool the rate ratio and 95% confidence intervals (95% CI) for hospital admissions.,Exacerbation reduction was compared against the COVID-19 Containment and Health Index.,A total of 13 of 745 studies met the inclusion criteria and were included in this review, with data from nine countries.,Nine studies could be included in the meta-analysis.,The pooled rate ratio of hospital admissions for COPD exacerbations during the pandemic period was 0.50 (95% CI 0.44-0.57).,Findings on the rate of community-treated exacerbations were inconclusive.,Three studies reported a significant decrease in the incidence of respiratory viral infections compared with the pre-pandemic period.,There was not a significant relationship between exacerbation reduction and the COVID-19 Containment and Health Index (rho = 0.20, p = 0.53).,There was a 50% reduction in admissions for COPD exacerbations during the COVID-19 pandemic period compared to pre-pandemic times, likely associated with a reduction in respiratory viral infections that trigger exacerbations.,Future guidelines should consider including recommendations on respiratory virus infection control measures to reduce the burden of COPD exacerbations beyond the pandemic period.

ICAM-1 is a major receptor for ~60% of human rhinoviruses, and non-typeable Haemophilus influenzae, two major pathogens in COPD.,Increased cell-surface expression of ICAM-1 in response to tobacco smoke exposure has been suggested.,We have investigated epithelial ICAM-1 expression in both the large and small airways, and lung parenchyma in smoking-related chronic airflow limitation (CAL) patients.,We evaluated epithelial ICAM-1 expression in resected lung tissue: 8 smokers with normal spirometry (NLFS); 29 CAL patients (10 small-airway disease; 9 COPD-smokers; 10 COPD ex-smokers); Controls (NC): 15 normal airway/lung tissues.,Immunostaining with anti-ICAM-1 monoclonal antibody was quantified with computerized image analysis.,The percent and type of cells expressing ICAM-1 in large and small airway epithelium and parenchyma were enumerated, plus percentage of epithelial goblet and submucosal glands positive for ICAM- 1.,A major increase in ICAM-1 expression in epithelial cells was found in both large (p < 0.006) and small airways (p < 0.004) of CAL subjects compared to NC, with NLFS being intermediate.,In the CAL group, both basal and luminal areas stained heavily for ICAM-1, so did goblet cells and sub-mucosal glands, however in either NC or NLFS subjects, only epithelial cell luminal surfaces stained.,ICAM-1 expression on alveolar pneumocytes (mainly type II) was slightly increased in CAL and NLFS (p < 0.01).,Pack-years of smoking correlated with ICAM-1 expression (r = 0.49; p < 0.03).,Airway ICAM-1 expression is markedly upregulated in CAL group, which could be crucial in rhinoviral and NTHi infections.,The parenchymal ICAM-1 is affected by smoking, with no further enhancement in CAL subjects.,The online version of this article (doi:10.1186/s12931-016-0483-8) contains supplementary material, which is available to authorized users.

Chronic Obstructive Pulmonary Disease (COPD) is associated with bronchial epithelial changes, including squamous cell metaplasia and goblet cell hyperplasia.,These features are partially attributed to activation of the epidermal growth factor receptor (EGFR).,Whereas smoking cessation reduces respiratory symptoms and lung function decline in COPD, inflammation persists.,We determined epithelial proliferation and composition in bronchial biopsies from current and ex-smokers with COPD, and its relation to duration of smoking cessation.,114 COPD patients were studied cross-sectionally: 99 males/15 females, age 62 ± 8 years, median 42 pack-years, no corticosteroids, current (n = 72) or ex-smokers (n = 42, median cessation duration 3.5 years), postbronchodilator FEV1 63 ± 9% predicted.,Squamous cell metaplasia (%), goblet cell (PAS/Alcian Blue+) area (%), proliferating (Ki-67+) cell numbers (/mm basement membrane), and EGFR expression (%) were measured in intact epithelium of bronchial biopsies.,Ex-smokers with COPD had significantly less epithelial squamous cell metaplasia, proliferating cell numbers, and a trend towards reduced goblet cell area than current smokers with COPD (p = 0.025, p = 0.001, p = 0.081, respectively), but no significant difference in EGFR expression.,Epithelial features were not different between short-term quitters (<3.5 years) and current smokers.,Long-term quitters (≥3.5 years) had less goblet cell area than both current smokers and short-term quitters (medians: 7.9% vs.,14.4%, p = 0.005; 7.9% vs.,13.5%, p = 0.008; respectively), and less proliferating cell numbers than current smokers (2.8% vs.,18.6%, p < 0.001).,Ex-smokers with COPD had less bronchial epithelial remodelling than current smokers, which was only observed after long-term smoking cessation (>3.5 years).,NCT00158847

Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation which flare-up during episodes of acute exacerbation (AECOPD).,Given the role of Toll-like receptors (TLRs) in the induction of inflammatory responses we investigated the involvement of TLRs in COPD pathogenesis.,The expression of TLR-2, TLR-4 and CD14 in monocytes was analyzed by flow cytometry.,To study the functional responses of these receptors, monocytes were stimulated with peptidoglycan or lipopolysaccharide and the amounts of TNFα and IL-6 secreted were determined by ELISA.,We found that the expression of TLR-2 was up-regulated in peripheral blood monocytes from COPD patients, either clinically stable or during AECOPD, as compared to never smokers or smokers with normal lung function.,Upon stimulation with TLR-2 ligand monocytes from COPD patients secreted increased amounts of cytokines than similarly stimulated monocytes from never smokers and smokers.,In contrast, the expressions of TLR-4 and CD14 were not significantly different between groups, and the response to lipopolysaccharide (a TLR-4 ligand) stimulation was not significantly different either.,At discharge from hospital TLR-2 expression was down-regulated in peripheral blood monocytes from AECOPD patients.,This could be due to the treatment with systemic steroids because, in vitro, steroids down-regulated TLR-2 expression in a dose-dependent manner.,Finally, we demonstrated that IL-6, whose plasma levels are elevated in patients, up-regulated in vitro TLR-2 expression in monocytes from never smokers.,Our results reveal abnormalities in TLRs expression in COPD patients and highlight its potential relationship with systemic inflammation in these patients.

The Phase IV, 8-week, randomized, double-blind, placebo-controlled ACTIVATE study (NCT02424344) evaluated the effect of aclidinium/formoterol (AB/FF) 400/12 μg twice daily on lung hyperinflation, exercise capacity, and physical activity in patients with moderate-to-severe COPD.,Patients received AB/FF (n=134) or placebo (n=133) (1:1) via the Genuair™/Pressair® dry powder inhaler for 8 weeks.,From Weeks 5 to 8, all patients participated in behavioral intervention (BI; daily messages providing step goals).,The primary end point was trough functional residual capacity (FRC) at Week 4.,Exercise endurance time and physical activity were assessed at Week 4 (pharmacotherapy only) and at Week 8 (8 weeks of pharmacotherapy plus 4 weeks of BI).,Other end points included post-dose FRC, residual volume, and inspiratory capacity (IC) at rest and during exercise.,After 4 weeks, trough FRC improved with AB/FF versus placebo but did not reach significance (125 mL; P=0.0690).,However, post-dose FRC, residual volume, and IC at rest improved significantly with AB/FF at Week 4 versus placebo (all P<0.0001).,AB/FF significantly improved exercise endurance time and IC at isotime versus placebo at Week 4 (P<0.01 and P<0.0001, respectively) and Week 8 (P<0.05 and P<0.0001, respectively).,AB/FF achieved higher step counts (P<0.01) with fewer inactive patients (P<0.0001) at Week 4 versus placebo.,Following BI, AB/FF maintained improvements in physical activity at Week 8 and nonsignificant improvements were observed with placebo.,AB/FF 400/12 μg demonstrated improvements in lung hyperinflation, exercise capacity, and physical activity versus placebo that were maintained following the addition of BI.,A 4-week period of BI might be too short to augment the improvements of physical activity observed with AB/FF.

This randomized, double-blind, Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).,Methods: Patients received aclidinium 400 μg twice daily (morning and evening), tiotropium 18 μg once daily (morning), or placebo for 6 weeks.,The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose (FEV1 AUC0-24) at week 6.,Secondary and additional endpoints included FEV1 AUC12-24, COPD symptoms (EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [E-RS] total score and additional symptoms questionnaire), and safety.,Results: Overall, 414 patients were randomized and treated (FEV1 1.63 L [55.8% predicted]).,Compared with placebo, FEV1 AUC0-24 and FEV1 AUC12-24 were significantly increased from baseline with aclidinium (Δ = 150 mL and 160 mL, respectively; p < 0.0001) and tiotropium (Δ = 140 mL and 123 mL, respectively; p < 0.0001) at week 6.,Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium (p < 0.0001) than tiotropium (p < 0.05) versus placebo.,Only aclidinium significantly reduced the severity of early-morning cough, wheeze, shortness of breath, and phlegm, and of nighttime symptoms versus placebo (p < 0.05).,Adverse-event (AE) incidence (28%) was similar between treatments.,Few anticholinergic AEs (<1.5%) or serious AEs (<3%) occurred in any group.,Conclusions: Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks.,Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium.,Aclidinium was generally well tolerated.

Fresh peripheral blood (PB) samples from 432 outpatients with stable chronic obstructive pulmonary disease (COPD) were examined.,Patients were classified into Group A (large SRA+ cells were undetected) and Group B (large SRA+ cells were detected) and followed‐up for 1 year.,Patients were further subdivided according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage.,Cox proportional hazard model had shown that Gold, Group, home oxygen therapy (HOT), and treatment were significant predictors of severe exacerbation.,Six of 353 patients in Group A and 29 of 79 in Group B developed severe exacerbation.,The rates of severe exacerbation were significantly higher in Group B patients, GOLD stage 2 than Group A, GOLD stage 2; in Group B, GOLD stage 3 than Group A, GOLD stage 3; and in all of Group B compared with in all of Group A.,The Kaplan‐Meier curves of Group B, GOLD stages 1-4, and of all of Group B showed significantly worse rates of severe exacerbation than those of Group A, Gold 1-4, and all of Group A, respectively.,The appearance of large SRA+ cells in the PB of patients with stable COPD may represent a useful biomarker for severe COPD exacerbation.

Exacerbations of COPD are managed differently, but whether treatment of one exacerbation predicts the likelihood of subsequent events is unknown.,We examined whether the treatment given for exacerbations predicted subsequent outcomes.,This was a post-hoc analysis of 17,135 patients with COPD from TIOtropium Safety and Performance In Respimat® (TIOSPIR®).,Patients treated with tiotropium with one or more moderate to severe exacerbations on study were analyzed using descriptive statistics, logistic and Cox regression analysis, and Kaplan-Meier plots.,Of 8,061 patients with moderate to severe exacerbation(s), demographics were similar across patients with exacerbations treated with antibiotics and/or steroids or hospitalization.,Exacerbations treated with systemic corticosteroids alone or in combination with antibiotics had the highest risk of subsequent exacerbation (HR: 1.21, P=0.0004 and HR: 1.33, P<0.0001, respectively), and a greater risk of having a hospitalized (severe) exacerbation (HR: 1.59 and 1.63, P<0.0001, respectively) or death (HR: 1.50, P=0.0059 and HR: 1.47, P=0.0002, respectively) compared with exacerbations treated with antibiotics alone.,Initial hospitalization led to the highest risk of subsequent hospitalization (all-cause or COPD related [severe exacerbation], HR: 3.35 and 4.31, P<0.0001, respectively) or death (all-cause or COPD related, HR: 3.53 and 5.54, P<0.0001, respectively) versus antibiotics alone.,These data indicate that the way exacerbations are treated initially is a useful guide to the patient’s subsequent clinical course.,Factors that clinicians consider when making treatment choices require further clarification.

We explore potential dysregulation of macrophage phenotypes in COPD pathogenesis through integrated study of human small airway tissue, bronchoalveolar lavage (BAL) and an experimental murine model of COPD.,We evaluated human airway tissue and BAL from healthy controls, normal lung function smokers (NLFS), and COPD subjects.,Both small airways and BAL cells were immunohistochemically stained with anti-CD68 for total macrophages and with anti-CD163 for M2, and anti-iNOS for M1 macrophages.,Multiplex ELISA measured BAL cytokines.,Comparable cigarette smoke-induced experimental COPD mouse model was assessed for relevant mRNA profiles.,We found an increase in pro-inflammatory M1s in the small airways of NLFS and COPD compared to controls with a reciprocal decrease in M2 macrophages, which remained unchanged among pathological groups.,However, luminal macrophages showed a dominant M2 phenotype in both NLFS and COPD subjects.,BAL cytokine skewed towards an M2 profile with increase in CCL22, IL-4, IL-13, and IL-10 in both NLFS and COPDs.,The mouse-model of COPD showed similar increase in mRNA for M2 markers.,Our finding suggests abnormal macrophage switching in both mucosal and luminal areas of COPD patients, that strongly associated with cytokine balance.,There may be potential for beneficial therapeutic cytokine manipulation of macrophage phenotypes in COPD.

Exercise intolerance in COPD seems to combine abnormal ventilatory mechanics, impaired O2 transport and skeletal muscle dysfunction.,However their relatie contribution and their influence on symptoms reported by patients remain to be clarified.,In order to clarify the complex interaction between ventilatory and neuromuscular exercise limiting factors and symptoms, we evaluated respiratory muscles and quadriceps contractile fatigue, dynamic hyperinflation and symptoms induced by exhaustive high-intensity cycling in COPD patients.,Fifteen gold II-III COPD patients (age = 67±6 yr; BMI = 26.6±4.2 kg.m-2) performed constant-load cycling test at 80% of their peak workload until exhaustion (9.3±2.4 min).,Before exercise and at exhaustion, potentiated twitch quadriceps strength (Qtw), transdiaphragmatic (Pdi,tw) and gastric (Pga,tw) pressures were evoked by femoral nerve, cervical and thoracic magnetic stimulation, respectively.,Changes in operational lung volumes during exercise were assessed via repetitive inspiratory capacity (IC) measurements.,Dyspnoea and leg discomfort were measured on visual analog scale.,At exhaustion, Qtw (-33±15%, >15% reduction observed in all patients but two) and Pdi,tw (-20±15%, >15% reduction in 6 patients) were significantly reduced (P<0.05) but not Pga,tw (-6±10%, >15% reduction in 3 patients).,Percentage reduction in Qtw correlated with the percentage reduction in Pdi,tw (r=0.66; P<0.05).,Percentage reductions in Pdi,tw and Pga,tw negatively correlated with the reduction in IC at exhaustion (r=-0.56 and r=-0.62, respectively; P<0.05).,Neither dyspnea nor leg discomfort correlated with the amount of muscle fatigue.,In conclusion, high-intensity exercise induces quadriceps, diaphragm and less frequently abdominal contractile fatigue in this group of COPD patients.,In addition, the rise in end-expiratory lung volume and diaphragm flattening associated with dynamic hyperinflation in COPD might limit the development of abdominal and diaphragm muscle fatigue.,This study underlines that both respiratory and quadriceps fatigue should be considered to understand the complex interplay of factors leading to exercise intolerance in COPD patients.

Inflammation and remodeling of the small airways are major determinants of the progression and severity of COPD.,The present study explored the correlation between sputum p38 mitogen-activated protein kinase (MAPK) activity and airway inflammation and reduction of lung function in the patients with chronic obstructive pulmonary disease (COPD).,Sputum samples were collected from 48 COPD patients and 12 healthy persons.,Sputum p38 MAPK activity was measured by Western blotting and sputum levels of CXCL8 and neutrophil, and lung function was measured.,The correlation between p38MAPK activity and airway inflammation and reduction of lung function was analyzed.,Our results showed the significantly increased expression of phospho-p38 MAPK and CXCL8 in the sputum samples of the COPD patients.,The p38 MAPK activity was remarkably correlated with the CXCL8 level and neutrophils infiltration in the airway, and the decline of lung function in the COPD patients.,These findings suggest the pivotal role of p38 MAPK in the airway inflammation of COPD patients.,We propose p38 MAPK as a potential target for the treatment of COPD.

The aim of the study was to investigate how the expression of adhesion molecules changes as neutrophils migrate from the circulation to the lung and if these changes differ between non-smoking subjects and smokers with and without COPD.,Non-smoking healthy subjects (n=22), smokers without (n=21) and with COPD (n=18) were included.,Neutrophils from peripheral blood, sputum and bronchial biopsies were analysed for cell surface expression of adhesion molecules (CD11b, CD62L, CD162).,Serum, sputum supernatant and BAL-fluid were analysed for soluble adhesion molecules (ICAM-1, -3, E-selectin, P-selectin, VCAM-1, PECAM-1).,Expression of CD11b was increased on circulating neutrophils from smokers with COPD.,It was also increased on sputum neutrophils in both smokers groups, but not in non-smokers, as compared to circulating neutrophils.,Serum ICAM-1 was higher in the COPD group compared to the other two groups (p<0.05) and PECAM-1 was lower in smokers without COPD than in non-smoking controls and the COPD group (p<0.05).,In BAL-fluid ICAM-1 was lower in the COPD group than in the other groups (p<0.05).,Thus, our data strongly support the involvement of a systemic component in COPD and demonstrate that in smokers neutrophils are activated to a greater extent at the point of transition from the circulation into the lungs than in non-smokers.

COPD is a significant cause of morbidity and mortality.,In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation.,Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy.,In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention.,In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13.,The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions.,We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD.

There are only scarce data regarding the evolution of the chronic obstructive pulmonary disease (COPD) assessment test (CAT) over time.,Our aim was to investigate the evolution of the CAT in a telehealthcare (THC) cohort and to evaluate its potential to predict exacerbations.,The CAT was measured weekly over up to 1 year in 40 COPD patients undergoing a THC intervention.,The evolution of the CAT was analyzed using linear regression.,The association between this evolution and the occurrence of exacerbations was evaluated using the Andersen-Gill formulation of the Cox proportional hazards model for the analysis of recurrent time-to-event data with time-varying predictors.,The median CAT at inclusion was 17 (interquartile range 13-22) points.,During the study, 25% of patients had a significant negative slope (median −7 points per year [ppy]), 38% were stable (median +0 ppy) and 38% had a significant positive slope (median +6 ppy).,The median slope of the CAT in the overall cohort was +1 (interquartile range −3 to +6) ppy.,A significant positive association was found between the change in CAT scores and the risk of exacerbations (hazard ratio =1.08, 95% CI: 1.03-1.13; p<0.001).,There was an 8% increase of the risk of exacerbation per unit increase in CAT.,We detected a significant learning effect in filling out the CAT in 18.4% of patients with a median learning phase of five filled questionnaires.,Sixty-three percent of the COPD patients monitored by THC experienced a stable or improved CAT during 1-year follow-up.,We found a significant positive association between the evolution of the CAT over time and the risk of exacerbations.,In about one-fifth of patients, there was a significant learning effect in filling out the CAT, before reliable results could be obtained.,The evolution of the CAT could help to assess the risk for future exacerbations.

Past studies have shown that mean values of Interleukin-6 (IL-6) and C-reactive protein (CRP) do not change significantly in COPD patients over a one-year period.,However, longer period follow-up studies are still lacking.,Thus, the aim of this study is to evaluate plasma CRP and IL-6 concentration over three years in COPD patients and to test the association between these inflammatory mediators and disease outcome markers.,A cohort of 77 outpatients with stable COPD was evaluated at baseline, and 53 (mean FEV1, 56% predicted) were included in the prospective study.,We evaluated Interleukin-6 (IL-6), C-reactive protein (CRP), six-minute walking distance (6MWD), and body mass index (BMI) at baseline and after three years.,Plasma concentration of IL-6 was measured by high sensitivity ELISA, and CRP was obtained by high sensitivity particle-enhanced immunonephelometry.,IL-6 increased significantly after 3 years compared to baseline measurements [0.8 (0.5-1.3) vs 2.4 (1.3-4.4) pg/ml; p < 0.001] and was associated with worse 6MWD performance.,In the Cox regression, increased IL-6 at baseline was associated with mortality [Hazard Ratio (95% CI) = 2.68 (0.13, 1.84); p = 0.02].,CRP mean values did not change [5 (1.6-7.9) vs 4.7 (1.7-10) pg/L; p = 0.84], although eleven patients (21%) presented with changes >3 mg/L in CRP after 3 years.,The systemic inflammatory process, evaluated by IL-6, seems to be persistent, progressive and associated with mortality and worse physical performance in COPD patients.,No.:NCT00605540

Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies.,To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).,Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years.,We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation.,Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs.,0.9 (1.1) per year, p<0.001) compared to non-inflamed ones.,As a descriptive study our results show associations but do not prove causality.,Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.,Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment.

COPD exacerbations and hospitalizations have been associated with poor prognosis for the COPD patient.,To evaluate the frequency and risk factors of COPD exacerbations, hospitalizations, and admissions to intensive care units (ICUs) in Greece by a nationwide cross-sectional study.,A nationwide observational, multicenter, cross-sectional study was conducted in the clinical practice setting of respiratory medicine physicians over a 6 month-period (October 2010 to March 2011).,A total of 6,125 COPD patients were recruited by 199 respiratory physicians.,Participants had a median age of 68.0 years, 71.3% were males, and 71.8% suffered from comorbidities.,The median disease duration was 10.0 years.,Of the patients, 45.3% were classified as having GOLD (Global initiative for chronic Obstructive Lung Disease) stage III or IV COPD.,Patients with four or more comorbidities had 78.5% and threefold-higher than expected number of exacerbations and hospitalizations, respectively, as well as fivefold-higher risk of admission to the ICU compared to those with no comorbidities.,Obese patients had 6.2% fewer expected exacerbations compared to those with a normal body mass index.,Patients with GOLD stage IV had 74.5% and fivefold-higher expected number of exacerbations and hospitalizations, respectively, and nearly threefold-higher risk of admission to the ICU compared to stage I patients.,An additional risk factor for exacerbations and hospitalizations was low compliance with treatment: 45% of patients reported forgetting to take their medication, and 81% reported a preference for a treatment with a lower dosing frequency.,Comorbidities, disease severity, and compliance with treatment were identified as the most notable risk factors for exacerbations, hospitalizations, and ICU admissions.,The results point to the need for a multifactorial approach for the COPD patient and for the development of strategies that can increase patient compliance with treatment.

Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear.,We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD.,Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007).,COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal.,Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry.,Model performance was assessed using standard criteria.,4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70.,The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76).,Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78).,The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80).,Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD.,Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD.

Development of adult respiratory disease is influenced by events in childhood.,The impact of childhood pneumonia on chronic obstructive pulmonary disease (COPD) is not well defined.,We hypothesize that childhood pneumonia is a risk factor for reduced lung function and COPD in adult smokers.,COPD cases and control smokers between 45-80 years old from the United States COPDGene Study were included.,Childhood pneumonia was defined by self-report of pneumonia at <16 years.,Subjects with lung disease other than COPD or asthma were excluded.,Smokers with and without childhood pneumonia were compared on measures of respiratory disease, lung function, and quantitative analysis of chest CT scans.,Of 10,192 adult smokers, 854 (8.4 %) reported pneumonia in childhood.,Childhood pneumonia was associated with COPD (OR 1.40; 95 % CI 1.17-1.66), chronic bronchitis, increased COPD exacerbations, and lower lung function: post-bronchodilator FEV1 (69.1 vs.,77.1 % predicted), FVC (82.7 vs.,87.4 % predicted), FEV1/FVC ratio (0.63 vs.,0.67; p < 0.001 for all comparisons).,Childhood pneumonia was associated with increased airway wall thickness on CT, without significant difference in emphysema.,Having both pneumonia and asthma in childhood further increased the risk of developing COPD (OR 1.85; 95 % CI 1.10-3.18).,Children with pneumonia are at increased risk for future smoking-related lung disease including COPD and decreased lung function.,This association is supported by airway changes on chest CT scans.,Childhood pneumonia may be an important factor in the early origins of COPD, and the combination of pneumonia and asthma in childhood may pose the greatest risk.,ClinicalTrials.gov, NCT00608764 (Active since January 28, 2008).,The online version of this article (doi:10.1186/s12931-015-0273-8) contains supplementary material, which is available to authorized users.

We analyzed the chest radiographs (CXRs) of 249 clinically healthy children, 230 from southwest Mexico City and 19 from Tlaxcala.,In contrast to children from Tlaxcala, children from southwest Mexico City were chronically exposed to ozone levels exceeding the U.S.,National Ambient Air Quality Standards for an average of 4.7 hr/day and to concentrations of particulate matter (PM) with aerodynamic diameters ≤2.5 μm (PM2.5) above the annual standard.,CXRs of Mexico City children demonstrated bilateral hyperinflation (151 of 230) and increased linear markings (121 of 230).,Hyperinflation and interstitial markings were significantly more common in Mexico City children (p < 0.0002 and 0.00006 respectively).,Mexico City boys had a higher probability of developing interstitial markings with age (p = 0.004).,Computed tomography (CT) scans were obtained in 25 selected Mexico City children with abnormal CXRs.,Mild bronchial wall thickening was seen in 10 of 25, prominent central airways in 4 of 25, air trapping in 8 of 21, and pulmonary nodules in 2 of 21.,Only 7.8% of Mexico City children had abnormal lung function tests based on predicted values.,These findings are consistent with bronchiolar, peribronchiolar, and/or alveolar duct inflammation, possibly caused by ozone, PM, and lipopolysaccharide exposure.,The epidemiologic implications of these findings are important for children residing in polluted environments, because bronchiolar disease could lead to chronic pulmonary disease later in life.

The airway smooth muscle (ASM) plays an indispensable role in airway structure and function.,Dysfunction in ASM plays a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and contributes to alterations of contractility, inflammatory response, immunoreaction, phenotype, quantity, and size of airways.,ASM makes a key contribution in COPD by various mechanisms including altered contractility and relaxation induce by [Ca2+]i, cell proliferation and hypertrophy, production and modulation of extracellular cytokines, and release of pro-and-anti-inflammatory mediators.,Multiple dysfunctions of ASM contribute to modulating airway responses to stimuli, remodeling, and fibrosis, as well as influence the compliance of lungs.,The present review highlights regulatory roles of multiple factors in the development of ASM dysfunction in COPD, aims to understand the regulatory mechanism by which ASM dysfunctions are initiated, and explores the clinical significance of ASM on alterations of airway structure and function in COPD and development of novel therapeutic strategies for COPD.

The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally.

The tissue turnover of unperturbed adult lung is remarkably slow.,However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration.,Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction.,Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis.,Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development.,Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors.,Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs.,With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality.,In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases.

Cigarette smoking is the major risk factor for COPD, leading to chronic airway inflammation.,We hypothesized that cigarette smoke induces structural and functional changes of airway epithelial mitochondria, with important implications for lung inflammation and COPD pathogenesis.,We studied changes in mitochondrial morphology and in expression of markers for mitochondrial capacity, damage/biogenesis and fission/fusion in the human bronchial epithelial cell line BEAS-2B upon 6-months from ex-smoking COPD GOLD stage IV patients to age-matched smoking and never-smoking controls.,We observed that long-term CSE exposure induces robust changes in mitochondrial structure, including fragmentation, branching and quantity of cristae.,The majority of these changes were persistent upon CSE depletion.,Furthermore, long-term CSE exposure significantly increased the expression of specific fission/fusion markers (Fis1, Mfn1, Mfn2, Drp1 and Opa1), oxidative phosphorylation (OXPHOS) proteins (Complex II, III and V), and oxidative stress (Mn-SOD) markers.,These changes were accompanied by increased levels of the pro-inflammatory mediators IL-6, IL-8, and IL-1β.,Importantly, COPD primary bronchial epithelial cells (PBECs) displayed similar changes in mitochondrial morphology as observed in long-term CSE-exposure BEAS-2B cells.,Moreover, expression of specific OXPHOS proteins was higher in PBECs from COPD patients than control smokers, as was the expression of mitochondrial stress marker PINK1.,The observed mitochondrial changes in COPD epithelium are potentially the consequence of long-term exposure to cigarette smoke, leading to impaired mitochondrial function and may play a role in the pathogenesis of COPD.

Community-acquired pneumonia (CAP) is more common in patients with COPD than in the adult general population, with studies of hospitalized CAP patients consistently reporting COPD as a frequent comorbidity.,However, despite an increasing recognition of its importance, large studies evaluating the incidence patterns over time, risk factors and burden of CAP in COPD are currently lacking.,A retrospective observational study using a large UK-based database of linked primary and secondary care records was conducted.,Patients with a diagnosis of COPD aged ≥40 years were followed up for 5 years from January 1, 2010.,CAP and exacerbation episodes were identified from hospital discharge data and primary care coding records, and rates were calculated per month, adjusting for mortality, and displayed over time.,In addition, baseline factors predicting future risk of CAP and hospital admission with CAP were identified.,A total of 14,513 COPD patients were identified: 13.4% (n=1,938) had ≥1 CAP episode, of whom 18.8% suffered from recurrent (≥2) CAP.,Highest rates of both CAP and exacerbations were seen in winter.,A greater proportion of frequent, compared to infrequent, exacerbators experienced recurrent CAP (5.1% versus 2.0%, respectively, P<0.001); 75.6% of CAP episodes were associated with hospital admission compared to 22.1% of exacerbations.,Older age and increasing grade of airflow limitation were independently associated with increased odds of CAP and hospital admission with CAP.,Other independent predictors of future CAP included lower body mass index, inhaled corticosteroid use, prior frequent exacerbations and comorbidities, including ischemic heart disease and diabetes.,CAP in COPD demonstrates clear seasonal patterns, with patient characteristics predictive of the odds of future CAP and hospital admission with CAP.,Highlighting this burden of COPD-associated CAP during the winter period informs us of the likely triggers and the need for more effective preventive strategies.

Chronic Obstructive Pulmonary Disease (COPD) is and will remain a major cause of morbidity and mortality worldwide.,The severity of airflow obstruction is known to relate to overall health status and mortality.,However, even allowing for common aetiological factors, a link has been identified between COPD and other systemic diseases such as cardiovascular disease, diabetes and osteoporosis.,COPD is known to be an inflammatory condition and neutrophil elastase has long been considered a significant mediator of the disease.,Pro-inflammatory cytokines, in particular TNF-α (Tumour Necrosis Factor alpha), may be the driving force behind the disease process.,However, the roles of inflammation and these pro-inflammatory cytokines may extend beyond the lungs and play a part in the systemic effects of the disease and associated co-morbidities.,This article describes the mechanisms involved and proposes a common inflammatory TNF-α phenotype that may, in part, account for the associations.

The causal association between depression, anxiety, and health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD) is unclear.,We therefore conducted a systematic review of prospective cohort studies that measured depression, anxiety, and HRQoL in COPD.,Electronic databases (Medline, Embase, Cumulative Index to Nursing and Allied Health Literature [CINAHL], British Nursing Index and Archive, PsycINFO and Cochrane database) were searched from inception to June 18, 2013.,Studies were eligible for inclusion if they: used a nonexperimental prospective cohort design; included patients with a diagnosis of COPD confirmed by spirometry; and used validated measures of depression, anxiety, and HRQoL.,Data were extracted and pooled using random effects models.,Six studies were included in the systematic review; of these, three were included in the meta-analysis for depression and two were included for the meta-analysis for anxiety.,Depression was significantly correlated with HRQoL at 1-year follow-up (pooled r=0.48, 95% confidence interval 0.37-0.57, P<0.001).,Anxiety was also significantly correlated with HRQoL at 1-year follow-up (pooled r=0.36, 95% confidence interval 0.23-0.48, P<0.001).,Anxiety and depression predict HRQoL in COPD.,However, this longitudinal analysis does not show cause and effect relationships between depression and anxiety and future HRQoL.,Future studies should identify psychological predictors of poor HRQoL in well designed prospective cohorts with a view to isolating the mediating role played by anxiety disorder and depression.

Gastroesophageal reflux disease (GERD) is one of the most common causes of chronic cough and a potential risk factor for exacerbation of chronic obstructive pulmonary disease (COPD).,The aim of this study was to investigate the prevalence and risk factors of GERD in patients with COPD and association between GERD and COPD exacerbation.,Data were collected from the National Health Insurance Database of Korea.,The subjects were 40 years old and older, who had COPD as primary or secondary diagnosis codes and utilized health care resource to receive prescriptions of COPD medication at least twice in 2009.,Univariate logistic regression was performed to understand the relationship between COPD and GERD, and multiple logistic regression analysis was performed with adjustment for several confounding factors.,The prevalence of GERD in COPD patients was 28% (39,987/141,057).,Old age, female gender, medical aid insurance type, hospitalization, and emergency room (ER) visit were associated with GERD.,Most of COPD medications except inhaled muscarinic antagonists were associated with GERD.,The logistic regression analysis showed that the presence of GERD was associated with increased risk of hospitalization (OR 1.54, CI 1.50 to 1.58, p<0.001) and frequent ER visits (OR 1.55, CI 1.48 to 1.62, p<0.001).,The prevalence of GERD in patients with COPD was high.,Old age, female gender, medical aid insurance type, and many COPD medications except inhaled muscarinic antagonists were associated with GERD.,The presence of GERD was associated with COPD exacerbation.

COPD is a multifactorial disease caused by environmental determinants as well as genetic risk factors.,The prevalence and mortality of COPD continue to increase, and underdiagnosis of COPD remains a critical issue.,Previous reports investigated promising microRNAs (miRNAs) to reveal the molecular mechanism for the development of COPD; however, diagnostic and therapeutic markers for COPD have not yet been found.,For this study, 20 representative COPD patients were separated into four groups based on increasing severity (A, B, C, and D) and compared to six healthy controls.,Small RNA profiles of peripheral leukocytes were differentially expressed miRNAs (analyzed via next-generation sequencing) were validated via quantitative reverse transcriptase-polymerase chain reaction.,Compared to healthy controls, 19 differentially expressed miRNAs were found in COPD patients.,For all COPD groups, miR-3177-3p was downregulated, while 17 miRNAs were upregulated.,Furthermore, the results revealed 21 differentially expressed miRNAs, of which miR-183-5p was continually downregulated from A to B to D.,Between respective bronchodilator reversibility positive and negative groups of COPD different groups (A, B, C, and D), 10 miRNAs were differentially expressed, while miR-100-5p was upregulated in the negative groups.,In conclusion, miR-106b-5p, miR-125a-5p, miR-183-5p, and miR-100-5p are central for the development of COPD.,The severity of COPD was attenuated by miR-106b-5p, thus suggesting this miRNA as potential target for disease treatment.

Chronic obstructive pulmonary disease (COPD) is a progressive, irreversible chronic inflammatory disorder typified by increased recruitment of monocytes, lymphocytes and neutrophils.,Because of this, as well as the convenience of peripheral blood nuclear cells (PBMCs) assessments, miRNA profiling of PBMCs has drawn increasing attention in recent years for various disease.,Therefore, we analyzed miRNA and mRNA profiles to understand their regulatory network between COPD subjects versus smokers without airflow limitation.,miRNA and mRNA profiling of PBMCs from pooled 17 smokers and 14 COPD subjects was detected by high-throughput microarray.,The expression of dysregulated miRNAs were validated by q-PCR.,The miRNA targets in dysregulated mRNAs were predicted and the pathway enrichment was analyzed.,miRNA microarray showed that 8 miRNAs were up-regulated and 3 miRNAs were down-regulated in COPD subjects compared with smokers; the upregulation of miR-24-3p, miR-93-5p, miR-320a and miR-320b and the downregulation of miR-1273 g-3p were then validated.,Bioinformatic analysis of regulatory network between miRNA and mRNA showed that NOD and TLR were the most enriched pathways. miR-24-3p was predicted to regulate IL-18, IL-1β, TNF, CCL3 and CCL4 and miR-93-5p to regulate IκBα.,The expression of miRNA and mRNA were dysregulated in PBMCs of COPD patients compared with smokers without airflow limitation.,The regulation network between the dysregulated miRNA and mRNA may provide potential therapeutic targets for COPD.

In patients with COPD, self-management skills are important to reduce the impact of exacerbations.,However, both detection and adequate response to exacerbations appear to be difficult for some patients.,Little is known about the underlying process of exacerbation-related self-management.,Therefore, the objective of this study was to identify and explain the underlying process of exacerbation-related self-management behavior.,A qualitative study using semi-structured in-depth interviews was performed according to the grounded theory approach, following a cyclic process in which data collection and data analysis alternated.,Fifteen patients (male n=8; age range 59-88 years) with mild to very severe COPD were recruited from primary and secondary care settings in the Netherlands, in 2015.,Several patterns in exacerbation-related self-management behavior were identified, and a conceptual model describing factors influencing exacerbation-related self-management was developed.,Acceptance, knowledge, experiences with exacerbations, perceived severity of symptoms and social support were important factors influencing exacerbation-related self-management.,Specific factors influencing recognition of exacerbations were heterogeneity of exacerbations and habituation to symptoms.,Feelings of fear, perceived influence on exacerbation course, patient beliefs, ambivalence toward treatment, trust in health care providers and self-empowerment were identified as specific factors influencing self-management actions.,This study provided insight into factors influencing exacerbation-related self-management behavior in COPD patients.,The conceptual model can be used as a framework for health care professionals providing self-management support.,In the development of future self-management interventions, factors influencing the process of exacerbation-related self-management should be taken into account.

Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death.

Few data exist on the understanding and adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in resource-limited settings, which are mostly in sub-Saharan Africa.,To assess physicians' understanding, adherence, and barriers to implementation of GOLD guidelines in Nigeria.,A questionnaire based on the recommendations of the guidelines was self-administered by 156 physicians in departments of internal and family medicine in selected hospitals to assess physician understanding of the GOLD guidelines and barriers to its implementation.,The medical records of patients with chronic obstructive pulmonary disease (COPD) were also reviewed to assess adherence to the guideline recommendations.,The performance score of all physicians was 22.37±0.39 (range 0-38).,Pulmonologists had the highest score (37.00±0.00) while medical officers had the lowest score (19.93±4.98) (F=10.16, df=5, p<0.001).,Forty one percent of physicians knew the spirometric criteria for diagnosing COPD and 26.9% could assess the severity.,In clinical practice, 32% of patients had brief smoking counselling despite 70% being smokers, 24% had spirometry and 18% had assessment of severity.,Almost 60% of patients were on oral aminophylline, 72% were on an inhaled long-acting β2-agonist and corticosteroid combination, 2% had pulmonary rehabilitation and no patients were vaccinated.,Self-reported adherence to the COPD guidelines was 23.7%.,Lack of familiarity (39.8%) was cited as the most common barrier to adherence to the guidelines.,The understanding of GOLD guidelines is satisfactory among Nigerian doctors managing patients with COPD but the level of adherence is poor.,Educational interventions are needed to improve the implementation of guideline-based management.

Chronic obstructive pulmonary disease (COPD) is the end result of a susceptible individual being exposed to sufficiently deleterious environmental stimuli.,More than 90% of COPD-related deaths occur in low- and middle-income countries (LMICs).,LMICs face unique challenges in managing COPD; for example, deficient primary care systems present challenges for proper diagnosis and management.,Formal diagnosis of COPD requires quality-assured spirometry, which is often limited to urban health centres.,Similarly, standard treatment options for COPD remain limited where few providers are trained to manage COPD.,The Global Excellence in COPD Outcomes (GECo) studies aim to assess the performance of a COPD case-finding questionnaire with and without peak expiratory flow (PEF) to diagnose COPD, and inform the effectiveness and implementation of COPD self-management Action Plans in LMIC settings.,The ultimate goal is to develop simple, low-cost models of care that can be implemented in LMICs.,This study will be carried out in Nepal, Peru and Uganda, three distinct LMIC settings.,We aim to assess the diagnostic accuracy of a simple questionnaire with and without PEF to case-find COPD (GECo1), and examine the effectiveness, cost-effectiveness and implementation of a community-health-worker-supported self-management Action Plan strategy for managing exacerbations of COPD (GECo2).,To achieve the first aim, we will enrol a randomly selected sample of up to 10,500 adults aged ≥ 40 years across our three sites, with the goal to enrol 240 participants with moderate-to-severe COPD in to GECo2.,We will apply two case-finding questionnaires (Lung Function Questionnaire and CAPTURE) with and without PEF and compare performance against spirometry.,We will report ROC areas, sensitivity and specificity.,Individuals who are identified as having COPD grades B-D will be invited to enrol in an effectiveness-implementation hybrid randomised trial of a multi-faceted COPD self-management Action Plan intervention delivered by CHWs.,The intervention group will receive (1) COPD education, (2) facilitated-self management Action Plans for COPD exacerbations and (3) monthly visits by community health workers.,The control group will receive COPD education and standard of care treatment provided by local health providers.,Beginning at baseline, we will measure quality of life with the EuroQol-5D (EQ-5D) and St.,George’s Respiratory Questionnaire (SGRQ) every 3 months over a period of 1 year.,The primary endpoint is SGRQ at 12 months.,Quality-adjusted life years (QALYs) using the Short-Form 36 version 2 will also be calculated.,We will additionally assess the acceptability and feasibility of implementing COPD Action Plans in each setting among providers and individuals with COPD.,This study should provide evidence to inform the use of pragmatic models of COPD diagnosis and management in LMIC settings.,NCT03359915 (GECo1).,Registered on 2 December 2017 and NCT03365713 (GECo2).,Registered on 7 December 2017.,Trial acronym: Global Excellence in COPD Outcomes (GECo1; GECo2).,The online version of this article (10.1186/s13063-018-2909-8) contains supplementary material, which is available to authorized users.

Systemic inflammatory factors are inconsistently associated with the pathogenesis of chronic obstructive pulmonary disease (COPD).,We conducted a systematic review and meta-analysis to summarize the evidence supporting the association between systemic inflammation and the risk of COPD.,Pertinent studies were retrieved from PubMed, EmBase, and the Cochrane Library until April 2015.,A random-effects model was used to process the data, and the analysis was further stratified by factors affecting these associations.,Sensitivity analyses for publication bias were performed.,We included 24 observational studies reporting data on 10,677 COPD patients and 28,660 controls.,Overall, we noted that COPD was associated with elevated serum CRP (SMD: 1.21; 95%CI: 0.92-1.50; P < 0.001), leukocytes (SMD: 1.07; 95%: 0.25-1.88; P = 0.010), IL-6 (SMD: 0.90; 95%CI: 0.48-1.31; P < 0.001), IL-8 (SMD: 2.34; 95%CI: 0.69-4.00; P = 0.006), and fibrinogen levels (SMD: 0.87; 95%CI: 0.44-1.31; P < 0.001) when compared with control.,However, COPD was not significantly associated with TNF-α levels when compared with control (SMD: 0.60; 95%CI: -0.46 to 1.67; P = 0.266).,Our findings suggested that COPD was associated with elevated serum CRP, leukocytes, IL-6, IL-8, and fibrinogen, without any significant relationship with TNF-α.

Polymorphonuclear neutrophils have in recent years attracted new attention due to their ability to release neutrophil extracellular traps (NETs).,These web-like extracellular structures deriving from nuclear chromatin have been depicted in ambiguous roles between antimicrobial defence and host tissue damage.,NETs consist of DNA strands of varying thickness and are decorated with microbicidal and cytotoxic proteins.,Their principal structure has in recent years been characterised at molecular and ultrastructural levels but many features that are of direct relevance to cytotoxicity are still incompletely understood.,These include the extent of chromatin decondensation during NET formation and the relative amounts and spatial distribution of the microbicidal components within the NET.,In the present work, we analyse the structure of NETs found in induced sputum of patients with acutely exacerbated chronic obstructive pulmonary disease (COPD) using confocal laser microscopy and electron microscopy.,In vitro induced NETs from human neutrophils serve for purposes of comparison and extended analysis of NET structure.,Results demonstrate that COPD sputa are characterised by the pronounced presence of NETs and NETotic neutrophils.,We provide new evidence that chromatin decondensation during NETosis is most extensive and generates substantial amounts of double-helix DNA in ‘beads-on-a-string’ conformation.,New information is also presented on the abundance and location of neutrophil elastase (NE) and citrullinated histone H3 (citH3).,NE occurs in high densities in nearly all non-fibrous constituents of the NETs while citH3 is much less abundant.,We conclude from the results that (i) NETosis is an integral part of COPD pathology; this is relevant to all future research on the etiology and therapy of the disease; and that (ii) release of ‘beads-on-a-string’ DNA studded with non-citrullinated histones is a common feature of in vivo NETosis; this is of relevance to both the antimicrobial and the cytotoxic effects of NETs.

Blood eosinophil counts and history of exacerbations have been proposed as predictors of patients with chronic obstructive pulmonary disease (COPD) who may benefit from triple therapy (inhaled corticosteroid, long-acting β2-agonist and long-acting muscarinic antagonist).,In a retrospective cohort analysis we examined the profiles of COPD patients from the UK Clinical Practice Research Datalink (CPRD) and US Optum Clinformatics™ Data Mart (Optum) databases with reference to exacerbation frequency and blood eosinophil distribution.,Of the 31,437 (CPRD) and 383,825 (Optum) patients with COPD, 15,364 (CPRD) and 139,465 (Optum) met the eligibility criteria and were included.,Among patients with ≥2 exacerbations and available eosinophil counts in the baseline period (CPRD, n = 3089 and Optum, n = 13414), 17.0 and 13.3% respectively had eosinophil counts ≥400 cells/μL.,Patients with ≥2 exacerbations or eosinophil count ≥400 cells/μL during first year, exacerbated at least once (CPRD, 82.8% vs Optum, 80.6%) or continued to have eosinophil count ≥300 cells/μL (76.8% vs 76.5%), respectively in the follow-up year.,In both years, a higher variability in the number of exacerbations and eosinophil count was observed in patients with one exacerbation and eosinophil counts between 300 and 400 cells/μL; patients with eosinophil count < 150 cells/μL had the lowest variability.,Approximately 10% patients had both ≥2 exacerbations and eosinophil count ≥300 cells/μL across the databases.,A high variability in blood eosinophil counts over two consecutive years was observed in UK and US patients with COPD and should be considered while making treatment decisions.,A small proportion of COPD patients had frequent exacerbations and eosinophil count ≥300 cells/μL.,The online version of this article (10.1186/s12931-019-1130-y) contains supplementary material, which is available to authorized users.

Severe exacerbations and mortality are major outcomes in COPD, and risk factors for these events are actively searched for.,Several predictors of mortality have been identified in COPD.,The inspiratory capacity/total lung capacity (IC/TLC) ratio has been shown to be a strong predictor of all cause and respiratory mortality in patients with COPD.,The major objectives of this study were to analyze which clinical parameters, including lung volumes, were the best predictors of the 5-year cumulative risk of hospital admissions or death and the 5-year risk of exacerbations, in stable COPD patients.,This study retrospectively reviewed data from 98 stable COPD patients, consecutively recruited in 2012.,Forced expiratory volume in 1 s (FEV1), modified Medical Research Council dyspnea scale, exacerbation history (ExH), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 groups, and lung volumes were reviewed.,Five years later, this population was evaluated for cumulative exacerbations, hospital admissions, and mortality.,All the population, and GOLD group D separately, were analyzed.,The cumulative 5-year combined risk of hospital admission or death was significantly predicted by the ExH and the IC/TLC ratio.,Analyzing separately group D, FEV1 was the only predictor of this outcome.,The frequency of exacerbations in the previous year was the best predictor of future cumulative 5-year risk of subsequent exacerbations, both for the total population and the GOLD D group.,ExH and IC/TLC ratio were the best predictors of the most severe outcomes in COPD (admissions or mortality), independently of COPD severity.,FEV1 was the only predictor of the cumulative 5-year combined risk of hospital admission or death in the GOLD D group.,ExH was the best predictor of 5-year cumulative future risk of exacerbations.,Besides FEV1 and ExH, the IC/TLC ratio can be a useful predictor of severe outcomes in COPD.

Free iron in lung can cause the generation of reactive oxygen species, an important factor in chronic obstructive pulmonary disease (COPD) pathogenesis.,Iron accumulation has been implicated in oxidative stress in other diseases, such as Alzheimer’s and Parkinson’s diseases, but little is known about iron accumulation in COPD.,We sought to determine if iron content and the expression of iron transport and/or storage genes in lung differ between controls and COPD subjects, and whether changes in these correlate with airway obstruction.,Explanted lung tissue was obtained from transplant donors, GOLD 2-3 COPD subjects, and GOLD 4 lung transplant recipients, and bronchoalveolar lavage (BAL) cells were obtained from non-smokers, healthy smokers, and GOLD 1-3 COPD subjects.,Iron-positive cells were quantified histologically, and the expression of iron uptake (transferrin and transferrin receptor), storage (ferritin) and export (ferroportin) genes was examined by real-time RT-PCR assay.,Percentage of iron-positive cells and expression levels of iron metabolism genes were examined for correlations with airflow limitation indices (forced expiratory volume in the first second (FEV1) and the ratio between FEV1 and forced vital capacity (FEV1/FVC)).,The alveolar macrophage was identified as the predominant iron-positive cell type in lung tissues.,Futhermore, the quantity of iron deposit and the percentage of iron positive macrophages were increased with COPD and emphysema severity.,The mRNA expression of iron uptake and storage genes transferrin and ferritin were significantly increased in GOLD 4 COPD lungs compared to donors (6.9 and 3.22 fold increase, respectively).,In BAL cells, the mRNA expression of transferrin, transferrin receptor and ferritin correlated with airway obstruction.,These results support activation of an iron sequestration mechanism by alveolar macrophages in COPD, which we postulate is a protective mechanism against iron induced oxidative stress.

Macrophages have been implicated in the pathogenesis of COPD.,M1 and M2 macrophages constitute subpopulations displaying pro- and anti-inflammatory properties.,We hypothesized that smoking cessation affects macrophage heterogeneity in the lung of patients with COPD.,Our aim was to study macrophage heterogeneity using the M2-marker CD163 and selected pro- and anti-inflammatory mediators in bronchoalveolar lavage (BAL) fluid and induced sputum from current smokers and ex-smokers with COPD.,114 COPD patients (72 current smokers; 42 ex-smokers, median smoking cessation 3.5 years) were studied cross-sectionally and underwent sputum induction (M/F 99/15, age 62 ± 8 [mean ± SD] years, 42 (31-55) [median (range)] packyears, post-bronchodilator FEV1 63 ± 9% predicted, no steroids past 6 months).,BAL was collected from 71 patients.,CD163+ macrophages were quantified in BAL and sputum cytospins.,Pro- and anti-inflammatory mediators were measured in BAL and sputum supernatants.,Ex-smokers with COPD had a higher percentage, but lower number of CD163+ macrophages in BAL than current smokers (83.5% and 68.0%, p = 0.04; 5.6 and 20.1 ×104/ml, p = 0.001 respectively).,The percentage CD163+ M2 macrophages was higher in BAL compared to sputum (74.0% and 30.3%, p < 0.001).,BAL M-CSF levels were higher in smokers than ex-smokers (571 pg/ml and 150 pg/ml, p = 0.001) and correlated with the number of CD163+ BAL macrophages (Rs = 0.38, p = 0.003).,No significant differences were found between smokers and ex-smokers in the levels of pro-inflammatory (IL-6 and IL-8), and anti-inflammatory (elafin, and Secretory Leukocyte Protease Inhibitor [SLPI]) mediators in BAL and sputum.,Our data suggest that smoking cessation partially changes the macrophage polarization in vivo in the periphery of the lung towards an anti-inflammatory phenotype, which is not accompanied by a decrease in inflammatory parameters.

The burden of chronic obstructive pulmonary disease (COPD) to patients and health services is steadily increasing.,Self-management supported by mobile device applications could improve outcomes for people with COPD.,Our aim was to synthesize evidence on the effectiveness of mobile health applications compared with usual care.,A systematic review was conducted to identify randomized controlled trials.,Outcomes of interest included exacerbations, physical function, and Quality of Life (QoL).,Where possible, outcome data were pooled for meta-analyses.,Of 1709 citations returned, 13 were eligible trials.,Number of exacerbations, quality of life, physical function, dyspnea, physical activity, and self-efficacy were reported.,Evidence for effectiveness was inconsistent between studies, and the pooled effect size for physical function and QoL was not significant.,There was notable variation in outcome measures used across trials.,Developing a standardized outcome-reporting framework for digital health interventions in COPD self-management may help standardize future research.

Self-management (SM) is defined as the provision of interventions to increase patients’ skills and confidence, empowering the individual to take an active part in their disease management.,There is uncertainty regarding the optimal format and the short- and long-term benefits of chronic obstructive pulmonary disease (COPD) SM interventions in adults.,Therefore, a high-quality overview of reviews was updated to examine their clinical effectiveness.,Sixteen reviews were identified, interventions were broadly classified as education or action plans, complex interventions with an SM focus, pulmonary rehabilitation (PR), telehealth and outreach nursing.,Systematic review and meta-analysis quality and the risk of bias of underlying primary studies were assessed.,Strong evidence was found that PR is associated with significant improvements in health-related quality of life (HRQoL).,Limited to moderate evidence for complex interventions (SM focus) with limited evidence for education, action plans, telehealth interventions and outreach nursing for HRQoL was found.,There was strong evidence that education is associated with a significant reduction in COPD-related hospital admissions, moderate to strong evidence that telehealth interventions and moderate evidence that complex interventions (SM focus) are associated with reduced health care utilization.,These findings from a large body of evidence suggesting that SM, through education or as a component of PR, confers significant health gains in people with COPD in terms of HRQoL.,SM supported by telehealth confers significant reductions in healthcare utilization, including hospitalization and emergency department visits.

Although COPD is a prevalent disease, it is undertreated, and there are no available data regarding previous treatment of COPD in Brazil.,This study aimed to determine the appropriateness of maintenance treatment in COPD patients prior to their hospitalization and to identify variables associated with inappropriate treatment.,This was an observational, cross-sectional, analytical study involving 50 inpatients with COPD at two hospitals in the city of Florianópolis, Brazil.,The patients completed a questionnaire on parameters related to the maintenance treatment of COPD.,Non-pharmacological management and pharmacological treatment were assessed based on the recommendations made by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) in 2011 and by the Brazilian National Ministry of Health in the chronic respiratory diseases section of its Caderno de Atenção Básica (CAB, Primary Care Guidebook).,In most of the patients, the COPD was classified as being severe or very severe.,Regarding non-pharmacological management, 33% of the patients were smokers, only 32% had been advised to receive the flu vaccine, 28% had received pneumococcal vaccine, and only 6.5% of the patients in the B, C, and D categories received pulmonary rehabilitation.,Regarding GOLD and CAB recommendations, pharmacological treatment was inappropriate in 50% and 74% of the patients, respectively.,Based on GOLD recommendations, 38% were undertreated.,A low level of education, low income, not receiving oxygen therapy, and not receiving the flu vaccine were associated with inappropriate treatment.,The application of various non-pharmacological management recommendations was unsatisfactory.,Regarding the GOLD recommendations, the high rate of inappropriate maintenance treatment was mainly due to undertreatment.,In Brazil, even in severe COPD cases, optimizing treatment to achieve greater benefits continues to be a challenge.,Embora a DPOC seja uma enfermidade prevalente, ela é subtratada, e dados sobre o tratamento prévio são desconhecidos em nosso meio.,Buscou-se verificar a adequação às recentes diretrizes no que se refere ao tratamento de manutenção em pacientes com DPOC antes de sua hospitalização e identificar possíveis variáveis associadas à inadequação do tratamento.,Estudo transversal, observacional e analítico, que incluiu 50 portadores de DPOC, internados em dois hospitais na cidade de Florianópolis (SC).,Aplicou-se um questionário sobre parâmetros relacionados ao tratamento de manutenção da DPOC.,Avaliou-se o manejo não farmacológico e a adequação do tratamento farmacológico à terapia preconizada pelo Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 e pelo Caderno de Atenção Básica (CAB) do Ministério da Saúde do Brasil sobre doenças respiratórias crônicas.,Na maioria dos pacientes, a DPOC foi classificada como grave ou muito grave.,Em relação ao manejo não farmacológico, 33% eram tabagistas, apenas 32% foram orientados a receber vacinação anti-influenza, 28% receberam vacina anti-pneumocócica, e somente 6,5% dos pacientes nas categorias GOLD B, C e D realizaram reabilitação respiratória.,O tratamento farmacológico foi inadequado em 50% e 74% da amostra, respectivamente, em relação às recomendações do GOLD e do CAB.,Baseado nas recomendações do GOLD, 38% eram subtratados.,Baixa escolaridade, baixa renda, não utilização de oxigenoterapia e ausência de vacinação anti-influenza associaram-se a inadequação do tratamento.,Não foram seguidas satisfatoriamente várias recomendações do manejo não farmacológico.,Segundo o GOLD, a elevada inadequação do tratamento de manutenção foi principalmente devida ao subtratamento.,No Brasil, mesmo nos casos mais graves, a otimização do tratamento da DPOC para se obter benefícios mais evidentes continua a ser um desafio.

Approximately 210 million people are estimated to have chronic obstructive pulmonary disease [COPD] worldwide.,The burden of disease is known to be high, though less is known about those of a younger age.,The aim of this study was to investigate the wider personal, economic and societal burden of COPD on a cross country working-age cohort.,A cross-country [Brazil, China, Germany, Turkey, US, UK] cross-sectional survey methodology was utilised to answer the research questions. 2426 participants aged 45-67 recruited via a number of recruitment methods specific to each country completed the full survey.,Inclusion criteria were a recalled physician diagnosis of COPD, a smoking history of > 10 pack years and the use of COPD medications in the previous 3 months prior to questioning.,The survey included items from the validated Work Productivity and Activity Impairment [WPAI] scale and the EuroQoL 5 Dimension [EQ-5D] scale.,Disease severity was measured using the 5-point MRC [Medical Research Council] dyspnoea scale as a surrogate measure.,64% had either moderate [n = 1012] or severe [n = 521] COPD, although this varied by country. 75% of the cohort reported at least one comorbid condition.,Quality of life declined with severity of illness [mild, mean EQ-5D score = 0.84; moderate 0.58; severe 0.41].,The annual cost of healthcare utilisation [excluding treatment costs and diagnostic tests] per individual was estimated to be $2,364 [£1,500].,For those remaining in active employment [n: 677]: lost time from work cost the individual an average of $880 [£556] per annum and lifetime losses of $7,365 [£4,661] amounting to $596,000 [£377,000] for the cohort. 447 [~40%] of the working population had retired prematurely because of COPD incurring individual estimated lifetime income losses of $316,000 [£200,000] or a combined total of $141 m [£89.6 m].,As the mean age of retirees was 58.3 and average time since retirement was 4 years, this suggests the average age of retirement is around 54.,This would mean a high societal and economic impact in all study countries, particularly where typical state retirement ages are higher, for example in Brazil, Germany and the UK [65] and the US [65,66,67], compared to Turkey [58 for women, 60 for men] and China [60].,Although generalisation across a broader COPD population is limited due to the varied participant recruitment methods, these data nevertheless suggest that COPD has significant personal, economic and societal burden on working age people.,Further efforts to improve COPD diagnosis and management are required.

A growing body of evidence indicates that matrix metalloproteinases (MMPs) play a role in the pathogenesis of COPD.,Therefore, we conducted a candidate gene association study of 4 promoter polymorphisms that are known to modify expression levels of the MMP-1, MMP-2, and MMP-9 genes and a Gln279Arg polymorphism in exon 6 of MMP-9 that modifies the substrate-binding region.,We examined the association of each variant and haplotypes in 385 male veterans with greater than 20 pack-years of cigarette smoking whose COPD status was characterized using spirometry.,The association of these polymorphisms was also examined with decline of pulmonary function in a subset of participants.,Only the 279Arg variant was more common in participants with COPD and the homozygous variant was associated with a 3-fold increased risk for COPD.,In the haplotype analysis, the haplotype comprising the 249Arg and the CA promoter polymorphism within the MMP-9 gene was associated with risk, suggesting that either 279Arg or a linked variant on this haplotype underlies the association.,No association of this polymorphism was found with decline in pulmonary function.,These studies show that variants of the MMP-9 gene are associated with COPD in this cohort of veterans.

The ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) is a measure used to diagnose airflow obstruction and is highly heritable.,We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs) associated with the FEV1/FVC ratio, analyzed as a percent of the predicted value.,Identified SNPs were examined in an independent set of 835 Family Heart Study participants enriched for airflow obstruction.,Four SNPs in tight linkage disequilibrium on chromosome 4q31 were associated with the percent predicted FEV1/FVC ratio with p-values of genome-wide significance in the Framingham sample (best p-value = 3.6e-09).,One of the four chromosome 4q31 SNPs (rs13147758; p-value 2.3e-08 in Framingham) was genotyped in the Family Heart Study and produced evidence of association with the same phenotype, percent predicted FEV1/FVC (p-value = 2.0e-04).,The effect estimates for association in the Framingham and Family Heart studies were in the same direction, with the minor allele (G) associated with higher FEV1/FVC ratio levels.,Results from the Family Heart Study demonstrated that the association extended to FEV1 and dichotomous airflow obstruction phenotypes, particularly among smokers.,The SNP rs13147758 was associated with the percent predicted FEV1/FVC ratio in independent samples from the Framingham and Family Heart Studies producing a combined p-value of 8.3e-11, and this region of chromosome 4 around 145.68 megabases was associated with COPD in three additional populations reported in the accompanying manuscript.,The associated SNPs do not lie within a gene transcript but are near the hedgehog-interacting protein (HHIP) gene and several expressed sequence tags cloned from fetal lung.,Though it is unclear what gene or regulatory effect explains the association, the region warrants further investigation.

Changes in extracellular matrix (ECM) components in the lungs are associated with the progression of respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome (ARDS).,Experimental and clinical studies have revealed that structural changes in ECM components occur under chronic inflammatory conditions, and these changes are associated with impaired lung function.,In bronchial asthma, elastic and collagen fiber remodeling, mostly in the airway walls, is associated with an increase in mucus secretion, leading to airway hyperreactivity.,In COPD, changes in collagen subtypes I and III and elastin, interfere with the mechanical properties of the lungs, and are believed to play a pivotal role in decreased lung elasticity, during emphysema progression.,In ARDS, interstitial edema is often accompanied by excessive deposition of fibronectin and collagen subtypes I and III, which can lead to respiratory failure in the intensive care unit.,This review uses experimental models and human studies to describe how inflammatory conditions and ECM remodeling contribute to the loss of lung function in these respiratory diseases.

Neutrophil influx into the airways is an important mechanism in the pathophysiology of the inflammatory process in the airways of patients with chronic obstructive pulmonary disease (COPD).,Previously it was shown that anticholinergic drugs reduce the release of non-neuronal paracrine mediators, which modulate inflammation in the airways.,On this basis, we investigated the ability of the long-acting anticholinergic tiotropium bromide to inhibit a) alveolar macrophage (AM)-mediated chemotaxis of neutrophils, and b) cellular release of reactive oxygen species (ROS).,AM and neutrophils were collected from 71 COPD patients.,Nanomolar concentrations of tiotropium bromide were tested in AM cultured up to 20 h with LPS (1 μg/ml).,AM supernatant was tested for TNFα, IL8, IL6, LTB4, GM-CSF, MIPα/β and ROS.,It was further used in a 96-well chemotaxis chamber to stimulate the migration of fluorescence labelled neutrophils.,Control stimulants consisted of acetylcholine (ACh), carbachol, muscarine or oxotremorine and in part PMA (phorbol myristate acetate, 0.1 μg/ml).,Potential contribution of M1-3-receptors was ascertained by a) analysis of mRNA transcription by RT-PCR, and b) co-incubation with selective M-receptor inhibitors.,Supernatant from AM stimulated with LPS induced neutrophilic migration which could be reduced by tiotropium in a dose dependent manner: 22.1 ± 10.2 (3 nM), 26.5 ± 18,4 (30 nM), and 37.8 ± 24.0 (300 nM, p < 0.001 compared to non-LPS activated AM).,Concomitantly TNFα release of stimulated AM dropped by 19.2 ± 7.2% of control (p = 0.001).,Tiotropium bromide did not affect cellular IL8, IL6, LTB4, GM-CSF and MIPα/β release in this setting.,Tiotropium (30 nM) reduced ROS release of LPS stimulated AM by 36.1 ± 15.2% (p = 0.002) and in carbachol stimulated AM by 46.2 ± 30.2 (p < 0.001).,M3R gene expression dominated over M2R and M1R.,Chemotaxis inhibitory effect of tiotropium bromide was mainly driven by M3R inhibition.,Our data confirm that inhibiting muscarinic cholinergic receptors with tiotropium bromide reduces TNFα mediated chemotactic properties and ROS release of human AM, and thus may contribute to lessen cellular inflammation.

Patients with chronic obstructive pulmonary disease (COPD) demonstrate a greater osteoporosis prevalence than the general population.,This osteoporosis risk may be enhanced by treatment with inhaled corticosteroids (ICSs), which are recommended for COPD management when combined with long-acting bronchodilators, but may also be associated with reduced bone mineral density (BMD).,We conducted a narrative literature review reporting results of randomized controlled trials (RCTs) of an ICS versus placebo over a treatment period of at least 12 months, with the aim of providing further insight into the link between bone fractures and ICS therapy.,As of 16 October 2017, we identified 17 RCTs for inclusion.,The ICSs studied were budesonide (six studies), fluticasone propionate (five studies), mometasone furoate (three studies), beclomethasone dipropionate, triamcinolone acetonide, and fluticasone furoate (one each).,We found no difference in the number of bone fractures among patients receiving ICSs versus placebo across the six identified RCTs reporting fracture data.,BMD data were available for subsets of patients in few studies, and baseline BMD data were rare; where these data were given, they were reported for treatment groups without stratification for factors known to affect BMD.,Risk factors for reduced BMD and fractures, such as smoking and physical activity, were also often not reported.,Furthermore, a standardized definition of the term “fracture” was not employed across these studies.,The exact relationship between long-term ICS use and bone fracture incidence in patients with stable COPD remains unclear in light of our review.,We have, however, identified several limiting factors in existing studies that may form the basis of future RCTs designed specifically to explore this relationship.

It remains unclear whether severe exacerbation and pneumonia of COPD differs between patients treated with budesonide/formoterol and those treated with fluticasone/salmeterol.,Therefore, we conducted a comparative study of those who used budesonide/formoterol and those treated with fluticasone/salmeterol for COPD.,Subjects in this population-based cohort study comprised patients with COPD who were treated with a fixed combination of budesonide/formoterol or fluticasone/salmeterol.,All patients were recruited from the Taiwan National Health Insurance database.,The outcomes including severe exacerbations, pneumonia, and pneumonia requiring mechanical ventilation (MV) were measured.,During the study period, 11,519 COPD patients receiving fluticasone/salmeterol and 7,437 patients receiving budesonide/formoterol were enrolled in the study.,Pairwise matching (1:1) of fluticasone/salmeterol and budesonide/formoterol populations resulted in to two similar subgroups comprising each 7,295 patients.,Patients receiving fluticasone/salmeterol had higher annual rate and higher risk of severe exacerbation than patients receiving budesonide/formoterol (1.2219/year vs 1.1237/year, adjusted rate ratio, 1.08; 95% CI, 1.07-1.10).,In addition, patients receiving fluticasone/salmeterol had higher incidence rate and higher risk of pneumonia than patients receiving budesonide/formoterol (12.11 per 100 person-years vs 10.65 per 100 person-years, adjusted hazard ratio [aHR], 1.13; 95% CI, 1.08-1.20).,Finally, patients receiving fluticasone/salmeterol had higher incidence rate and higher risk of pneumonia requiring MV than patients receiving budesonide/formoterol (3.94 per 100 person-years vs 3.47 per 100 person-years, aHR, 1.14; 95% CI, 1.05-1.24).,A similar trend was seen before and after propensity score matching analysis, intention-to-treat, and as-treated analysis with and without competing risk.,Based on this retrospective observational study, long-term treatment with fixed combination budesonide/formoterol was associated with fewer severe exacerbations, pneumonia, and pneumonia requiring MV than fluticasone/salmeterol in COPD patients.

Incidence and prognosis for severe asthma-COPD overlap is poorly characterized.,We investigated incidence and long-term outcome for patients with asthma-COPD overlap compared to asthma and COPD alone.,A total of 57,053 adults (aged 50-64 years) enrolled in the Danish Diet, Cancer, and Health cohort (1993-1997) were followed in the National Patients Registry for admissions for asthma (DJ45-46) and COPD (DJ40-44) and vital status.,Asthma-COPD overlap was defined as at least one hospital admission for asthma and one for COPD (different time points), and incident asthma-COPD overlap as at least one of the diagnoses occurring after enrollment into the Diet, Cancer, and Health cohort.,A total of 1,845 (3.2%) and 4,037 (7.1%) participants had admissions for asthma and COPD, respectively, with 662 (1.2%) participants with asthma-COPD overlap.,Incidence rate of asthma-COPD overlap per 1,000 person-years was higher in women (0.73) than in men (0.54) (P<0.02).,Mortality rate was higher in asthma-COPD overlap (25.9 per 1,000 person-years) compared with COPD (23.1, P<0.05) and asthma (7.9, P<0.001) alone.,Compared to COPD alone, mortality was higher in women with asthma-COPD overlap (19.6 and 25.5, respectively; P<0.01), and the excess mortality rate for asthma-COPD overlap patients was most prominent for younger age groups (12.9 compared to 7.2 and 4.6 for COPD and asthma alone, respectively; P<0.01).,This large population-based study revealed a higher incidence of severe asthma-COPD overlap in women compared to men, and furthermore that all-cause mortality is higher in women and younger subjects with asthma-COPD overlap compared with those with asthma or COPD alone.

Background.,An increase of chronic obstructive pulmonary disease (COPD) prevalence was reported in Canada despite the decline of the main risk factor.,Objectives.,To estimate incidence, prevalence, and mortality of COPD from 2001 to 2011 and establish the COPD burden by the evaluation of the age-period-cohort effects on incidence trends and the comorbidities prevalence estimations.,Methods.,A retrospective population-based cohort was built using Quebec health administrative data.,Change in trends was measured by relative percentage of changes and by joinpoint regression.,After a descriptive analysis of the trends, an age-period-cohort analysis was performed on incidence rates.,Results.,Overall increase in prevalence along with a decrease of incidence and all-cause mortality was observed.,Over time, all age-standardized trends were higher in men than women.,Despite higher rates, the number of incident and prevalent cases in women exceeds men since 2004.,The curve analysis by age groups showed over time a downshift for both sexes in incidence and all-cause mortality.,Further analysis showed the presence of a cohort effect in women.,Conclusion.,The burden of COPD has risen over time.,Women younger than 65 years old have been identified as at-risk group for healthcare planning.

Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD.,Despite guideline recommendations that combined long-acting β2-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk.,This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens.,The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD.,This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 µg and 2.5/5 µg) via Respimat® and twice-daily salmeterol + fluticasone propionate (50/500 µg and 50/250 µg) via Accuhaler® for 6 weeks.,The primary end point was change in forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 12 hours (AUC0-12) relative to the baseline after 6 weeks.,Tiotropium + olodaterol 5/5 µg and 2.5/5 µg demonstrated statistically significant improvements in FEV1 AUC0-12 compared to salmeterol + fluticasone propionate (improvements from baseline were 317 mL and 295 mL with tiotropium + olodaterol 5/5 µg and 2.5/5 µg, and 188 mL and 192 mL with salmeterol + fluticasone propionate 50/500 µg and 50/250 µg, respectively).,Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV1 area under the curve from 0 hour to 24 hours (AUC0-24).,Once-daily tiotropium + olodaterol in participants with moderate-to-severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate.,Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD.

Inhaled corticosteroids (ICS), especially when prescribed in combination with long-acting β2 agonists have been shown to improve COPD outcomes.,Although there is consistent evidence linking ICS with adverse effects such as pneumonia, the complete risk profile is unclear with conflicting evidence on any association between ICS and the incidence or worsening of existing diabetes, cataracts and fractures.,We investigated this using record linkage in a Dundee COPD population.,A record linkage study linking COPD and diabetes datasets with prescription, hospitalisation and mortality data via a unique Community Health Index (CHI) number.,A Cox regression model was used to determine the association between ICS use and new diabetes or worsening of existing diabetes and hospitalisations for pneumonia, fractures or cataracts after adjusting for potential confounders.,A time dependent analysis of exposure comparing time on versus off ICS was used to take into account patients changing their exposure status during follow-up and to prevent immortal time bias.,4305 subjects (3243 exposed to ICS, total of 17,229 person-years of exposure and 1062 non exposed, with a follow-up of 4,508 patient-years) were eligible for the study.,There were 239 cases of new diabetes (DM) and 265 cases of worsening DM, 550 admissions for pneumonia, 288 hospitalisations for fracture and 505 cataract related admissions.,The hazard ratio for the association between cumulative ICS and outcomes were 0.70 (0.43-1.12), 0.57 (0.24-1.37), 1.38 (1.09-1.74), 1.08 (0.73-1.59) and 1.42 (1.07-1.88) after multivariate analysis respectively.,The use of ICS in our cohort was not associated with new onset of diabetes, worsening of existing diabetes or fracture hospitalisation.,There was however an association with increased cataracts and pneumonia hospitalisations.

Concerning COPD, pulmonary rehabilitation (PR) has a positive effect on disease progression and mortality, is cost-effective, and is a part of recommendations of international guidelines.,Only a minority of patients profit from conventional PR due to a lack of resources, physicians’ guideline adherence, or patients’ motivation.,Novel digital therapies like Kaia COPD, a smartphone application that digitizes PR in COPD, are promising solutions to fill this void.,Kaia COPD provides a digital version of PR and is certified as a class-I medical device in the European Union.,We investigated anonymized data from users of the Kaia COPD app on in-app retention and the change in health-related quality of life (COPD assessment test and Chronic Respiratory Disease Questionnaire [CRQ]) during a period of 20 exercise days with the app.,Of 349 app downloads, 56 users fulfilled inclusion criteria and 34 (61%) had finished day 20 at the time of analysis and were included.,Users took 33±11 days to complete the 20-day core program.,Users finishing the program reduced their COPD assessment test scores (mean 2.5 units from 21.6±7.7 to 19.1±8.4 units, P=0.008).,In finishers, there was a statistically significant effect above the minimum clinically important threshold of the CRQ score on the domains of fatigue, mastery, and emotional function.,There was a statistically significant but not clinically relevant effect on the domain of dyspnea of CRQ.,Digitalizing PR with a smartphone app is feasible and accepted by selected patients.,The app leads to short-term improvement of health-related quality of life in patients completing a 20-day core program.,Due to its observational character, this study has several methodological limitations and was intended to show the feasibility and to extrapolate effect sizes for planned prospective randomized-controlled trials to confirm these findings.

Physical inactivity is associated with poor outcomes in COPD, and as a result, interventions to improve physical activity (PA) are a current research focus.,However, many trials have been small and inconclusive.,The aim of this systematic review and meta-analysis was to study the effects of randomized controlled trials (RCTs) targeting PA in COPD.,Databases (Physiotherapy Evidence Database [PEDro], Embase, MEDLINE, CINAHL and the Cochrane Central Register for Controlled Trials) were searched using the following keywords: “COPD”, “intervention” and “physical activity” from inception to May 20, 2016; published RCTs that aimed to increase PA in individuals with COPD were included.,The PEDro scale was used to rate study quality.,Standardized mean differences (effect sizes, ESs) with 95% confidence intervals (CIs) were determined.,Effects of included interventions were also measured according to the minimal important difference (MID) in daily steps for COPD (599 daily steps).,A total of 37 RCTs with 4,314 participants (mean forced expiratory volume in one second (FEV1) % predicted 50.5 [SD=10.4]) were identified.,Interventions including exercise training (ET; n=3 studies, 103 participants) significantly increased PA levels in COPD compared to standard care (ES [95% CI]; 0.84 [0.44-1.25]).,The addition of activity counseling to pulmonary rehabilitation (PR; n=4 studies, 140 participants) showed important effects on PA levels compared to PR alone (0.47 [0.02-0.92]), achieving significant increases that exceeded the MID for daily steps in COPD (mean difference [95% CI], 1,452 daily steps [549-2,356]).,Reporting of methodological quality was poor in most included RCTs.,Interventions that included ET and PA counseling during PR were effective strategies to improve PA in COPD.

Umeclidinium/vilanterol (UMEC/VI) is a novel fixed dose combination of a long-acting muscarinic receptor antagonist (LAMA) and a long-acting beta 2 receptor antagonist (LABA) agent.,This analysis evaluated the incremental cost-effectiveness ratio (ICER) of UMEC/VI compared with tiotropium (TIO), from the Spanish National Health System (NHS) perspective.,A previously published linked equations cohort model based on the epidemiological longitudinal study ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points) was used.,Patients included were COPD patients with a post-bronchodilator forced expiratory volume in 1 second (FEV1) ≤70% and the presence of respiratory symptoms measured with the modified Medical Research Council dyspnea scale (modified Medical Research Council ≥2).,Treatment effect, expressed as change in FEV1 from baseline, was estimated from a 24-week head-to-head phase III clinical trial comparing once-daily UMEC/VI with once-daily TIO and was assumed to last 52 weeks following treatment initiation (maximum duration of UMEC/VI clinical trials).,Spanish utility values were derived from a published local observational study.,Unitary health care costs (€2015) were obtained from local sources.,A 3-year time horizon was selected, and 3% discount was applied to effects and costs.,Results were expressed as cost/quality-adjusted life years (QALYs).,Univariate and probabilistic sensitivity analysis (PSA) was performed.,UMEC/VI produced additional 0.03 QALY and €590 vs TIO, leading to an ICER of €21,475/QALY.,According to PSA, the probability of UMEC/VI being cost-effective was 80.3% at a willingness-to-pay of €30,000/QALY.,UMEC/VI could be considered as a cost-effective treatment alternative compared with TIO in symptomatic COPD patients from the Spanish NHS perspective.

Chronic obstructive pulmonary disease (COPD) exacerbations account for a substantial proportion of COPD-related costs.,To describe COPD exacerbation patterns and assess the association between exacerbation frequency and health care resource utilization (HCRU) and costs in patients with COPD in a Medicare population.,A retrospective cohort study utilizing data from a large US national health plan was conducted including patients with a COPD diagnosis during January 1, 2007 to December 31, 2012, aged 40-89 years and continuously enrolled in a Medicare Advantage Prescription Drug plan.,Exacerbation frequency, HCRU, and costs were assessed during a 24-month period following the first COPD diagnosis (follow-up period).,Four cohorts were created based on exacerbation frequency (zero, one, two, and ≥three).,HCRU and costs were compared among the four cohorts using chi-square tests and analysis of variance, respectively.,A trend analysis was performed to assess the association between exacerbation frequency and costs using generalized linear models.,Of the included 52,459 patients, 44.3% had at least one exacerbation; 26.3%, 9.5%, and 8.5% had one, two, and ≥three exacerbations in the 24-month follow-up period, respectively.,HCRU was significantly different among cohorts (all P<0.001).,In patients with zero, one, two, and ≥three exacerbations, the percentages of patients experiencing all-cause hospitalizations were 49.7%, 66.4%, 69.7%, and 77.8%, respectively, and those experiencing COPD-related hospitalizations were 0%, 40.4%, 48.1%, and 60.5%, respectively.,Mean all-cause total costs (medical and pharmacy) were more than twofold greater in patients with ≥three exacerbations compared to patients with zero exacerbations ($27,133 vs $56,033; P<0.001), whereas a greater than sevenfold difference was observed in mean COPD-related total costs ($1,605 vs $12,257; P<0.001).,COPD patients frequently experience exacerbations.,Increasing exacerbation frequency is associated with a multiplicative increase in all-cause and COPD-related costs.,This underscores the importance of identifying COPD patients at risk of having frequent exacerbations for appropriate disease management.

Quercetin is a plant flavonoid and has potent antioxidant and anti-inflammatory properties.,In a preclinical model of chronic obstructive pulmonary disease (COPD), quercetin reduced markers of both oxidative stress and lung inflammation and also reduced rhinovirus-induced progression of lung disease.,Although quercetin appears to be an attractive natural alternative to manage COPD, the safety of quercetin supplementation in this population is unknown.,We recruited COPD patients with mild-to-severe lung disease with FVE1 ranging between >35% and <80% and supplemented with either placebo or quercetin at 500, 1000 or 2000 mg/day in a dose-escalation manner.,The duration of quercetin supplementation was 1 week.,Patients had no study drug-related severe adverse events based on blood tests, which included both complete blood counts and evaluation of comprehensive metabolic panel.,One of the patients reported mild adverse events included gastro-oesophageal reflux disease, which was observed in both placebo and quercetin groups.,Quercetin was safely tolerated up to 2000 mg/day as assessed by lung function, blood profile and COPD assessment test questionnaire.,NCT01708278

FEV1 is universally used as a measure of severity in COPD.,Current thresholds are based on expert opinion and not on evidence.,We aimed to identify the best FEV1 (% predicted) and dyspnea (mMRC) thresholds to predict 5-yr survival in COPD patients.,We conducted a patient-based pooled analysis of eleven COPD Spanish cohorts (COCOMICS).,Survival analysis, ROC curves, and C-statistics were used to identify and compare the best FEV1 (%) and mMRC scale thresholds that predict 5-yr survival.,A total of 3,633 patients (93% men), totaling 15,878 person-yrs. were included, with a mean age 66.4±9.7, and predicted FEV1 of 53.8% (±19.4%).,Overall 975 (28.1%) patients died at 5 years.,The best thresholds that spirometrically split the COPD population were: mild ≥70%, moderate 56-69%, severe 36-55%, and very severe ≤35%.,Survival at 5 years was 0.89 for patients with FEV1≥70 vs.,0.46 in patients with FEV1 ≤35% (H.R: 6; 95% C.I.: 4.69-7.74).,The new classification predicts mortality significantly better than dyspnea (mMRC) or FEV1 GOLD and BODE cutoffs (all p<0.001).,Prognostic reliability is maintained at 1, 3, 5, and 10 years.,In younger patients, survival was similar for FEV1 (%) values between 70% and 100%, whereas in the elderly the relationship between FEV1 (%) and mortality was inversely linear.,The best thresholds for 5-yr survival were obtained stratifying FEV1 (%) by ≥70%, 56-69%, 36-55%, and ≤35%.,These cutoffs significantly better predict mortality than mMRC or FEV1 (%) GOLD and BODE cutoffs.

Cigarette smoking (CS), the main risk factor for COPD (chronic obstructive pulmonary disease) in developed countries, decreases alveolar macrophages (AM) clearance of both apoptotic cells and bacterial pathogens.,This global deficit of AM engulfment may explain why active smokers have worse outcomes of COPD exacerbations, episodes characterized by airway infection and inflammation that carry high morbidity and healthcare cost.,When administered as intravenous supplementation, the acute phase-reactant alpha-1 antitrypsin (A1AT) reduces the severity of COPD exacerbations in A1AT deficient (AATD) individuals and of bacterial pneumonia in murine models, but the effect of A1AT on AM scavenging functions has not been reported.,Apoptotic cell clearance (efferocytosis) was measured in human AM isolated from patients with COPD, in primary rat AM or differentiated monocytes exposed to CS ex vivo, and in AM recovered from mice exposed to CS.,A1AT (100 μg/mL, 16 h) significantly ameliorated efferocytosis (by ~50%) in AM of active smokers or AM exposed ex vivo to CS.,A1AT significantly improved AM global engulfment, including phagocytosis, even when cells were simultaneously challenged with apoptotic and Fc-coated (bacteria-like) targets.,The improved efferocytosis in A1AT-treated macrophages was associated with inhibition of tumor necrosis factor-α converting enzyme (TACE) activity, decreased mannose receptor shedding, and markedly increased abundance of efferocytosis receptors (mannose- and phosphatidyl serine receptors and the scavenger receptor B2) on AM plasma membrane.,Directed airway A1AT treatment (via inhalation of a nebulized solution) restored in situ airway AM efferocytosis after CS exposure in mice.,The amelioration of CS-exposed AM global engulfment may render A1AT as a potential therapy for COPD exacerbations.

An imbalance between proteolytic enzymes and their inhibitors is thought to be involved in the pathogenesis of chronic obstructive pulmonary disease.,Matrix metalloproteinase-1, also known as interstitial collagenase, has been implicated as a potentially important proteinase in the genesis of chronic obstructive pulmonary disease and, more specifically, emphysema.,We performed quantitative immunohistochemical assessment of matrix metalloproteinase-1 expression in the resected lung of 20 smokers/ex-smokers who had varying severity of airflow obstruction and emphysema and compared this with the lungs of 5 nonsmokers.,Emphysema was measured using a morphometric measure of the lungs’ surface area/volume ratio and with qualitative and quantitative computed tomography (CT) measures of emphysema.,There were significantly more matrix metalloproteinase-1-expressing alveolar macrophages and type II pneumocytes as well as a greater percentage of small airways that stained positively for matrix metalloproteinase-1 in the lungs of smokers than in those of nonsmokers (p < 0.0001, p < 0.0001, and p = 0.0003, respectively).,The extent of staining of type II pneumocytes and airways for matrix metalloproteinase-1 was significantly related to the extent of smoking (p = 0.012 and p = 0.013, respectively).,In addition, the extent of matrix metalloproteinase-1 staining of alveolar macrophages was related to the lung surface area/volume ratio and to qualitative estimates of emphysema on CT.,These findings suggest that cigarette smoking increases expression of matrix metalloproteinase-1 in alveolar macrophages as well as in alveolar and small airway epithelial cells.,Smokers who develop emphysema have increased alveolar macrophage expression of matrix metalloproteinase-1.,The online version of this article (doi:10.1007/s00408-014-9585-6) contains supplementary material, which is available to authorized users.

The anti-oxidant and anti-inflammatory actions of phytochemicals and the smooth muscle relaxant actions of theophylline present in tea may confer pulmonary protection and reduce COPD risk.,We investigated tea consumption (black, oolong, or green) association with COPD risks in a population-based cohort study of older adults aged ≥55.,GOLD criteria was used to identify prevalent and incident cases of COPD (FEV1/FVC <0.70) among 4617 participants and 920 participants free of COPD at baseline who were assessed at follow-up 4.5 years later.,Prevalent cases of COPD consumed less tea than their non-COPD counterparts.,Estimated odds ratio (OR) and 95% confidence intervals (95% CI) of association with prevalent COPD, adjusted for age, sex, ethnicity, housing type, smoking, alcohol, physical activity and BMI declined across tea consumption levels (p-trend=0.048), and was lowest for ≥3 cups/day (OR=0.77, 95% CI=0.61-0.96).,The cumulated incidence of COPD declined across tea consumption categories (p-trend=0.012) and the lowest OR of association (OR=0.35, 95% CI=0.17-0.69) with consuming ≥3 cups/day after co-variate adjustment.,Different kinds of tea showed similar non-significant trends of associations but appeared to be strongest for green tea.,Tea consumption in this Asian population was associated with lowered COPD prevalence and incidence.

Object.,Results on the associations of fruit and vegetable intake with risk of chronic obstructive pulmonary disease (COPD) are still in conflict.,Hence, we conducted a meta-analysis to quantitatively evaluate the association between fruit and vegetable intake and the risk of COPD.,PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) were searched for relevant studies published up to September 2019.,Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated with the random effects model (REM).,Dose-response relationship was assessed by the restricted cubic spline model.,There are 8 studies involving 5,787 COPD cases among 244,154 participants included in this meta-analysis.,For the highest versus the lowest level, the pooled RR of COPD was 0.75 (95% CI, 0.68-0.84; I2 = 46.7%) for fruits plus vegetables, 0.72 (95% CI, 0.66-0.79; I2 = 46.7%) for fruits plus vegetables, 0.72 (95% CI, 0.66-0.79; I2 = 46.7%) for fruits plus vegetables, 0.72 (95% CI, 0.66-0.79; Pnon−linearity < 0.01).,This meta-analysis indicates that fruit and vegetable intake might be related to a lower risk of COPD.

COPD patients are burdened with a daily risk of acute exacerbation and loss of control, which could be mitigated by effective, on-demand decision support tools.,In this study, we present a machine learning-based strategy for early detection of exacerbations and subsequent triage.,Our application uses physician opinion in a statistically and clinically comprehensive set of patient cases to train a supervised prediction algorithm.,The accuracy of the model is assessed against a panel of physicians each triaging identical cases in a representative patient validation set.,Our results show that algorithm accuracy and safety indicators surpass all individual pulmonologists in both identifying exacerbations and predicting the consensus triage in a 101 case validation set.,The algorithm is also the top performer in sensitivity, specificity, and ppv when predicting a patient’s need for emergency care.

Moderate-intensity exercise training improves skeletal muscle aerobic capacity and increased oxidative enzyme activity, as well as exercise tolerance in COPD patients.,To investigate whether the home-based exercise training program can reduce inflammatory biomarkers in patients with COPD, twelve patients using mobile phone assistance and 14 with free walk were assessed by incremental shuttle walk test (ISWT), spirometry, strength of limb muscles, and serum C-reactive protein (CRP) and inflammatory cytokines.,Patients in the mobile phone group improved their ISWT walking distance, with decrease in serum CRP after 2 months, and sustained at 6 months.,Patients in the control group had no improvement.,Serum IL-8 in the mobile phone group was significantly reduced at 2, 3 and 6 months after doing home exercise training compared to baseline.,IL-6 and TNF-α were significantly elevated at 3 and 6 months in control group, while there were no changes in mobile phone group.,The strength of limb muscles was significantly greater compared to baseline at 3 and 6 months in the mobile phone group.,A mobile-phone-based system can provide an efficient home endurance exercise training program with improved exercise capacity, strength of limb muscles and a decrease in serum CRP and IL-8 in COPD patients.,Decreased systemic inflammation may contribute to these clinical benefits.,(Clinical trial registration No.: NCT01631019)

The global prevalence of physiologically defined chronic obstructive pulmonary disease (COPD) in adults aged >40 yr is approximately 9-10 per cent.,Recently, the Indian Study on Epidemiology of Asthma, Respiratory Symptoms and Chronic Bronchitis in Adults had shown that the overall prevalence of chronic bronchitis in adults >35 yr is 3.49 per cent.,The development of COPD is multifactorial and the risk factors of COPD include genetic and environmental factors.,Pathological changes in COPD are observed in central airways, small airways and alveolar space.,The proposed pathogenesis of COPD includes proteinase-antiproteinase hypothesis, immunological mechanisms, oxidant-antioxidant balance, systemic inflammation, apoptosis and ineffective repair.,Airflow limitation in COPD is defined as a postbronchodilator FEV1 (forced expiratory volume in 1 sec) to FVC (forced vital capacity) ratio <0.70.,COPD is characterized by an accelerated decline in FEV1.,Co morbidities associated with COPD are cardiovascular disorders (coronary artery disease and chronic heart failure), hypertension, metabolic diseases (diabetes mellitus, metabolic syndrome and obesity), bone disease (osteoporosis and osteopenia), stroke, lung cancer, cachexia, skeletal muscle weakness, anaemia, depression and cognitive decline.,The assessment of COPD is required to determine the severity of the disease, its impact on the health status and the risk of future events (e.g., exacerbations, hospital admissions or death) and this is essential to guide therapy.,COPD is treated with inhaled bronchodilators, inhaled corticosteroids, oral theophylline and oral phosphodiesterase-4 inhibitor.,Non pharmacological treatment of COPD includes smoking cessation, pulmonary rehabilitation and nutritional support.,Lung volume reduction surgery and lung transplantation are advised in selected severe patients.,Global strategy for the diagnosis, management and prevention of Chronic Obstructive Pulmonary Disease guidelines recommend influenza and pneumococcal vaccinations.

Pulmonary hypertension is a frequent complication of chronic obstructive pulmonary disease (COPD) and associated with a worse survival and increased risk of hospitalization for exacerbation of COPD.,However, little information exists regarding the potential role of systemic inflammation in pulmonary hypertension of COPD.,The purpose of the present study was to investigate the degree of C-reactive protein (CRP) and endothelin-1 (ET-1) levels in COPD patient with and without pulmonary hypertension.,The levels of CRP and ET-1 were investigated in 58 COPD patient with pulmonary hypertension and 50 patients without pulmonary hypertension.,Pulmonary hypertension was defined as a systolic pulmonary artery pressure (Ppa) ≥35 mmHg assessed by Doppler echocardiography.,Plasma CRP and ET-1 levels were significantly higher in patients with pulmonary hypertension than in patients without hypertension.,There were significant positive correlations between the plasma ET-1 level and CRP level in the whole study groups.,For COPD patients, systolic Ppa correlated significantly with plasma CRP levels and plasma ET-1 levels.,These findings support a possibility that CRP and ET-1 correlate to pulmonary hypertension in COPD patients.

When discontinuation in COPD randomized controlled trials (RCTs) is unevenly distributed between treatments (differential dropout), the capacity to demonstrate treatment effects may be reduced.,We investigated the impact of the time of differential dropout on exacerbation outcomes in RCTs, in relation to study duration and COPD severity.,A post hoc analysis of 2,345 patients from three RCTs of 6- and 12-month duration was performed to compare budesonide/formoterol and formoterol in moderate, severe, and very severe COPD.,Outcomes were exacerbation rate, time-to-first exacerbation, or discontinuation; patients were stratified by disease severity.,Outcomes were studied by censoring data monthly from 1 to 12 months.,In patients treated with budesonide/formoterol, annualized exacerbation rates (AERs) were comparable for each study duration (rate ratio [RR] =0.6).,With formoterol, the AER decreased with study duration (RR =1.20 at 1 month to RR =0.86 at 12 months).,There was a treatment-related difference in exacerbation rates of 45%-48% for shorter study durations (≤4 months) and 27% for 12-month duration.,This treatment-related difference in exacerbation rates was comparable for the three disease severities in studies ≤4 months (range: 39%-51%), but this difference decreased with longer study durations, especially in more severe groups (22% and 29% at 12 months).,There were fewer discontinuations with budesonide/formoterol; the treatment-related difference in time-to-first discontinuation decreased by study duration (35%, 30%, 26%, and 22% at 3, 6, 9, and 12 months, respectively).,Numbers of differential dropouts increased with increasing disease severity, being greatest during second, third, and fourth months.,COPD severity and study duration impact exacerbation as an outcome in double-blind RCTs.,This effect is most obvious in patients with severe/very severe COPD and in studies that are longer than 4 months.,Early differential dropout particularly impacts study outcome, producing a “healthy survivor effect,” which reduces estimations of treatment impact on exacerbations.

Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease characterized by nonreversible airway obstruction.,Well-characterized symptoms such as exertional dyspnea and fatigue have a negative impact on patients’ quality of life (QoL) and restrict physical activity in daily life.,The impact of COPD symptoms on QoL is often underestimated; for example, 36% of patients who describe their symptoms as being mild-to-moderate also admit to being too breathless to leave the house.,Additionally, early morning and nighttime symptoms are a particular problem.,Methods are available to allow clinicians to accurately assess COPD symptoms, including patient questionnaires.,Integrated approaches to COPD management, particularly pulmonary rehabilitation, are effective strategies for addressing symptoms, improving exercise capacity and, potentially, also increasing physical activity.,Inhaled bronchodilators continue to be the mainstay of drug therapy in COPD, where options can be tailored to meet patients’ needs with careful selection of the inhaled medication and the device used for its delivery.,Overall, an integrated approach to disease management should be considered for improving QoL and subsequent patient outcomes in COPD.

Limited studies have examined red meat consumption in relation to risk of chronic obstructive pulmonary disease (COPD), and none have examined the impact of long-term diet on COPD risk.,We sought to investigate the association between long-term red meat consumption and risk of COPD.,The population-based prospective Swedish Mammography Cohort included 34,053 women, aged 48-83 years, followed for the current analyses from 2002 to 2014.,Unprocessed and processed red meat consumption was assessed with a self-administered questionnaire in 1987 and 1997.,Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).,Over a mean follow-up of 11.6 years (2002-2014; 393,831 person-years), 1488 COPD cases were ascertained via linkage to the Swedish health registers.,A positive association between long-term processed red meat (average from 1987 to 1997) and risk of COPD was observed.,In contrast, no association was observed with unprocessed red meat with corresponding HRs of 1.36 (95% CI 1.03-1.79) for processed and 0.87 (95% CI 0.74-1.02) for unprocessed red meat among women who consumed ≥ 50 g/day compared to < 25 g/day.,The observed association with processed meat was confined to ex-smokers (P for interaction = 0.30); women consuming of ≥ 50 g/day of processed meat had a 2.3-fold (95% CI 1.24-4.12) higher risk of COPD than those consuming < 25 g/day.,No similar associations were observed among current or never smokers.,In this prospective cohort of women with moderate red meat consumption, long-term processed red meat consumption was associated with an increased risk of COPD particularly among ex-smokers.,The online version of this article (10.1007/s00394-018-1658-5) contains supplementary material, which is available to authorized users.

Lung cancer and chronic obstructive pulmonary disease have shared etiology, including key etiological changes (e.g., DNA damage and epigenetics change) and lung function impairment.,Focusing on those shared targets may help in the prevention of both.,Certain micronutrients (vitamins and minerals) and phytochemicals (carotenoids and phenols) have potent antioxidant or methyl-donating properties and thus have received considerable interest.,We reviewed recent papers probing into the potential of nutrients with respect to lung function preservation and prevention of lung cancer risk, and suggest several hypothetical intervention patterns.,Intakes of vitamins (i.e., A, C, D, E, B12), carotenoids, flavonoids, curcumins, resveratrol, magnesium, and omega-3 fatty acids all show protective effects against lung function loss, some mainly by improving average lung function and others through reducing decline rate.,Dietary interventions early in life may help lung function reserve over the lifespan.,Protective nutrient interventions among smokers are likely to mitigate the effects of cigarettes on lung health.,We also discuss their underlying mechanisms and some possible causes for the inconsistent results in observational studies and supplementation trials.,The role of the lung microbiome on lung health and its potential utility in identifying protective nutrients are discussed as well.,More prospective cohorts and well-designed clinical trials are needed to promote the transition of individualized nutrient interventions into health policy.

To systematically review clinical and biochemical characteristics associated with the severity of the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐related disease (COVID‐19).,Systematic review of observational studies from PubMed, ISI Web of Science, SCOPUS and Cochrane databases including people affected by COVID‐19 and reporting data according to the severity of the disease.,Data were combined with odds ratio (OR) and metanalysed.,Severe COVID‐19 was defined by acute respiratory distress syndrome, intensive care unit admission and death.,We included 12 studies with 2794 patients, of whom 596 (21.33%) had severe disease.,A slightly higher age was found in severe vs non‐severe disease.,We found that prevalent cerebrovascular disease (odds ratio [OR] 3.66, 95% confidence interval [CI] 1.73‐7.72), chronic obstructive pulmonary disease (OR: 2.39, 95% CI 1.10‐5.19), prevalent cardiovascular disease (OR: 2.84, 95% CI 1.59‐5.10), diabetes (OR: 2.78, 95% CI 2.09‐3.72), hypertension (OR: 2.24, 95% CI 1.63‐3.08), smoking (OR: 1.54, 95% CI 1.07‐2.22) and male sex (OR: 1.22, 95% CI 1.01‐1.49) were associated with severe disease.,Furthermore, increased procalcitonin (OR: 8.21, 95% CI 4.48‐15.07), increased D‐Dimer (OR: 5.67, 95% CI 1.45‐22.16) and thrombocytopenia (OR: 3.61, 95% CI 2.62‐4.97) predicted severe infection.,Characteristics associated with the severity of SARS‐CoV‐2 infection may allow an early identification and management of patients with poor outcomes.

Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020.,No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers.,We systematically searched electronic databases from inception to March 24, 2020.,Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.,Study quality was assessed using a modified version of the Newcastle-Ottawa Scale.,We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI).,In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed.,A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients.,All studies were included in the meta-analysis.,The crude case fatality rate of COVID-19 was 7.4%.,The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively.,COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)].,This was associated with higher mortality (60%).,Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications.,The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers.,Current smokers also had a higher mortality rate of 38.5%.,Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD.,Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate.,Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers.

Lung hyperinflation and exercise intolerance are hallmarks of chronic obstructive pulmonary disease (COPD).,However, their relationship remains uncertain.,A combined analysis of two placebo-controlled, randomized studies examined the effects of the long-acting muscarinic antagonist umeclidinium (UMEC) and long-acting β2-agonist vilanterol (VI) separately and in combination on static hyperinflation, exercise endurance time (EET), and their relationship in patients with COPD.,Patients with moderate-to-severe stable COPD and resting functional residual capacity >120% predicted were randomized to UMEC/VI 62.5/25 μg, UMEC 62.5 μg, VI 25 μg, or placebo for 12 weeks.,Inspiratory capacity (IC), residual volume (RV), total lung capacity (TLC), and EET in an endurance shuttle-walk test were measured.,In this post hoc analysis, IC/TLC, RV/TLC, and IC were used as hyperinflation markers.,After 12 weeks, UMEC/VI and UMEC and VI showed significant improvements in hyperinflation versus placebo when measured by absolute change from baseline in IC/TLC (trough and 3 hours postdose [P≤0.011]).,UMEC/VI showed significant improvements versus UMEC and VI in absolute changes in IC/TLC (trough and 3 hours postdose [P≤0.001]).,Statistical significance for comparisons with placebo and between treatments for absolute changes in IC and percentage changes in RV/TLC followed similar patterns to those for absolute changes in IC/TLC.,UMEC/VI showed significant improvements in EET versus placebo at day 2 and week 12, measured as change from baseline in seconds (P≤0.002) and as a percentage from baseline (P≤0.005).,There was a lack of evidence to suggest a correlation between improvements in static hyperinflation and EET at any time point.,Although the dual bronchodilator UMEC/VI demonstrated greater improvements in static hyperinflation markers than UMEC or VI and significant improvements in exercise endurance, no direct relationship was observed between static hyperinflation and exercise endurance.

Tiotropium-olodaterol, formulated in the Respimat soft-mist inhaler, is an inhaled fixed-dose combination (FDC) of a long-acting muscarinic antagonist (LAMA) and a long-acting β2-agonist (LABA), commercialized under the name of Spiolto or Stiolto.,The efficacy of tiotropium-olodaterol 5-5 μg once daily in adult patients with COPD was documented in eleven large, multicenter trials of up to 52 weeks duration.,Tiotropium-olodaterol 5-5 μg not only improved spirometric values to a significantly greater extent than placebo but also resulted in statistically significant beneficial effects on dyspnea, markers of hyperinflation, use of rescue medication, health-related quality of life, and exercise endurance.,Improvements exceeded the minimal clinically important difference (MCID) for forced expiratory volume in 1 second (FEV1), dyspnea, and quality of life.,Differences between tiotropium-olodaterol 5-5 μg and the respective monocomponents were statistically significant for FEV1, dyspnea, markers of hyperinflation, use of rescue medication, and health-related quality of life, but did not reach the MCID.,However, dual bronchodilatation significantly increased the number of patients who exceeded the MCID for dyspnea and quality of life.,Moreover, tiotropium-olodaterol 5-5 μg was significantly more effective than salmeterol-fluticasone (FDC) twice daily at improving pulmonary function.,Differences between tiotropium-olodaterol and other LAMA/LABA FDCs were not observed for FEV1 or other efficacy markers.,Therefore, tiotropium-olodaterol is a valuable option in the treatment of COPD patients who remain symptomatic under monotherapy.

COPD exacerbation is characterized by worsening of symptoms, warranting change in treatment.,Systemic and airway inflammation play roles in the pathogenesis of COPD exacerbation.,We hypothesized whether increased serum inflammatory biomarkers are associated with the clinical outcomes of COPD exacerbation caused by different infectious pathogens.,COPD patients with exacerbation were recruited from a hospital emergency department during 2014-2015.,Serum procalcitonin (PCT) and C-reactive protein (CRP) were measured.,Dyspnea, eosinopenia, consolidation, acidemia, and atrial fibrillation (DECAF) score was calculated for predicting mortality.,Multiplex polymerase chain reaction was carried out for respiratory viral assay from nasopharyngeal swabs, and sputum bacterial culture was also performed.,Hospital mortality, invasive mechanical ventilation requirement, and length of hospital stay (LOS) were evaluated, and their associations with clinical characteristics, DECAF score, and serum biomarkers were examined.,A total of 62 COPD patients were enrolled.,These patients were classified as Global Initiative for Obstructive Lung Disease (GOLD) stage 2, 3, and 4 in 12.9%, 6.4%, and 80.7% of cases, respectively.,Isolated bacterial exacerbation was recovered in 30.6% of exacerbation episodes: Klebsiella pneumoniae was the most commonly identified bacteria.,Viral pathogens and coinfections were noted in 9.6% and 16.1% of exacerbated patients, respectively.,Influenza was the most commonly detected viral pathogen.,Serum biomarkers and DECAF score for viruses, bacteria, coinfection, and noninfectious causes of exacerbations were similar.,Neither DECAF score nor serum biomarkers were able to differentiate patients with and without mortality or requiring mechanical ventilation.,Increased serum PCT was noted in patients with LOS ≥7 days when compared with those with LOS <7 days (0.38 ng/mL vs 0.1 ng/mL; P=0.035).,Increased serum PCT is associated with longer LOS in COPD exacerbation.,However, CRP and DECAF score play limited roles in predicting clinical outcome and lack an association with causes of exacerbation.

Exacerbations of COPD are frequent and commonly triggered by respiratory tract infections.,The purpose of our study was to investigate innate immunity in stable COPD patients.,Induced sputum was collected from 51 stable consecutive COPD patients recruited from the COPD Clinic of CHU Liege and 35 healthy subjects.,Expression of interferons beta (IFN-β) and lambda1 (IL-29), IFN-stimulated genes (ISGs) MxA, OAS, and viperin were measured in total sputum cells by reverse transcription quantitative polymerase chain reaction (RT-qPCR).,The presence of Picornaviruses was assessed by RT-PCR, while potential pathogenic microorganisms (PPM) were identified by sputum bacteriology.,Expression of IL-29 was found in 16 of 51 COPD patients (31%) and in nine of 35 healthy subjects (26%), while IFN-β was detected in six of 51 COPD patients (12%) and in two of 35 healthy subjects (6%).,ISGs were easily detectable in both groups.,In the whole group of COPD patients, OAS expression was decreased (P<0.05), while that of viperin was increased (P<0.01) compared to healthy subjects.,No difference was found with respect to MxA.,COPD patients from group D of Global Initiative for Chronic Obstructive Lung Disease (GOLD) had reduced expression of all three ISGs (P<0.01 for MxA, P<0.05 for OAS, and P<0.01 for viperin) as compared to those of group B patients.,Picornaviruses were detected in eight of 51 (16%) COPD patients vs four of 33 (12%) healthy subjects, while PPM were detected in seven of 39 (18%) COPD patients and associated with raised sputum neutrophil counts.,IFN-β expression was raised when either picornavirus or PPM were detected (P=0.06), but no difference was seen regarding IL-29 or ISGs.,ISGs expression was reduced in severe COPD that may favor exacerbation and contribute to disease progress by altering response to infection.

The ratio of neutrophils to lymphocytes (NLR) is a widely available marker of inflammation.,Several types of inflammatory cells and mediators have been found to be involved in the progression of chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association of the NLR with severity of airflow limitation and disease exacerbations in a COPD population.,We analyzed 885 patients from the Korean COPD Subtype Study cohort that recruited subjects with COPD from 44 referral hospitals.,We determined the relationship of NLR levels to severity of lung function using a linear regression model.,In addition, we analyzed the experiences of COPD exacerbation according to the NLR quartiles.,NLR levels were inversely associated with severity of airflow limitation as measured by FEV1% predicted and absolute values after adjustments for age, gender, body mass index, pack-years of smoking, and the use of inhaled corticosteroid (P<0.001, respectively).,In the multivariate binary regression model, the NLR 4th quartile (vs. 1st quartile) was found to be a significant predictor of exacerbations during 1-year follow-up (OR = 2.05, 95% CI = 1.03 to 4.06, P = 0.041).,Adding an NLR to FEV1 significantly improved prediction for exacerbations during 1-year follow-up as measured by the net reclassification improvement (NRI = 7.8%, P = 0.032) and the integrated discrimination improvement (IDI = 0.014, P = 0.021).,The NLR showed a significant inverse relationship to airflow limitation and was a prognostic marker for future exacerbations in patients with COPD.

We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.,Three studies of ≥1-year duration met the inclusion criteria.,Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%).,At baseline, 57-75% of patients had ≥2% blood eosinophils.,Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.,For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001).,No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively).,In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo).,No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.,Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations.

Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns.,The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large‐scale ‘omics’ and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years.,The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms.,A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS.,Recruitment to the national, multicentre study has recently started.

The relationship between patient-reported symptoms and objective measures of lung function is poorly understood.,To determine the association between responsiveness to bronchodilator and respiratory symptoms in random population samples.,4669 people aged 40 years and older from 8 sites in Canada completed interviewer-administered respiratory questionnaires and performed spirometry before and after administration of 200 ug of inhaled salbutamol.,The effect of anthropometric variables, smoking exposure and doctor-diagnosed asthma (DDA) on bronchodilator responsiveness in forced expiratory volume in 1 second (FEV1) and in forced vital capacity (FVC) were evaluated.,Multiple logistic regression was used to test for association between quintiles of increasing changes in FEV1 and in FVC after bronchodilator and several respiratory symptoms.,Determinants of bronchodilator change in FEV1 and FVC included age, DDA, smoking, respiratory drug use and female gender [p<0.005 to p<0.0001 ].,In subjects without doctor-diagnosed asthma or COPD, bronchodilator response in FEV1 was associated with wheezing [p for trend<0.0001], while bronchodilator response for FVC was associated with breathlessness. [p for trend <0.0001].,Bronchodilator responsiveness in FEV1 or FVC are associated with different respiratory symptoms in the community.,Both flow and volume bronchodilator responses are useful parameters which together can be predictive of both wheezing and breathlessness in the general population.

CHF6001 is a novel inhaled phosphodiesterase-4 inhibitor.,This Phase IIa study assessed the effects of CHF6001 on markers of inflammation in induced sputum and blood in patients with chronic obstructive pulmonary disease (COPD).,This was a multicentre, three-period (each 32 days), three-way, placebo-controlled, double-blind, complete-block crossover study.,Eligible patients had COPD, chronic bronchitis, and were receiving inhaled triple therapy for ≥2 months.,Patients received CHF6001 800 or 1600 μg, or matching placebo twice daily via multi-dose dry-powder inhaler (NEXThaler).,Induced sputum was collected pre-dose on Day 1, and post-dose on Days 20, 26 and 32.,Blood was sampled pre-dose on Day 1, and pre- and post-dose on Day 32.,Of 61 randomised patients, 54 (88.5%) completed the study.,There were no significant differences between groups for overall sputum cell count, or absolute numbers of neutrophils, eosinophils or lymphocytes.,CHF6001 800 μg significantly decreased the absolute number and percentage of macrophages vs placebo.,In sputum, compared with placebo both CHF6001 doses significantly decreased leukotriene B4, C-X-C motif chemokine ligand 8, macrophage inflammatory protein 1β, matrix metalloproteinase 9, and tumour necrosis factor α (TNFα).,In blood, both CHF6001 doses significantly decreased serum surfactant protein D vs placebo.,CHF6001 1600 μg significantly decreased TNFα ex-vivo (after incubation with lipopolysaccharide).,The data from this study show that CHF6001 inhaled twice daily has anti-inflammatory effects in the lungs of patients with COPD already treated with triple inhaled therapy.,The study is registered on ClinicalTrials.gov (NCT03004417).,The online version of this article (10.1186/s12931-019-1142-7) contains supplementary material, which is available to authorized users.

DINO and DACOTA were prospective, noninterventional studies assessing the health status and quality of life of patients with COPD newly treated with roflumilast 500 μg once-daily add-on therapy.,Patients were evaluated over 6 months.,Clinical COPD questionnaire (CCQ) and COPD assessment test (CAT) scores were recorded at baseline and after 3 and 6 months.,In DACOTA, post-bronchodilator FEV1 was recorded at each time point.,Of 5,462 and 3,645 patients recruited into DINO and DACOTA, respectively, 3,274 patients in DINO and 916 patients in DACOTA completed the 6-month visit.,Almost all patients had severe or very severe airway obstruction; mean baseline CCQ total score was 3.9 in DINO and 3.7 in DACOTA.,Overall, 33.8% of patients in DACOTA and 30.6% in DINO discontinued treatment prematurely.,Significant and clinically relevant improvements in CCQ total scores were observed in both studies (mean change from baseline of 1.36 in DINO and 0.91 in DACOTA at Month 6 [all P<0.001]).,Changes in CAT total score from baseline to Month 6 indicated that the average clinical impact of COPD was reduced from a severe (score: 21-30) to a moderate (score: 11-20) impairment.,In DACOTA, mean change in post-bronchodilator FEV1 was 202 mL (P<0.001).,Diarrhea, nausea, and weight decrease were the most frequently reported adverse drug reactions.,In real-life clinical practice, roflumilast treatment as an add-on therapy is associated with clinically relevant improvements in health status and quality of life.

To obtain evidence whether the online pulmonary rehabilitation(PR) programme ‘my-PR’ is non-inferior to a conventional face-to-face PR in improving physical performance and symptom scores in patients with COPD.,A two-arm parallel single-blind, randomised controlled trial.,The online arm carried out pulmonary rehabilitation in their own homes and the face to face arm in a local rehabilitation facility.,90 patients with a diagnosis of chronic obstructive pulmonary disease (COPD), modified Medical Research Council score of 2 or greater referred for pulmonary rehabilitation (PR), randomised in a 2:1 ratio to online (n=64) or face-to-face PR (n=26).,Participants unable to use an internet-enabled device at home were excluded.,Coprimary outcomes were 6 min walk distance test and the COPD assessment test (CAT) score at completion of the programme.,A 6-week PR programme organised either as group sessions in a local rehabilitation facility, or online PR via log in and access to 'myPR’.,The adjusted mean difference for the 6 min walk test (6MWT) between groups for the intention-to-treat (ITT) population was 23.8 m with the lower 95% CI well above the non-inferiority threshold of −40.5 m at −4.5 m with an upper 95% CI of +52.2 m.,This result was consistent in the per-protocol (PP) population with a mean adjusted difference of 15 m (−13.7 to 43.8).,The CAT score difference in the ITT was −1.0 in favour of the online intervention with the upper 95% CI well below the non-inferiority threshold of 1.8 at 0.86 and the lower 95% CI of −2.9.,The PP analysis was consistent with the ITT.,PR is an evidenced-based and guideline-mandated intervention for patients with COPD with functional limitation.,A 6-week programme of online-supported PR was non-inferior to a conventional model delivered in face-to-face sessions in terms of effects on 6MWT distance, and symptom scores and was safe and well tolerated.

Chronic obstructive pulmonary disease (COPD) is an obstructive and progressive airway disease associated with an important reduction in daily physical activity and psychological problems that contribute to the patient’s disability and poor health-related quality of life (HRQoL).,Nowadays, pulmonary rehabilitation (PR) plays an essential role in the management of symptomatic patients with COPD, by breaking the vicious circle of dyspnea-decreased activity-deconditioning-isolation.,Indeed the main benefits of comprehensive PR programs for patients with COPD include a decrease in symptoms (dyspnea and fatigue), improvements in exercise tolerance and HRQoL, reduction of health care utilization (particularly bed-days), as well as an increase in physical activity.,Several randomized studies and meta-analyses greatly established the benefits of PR, which additionally, is recommended in a number of influential guidelines.,This review aimed to highlight the impact of PR on COPD patients, focusing on the clinical usefulness of PR, which provides patients a good support for change.

This nationwide study was performed to evaluate the evolution of distributions of patients with COPD according to the 2011 and 2017 Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines and to assess the concordance between the prescribed medications and the pharmacological management recommended by the two distinct classification systems in Taiwan.,Data were retrospectively retrieved from stable COPD patients in 11 participating hospitals across Taiwan.,Patients were grouped according to GOLD 2011 and 2017 guidelines respectively.,Definitions of undertreatment and overtreatment were based on the pharmacological recommendations in the individual guidelines.,A total of 1,053 COPD patients were included.,The percentages of patients in GOLD 2011 groups A, B, C and D were 18.4%, 40.6%, 6.7% and 34.2%, respectively.,When reclassified according to the GOLD 2017, the percentages of group A and B increased to 23.3% and 63.2%, and groups C and D decreased to 1.9% and 11.6%, respectively.,Up to 67% of patients in GOLD 2011 groups C and D were reclassified to GOLD 2017 groups A and B.,The pharmacological concordance rate was 60.9% for GOLD 2011 and decreased to 44.9% for GOLD 2017.,Overtreatment was found in 29.5% of patients according to GOLD 2011 and the rate increased to 46.1% when classified by the GOLD 2017.,The major cause of overtreatment was unnecessary inhaled corticosteroids and the main cause of undertreatment was a lack of maintenance long-acting bronchodilators.,The distribution of COPD patients in Taiwan was more uneven with the GOLD 2017 than with the GOLD 2011.,A pharmacological discordance to the guidelines was identified.,Updated guidelines with reclassification of COPD patients resulted in more discordance between prescribed medications and the guidelines.,Physicians should make proper adjustments of the prescriptions according to the updated guidelines to ensure the mostly appropriate treatment for COPD patients.

As part of the Respiratory Disease Specific Program (DSP) conducted to provide observations of clinical practice from a physician and matched patient viewpoint, this study aimed to establish how patients with COPD are treated according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification system and to quantify the symptom burden.,Data were obtained from the Respiratory DSP, a cross-sectional survey of patients with a diagnosis of COPD consulting for routine care in France, Germany, Italy, Spain, the UK, and the USA during the third quarter of 2013.,Patients’ exacerbation risk and symptom data were used for classification into GOLD groups A−D based on GOLD 2014 criteria.,Prescribing practices were stratified by physician type and time since patient diagnosis.,A total of 903 physicians participated in the Respiratory DSP, with data from 1,641 patients included in this analysis.,Most patients were classified into GOLD groups B (n=742; 45.2%) and D (n=704; 42.9%).,Patients in groups A and D were most likely to be treated in line with GOLD recommendations (61.5% and 77.5%, respectively), compared with 40.1% for group B.,Patients with a diagnosis within the past 12 months were more likely to be treated according to recommendations.,Inhaled corticosteroids (ICSs) in combination with one or more long-acting bronchodilator were prescribed across all GOLD groups.,Patterns of treatment were, in general, similar for patients treated by a primary care physician or a pulmonologist.,COPD assessment test scores ≥10 indicating a high symptom burden were reported for >80% of patients.,This analysis confirmed a high symptom burden among patients with COPD and indicates some misalignment of prescribing with GOLD recommendations, particularly regarding the role of ICS/long-acting β2-agonist (LABA) and ICS/LABA + long-acting muscarinic antagonist combinations across the different GOLD groups.

Few studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related.,This observational study assessed the prevalence, severity and relationship between night-time, early morning and daytime COPD symptoms and explored the relationship between 24-hour symptoms and other patient-reported outcomes.,The study enrolled patients with stable COPD in clinical practice.,Baseline night-time, early morning and daytime symptoms (symptom questionnaire), severity of airflow obstruction (FEV1), dyspnoea (modified Medical Research Council Dyspnoea Scale), health status (COPD Assessment Test), anxiety and depression levels (Hospital Anxiety and Depression Scale), sleep quality (COPD and Asthma Sleep Impact Scale) and physical activity level (sedentary, moderately active or active) were recorded.,The full analysis set included 727 patients: 65.8% male, mean ± standard deviation age 67.2 ± 8.8 years, % predicted FEV1 52.8 ± 20.5%.,In each part of the 24-hour day, >60% of patients reported experiencing ≥1 symptom in the week before baseline.,Symptoms were more common in the early morning and daytime versus night-time (81.4%, 82.7% and 63.0%, respectively).,Symptom severity was comparable for each period assessed.,Overall, in the week before baseline, 56.7% of patients had symptoms throughout the whole 24-hour day (3 parts of the day); 79.9% had symptoms in ≥2 parts of the 24-hour day.,Symptoms during each part of the day were inter-related, irrespective of disease severity (all p < 0.001).,Early morning and daytime symptoms were associated with the severity of airflow obstruction (p < 0.05 for both).,Night-time, early morning and daytime symptoms were all associated with worse dyspnoea, health status and sleep quality, and higher anxiety and depression levels (all p < 0.001 versus patients without symptoms in each corresponding period).,In each part of the 24-hour day, there was also an association between symptoms and a patient’s physical activity level (p < 0.05 for each period).,More than half of patients experienced COPD symptoms throughout the whole 24-hour day.,There was a significant relationship between night-time, early morning and daytime symptoms.,In each period, symptoms were associated with worse patient-reported outcomes, suggesting that improving 24-hour symptoms should be an important consideration in the management of COPD.,The online version of this article (doi:10.1186/s12931-014-0122-1) contains supplementary material, which is available to authorized users.

This randomized, double-blind, Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).,Methods: Patients received aclidinium 400 μg twice daily (morning and evening), tiotropium 18 μg once daily (morning), or placebo for 6 weeks.,The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose (FEV1 AUC0-24) at week 6.,Secondary and additional endpoints included FEV1 AUC12-24, COPD symptoms (EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [E-RS] total score and additional symptoms questionnaire), and safety.,Results: Overall, 414 patients were randomized and treated (FEV1 1.63 L [55.8% predicted]).,Compared with placebo, FEV1 AUC0-24 and FEV1 AUC12-24 were significantly increased from baseline with aclidinium (Δ = 150 mL and 160 mL, respectively; p < 0.0001) and tiotropium (Δ = 140 mL and 123 mL, respectively; p < 0.0001) at week 6.,Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium (p < 0.0001) than tiotropium (p < 0.05) versus placebo.,Only aclidinium significantly reduced the severity of early-morning cough, wheeze, shortness of breath, and phlegm, and of nighttime symptoms versus placebo (p < 0.05).,Adverse-event (AE) incidence (28%) was similar between treatments.,Few anticholinergic AEs (<1.5%) or serious AEs (<3%) occurred in any group.,Conclusions: Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks.,Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium.,Aclidinium was generally well tolerated.

Observational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS)-containing medications in patients with chronic obstructive pulmonary disease (COPD).,New-user observational cohort designs may minimize biases associated with previous case-control designs.,To estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy.,Pneumonia events in COPD patients ≥45 years old were compared among new users of ICS medications (n = 11,555; ICS, ICS/long-acting β2-agonist [LABA] combination) and inhaled LABD monotherapies (n = 6,492; LABA, long-acting muscarinic antagonists) using Cox proportional hazards models, with propensity scores to adjust for confounding.,Setting: United Kingdom electronic medical records with linked hospitalization and mortality data (2002-2010).,New users were censored at earliest of: pneumonia event, death, changing/discontinuing treatment, or end of follow-up.,Outcomes: severe pneumonia (primary) and any pneumonia (secondary).,Following adjustment, new use of ICS-containing medications was associated with an increased risk of pneumonia hospitalization (n = 322 events; HR = 1.55, 95% CI: 1.14, 2.10) and any pneumonia (n = 702 events; HR = 1.49, 95% CI: 1.22, 1.83).,Crude incidence rates of any pneumonia were 48.7 and 30.9 per 1000 person years among the ICS-containing and LABD cohorts, respectively.,Excess risk of pneumonia with ICS was reduced when requiring ≥1 month or ≥ 6 months of new use.,There was an apparent dose-related effect, with greater risk at higher daily doses of ICS.,There was evidence of channeling bias, with more severe patients prescribed ICS, for which the analysis may not have completely adjusted.,The results of this new-user cohort study are consistent with published findings; ICS were associated with a 20-50% increased risk of pneumonia in COPD, which reduced with exposure time.,This risk must be weighed against the benefits when prescribing ICS to patients with COPD.

The coexistence of COPD and asthma is widely recognized but has not been well described.,This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma.,We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study.,119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma.,These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001).,More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001).,Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001).,Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT.,There were no differences in spirometry or CT measurements of emphysema or airway wall thickness.,Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life.,They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history.,ClinicalTrials.gov: NCT00608764

The long-acting muscarinic antagonists umeclidinium (UMEC) and tiotropium (TIO) are approved once-daily maintenance therapies for COPD.,This study investigated the efficacy and safety of UMEC versus TIO in COPD.,This was a 12-week, multicenter, randomized, blinded, double-dummy, parallel-group, non-inferiority study.,Patients were randomized 1:1 to UMEC 62.5 μg plus placebo or TIO 18 μg plus placebo.,The primary end point was trough forced expiratory volume in 1 second (FEV1) at day 85 (non-inferiority margin −50 mL; per-protocol [PP] population).,Other end points included weighted mean FEV1 over 0-24 and 12-24 hours post-dose.,Patient-reported outcomes comprised Transition Dyspnea Index score, St George’s Respiratory Questionnaire total score, and COPD Assessment Test score.,Adverse events were also assessed.,In total, 1,017 patients were randomized to treatment.,In the PP population, 489 and 487 patients received UMEC and TIO, respectively.,In the PP population, change from baseline in trough FEV1 was greater with UMEC versus TIO at day 85, meeting non-inferiority and superiority margins (difference: 59 mL; 95% confidence interval [CI]: 29-88; P<0.001).,Similar results were observed in the intent-to-treat analysis of trough FEV1 at day 85 (53 mL, 95% CI: 25-81; P<0.001).,Improvements in weighted mean FEV1 over 0-24 hours post-dose at day 84 were similar with UMEC and TIO but significantly greater with UMEC versus TIO over 12-24 hours post-dose (70 mL; P=0.015).,Clinically meaningful improvements in Transition Dyspnea Index and St George’s Respiratory Questionnaire were observed with both treatments at all time points.,No differences were observed between UMEC and TIO in patient-reported outcomes.,Overall incidences of adverse events were similar for UMEC and TIO.,UMEC 62.5 μg demonstrated superior efficacy to TIO 18 μg on the primary end point of trough FEV1 at day 85.,Safety profiles were similar for both treatments.

Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations.,This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).,We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers.,In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.,COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function.,Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage.,The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study.,The distribution of these variables within each GOLD stage was wide.,Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation.,The amount of emphysema increased with GOLD severity.,The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage.,Some gender differences were also identified.,The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease.

Necroptosis has emerged as a potential mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Here, we found that markers of necroptosis, including high mobility group box 1 release and phosphorylation of mixed lineage kinase domain-like protein (p-MLKL), were markedly induced in the late stage of cigarette smoking-induced (CS-induced) emphysema in mouse lung tissue as well as in lung epithelial cells and organoids with higher dosage of or more prolonged exposure to cigarette smoking extract (CSE).,Apoptotic signals were also detected and maximally induced in the early stage of CS-exposed mice and CSE-treated epithelial cells.,Inhibition of apoptosis by Z-VAD, a pan-caspase inhibitor, switched the cellular stress to enhanced necroptosis in lung epithelial cells and organoids treated with CSE.,Depletion or inhibition of receptor-interacting protein kinase 3 (RIP3) or MLKL attenuated the CSE-induced cell death, suggesting that necroptosis contributes to CSE-induced cell death.,Silencing or inhibition of RIP1 had no protective effect, indicating a RIP1-independent RIP3 activation pathway.,CSE-induced necroptosis released more damage-associated molecular patterns and evoked greater engulfment but slower clearance by bone marrow-derived macrophages, leading to enhanced expression of proinflammatory cytokines Tnfα and Il6.,Finally, our in vivo data verified that inhibition of necroptosis by RIP3 inhibitor GSK’872 protected mice from CS-induced emphysema and suppressed the lung inflammation.,In conclusion, we provide evidence that necroptosis contributes to the pathogenesis of COPD.,Targeting RIP3 and its downstream pathway may be an effective therapy for COPD.

Current drug therapy fails to reduce lung destruction of chronic obstructive pulmonary disease (COPD).,AMP-activated protein kinase (AMPK) has emerged as an important integrator of signals that control energy balance and lipid metabolism.,However, there are no studies regarding the role of AMPK in reducing inflammatory responses and cellular senescence during the development of emphysema.,Therefore, we hypothesize that AMPK reduces inflammatroy responses, senescence, and lung injury.,To test this hypothesis, human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (SAECs) were treated with cigarette smoke extract (CSE) in the presence of a specific AMPK activator (AICAR, 1 mM) and inhibitor (Compound C, 5 μM).,Elastase injection was performed to induce mouse emphysema, and these mice were treated with a specific AMPK activator metformin as well as Compound C.,AICAR reduced, whereas Compound C increased CSE-induced increase in IL-8 and IL-6 release and expression of genes involved in cellular senescence.,Knockdown of AMPKα1/α2 increased expression of pro-senescent genes (e.g., p16, p21, and p66shc) in BEAS-2B cells.,Prophylactic administration of an AMPK activator metformin (50 and 250 mg/kg) reduced while Compound C (4 and 20 mg/kg) aggravated elastase-induced airspace enlargement, inflammatory responses and cellular senescence in mice.,This is in agreement with therapeutic effect of metformin (50 mg/kg) on airspace enlargement.,Furthermore, metformin prophylactically protected against but Compound C further reduced mitochondrial proteins SOD2 and SIRT3 in emphysematous lungs.,In conclusion, AMPK reduces abnormal inflammatory responses and cellular senescence, which implicates as a potential therapeutic target for COPD/emphysema.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide.,Few studies have focused on the quality of life (QoL) associated medical costs for COPD in China.,A cross-sectional survey of 678 COPD patients was conducted in four major cities (Beijing, Shanghai, Guangzhou and Chengdu), China, in 2011.,Data on socio-demographic information, health conditions and medical costs were collected through a face-to-face interview combined with medical record searching.,The EuroQol (EQ-5D) health questionnaire was applied to assess the QoL of COPD patients.,Among 678 patients with COPD, nearly 40% had difficulties in mobility, usual activities and pain/discomfort, one third had various degrees of anxiety/depression, and one fifth had difficulties in self-care.,The COPD patients had a median utility score of 0.768 and a median visual analog scale score of 70.,The degree of difficulties in any dimensions significantly increased, and utility and health scores decreased with severity of the disease.,Age, gender and disease severity were significantly associated with the quality of life after taking other covariates into consideration.,Poorer QoL was a significant indicator of higher direct medical costs for COPD patients.,Impaired quality of life was significantly linked to increased medical costs for COPD patients and could be an important measure for policy- and decision-making in COPD care.

Numerous instruments are available to measure health-related quality of life (HRQoL) in patients with Chronic Obstructive Pulmonary Disease (COPD), covering a wide array of domains ranging from symptoms such as dyspnea, cough and wheezing, to social and emotional functioning.,Currently no information or guide is available yet to aid the selection of domains for a particular study or disease population.,The aim of this paper is to identify which domains of HRQoL are most important with respect to COPD, from the patient perspective.,Twenty-one Dutch patients with COPD were asked to describe important domains impacted by COPD freely; second, they were presented with cues (domains from the Patient-Reported Outcomes Measurement Information System (PROMIS) framework) and were asked to select the domains that were most relevant to them.,During the interview, the patients were asked to indicate in which way the selected domains impact their lives.,Both the answers to the open question, and the patient statements motivating nomination of PROMIS domains were coded into themes.,The most relevant (sub)domains of HRQoL for patients with COPD were: physical health (fatigue, physical functioning), social health (instrumental support, ability to participate in social roles and activities, companionship, and emotional support), and coping with COPD.,We identified which domains of HRQoL are most important to patients with COPD.,One of these (coping with COPD) is not explicitly covered by PROMIS, or by traditional questionnaires that are used to measure HRQoL in COPD.

The World Health Organization has indicated that chronic obstructive pulmonary disease (COPD) may become the third leading cause of death by 2030.,Acute exacerbation of COPD (AECOPD) is an important process in clinical treatment.,Recent studies have shown that Chinese medical injections (CMI) are effective against AECOPD, but the effective difference among different CMIs remains unclear.,The aim of this network meta-analysis (NMA) is to compare the therapeutic effect of various CMIs.,We conducted an overall, systematic literature search in the China National Knowledge Infrastructure, Wanfang, VIP, SinoMed, PubMed, Embase, Cochrane Library, and Web of Science databases to retrieve randomized controlled trials (RCTs) of CMIs for AECOPD published up to January 2021.,The Cochrane risk of bias tool was used to assess the risk of bias.,Stata 13.1 and WinBUGS 14.3 were used for data analyses.,In total, 103 RCTs involving 8767 participants and 23 CMIs were included.,The results indicated that among all treatments conventional Western medical therapy (WM) plus Dengzhanxixin injection (DZXX) led to the best improvement in the clinical efficacy and the ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) (FEV1/FVC), with surface under the cumulative ranking curve (SUCRA)=80.47% and 98.55%, respectively.,Moreover, Shenmai injection (SM) plus WM and Reduning injection (RDN) plus WM led to the best improvement in the FEV1 (SUCRA=80.18%) and the ratio of forced expiratory volume in one second to the predicted value (FEV1%, SUCRA=87.28%).,Shengmai injection (SGM) plus WM led to the most considerable shortening in the length of hospital stay (SUCRA=94.70%).,Cluster analysis revealed that WM+DZXX had the most favorable response for clinical efficacy and FEV1, as well as clinical efficacy and FEV1/FVC, WM+RDN had the most favorable response for clinical efficacy and FEV1%, WM+SGM had the most favorable response for clinical efficacy and length of hospital stay.,WM+DZXX, WM+RDN, and WM+SGM were noted to be the optimum treatment regimens for improving in clinical efficacy, FEV1, FEV1/FVC, FEV1% and reducing the hospital stay length of AECOPD patients.,Considering the limitations this NMA may have, the current results warrant further verification via additional high-quality studies.

How to identify the optimum switch point of sequential invasive and noninvasive ventilation is the focus of clinical attention on the patients suffering from acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated by acute respiratory failure (ARF).,This study aims to explore the clinical significance of taking the change rate of procalcitonin (PCT) as identifying the timing of weaning on the mechanical ventilation for the patients of AECOPD followed by ARF as a complication.,There were altogether 140 patients of AECOPD complicated with ARF, who were randomly selected and divided into a study group and a control group respectively.,A change rate of serum PCT level exceeding 50% was taken as the switch point selection of tracheal intubation removal for the patients of the study group, while the ‘pulmonary infection control (PIC) window’ was done for those in the control group.,With CRP, IL-6, TNF-a, PaCO2, PaO2, and Lac having been detected before and after treatment to them all, clinical indexes were obtained and compared between these two groups.,The CRP, TNF-a, and IL-6 levels of the patients in the study group after treatment (p < 0.05) were lower than those in the control group.,There was no significant difference in PaCO2, PaO2, and Lac between these two groups before and after treatment (p > 0.05).,Even so, some other indexes available for the study group of patients were found to be lower than those for the control group (p < 0.05) in the following aspects: duration of invasive ventilation support, total time of mechanical ventilation support, incidence rate of ventilator-associated pneumonia, 48-hour reintubation rate, incidence rate of upper gastrointestinal bleeding, hospitalization time of critical respiratory illness, total hospitalization time, RICU treatment cost, total treatment cost, and mortality.,It is preferable to take the change rate of PCT level exceeding 50% as the switch point of weaning time in sequential mechanical ventilation rather than the PIC window.,Abbreviations,AECOPD: acute exacerbation of chronic obstructive pulmonary disease; ARF: acute respiratory failure; PCT: procalcitonin; PaO2: the oxygen partial pressure; PaCO2: the partial pressure of carbon dioxide; TNF-a: serum tumor necrosis factor-a; IL-6: interleukin-6; CRP: serum C-reactive protein; PIC window: pulmonary infection control window; RICU: respiration and intensive care unit

Randomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as β2-agonist (LABA)/muscarinic antagonist (LAMA), have favorable efficacy compared with commonly used COPD treatments.,The objective of this analysis was to compare the efficacy and safety of LABA/LAMA with LAMA or LABA/inhaled corticosteroid (ICS) in adults with stable moderate-to-very-severe COPD.,This systematic review and meta-analysis (PubMed/MEDLINE, Embase, Cochrane Library and clinical trial/manufacturer databases) included RCTs comparing ≥12 weeks’ LABA/LAMA treatment with LAMA and/or LABA/ICS (approved doses only).,Eligible studies were independently selected by two authors using predefined data fields; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.,Eighteen studies (23 trials) were eligible (N=20,185).,LABA/LAMA significantly improved trough forced expiratory volume in 1 second (FEV1) from baseline to week 12 versus both LAMA and LABA/ICS (0.07 L and 0.08 L, P<0.0001), with patients more likely to achieve clinically important improvements in FEV1 of >100 mL (risk ratio [RR]: 1.33, 95% confidence interval [CI]: [1.20, 1.46] and RR: 1.44, 95% CI: [1.33, 1.56], respectively, the number needed to treat being eight and six, respectively).,LABA/LAMA improved transitional dyspnea index and St George’s Respiratory Questionnaire scores at week 12 versus LAMA (both P<0.0001), but not versus LABA/ICS, and reduced rescue medication use versus both (P<0.0001 and P=0.001, respectively).,LABA/LAMA significantly reduced moderate/severe exacerbation rate compared with LABA/ICS (RR 0.82, 95% CI: [0.75, 0.91]).,Adverse event (AE) incidence was no different for LABA/LAMA versus LAMA treatment, but it was lower versus LABA/ICS (RR 0.94, 95% CI: [0.89, 0.99]), including a lower pneumonia risk (RR 0.59, 95% CI: [0.43, 0.81]).,LABA/LAMA presented a lower risk for withdrawals due to lack of efficacy versus LAMA (RR: 0.66, 95% CI: [0.51, 0.87]) and due to AEs versus LABA/ICS (RR: 0.83, 95% CI: [0.69, 0.99]).,The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD.,These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use.

Few studies have evaluated the associations between respiratory parameters and pain in chronic obstructive pulmonary disease (COPD).,The purpose of this study is to evaluate the differences in respiratory parameters between COPD patients who did and did not have pain.,In this cross-sectional study respiratory parameters were measured by spirometry and the St Georges Respiratory Questionnaire.,Patients responded to a single question that asked if they were generally bothered by pain.,Of the 100 patients, 45% reported that they were generally bothered by pain.,Patients who had pain reported a higher number of comorbidities (P < 0.001) and higher breathlessness scores (P = 0.003).,Physical dimensions of breathlessness were significantly associated with pain (P ≤ 0.03).,The results of logistic regression analysis determined that a higher number of comorbidities (OR = 0.28; P = 0.026) and higher breathlessness scores (OR = 1.03; P = 0.003) made significant unique contributions to the prediction of pain group membership.,Comorbidity and breathlessness were risk factors for pain and the physical dimensions of breathlessness were associated with pain.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity.

Information about daily physical activity levels (PAL) in subjects with undiagnosed chronic obstructive pulmonary disease (COPD) is scarce.,This study aims to assess PA and to investigate the associations between PA and clinical characteristics in subjects with newly diagnosed COPD.,Fifty-nine subjects with a new spirometry-based diagnosis of mild (n=38) and moderate (n=21) COPD (63±6 years, 68% male) were matched with 65 smoking controls (62±7 years, 75% male).,PA (daily steps, time spent in moderate-to-vigorous intense physical activities (MVPA) and PAL) was measured by accelerometry.,Dyspnoea, complete pulmonary function tests, peripheral muscle strength and exercise capacity served as clinical characteristics.,PA was significantly lower in COPD versus smoking controls (7986±2648 vs 9765±3078 steps, 64 (27-120) vs 110 (55-164) min of MVPA, 1.49±0.21 vs 1.62±0.24 PAL respectively, all p<0.05).,Subjects with COPD with either mild symptoms of dyspnoea (mMRC 1), those with lower diffusion capacity (TL,co), low 6 min walking distance (6MWD) or low maximal oxygen uptake (VO2 peak) had significantly lower PA.,Multiple regression analysis identified 6 MWD and TL,co as independent predictors of PA in COPD.,The reduction in PA starts early in the disease, even when subjects are not yet diagnosed with COPD.,Inactivity is more pronounced in subjects with mild symptoms of dyspnoea, lower levels of diffusion capacity and exercise capacity.

Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants.,We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD.,Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD.,By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung.,IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD.,Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC.,Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD.,Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD.

Substantial evidence suggests that there is genetic susceptibility to chronic obstructive pulmonary disease (COPD).,To identify common genetic risk variants, we performed a genome-wide association study in 2940 cases and 1380 smoking controls with normal lung function.,We demonstrate a novel susceptibility locus at 4q22.1 in FAM13A (rs7671167, OR=0.76, P=8.6×10−8) and provide evidence of replication in one case-control and two family-based cohorts (for all studies, combined P=1.2×10−11).

The poor recognition and related underdiagnosis of COPD contributes to an underestimation of mortality in subjects with COPD.,Data derived from population studies can advance our understanding of the true burden of COPD.,The objective of this report was to evaluate the impact of COPD on mortality and its predictors in a cohort of subjects with and without COPD recruited during the twenty first century.,All subjects with COPD (n = 993) defined according to the GOLD spirometric criteria, FEV1/FVC < 0.70, and gender- and age-matched subjects without airway obstruction, non-COPD (n = 993), were identified in a clinical follow-up survey of the Obstructive Lung Disease in Northern Sweden (OLIN) Studies cohorts in 2002-2004.,Mortality was observed until the end of year 2007.,Baseline data from examination at recruitment were used in the risk factor analyses; age, smoking status, lung function (FEV1 % predicted) and reported heart disease.,The mortality was significantly higher among subjects with COPD, 10.9%, compared to subjects without COPD, 5.8% (p < 0.001).,Mortality was associated with higher age, being a current smoker, male gender, and COPD.,Replacing COPD with FEV1 % predicted in the multivariate model resulted in the decreasing level of FEV1 being a significant risk factor for death, while heart disease was not a significant risk factor for death in any of the models.,In this cohort COPD and decreased FEV1 were significant risk factors for death when adjusted for age, gender, smoking habits and reported heart disease.

Matrix metalloproteinase-9 (MMP-9) may be important in the progression of emphysema, but there have been few longitudinal clinical studies of MMP-9 including pulmonary status and COPD exacerbation outcomes.,We utilized data from the placebo arm (n = 126) of a clinical trial of patients with alpha1-antitrypsin deficiency (AATD) and emphysema to examine the links between plasma MMP-9 levels, pulmonary status, and COPD exacerbations over a one year observation period.,Pulmonary function, computed tomography lung density, incremental shuttle walk test (ISWT), and COPD exacerbations were assessed at regular intervals over 12 months.,Prospective analyses used generalized estimating equations to incorporate repeated longitudinal measurements of MMP-9 and all endpoints, controlling for age, gender, race-ethnicity, leukocyte count, and tobacco history.,A secondary analysis also incorporated highly-sensitive C-reactive protein levels in predictive models.,At baseline, higher plasma MMP-9 levels were cross-sectionally associated with lower FEV1 (p = 0.03), FVC (p < 0.001), carbon monoxide transfer factor (p = 0.03), resting oxygen saturation (p = 0.02), and ISWT distance walked (p = 0.02) but were not associated with radiographic lung density or total lung capacity (TLC).,In longitudinal analyses, MMP-9 predicted a further decline in transfer factor (p = 0.04) and oxygen saturation (p < 0.001).,MMP-9 also predicted worsening lung density (p = 0.003), increasing TLC (p = 0.02), and more frequent COPD exacerbations over follow-up (p = 0.003).,Controlling additionally for hs-CRP levels did not substantively change the longitudinal associations between MMP-9 and these outcomes.,Increased plasma MMP-9 levels generally predicted pulmonary status declines, including worsening transfer factor and lung density as well as greater COPD exacerbations in AATD-associated emphysema.

Chronic obstructive pulmonary disease (COPD) significantly increases the risk of developing cancer.,Biomarker studies frequently follow a case-control set-up in which patients diagnosed with a disease are compared to controls.,Longitudinal cohort studies such as the COPD-centered German COPD and SYstemic consequences-COmorbidities NETwork (COSYCONET) study provide the patient and biomaterial base for discovering predictive molecular markers.,We asked whether microRNA (miRNA) profiles in blood collected from COPD patients prior to a tumor diagnosis could support an early diagnosis of tumor development independent of the tumor type.,From 2741 participants of COSYCONET diagnosed with COPD, we selected 534 individuals including 33 patients who developed cancer during the follow-up period of 54 months and 501 patients who did not develop cancer, but had similar age, gender and smoking history.,Genome-wide miRNA profiles were generated and evaluated using machine learning techniques.,For patients developing cancer we identified nine miRNAs with significantly decreased abundance (two-tailed unpaired t-test adjusted for multiple testing P < 0.05), including members of the miR-320 family.,The identified miRNAs regulate different cancer-related pathways including the MAPK pathway (P = 2.3 × 10−5).,We also observed the impact of confounding factors on the generated miRNA profiles, underlining the value of our matched analysis.,For selected miRNAs, qRT-PCR analysis was applied to validate the results.,In conclusion, we identified several miRNAs in blood of COPD patients, which could serve as candidates for biomarkers to help identify COPD patients at risk of developing cancer.

Smoking is the leading cause of COPD.,Exploring molecular markers and understanding the pathogenic mechanisms of smoking-related COPD are helpful for early clinical diagnosis and treatment of the disease.,This study aims to identify specific circulating microRNAs (miRNAs) from the blood of COPD patients with a long history of smoking.,Blood samples from four different groups were collected, and miRNA microarray was performed.,Differential expression of miRNAs was verified by quantitative polymerase chain reaction.,In vitro, THP-1 cells were cultured and stimulated with cigarette smoke extract (CSE) or transfected with miR-149-3p inhibitor/mimics.,Protein levels of Toll-like receptor 4 (TLR-4) and nuclear factor κB (NF-κB) were detected using Western blot and immunofluorescence.,Interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels were determined by an enzyme-linked immunosorbent assay.,miRNA profiling revealed that the expression of 56 miRNAs was changed between the four groups.,Expression of miR-149-3p in group C (non-smoker non-COPD) was higher than in group S (smoker non-COPD), S-COPD (smoker with stable COPD) and AE-COPD (smoker with acute exacerbation COPD).,CSE stimulation down-regulated the expression of miR-149-3p and up-regulated the TLR-4 and NF-κB levels in THP-1 cells.,Transfecting miR-149-3p inhibitors in THP-1 cells also increased the expression of its target genes.,Furthermore, overexpression of miR-149-3p inhibited the TLR-4/NF-κB signaling pathways and reduced the secretion of IL-1β and TNF-α.,This study found that smoking can induce differential expression of circulating miR-NAs, such as down-regulation of miR-149-3p.,Reducing miR-149-3p may increase the inflammatory response in COPD patients through the regulation of the TLR-4/NF-κB signaling pathway.

There is growing evidence that home telemonitoring can be advantageous in societies with increasing prevalence of chronic diseases.,The main objective of this study is to evaluate the effect of a primary care-based telemonitoring intervention on the number and length of hospital admissions.,A randomised controlled trial was carried out across 20 health centres in Bilbao (Basque Country, Spain) to assess the impact of home telemonitoring on in-home chronic patients compared with standard care.,The study lasted for one year.,Fifty-eight in-home patients, diagnosed with heart failure (HF) and/or chronic lung disease (CLD), aged 14 or above and with two or more hospital admissions in the previous year were recruited.,The intervention consisted of daily patient self-measurements of respiratory-rate, heart-rate, blood pressure, oxygen saturation, weight, body temperature and the completion of a health status questionnaire using PDAs.,Alerts were generated when pre-established thresholds were crossed.,The control group (CG) received usual care.,The primary outcome measure was the number of hospital admissions that occurred at 12 months post-randomisation.,The impact of telemonitoring on the length of hospital stay, use of other healthcare resources and mortality was also explored.,The intervention group (IG) included 28 patients and the CG 30.,Patient baseline characteristics were similar in both groups.,Of the 21 intervention patients followed-up for a year, 12 had some admissions (57.1%), compared to 19 of 22 controls (86.4%), being the difference statistically significant (p = 0.033, RR 0.66; 95%CI 0.44 to 0.99).,The mean hospital stay was overall 9 days (SD 4.3) in the IG versus 10.7 (SD 11.2) among controls, and for cause-specific admissions 9 (SD 4.5) vs.,11.2 (SD 11.8) days, both without statistical significance (p = 0.891 and 0.927, respectively).,Four patients need to be telemonitored for a year to prevent one admission (NNT).,There were more telephone contacts in the IG than in the CG (22.6 -SD 16.1- vs.,8.6 -SD 7.2-, p = 0.001), but fewer home nursing visits (15.3 -SD 11.6- vs.,25.4 -SD 26.3-, respectively), though the difference was not statistically significant (p = 0.3603).,This study shows that telemonitoring of in-home patients with HF and/or CLD notably increases the percentage of patients with no hospital admissions and indicates a trend to reduce total and cause-specific hospitalisations and hospital stay.,Home telemonitoring can constitute a beneficial alternative mode of healthcare provision for medically unstable elderly patients.,Current Controlled Trials ISRCTN89041993

Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability internationally.,Alveolar hypoxia and consequent hypoxemia increase in prevalence as disease severity increases.,Ventilation/perfusion mismatch resulting from progressive airflow limitation and emphysema is the key driver of this hypoxia, which may be exacerbated by sleep and exercise.,Uncorrected chronic hypoxemia is associated with the development of adverse sequelae of COPD, including pulmonary hypertension, secondary polycythemia, systemic inflammation, and skeletal muscle dysfunction.,A combination of these factors leads to diminished quality of life, reduced exercise tolerance, increased risk of cardiovascular morbidity, and greater risk of death.,Concomitant sleep-disordered breathing may place a small but significant subset of COPD patients at increased risk of these complications.,Long-term oxygen therapy has been shown to improve pulmonary hemodynamics, reduce erythrocytosis, and improve survival in selected patients with severe hypoxemic respiratory failure.,However, the optimal treatment for patients with exertional oxyhemoglobin desaturation, isolated nocturnal hypoxemia, or mild-to-moderate resting daytime hypoxemia remains uncertain.

Sexual function is often affected in patients suffering from chronic diseases especially chronic obstructive pulmonary disease (COPD).,However, the effect of COPD on sexual satisfaction is underappreciated in clinical practice.,The aim of this study is to evaluate the impact of COPD on patient’s sexuality and the explanatory variables of sexual dissatisfaction.,Questionnaires were emailed to participants and they submitted their responses on the Santé Respiratoire France website.,Data about sexual well-being (Arizona Sexual Experience Scale, ASEX), Quality of life (VQ11), anxiety, depression (Hospitalized anxiety and depression, HAD) and self-declared COPD grade were collected.,Seven hundred and fifty one subjects were included and were characterized as follows: women-51%, mean age-61 years, in a couple-62% and 70%-retired.,Every grade of COPD was represented.,Out of 751 participants, 301 participants (40%) had no sexual activity and 450 (60%) had sexual activity.,From the 450 participants, 60% needed to change their sexual life because of their disease (rhythm, frequency and position).,Subjects often used medications to improve sexual performance (43% used short-acting bronchodilator and 13% -specific erectile dysfunction drugs).,ASEX questionnaire confirmed patients’ dissatisfaction (diminution of sexual appetite for 68% and sexual desire for 60%) because of breathlessness and fatigue.,Eighty one percent of the responders had an altered quality of life (VQ11 mean score 35) and frequent suspected anxiety or depression (HAD mean score 10.8).,Ninety percent declared that sexual dysfunction had never been discussed by their doctors, while 36% of patients would have preferred to undergo a specialized consultation.,Sexual dysfunction is frequent among COPD patients and leads to an altered well-being, however being a cultural taboo, it remains frequently neglected.,Sexual guidance should be a part of patient’s consultations improve quality of sexual life.

Rationale: People living with both chronic obstructive pulmonary disease (COPD) and frailty have high potential to benefit from pulmonary rehabilitation but face challenges completing programs.,However, research to understand ways to optimize participation in this group is lacking.,Objectives: To explore the experiences, needs, and preferences of people with COPD and frailty referred for outpatient pulmonary rehabilitation.,Methods: Semistructured interviews with people with COPD and physical frailty, purposively sampled by age, living status, level of frailty, and completion of pulmonary rehabilitation.,Thematic analysis with a critical realist perspective was used, involving relevant stakeholders with clinical, academic, and lived experience for interpretive rigor.,Results: Nineteen people with COPD and frailty were interviewed, with a median age of 78 years (range, 58-88).,Nine did not complete their pulmonary rehabilitation program.,Four themes were identified: striving to adapt to multidimensional loss, tensions of balancing support with independence, pulmonary rehabilitation as a challenge worth facing, and overcoming unpredictable disruptions to participation.,Participants described constantly adapting to their changing health and resulting multidimensional losses (e.g., functional abilities, relationships, confidence).,This involved traversing between independence and seeking support, set against a mismatch between their needs and what support is available.,People with COPD and frailty can be highly motivated to participate in pulmonary rehabilitation, despite the physical and mental demands it entails, and report a range of benefits.,Yet in the context of changeable health, they must often overcome multiple unpredictable disruptions to completing rehabilitation programs.,Participant determination and flexibility of services can facilitate ongoing attendance, but for some, these unpredictable disruptions erode their motivation to attend.,Conclusions: People with COPD and frailty experience accumulating, multidimensional loss.,This group are motivated to complete pulmonary rehabilitation but often require additional support and flexibility owing to fluctuating and unpredictable health.,Person-centered approaches should be considered to minimize disruptive health events and support pulmonary rehabilitation participation and completion.,Service adaptations could allow more flexibility to meet the changing needs of this group and enable communication around how pulmonary rehabilitation might align with their priorities.

Dysbiosis of the gut microbiome is involved in the pathogenesis of various diseases, but the contribution of gut microbes to the progression of chronic obstructive pulmonary disease (COPD) is still poorly understood.,We carried out 16S rRNA gene sequencing and short-chain fatty acid analyses in stool samples from a cohort of 73 healthy controls, 67 patients with COPD of GOLD stages I and II severity, and 32 patients with COPD of GOLD stages III and IV severity.,Fecal microbiota from the three groups were then inoculated into recipient mice for a total of 14 times in 28 days to induce pulmonary changes.,Furthermore, fecal microbiota from the three groups were inoculated into mice exposed to smoke from biomass fuel to induce COPD-like changes.,We observed that the gut microbiome of COPD patients varied from that of healthy controls and was characterized by a distinct overall microbial diversity and composition, a Prevotella-dominated gut enterotype and lower levels of short-chain fatty acids.,After 28 days of fecal transplantation from COPD patients, recipient mice exhibited elevated lung inflammation.,Moreover, when mice were under both fecal transplantation and biomass fuel smoke exposure for a total of 20 weeks, accelerated declines in lung function, severe emphysematous changes, airway remodeling and mucus hypersecretion were observed.,These data demonstrate that altered gut microbiota in COPD patients is associated with disease progression in mice model.,The online version contains supplementary material available at 10.1186/s12931-021-01872-z.

The aim of this study was to examine the effects of exposure to air pollution and cigarette smoke on respiratory function, respiratory symptoms, and the prevalence of COPD in individuals aged ≥50 years.,We used spirometry and medical questionnaires to screen 433 individuals from Omuta City, Japan, an area with high levels of air pollution.,Non smokers had a high estimated COPD prevalence rate of 16%.,Among smokers, the estimated prevalence of COPD was 29% in seniors (50- to 74-years group) and 37% in the elderly (>75 years group).,We also found a correlation between levels of suspended particulate matter and COPD.,Both smoking and chronic exposure to air pollution (>5 years) decreased respiratory function, exacerbated respiratory symptoms, and increased the prevalence of COPD.,We strongly recommend periodic screening for the elderly patients to facilitate early detection of respiratory disease.

Asthma and chronic obstructive pulmonary disease (COPD) display features of overlap in airway physiology and airway inflammation.,Whether inflammatory phenotypes in airway disease describe similar mediator expression is unknown.,To explore the relationship of airway inflammation and cytokine and chemokine expression in asthma and COPD.,Subjects with asthma and COPD (n = 54 and n = 49) were studied.,Clinical characteristics and sputum were collected at entry into the study.,A 2-step sputum processing method was performed for supernatant and cytospin preparation.,Meso Scale Discovery and Luminex platforms were used to measure cytokines, chemokines and matrix metalloproteinase levels.,Analytes sensitive to dithiothreitol (DTT) that had increased recovery in the 2-step sputum process were IL-1β, 4, 5, 10, 13, IFN-γ, TNFRI, GM-CSF, CCL2, 3, 4, 5, 13 and 17.,There was a differential expression in IL-8, TNFRI and TNFRII between asthma and COPD [mean fold difference (95% CI): IL-8, 2.6 (1.3-5.4), p = 0.01; TNFRI, 2.1 (1.3-5.4), p = 0.03; TNFRII, 2.6 (1.2-5.6), p = 0.02].,In neutrophilic and eosinophilic airway inflammation, TNFα, TNFRI, TNFRII, IL-6, IL-8 and IL-5 could differentiate between these phenotypes.,However, these phenotypes were unrelated to the diagnosis of asthma or COPD.,Recovery of sputum mediators sensitive to DTT can be improved using the described sputum processing technique.,Within airway inflammatory sub-phenotypes there is a differential pattern of mediator expression that is independent of disease.,Whether these inflammatory phenotypes in asthma and COPD confer distinct pathogeneses, therapeutic responses and clinical phenotypes needs to be further evaluated.

One hundred million deaths were caused by tobacco in the 20th century, and it is estimated that there will be up to one billion deaths attributed to tobacco use in the 21st century.,Chronic obstructive pulmonary disease (COPD) is rapidly becoming a global public health crisis with smoking being recognized as its most important causative factor.,The most effective available treatment for COPD is smoking cessation.,There is mounting evidence that the rate of progression of COPD can be reduced when patients at risk of developing the disease stop smoking, while lifelong smokers have a 50% probability of developing COPD during their lifetime.,More significantly, there is also evidence that the risk of developing COPD falls by about half with smoking cessation.,Several pharmacological interventions now exist to aid smokers in cessation; these include nicotine replacement therapy, bupropion, and varenicline.,All pharmacotherapies for smoking cessation are more efficacious than placebo, with odds ratios of about 2.,Pharmacologic therapy should be combined with nonpharmacologic (behavioral) therapy.,Unfortunately, despite the documented efficacy of these agents, the absolute number of patients who are abstinent from smoking at 12 months of follow-up is low.

To describe a murine model of emphysema induced by a combination of exposure to cigarette smoke (CS) and instillation of porcine pancreatic elastase (PPE).,A total of 38 C57BL/6 mice were randomly divided into four groups: control (one intranasal instillation of 0.9% saline solution); PPE (two intranasal instillations of PPE); CS (CS exposure for 60 days); and CS + PPE (two intranasal instillations of PPE + CS exposure for 60 days).,At the end of the experimental protocol, all animals were anesthetized and tracheostomized for calculation of respiratory mechanics parameters.,Subsequently, all animals were euthanized and their lungs were removed for measurement of the mean linear intercept (Lm) and determination of the numbers of cells that were immunoreactive to macrophage (MAC)-2 antigen, matrix metalloproteinase (MMP)-12, and glycosylated 91-kDa glycoprotein (gp91phox) in the distal lung parenchyma and peribronchial region.,Although there were no differences among the four groups regarding the respiratory mechanics parameters assessed, there was an increase in the Lm in the CS + PPE group.,The numbers of MAC-2-positive cells in the peribronchial region and distal lung parenchyma were higher in the CS + PPE group than in the other groups, as were the numbers of cells that were positive for MMP-12 and gp91phox, although only in the distal lung parenchyma.,Our model of emphysema induced by a combination of PPE instillation and CS exposure results in a significant degree of parenchymal destruction in a shorter time frame than that employed in other models of CS-induced emphysema, reinforcing the importance of protease-antiprotease imbalance and oxidant-antioxidant imbalance in the pathogenesis of emphysema.

Eosinophilic airway inflammation is observed in 10-30% of COPD subjects.,Whether increased eosinophils or impairment in their clearance by macrophages is associated with the severity and frequency of exacerbations is unknown.,We categorised 103 COPD subjects into 4 groups determined by the upper limit of normal for their cytoplasmic macrophage red hue (<6%), an indirect measure of macrophage efferocytosis of eosinophils, and area under the curve sputum eosinophil count (≥3%/year).,Eosinophil efferocytosis by monocyte-derived macrophages was studied in 17 COPD subjects and 8 normal controls.,There were no differences in baseline lung function, health status or exacerbation frequency between the groups: A-low red hue, high sputum eosinophils (n = 10), B-high red hue, high sputum eosinophils (n = 16), C-low red hue, low sputum eosinophils (n = 19) and D- high red hue, low sputum eosinophils (n = 58).,Positive bacterial culture was lower in groups A (10%) and B (6%) compared to C (44%) and D (21%) (p = 0.01).,The fall in FEV1 from stable to exacerbation was greatest in group A (ΔFEV1 [95 % CI] -0.41 L [-0.65 to -0.17]) versus group B (-0.16 L [-0.32 to -0.011]), C (-0.11 L [-0.23 to -0.002]) and D (-0.16 L [-0.22 to -0.10]; p = 0.02).,Macrophage efferocytosis of eosinophils was impaired in COPD versus controls (86 [75 to 92]% versus 93 [88 to 96]%; p = 0.028); was most marked in group A (71 [70 to 84]%; p = 0.0295) and was inversely correlated with exacerbation frequency (r = -0.63; p = 0.006).,Macrophage efferocytosis of eosinophils is impaired in COPD and is related to the severity and frequency of COPD exacerbations.

The minimal clinically important difference (MCID) defines to what extent change on a health status instrument is clinically relevant, which aids scientists and physicians in measuring therapy effects.,This is the first study that aimed to establish the MCID of the Clinical chronic obstructive pulmonary disease (COPD) Questionnaire (CCQ), the COPD Assessment Test (CAT) and the St George’s Respiratory Questionnaire (SGRQ) in the same pulmonary rehabilitation population using multiple approaches.,In total, 451 COPD patients participated in a 3-week Pulmonary Rehabilitation (PR) programme (58 years, 65% male, 43 pack-years, GOLD stage II/III/IV 50/39/11%).,Techniques used to assess the MCID were anchor-based approaches, including patient-referencing, criterion-referencing and questionnaire-referencing, and the distribution-based methods standard error of measurement (SEM), 1.96SEM and half standard deviation (0.5s.d.).,Patient- and criterion-referencing led to MCID estimates of 0.56 and 0.62 (CCQ); 3.12 and 2.96 (CAT); and 8.40 and 9.28 (SGRQ).,Questionnaire-referencing suggested MCID ranges of 0.28-0.61 (CCQ), 1.46-3.08 (CAT) and 6.86-9.47 (SGRQ).,The SEM, 1.96SEM and 0.5s.d. were 0.29, 0.56 and 0.46 (CCQ); 3.28, 6.43 and 2.80 (CAT); 5.20, 10.19 and 6.06 (SGRQ).,Pooled estimates were 0.52 (CCQ), 3.29 (CAT) and 7.91 (SGRQ) for improvement.,MCID estimates differed depending on the method used.,Pooled estimates suggest clinically relevant improvements needing to exceed 0.40 on the CCQ, 3.00 on the CAT and 7.00 on the SGRQ for moderate to very severe COPD patients.,The MCIDs of the CAT and SGRQ in the literature might be too low, leading to overestimation of treatment effects for patients with COPD.

Objective To assess the long term effects of two different modes of disease management (comprehensive self management and routine monitoring) on quality of life (primary objective), frequency and patients’ management of exacerbations, and self efficacy (secondary objectives) in patients with chronic obstructive pulmonary disease (COPD) in general practice.,Design 24 month, multicentre, investigator blinded, three arm, pragmatic, randomised controlled trial.,Setting 15 general practices in the eastern part of the Netherlands.,Participants Patients with COPD confirmed by spirometry and treated in general practice.,Patients with very severe COPD or treated by a respiratory physician were excluded.,Interventions A comprehensive self management programme as an adjunct to usual care, consisting of four tailored sessions with ongoing telephone support by a practice nurse; routine monitoring as an adjunct to usual care, consisting of 2-4 structured consultations a year with a practice nurse; or usual care alone (contacts with the general practitioner at the patients’ own initiative).,Outcome measures The primary outcome was the change in COPD specific quality of life at 24 months as measured with the chronic respiratory questionnaire total score.,Secondary outcomes were chronic respiratory questionnaire domain scores, frequency and patients’ management of exacerbations measured with the Nijmegen telephonic exacerbation assessment system, and self efficacy measured with the COPD self-efficacy scale.,Results 165 patients were allocated to self management (n=55), routine monitoring (n=55), or usual care alone (n=55).,At 24 months, adjusted treatment differences between the three groups in mean chronic respiratory questionnaire total score were not significant.,Secondary outcomes did not differ, except for exacerbation management.,Compared with usual care, more exacerbations in the self management group were managed with bronchodilators (odds ratio 2.81, 95% confidence interval 1.16 to 6.82) and with prednisolone, antibiotics, or both (3.98, 1.10 to 15.58).,Conclusions Comprehensive self management or routine monitoring did not show long term benefits in terms of quality of life or self efficacy over usual care alone in COPD patients in general practice.,Patients in the self management group seemed to be more capable of appropriately managing exacerbations than did those in the usual care group.,Trial registration Clinical trials NCT00128765.

Addition of a second bronchodilator from a different pharmacological class may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) whose symptoms are insufficiently controlled by bronchodilator monotherapy.,GLOW6 evaluated the efficacy and safety of once-daily coadministration of the long-acting β2-agonist indacaterol (IND) and the long-acting muscarinic antagonist glycopyrronium (GLY) versus IND alone in patients with moderate-to-severe COPD.,In this randomized, double-blind, parallel group, placebo-controlled, 12-week study, patients were randomized 1:1 to IND 150 μg and GLY 50 μg daily (IND + GLY) or IND 150 μg daily and placebo (IND + PBO) (all delivered via separate Breezhaler® devices).,The primary objective was to demonstrate the superiority of IND + GLY versus IND + PBO for trough forced expiratory volume in 1 second (FEV1) at week 12.,Other end points included trough FEV1 at day 1, FEV1 area under the curve from 30 minutes to 4 hours (AUC30min-4h), peak FEV1, inspiratory capacity and trough forced vital capacity (FVC) at day 1 and week 12, and transition dyspnea index (TDI) focal score, COPD symptoms, and rescue medication use over 12 weeks.,A total of 449 patients were randomized (IND + GLY, 226; IND + PBO, 223); 94% completed the study.,On day 1 and at week 12, IND + GLY significantly improved trough FEV1 versus IND + PBO, with treatment differences of 74 mL (95% CI 46-101 mL) and 64 mL (95% CI 28-99 mL), respectively (both P<0.001).,IND + GLY significantly improved postdose peak FEV1, FEV1 AUC30min-4h, and trough FVC at day 1 and week 12 versus IND + PBO (all P<0.01).,TDI focal score and COPD symptoms (percentage of days able to perform usual daily activities and change from baseline in mean daytime respiratory score) were significantly improved with IND + GLY versus IND + PBO (P<0.05).,The incidence of adverse events was similar for the two treatment groups.,In patients with moderate-to-severe COPD, once-daily coadministration of IND and GLY provides significant and sustained improvement in bronchodilation versus IND alone from day 1, with significant improvements in patient-centered outcomes.

Two once-daily long-acting muscarinic antagonists (LAMAs) are currently available for the treatment of chronic obstructive pulmonary disease (COPD) - tiotropium and glycopyrronium.,Previous studies have compared glycopyrronium with open-label tiotropium.,In the GLOW5 study, we compare glycopyrronium with blinded tiotropium.,In this blinded, double-dummy, parallel group, 12-week study, patients with moderate-to-severe COPD were randomized 1:1 to glycopyrronium 50 μg once daily or tiotropium 18 μg once daily.,The primary objective was to demonstrate the non-inferiority of glycopyrronium versus blinded tiotropium with respect to trough forced expiratory volume in 1 second (FEV1) following 12 weeks of treatment (non-inferiority margin: -50 mL).,Secondary objectives were to evaluate glycopyrronium versus tiotropium for other spirometric outcomes, breathlessness (Transition Dyspnea Index; TDI), health status (St George’s Respiratory Questionnaire; SGRQ), daily rescue medication use, COPD exacerbations and COPD symptoms over 12 weeks of treatment.,657 patients were randomized (glycopyrronium: 327; tiotropium: 330); 96% (630 patients) completed the study.,Least squares mean trough FEV1 for both glycopyrronium and tiotropium was 1.405 L at Week 12, meeting the criterion for non-inferiority (mean treatment difference: 0 mL, 95% CI: -32, 31 mL).,Glycopyrronium demonstrated rapid bronchodilation following first dose on Day 1, with significantly higher FEV1 at all time points from 0-4 h post-dose versus tiotropium (all p < 0.001).,FEV1 area under the curve from 0-4 h (AUC0-4h) post-dose with glycopyrronium was significantly superior to tiotropium on Day 1 (p < 0.001) and was comparable to tiotropium at Week 12.,Glycopyrronium demonstrated comparable improvements to tiotropium in TDI focal score, SGRQ total score, rescue medication use and the rate of COPD exacerbations (all p = not significant).,Patients on glycopyrronium also had a significantly lower total COPD symptom score versus patients on tiotropium after 12 weeks (p = 0.035).,Adverse events were reported by a similar percentage of patients receiving glycopyrronium (40.4%) and tiotropium (40.6%).,In patients with moderate-to-severe COPD, 12-week blinded treatment with once-daily glycopyrronium 50 μg or tiotropium 18 μg, provided similar efficacy and safety, with glycopyrronium having a faster onset of action on Day 1 versus tiotropium.,ClinicalTrial.gov, NCT01613326

The response to treatment and progression of Chronic Obstructive Pulmonary Disease (COPD) varies significantly.,Small airways disease (SAD) is being increasingly recognized as a key pathological feature of COPD.,Studies have brought forward pathological evidence of small airway damage preceding the development of emphysema and the detection of obstruction using traditional spirometry.,In recent years, there has been a renewed interest in the early detection of SAD and this has brought along an increased demand for physiological tests able to identify and quantify SAD.,Early detection of SAD allows early targeted therapy and this suggests the potential for altering the course of disease.,The aim of this article is to review the evidence available on the physiological testing of small airways.,The first half will focus on the role of lung function tests such as maximum mid-expiratory flow, impulse oscillometry and lung clearance index in detecting and quantifying SAD.,The role of Computed Tomography (CT) as a radiological biomarker will be discussed as well as the potential of recent CT analysis software to differentiate normal aging of the lungs to pathology.,The evidence behind SAD biomarkers sourced from blood as well as biomarkers sourced from sputum and broncho-alveolar lavage (BAL) will be reviewed.,This paper focuses on CC-16, sRAGE, PAI-1, MMP-9 and MMP-12.

To investigate associations between occupational inhalation risks and fractional exhaled nitric oxide (FeNO) levels in patients with chronic obstructive pulmonary disease (COPD).,Data of 16,486 subjects who had undergone spirometry with pre-bronchodilator and post-bronchodilator lung function assessment were retrieved from the National Health and Nutrition Examination Survey, 2007-2012 database.,After excluding 2,638 subjects with missing spirometry values, data of 13,336 subjects were included for analysis.,Factors associated with occupational inhalation, FeNO levels and COPD were analyzed using logistic regression analysis.,COPD was associated with occupational exposures to mineral dusts, organic dusts, exhaust fumes, other fumes, and second-hand smoking (P<0.05).,Long-term exposure to these occupational hazards carried significantly higher risk for subjects with COPD than for controls (crude odds ratios [ORs]: mineral dusts: 2.364, organic dusts: 2.427, exhaust fumes: 2.728, other fumes: 2.144).,In subgroup analysis, COPD correlated positively with long-term exposures to organic dusts and exhaust fumes in subjects with FeNO ≤50 ppb (ORs 1.361 and 1.314, respectively); conversely, COPD correlated negatively with intermediate to long-term exposures to organic dusts and exhaust fumes in those with FeNO >50 ppb (ORs 0.058 and 0.210, respectively).,Occupational exposures to airborne pollutants carries higher risk of COPD than non-exposure and the risk is higher the longer the duration of exposure.,Exposure-response relationships are inconsistent in subjects with suspected asthmatic airway inflammation (FeNO ≥50 ppb).,More careful risk assessment is needed in occupational inhalation exposure, since COPD with asthmatic airway inflammation, or asthma-COPD overlapping syndrome, may have the distinguishing features of both COPD and asthma.

The mechanisms underlying altered susceptibility and propensity to severe Coronavirus disease 2019 (COVID-19) disease in at-risk groups such as patients with chronic obstructive pulmonary disease (COPD) are poorly understood.,Inhaled corticosteroids (ICSs) are widely used in COPD, but the extent to which these therapies protect or expose patients to risk of severe COVID-19 is unknown.,The aim of this study was to evaluate the effect of ICSs following pulmonary expression of the SARS-CoV-2 viral entry receptor angiotensin-converting enzyme-2 (ACE2).,We evaluated the effect of ICS administration on pulmonary ACE2 expression in vitro in human airway epithelial cell cultures and in vivo in mouse models of ICS administration.,Mice deficient in the type I IFN-α/β receptor (Ifnar1−/−) and administration of exogenous IFN-β were used to study the functional role of type-I interferon signaling in ACE2 expression.,We compared sputum ACE2 expression in patients with COPD stratified according to use or nonuse of ICS.,ICS administration attenuated ACE2 expression in mice, an effect that was reversed by exogenous IFN-β administration, and Ifnar1−/− mice had reduced ACE2 expression, indicating that type I interferon contributes mechanistically to this effect.,ICS administration attenuated expression of ACE2 in airway epithelial cell cultures from patients with COPD and in mice with elastase-induced COPD-like changes.,Compared with ICS nonusers, patients with COPD who were taking ICSs also had reduced sputum expression of ACE2.,ICS therapies in COPD reduce expression of the SARS-CoV-2 entry receptor ACE2.,This effect may thus contribute to altered susceptibility to COVID-19 in patients with COPD.

Morbidity and mortality from COVID‐19 caused by novel coronavirus SARS‐CoV‐2 is accelerating worldwide, and novel clinical presentations of COVID‐19 are often reported.,The range of human cells and tissues targeted by SARS‐CoV‐2, its potential receptors and associated regulating factors are still largely unknown.,The aim of our study was to analyze the expression of known and potential SARS‐CoV‐2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID‐19.,We performed RNA sequencing and explored available RNA‐Seq databases to study gene expression and co‐expression of ACE2, CD147 (BSG), and CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4+ and CD8+ T cells, B cells, and plasmablasts.,We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID‐19 risk factor status.,ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA andPPIB), CD26 (DPP4), and related molecules were expressed in both epithelium and in immune cells.,We also observed a distinct age‐related expression profile of these genes in the PBMCs and T cells from healthy children and adults.,Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2‐ and CD147‐related genes in the bronchial biopsy, BAL, or blood.,Additionally, CD147‐related genes correlated positively with age and BMI.,Interestingly, we also observed higher expression of CD147‐related genes in the lesional skin of patients with atopic dermatitis.,Our data suggest different receptor repertoire potentially involved in the SARS‐CoV‐2 infection at the epithelial barriers and in the immune cells.,Altered expression of these receptors related to age, gender, obesity and smoking, as well as with the disease status, might contribute to COVID‐19 morbidity and severity patterns.,ACE2 and TMPRSS2 expression is unique for the epithelial barrier sites, whereas CD147, cyclophilins, and CD26 are expressed in both, epithelial and immune cells.,Age is a factor associated with the differential expression profiles of ACE2‐, CD147‐ and CD26‐related genes in the PBMCs and naive CD4+ T cells from healthy children and adults.,Asthma, COPD, hypertension, smoking, obesity, and male gender generally lead to the higher expression of ACE2‐ and CD147‐related genes in the bronchial biopsy, BAL or blood.,Abbreviations: ACE2, angiotensin‐converting enzyme 2; AD, atopic dermatitis; BAL, bronchoalveolar lavage; COPD, chronic obstructive pulmonary disease; CypA, cyclophilin A; CypB, cyclophilin B; GLUT1, glucose transporter 1; ILC, innate lymphoid cell; MCTs, monocarboxylate transporters; NF‐ATs, nuclear factor of activated T cells; PBMCs, peripheral blood mononuclear cells; SARS‐CoV‐2; severe acute respiratory syndrome coronavirus 2; SLC6A19, sodium‐dependent neutral amino acid transporter B(0)AT1; S100A9, protein S100‐A9; TMPRSS2, transmembrane protease serine.

Functional deficiency of mannose-binding lectin (MBL) may contribute to the pathogenesis of chronic obstructive pulmonary disease.,We hypothesized that specific MBL2 gene polymorphisms and circulating MBL protein levels are associated with clinically relevant outcomes in the Predicting Outcome using systemic Markers In Severe Exacerbations of COPD PROMISE-COPD cohort.,We followed 277 patients with stable COPD GOLD stage II-IV COPD over a median period of 733 days (IQR 641-767) taking survival as the primary outcome parameter.,Patients were dichotomized as frequent (≥2 AECOPD/year) or infrequent exacerbators.,Serum MBL levels and single nucleotide polymorphisms of the MBL2 gene were assessed at baseline.,The MBL2-HYPD haplotype was significantly more prevalent in frequent exacerbators (OR: 3.33; 95 % CI, 1.24-7.14, p = 0.01).,The median serum MBL concentration was similar in frequent (607 ng/ml, [IQR; 363.0-896.0 ng/ml]) and infrequent exacerbators (615 ng/ml, [IQR; 371.0-942.0 ng/ml]).,Serum MBL was not associated with lung function characteristics or bacterial colonization in sputum.,However, high serum MBL at stable state was associated with better survival compared to low MBL (p = 0.046, log rank test).,In COPD, the HYPD haplotype of MBL2 gene is associated with frequent exacerbations and high serum MBL is linked to increased survival.,The PROMISE-COPD study was registered at www.controlled-trials.com under the identifier ISRCTN99586989.,The online version of this article (doi:10.1186/s12931-015-0306-3) contains supplementary material, which is available to authorized users.

We have previously established that a defect in the ability of alveolar macrophages (AM) to phagocytose apoptotic cells (efferocytosis) and pathogens is a potential therapeutic target in COPD.,We further showed that levels of mannose binding lectin (MBL; required for effective macrophage phagocytic function) were reduced in the airways but not circulation of COPD patients.,We hypothesized that increased oxidative stress in the airway could be a cause for such disturbances.,We therefore studied the effects of oxidation on the structure of the MBL molecule and its functional interactions with macrophages.,Oligomeric structure of plasma derived MBL (pdMBL) before and after oxidation (oxMBL) with 2,2′-azobis(2-methylpropionamidine)dihydrochroride (AAPH) was investigated by blue native PAGE.,Macrophage function in the presence of pd/oxMBL was assessed by measuring efferocytosis, phagocytosis of non-typeable Haemophilus influenzae (NTHi) and expression of macrophage scavenger receptors.,Oxidation disrupted higher order MBL oligomers.,This was associated with changed macrophage function evident by a significantly reduced capacity to phagocytose apoptotic cells and NTHi in the presence of oxMBL vs pdMBL (eg, NTHi by 55.9 and 27.0% respectively).,Interestingly, oxidation of MBL significantly reduced macrophage phagocytic ability to below control levels.,Flow cytometry and immunofluorescence revealed a significant increase in expression of macrophage scavenger receptor (SRA1) in the presence of pdMBL that was abrogated in the presence of oxMBL.,We show the pulmonary macrophage dysfunction in COPD may at least partially result from an oxidative stress-induced effect on MBL, and identify a further potential therapeutic strategy for this debilitating disease.

Chronic obstructive pulmonary disease (COPD) is a prevalent illness that, due to its symptoms and treatment, entails a significant burden for the affected person, and his/her family, health care and private finances.,Today, knowledge and understanding are sparse regarding COPD-affected persons’ own lived experiences and about the symptom burden and its effect on their daily life.,Due to this knowledge gap the aim of this study was to identify and describe the symptom burden and its effect on daily life in people with COPD, based on their own lived experiences.,Eleven males and 14 females in GOLD stages III and IV, in an age range of 58-82 years, were interviewed.,An interview guide was used to direct the face-to-face interviews.,Data was analyzed with thematic analysis following the six steps according to Braun and Clarke.,The results highlighted one theme: an altered everyday life.,The altered everyday life leads to a need for support to handle everyday life and for different strategies to live as desired.,Persons with COPD need to take each day as it comes and their life is not easy to plan since it depends on how they feel from day to day.,Life is handled with several strategies such as breathing techniques, and ways to take care of the home and garden as well as the emotions.,Support from the next of kin, society and the health care service is important.,This study provides the insight that persons with COPD in stages III and IV have an altered life caused by the symptom burden.,They must struggle with strategies to handle everyday life.,There is a need of support from the next of kin and society to facilitate daily living, but this support needs to be well-balanced.

Previous studies suggest that gender differences exist in COPD diagnosis and symptoms; these differences may be more pronounced in younger adults.,Our objective was to explore age-associated gender differences across a range of COPD severities.,A total of 4,484 current and former smokers with COPD from the Genetic Epidemiology of COPD cohort were investigated using regression modeling to explore the association between gender, age, disease severity, and the contributing elements of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification system (symptoms, exacerbation risk, airflow limitation).,The age-gender interaction was observed across multiple age categories.,Compared to men with COPD, younger women with COPD had a greater likelihood of more severe dyspnea, airflow limitation, greater risk for exacerbations, and categorization in GOLD groups B and D.,These differences were less pronounced in older women with COPD.,However, older women remained more likely to experience severe dyspnea and to manifest more severe COPD (B vs A) than older men, despite lower pack-years of smoking.,These data demonstrate the significant symptom burden of COPD in women, especially younger women.,More research is needed to understand the pathogenesis of increased severity of COPD in women and to develop gender-targeted clinical assessment and management approaches to improve outcomes for women and men with COPD at all ages.

Objective: This study aimed to investigate the quantitative effects of outdoor air pollution, represented by 10 µg/m3 increment of PM10, on chronic obstructive pulmonary disease in China, United States and European Union through systematic review and meta-analysis.,Methods: Publications in English and Chinese from PubMed and EMBASE were selected.,The Cochrane Review Handbook of Generic Inverse Variance was used to synthesize the pooled effects on incidence, prevalence, mortality and hospital admission.,Results: Outdoor air pollution contributed to higher incidence and prevalence of COPD.,Short-term exposure was associated with COPD mortality increased by 6%, 1% and 1% in the European Union, the United States and China, respectively (p < 0.05).,Chronic PM exposure produced a 10% increase in mortality.,In a short-term exposure to 10 µg/m3 PM10 increment COPD mortality was elevated by 1% in China (p < 0.05) and hospital admission enrollment was increased by 1% in China, 2% in United States and 1% in European Union (p < 0.05).,Conclusions: Outdoor air pollution contributes to the increasing burdens of COPD.10 µg/m3 increase of PM10 produced significant condition of COPD death and exacerbation in China, United States and European Union.,Controlling air pollution will have substantial benefit to COPD morbidity and mortality.

Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking.,However, COPD mortality is high in poor countries with low smoking rates.,Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD.,We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI).,National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence.,The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked.,National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men rs=0.73, p=0.0001; women rs=0.90, p<0.0001; 60+ years: men rs=0.63, p=0.0022; women rs=0.37, p=0.1) than obstruction (<60 years: men rs=0.28, p=0.20; women rs=0.17, p<0.46; 60+ years: men rs=0.28, p=0.23; women rs=0.22, p=0.33).,Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$15 000.,Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$15 000.,Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high ‘COPD’ mortality in poor countries.

Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.,For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler.,Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).,295 and 291 patients were treated in MORACTO 1 and 2, respectively.,Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001).,Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).,Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies.,Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.,T/O reduces lung hyperinflation in COPD versus T, O or placebo and increases exercise endurance versus placebohttp://ow.ly/ml3G307XW6a

Indacaterol is a long-acting beta-2 agonist for once-daily treatment of COPD.,We evaluated the effects of indacaterol 150 μg on lung hyperinflation compared with placebo and open-label tiotropium 18 μg.,We measured physical activity during treatment with indacaterol 150 μg and matched placebo.,We performed a randomized, three-period, cross-over study (21 days of treatment separated by two wash-out periods of 13 days) with indacaterol 150 μg or matching placebo and tiotropium 18 μg.,Lung function was assessed by body plethysmography and spirometry.,Physical activity was measured for one week by a multisensory armband at the end of both treatment periods with indacaterol/matched placebo.,The primary endpoint was peak inspiratory capacity at the end of each treatment period.,129 patients (mean age, 61 years; mean post-bronchodilator FEV1, 64%), were randomized and 110 patients completed the study.,Peak inspiratory capacity was 0.22 L greater with Indacaterol at day 21 compared to placebo (p < 0.001).,Similar results were observed for tiotropium.,Both bronchodilators also significantly improved other parameters of lung hyperinflation compared with placebo.,All parameters of physical activity were significantly increased during treatment with indacaterol versus placebo.,Indacaterol 150 μg improved lung hyperinflation in patients with moderate COPD, which was associated with an increase of physical activity.,ClinicalTrials.gov registration number: NCT01012765.

The authors describe the pathophysiological mechanisms leading to development of acidosis in patients with chronic obstructive pulmonary disease and its deleterious effects on outcome and mortality rate.,Renal compensatory adjustments consequent to acidosis are also described in detail with emphasis on differences between acute and chronic respiratory acidosis.,Mixed acid-base disturbances due to comorbidity and side effects of some drugs in these patients are also examined, and practical considerations for a correct diagnosis are provided.

COPD is currently the fourth cause of morbidity and mortality in the developed world.,Patients with COPD experience a progressive deterioration and disability, which lead to a worsening in their health-related quality of life (HRQoL).,The aim of this work is to assess the Health-Related Quality of Life (HRQoL) of patients with stable COPD followed in primary care and to identify possible predictors of disease.,It is a multicenter, epidemiological, observational, descriptive study.,Subjects of both sexes, older than 40 years and diagnosed of COPD at least 12 months before starting the study were included.,Sociodemographic data, severity of disease, comorbidity, and use of health resources in the previous 12 months were collected.,All patients were administered a generic quality-of-life questionnaire, the SF-12, that enables to calculate two scores, the physical (PCS-12) and the mental (MCS-12) component summary scores.,10,711 patients were evaluated (75.6% men, 24.4% women), with a mean age of 67.1 years (SD 9.66).,The mean value of FEV1 was 35.9 ± 10.0%.,Mean PCS-12 and MCS-12 scores were 36.0 ± 9.9 and 48.3 ± 10.9, respectively.,Compared to the reference population, patients with COPD had a reduction of PCS-12, even in mild stages of the disease.,The correlation with FEV1 was higher for PCS-12 (r = 0.38) than for MCS-12 (r = 0.12).,Predictors for both HRQoL components were sex, FEV1, use of oxygen therapy, and number of visits to emergency rooms and hospital admissions.,Other independent predictors of PCS-12 were age, body mass index and educational level.,Patients with stable COPD show a reduction of their HRQoL, even in mild stages of the disease.,The factors determining the HRQoL include sex, FEV1, use of oxygen therapy, and number of visits to emergency rooms and hospital admissions.

We hypothesized that bronchodilator treatment not only improves hyperinflation and endurance capacity but also muscular efficiency in stable chronic obstructive pulmonary disease (COPD).,We aimed to demonstrate that tiotropium and salmeterol improve muscular efficiency compared with placebo.,Twenty-five COPD patients were studied, including 20 males of mean (standard deviation) age 62 years (7 years) with baseline forced expiratory volume in 1 second of 41% (10%) predicted, and maximal workload of 101 Watt (36 Watt).,Subjects were randomized for 6-week treatment with tiotropium 18 μg once daily, salmeterol 50 μg twice daily, or placebo using a double-blind, crossover design.,Muscular efficiency and endurance time were measured during cycling at 50% of maximal work load.,Resting energy expenditure was measured using a ventilated hood.,Muscular efficiency after tiotropium, salmeterol, and placebo treatment was 14.6%, 14.4%, and 14.4%, respectively (P > 0.05), and resting energy expenditure was 1485 kcal/24 hours, 1709 kcal/24 hours, and 1472 kcal/24 hours (P > 0.05), respectively.,Endurance time after tiotropium treatment was significantly higher than that after placebo (27.0 minutes versus 19.3 minutes [P = 0.02]), whereas endurance time after salmeterol treatment was not higher than that after placebo (23.3 minutes [P = 0.22]).,In this small study, we were not able to demonstrate that bronchodilator therapy improved muscular efficiency.,Apparently, reduced costs of breathing relative to total energy expenditure were too small to be detected.

Chronic obstructive pulmonary disease (COPD) is characterized by poorly reversible airflow limitation.,The pathological hallmarks of COPD are inflammation of the peripheral airways and destruction of lung parenchyma or emphysema.,The functional consequences of these abnormalities are expiratory airflow limitation and dynamic hyperinflation, which then increase the elastic load of the respiratory system and decrease the performance of the respiratory muscles.,These pathophysiologic features contribute significantly to the development of dyspnea, exercise intolerance and ventilatory failure.,Several treatments may palliate flow limitation, including interventions that modify the respiratory pattern (deeper, slower) such as pursed lip breathing, exercise training, oxygen, and some drugs.,Other therapies are aimed at its amelioration, such as bronchodilators, lung volume reduction surgery or breathing mixtures of helium and oxygen.,Finally some interventions, such as inspiratory pressure support, alleviate the threshold load associated to flow limitation.,The degree of flow limitation can be assessed by certain spirometry indexes, such as vital capacity and inspiratory capacity, or by other more complexes indexes such as residual volume/total lung capacity or functional residual capacity/total lung capacity.,Two of the best methods to measure flow limitation are to superimpose a flow-volume loop of a tidal breath within a maximum flow-volume curve, or to use negative expiratory pressure technique.,Likely this method is more accurate and can be used during spontaneous breathing.,A definitive definition of dynamic hyperinflation is lacking in the literature, but serial measurements of inspiratory capacity during exercise will document the trend of end-expiratory lung volume and allow establishing relationships with other measurements such as dyspnea, respiratory pattern, exercise tolerance, and gas exchange.

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible, progressive obstruction of lung airflow.,Dyspnea (shortness of breath [SOB]) is the COPD symptom which most negatively impacts patients’ daily activities.,To assess how SOB affects daily activities, 37 items were drafted through focus group discussions and cognitive interviews with COPD patients to develop a patient-reported outcome instrument: the Shortness of Breath with Daily Activities questionnaire (SOBDA).,Psychometric analysis was conducted to reduce the number of items and evaluate the measurement properties of the final SOBDA.,Prospective, observational study of 334 COPD patients, recruited from 24 pulmonology and internal medicine clinics in the United States.,The 37-item SOBDA was administered to patients each evening for 28 days using an electronic diary.,Patients answered every item and rated their level of SOB experienced that day during specific activities.,Item selection was conducted by examining item characteristics, dimensionality, and Rasch model analysis results.,The decision to delete an item was based on psychometric evidence, content validity, and expert clinical input.,The final SOBDA instrument was evaluated for internal consistency, reproducibility, convergent validity, known-groups validity, and responsiveness.,Twenty-four items from the 37-item pool were removed following the item selection process: nine items were removed due to high item-to-item correlations; five due to floor effects; three due to infrequent activity; one due to gender bias; two due to low factor loadings; three due to unordered response options; and one due to expert’s discretion.,Internal consistency and reproducibility of the final SOBDA were demonstrated by Cronbach Alpha = 0.87, and intra-class correlation coefficient = 0.91.,Convergent validity was demonstrated by high correlation with the CRQ-SAS (0.60) and SGRQ-C (0.61).,Known groups validity was demonstrated by significant difference between ratings of the mMRC and clinical global rating of severity.,Evaluation of the ability to detect change was not performed owing to too few responders at the end of the study.,Through the empirical item reduction process, 13 items were selected from the 37-item pool generated during qualitative development.,The final 13-item SOBDA is a reliable and valid instrument for use in clinical trials.

Measuring dyspnea intensity associated with exercise provides insights into dyspnea-limited exercise capacity, and has been used to evaluate treatment outcomes for chronic obstructive pulmonary disease (COPD).,Three patient-reported outcome scales commonly cited for rating dyspnea during exercise are the modified Borg scale (MBS), numerical rating scale for dyspnea (NRS-D), and visual analogue scale for dyspnea (VAS-D).,Various versions of each scale were found.,Our objective was to evaluate the content validity of scales commonly used in COPD studies, to explore their ability to capture patients’ experiences of dyspnea during exercise, and to evaluate a standardized version of the MBS.,A two-stage procedure was used, with each stage involving one-on-one interviews with COPD patients who had recently completed a clinic-based exercise event on a treadmill or cycle ergometer.,An open-ended elicitation interview technique was used to understand patients’ experiences of exercise-induced dyspnea, followed by patients completing the three scales.,The cognitive interviewing component of the study involved specific questions to evaluate the patients’ perspectives of the content and format of the scales.,Results from Stage 1 were used to develop a standardized version of the MBS, which was then subjected to further content validity assessment during Stage 2.,Thirteen patients participated in the two-stage process (n = 6; n = 7).,Mean forced expiratory volume in 1 second (FEV1) percent predicted was 40%, mean age 57 years, and 54% were male.,Participants used a variety of terms to describe the intensity and variability of exercise-induced dyspnea.,Subjects understood the instructions and format of the standardized MBS, and were able to easily select a response to report the level of dyspnea associated with their recent standardized exercise.,This study provides initial evidence in support of using a standardized version of the MBS version for quantifying dyspnea intensity associated with exercise in patients with COPD.

The long-acting muscarinic antagonists umeclidinium (UMEC) and tiotropium (TIO) are approved once-daily maintenance therapies for COPD.,This study investigated the efficacy and safety of UMEC versus TIO in COPD.,This was a 12-week, multicenter, randomized, blinded, double-dummy, parallel-group, non-inferiority study.,Patients were randomized 1:1 to UMEC 62.5 μg plus placebo or TIO 18 μg plus placebo.,The primary end point was trough forced expiratory volume in 1 second (FEV1) at day 85 (non-inferiority margin −50 mL; per-protocol [PP] population).,Other end points included weighted mean FEV1 over 0-24 and 12-24 hours post-dose.,Patient-reported outcomes comprised Transition Dyspnea Index score, St George’s Respiratory Questionnaire total score, and COPD Assessment Test score.,Adverse events were also assessed.,In total, 1,017 patients were randomized to treatment.,In the PP population, 489 and 487 patients received UMEC and TIO, respectively.,In the PP population, change from baseline in trough FEV1 was greater with UMEC versus TIO at day 85, meeting non-inferiority and superiority margins (difference: 59 mL; 95% confidence interval [CI]: 29-88; P<0.001).,Similar results were observed in the intent-to-treat analysis of trough FEV1 at day 85 (53 mL, 95% CI: 25-81; P<0.001).,Improvements in weighted mean FEV1 over 0-24 hours post-dose at day 84 were similar with UMEC and TIO but significantly greater with UMEC versus TIO over 12-24 hours post-dose (70 mL; P=0.015).,Clinically meaningful improvements in Transition Dyspnea Index and St George’s Respiratory Questionnaire were observed with both treatments at all time points.,No differences were observed between UMEC and TIO in patient-reported outcomes.,Overall incidences of adverse events were similar for UMEC and TIO.,UMEC 62.5 μg demonstrated superior efficacy to TIO 18 μg on the primary end point of trough FEV1 at day 85.,Safety profiles were similar for both treatments.

The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally.

Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users.

The long-acting muscarinic antagonist (LAMA) umeclidinium (UMEC) and the combination of UMEC with the long-acting β2-agonist (LABA) vilanterol (UMEC/VI) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD) in the US and EU.,They are not indicated for the treatment of asthma.,In this 52-week, double-blind, placebo-controlled, parallel-group safety study (GSK study DB2113359; NCT01316887), patients were randomized 2:2:1 to UMEC/VI 125/25 mcg, UMEC 125 mcg, or placebo.,Study endpoints included adverse events (AEs), clinical chemistry and hematology parameters, vital signs, 12-lead, and 24-hour Holter electrocardiograms.,COPD exacerbations and rescue medication use were assessed as safety parameters; lung function was also evaluated.,The incidence of on-treatment AEs, serious AEs (SAEs), and drug-related AEs was similar between treatment groups (AEs: 52-58%; SAEs: 6-7%; drug-related AEs: 12-13%).,Headache was the most common AE in each treatment group (8-11%).,AEs associated with the LAMA and LABA pharmacologic classes occurred at a low incidence across treatment groups.,No clinically meaningful effects on vital signs or laboratory assessments were reported for active treatments versus placebo.,The incidences of atrial arrhythmias with UMEC/VI 125/25 mcg were similar to placebo; for UMEC 125 mcg, the incidences of ectopic supraventricular beats, sustained supraventricular tachycardia, and ectopic supraventricular rhythm were ≥2% greater than placebo.,With active treatments, COPD exacerbations were fewer (13-15% of patients reporting ≥1 exacerbation) and on average less rescue medication was required (1.6-2.2 puffs/day) versus placebo (24% reporting ≥1 exacerbation, 2.6 puffs/day).,Both active treatments improved lung function versus placebo.,UMEC/VI 125/25 mcg and UMEC 125 mcg were well tolerated over 12 months in patients with COPD.

Asthma-COPD overlap (ACO) is a term that encompasses patients with characteristics of two conditions, smoking asthmatics or COPD patients with asthma-like features such as high bronchodilator response or blood eosinophil count ≥300 cells/μL.,The aim of this study was to compare the different phenotypes inside the ACO definition in a real-life population cohort.,We analyzed patients from the MAJORICA cohort who had a diagnosis of asthma and/or COPD based on current guidelines, laboratory data in 2014 and follow-up until 2015.,Prevalence of ACO according to the different criteria, demographic, clinical and functional characteristics, prescriptions and use of health resources data were compared between three groups.,We included 603 patients.,Prevalence of smoking asthmatics was 14%, COPD patients with high bronchodilator response 1.5% and eosinophilic COPD patients 12%.,Smoking asthmatics were younger and used more rescue inhalers, corticosteroids and health resources.,Conversely, eosinophilic COPD patients were older than the other groups, often treated with corticosteroids and had lower use of health resources.,Most of the COPD patients with high bronchodilator response were included in the eosinophilic COPD group.,ACO includes two conditions (smoking asthmatics and eosinophilic COPD patients) with different medication requirement and prognosis that should not be pooled together.,Use of ≥300 blood eosinophils/μL as a treatable trait should be recommended.

Fractional exhaled nitric oxide (FeNO) is an easy, sensitive, reproducible, and noninvasive marker of eosinophilic airway inflammation.,Accordingly, FeNO is extensively used to diagnose and manage asthma.,Patients with COPD who share some of the features of asthma have a condition called asthma-COPD overlap syndrome (ACOS).,The feasibility of using FeNO to differentiate ACOS patients from asthma and COPD patients remains unclear.,From February 2013 to May 2016, patients suspected with asthma and COPD through physician’s opinion were subjected to FeNO measurement, pulmonary function test (PFT), and bronchial hyperresponsiveness or bronchodilator test.,Patients were divided into asthma alone group, COPD alone group, and ACOS group according to a clinical history, PFT values, and bronchial hyperresponsiveness or bronchodilator test.,Receiver operating characteristic (ROC) curves were obtained to elucidate the clinical functions of FeNO in diagnosing ACOS.,The optimal operating point was also determined.,A total of 689 patients were enrolled in this study: 500 had asthma, 132 had COPD, and 57 had ACOS.,The FeNO value in patients with ACOS was 27 (21.5) parts per billion (ppb; median [interquartile range]), which was significantly higher than that in the COPD group (18 [11] ppb).,The area under the ROC curve was estimated to be 0.783 for FeNO.,Results also revealed an optimal cutoff value of >22.5 ppb FeNO for differentiating ACOS from COPD patients (sensitivity 70%, specificity 75%).,FeNO measurement is an easy, noninvasive, and sensitive method for differentiating ACOS from COPD.,This technique is a new perspective for the management of COPD patients.

In chronic obstructive pulmonary disease (COPD) apoptotic bronchial epithelial cells are increased, and their phagocytosis by alveolar macrophages (AM) is decreased alongside bacterial phagocytosis.,Epithelial cellular lipids, including those exposed on uncleared apoptotic bodies, can become oxidized, and may be recognized and presented as non-self by antigen presenting cells.,CD1b is a lipid-presenting protein, previously only described in dendritic cells.,We investigated whether CD1b is upregulated in COPD AM, and whether lipid oxidation products are found in the airways of cigarette smoke (CS) exposed mice.,We also characterise CD1b for the first time in a range of macrophages and assess CD1b expression and phagocytic function in response to oxidised lipid.,Bronchoalveolar lavage and exhaled breath condensate were collected from never-smoker, current-smoker, and COPD patients and AM CD1b expression and airway 8-isoprostane levels assessed.,Malondialdehyde was measured in CS-exposed mouse airways by confocal/immunofluorescence.,Oxidation of lipids produced from CS-exposed 16HBE14o- (HBE) bronchial epithelial cells was assessed by spectrophotometry and changes in lipid classes assessed by mass spectrometry.,16HBE cell toxicity was measured by flow cytometry as was phagocytosis, CD1b expression, HLA class I/II, and mannose receptor (MR) in monocyte derived macrophages (MDM).,AM CD1b was significantly increased in COPD smokers (4.5 fold), COPD ex-smokers (4.3 fold), and smokers (3.9 fold), and AM CD1b significantly correlated with disease severity (FEV1) and smoking pack years.,Airway 8-isoprostane also increased in smokers and COPD smokers and ex-smokers.,Malondialdehyde was significantly increased in the bronchial epithelium of CS-exposed mice (MFI of 18.18 vs 23.50 for control).,Oxidised lipid was produced from CS-exposed bronchial epithelial cells (9.8-fold of control) and showed a different overall lipid makeup to that of control total cellular lipid.,This oxidised epithelial lipid significantly upregulated MDM CD1b, caused bronchial epithelial cell toxicity, and reduced MDM phagocytic capacity and MR in a dose dependent manner.,Increased levels of oxidised lipids in the airways of COPD patients may be responsible for reduced phagocytosis and may become a self-antigen to be presented by CD1b on macrophages to perpetuate disease progression despite smoking cessation.

Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality around the world.,The aim of our study was to determine the association between specific comorbidities and COPD severity.,Pulmonologists included patients with COPD using a web-site questionnaire.,Diagnosis of COPD was made using spirometry post-bronchodilator FEV1/FVC < 70%.,The questionnaire included the following domains: demographic criteria, clinical symptoms, functional tests, comorbidities and therapeutic management.,COPD severity was classified according to GOLD 2011.,First we performed a principal component analysis and a non-hierarchical cluster analysis to describe the cluster of comorbidities.,One thousand, five hundred and eighty-four patients were included in the cohort during the first 2 years.,The distribution of COPD severity was: 27.4% in group A, 24.7% in group B, 11.2% in group C, and 36.6% in group D.,The mean age was 66.5 (sd: 11), with 35% of women.,Management of COPD differed according to the comorbidities, with the same level of severity.,Only 28.4% of patients had no comorbidities associated with COPD.,The proportion of patients with two comorbidities was significantly higher (p < 0.001) in GOLD B (50.4%) and D patients (53.1%) than in GOLD A (35.4%) and GOLD C ones (34.3%).,The cluster analysis showed five phenotypes of comorbidities: cluster 1 included cardiac profile; cluster 2 included less comorbidities; cluster 3 included metabolic syndrome, apnea and anxiety-depression; cluster 4 included denutrition and osteoporosis and cluster 5 included bronchiectasis.,The clusters were mostly significantly associated with symptomatic patients i.e.,GOLD B and GOLD D.,This study in a large real-life cohort shows that multimorbidity is common in patients with COPD.,The online version of this article (10.1186/s12890-018-0684-7) contains supplementary material, which is available to authorized users.

Self-management interventions for chronic obstructive pulmonary disease (COPD) can improve quality of life, reduce hospital admissions, and improve symptoms.,However, many factors impede engagement for patients and practitioners.,Qualitative research, with its focus on subjective experience, can provide invaluable insights into such factors.,Therefore, a systematic review and synthesis of qualitative evidence on COPD self-management from the perspective of patients, carers, and practitioners was conducted.,Following a systematic search and screening, 31 studies were appraised and data extracted for analysis.,This review found that patients can adapt to COPD; however, learning to self-manage is often a protracted process.,Emotional needs are considerable; frustration, depression, and anxiety are common.,In addition, patients can face an assortment of losses and limitations on their lifestyle and social interaction.,Over time, COPD can consume their existence, reducing motivation.,Support from family can prove vital, yet tinged with ambivalence and burden.,Practitioners may not have sufficient time, resources, or appropriate skills or confidence to provide effective self-management support, particularly in regard to patients’ psychosocial needs.,This can compound patients’ capability to engage in self-management.,For COPD self-management to be effective, patients’ psychosocial needs must be prioritised alongside medication and exacerbation management.,In addition, patients’ personal beliefs regarding COPD and its management should be reviewed periodically to avoid problematic behaviours and enhance positive adaptions to the disease.,Patients with COPD are not a homogenous group and no one intervention will prove effective for all.,Finally, practitioners require greater education, training, and support to successfully assist patients.

In chronic obstructive pulmonary disease (COPD), the problem of poor patient participation in studies of self-management (SM) and pulmonary rehabilitation (PR) programmes (together referred to as COPD support programmes) is established.,Understanding this problem beyond the previously reported socio-demographics and clinical factors is critical.,The aim of this study was to explore factors that explain patient participation in studies of COPD support programmes.,Thematic ‘framework’ synthesis was conducted on literature published from 1984 to 1 February 2015.,Emergent themes and subthemes were mapped onto the adapted ‘attitude-social influence-external barriers’ and the ‘self-regulation’ models to produce analytical themes.,Ten out of 12 studies were included: PR (n=9) and SM (n=1).,Three descriptive themes with 38 subthemes were mapped onto the models' constructs, and it generated four analytical themes: ‘attitude’, ‘social influences’ and ‘illness’ and ‘intervention representations’.,The following factors influenced (1) attendance-helping oneself through health improvements, perceived control of worsening condition, perceived benefits and positive past experience of the programme, as well as perceived positive influence of professionals; (2) non-attendance-perceived negative effects and negative past experience of the programme, perceived physical/practical concerns related to attendance, perceived severity of condition/symptoms and perceived negative influence of professionals/friends; (3) dropout-no health improvements perceived after attending a few sessions of the programme, perceived severity of the condition and perceived physical/practical concerns related to attendance.,Psychosocial factors including perceived practical/physical concerns related to attendance influenced patients’ participation in COPD support programmes.,Addressing the negative beliefs/perceptions via behaviour change interventions may help improve participation in COPD support programmes and, ultimately, patient outcomes.

Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation.

Viral infection is a common trigger for acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,The aim of this study is to investigate the expression of cytokines in AECOPD.,Patients with AECOPD requiring hospitalization were recruited.,Meanwhile healthy volunteers of similar age that accepted routine check-ups and showed no clinical symptoms of inflammatory diseases were also recruited.,Induced sputum and serum were collected.,Induced sputum of participants was processed and tested for thirteen viruses and bacteria.,Forty cytokines were assayed in serum using the Quantibody Human Inflammation Array 3 (Ray Biotech, Inc.).,The most common virus detected in virus positive AECOPD (VP) was influenza A (16%).,No virus was found in controls.,Circulating levels of IL-6, TNF-α, and MCP-1 were elevated in VP and coinfection subjects (p < 0.05), while the levels of 37 other cytokines showed no difference, compared with virus negative groups and controls (p > 0.05).,Additionally, VP patients were less likely to have received influenza vaccination.,VP patients had a systemic inflammation response involving IL-6, TNF-α, and MCP-1 which may be due to virus-induced activation of macrophages.,There are important opportunities for further investigating AECOPD mechanisms and for the development of better strategies in the management and prevention of virus-related AECOPD.

The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally.

Anxiety and depression are common co-morbidities in patients with chronic obstructive pulmonary disease (COPD).,Serious implications can result from psychological difficulties in COPD including reduced survival, lower quality of life, and reduced physical and social functioning, increased use of health care resources and are associated with unhealthy behaviours such as smoking.,Cognitive behavioural therapy (CBT) is a psychological intervention which is recommended for the treatment of many mental health problems including anxiety and depression.,Unfortunately access to trained CBT therapists is limited.,The aim of this study is to test the hypothesis that CBT delivered by respiratory nurses is effective in the COPD population.,In this paper the design of the Newcastle Chronic Obstructive Pulmonary Disease Cognitive Behavioural Therapy Study (Newcastle COPD CBT Care Study) is described.,This is a prospective open randomised controlled trial comparing CBT with self-help leaflets.,The primary outcome measure is the Hospital Anxiety & Depression Scale (HADS) - anxiety subscale.,Secondary outcome measures include disease specific quality of life COPD Assessment Tool (CAT), generic quality of life (EQ5D) and HADS-depression subscale.,Patients will be followed up at three, six and 12 months following randomisation.,This is the first randomised controlled trial to evaluate the use of cognitive behavioural therapy undertaken by respiratory nurses.,Recruitment has commenced and should be complete by February 2014.,Current Controlled Trials, ISRCTN55206395

Data on patients with coronavirus disease 2019 (COVID-19) who return to hospital after discharge are scarce.,Characterization of these patients may inform post-hospitalization care.,To describe clinical characteristics of patients with COVID-19 who returned to the emergency department (ED) or required readmission within 14 days of discharge.,Retrospective cohort study of SARS-COV-2-positive patients with index hospitalization between February 27 and April 12, 2020, with ≥ 14-day follow-up.,Significance was defined as P < 0.05 after multiplying P by 125 study-wide comparisons.,Hospitalized patients with confirmed SARS-CoV-2 discharged alive from five New York City hospitals.,Readmission or return to ED following discharge.,Of 2864 discharged patients, 103 (3.6%) returned for emergency care after a median of 4.5 days, with 56 requiring inpatient readmission.,The most common reason for return was respiratory distress (50%).,Compared with patients who did not return, there were higher proportions of COPD (6.8% vs 2.9%) and hypertension (36% vs 22.1%) among those who returned.,Patients who returned also had a shorter median length of stay (LOS) during index hospitalization (4.5 [2.9,9.1] vs 6.7 [3.5, 11.5] days; Padjusted = 0.006), and were less likely to have required intensive care on index hospitalization (5.8% vs 19%; Padjusted = 0.001).,A trend towards association between absence of in-hospital treatment-dose anticoagulation on index admission and return to hospital was also observed (20.9% vs 30.9%, Padjusted = 0.06).,On readmission, rates of intensive care and death were 5.8% and 3.6%, respectively.,Return to hospital after admission for COVID-19 was infrequent within 14 days of discharge.,The most common cause for return was respiratory distress.,Patients who returned more likely had COPD and hypertension, shorter LOS on index-hospitalization, and lower rates of in-hospital treatment-dose anticoagulation.,Future studies should focus on whether these comorbid conditions, longer LOS, and anticoagulation are associated with reduced readmissions.,The online version of this article (10.1007/s11606-020-06120-6) contains supplementary material, which is available to authorized users.

The potential detrimental effects of steroids on the immune system to fight viral infections had always been a concern for patients on long term steroids in chronic conditions.,A recent warning from WHO on systemic corticosteroid use amid COVID-19 raised suspicion among public and healthcare professionals regarding the safety of steroid use during the SARS-CoV-2 pandemic.,The corticosteroids (inhaled and oral) are commonly prescribed in the management of asthma and COPD patients and any unsolicited changes in medications use may lead to potentially severe exacerbations and may risk patient lives.,This article provides a critical review of clinical evidence and offers a detailed discussion on the safety and efficacy of corticosteroids in asthma and COPD patients, both with and without COVID-19.

Objective.,The aim of this study was to investigate the association between COPD and major adverse cardiovascular and cerebral events (MACCE) in patients undergoing percutaneous coronary intervention (PCI).,Methods. 2,362 patients who underwent PCI were included in this study.,Subjects were divided into 2 groups: with COPD (n = 233) and without COPD (n = 2,129).,Cox proportional hazards models were analyzed to determine the effect of COPD on the incidence of MACCE.,Results.,The patients with COPD were older (P < 0.0001) and were more likely to be current smokers (P = 0.02) and have had hypertension (P = 0.02) and diabetes mellitus (P = 0.01).,Prevalence of serious cardiovascular comorbidity was higher in the patients with COPD, including a history of MI (P = 0.02) and HF (P < 0.0001).,Compared with non-COPD group, the COPD group showed a higher risk of all-cause death (hazard ratio (HR): 2.45, P < 0.0001), cardiac death (HR: 2.53, P = 0.0002), MI (HR: 1.387, P = 0.027), and HF (HR: 2.25, P < 0.0001).,Conclusions.,Patients with CAD and concomitant COPD are associated with a higher incidence of MACCE (all-cause death, cardiac death, MI, and HF) compared to patients without COPD.,The patients with a history of COPD have higher in-hospital and long-term mortality rates than those without COPD after PCI.

Cardiovascular diseases, osteoporosis, and depression are identified comorbidities of chronic obstructive pulmonary disease (COPD), but there have been few reports of chronic kidney disease (CKD) as a comorbidity of COPD.,The objective of this study was to investigate the prevalence of CKD in COPD patients using estimated glomerular filtration rate (eGFR) based on creatinine (Cr) and cystatin C (Cys) levels.,The prevalence of CKD and the values of various CKD-related parameters were compared between 108 stable COPD outpatients (COPD group) and a non-COPD control group consisting of 73 patients aged 60 years or more without a history of COPD or kidney disease.,CKD was defined as an eGFR less than 60 mL/min/1.73 m2.,The Cr level was significantly higher in the COPD group, but eGFR based on serum Cr (eGFRCr) was not significantly different between the two groups (73.3±25.3 vs 79.7±15.5 mL/min/1.73 m2).,The Cys level was significantly higher and eGFR based on serum Cys (eGFRCys) was significantly lower in the COPD group (60.0±19.4 vs 74.0±13.5 mL/min/1.73 m2, P<0.0001).,The prevalence of CKD evaluated based on eGFRCr was 31% in the COPD group and 8% in the non-COPD group with an odds ratio of 4.91 (95% confidence interval, 1.94-12.46, P=0.0008), whereas the evaluated prevalence based on eGFRCys was 53% in the COPD group and 15% in the non-COPD group with an odds ratio of 6.30 (95% confidence interval, 2.99-13.26, P<0.0001), demonstrating a higher prevalence of CKD when based on eGFRCys rather than on eGFRCr.,CKD is a comorbidity that occurs frequently in COPD patients, and we believe that renal function in Japanese COPD patients should preferably be evaluated based not only on Cr but on Cr in combination with Cys.

Despite the availability of guideline recommendations, diagnostic confusion between COPD and asthma appears common, and often it is very difficult to decide whether the obstruction is caused by asthma or COPD in a patient with airway obstruction.,However, there are well-defined features that help in differentiating asthma from COPD in the presence of fixed airflow obstruction.,Nonetheless, the presentations of asthma and COPD can converge and mimic each other, making it difficult to give these patients a diagnosis of either condition.,The association of asthma and COPD in the same patient has been designated mixed asthma-COPD phenotype or overlap syndrome.,However, since the absence of a clear definition and the inclusion of patients with different characteristics under this umbrella term, it may not facilitate treatment decisions, especially in the absence of clinical trials addressing this heterogeneous population.,We are realizing that neither asthma nor COPD are single diseases, but rather syndromes consisting of several endotypes and phenotypes, consequently comprising a spectrum of diseases that must be recognized and adequately treated with targeted therapy.,Therefore, we must treat patients by personalizing therapy on the basis of those treatable traits present in each subject.

This study was conducted in order to investigate the differences in the respiratory physiology of patients with chronic obstructive pulmonary disease (COPD), asthma-COPD overlap syndrome (ACOS), and asthma with airflow limitation (asthma FL+).,The medical records for a series of all stable patients with persistent airflow limitation due to COPD, ACOS, or asthma were retrospectively reviewed and divided into the COPD group (n=118), the ACOS group (n=32), and the asthma FL+ group (n=27).,All the patients underwent chest high-resolution computed tomography (HRCT) and pulmonary function tests, including respiratory impedance.,The low attenuation area score on chest HRCT was significantly higher in the COPD group than in the ACOS group (9.52±0.76 vs 5.09±1.16, P<0.01).,The prevalence of bronchial wall thickening on chest HRCT was significantly higher in the asthma FL+ group than in the COPD group (55.6% vs 25.0%, P<0.01).,In pulmonary function, forced expiratory volume in 1 second (FEV1) and peak expiratory flow rate were significantly higher in the asthma FL+ group than in the ACOS group (76.28%±2.54% predicted vs 63.43%±3.22% predicted, P<0.05 and 74.40%±3.16% predicted vs 61.08%±3.54% predicted, P<0.05, respectively).,Although residual volume was significantly lower in the asthma FL+ group than in the COPD group (112.05%±4.34% predicted vs 137.38%±3.43% predicted, P<0.01) and the ACOS group (112.05%±4.34% predicted vs148.46%±6.25% predicted, P<0.01), there were no significant differences in functional residual capacity or total lung capacity.,The increase in FEV1 in response to short-acting β2-agonists was significantly greater in the ACOS group than in the COPD group (229±29 mL vs 72±10 mL, P<0.01) and the asthma FL+ group (229±29 mL vs 153±21 mL, P<0.05).,Regarding respiratory impedance, resistance at 5 Hz and resistance at 20 Hz, which are oscillatory parameters of respiratory resistance, were significantly higher in the asthma FL+ group than in the COPD group at the whole-breath (4.29±0.30 cmH2O/L/s vs 3.41±0.14 cmH2O/L/s, P<0.01 and 3.50±0.24 cmH2O/L/s vs 2.68±0.10 cmH2O/L/s, P<0.01, respectively), expiratory, and inspiratory phases.,Although persistent airflow limitation occurs in patients with COPD, ACOS, and asthma FL+, they may have distinct characteristics of the respiratory physiology and different responsiveness to bronchodilators.

COPD is a widespread inflammatory respiratory disorder characterized by a progressive, poorly reversible airflow limitation.,Currently available therapies are mostly based on those used to treat asthma.,However, such compounds are not able to effectively reduce the gradual functional deterioration, as well as the ongoing airway and lung inflammation occurring in COPD patients.,Therefore, there is an urgent need to improve the efficacy of the existing drug classes and to develop new treatments, targeting the main cellular and molecular mechanisms underlying disease pathogenesis.,These therapeutic strategies will be highlighted in the present review.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation.,Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear.,Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7).,Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro.,In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy.,CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression.,Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression.,Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion.,Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis.,Egr-1 −/− mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema.,We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo.,The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury.

To examine the association between exacerbation frequency and mortality following an acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,Cohort study using medical databases.,Northern Denmark.,On 1 January 2005, we identified all patients with prevalent hospital-diagnosed chronic obstructive pulmonary disease (COPD) who had at least one AECOPD during 1 January 2005 to 31 December 2009.,We followed patients from the first AECOPD during this period until death, emigration or 31 December 2009, whichever came first.,We flagged all AECOPD events during follow-up and characterised each by the exacerbation frequency (0, 1, 2 or 3+) in the prior 12-month period.,Using Cox regression, we computed 0-30-day and 31-365-day age-adjusted, sex-adjusted, and comorbidity-adjusted mortality rate ratios (MRRs) with 95% CIs entering exacerbation frequency as a time-varying exposure.,We identified 16 647 eligible patients with prevalent COPD, of whom 6664 (40%) developed an AECOPD and were thus included in the study cohort.,The 0-30-day MRRs were 0.97 (95% CI 0.80 to 1.18), 0.90 (95% CI 0.70 to 1.15) and 1.03 (95% CI 0.81 to 1.32) among patients with AECOPD with 1, 2 and 3+ AECOPDs versus no AECOPD within the past 12 months, respectively.,The corresponding MRRs were 1.47 (95% CI 1.30 to 1.66), 1.89 (95% CI 1.59 to 2.25) and 1.59 (95% CI 1.23 to 2.05) for days 31-365.,Among patients with AECOPD, one or more exacerbations in the previous year were not associated with 30-day mortality but were associated with an increased 31-365-day mortality.

Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a leading cause of hospitalizations and readmissions in the US.,Reducing the frequency of hospital readmission is a high priority of US health care organizations and government agencies.,This study evaluated the risk factors associated with readmissions among commercially insured adults aged 40-65 years in the US who were hospitalized for COPD.,This retrospective cohort study used anonymized claims data from the Truven Health MarketScan® Commercial Claims and Encounters database.,The patients included were aged 40-65 years, had an index hospitalization with a primary diagnosis of COPD between July 1, 2008 and June 30, 2010 (continuously enrolled 12 months before and after), and were alive at hospital discharge.,Patients with cystic fibrosis or tuberculosis or who were transferred to another inpatient facility after hospital discharge were excluded.,All readmissions regardless of diagnosis, and separately a subset of all readmissions that had COPD as a primary or secondary diagnosis (COPD-related), were examined.,Univariate descriptive statistics and multivariable regression methods were used.,Of the 18,568 patients with index COPD hospitalizations, 6,095 (32.83%) met the eligibility criteria.,Of those, 503 (8.25%) were readmitted within the first 30 days post-index hospitalization and 2,527 (41.46%) within the first year (COPD-related 340 [5.58%] and 1,681 [27.58%], respectively).,The median time to the first readmission post initial discharge was 4.0 months, with a mean of 5.0 ± 3.4 months.,Multivariable regression analyses showed that comorbid conditions and health care utilization in the pre-index period were significant predictors for readmission both 30 and 90 days following index hospitalization.,A relatively high readmission rate was observed for patients aged 40-65 years.,The results suggest that attention to patient comorbidities and pre-index/index health care service utilization may help identify hospitalized COPD patients at higher risk for readmission.

This study investigates the role of proinflammatory monocytes recruited from blood circulation and recovered in bronchoalveolar lavage (BAL) fluid in mediating the lung damage in a model of acute cigarette smoke (CS)-induced lung inflammation in two strains of mice with different susceptibility to develop emphysema (susceptible -C57BL/6J and non susceptible -129S2/SvHsd).,Exposure to whole-body CS for 3 consecutive research cigarettes in one single day induced acute inflammation in the lung of mice.,Analysis of BAL fluid showed more influx of recently migrated monocytes at 72 h after CS-exposition in susceptible compared to non susceptible mice.,It correlated with an increase in MMP-12 and TNF-α protein levels in the lung tissue, and with an increment of NF-κB translocation to the nucleus measured by electrophoretic mobility shift assay in C57BL/6J mice.,To determine the functional role of these proinflammatory monocytes in mediating CS-induced airway inflammation, alveolar macrophages and blood monocytes were transiently removed by pretreatment with intratracheal and intravenous liposome-encapsulated CL2MDP, given 2 and 4 days prior to CS exposure and their repopulation was studied.,Monocytes/macrophages were maximally depleted 48 h after last liposome application and subsequently recently migrated monocytes reappeared in BAL fluid of susceptible mice at 72 h after CS exposure.,Recently migrated monocytes influx to the lung correlated with an increase in the MMP-12 protein level in the lung tissue, indicating that the increase in proinflammatory monocytes is associated with a major tissue damaging.,Therefore our data confirm that the recruitment of proinflammatory recently migrated monocytes from the blood are responsible for the increase in MMP-12 and has an important role in the pathogenesis of lung disease induced by acute lung inflammation.,These results could contribute to understanding the different susceptibility to CS of these strains of mice.

Macrophages have been implicated in the pathogenesis of COPD.,M1 and M2 macrophages constitute subpopulations displaying pro- and anti-inflammatory properties.,We hypothesized that smoking cessation affects macrophage heterogeneity in the lung of patients with COPD.,Our aim was to study macrophage heterogeneity using the M2-marker CD163 and selected pro- and anti-inflammatory mediators in bronchoalveolar lavage (BAL) fluid and induced sputum from current smokers and ex-smokers with COPD.,114 COPD patients (72 current smokers; 42 ex-smokers, median smoking cessation 3.5 years) were studied cross-sectionally and underwent sputum induction (M/F 99/15, age 62 ± 8 [mean ± SD] years, 42 (31-55) [median (range)] packyears, post-bronchodilator FEV1 63 ± 9% predicted, no steroids past 6 months).,BAL was collected from 71 patients.,CD163+ macrophages were quantified in BAL and sputum cytospins.,Pro- and anti-inflammatory mediators were measured in BAL and sputum supernatants.,Ex-smokers with COPD had a higher percentage, but lower number of CD163+ macrophages in BAL than current smokers (83.5% and 68.0%, p = 0.04; 5.6 and 20.1 ×104/ml, p = 0.001 respectively).,The percentage CD163+ M2 macrophages was higher in BAL compared to sputum (74.0% and 30.3%, p < 0.001).,BAL M-CSF levels were higher in smokers than ex-smokers (571 pg/ml and 150 pg/ml, p = 0.001) and correlated with the number of CD163+ BAL macrophages (Rs = 0.38, p = 0.003).,No significant differences were found between smokers and ex-smokers in the levels of pro-inflammatory (IL-6 and IL-8), and anti-inflammatory (elafin, and Secretory Leukocyte Protease Inhibitor [SLPI]) mediators in BAL and sputum.,Our data suggest that smoking cessation partially changes the macrophage polarization in vivo in the periphery of the lung towards an anti-inflammatory phenotype, which is not accompanied by a decrease in inflammatory parameters.

Chronic obstructive pulmonary disease (COPD) constitutes a major health challenge in Central and Eastern European (CEE) countries.,However, clinical phenotypes, symptom load, and treatment habits of patients with COPD in CEE countries remain largely unknown.,This paper provides a rationale for phenotyping COPD and describes the methodology of a large study in CEE.,The POPE study is an international, multicenter, observational cross-sectional survey of patients with COPD in CEE.,Participation in the study is offered to all consecutive outpatients with stable COPD in 84 centers across the CEE region if they fulfill the following criteria: age >40 years, smoking history ≥10 pack-years, a confirmed diagnosis of COPD with postbronchodilator FEV1/FVC <0.7, and absence of COPD exacerbation ≥4 weeks.,Medical history, risk factors for COPD, comorbidities, lung function parameters, symptoms, and pharmaceutical and nonpharmaceutical treatment are recorded.,The POPE project is registered in ClinicalTrials.gov with the identifier NCT02119494.,The primary aim of the POPE study was to phenotype patients with COPD in a real-life setting within CEE countries using predefined classifications.,Secondary aims of the study included analysis of differences in symptoms, and diagnostic and therapeutic behavior in participating CEE countries.,There is increasing acceptance toward a phenotype-driven therapeutic approach in COPD.,The POPE study may contribute to reveal important information regarding phenotypes and therapy in real-life CEE.

This study was conducted to determine COPD severity at the time of diagnosis as confirmed by spirometry in patients treated in a US managed care setting.,All patients with one or more inpatient stays, one or more emergency department visits, or two or more outpatient visits with diagnosis codes for COPD during 1994-2006 were identified from the Lovelace Patient Database.,From this group, a subset of continuously enrolled patients with evidence in claims of a first available pulmonary function test or pulmonary clinic visit and a confirmatory claim for a COPD diagnosis was selected.,Medical chart abstraction was undertaken for this subset to gather information for diagnosis and severity staging of each patient based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD.,Of the 12,491 patients with a primary or secondary COPD diagnosis between 1994 and 2006, there were 1520 continuously enrolled patients who comprised the study cohort.,Among the 648 eligible records from patients with evidence of a pulmonary function test, 366 were identified by spirometry as having COPD of GOLD stage I or higher (average percentage of predicted forced expiratory volume in 1 second: 60%): 19% were diagnosed at the stage of mild disease (GOLD stage I); 50% at moderate disease (GOLD stage II); and 31% at severe or very severe disease (GOLD stage III or IV, respectively).,The majority of patients in these groups were not receiving maintenance treatment.,The results demonstrate a very low incidence of early-stage diagnosis, confirmed by a pulmonary function test, of COPD in a large US sample and support calls for increased screening for COPD and treatment upon diagnosis.