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To estimate patient- and episode-level direct costs of chronic obstructive pulmonary disease (COPD) among commercially insured patients in the US.,In this retrospective claims-based analysis, commercial enrollees with evidence of COPD were grouped into five mutually exclusive cohorts based on the most intensive level of COPD-related care they received in 2006, ie, outpatient, urgent outpatient (outpatient care in addition to a claim for an oral corticosteroid or antibiotic within seven days), emergency department (ED), standard inpatient admission, and intensive care unit (ICU) cohorts.,Patient- level COPD-related annual health care costs, including patient- and payer-paid costs, were compared among the cohorts.,Adjusted episode-level costs were calculated.,Of the 37,089 COPD patients included in the study, 53% were in the outpatient cohort, 37% were in the urgent outpatient cohort, 3% were in the ED cohort, and the standard admission and ICU cohorts together comprised 6%.,Mean (standard deviation, SD) annual COPD-related health care costs (2008 US$) increased across the cohorts (P < 0.001), ranging from $2003 ($3238) to $43,461 ($76,159) per patient.,Medical costs comprised 96% of health care costs for the ICU cohort.,Adjusted mean (SD) episode-level costs were $305 ($310) for an outpatient visit, $274 ($336) for an urgent outpatient visit, $327 ($65) for an ED visit, $9745 ($2968) for a standard admission, and $33,440 for an ICU stay.,Direct costs of COPD-related care for commercially insured patients are driven by hospital stays with or without ICU care.,Exacerbation prevention resulting in reduced need for inpatient care could lower costs.

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.

Rationale: Bronchoscopic lung volume reduction with Zephyr Valves improves lung function, exercise tolerance, and quality of life of patients with hyperinflated emphysema and little to no collateral ventilation.,Objectives:Post hoc analysis of patient-reported outcomes (PROs), including multidimensional measures of dyspnea, activity, and quality of life, in the LIBERATE (Lung Function Improvement after Bronchoscopic Lung Volume Reduction with Pulmonx Endobronchial Valves used in Treatment of Emphysema) study are reported.,Methods: A total of 190 patients with severe heterogeneous emphysema and little to no collateral ventilation in the target lobe were randomized 2:1 to the Zephyr Valve or standard of care.,Changes in PROs at 12 months in the two groups were compared: dyspnea with the Transitional Dyspnea Index (TDI), focal score; the Chronic Obstructive Pulmonary Disease Assessment Test (CAT; breathlessness on hill/stairs); Borg; the EXAcerbations of Chronic pulmonary disease Tool-PRO, dyspnea domain; activity with the TDI, magnitude of task/effort/functional impairment, CAT (limited activities), and the St.,George’s Respiratory Questionnaire (SGRQ), activity domain; and psychosocial status with the SGRQ, impacts domain, and CAT (confidence and energy).,Results: At 12 months, patients using the Zephyr Valve achieved statistically significant and clinically meaningful improvements in the SGRQ; CAT; and the TDI, focal score, compared with standard of care.,Improvements in the SGRQ were driven by the impacts and activity domains (P < 0.05 and P < 0.001, respectively).,Reduction in CAT was through improvements in breathlessness (P < 0.05), energy level (P < 0.05), activities (P < 0.001), and increased confidence when leaving home (P < 0.05).,The TDI measures of effort, task, and functional impairment were uniformly improved (P < 0.001).,The EXAcerbations of Chronic Pulmonary Disease Tool (EXACT)-PRO, dyspnea domain, was significantly improved in the Zephyr Valve group.,Improvements correlated with changes in residual volume and residual volume/TLC ratio.,Conclusions: Patients with severe hyperinflated emphysema achieving lung volume reductions with Zephyr Valves experience improvements in multidimensional scores for breathlessness, activity, and psychosocial parameters out to at least 12 months.,Clinical trial registered with www.clinicaltrials.gov (NCT01796392).

Oxidative stress contributes to chronic obstructive pulmonary disease (COPD) exacerbations and antioxidants can decrease exacerbation rates, although we lack data about the effect of such drugs on exacerbation duration.,The RESTORE (Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD) study was a prospective randomised, double-blind, placebo-controlled study, enrolling patients aged 40-80 years with Global Initiative for Chronic Obstructive Lung Disease stage II/III.,Patients received erdosteine 300 mg twice daily or placebo added to usual COPD therapy for 12 months.,The primary outcome was the number of acute exacerbations during the study.,In the pre-specified intention-to-treat population of 445 patients (74% male; mean age 64.8 years, forced expiratory volume in 1 s 51.8% predicted) erdosteine reduced the exacerbation rate by 19.4% (0.91 versus.,1.13 exacerbations·patient−1·year−1 for erdosteine and placebo, respectively; p=0.01), due to an effect on mild events; the reduction in the rate of mild exacerbations was 57.1% (0.23 versus 0.54 exacerbations·patient−1·year−1 for erdosteine and placebo, respectively; p=0.002).,No significant difference was observed in the rate of moderate and severe exacerbations (0.68 versus 0.59 exacerbations·patient−1·year−1 for erdosteine and placebo, respectively; p=0.054) despite a trend in favour of the comparison group.,Erdosteine decreased the exacerbation duration irrespective of event severity by 24.6% (9.55 versus 12.63 days for erdosteine and placebo, respectively; p=0.023).,Erdosteine significantly improved subject and physician subjective severity scores (p=0.022 and p=0.048, respectively), and reduced the use of reliever medication (p<0.001), but did not affect the St George's Respiratory Questionnaire score or the time to first exacerbation.,In patients with COPD, erdosteine can reduce both the rate and duration of exacerbations.,The percentage of patients with adverse events was similar in both the placebo and erdosteine treatment groups.,RESTORE study: erdosteine reduces both rate and duration of COPD exacerbations with a placebo-like safety profilehttp://ow.ly/BbGI30dRdEt

The aim of this study was to assess the current evidence for long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combinations (FDCs) in the treatment of COPD.,A systematic literature search of randomized controlled trials published in English up to September 2017 of LABA/LAMA FDCs vs LABA or LAMA or LABA/inhaled corticosteroid (ICS) FDCs in COPD patients was performed using PubMed, Embase, Scopus, and Google Scholar.,Outcomes including forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index (TDI) scores, St George’s Respiratory Questionnaire (SGRQ) scores, exacerbations, exercise tolerance (endurance time [ET]), inspiratory capacity (IC), and rescue medication use were evaluated.,In total, 27 studies were included in the review.,LABA/LAMA FDCs significantly improved lung function (FEV1) at 12 weeks compared with LABA or LAMA or LABA/ICS.,These effects were maintained over time.,Significant improvements with LABA/LAMA FDCs vs each evaluated comparator were also observed in TDI and SGRQ scores, even if significant differences between different LABA/LAMA FDCs were detected.,Only the LABA/LAMA FDC indacaterol/glycopyrronium has shown superiority vs LAMA and LABA/ICS for reducing exacerbation rates, while olodaterol/tiotropium and indacaterol/glycopyrronium have been shown to improve ET and IC vs the active comparators.,Rescue medication use was significantly reduced by LABA/LAMA FDCs vs the evaluated comparators.,LABA/LAMA FDCs were safe, with no increase in the risk of adverse events with LABA/LAMA FDCs vs the monocomponents.,Evidence supporting the efficacy of LABA/LAMA FDCs for COPD is heterogeneous, particularly for TDI and SGRQ scores, exacerbation rates, ET, and IC.,So far, indacaterol/glycopyrronium is the LABA/LAMA FDC that has the strongest evidence for superiority vs LABA, LAMA, and LABA/ICS FDCs across the evaluated outcomes.,LABA/LAMA FDCs were safe; however, more data should be collected in a real-world setting to confirm their safety.

COPD is a major global cause of mortality and morbidity.,PINNACLE-4 evaluated the efficacy and safety of GFF MDI (glycopyrrolate/formoterol fumarate metered dose inhaler) in patients from Asia, Europe, and the USA with moderate-to-very severe COPD.,In this double-blind, placebo-controlled, Phase III study, patients were randomized to treatment with GFF MDI 18/9.6 μg, glycopyrrolate (GP) MDI 18 μg, formoterol fumarate (FF) MDI 9.6 μg, or placebo MDI (all twice daily) for 24 weeks.,Lung function, patient-reported outcomes (symptoms and health-related quality of life), and safety were assessed.,Of the 1,756 patients randomized, 1,740 patients were included in the intent-to-treat population (mean age 64.2 years, 74.1% male, and 40.2% Asian).,GFF MDI significantly improved morning predose trough FEV1 at Week 24 (primary endpoint) vs placebo MDI, GP MDI, and FF MDI (least squares mean differences: 165, 59, and 72 mL, respectively; all P<0.0001).,GFF MDI also significantly improved other lung function endpoints vs placebo MDI, GP MDI, and FF MDI and patient-reported outcomes vs placebo MDI and GP MDI.,A larger proportion of patients treated with GFF MDI achieved the minimum clinically important difference in Transition Dyspnea Index score vs GP MDI and placebo MDI and in St George’s Respiratory Questionnaire score vs placebo MDI.,Adverse event rates were similar across treatment groups.,These results demonstrated the efficacy of GFF MDI in patients with moderate-to-very severe COPD.,GFF MDI was well tolerated, with a safety profile commensurate with long-acting bronchodilators.

Progression of chronic obstructive pulmonary disease (COPD) is linked to episodes of exacerbations caused by bacterial infections due to Streptococcus pneumoniae.,Our objective was to identify during COPD, factors of susceptibility to bacterial infections among cytokine network and their role in COPD exacerbations.,S. pneumoniae was used to sub-lethally challenge mice chronically exposed to air or cigarette smoke (CS) and to stimulate peripheral blood mononuclear cells (PBMC) from non-smokers, smokers and COPD patients.,The immune response and the cytokine production were evaluated.,Delayed clearance of the bacteria and stronger lung inflammation observed in infected CS-exposed mice were associated with an altered production of IL-17 and IL-22 by innate immune cells.,This defect was related to a reduced production of IL-1β and IL-23 by antigen presenting cells.,Importantly, supplementation with recombinant IL-22 restored bacterial clearance in CS-exposed mice and limited lung alteration.,In contrast with non-smokers, blood NK and NKT cells from COPD patients failed to increase IL-17 and IL-22 levels in response to S. pneumoniae, in association with a defect in IL-1β and IL-23 secretion.,This study identified IL-17 and IL-22 as susceptibility factors in COPD exacerbation.,Therefore targeting such cytokines could represent a potent strategy to control COPD exacerbation.

COPD patients may be at increased risk for vitamin D (25(OH)D) deficiency, but risk factors for deficiency among COPD patients have not been extensively reported.,Serum 25(OH)D levels were measured by liquid chromatography double mass spectrometry in subjects aged 40-76 years from Western Norway, including 433 COPD patients (GOLD stage II-IV) and 325 controls.,Levels <20 ng/mL defined deficiency.,Season, sex, age, body mass index (BMI), smoking, GOLD stage, exacerbation frequency, arterial oxygen tension (PaO2), respiratory symptoms, depression (CES-D score≥16), comorbidities (Charlson score), treatment for osteoporosis, use of inhaled steroids, and total white blood count were examined for associations with 25(OH)D in both linear and logistic regression models.,COPD patients had an increased risk for vitamin D deficiency compared to controls after adjustment for seasonality, age, smoking and BMI.,Variables associated with lower 25(OH)D levels in COPD patients were obesity ( = −6.63), current smoking ( = −4.02), GOLD stage III- IV ( = −4.71, = −5.64), and depression ( = −3.29).,Summertime decreased the risk of vitamin D deficiency (OR = 0.22).,COPD was associated with an increased risk of vitamin D deficiency, and important disease characteristics were significantly related to 25(OH)D levels.

There is a wide variability in measurement methodology of physical activity.,This study investigated the effect of different analysis techniques on the statistical power of physical activity outcomes after pulmonary rehabilitation.,Physical activity was measured with an activity monitor armband in 57 patients with COPD (mean ± SD age, 66 ± 7 years; FEV1, 46 ± 17% predicted) before and after 3 months of pulmonary rehabilitation.,The choice of the outcome (daily number of steps [STEPS], time spent in at least moderate physical activity [TMA], mean metabolic equivalents of task level [METS], and activity time [ACT]), impact of weekends, number of days of assessment, postprocessing techniques, and influence of duration of daylight time (DT) on the sample size to achieve a power of 0.8 were investigated.,The STEPS and ACT (1.6-2.3 metabolic equivalents of task) were the most sensitive outcomes.,Excluding weekends decreased the sample size for STEPS (83 vs 56), TMA (160 vs 148), and METS (251 vs 207).,Using 4 weekdays (STEPS and TMA) or 5 weekdays (METS) rendered the lowest sample size.,Excluding days with < 8 h wearing time reduced the sample size for STEPS (56 vs 51).,Differences in DT were an important confounder.,Changes in physical activity following pulmonary rehabilitation are best measured for 4 weekdays, including only days with at least 8 h of wearing time (during waking hours) and considering the difference in DT as a covariate in the analysis.,ClinicalTrials.gov; No.: NCT00948623; URL: www.clinicaltrials.gov

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 characterized by a persistent blockage of airflow, prompting episodes of shortness of breath, commonly leading to hospitalization.,Hospitalization may lead to a decline in physical activity following discharge.,Physical activity has been shown to improve symptoms of COPD and reduce readmissions, and to decrease morbidity and mortality.,This study aims to explore, from the perspectives of people with COPD, the barriers to and enablers of participation in physical activity following hospitalization for COPD.,This study had a qualitative descriptive design and included semistructured interviews with 28 adult COPD patients who had been admitted to hospital with a primary diagnosis of exacerbation of COPD.,A plethora of barriers to but fewer enablers of participation in physical activity and pulmonary rehabilitation were identified for this cohort of people.,The main barriers identified were health-related (comorbidities, COPD symptoms, and physical injury or illness) environment-related (weather, transport, and finance), and self-related.,The main enabling factors reported were access to health professionals and equipment, social support, routine and extracurricular activities, personal goals and motivation, and the effect of physical activity and “feeling better”.,This research provides a snapshot of the barriers to and enablers of physical activity and pulmonary rehabilitation in people with COPD.,It is evident that there are significant barriers which hinder the ability of people with COPD to undertake and continue participation in physical activity and pulmonary rehabilitation.,While there are some enablers that may counter these barriers, it is clear that health professionals dealing with people suffering from COPD need to actively recognize and address barriers to physical activity and pulmonary rehabilitation.,Hospital admission may create an opportunity for implementation of interventions promoting physical activity (such as referral to pulmonary rehabilitation), which may assist in reducing hospital readmission, as well as decreasing morbidity and mortality.

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

Oxidative stress contributes to chronic obstructive pulmonary disease (COPD) exacerbations and antioxidants can decrease exacerbation rates, although we lack data about the effect of such drugs on exacerbation duration.,The RESTORE (Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD) study was a prospective randomised, double-blind, placebo-controlled study, enrolling patients aged 40-80 years with Global Initiative for Chronic Obstructive Lung Disease stage II/III.,Patients received erdosteine 300 mg twice daily or placebo added to usual COPD therapy for 12 months.,The primary outcome was the number of acute exacerbations during the study.,In the pre-specified intention-to-treat population of 445 patients (74% male; mean age 64.8 years, forced expiratory volume in 1 s 51.8% predicted) erdosteine reduced the exacerbation rate by 19.4% (0.91 versus.,1.13 exacerbations·patient−1·year−1 for erdosteine and placebo, respectively; p=0.01), due to an effect on mild events; the reduction in the rate of mild exacerbations was 57.1% (0.23 versus 0.54 exacerbations·patient−1·year−1 for erdosteine and placebo, respectively; p=0.002).,No significant difference was observed in the rate of moderate and severe exacerbations (0.68 versus 0.59 exacerbations·patient−1·year−1 for erdosteine and placebo, respectively; p=0.054) despite a trend in favour of the comparison group.,Erdosteine decreased the exacerbation duration irrespective of event severity by 24.6% (9.55 versus 12.63 days for erdosteine and placebo, respectively; p=0.023).,Erdosteine significantly improved subject and physician subjective severity scores (p=0.022 and p=0.048, respectively), and reduced the use of reliever medication (p<0.001), but did not affect the St George's Respiratory Questionnaire score or the time to first exacerbation.,In patients with COPD, erdosteine can reduce both the rate and duration of exacerbations.,The percentage of patients with adverse events was similar in both the placebo and erdosteine treatment groups.,RESTORE study: erdosteine reduces both rate and duration of COPD exacerbations with a placebo-like safety profilehttp://ow.ly/BbGI30dRdEt

Oxidative stress is an important feature in the pathogenesis of COPD.,Targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to be beneficial in the treatment of COPD.,Antioxidant agents such as thiol molecules (glutathione and mucolytic drugs, such as N-acetyl-L-cysteine and N-acystelyn), dietary polyphenols (curcumin, resveratrol, green tea, catechins/quercetin), erdosteine, and carbocysteine lysine salt, all have been reported to control nuclear factor-kappaB (NF-κ B) activation, regulation of glutathione biosynthesis genes, chromatin remodeling, and hence inflammatory gene expression.,Specific spin traps such as α-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a superoxide dismutase mimetic M40419 have also been reported to inhibit cigarette smoke-induced inflammatory responses in vivo.,Since a variety of oxidants, free radicals, and aldehydes are implicated in the pathogenesis of COPD, it is possible that therapeutic administration of multiple antioxidants will be effective in the treatment of COPD.,Various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in COPD are discussed.

The landmark study of Fletcher and Peto on the natural history of tobacco smoke-related chronic airflow obstruction suggested that decline in the forced expiratory volume in the first second (FEV1) in chronic obstructive pulmonary disease (COPD) is slow at the beginning, becoming faster with more advanced disease.,The present authors reviewed spirometric data of COPD patients included in the placebo arms of recent clinical trials to assess the lung function decline of each stage, defined according to the severity of airflow obstruction as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,In large COPD populations the mean rate of FEV1 decline in GOLD stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year, respectively, and lower than 35 mL/year in GOLD stage IV.,Few data on FEV1 decline are available for GOLD stage I.,Hence, the loss of lung function, assessed as expiratory airflow reduction, seems more accelerated and therefore more relevant in the initial phases of COPD.,To have an impact on the natural history of COPD, it is logical to look at the effects of treatment in the earlier stages.

Indacaterol is a once-daily long-acting inhaled β2-agonist indicated for maintenance treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD).,The large inter-patient and inter-study variability in forced expiratory volume in 1 second (FEV1) with bronchodilators makes determination of optimal doses difficult in conventional dose-ranging studies.,We considered alternative methods of analysis.,We utilized a novel modelling approach to provide a robust analysis of the bronchodilatory dose response to indacaterol.,This involved pooled analysis of study-level data to characterize the bronchodilatory dose response, and nonlinear mixed-effects analysis of patient-level data to characterize the impact of baseline covariates.,The study-level analysis pooled summary statistics for each steady-state visit in 11 placebo-controlled studies.,These study-level summaries encompassed data from 7476 patients at indacaterol doses of 18.75-600 μg once daily, and showed that doses of 75 μg and above achieved clinically important improvements in predicted trough FEV1 response.,Indacaterol 75 μg achieved 74% of the maximum effect on trough FEV1, and exceeded the midpoint of the 100-140 mL range that represents the minimal clinically important difference (MCID; ≥120 mL vs placebo), with a 90% probability that the mean improvement vs placebo exceeded the MCID.,Indacaterol 150 μg achieved 85% of the model-predicted maximum effect on trough FEV1 and was numerically superior to all comparators (99.9% probability of exceeding MCID).,Indacaterol 300 μg was the lowest dose that achieved the model-predicted maximum trough response.,The patient-level analysis included data from 1835 patients from two dose-ranging studies of indacaterol 18.75-600 μg once daily.,This analysis provided a characterization of dose response consistent with the study-level analysis, and demonstrated that disease severity, as captured by baseline FEV1, significantly affects the dose response, indicating that patients with more severe COPD require higher doses to achieve optimal bronchodilation.,Comprehensive assessment of the bronchodilatory dose response of indacaterol in COPD patients provided a robust confirmation that 75 μg is the minimum effective dose, and that 150 and 300 μg are expected to provide optimal bronchodilation, particularly in patients with severe disease.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is one of the leading causes of hospitalization and is associated with considerable mortality, for which clinicians are seeking useful and easily obtained biomarkers for prognostic evaluation.,This study aimed to determine the potential role of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) as prognostic makers for hospital mortality in patients with AECOPD.,We included 303 patients with AECOPD in this retrospective study.,Clinical characteristics, NLR, PLR, and serum levels of C-reactive protein (CRP) and other data were collected.,Relationships between NLR/PLR and CRP were evaluated by Pearson’s correlation test.,Receiver operating characteristics curve and the area under the curve (AUC) were used to assess the ability of NLR and PLR to predict hospital mortality in patients with AECOPD.,Mean levels of NLR and PLR of all patients with AECOPD were 7.92±8.79 and 207.21±148.47, respectively.,NLR levels correlated with serum CRP levels (r=0.281, P<0.05).,The overall hospital mortality rate was 12.21% (37/303).,Levels of NLR and PLR were signifi-cantly higher among non-survivors compared to survivors of AECOPD (both P<0.05).,At a cut-off value of 6.24, the sensitivity and specificity of the NLR in predicting hospital mortality were 81.08% and 69.17%, respectively, with an AUC of 0.803.,At a cut-off of 182.68, the corresponding sensitivity, specificity and AUC of PLR were 64.86%, 58.27%, and 0.639.,The combination of NLR, PLR, and CRP increased the prognostic sensitivity.,NLR and PLR levels were increased in non-survivor patients with AECOPD, and the NLR may be simple and useful prognostic marker for hospital mortality in patients with AECOPD.,More studies should be carried out to confirm our findings.

COPD exacerbations requiring hospitalization increase morbidity and mortality.,Although most COPD exacerbations are neutrophilic, approximately 10%-25% of exacerbations are eosinophilic.,We aimed to evaluate mortality and outcomes of eosinophilic and non-eosinophilic COPD exacerbations and identify new biomarkers that predict survival.,A retrospective observational cohort study was carried out in a tertiary teaching hospital from January 1, 2014 to November 1, 2014.,All COPD patients hospitalized with exacerbations were enrolled in the study at their initial hospitalization and followed-up for 6 months after discharge.,Electronic data were collected from the hospital database.,Subjects’ characteristics, hemogram parameters, CRP levels, neutrophil-to-lymphocyte ratio (NLR), platelet-to-mean platelet volume ratio on admission and discharge, length of hospital stay (days), readmissions, and mortality were recorded.,Patients were grouped according to peripheral blood eosinophil (PBE) levels: Group 1, >2% PBE, eosinophilic; Group 2, non-eosinophilic ≤2%.,Patient survival after hospital discharge was evaluated by Kaplan-Meier survival analysis.,A total of 1,704 patients hospitalized with COPD exacerbation were included.,Approximately 20% were classified as eosinophilic.,Six-month mortality was similar in eosinophilic and non-eosinophilic groups (14.2% and 15.2%, respectively); however, the hospital stay length and readmission rate were longer and higher in the non-eosinophilic group (P<0.001 and P<0.01, respectively).,CRP and NLR were significantly higher in the non-eosinophilic group (both P<0.01).,The platelet-to-mean platelet volume ratio was not different between the two groups.,Cox regression analysis showed that survival was negatively influenced by elevated CRP (P<0.035) and NLR (P<0.001) in the non-eosinophilic group.,Non-eosinophilic patients with COPD exacerbations with high CRP and NLR values had worse outcomes than eosinophilic patients.,PBE and NLR can be helpful markers to guide treatment decisions.

The purpose of this study was to quantitatively assess the effects of water-based Liuzijue exercise on patients with COPD and compare it with land-based Liuzijue exercise.,Participants were randomly allocated to one of three groups: the water-based Liuzijue exercise group (WG), the land-based Liuzijue exercise group (LG), and the control group (CG).,CG participants accepted no exercise intervention, while training groups performed Liuzijue exercise according to Health Qigong Liuzijue (People’s Republic of China) in different environments for 60-min sessions twice a week for 3 months.,Of the 50 patients enrolled, 45 (90%) completed the 3-month intervention.,The CG showed decreased expiratory muscle strength, extensor and flexor endurance ratio (ER) of the elbow joints and flexor peak torque (PT), total work (TW), and ER of the knee joints (p<0.05).,Both training groups showed improved respiratory muscle strength, which differed from the CG (p<0.001).,In addition, extensor and flexor TW of the elbow joints in the training groups were increased (p<0.01), and the WG differed from the CG in extensor TW and ER and flexor TW (p<0.01), while the LG differed from the CG in flexor TW and extensor ER (p<0.05).,PT, PT/body weight (BW), and TW in the knee joint extensor in the training groups were increased as well (PT and PT/BW: p<0.05, TW: p<0.01), and the WG differed from the CG in terms of knee joints outcomes, while the LG differed from the CG in flexor TW only (p<0.05).,Water-based Liuzijue exercise has beneficial effects on COPD patients’ respiratory muscle strength and peripheral skeletal muscle function, and additional benefits may exist in endurance of upper limbs and strength and endurance of lower limbs when compared with land-based Liuzijue exercise.

Breathlessness is a primary clinical feature of chronic obstructive pulmonary disease (COPD).,We aimed to describe the frequency of and factors associated with breathlessness in a cohort of COPD patients identified from the Clinical Practice Research Datalink (CPRD), a general practice electronic medical records database.,Patients with a record of COPD diagnosis after January 1 2008 were identified in the CPRD.,Breathlessness was assessed using the Medical Research Council (MRC) dyspnoea scale, with scoring ranging from 1-5, which has been routinely administered as a part of the regular assessment of patients with COPD in the general practice since April 2009.,Stepwise multivariate logistic regression estimated independent associations with dyspnoea.,Negative binomial regression evaluated a relationship between breathlessness and exacerbation rate during follow-up.,The total cohort comprised 49,438 patients diagnosed with COPD; 40,425 (82%) had any MRC dyspnoea grade recorded.,Of those, 22,770 (46%) had moderate-to-severe dyspnoea (MRC≥3).,Breathlessness increased with increasing airflow limitation; however, moderate-to-severe dyspnoea was also observed in 32% of patients with mild airflow obstruction.,Other factors associated with increased dyspnoea grade included female gender, older age (≥70 years), obesity (BMI ≥30), history of moderate-to-severe COPD exacerbations, and frequent visits to the general practitioner.,Patients with worse breathlessness were at higher risk of COPD exacerbations during follow-up.,Moderate-to-severe dyspnoea was reported by >40% of patients diagnosed with COPD in primary care.,Presence of dyspnoea, including even a perception of mild dyspnoea (MRC = 2), was associated with increased disease severity and a higher risk of COPD exacerbations during follow-up.

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.

Tumor necrosis factor alpha (TNFα) is the most widely studied pleiotropic cytokine of the TNF superfamily.,In pathophysiological conditions, generation of TNFα at high levels leads to the development of inflammatory responses that are hallmarks of many diseases.,Of the various pulmonary diseases, TNFα is implicated in asthma, chronic bronchitis (CB), chronic obstructive pulmonary disease (COPD), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).,In addition to its underlying role in the inflammatory events, there is increasing evidence for involvement of TNFα in the cytotoxicity.,Thus, pharmacological agents that can either suppress the production of TNFα or block its biological actions may have potential therapeutic value against a wide variety of diseases.,Despite some immunological side effects, anti-TNFα therapeutic strategies represent an important breakthrough in the treatment of inflammatory diseases and may have a role in pulmonary diseases characterized by inflammation and cell death.

Tiotropium is a long-acting inhaled anticholinergic developed for the treatment of chronic obstructive pulmonary disease (COPD) and has been available since 2002.,We sought to update an evaluation of the safety of tiotropium in the HandiHaler® formulation as significant clinical trial data have become available over time.,Pooled analysis of adverse event reporting from phase III and IV tiotropium HandiHaler® clinical trials with the following characteristics was performed: randomized, double-blind, parallel group, placebo-controlled design, tiotropium 18 μg once-daily dosing, COPD indication, duration of at least four weeks.,Incidence rates by treatment group, rate differences (tiotropium-placebo), and 95% confidence intervals were determined.,Twenty-six trials were identified involving 17,014 patients.,Mean age was 65 years, mean forced expiratory volume in one second was 1.16 L (41% predicted), 76% men.,Total exposure to study drug was 11,958 patient-years (tiotropium) and 10,578 patient-years (placebo).,Tiotropium was associated with a reduced risk (expressed as rate difference [95% confidence interval] per 100 patients-years at risk) for an adverse event (−17.5 [−22.9, −12.2]), serious adverse event (−1.41 [−2.81, −0.00]) and a fatal event (−0.63 [−1.14, −0.12]).,A reduced risk was present for adverse events that were cardiac (−0.79 [−1.48, −0.09]), lower respiratory (−14.2 [−17.0, −11.5]) and for a composite endpoint of major adverse cardiovascular events (−0.45 [−0.85, −0.05]).,Typical expected inhaled anticholinergic effects such as dry mouth, constipation, and urinary difficulties were observed in the safety database.,The safety data review does not indicate an increased risk for death or cardiovascular morbidity during tiotropium treatment in patients with COPD.

Clinical trials of tiotropium have principally recruited patients from secondary care with more severe chronic obstructive pulmonary disease (COPD), and typically had included limitation of concomitant medication.,In primary care, which is the most common setting for COPD management, many patients may have milder disease, and also may take a broad range of concomitant medication.,This randomised, placebo-controlled, parallel-group, 12-week, 44-centre study investigated the efficacy (trough forced expiratory volume in 1 second [FEV1] response) and safety of additional treatment with once-daily tiotropium 18 μg via the HandiHaler® in a primary care COPD population (tiotropium: N = 191, FEV1 = 1.25 L [47.91% predicted]; placebo: N = 183, FEV1 = 1.32 L [49.86% predicted]).,Secondary endpoints included: trough forced vital capacity (FVC) response, weekly use of rescue short-acting β-agonist, and exacerbation of COPD (complex of respiratory symptoms/events of >3 days in duration requiring a change in treatment).,Treatment effects were determined using non-parametric analysis.,At Week 12, median improvement in trough FEV1 response with tiotropium versus placebo was 0.06 L (p = 0.0102).,The improvement was consistent across baseline treatment and COPD severity.,Median improvement in FVC at 2, 6 and 12 weeks was 0.12 L (p < 0.001).,The percentage of patients with ≥1 exacerbation was reduced (tiotropium 9.5%; placebo 17.9%; p = 0.0147), independent of disease severity.,Rescue medication usage was significantly reduced in the tiotropium group compared with placebo.,Adverse event profile was consistent with previous studies.,Tiotropium provides additional benefits to usual primary care management in a representative COPD population.,The identifier is: NCT00274079.

Tiotropium is prescribed for the treatment of chronic obstructive pulmonary disease (COPD) and delivered via HandiHaler® (18 μg once daily) or Respimat® Soft Mist™ inhaler (5 μg once daily).,The recent TIOtropium Safety and Performance In Respimat® (TIOSPIR™) study demonstrated that both exhibit similar safety profiles.,This analysis provides an updated comprehensive safety evaluation of tiotropium® using data from placebo-controlled HandiHaler® and Respimat® trials.,Pooled analysis of adverse event (AE) data from tiotropium HandiHaler® 18 μg and Respimat® 5 μg randomized, double-blind, parallel-group, placebo-controlled, clinical trials in patients with COPD (treatment duration ≥4 weeks).,Incidence rates, rate ratios (RRs), and 95% confidence intervals (CIs) were determined for HandiHaler® and Respimat® trials, both together and separately.,In the 28 HandiHaler® and 7 Respimat® trials included in this analysis, 11,626 patients were treated with placebo and 12,929 with tiotropium, totaling 14,909 (12,469 with HandiHaler®; 2,440 with Respimat®) patient-years of tiotropium exposure.,Mean age was 65 years, and mean prebronchodilator forced expiratory volume in 1 second (FEV1) was 1.16 L (41% predicted).,The risk (RR [95% CI]) of AEs (0.90 [0.87, 0.93]) and of serious AEs (SAEs) (0.94 [0.89, 0.99]) was significantly lower in the tiotropium than in the placebo group (HandiHaler® and Respimat® pooled results), and there was a numerically lower risk of fatal AEs (FAEs) (0.90 [0.79, 1.01]).,The risk of cardiac AEs (0.93 [0.85, 1.02]) was numerically lower in the tiotropium group.,Incidences of typical anticholinergic AEs, but not SAEs, were higher with tiotropium.,Analyzed separately by inhaler, the risks of AE and SAE in the tiotropium groups remained lower than in placebo and similarly for FAEs.,This analysis indicates that tiotropium is associated with lower rates of AEs, SAEs, and similar rates of FAEs than placebo when delivered via HandiHaler® or Respimat® (overall and separately) in patients with COPD.

Tiotropium (Spiriva) is an inhaled muscarinic antagonist for patients with chronic obstructive pulmonary disease (COPD), and is available in two forms: the HandiHaler and the Respimat inhaler.,The aim of this study was to investigate the handling of and preference for each device immediately after switching from the HandiHaler to the Respimat and 2-3 years after the switch.,The study comprised two surveys.,A questionnaire was first administered to 57 patients with COPD (male:female 52:5, mean age 73.6±7.1 years) 8 weeks after switching from the HandiHaler (18 μg) to the Respimat (5 μg).,A second similar but simplified questionnaire was administered to 39 of these patients who continued to use the Respimat and were available for follow-up after more than 2 years.,Pulmonary function was also measured during each period.,In the first survey, 17.5% of patients preferred the HandiHaler, and 45.6% preferred the Respimat.,There were no significant changes in pulmonary function or in the incidence of adverse events after the switch.,In the second survey, performed 2-3 years later, the self-assessed handling of the Respimat had significantly improved, and the number of patients who preferred the Respimat had increased to 79.5%.,The efficacy of the Respimat was similar to that of the HandiHaler.,This was clear immediately after the switch, even in elderly patients with COPD who were long-term users of the HandiHaler.,The preference for the Respimat increased with continued use.

To explore the effects of group singing therapy on depression symptoms and quality of life of patients with stable chronic obstructive pulmonary disease (COPD).,Patients with COPD were randomly allocated to intervention (n = 30) and control groups (n = 30).,The intervention group received group singing therapy once a week for 24 sessions along with routine health education, whereas the control group only received the routine health education.,All patients were administered the Hospital Anxiety and Depression Scale depression subscale (HADS-D) and the Clinical COPD Questionnaire (CCQ).,Data were collected at baseline and at 1, 3, and 6 months.,Fifty-six participants completed this trial.,Significant between-group differences were observed with respect to the main effect of group and time as well as the effect of group × time interaction on HADS-D score.,The HADS-D score was significantly improved 1, 3, 6 months after group singing therapy.,The CCQ total scores were significantly different between the two groups with respect to the main effect of group and time and the group × time interaction effect.,Significantly better CCQ was detected in the intervention group at 3 months and 6 months after intervention.,Group singing therapy reduces depressive symptoms and improves the quality of life of patients with stable COPD.

More than one third of individuals with chronic obstructive pulmonary disease (COPD) experience comorbid symptoms of depression and anxiety.,This review aims to provide an overview of the burden of depression and anxiety in those with COPD and to outline the contemporary advances and challenges in the management of depression and anxiety in COPD.,Symptoms of depression and anxiety in COPD lead to worse health outcomes, including impaired health-related quality of life and increased mortality risk.,Depression and anxiety also increase health care utilization rates and costs.,Although the quality of the data varies considerably, the cumulative evidence shows that complex interventions consisting of pulmonary rehabilitation interventions with or without psychological components improve symptoms of depression and anxiety in COPD.,Cognitive behavioral therapy is also an effective intervention for managing depression in COPD, but treatment effects are small.,Cognitive behavioral therapy could potentially lead to greater benefits in depression and anxiety in people with COPD if embedded in multidisciplinary collaborative care frameworks, but this hypothesis has not yet been empirically assessed.,Mindfulness-based treatments are an alternative option for the management of depression and anxiety in people with long-term conditions, but their efficacy is unproven in COPD.,Beyond pulmonary rehabilitation, the evidence about optimal approaches for managing depression and anxiety in COPD remains unclear and largely speculative.,Future research to evaluate the effectiveness of novel and integrated care approaches for the management of depression and anxiety in COPD is warranted.

Reducing the severity of respiratory symptoms is a key goal in the treatment of chronic obstructive pulmonary disease (COPD).,We evaluated the effect of aclidinium bromide 400 μg twice daily (BID) on respiratory symptoms, assessed using the Evaluating Respiratory Symptoms in COPD (E-RS™: COPD) scale (formerly EXACT-RS).,Data were pooled from the aclidinium 400 μg BID and placebo arms of two 24-week, double-blind, randomized Phase III studies evaluating aclidinium monotherapy (ATTAIN) or combination therapy (AUGMENT COPD I) in patients with moderate to severe airflow obstruction.,Patients were stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) Groups A-D.,Change from baseline in E-RS scores, proportion of responders (patients achieving pre-defined improvements in E-RS scores), and net benefit (patients who improved minus patients who worsened) were analyzed.,Of 1210 patients, 1167 had data available for GOLD classification.,Mean (standard deviation) age was 63.2 (8.6) years, 60.7 % were male, and mean post-bronchodilator forced expiratory volume in 1 s was 54.4 % predicted.,Compared with placebo, aclidinium 400 μg BID significantly improved RS-Total (2.38 units vs 0.79 units, p < 0.001) and domain scores (all p < 0.001) at Week 24, and doubled the likelihood of being an RS-Total score responder (p < 0.05), irrespective of GOLD group.,The net benefit for RS-Total (Overall: 56.9 % vs 19.4 %; A + C: 65.7 % vs 6.3 %; B + D: 56.0 % vs 20.8 %, for aclidinium 400 μg BID and placebo respectively; all p < 0.05) and domain scores (all p < 0.05) was significantly greater with aclidinium compared with placebo, in both GOLD Groups A + C and B + D.,Aclidinium 400 μg BID significantly improved respiratory symptoms regardless of the patients’ level of symptoms at baseline.,Net treatment benefit was similar in patients with low or high levels of symptoms.,ATTAIN (ClinicalTrials.gov identifier: NCT01001494) and AUGMENT COPD I (ClinicalTrials.gov identifier: NCT01437397).,The online version of this article (doi:10.1186/s12931-016-0372-1) contains supplementary material, which is available to authorized users.

Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms and pathological consequences.,Although primarily viewed as a respiratory disease, COPD has both pulmonary and extrapulmonary effects, which have an impact on many aspects of physical, emotional, and mental well-being.,Traditional assessment of COPD relies heavily on measuring lung function, specifically forced expiratory volume in 1 second (FEV1).,However, the evidence suggests that FEV1 is a relatively poor correlate of symptoms such as breathlessness and the impact of COPD on daily life.,Furthermore, many consequences of the disease, including anxiety and depression and the ability to perform daily activities, can only be described and reported reliably by the patient.,Thus, in order to provide a comprehensive view of the effects of interventions in clinical trials, it is essential that spirometry is accompanied by assessments using patient-reported outcome (PRO) instruments.,We provide an overview of patient-reported outcome concepts in COPD, such as breathlessness, physical functioning, and health status, and evaluate the tools used for measuring these concepts.,Particular attention is given to the newly developed instruments emerging in response to recent regulatory guidelines for the development and use of PROs in clinical trials.,We conclude that although data from the development and validation of these new PRO instruments are emerging, to build the body of evidence that supports the use of a new instrument takes many years.,Furthermore, new instruments do not necessarily have better discriminative or evaluative properties than older instruments.,The development of new PRO tools, however, is crucial, not only to ensure that key COPD concepts are being reliably measured but also that the relevant treatment effects are being captured in clinical trials.,In turn, this will help us to understand better the patient’s experience of the disease.

This study aims: (1) to describe the pattern and extent of multimorbidity and polypharmacy in UK Biobank participants with chronic obstructive pulmonary disease (COPD) and (2) to identify which comorbidities are associated with increased risk of adverse drug reactions (ADRs) resulting from polypharmacy.,Cross-sectional.,Community cohort.,UK Biobank participants comparing self-reported COPD (n=8317) with no COPD (n=494 323).,Multimorbidity (≥4 conditions) and polypharmacy (≥5 medications) in participants with COPD versus those without.,Risk of ADRs (taking ≥3 medications associated with falls, constipation, urinary retention, central nervous system (CNS) depression, bleeding or renal injury) in relation to the presence of COPD and individual comorbidities.,Multimorbidity was more common in participants with COPD than those without (17% vs 4%).,Polypharmacy was highly prevalent (52% with COPD taking ≥5 medications vs 18% in those without COPD).,Adjusting for age, sex and socioeconomic status, those with COPD were significantly more likely than those without to be prescribed ≥3 medications contributing to falls (OR 2.27, 95% CI 2.13 to 2.42), constipation (OR 3.42, 95% CI 3.10 to 3.77), urinary retention (OR 3.38, 95% CI 2.94 to 3.87), CNS depression (OR 3.75, 95% CI 3.31 to 4.25), bleeding (OR 4.61, 95% CI 3.35 to 6.19) and renal injury (OR 2.22, 95% CI 1.86 to 2.62).,Concomitant cardiovascular disease was associated with the greatest risk of taking ≥3 medications associated with falls/renal injury.,Concomitant mental health conditions were most strongly associated with medications linked with CNS depression/urinary retention/bleeding.,Multimorbidity is common in COPD and associated with high levels of polypharmacy.,Co-prescription of drugs with various ADRs is common.,Future research should examine the effects on healthcare outcomes of co-prescribing multiple drugs with similar potential ADRs.,Clinical guidelines should emphasise assessment of multimorbidity and ADR risk.

COPD often coexists with chronic conditions that may influence disease prognosis.,We investigated associations between chronic (co)morbidities and exacerbations in primary care COPD patients.,Retrospective cohort study based on 2012-2013 electronic health records from 179 Dutch general practices.,Comorbidities from patients with physician-diagnosed COPD were categorized according to International Classification of Primary Care (ICPC) codes.,Chi-squared tests, uni- and multivariable logistic, and Cox regression analyses were used to study associations with exacerbations, defined as oral corticosteroid prescriptions.,Fourteen thousand six hundred three patients with COPD could be studied (mean age 67 (SD 12) years, 53% male) for two years.,At baseline 12,826 (88%) suffered from ≥1 comorbidities, 3263 (22%) from ≥5.,The most prevalent comorbidities were hypertension (35%), coronary heart disease (19%), and osteoarthritis (18%).,Several comorbidities showed statistically significant associations with frequent (i.e., ≥2/year) exacerbations: heart failure (odds ratio [OR], 95% confidence interval: 1.72; 1.38-2.14), blindness & low vision (OR 1.46; 1.21-1.75), pulmonary cancer (OR 1.85; 1.28-2.67), depression 1.48; 1.14-1.91), prostate disorders (OR 1.50; 1.13-1.98), asthma (OR 1.36; 1.11-1.70), osteoporosis (OR 1.41; 1.11-1.80), diabetes (OR 0.80; 0.66-0.97), dyspepsia (OR 1.25; 1.03-1.50), and peripheral vascular disease (OR 1.20; 1.00-1.45).,From all comorbidity categories, having another chronic respiratory disease beside COPD showed the highest risk for developing a new exacerbation (Cox hazard ratio 1.26; 1.17-1.36).,Chronic comorbidities are highly prevalent in primary care COPD patients.,Several chronic comorbidities were associated with having frequent exacerbations and increased exacerbation risk.

To evaluate the relationship between alcohol consumption and the risk of acute exacerbation of COPD (AECOPD).,We conducted a secondary analysis of data previously collected in a large, multicenter trial of daily azithromycin in COPD.,To analyze the relationship between amount of baseline self-reported alcohol consumption in the past 12 months and subsequent AECOPD, we categorized the subjects as minimal (<1 drink/month), light-to-moderate (1-60 drinks/month), or heavy alcohol users (>60 drinks/month).,The primary outcome was time to first AECOPD and the secondary outcome was AECOPD rate during the 1-year study period.,Of the 1,142 enrolled participants, 1,082 completed baseline alcohol questionnaires and were included in this analysis.,Six hundred and forty-five participants reported minimal alcohol intake, 363 reported light-to-moderate intake, and 74 reported heavy intake.,There were no statistically significant differences in median time to first AECOPD among minimal (195 days), light-to-moderate (241 days), and heavy drinkers (288 days) (P=0.11).,The mean crude rate of AECOPD did not significantly differ between minimal (1.62 events per year) and light-to-moderate (1.44 events per year) (P=0.095), or heavy drinkers (1.68 events per year) (P=0.796).,There were no significant differences in hazard ratios for AECOPD after adjustment for multiple covariates.,Among persons with COPD at high risk of exacerbation, we found no significant relationship between self-reported baseline alcohol intake and subsequent exacerbations.,The number of patients reporting heavy alcohol intake was small and further study is needed to determine the effect of heavy alcohol intake on AECOPD risk.

Adverse childhood experiences (ACEs) before age 18 have been repeatedly associated with several chronic diseases in adulthood such as depression, heart disease, cancer, diabetes, and stroke.,We examined sex-specific relationships between individual ACEs and the number of ACEs with chronic obstructive pulmonary disease (COPD) in the general population.,Data from 26,546 women and 19,015 men aged ≥18 years in five states of the 2011 Behavioral Risk Factor Surveillance System were analyzed.,We used log-linear regression to estimate prevalence ratios (PRs) and their corresponding 95% confidence intervals (CIs) for the relationship of eight ACEs with COPD after adjustment for age group, race/ethnicity, marital status, educational attainment, employment, asthma history, health insurance coverage, and smoking status.,Some 63.8% of women and 62.2% of men reported ≥1 ACE.,COPD was reported by 4.9% of women and 4.0% of men.,In women, but not in men, there was a higher likelihood of COPD associated with verbal abuse (PR =1.30, 95% CI: 1.05, 1.61), sexual abuse (PR =1.69, 95% CI: 1.36, 2.10), living with a substance abusing household member (PR =1.49, 95% CI: 1.23, 1.81), witnessing domestic violence (PR =1.40, 95% CI: 1.14, 1.72), and parental separation/divorce (PR =1.47, 95% CI: 1.21, 1.80) during childhood compared to those with no individual ACEs.,Reporting ≥5 ACEs (PR =2.08, 95% CI: 1.55, 2.80) compared to none was associated with a higher likelihood of COPD among women only.,ACEs are related to COPD, especially among women.,These findings underscore the need for further research that examines sex-specific differences and the possible mechanisms linking ACEs and COPD.,This work adds to a growing body of research suggesting that ACEs may contribute to health problems later in life and suggesting a need for program and policy solutions.

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with a significant mortality, health and economic burden.,Their diagnosis, assessment and management remain suboptimal and unchanged for decades.,Recent clinical and translational studies revealed that the significant heterogeneity in mechanisms and outcomes of exacerbations could be resolved by grouping them etiologically.,This is anticipated to lead to a better understanding of the biological processes that underlie each type of exacerbation and to allow the introduction of precision medicine interventions that could improve outcomes.,This review summarises novel data on the diagnosis, phenotyping, targeted treatment and prevention of COPD exacerbations.

Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation of the airways and progressive destruction of lung parenchyma, a process that in most cases is initiated by cigarette smoking.,Several mechanisms are involved in the development of the disease: influx of inflammatory cells into the lung (leading to chronic inflammation of the airways), imbalance between proteolytic and anti-proteolytic activity (resulting in the destruction of healthy lung tissue) and oxidative stress.,Recently, an increasing number of data suggest a fourth important mechanism involved in the development of COPD: apoptosis of structural cells in the lung might possibly be an important upstream event in the pathogenesis of COPD.,There is an increase in apoptotic alveolar epithelial and endothelial cells in the lungs of COPD patients.,Since this is not counterbalanced by an increase in proliferation of these structural cells, the net result is destruction of lung tissue and the development of emphysema.,Data from animal models suggest a role for Vascular Endothelial Growth Factor (VEGF) in the induction of apoptosis of structural cells in the lung.,Other mediators of apoptosis, such as caspase-3 and ceramide, could be interesting targets to prevent apoptosis and the development of emphysema.,In this review, recent data on the role of apoptosis in COPD from both animal models as well as from studies on human subjects will be discussed.,The aim is to provide an up to date summary on the increasing knowledge on the role of apoptosis in COPD and pulmonary emphysema.

In most countries, nearly 6% of the adults are suffering from chronic obstructive pulmonary disease (COPD), which puts a huge economic burden on the society.,Moreover, COPD has been considered as an independent risk factor for pulmonary embolism (PE).,In this review, we summarized the existing evidence that demonstrates the associations between COPD exacerbation and PE from various aspects, including epidemiology, pathophysiological changes, risk factors, clinical features, management, and prognosis.,We searched the terms “chronic obstructive pulmonary disease,” “pulmonary embolism,” “exacerbations,” and “thromboembolic” in PubMed database and collected the results up to April 2018.,The language was limited to English.,We thoroughly examined the titles and abstracts of all studies that met our search strategy.,The data from prospective studies, meta-analyses, retrospective studies, and recent reviews were selected for preparing this review.,The prevalence of PE in patients with COPD exacerbation varied a lot among different studies, mainly due to the variations in race, sample size, study design, research setting, and enrollment criteria.,Overall, whites and African Americans showed significantly higher prevalence of PE than Asian people, and the hospitalized patients showed higher prevalence of PE compared to those who were evaluated in emergency department.,PE is easily overlooked in patients with COPD exacerbation due to the similar clinical symptoms.,However, several factors have been identified to contribute to the increased risk of PE during COPD exacerbation.,Obesity and lower limb asymmetry were described as independent predictors for PE.,Moreover, due to the high risk of PE, thromboprophylaxis has been used as an important treatment for hospitalized patients with COPD exacerbation.,According to the previous studies, COPD patients with PE experienced an increased risk of death and prolonged length of hospital stay.,Therefore, the thromboembolic risk in patients with acute exacerbation of COPD, especially in the hospitalized patients, should carefully be evaluated.

The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality.

Complications of pneumonia development in patients with chronic obstructive pulmonary disease (COPD) receiving inhaled corticosteroid (ICS) therapy have been documented.,The aim of this study was to focus on clinical efficacy and the incidence of pneumonia between COPD patients receiving medium and high doses of ICS.,This prospective, randomized study included COPD patients identified from three tertiary medical centers from 2010 to 2012.,The patients were randomized into two groups: high dose (HD; fluticasone 1,000 μg + salmeterol 100 μg/day) and medium dose (MD; fluticasone 500 μg + salmeterol 100 μg/day).,Lung function with forced expiratory volume in 1 second (FEV1), forced vital capacity, and COPD-assessment test (CAT) were checked every 2 months.,The frequency of acute exacerbations and number of pneumonia events were measured.,The duration of the study period was 1 year.,In total, 237 COPD patients were randomized into the two treatment arms (115 in the HD group, 122 in the MD group).,The FEV1 level was significantly improved in the patients in the HD group compared with those in the MD group (HD 103.9±26.6 mL versus MD 51.4±19.7 mL, P<0.01) at the end of the study.,CAT scores were markedly improved in patients using an HD compared to those using an MD (HD 13±5 versus MD 16±7, P=0.05).,There was a significant difference in the percentage of annual rates in acute exacerbations (HD 0.16 versus MD 0.34, P<0.01) between the two groups.,The incidence of pneumonia was similar in the two groups (HD 0.08 versus MD 0.10, P=0.38).,COPD patients treated with high doses of ICS had more treatment benefits and no significant increases in the incidence in pneumonia.,Higher-dose ICS treatment may be suitable for COPD therapy.

Chronic obstructive pulmonary disease (COPD), lung cancer, and tuberculosis are three leading causes of death in China, where prevalences of smoking and solid-fuel use are also high.,We aimed to predict the effects of risk-factor trends on COPD, lung cancer, and tuberculosis.,We used representative data sources to estimate past trends in smoking and household solid-fuel use and to construct a range of future scenarios.,We obtained the aetiological effects of risk factors on diseases from meta-analyses of epidemiological studies and from large studies in China.,We modelled future COPD and lung cancer mortality and tuberculosis incidence, taking into account the accumulation of hazardous effects of risk factors on COPD and lung cancer over time, and dependency of the risk of tuberculosis infection on the prevalence of disease.,We quantified the sensitivity of our results to methods and data choices.,If smoking and solid-fuel use remain at current levels between 2003 and 2033, 65 million deaths from COPD and 18 million deaths from lung cancer are predicted in China; 82% of COPD deaths and 75% of lung cancer deaths will be attributable to the combined effects of smoking and solid-fuel use.,Complete gradual cessation of smoking and solid-fuel use by 2033 could avoid 26 million deaths from COPD and 6·3 million deaths from lung cancer; interventions of intermediate magnitude would reduce deaths by 6-31% (COPD) and 8-26% (lung cancer).,Complete cessation of smoking and solid-fuel use by 2033 would reduce the projected annual tuberculosis incidence in 2033 by 14-52% if 80% DOTS coverage is sustained, 27-62% if 50% coverage is sustained, or 33-71% if 20% coverage is sustained.,Reducing smoking and solid-fuel use can substantially lower predictions of COPD and lung cancer burden and would contribute to effective tuberculosis control in China.,International Union Against Tuberculosis and Lung Disease.

Patients with COPD have had a lower tendency to quit smoking compared to patients with coronary heart disease (CHD).,We wanted to investigate if this is still true in a Norwegian population.,Our data came from the fifth and sixth Tromsø surveys, which took place in 2001-2002 and 2007-2008.,The predictors of smoking cessation were evaluated in a cohort of 4,497 participants who had stated their smoking status in both surveys.,Of the 4,497 subjects in the cohort, 1,150 (25.6%) reported daily smoking in Tromsø 5.,In Tromsø 6, 428 had quit (37.2%).,A new diagnosis of obstructive lung disease (asthma or COPD) and CHD were both associated with increased quitting rates, 50.6% (P=0.01) and 52.1% (P=0.02), respectively.,In multivariable logistic regression analysis with smoking cessation as outcome, the odds ratios (ORs) of a new diagnosis of obstructive lung disease and of CHD were 1.7 (1.1-2.7) and 1.7 (1.0-2.9), respectively.,Male sex had an OR of 1.4 (1.1-1.8) compared to women in the multivariable model, whereas the ORs of an educational length of 13-16 years and ≥17 years compared to shorter education were 1.6 (1.1-2.2) and 2.5 (1.5-4.1), respectively.,The general trend of smoking cessation in the population was confirmed.,Increased rates of smoking cessation were associated with a new diagnosis of heart or lung disease, and obstructive lung disease was just as strongly linked to smoking cessation as was CHD.,This should encourage the pursuit of early diagnosis of COPD.

Objective: To explore the associations between decreased pulse oximetry values (SpO2) and clinical, laboratory, and demographic variables in general practice patients diagnosed with asthma or chronic obstructive pulmonary disease (COPD), including those with both COPD and asthma in combination.,Design/setting: A cross-sectional study in seven Norwegian general practices of patients aged 40 years or over who were diagnosed by their general practitioner (GP) with asthma and/or COPD.,The patients were examined during a stable phase of their disease.,Patients diagnosed with COPD (including those with combined COPD/asthma) and those diagnosed with asthma only were analysed separately.,Main outcome measures: Decreased SpO2 values (≤ 95% and ≤ 92%).,Results: Of 372 patients included (mean age 61.5 years, 62% women), 82 (22.0%) had SpO2 ≤ 95%, of which 11 had SpO2 ≤ 92%.,In both asthma and COPD patients, SpO2 ≤ 95% was significantly associated with reduced lung function (spirometry), a diagnosis of coronary heart disease and older age (≥ 65 years).,In the COPD group, haemoglobin above normal was associated with SpO2 ≤ 95%.,These associations were confirmed by multivariable logistic regression, where FEV1% predicted < 50 was the strongest predictor of SpO2 ≤ 95% (odds ratio 6.8, 95% confidence interval 2.8-16.4).,Conclusion.,Pulse oximetry represents a useful diagnostic adjunct for assessing the severity of obstructive pulmonary disease.,Decreased pulse oximetry values in stable-phase patients with asthma and/or COPD should prompt the GP to consider revising the diagnosis and treatment and to look for co-morbidities.Key PointsDespite its common use in general practice, the diagnostic benefits of pulse oximetry remain to be established.Decreased pulse oximetry values are associated with both reduced lung function (spirometry) and with a diagnosis of coronary heart disease.Decreased pulse oximetry values may reflect suboptimal treatment and/or undiagnosed comorbidity.Pulse oximetry may therefore be a useful measure in the follow-up of asthma and COPD patients in general practice.,Despite its common use in general practice, the diagnostic benefits of pulse oximetry remain to be established.,Decreased pulse oximetry values are associated with both reduced lung function (spirometry) and with a diagnosis of coronary heart disease.,Decreased pulse oximetry values may reflect suboptimal treatment and/or undiagnosed comorbidity.,Pulse oximetry may therefore be a useful measure in the follow-up of asthma and COPD patients in general practice.

The “can do, do do” concept aims at identifying subgroups among persons with chronic obstructive pulmonary disease (COPD).,Following a two-dimensional categorization, individuals are binarily classified with respect to their levels of physical capacity (“can’t do” or “can do”) and physical activity (“don’t do” or “do do”), resulting in four disjunct quadrants.,The approach has been debated recently and the latest articles have concluded that the quadrants should be specifically examined in terms of psychological aspects of physical activity.,Therefore, the goal of the present study was to explore the role of psychological variables in physical activity in the context of the “can do, do do” quadrant concept.,Within the scope of secondary data analyses of the “Stay Active After Rehabilitation” (STAR) randomized controlled trial, a total of 298 COPD rehabilitants of an inpatient pulmonary rehabilitation program were grouped into the suggested quadrants.,We set fixed cut-offs at 70% of relative 6-min walking test performances for healthy individuals (physical capacity dimension) and 5.000 steps per day (physical activity dimension).,Univariate and multivariate logistic regression analyses served to analyze whether depression scores, fear avoidance behaviors, disease-specific anxiety, self-concordance for physical activity, and five indicators of physical activity-related health competence (PAHCO) effectively discriminated between the “don’t do” and “do do” groups.,Among persons with lower relative physical capacity, depression scores, fear avoidance behaviors, and disease-specific anxiety (univariate case) significantly differentiated between the more and the less active.,Among persons with higher relative physical capacity, fear avoidance behaviors, disease-specific anxiety, as well as three PAHCO indicators (physical activity-specific self-efficacy, self-control, and affect regulation) significantly separated the more and the less active.,In multivariate analyses, only fear avoidance behaviors and affect regulation discriminated among individuals with better relative physical capacity.,The findings identified important psychological and competence-oriented variables that explain discrepancies in the quadrant concept.,Based on this, we discuss implications for physical activity promotion in individuals with COPD.,Respiratory research can benefit from future studies complementing the quadrant concept through further behavioral analyses.,Trial registration Clinicaltrials.gov, ID: NCT02966561.,Registered 17 November, 2016, https://clinicaltrials.gov/ct2/show/NCT02966561.

Information concerning how climate and atmospheric pollutants affects physical activity in COPD patients is lacking and might be valuable in determining when physical activity should be encouraged.,Seventy-three stable COPD patients recorded on daily diary cards worsening of respiratory symptoms, peak expiratory flow rate, hours spent outside the home and the number of steps taken per day.,Pedometry data was recorded on 16,478 days, an average of 267 days per patient (range 29-658).,Daily data for atmospheric PM10 and ozone (O3) were obtained for Bloomsbury Square, Central London from the Air Quality Information Archive databases.,Daily weather data were obtained for London Heathrow from the British Atmospheric Data Archive.,Colder weather below 22.5 °C, reduced daily step count by 43.3 steps day per°C (95 % CI 2.14 to 84.4; p = 0.039) and activity was lower on rainy than dry days (p = 0.002) and on overcast compared to sunny days (p < 0.001).,Daily step count was 434 steps per day lower on Sunday than Saturday (p < 0.001) and 353 steps per day lower on Saturday than Friday (p < 0.001).,After allowance for these effects, higher O3 levels decreased activity during the whole week (-8 steps/ug/m3; p = 0.005) and at weekends (-7.8 steps/ug/m3; p = 0.032).,Whilst, during the week PM10 reduced activity (p = 0.018) but not during the weekend.,Inactivity of COPD patients is greatest on cold, wet and overcast days and at the weekends.,This study also provides evidence of an independent effect of atmospheric pollution at high levels.,The online version of this article (doi:10.1186/s12931-015-0229-z) contains supplementary material, which is available to authorized users.

Cigarette smoking is the main risk factor for COPD (Chronic Obstructive Pulmonary Disease), yet only a subset of smokers develops COPD.,Family members of patients with severe early-onset COPD have an increased risk to develop COPD and are therefore defined as “susceptible individuals”.,Here we perform unbiased analyses of proteomic profiles to assess how “susceptible individuals” differ from age-matched “non-susceptible individuals” in response to cigarette smoking.,Epithelial lining fluid (ELF) was collected at baseline and 24 hours after smoking 3 cigarettes in young individuals susceptible or non-susceptible to develop COPD and older subjects with established COPD.,Controls at baseline were older healthy smoking and non-smoking individuals.,Five samples per group were pooled and analysed by stable isotope labelling (iTRAQ) in duplicate.,Six proteins were selected and validated by ELISA or immunohistochemistry.,After smoking, 23 proteins increased or decreased in young susceptible individuals, 7 in young non-susceptible individuals, and 13 in COPD in the first experiment; 23 proteins increased or decreased in young susceptible individuals, 32 in young non-susceptible individuals, and 11 in COPD in the second experiment.,SerpinB3 and Uteroglobin decreased after acute smoke exposure in young non-susceptible individuals exclusively, whereas Peroxiredoxin I, S100A9, S100A8, ALDH3A1 (Aldehyde dehydrogenase 3A1) decreased both in young susceptible and non-susceptible individuals, changes being significantly different between groups for Uteroglobin with iTRAQ and for Serpin B3 with iTRAQ and ELISA measures.,Peroxiredoxin I, SerpinB3 and ALDH3A1 increased in COPD patients after smoking.,We conclude that smoking induces a differential protein response in ELF of susceptible and non-susceptible young individuals, which differs from patients with established COPD.,This is the first study applying unbiased proteomic profiling to unravel the underlying mechanisms that induce COPD.,Our data suggest that SerpinB3 and Uteroglobin could be interesting proteins in understanding the processes leading to COPD.

Obesity becomes pandemic, predisposing these individuals to great risk for lung injury.,In this review, we focused on the anti-inflammatories and addressed the following aspects: adipocytokines and obesity, inflammation and other mechanisms, adipocytokines and lung injury in obesity bridged by inflammation, and potential therapeutic targets.,To sum up, the majority of evidence supported that adiponectin, omentin, and secreted frizzled-related protein 5 (SFRP5) were reduced significantly in obesity, which is associated with increased inflammation, indicated by increase of TNFα and IL-6, through activation of toll-like receptor (TLR4) and nuclear factor light chain κB (NF-κB) signaling pathways.,Administration of these adipocytokines promotes weight loss and reduces inflammation.,Zinc-α2-glycoprotein (ZAG), vaspin, IL-10, interleukin-1 receptor antagonist (IL-1RA), transforming growth factor β (TGF-β1), and growth differentiation factor 15 (GDF15) are also regarded as anti-inflammatories.,There were controversial reports.,Furthermore, there is a huge lack of studies for obesity related lung injury.,The effects of adiponectin on lung transplantation, asthma, chronic obstructive pulmonary diseases (COPD), and pneumonia were anti-inflammatory and protective in lung injury.,Administration of IL-10 agonist reduces mortality of acute lung injury in rabbits with acute necrotizing pancreatitis, possibly through inhibiting proinflammation and strengthening host immunity.,Very limited information is available for other adipocytokines.

It’s currently well known that smoking and increasing age constitute the most important risk factors for chronic obstructive pulmonary disease (COPD).,However, little is known about COPD among nonsmokers.,The present study aimed to investigate prevalence, risk factors and the profiles of COPD among nonsmokers based on the Tunisian Burden of Obstructive Lung Disease (BOLD) study.,807 adults aged 40 years+ were randomly selected from the general population.,We collected information about history of respiratory disease, risk factors for COPD and quality of life.,Post-bronchodilator spirometry was performed for assessment of COPD.,COPD diagnostic was based on the post-bronchodilator FEV1/FVC ratio, according to the Global Initiative for Obstructive Lung Disease (GOLD) guidelines.,The lower limit of normal (LLN) was determined as an alternative threshold for the FEV1/FVC ratio.,Among 485 nonsmokers, 4.7% met the criteria for GOLD grade I and higher COPD.,These proportions were similar even when the LLN was used as a threshold.,None of the nonsmokers with COPD reported a previous doctor diagnosis of COPD compared to 7.1% of smokers.,Nonsmokers accounted for 45.1% of the subjects fulfilling the GOLD spirometric criteria of COPD.,Nonsmokers were predominately men and reported more asthma problems than obstructed smokers.,Among nonsmokers significantly more symptoms and higher co-morbidity were found among those with COPD.,Increasing age, male gender, occupational exposure, lower body mass index and a previous diagnosis of asthma are associated with increased risk for COPD in nonsmokers.,This study confirms previous evidence that nonsmokers comprise a substantial proportion of individuals with COPD.,Nonsmokers with COPD have a specific profile and should, thus, receive far greater attention to prevent and treat chronic airway obstruction.

Exposure to environmental tobacco smoke (ETS), which contains potent respiratory irritants, may lead to chronic airway inflammation and obstruction.,Although ETS exposure appears to cause asthma in children and adults, its role in causing COPD has received limited attention in epidemiologic studies.,Using data from a population-based sample of 2,113 U.S. adults aged 55 to 75 years, we examined the association between lifetime ETS exposure and the risk of developing COPD.,Participants were recruited from all 48 contiguous U.S. states by random digit dialing.,Lifetime ETS exposure was ascertained by structured telephone interview.,We used a standard epidemiologic approach to define COPD based on a self-reported physician diagnosis of chronic bronchitis, emphysema, or COPD.,Higher cumulative lifetime home and work exposure were associated with a greater risk of COPD.,The highest quartile of lifetime home ETS exposure was associated with a greater risk of COPD, controlling for age, sex, race, personal smoking history, educational attainment, marital status, and occupational exposure to vapors, gas, dusts, or fumes during the longest held job (OR 1.55; 95% CI 1.09 to 2.21).,The highest quartile of lifetime workplace ETS exposure was also related to a greater risk of COPD (OR 1.36; 95% CI 1.002 to 1.84).,The population attributable fraction was 11% for the highest quartile of home ETS exposure and 7% for work exposure.,ETS exposure may be an important cause of COPD.,Consequently, public policies aimed at preventing public smoking may reduce the burden of COPD-related death and disability, both by reducing direct smoking and ETS exposure.

COPD is a heterogeneous disease, and the available prognostic indexes are therefore limited.,This study aimed to identify the factors associated with acute exacerbation leading to hospitalization.,This was a retrospective study of consecutive patients with COPD (meeting the Global Initiative for Chronic Obstructive Lung Disease [GOLD] diagnostic criteria) hospitalized at the Ninth Hospital of Xi’an Affiliated Hospital of Xi’an Jiaotong University between October 2014 and September 2016.,During follow-up after first hospitalization, the patients who had been rehospitalized within 1 year for acute exacerbation were grouped into the frequent exacerbation (FE) group, while the others were grouped into the infrequent exacerbation (IE) group.,The baseline demographic, clinical, laboratory, pulmonary function, and imaging data were compared between the two groups.,Compared with the IE group, the FE group had lower forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) (P=0.005), FEV1%pred (P=0.002), maximal mid-expiratory flow (MMEF25-75%pred) (P=0.003), and ratio of carbon monoxide diffusion capacity to alveolar ventilation (DLCO/VA) (P=0.03) and higher resonant frequency (Fres; P=0.04).,According to generations of bronchi, the percentage of the wall area (%WA) of lobes was found to be higher in the FE group.,Emphysema index (EI), mean emphysema density (MED)whole and MEDleft lung in the FE group were significantly worse than in the IE group (P<0.05).,Using logistic regression, exacerbation hospitalizations in the past year (odds ratio [OR] 14.4, 95% CI 6.1-34.0, P<0.001) and EI >10% (OR 2.9, 95% CI 1.2-7.1, P=0.02) were independently associated with frequent acute exacerbation of COPD (AECOPD) hospitalization.,Exacerbation hospitalizations in the past year and imaging features of emphysema (EI) were independently associated with FE hospitalization.

COPD is a heterogeneous disease characterized by airflow obstruction and diagnosed by lung function.,CT imaging is emerging as an important, noninvasive tool in phenotyping COPD.,However, the use of CT imaging in defining the disease heterogeneity above lung function is not fully known.,Seventy-five patients with COPD (58 men, 17 women) were studied with CT imaging and with measures of airway inflammation.,Airway physiology and health status were also determined.,The presence of emphysema (EM), bronchiectasis (BE), and bronchial wall thickening (BWT) was found in 67%, 27%, and 27% of subjects, respectively.,The presence of EM was associated with lower lung function (mean difference % FEV1, −20%; 95% CI, −28 to −11; P < .001).,There was no difference in airway inflammation, exacerbation frequency, or bacterial load in patients with EM alone or with BE and/or BWT ± EM.,The diffusing capacity of the lung for carbon monoxide/alveolar volume ratio was the most sensitive and specific parameter in identifying EM (area under the receiver operator characteristic curve, 0.87; 95% CI, 0.79-0.96).,Physiologic cluster analysis identified three clusters, two of which were EM predominant and the third characterized by a heterogeneous combination of EM and BE.,The application of CT imaging can be useful as a tool in the multidimensional approach to phenotyping patients with COPD.

Early identification of patients with a prolonged stay due to acute exacerbation of chronic obstructive pulmonary disease (COPD) may reduce risk of adverse event and treatment costs.,This study aimed to identify predictors of prolonged stay after acute exacerbation of COPD based on variables on admission; the study also looked to establish a prediction model for length of stay (LOS).,We extracted demographic and clinical data from the medical records of 599 patients discharged after an acute exacerbation of COPD between March 2006 and December 2008 at Oslo University Hospital, Aker.,We used logistic regression analyses to assess predictors of a length of stay above the 75th percentile and assessed the area under the receiving operating characteristic curve to evaluate the model’s performance.,We included 590 patients (54% women) aged 73.2±10.8 years (mean ± standard deviation) in the analyses.,Median LOS was 6.0 days (interquartile range [IQR] 3.5-11.0).,In multivariate analysis, admission between Thursday and Saturday (odds ratio [OR] 2.24 [95% CI 1.60-3.51], P<0.001), heart failure (OR 2.26, 95% CI 1.34-3.80), diabetes (OR 1.90, 95% CI 1.07-3.37), stroke (OR 1.83, 95% CI 1.04-3.21), high arterial PCO2 (OR 1.26 [95% CI 1.13-1.41], P<0.001), and low serum albumin level (OR 0.92 [95% CI 0.87-0.97], P=0.001) were associated with a LOS >11 days.,The statistical model had an area under the receiver operating characteristic curve of 0.73.,Admission between Thursday and Saturday, heart failure, diabetes, stroke, high arterial PCO2, and low serum albumin level were associated with a prolonged LOS.,These findings may help physicians to identify patients that will need a prolonged LOS in the early stages of admission.,However, the predictive model exhibited suboptimal performance and hence is not ready for clinical use.

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.

Once-daily dual-bronchodilator therapy with combined indacaterol and glycopyrronium bromide in one device (Ultibro, Breezhaler), often called QVA149, was first approved in 2013 in Japan and Europe.,As of November 2014, more than 40 countries had approved this medication except for the USA.,This is the first dual bronchodilator in one device.,Now, the Breezhaler is the only device that can provide long-acting muscarinic antagonist (glycopyrronium bromide), long-acting beta agonist (indacaterol), and a combination of the two medications (QVA149).,The choice among the three medications allows a patient to use the same inhalation device even when the regimen is changed from single-bronchodilator therapy to dual-bronchodilator therapy.,In addition, the quick bronchodilation effect and once-daily administration can improve patient adherence to medical treatment for chronic obstructive pulmonary disease (COPD).,To our knowledge, as of November 2014, the safety and the efficacy of QVA149 have been evaluated in 14 randomized controlled trials.,The 14 trials generally showed good safety profiles, and there were better or not-inferior bronchodilator effects of QVA149 when compared with placebo, or other inhaled medication.,According to the Japanese Respiratory Society guidelines, QVA149 is a combination of the two first-line bronchodilators.,Our meta-analysis indicated that QVA149 is superior to the salmeterol-fluticasone combination to treat COPD in respect of the frequency of adverse effects, exacerbation, pneumonia, and improvement of trough forced expiratory volume in 1 second (FEV1).,Thus, we believe that QVA149 can be a key medication for COPD treatments.

Randomised, double-blind, controlled trials are considered the gold standard for evaluating a pharmacological agent, as they minimise any potential bias.,However, it is not always possible to perform double-blind trials, particularly for medications delivered via specific devices, e.g. inhalers.,In such cases, open-label studies can be employed instead.,Methods used to minimise any potential bias introduced by open-label study design include randomisation, crossover study design, and objective measurements of primary efficacy and safety variables.,Concise reviews analysing the effect of blinding procedures of comparator drugs on outcomes in respiratory trials are limited.,Here, we compare data from different chronic obstructive pulmonary disease trials with once-daily indacaterol versus a blinded or non-blinded comparator.,The clinical trial programme for indacaterol, a once-daily, long-acting β2-agonist, used tiotropium as a comparator either in an open-label or blinded fashion.,Data from these studies showed that the effects of tiotropium were consistent for forced expiratory volume in 1 second, an objective measure, across blinded and non-blinded studies.,The data were consistent with previous studies of double-blind tiotropium, suggesting that the open-label use of tiotropium did not introduce treatment bias.,The effect of tiotropium on subjective measures (St George’s Respiratory Questionnaire; transition dyspnoea index) varied slightly across blinded and non-blinded studies, indicating that minimal bias was introduced by using open-label tiotropium.,Importantly, the studies used randomised, open-label tiotropium patients to treatment allocation, a method shown to minimise bias to a greater degree than blinding.,In conclusion, it is important when reporting a clinical trial to be transparent about who was blinded and how the blinding was performed; if the design is open-label, additional efforts must be made to minimise risk of bias.,If these recommendations are followed, and the data are considered in the full knowledge of any potential sources of bias, results with tiotropium suggest that data from open-label studies can provide valuable and credible evidence of the effects of therapy.

Extracellular matrix (ECM) creates the tissue microenvironment and serves a role in airway wall remodeling in chronic obstructive pulmonary disease (COPD).,However, the biological function of ECM in COPD remains to be elucidated.,In the present study, 24 healthy Sprague Dawley rats were randomized to normal and COPD groups.,COPD was established by intratracheal injection with lipopolysaccharide over 30 days.,Subsequently, airway smooth muscle cells (ASMCs) were isolated from rats and served as a model to assess the effects of three ECM components, including collagen type I, laminin and collagen type III (COL-3).,Functional analysis in vitro, using cell counting kit-8, flow cytometry, wound healing and cell adhesion assays indicated that the ECM components could promote cell proliferation, cell cycle progression, migration and adhesion ability, respectively.,Furthermore, as demonstrated by ELISA, treatment with ECM components increased levels of C-X-C motif chemokine ligand 1 (CXCL1), CXCL8 and interleukin-6 in ASMCs.,Expression of transforming growth factor β1 (TGFβ1), fibroblast growth factor-1 (FGF-1) and tissue inhibitor of metalloproteinase 1 (TIMP1) was increased, and expression of matrix metalloproteinase-9 (MMP-9) was decreased following treatment with ECM components, as demonstrated by reverse transcription-quantitative polymerase chain reaction and western blot analysis.,Additionally, specific activation of phosphoinositide 3-kinase (PI3K) signaling, using insulin-like growth factor-1 (IGF-1), promoted cell proliferation and cell cycle progression, increased expression of TGFβ1, FGF-1, PI3K, AKT, phospho-AKT, serine/threonine-protein kinase mTOR (mTOR), phospho-mTOR and TIMP1, promoted cell migration capacity and reduced the expression level of MMP-9 in cells from COPD rats.,Consistently, PI3K inhibitor LY294002 exerted the opposite effect to IGF-1.,In conclusion, ECM proteins promoted proliferation, migration and adhesion of ASMCs form rat models of COPD through activation of the PI3K/AKT signaling pathway.

Chronic obstructive pulmonary disease (COPD) is characterized by the progression of irreversible airflow limitation and is a leading cause of morbidity and mortality worldwide.,Although several crucial mechanisms of COPD pathogenesis have been studied, the precise mechanism remains unknown.,Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are released from almost all cell types and are recognized as novel cell-cell communication tools.,They have been shown to carry and transfer a wide variety of molecules, such as microRNAs, messenger RNAs, and proteins, which are involved in physiological functions and the pathology of various diseases.,Recently, EVs have attracted considerable attention in pulmonary research.,In this review, we summarize the recent findings of EV-mediated COPD pathogenesis.,We also discuss the potential clinical usefulness of EVs as biomarkers and therapeutic agents for the treatment of COPD.

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.

The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known.,We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database.,951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012.,Individuals were selected for ≥1 of 8 algorithms to identify people with COPD.,General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested.,All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard.,The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed.,951 questionnaires were sent and 738 (78%) returned.,After quality control, 696 (73.2%) patients were included in the final analysis.,All four algorithms including a specific COPD diagnostic code performed well.,Using a diagnostic code alone, the PPV was 86.5% (77.5-92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7-94.5%) but reduced case numbers by 10%.,Algorithms without specific diagnostic codes had low PPVs (range 12.2-44.4%).,Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes.,Requiring spirometry or COPD medications only marginally improved accuracy.,The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004.

Lower airway bacterial colonisation (LABC) in COPD patients is associated with increased exacerbation frequency and faster lung function decline.,Defective macrophage phagocytosis in COPD drives inflammation, but how defective macrophage function contributes to exacerbations is not clear.,This study investigated the association between macrophage phagocytosis and exacerbation frequency, LABC and clinical parameters.,Monocyte-derived macrophages (MDM) were generated from 92 stable COPD patients, and at the onset of exacerbation in 39 patients.,Macrophages were exposed to fluorescently labelled Haemophilus influenzae or Streptococcus pneumoniae for 4 h, then phagocytosis measured by fluorimetry and cytokine release by ELISA.,Sputum bacterial colonisation was measured by PCR.,Phagocytosis of H. influenzae was negatively correlated with exacerbation frequency (r = 0.440, p < 0.01), and was significantly reduced in frequent vs. infrequent exacerbators (1.9 × 103 RFU vs.,2.5 × 103 RFU, p < 0.01).,There was no correlation for S. pneumoniae.,There was no association between phagocytosis of either bacteria with age, lung function, smoking history or treatment with inhaled corticosteroids, or long-acting bronchodilators.,Phagocytosis was not altered during an exacerbation, or in the 2 weeks post-exacerbation.,In response to phagocytosis, MDM from exacerbating patients showed increased release of CXCL-8 (p < 0.001) and TNFα (p < 0.01) compared to stable state.,Impaired COPD macrophage phagocytosis of H. influenzae, but not S. pneumoniae is associated with exacerbation frequency, resulting in pro-inflammatory macrophages that may contribute to disease progression.,Targeting these frequent exacerbators with drugs that improve macrophage phagocytosis may prove beneficial.,The online version contains supplementary material available at 10.1186/s12931-021-01718-8.

Changes in microbial community composition in the lung of patients suffering from moderate to severe COPD have been well documented.,However, knowledge about specific microbiome structures in the human lung associated with CT defined abnormalities is limited.,Bacterial community composition derived from brush samples from lungs of 16 patients suffering from different CT defined subtypes of COPD and 9 healthy subjects was analyzed using a cultivation independent barcoding approach applying 454-pyrosequencing of 16S rRNA gene fragment amplicons.,We could show that bacterial community composition in patients with changes in CT (either airway or emphysema type changes, designated as severe subtypes) was different from community composition in lungs of patients without visible changes in CT as well as from healthy subjects (designated as mild COPD subtype and control group) (PC1, Padj = 0.002).,Higher abundance of Prevotella in samples from patients with mild COPD subtype and from controls and of Streptococcus in the severe subtype cases mainly contributed to the separation of bacterial communities of subjects.,No significant effects of treatment with inhaled glucocorticoids on bacterial community composition were detected within COPD cases with and without abnormalities in CT in PCoA.,Co-occurrence analysis suggests the presence of networks of co-occurring bacteria.,Four communities of positively correlated bacteria were revealed.,The microbial communities can clearly be distinguished by their associations with the CT defined disease phenotype.,Our findings indicate that CT detectable structural changes in the lung of COPD patients, which we termed severe subtypes, are associated with alterations in bacterial communities, which may induce further changes in the interaction between microbes and host cells.,This might result in a changed interplay with the host immune system.

The time of year when patients experience exacerbations of chronic obstructive pulmonary disease is a much-overlooked feature of the disease.,The higher incidence of exacerbations in winter has important consequences for patients in terms of increased morbidity and mortality.,The seasonality also imposes a considerable burden on already-overloaded health care services, with both primary care consultations and hospital admissions increasing in number.,The seasonality of exacerbations varies with latitude, and is greater in more temperate climates, where there may be less protection from outdoor and indoor cold exposure.,The precise causes of the seasonality are unknown, but thought to be partly due to the increased prevalence of respiratory viral infections circulating in cold, damp conditions.,Increased susceptibility to viral infection may also be a mechanism mediated through increased airway inflammation or possibly reduced vitamin D levels.,The seasonality of exacerbations informs us about the triggers of exacerbations and suggests possible strategies to reduce their number.

Tiotropium bromide is an effective therapy for COPD patients.,Comparing across programs tiotropium Respimat® Soft Mist™ inhaler was at least as efficacious as tiotropium HandiHaler®, however, concerns have been raised about tiotropium’s safety when given via Respimat®.,The TIOSPIR® trial (NCT01126437) compares the safety and efficacy of tiotropium Respimat® 5 μg once daily (marketed) and 2.5 μg once daily (investigational) with tiotropium HandiHaler® 18 μ once daily (marketed).,The hypotheses to be tested are 1). that tiotropium Respimat® 5 μg once daily and Respimat® 2.5 μg once daily are non-inferior to HandiHaler® in terms of all-cause mortality, and 2). that tiotropium Respimat® 5 μg once daily is superior to HandiHaler® in terms of time to first exacerbation.,A spirometry substudy evaluates the bronchodilator efficacy.,The trial is a randomized, double-blind, double dummy, event-driven, parallel group study.,Participants can use any background treatment for COPD except inhaled anticholinergic agents.,The study encompasses a wide range of COPD patients, e.g. patients with stable cardiac diseases including arrhythmia can be included.,Clinical sites are international and include both primary care as well as specialists.,To date, over 17,000 participants have been randomized from over 1200 sites in 50 countries with an anticipated treatment duration of 2-3 years.,TIOSPIR® will provide precise estimates of the relative safety and efficacy of the Respimat® and HandiHaler® formulations of tiotropium, assess potential dose-dependence of important outcomes and provide information on the clinical epidemiology of COPD in a large international patient cohort.

Cigarette smoke exposure is a major risk factor in chronic obstructive pulmonary disease (COPD) and its interactions with genetic variants could affect lung function.,However, few gene-smoking interactions have been reported.,In this report, we evaluated the effects of gene-smoking interactions on lung function using Korea Associated Resource (KARE) data with the spirometric variables-forced expiratory volume in 1 s (FEV1).,We found that variations in FEV1 were different among smoking status.,Thus, we considered a linear mixed model for association analysis under heteroscedasticity according to smoking status.,We found a previously identified locus near SOX9 on chromosome 17 to be the most significant based on a joint test of the main and interaction effects of smoking.,Smoking interactions were replicated with Gene-Environment of Interaction and phenotype (GENIE), Multi-Ethnic Study of Atherosclerosis-Lung (MESA-Lung), and COPDGene studies.,We found that individuals with minor alleles, rs17765644, rs17178251, rs11870732, and rs4793541, tended to have lower FEV1 values, and lung function decreased much faster with age for smokers.,There have been very few reports to replicate a common variant gene-smoking interaction, and our results revealed that statistical models for gene-smoking interaction analyses should be carefully selected.

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.

Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV1.,There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline in FEV1.,A cohort of 148 COPD patients (100 men) was monitored daily for a median of 2.91 years (interquartile range [IQR], 2.1 to 4.8).,At recruitment, median age was 68.5 years (IQR, 62.5 to 73.6) and FEV1 as percentage of predicted (FEV1%Pred) was 38.5% (IQR, 27.7 to 50.3).,During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR, 1.48 to 3.96) and FEV1 declined by 40.2 mL/yr or as FEV1%Pred by 1.5%/yr.,Concerning inflammatory markers, sputum interleukin (IL)-6 rose by 9 pg/mL/yr, sputum neutrophil count rose by 1.64 × 106 cells per gram sputum per year, an plasma fibrinogen rose by 0.10 g/L/yr (all p < 0.05).,Patients with frequent exacerbations (≥ 2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063 g/L/yr (p = 0.046, n = 130) and 29.5 pg/mL/yr (p < 0.001, n = 98), respectively, compared to patients with infrequent exacerbations (< 2.52/yr).,Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV1%Pred decline of 0.42%/yr (p = 0.018).,Similarly, a high neutrophil count or fibrinogen were associated with a faster FEV1%Pred decline of 0.97%/yr (p = 0.001) and 0.40%/yr (p = 0.014), respectively.,In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function.

Oxidative stress is associated with the pathogenesis of cigarette smoke related lung diseases, but longitudinal effects of smoking cessation on oxidant markers in the airways are unknown.,This study included 61 smokers; 21 with chronic bronchitis or COPD, 15 asthmatics and 25 asymptomatic smokers followed up for 3 months after smoking cessation.,Fractional exhaled nitric oxide (FeNO), sputum neutrophil counts, sputum 8-isoprostane, nitrotyrosine and matrix metalloproteinase-8 (MMP-8) were investigated at baseline and 1 and 3 months after smoking cessation.,After 3 months 15 subjects had succeeded in quitting of smoking and in these subjects symptoms improved significantly.,Unexpectedly, however, sputum neutrophils increased (p = 0.046) after smoking cessation in patients with chronic bronchitis/COPD.,At baseline, the other markers did not differ between the three groups so these results were combined for further analysis.,Sputum 8-isoprostane declined significantly during the follow-up at 3 months (p = 0.035), but levels still remained significantly higher than in non-smokers.,The levels of FeNO, nitrotyrosine and MMP-8 did not change significantly during the 3 months after smoking cessation.,Whilst symptoms improve after smoking cessation, the oxidant and protease burden in the airways continues for months.

Background: Two studies were undertaken to characterize the maximal effort inhalation profiles of healthy subjects and patients with asthma or chronic obstructive pulmonary disease (COPD) through a moderate-resistance dry powder inhaler (DPI).,Correlations between inhaler-specific inhalation characteristics and inhaler-independent lung function parameters were investigated.,Methods: Healthy subjects (n = 15), patients with mild, moderate, or severe asthma (n = 45), and patients with mild, moderate, severe, or very-severe COPD (n = 60) were included in the studies.,Inhalation pressure drop versus time profiles were recorded using an instrumented ELLIPTA® DPI or bespoke resistor component with equivalent resistivity.,Inhaler-independent lung function assessments included pharyngometry, spirometry, plethysmography, and diffusion.,Results: For the inhaler-specific inhalation profiles, the mean maximal effort peak inspiratory flow rates (PIFRs) varied across the subgroups from 65.8-110.6 L/min (range: 41.6-142.9).,Peak pressure drop, PIFR, inhaled volume, and average inhalation flow rate (primary endpoints) did not differ markedly between healthy subjects and patients with asthma or mild COPD.,Moderate, severe, and very-severe COPD patients demonstrated lower mean peak pressure drops, PIFRs and inhaled volumes, which tended to decrease with increasing COPD severity.,Severe and very-severe COPD patients demonstrated shorter mean inhalation times compared with all other participants.,Inhaler-independent lung function parameters were consistent with disease severity, and statistically significant (p < 0.05) strong correlations (R > 0.7) with components of the inhaler-specific inhalation profiles were observed in the COPD cohort; correlations in the asthma cohort tended to be weaker.,Conclusions: All participants achieved a maximal effort PIFR ≥ 41.6 L/min through the moderate resistance of the ELLIPTA inhaler.,Patients with asthma achieved similar inhalation profiles to healthy subjects, but increasing COPD severity tended to reduce a patient's inhalation capability.,Correlation analyses suggest that some lung function parameters may be a useful indicator of ability to inhale efficiently through a moderate-resistance DPI, such as the ELLIPTA inhaler.

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

Underlying chronic respiratory disease may be associated with the severity of coronavirus disease 2019 (COVID-19).,This study investigated the impact of chronic obstructive pulmonary disease (COPD) on the risk for respiratory failure and mortality in COVID-19 patients.,A nationwide retrospective cohort study was conducted in 4610 patients (≥ 40 years old) infected with COVID-19 between January 20 and May 27, 2020, using data from the Ministry of Health and Welfare and Health Insurance Review and Assessment Service in Korea.,The clinical course and various clinical features were compared between COPD and non-COPD patients, and the risks of respiratory failure and all-cause mortality in COPD patients were analyzed using a multivariate logistic regression model.,Among 4610 COVID-19 patients, 4469 (96.9%) and 141 (3.1%) were categorized into the non-COPD and COPD groups, respectively.,The COPD group had greater proportions of older (≥ 60 years old) (78.0% vs.,45.2%, P < 0.001) and male (52.5% vs.,36.6%, P < 0.001) patients than the non-COPD group.,Relatively greater proportions of patients with COPD received intensive critical care (7.1% vs.,3.7%, P = 0.041) and mechanical ventilation (5.7% vs.,2.4%, P = 0.015).,Multivariate analyses showed that COPD was not a risk factor for respiratory failure but was a significant independent risk factor for all-cause mortality (OR = 1.80, 95% CI 1.11-2.93) after adjustment for age, sex, and Charlson Comorbidity Index score.,Among COVID-19 patients, relatively greater proportions of patients with COPD received mechanical ventilation and intensive critical care.,COPD is an independent risk factor for all-cause mortality in COVID-19 patients in Korea.

An outbreak of Corona Virus Disease 2019 (COVID-19) has spread rapidly reaching over 3 million of confirmed cases worldwide.,The association of respiratory diseases and smoking, both highly prevalent globally, with COVID-19 severity has not been elucidated.,Given the gap in the evidence and the growing prevalence of COVID-19, the objective of this study was to explore the association of underlying respiratory diseases and smoking with severe outcomes in patients with COVID-19 infection.,A systematic search was performed to identify studies reporting prevalence of respiratory diseases and/or smoking in relation with disease severity in patients with confirm COVID-19, published between January 1 to April 15, 2020 in English language.,Pooled odds-ratio (OR) and 95% confidence intervals (95% CI) were calculated.,Twenty two studies met the inclusion criteria.,All the studies presented data of 13,184 COVID-19 patients (55% males).,Patients with severe outcomes were older and a larger percentage were males compared with the non-severe.,Pooled analysis showed that prevalence of respiratory diseases (OR 4.21; 95% CI, 2.9-6.0) and smoking (current smoking OR 1.98; 95% CI, 1.16-3.39 and former smoking OR 3.46; 95% CI, 2.46-4.85) were significantly associated with severe COVID-19 outcomes.,Results suggested that underlying respiratory diseases, specifically COPD, and smoking were associated with severe COVID-19 outcomes.,These findings may support the planning of preventive interventions and could contribute to improvements in the assessment and management of patient risk factors in clinical practice, leading to the mitigation of severe outcomes in patients with COVID-19 infection.

The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment.,The effect of this combination on symptoms of COPD and exacerbations is less well established.,We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).,Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®.,Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.,The pooled intent-to-treat population included 3394 patients.,Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05).,Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05).,The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05).,Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies.,Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).,Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD.,Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.,NCT01462942 and NCT01437397 (ClinicalTrials.gov),The online version of this article (doi:10.1186/s12931-015-0250-2) contains supplementary material, which is available to authorized users.

Fixed dose combination (FDC) dual bronchodilators that co-administer a long acting β2-adrenoceptor agonist (LABA) and a long acting muscarinic antagonist (LAMA) are a new class of inhaled treatment for chronic obstructive pulmonary disease (COPD).,This review focuses on the clinical evidence for the benefit of LABA/LAMA FDCs compared with monocomponent treatments, and also compared with active comparators that are widely used for the treatment of COPD, namely tiotropium and salmeterol-fluticasone.,Novel FDC dual bronchodilators include QVA149 and umeclidinium/vilanterol (UMEC/VI).,Long term clinical trials show that QVA149 and UMEC/VI are superior to monocomponent therapy in terms of trough forced expiratory volume in 1 s (FEV1), although the FEV1 improvement was limited to approximately 80-90% of the added monocomponent values.,This suggests that the effect of combining a LABA and a LAMA is not fully additive.,LABA/LAMA FDC were associated with the largest mean changes in symptoms and health status that were above the minimal clinically important difference, in contrast to the monocomponents.,Furthermore, these LABA/LAMA FDCs demonstrated superiority over the active comparators tiotropium and salmeterol-fluticasone in terms of trough FEV1 and patient-reported outcomes.,LABA/LAMA FDCs offer a simplified means of maximizing bronchodilation for COPD patients, with the improvements in lung function being mirrored by benefits in terms of symptoms and exacerbations.,The use of LABA/LAMA FDCs in clinical practice is set to grow and further studies are needed to define their optimal place in treatment guidelines.

Admission to hospital with chronic obstructive pulmonary disease (COPD) is associated with deprivation and season.,However, it is not known whether deprivation and seasonality act synergistically to influence the risk of hospital admission with COPD.,To investigate whether the relationship between season/temperature and admission to hospital with COPD differs with deprivation.,All COPD admissions (ICD10 codes J40-J44 and J47) were obtained for the decade 2001-2010 for all Scottish residents by month of admission and 2009 Scottish Index of Multiple Deprivation (SIMD) quintile.,Confidence intervals for rates and absolute differences in rates were calculated and the proportion of risk during winter attributable to main effects and interactions were estimated.,Monthly rates of admission by average daily minimum temperatures were plotted for each quintile of SIMD.,Absolute differences in admission rates between winter and summer increased with greater deprivation.,In the most deprived quintile, in winter 19.4% (95% CI 17.3% to 21.4%) of admissions were attributable to season/deprivation interaction, 61.2% (95% CI 59.5% to 63.0%) to deprivation alone, and 5.2% (95% CI 4.3% to 6.0%) to winter alone.,Lower average daily minimum temperatures over a month were associated with higher admission rates, with stronger associations evident in the more deprived quintiles.,Winter and socioeconomic deprivation-related factors appear to act synergistically, increasing the rate of COPD admissions to hospital more among deprived people than among affluent people in winter than in the summer months.,Similar associations were observed for admission rates and temperatures.,Interventions effective at reducing winter admissions for COPD may have potential for greater benefit if delivered to more deprived groups.

25-hydroxyvitamin D deficiency is associated with COPD and increased susceptibility to infection in the general population.,We investigated whether COPD patients deficient in 25-hydroxyvitamin D were more likely to be frequent exacerbators, had reduced outdoor activity and were more susceptible to human rhinovirus (HRV) exacerbations than those with insufficient and normal levels.,We also investigated whether the frequency of FokI, BsmI and TaqIα 25-hydroxyvitamin D receptor (VDR) polymorphisms differed between frequent and infrequent exacerbators.,There was no difference in 25-hydroxyvitamin D levels between frequent and infrequent exacerbators in the summer; medians 44.1nmol/L (29.1 - 68.0) and 39.4nmol/L (22.3 - 59.2) or winter; medians 24.9nmol/L (14.3 - 43.1) and 27.1nmol/L (19.9 - 37.6).,Patients who spent less time outdoors in the 14 days prior to sampling had lower 25-hydroxyvitamin D levels (p = 0.02).,Day length was independently associated with 25-hydroxyvitamin D levels (p = 0.02).,There was no difference in 25-hydroxyvitamin D levels between baseline and exacerbation; medians 36.2nmol/L (IQR 22.4-59.4) and 33.3nmol/L (23.0-49.7); p = 0.43.,HRV positive exacerbations were not associated with lower 25-hydroxyvitamin D levels at exacerbation than exacerbations that did not test positive for HRV; medians 30.0nmol/L (20.4 - 57.8) and 30.6nmol/L (19.4 - 48.7).,There was no relationship between exacerbation frequency and any VDR polymorphisms (all p > 0.05).,Low 25-hydroxyvitamin D levels in COPD are not associated with frequent exacerbations and do not increase susceptibility to HRV exacerbations.,Independent of day length, patients who spend less time outdoors have lower 25-hydroxyvitamin D concentration.

Penehyclidine hydrochloride is a selective antagonist of M1 and M3 receptors.,Clinical studies suggest that it is a potential drug for the treatment of chronic obstructive pulmonary disease (COPD).,The purpose of this study was to evaluate the effect of penehyclidine hydrochloride on the inflammatory response of lung tissue during mechanical ventilation in rats with COPD and explore the role of the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) signaling pathway.,Eight-week-old male Sprague Dawley rats were exposed to cigarette smoke for 30 minutes every day for two months, and on the first and thirtieth days, 200 ug of lipopolysaccharide was injected into the trachea.,Two months later, the rats were randomly divided into the control group (C), model group (M), model + normal saline group (N), and penehyclidine hydrochloride group (H) to undergo anesthesia and mechanical ventilation.,In group H, 1 mg/kg of penehyclidine hydrochloride was injected intravenously.,The results showed that: ① Compared with group C, the other groups all showed typical chronic obstructive pathological changes in the lung tissue; their wet/dry weight ratio (W/D), TNF-α, JNK, and p-JNK levels increased (P < 0.05), and their interleukin (IL)-10 levels decreased (P < 0.05).,② Compared with group M, there was no significant change in the lung tissue indexes in group N (P > 0.05).,③ Compared with group N, the W/D, TNF-α, JNK, and p-JNK levels in group H decreased (P < 0.05), while the levels of IL-10 increased (P < 0.05).,Penehyclidine hydrochloride can alleviate the pulmonary inflammatory response in rats with COPD undergoing mechanical ventilation.,The JNK/SAPK signaling pathway may be involved in this process.

COPD is characterized by a pulmonary and systemic inflammatory process.,Several authors have reported the elevation of multiple inflammatory markers in patients with COPD; however, their use in routine clinical practice has limitations.,The neutrophil-to-lymphocyte ratio (NLR) is a useful and cost-effective inflammatory marker derived from routine complete blood count.,We performed a systematic literature review using the PRISMA statement.,Twenty-two articles were included, recruiting 7,601 COPD patients and 784 healthy controls.,Compared with controls, COPD patients had significantly higher NLR values.,We found a significant correlation between the NLR and clinical/functional parameters (FEV1, mMRC, and BODE index) in COPD patients.,Elevation of the NLR is associated with the diagnosis of acute exacerbation of COPD (pooled data propose a cut-off value of 3.34 with a median sensitivity, specificity, and area under the curve of 80%, 86%, and 0.86, respectively).,Additionally, increased NLR is also associated with the diagnosis of a bacterial infection in exacerbated patients, with a cut-off value of 7.30, although with a low sensitivity and specificity.,The NLR is an independent predictor of in-hospital and late mortality after exacerbation.,In conclusion, the NLR could be a useful marker in COPD patients; however, further studies are needed to better identify the clinical value of the NLR.

Both chronic Obstruction Pulmonary Disease (COPD) and lung cancer are leading causes of death globally.,Although COPD and lung cancer coexist frequently, it is unknown whether lung cancer patients with COPD harbor distinct genomic characteristics compared to those without COPD.,In this study, we retrospectively analyzed genomic sequencing data from 272 patients with lung adenocarcinoma (LUAD) and compared the genetic alterations in LUAD patients with and without COPD.,Integrative analysis of whole-genome and exome sequencing data revealed that COPD and non-COPD groups showed high concordance in mutational burden and spectra.,Notably, we also found that EGFR mutations were more prevalent in LUAD patients without COPD, whereas mutated LRP1B was more frequently observed in LUAD patients with COPD.,In addition, multi-variable analysis with logistic regression demonstrated that mutation of LRP1B was a predictive marker for the presence of COPD in the patients with LUAD.,Our analysis demonstrated for the first time the high concordance in genomic alterations between the tumors from LUAD patients with and without COPD.,We also identified higher prevalence of LRP1B among the LUAD patients with COPD, which might help understand the underlying mechanisms which link COPD and lung cancer.

There is increasing evidence that a specific immune response contributes to the pathogenesis of COPD.,B-cell follicles are present in lung tissue and increased anti-elastin titers have been found in plasma of COPD patients.,Additionally, regulatory T cells (Tregs) have been implicated in its pathogenesis as they control immunological reactions.,We hypothesize that the specific immune response in COPD is smoke induced, either by a direct effect of smoking or as a result of smoke-induced lung tissue destruction (i.e. formation of neo-epitopes or auto antigens).,Furthermore, we propose that Tregs are involved in the suppression of this smoke-induced specific immune response.,The presence of B cells, memory B cells and Tregs was assessed by flow cytometry in peripheral blood of 20 COPD patients and 29 healthy individuals and related to their current smoking status.,COPD patients had lower (memory) B-cell percentages and higher Treg percentages in peripheral blood than healthy individuals, with a significant negative correlation between these cells.,Interestingly, current smokers had higher percentages of (class-switched) memory B cells than ex-smokers and never smokers, irrespective of COPD.,This increase in (class-switched) memory B cells in current smokers is intriguing and suggests that smoke-induced neo-antigens may be constantly induced in the lung.,The negative correlation between B cells and Tregs in blood is in line with previously published observations that Tregs can suppress B cells.,Future studies focusing on the presence of these (class switched) memory B cells in the lung, their antigen specificity and their interaction with Tregs are necessary to further elucidate the specific B-cell response in COPD.

Acute Exacerbations of COPD (AECOPD) identified from electronic healthcare records (EHR) are important for research, public health and to inform healthcare utilisation and service provision.,However, there is no standardised method of identifying AECOPD in UK EHR.,We aimed to validate the recording of AECOPD in UK EHR.,We randomly selected 1385 patients with COPD from the Clinical Practice Research Datalink.,We selected dates of possible AECOPD based on 15 different algorithms between January 2004 and August 2013.,Questionnaires were sent to GPs asking for confirmation of their patients’ AECOPD on the dates identified and for any additional relevant information.,Responses were reviewed independently by two respiratory physicians.,Positive predictive value (PPV) and sensitivity were calculated.,The response rate was 71.3%.,AECOPD diagnostic codes, lower respiratory tract infection (LRTI) codes, and prescriptions of antibiotics and oral corticosteroids (OCS) together for 5-14 days had a high PPV (>75%) for identifying AECOPD.,Symptom-based algorithms and prescription of antibiotics or OCS alone had lower PPVs (60-75%).,A combined strategy of antibiotic and OCS prescriptions for 5-14 days, or LRTI or AECOPD code resulted in a PPV of 85.5% (95% CI, 82.7-88.3%) and a sensitivity of 62.9% (55.4-70.4%).,Using a combination of diagnostic and therapy codes, the validity of AECOPD identified from EHR can be high.,These strategies are useful for understanding health-care utilisation for AECOPD, informing service provision and for researchers.,These results highlight the need for common coding strategies to be adopted in primary care to allow easy and accurate identification of events.

This study aimed to characterize patients with chronic obstructive pulmonary disease (COPD) newly prescribed a long-acting bronchodilator (LABD), and to assess changes in medication over 24 months.,A cohort of patients with COPD aged ≥40 years newly prescribed an LABD between January 1, 2007 and December 31, 2009 were identified from the Truven Marketscan® Commercial Database (Truven Health Analytics, Ann Arbor, MI, USA) and followed for 24 months.,Inclusion criteria included no prior prescription for an LABD or inhaled corticosteroids for 12 months prior to the LABD index date (baseline).,Patient characteristics were examined.,As LABDs were mainly long-acting muscarinic antagonists (LAMAs), additions, switches, discontinuation, adherence to (medication possession ratio), and persistence (proportion of days covered) with LAMA monotherapy were assessed for 24 months following the index date.,Adherence and persistence with long-acting β2-agonists (LABAs) were also assessed.,A cohort of 3,268 patients aged 40-65 years was identified (mean age 55.8 years, 48% male).,LAMA monotherapy was prescribed to 93% of patients who received an LABD.,During the 24-month follow-up, 16% of these patients added COPD medication, 10% switched to an inhaled corticosteroid-containing medication, and 25% discontinued after one LAMA prescription at baseline.,Over 12 and 24 months, adherence to LAMA was 40% and 33%, respectively, and adherence to LABA was 29% and 24%, respectively.,Over the same time periods, persistence with LAMA monotherapy was 19% and 15%, respectively, and persistence with LABA was 9% and 7%, respectively.,Adherence to newly initiated LAMA monotherapy was low, with one in four patients adding to or switching from LAMA and many patients discontinuing therapy.,Adherence to LABA was also low.,These results suggest that additional medication to a single LABD may be required in some patients with COPD to achieve optimal disease control.

Sphingolipid bioactivities in the respiratory airways and the roles of the proteins that handle them have been extensively investigated.,Gas or inhaled particles or microorganisms come into contact with mucus components, epithelial cells, blood barrier, and immune surveillance within the airways.,Lung structure and functionality rely on a complex interplay of polar and hydrophobic structures forming the surfactant layer and governing external-internal exchanges, such as glycerol-phospholipids sphingolipids and proteins.,Sphingolipids act as important signaling mediators involved in the control of cell survival and stress response, as well as secreted molecules endowed with inflammation-regulatory activities.,Most successful respiratory infection and injuries evolve in the alveolar compartment, the critical lung functional unit involved in gas exchange.,Sphingolipid altered metabolism in this compartment is closely related to inflammatory reaction and ceramide increase, in particular, favors the switch to pathological hyperinflammation.,This short review explores a few mechanisms underlying sphingolipid involvement in the healthy lung (surfactant production and endothelial barrier maintenance) and in a selection of lung pathologies in which the impact of sphingolipid synthesis and metabolism is most apparent, such as acute lung injury, or chronic pathologies such as cystic fibrosis and chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a multifaceted condition that cannot be fully described by the severity of airway obstruction.,The limitations of spirometry and clinical history have prompted researchers to investigate a multitude of surrogate biomarkers of disease for the assessment of patients, prediction of risk, and guidance of treatment.,The aim of this review is to provide a comprehensive summary of observations for a selection of recently investigated pulmonary inflammatory biomarkers (Surfactant protein D (SP-D), Club cell protein 16 (CC-16), and Pulmonary and activation-regulated chemokine (PARC/CCL-18)) and systemic inflammatory biomarkers (C-reactive protein (CRP) and fibrinogen) with COPD.,The relevance of these biomarkers for COPD is discussed in terms of their biological plausibility, their independent association to disease and hard clinical outcomes, their modification by interventions, and whether changes in clinical outcomes are reflected by changes in the biomarker.

Marked accumulation of alveolar macrophages (AM) conferred by apoptosis resistance has been implicated in pathogenesis of chronic obstructive pulmonary disease (COPD).,Apoptosis inhibitor of macrophage (AIM), has been shown to be produced by mature tissue macrophages and AIM demonstrates anti-apoptotic property against multiple apoptosis-inducing stimuli.,Accordingly, we attempt to determine if AIM is expressed in AM and whether AIM is involved in the regulation of apoptosis in the setting of cigarette smoke extract (CSE) exposure.,Immunohistochemical evaluations of AIM were performed.,Immunostaining was assessed by counting total and positively staining AM numbers in each case (n = 5 in control, n = 5 in non-COPD smoker, n = 5 in COPD).,AM were isolated from bronchoalveolar lavage fluid (BALF).,The changes of AIM expression levels in response to CSE exposure in AM were evaluated.,Knock-down of anti-apoptotic Bcl-xL was mediated by siRNA transfection.,U937 monocyte-macrophage cell line was used to explore the anti-apoptotic properties of AIM.,The numbers of AM and AIM-positive AM were significantly increased in COPD lungs.,AIM expression was demonstrated at both mRNA and protein levels in isolated AM, which was enhanced in response to CSE exposure.,AIM significantly increased Bcl-xL expression levels in AM and Bcl-xL was involved in a part of anti-apoptotic mechanisms of AIM in U937 cells in the setting of CSE exposure.,These results suggest that AIM expression in association with cigarette smoking may be involved in accumulation of AM in COPD.

COPD is a leading cause of morbidity and mortality, characterized by a chronic abnormal inflammatory response to noxious agents.,Apoptosis is a physiologic process, critical to cellular homeostasis, in which cell death follows a programmed sequence of events.,Apoptosis has been recognized to play an important role in clinical and experimental models of lung diseases.,Abnormal apoptotic events in smokers’ and in emphysematous lungs have been shown in epithelial and endothelial lung cells, neutrophils, lymphocytes, and myocytes.,Many factors associated with COPD, including cigarette smoke, have the potential to cause apoptosis of alveolar epithelial cells, the main sites of vascular endothelial growth factor (VEGF) production.,The decreased expression of VEGF, a known survival factor for endothelial cells, and its receptor, results in lung septal endothelial cell death, leading perhaps to the emphysema observed in COPD.,In smokers who develop COPD there is an activation of adaptive immunity, with an infiltration of CD4+ and, especially, CD8 + cells.,CD8 + cells are cytotoxic to epithelial cells through the release of granzymes and perforin, which can further induce apoptosis of alveolar cells.,Moreover, any reduction in neutrophil apoptosis or dysregulation of macrophage uptake of apoptotic neutrophils could lead to chronic inflammation and tissue injury.,Increased rates of T-cell apoptosis may lead to a defective immune response to infective organisms, contributing to the high frequency of infections seen in COPD.,Increased apoptosis of skeletal muscle could be responsible for the skeletal muscle atrophy, the main cause of unexplained weight loss in patients with COPD.,This paper is a review of the current knowledge on the apoptotic pathways involved in COPD pathogenesis and their interaction with other known contributing factors.

Patients with chronic obstructive pulmonary disease (COPD) often have multiple underlying comorbidities, which may lead to increased health care resource utilization (HCRU) and costs.,To describe the comorbidity profiles of COPD patients and examine the associations between the presence of comorbidities and HCRU or health care costs.,A retrospective cohort study utilizing data from a large US national health plan with a predominantly Medicare population was conducted.,COPD patients aged 40-89 years and continuously enrolled for 12 months prior to and 24 months after the first COPD diagnosis during the period of January 01, 2009, through December 31, 2010, were selected.,Eleven comorbidities of interest were identified 12 months prior through 12 months after COPD diagnosis.,All-cause and COPD-related hospitalizations and costs were assessed 24 months after diagnosis, and the associations with comorbidities were determined using multivariate statistical models.,Ninety-two percent of 52,643 COPD patients identified had at least one of the 11 comorbidities.,Congestive heart failure (CHF), coronary artery disease, and cerebrovascular disease (CVA) had the strongest associations with all-cause hospitalizations (mean ratio: 1.56, 1.32, and 1.30, respectively; P<0.0001); other comorbidities examined had moderate associations.,CHF, anxiety, and sleep apnea had the strongest associations with COPD-related hospitalizations (mean ratio: 2.01, 1.32, and 1.21, respectively; P<0.0001); other comorbidities examined (except chronic kidney disease [CKD], obesity, and osteoarthritis) had moderate associations.,All comorbidities assessed (except obesity and CKD) were associated with higher all-cause costs (mean ratio range: 1.07-1.54, P<0.0001).,CHF, sleep apnea, anxiety, and osteoporosis were associated with higher COPD-related costs (mean ratio range: 1.08-1.67, P<0.0001), while CVA, CKD, obesity, osteoarthritis, and type 2 diabetes were associated with lower COPD-related costs.,This study confirms that specific comorbidities among COPD patients add significant burden with higher HCRU and costs compared to patients without these comorbidities.,Payers may use this information to develop tailored therapeutic interventions for improved management of patients with specific comorbidities.

The morbidity and mortality associated with COPD exacts a considerable economic burden.,Comorbidities in COPD are associated with poor health outcomes and increased costs.,Our objective was to assess the impact of comorbidities on COPD-associated costs in a large administrative claims dataset.,This was a retrospective observational study of data from the Truven Health MarketScan Commercial Claims and Encounters and the MarketScan Medicare Supplemental Databases from January 1, 2009, to September 30, 2012.,Resource consumption was measured from the index date (date of first occurrence of non-rule-out COPD diagnosis) to 360 days after the index date.,Resource use (all-cause and disease-specific [ie, COPD- or asthma-related] ED visits, hospitalizations, office visits, other outpatient visits, and total length of hospital stay) and health-care costs (all-cause and disease-specific costs for ED visits, hospitalizations, office visits, and other outpatient visits and medical, prescription, and total health-care costs) were assessed.,Generalized linear models were used to evaluate the impact of comorbidities on total health-care costs, adjusting for age, sex, geographic location, baseline health-care use, employment status, and index COPD medication.,Among 183,681 patients with COPD, the most common comorbidities were cardiovascular disease (34.8%), diabetes (22.8%), asthma (14.7%), and anemia (14.2%).,Most patients (52.8%) had one or two comorbidities of interest.,The average all-cause total health-care costs from the index date to 360 days after the index date were highest for patients with chronic kidney disease ($41,288) and anemia ($38,870).,The impact on total health-care costs was greatest for anemia ($10,762 more, on average, than a patient with COPD without anemia).,Our analysis demonstrated that high resource use and costs were associated with COPD and multiple comorbidities.

Chronic obstructive pulmonary disease (COPD) is a prevalent chronic airway disease with varied frequencies of acute exacerbations, which are the main cause of morbidity and mortality of the disease.,It is, therefore, urgent to develop novel therapies for COPD and its exacerbations, which rely heavily on understanding of the pathogenesis and investigation for potential targets.,Current evidence indicates that natural killer (NK) cells play important roles in the pathological processes of COPD.,Although novel data are revealing the significance of NK cells in maintaining immune system homeostasis and their involvement in pathogenesis of COPD, the specific mechanisms are largely unknown.,Specific and in-depth studies elucidating the underlying mechanisms are therefore needed.,In this review, we provided a brief overview of the biology of NK cells, from its development to receptors and functions, and outlined their subsets in peripheral blood and lungs.,Then we reviewed published findings highlighting the important roles played by NK cells in COPD and its exacerbations, with a view of providing the current state of knowledge in this area to facilitate related in-depth research.

In chronic obstructive pulmonary disease (COPD), endothelial dysfunction and stiffness of systemic arteries may contribute to increased cardiovascular risk.,Pulmonary vascular disease (PVD) is frequent in COPD.,The association between PVD and systemic vascular dysfunction has not been thoroughly evaluated in COPD.,A total of 108 subjects were allocated into four groups (non-smoking controls, smoking controls, COPD without PVD and COPD with PVD).,In systemic arteries, endothelial dysfunction was assessed by flow-mediated dilation (FMD) and arterial stiffness by pulse wave analysis (PWA) and pulse wave velocity (PWV).,PVD was defined by a mean pulmonary artery pressure (PAP) ≥25 mmHg at right heart catheterization or by a tricuspid regurgitation velocity >2.8 m/s at doppler echocardiography.,Biomarkers of inflammation and endothelial damage were assessed in peripheral blood.,FMD was lower in COPD patients, with or without PVD, compared to non-smoking controls; and in patients with COPD and PVD compared to smoking controls.,PWV was higher in COPD with PVD patients compared to both non-smoking and smoking controls in a model adjusted by age and the Framingham score; PWV was also higher in patients with COPD and PVD compared to COPD without PVD patients in the non-adjusted analysis.,FMD and PWV correlated significantly with forced expiratory volume in the first second (FEV1), diffusing capacity for carbon monoxide (DLCO) and systolic PAP.,FMD and PWV were correlated in all subjects.,We conclude that endothelial dysfunction of systemic arteries is common in COPD, irrespective if they have PVD or not.,COPD patients with PVD show increased stiffness and greater impairment of endothelial function in systemic arteries.,These findings suggest the association of vascular impairment in both pulmonary and systemic territories in a subset of COPD patients.

To compare efficacy of indacaterol to that of fixed-dose combination (FDC) formoterol and budesonide (FOR/BUD) and FDC salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on the available randomized clinical trials (RCTs).,Fifteen placebo-controlled RCTs were included that evaluated: indacaterol 150 μg (n = 5 studies), indacaterol 300 μg (n = 4), FOR/BUD 9/160 μg (n = 2), FOR/BUD 9/320 μg (n = 3), SAL/FP 50/500 μg (n = 5), and SAL/FP 50/250 μg (n = 1).,Outcomes of interest were trough forced expiratory volume in 1 second (FEV1), total scores for St.,George’s Respiratory Questionnaire (SGRQ), and transition dyspnea index (TDI).,All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained.,Treatment-by-covariate interactions were included where possible to improve the similarity of the trials.,Indacaterol 150 μg resulted in a higher change from baseline (CFB) in FEV1 at 12 weeks compared to FOR/BUD 9/160 μg (difference in CFB 0.11 L [95% credible intervals: 0.08, 0.13]) and FOR/BUD 9/320 μg (0.09 L [0.06, 0.11]) and was comparable to SAL/FP 50/250 μg (0.02 L [−0.04, 0.08]) and SAL/FP 50/500 μg (0.03 L [0.00, 0.06]).,Similar results were observed for indacaterol 300 μg at 12 weeks and indacaterol 150/300 μg at 6 months.,Indacaterol 150 μg demonstrated comparable improvement in SGRQ total score at 6 months versus FOR/BUD (both doses), and SAL/FP 50/500 μg (−2.16 point improvement [−4.96, 0.95]).,Indacaterol 150 and 300 μg demonstrated comparable TDI scores versus SAL/FP 50/250 μg (0.21 points (−0.57, 0.99); 0.39 [−0.39, 1.17], respectively) and SAL/FP 50/500 μg at 6 months.,Indacaterol monotherapy is expected to be at least as good as FOR/BUD (9/320 and 9/160 μg) and comparable to SAL/FP (50/250 and 50/500 μg) in terms of lung function.,Indacaterol is also expected to be comparable to FOR/BUD (9/320 and 9/160 μg) and SAL/FP 50/500 μg in terms of health status and to SAL/FP (50/250 and 50/500 μg) in terms of breathlessness.

Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and mortality.,Caring for patients with COPD, particularly those with advanced disease who experience frequent exacerbations, places a significant burden on health care budgets, and there is a global need to reduce the financial and personal burden of COPD.,Evolving scientific evidence on the natural history and clinical course of COPD has fuelled a fundamental shift in our approach to the disease.,The emergence of data highlighting the heterogeneity in rate of lung function decline has altered our perception of disease progression in COPD and our understanding of appropriate strategies for the management of stable disease.,These data have demonstrated that early, effective, and prolonged bronchodilation has the potential to slow the rate of decline in lung function and to reduce the frequency of exacerbations that contribute to functional decline.,The goals of therapy for COPD are no longer confined to controlling symptoms, reducing exacerbations, and maintaining quality of life, and slowing disease progression is now becoming an achievable aim.,A challenge for the future will be to capitalize on these observations by improving the identification and diagnosis of patients with COPD early in the course of their disease, so that effective interventions can be introduced before the more advanced, disabling, and costly stages of the disease.,Here we critically review emerging data that underpin the advances in our understanding of the clinical course and management of COPD, and evaluate both current and emerging pharmacologic options for effective maintenance treatment.

Spirometric diagnosis of chronic obstructive pulmonary disease (COPD) is based on the ratio of forced expiratory volume in 1 second (FEV1)/vital capacity (VC), either as a fixed value <0.7 or below the lower limit of normal (LLN).,Forced vital capacity (FVC) is a proxy for VC.,The first aim was to compare the use of FVC and VC, assessed as the highest value of FVC or slow vital capacity (SVC), when assessing the FEV1/VC ratio in a general population setting.,The second aim was to evaluate the characteristics of subjects with COPD who obtained a higher SVC than FVC.,Subjects (n=1,050) aged 50-64 years were investigated with FEV1, FVC, and SVC after bronchodilation.,Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPDFVC was defined as FEV1/FVC <0.7, GOLDCOPDVC as FEV1/VC <0.7 using the maximum value of FVC or SVC, LLNCOPDFVC as FEV1/FVC below the LLN, and LLNCOPDVC as FEV1/VC below the LLN using the maximum value of FVC or SVC.,Prevalence of GOLDCOPDFVC was 10.0% (95% confidence interval [CI] 8.2-12.0) and the prevalence of LLNCOPDFVC was 9.5% (95% CI 7.8-11.4).,When estimates were based on VC, the prevalence became higher; 16.4% (95% CI 14.3-18.9) and 15.6% (95% CI 13.5-17.9) for GOLDCOPDVC and LLNCOPDVC, respectively.,The group of additional subjects classified as having COPD based on VC, had lower FEV1, more wheeze and higher residual volume compared to subjects without any COPD.,The prevalence of COPD was significantly higher when the ratio FEV1/VC was calculated using the highest value of SVC or FVC compared with using FVC only.,Subjects classified as having COPD when using the VC concept were more obstructive and with indications of air trapping.,Hence, the use of only FVC when assessing airflow limitation may result in a considerable under diagnosis of subjects with mild COPD.

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.

Multimorbidity, the presence of 2 or more chronic conditions, frequently affects people with chronic obstructive pulmonary disease (COPD).,Many have high-cost, highly complex conditions that have a substantial impact on state Medicaid programs.,We quantified the cost of Medicaid-insured patients with COPD co-diagnosed with other chronic disorders.,We used nationally representative Medicaid claims data to analyze the impact of comorbidities (other chronic conditions) on the disease burden, emergency department (ED) use, hospitalizations, and total health care costs among 291,978 adult COPD patients.,We measured the prevalence of common conditions and their influence on COPD-related and non-COPD-related resource use by using the Elixhauser Comorbidity Index.,Elixhauser comorbidity counts were clustered from 0 to 7 or more.,We performed multivariable logistic regression to determine the odds of ED visits by Elixhauser scores adjusting for age, sex, race/ethnicity, and residence.,Acute care, hospital bed days, and total Medicaid-reimbursed costs increased as the number of comorbidities increased.,ED visits unrelated to COPD were more common than visits for COPD, especially in patients self-identified as black or African American (designated black).,Hypertension, diabetes, affective disorders, hyperlipidemia, and asthma were the most prevalent comorbid disorders.,Substance abuse, congestive heart failure, and asthma were commonly associated with ED visits for COPD.,Female sex was associated with COPD-related and non-COPD-related ED visits.,Comorbidities markedly increased health services use among people with COPD insured with Medicaid, although ED visits in this study were predominantly unrelated to COPD.,Achieving excellence in clinical practice with optimal clinical and economic outcomes requires a whole-person approach to the patient and a multidisciplinary health care team.

Patients with chronic obstructive pulmonary disease (COPD) often have multiple underlying comorbidities, which may lead to increased health care resource utilization (HCRU) and costs.,To describe the comorbidity profiles of COPD patients and examine the associations between the presence of comorbidities and HCRU or health care costs.,A retrospective cohort study utilizing data from a large US national health plan with a predominantly Medicare population was conducted.,COPD patients aged 40-89 years and continuously enrolled for 12 months prior to and 24 months after the first COPD diagnosis during the period of January 01, 2009, through December 31, 2010, were selected.,Eleven comorbidities of interest were identified 12 months prior through 12 months after COPD diagnosis.,All-cause and COPD-related hospitalizations and costs were assessed 24 months after diagnosis, and the associations with comorbidities were determined using multivariate statistical models.,Ninety-two percent of 52,643 COPD patients identified had at least one of the 11 comorbidities.,Congestive heart failure (CHF), coronary artery disease, and cerebrovascular disease (CVA) had the strongest associations with all-cause hospitalizations (mean ratio: 1.56, 1.32, and 1.30, respectively; P<0.0001); other comorbidities examined had moderate associations.,CHF, anxiety, and sleep apnea had the strongest associations with COPD-related hospitalizations (mean ratio: 2.01, 1.32, and 1.21, respectively; P<0.0001); other comorbidities examined (except chronic kidney disease [CKD], obesity, and osteoarthritis) had moderate associations.,All comorbidities assessed (except obesity and CKD) were associated with higher all-cause costs (mean ratio range: 1.07-1.54, P<0.0001).,CHF, sleep apnea, anxiety, and osteoporosis were associated with higher COPD-related costs (mean ratio range: 1.08-1.67, P<0.0001), while CVA, CKD, obesity, osteoarthritis, and type 2 diabetes were associated with lower COPD-related costs.,This study confirms that specific comorbidities among COPD patients add significant burden with higher HCRU and costs compared to patients without these comorbidities.,Payers may use this information to develop tailored therapeutic interventions for improved management of patients with specific comorbidities.

Both stable chronic obstructive pulmonary disease (COPD) and acute exacerbations represent leading causes of death, disability and healthcare expenditure.,They are complex, heterogeneous and their mechanisms are poorly understood.,The role of respiratory viruses has been studied extensively but is still not adequately addressed clinically.,Through a rigorous evidence update, we aim to define the prevalence and clinical burden of the different respiratory viruses in stable COPD and exacerbations, and to investigate whether viral load of usual respiratory viruses could be used for diagnosis of exacerbations triggered by viruses, which are currently not diagnosed or treated aetiologically.,Based on a prospectively registered protocol, we will systematically review the literature using standard methods recommended by the Cochrane Collaboration and the Grading of Recommendations Assessment, Development and Evaluation working group.,We will search Medline/PubMed, Excerpta Medica dataBASE (EMBASE), the Cochrane Library, the WHO’s Clinical Trials Registry and the proceedings of relevant international conferences on 2 March 2020.,We will evaluate: (A) the prevalence of respiratory viruses in stable COPD and exacerbations, (B) differences in the viral loads of respiratory viruses in stable COPD vs exacerbations, to explore whether the viral load of prevalent respiratory viruses could be used as a diagnostic biomarker for exacerbations triggered by viruses and (C) the association between the presence of respiratory viruses and clinical outcomes in stable COPD and in exacerbations.,Ethics approval is not required since no primary data will be collected.,Our findings will be presented in national and international scientific conferences and will be published in peer reviewed journals.,Respiratory viruses currently represent a lost opportunity to improve the outcomes of both stable COPD and exacerbations.,Our work aspires to ‘demystify’ the prevalence and clinical burden of viruses in stable COPD and exacerbations and to promote clinical and translational research.,CRD42019147658.

Chronic Obstructive Pulmonary Disease (COPD) is characterised by reduced lung function and is the third leading cause of death globally.,Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97.,A genetic risk score was associated with COPD susceptibility (odds ratios per standard deviation of the risk score (~6 alleles) (95% confidence interval) 1.24 (1.20-1.27), P=5.05x10-49) and we observed a 3.7 fold difference in COPD risk between highest and lowest genetic risk score deciles in UK Biobank.,The 97 signals show enrichment in development, elastic fibres and epigenetic regulation pathways.,We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.

COPD is a leading cause of morbidity and mortality worldwide.,Patients with COPD often require admission to intensive care units (ICU) during an acute exacerbation.,This study aimed to identify the factors independently associated with hospital mortality in patients requiring ICU admission for acute exacerbation of COPD.,Patients admitted to the ICU of Frankston Hospital between January 2005 and June 2016 with an admission diagnosis of COPD were retrospectively identified from ICU databases.,Patients’ comorbidities, arterial blood gas results, and in-patient interventions were retrieved from their medical records.,Outcomes analyzed included hospital and ICU length of stay (LOS) and mortality.,A total of 305 patients were included.,Mean age was 67.4 years.,A total of 77% of patients required non-invasive ventilation; and 38.7% required invasive mechanical ventilation (IMV) for a median of 127.2 hours (SD =179.5).,Mean ICU LOS was 4.5 days (SD =5.96), and hospital LOS was 11.6 days (SD =13).,In-hospital mortality was 18.7%.,Multivariate analysis revealed that patient age (odds ratio [OR] =1.06; 95% CI: 1.031-1.096), ICU LOS (OR =1.26; 95% CI: 1.017-1.571), Acute Physiology and Chronic Health Evaluation-II score (OR =1.07; 95% CI: 1.012-1.123), and requirement for IMV (OR =4.09; 95% CI: 1.791-9.324) to be significantly associated with in-hospital mortality.,Patient age, requirement for IMV, and illness severity were associated with poor patient outcomes.

Chronic obstructive pulmonary disease (COPD) is a major cause of mortality worldwide.,Patients with COPD frequently have systemic comorbidities that often require unscheduled hospitalization for exacerbation and deterioration of physical conditions, and can have a poor prognosis.,We verified factors affecting patients’ short-term mortality, using a national inpatient database in Japan.,We retrospectively collected data for COPD patients (age: >40 years) with emergency admission between July 2010 and March 2013, using the Diagnosis Procedure Combination database.,We performed multivariate logistic analyses fitted with a generalized estimating equation to assess factors associated with all-cause in-hospital mortality.,A total of 177,207 patients (mean age: 77.5 years; males: 72.9%) were identified.,All-cause in-hospital death occurred in 23,614 patients (13.7%).,Higher mortality was associated with older age, male sex, lower body mass index, more severe dyspnea, lower level of consciousness, and worse activities of daily life.,Higher mortality was also associated with comorbid conditions, including bacterial pneumonia, aspiration pneumonia, interstitial pneumonitis, pulmonary embolism, respiratory failure, lung cancer, heart failure, cerebral infarction, liver cirrhosis, and chronic renal failure.,Our study demonstrated that all-cause in-hospital mortality in patients with COPD who required emergency hospitalization was associated with deteriorated general conditions and comorbidities at admission.,Physicians should take into account these prognostic factors to choose better treatment options for COPD patients.

The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999-2000.,Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples.,Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments.,Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis.,The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale.,Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey.,COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%-9%.,In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%-14%) than among women (range 5%-11%).,A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries.,Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment.,This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey.,A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey.

Chronic obstructive lung disease (COPD) exacerbations are a significant cause of morbidity and mortality.,Data regarding factors which causes or prevents exacerbations is very limited.,The aim of this systematic review is to summarize the results from available studies to identify potential risk factors for hospital admission and/or re-admission among patients experiencing COPD exacerbations.,We undertook a systematic review of the literature.,Potential studies were identified by searching the electronic databases: PubMed, EMBASE, BIOSIS, CINAHL, PsycINFO, Cochrane library, reference lists in trial reports, and other relevant articles.,Seventeen articles that met the predefined inclusion criteria were identified.,Heterogeneity of study designs, risk factors and outcomes restrict the result to only a systematic review and precluded a formal meta-analysis.,In this review, three predictive factors: previous hospital admission, dyspnea and oral corticosteroids were all found to be significant risk factors of readmissions and variables including using long term oxygen therapy, having low health status or poor health related quality of life and not having routine physical activity were all associated with an increased risk of both admission and readmission to hospital.,There are a number of potential modifiable factors that are independently associated with a higher risk of COPD exacerbation requiring admission/readmission to the hospital.,Identifying these factors and the development of targeted interventions could potentially reduce the number and severity of such exacerbations.

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.

The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment.,The effect of this combination on symptoms of COPD and exacerbations is less well established.,We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).,Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®.,Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.,The pooled intent-to-treat population included 3394 patients.,Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05).,Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05).,The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05).,Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies.,Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).,Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD.,Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.,NCT01462942 and NCT01437397 (ClinicalTrials.gov),The online version of this article (doi:10.1186/s12931-015-0250-2) contains supplementary material, which is available to authorized users.

Caregivers of individuals with COPD have a key role in maintaining patient adherence and optimizing patient function.,However, no systematic review has examined how the caregiver role has been operationalized in interventions to improve outcomes of individuals with COPD or the quality or effectiveness of these interventions.,The aims of this review were to 1) determine whether caregivers have been involved as part of interventions to improve outcomes of individuals with COPD; 2) determine the risk of bias within included intervention studies; and 3) examine the effectiveness of interventions that have involved caregivers in improving outcomes of individuals with COPD.,The electronic databases of Medline, Embase, PsycINFO, and Cochrane Library were searched from January 2000 to November 2015.,Experimental studies testing interventions that involved a caregiver to improve COPD patient outcomes were eligible.,Nine studies involving caregivers met inclusion criteria.,No studies reported any intervention components targeted solely at caregivers, with most instead including caregivers in dyadic or group education sessions about COPD delivered by health care professionals.,The risk of bias identified in included studies was mixed.,Seven of the nine studies were effective in improving a broad range of outcomes.,These findings highlight that there is an urgent need for methodologically rigorous interventions to examine the effectiveness of strategies to assist caregivers to provide direct care, encourage adherence to health care provider recommendations, act as a health care advocate, and provide emotional and psychosocial support to individuals with COPD.

Chronic obstructive pulmonary disease (COPD) is a very prevalent and invalidating disease.,The aim of this study was to analyze the burden borne by informal caregivers of patients with COPD.,We used the Survey on Disabilities, Personal Autonomy, and Dependency Situations (Encuesta sobre Discapacidad, Autonomía personal y Situaciones de Dependencia [EDAD]-2008) to obtain information on the characteristics of disabled individuals with COPD and their caregivers in Spain.,Additionally, statistical multivariate analyses were performed to analyze the impact that an increase in dependence would have on the problems for which caregivers provide support, in terms of health, professional, and leisure/social dimensions.,A total of 461,884 individuals with one or more disabilities and with COPD were identified, and 220,892 informal caregivers were estimated.,Results showed that 35% of informal caregivers had health-related problems due to the caregiving provided; 83% had leisure/social-related problems; and among caregivers of working age, 38% recognized having profession-related problems.,The probability of a problem arising was significantly associated with the degree of dependence of the patient receiving care.,Caregivers of patients with great dependence showed a 39% higher probability of presenting health-related problems, 27% more professional problems, and 23% more leisure problems compared with those with nondependent patients.,The results show the large impact on society in terms of the welfare of informal caregivers of patients with COPD.,A higher level of dependence was associated with more severe problems in caregivers, in all dimensions.

Patients with chronic obstructive pulmonary disease (COPD) often have multiple underlying comorbidities, which may lead to increased health care resource utilization (HCRU) and costs.,To describe the comorbidity profiles of COPD patients and examine the associations between the presence of comorbidities and HCRU or health care costs.,A retrospective cohort study utilizing data from a large US national health plan with a predominantly Medicare population was conducted.,COPD patients aged 40-89 years and continuously enrolled for 12 months prior to and 24 months after the first COPD diagnosis during the period of January 01, 2009, through December 31, 2010, were selected.,Eleven comorbidities of interest were identified 12 months prior through 12 months after COPD diagnosis.,All-cause and COPD-related hospitalizations and costs were assessed 24 months after diagnosis, and the associations with comorbidities were determined using multivariate statistical models.,Ninety-two percent of 52,643 COPD patients identified had at least one of the 11 comorbidities.,Congestive heart failure (CHF), coronary artery disease, and cerebrovascular disease (CVA) had the strongest associations with all-cause hospitalizations (mean ratio: 1.56, 1.32, and 1.30, respectively; P<0.0001); other comorbidities examined had moderate associations.,CHF, anxiety, and sleep apnea had the strongest associations with COPD-related hospitalizations (mean ratio: 2.01, 1.32, and 1.21, respectively; P<0.0001); other comorbidities examined (except chronic kidney disease [CKD], obesity, and osteoarthritis) had moderate associations.,All comorbidities assessed (except obesity and CKD) were associated with higher all-cause costs (mean ratio range: 1.07-1.54, P<0.0001).,CHF, sleep apnea, anxiety, and osteoporosis were associated with higher COPD-related costs (mean ratio range: 1.08-1.67, P<0.0001), while CVA, CKD, obesity, osteoarthritis, and type 2 diabetes were associated with lower COPD-related costs.,This study confirms that specific comorbidities among COPD patients add significant burden with higher HCRU and costs compared to patients without these comorbidities.,Payers may use this information to develop tailored therapeutic interventions for improved management of patients with specific comorbidities.

Chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality worldwide, often occurs in the presence of comorbidities, which may influence experience and management of the disease.,No prior research seems to have gained perspectives of newly diagnosed primary care COPD patients in the context of multimorbidity.,This qualitative study aimed to explore the impact of a new diagnosis of COPD in the context of multimorbidity and also sought to gain a better understanding of how patients react to the diagnosis and incorporate it into their lives.,Participants were identified from a cohort of primary care patients with multimorbidity recently diagnosed with COPD.,Data was collected via semi-structured interviews from nine male and eight female participants.,Thematic analysis was performed and the data interpreted from a constructivist perspective.,Five core themes regarding COPD were induced: (i) reaction to diagnosis, (ii) impact on function and health behaviour, (iii) factors influencing self-management capacity, (iv) healthcare utilisation and (v) interplay of comorbidities.,Most participants had difficulty recognising the importance of COPD and its long-term implications.,For many, the salience of another chronic condition outweighed COPD.,Self-management capacity and utilisation of healthcare services were challenged by low prioritisation of COPD among other comorbidities.,This study provides an insight into how primary care patients feel about being diagnosed with COPD, as well as their prioritisation of the disease in the context of multimorbidity.,It highlights the need for tailored education and personalised management incorporating patients’ perspectives in primary care.

Previous studies have suggested that β2-adrenergic receptor (ADRB2) is associated with COPD.,However, the role of genetic polymorphisms in ADRB2 on COPD has not been evaluated yet.,In this study, SNaPshot genotyping, luciferase assay, chromatin immunoprecipitation and real-time polymerase chain reaction were adopted to investigate the association between ADRB2 genetic polymorphisms and COPD, comprehensively.,One single nucleotide polymorphism (rs12654778), located upstream of ADRB2, showed a significant association with COPD by the logistic regression analysis after adjusting for age, sex and smoking history (p=0.04) in 200 COPD patients and 222 controls from southwest Chinese population.,Furthermore, the luciferase assay indicated that rs12654778-A allele reduced the relative promoter activity by ~26% compared with rs12654778-G allele (p=0.0034).,The chromatin immunoprecipitation analysis demonstrated that rs12654778 modulated the binding affinity of transcription factor neurofibromin 1.,In addition, a significantly reduced expression of ADRB2 in COPD patients was observed, compared with normal controls (p=0.017).,Our findings suggest a previously unknown mechanism linking allele-specific effects of rs12654778 on ADRB2 expression to COPD onset, for the first time.

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression.,A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs).,PQTLs consistently replicated between the two cohorts.,Features of pQTLs were compared to previously reported expression QTLs (eQTLs).,Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests.,We identified 527 highly significant (p < 8 X 10−10) pQTLs in 38 (43%) of blood proteins tested.,Most pQTL SNPs were novel with low overlap to eQTL SNPs.,The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC).,Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes.,Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins.,The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates.,Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema.,In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms.,Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group.

Krasnoyarsk region is a territory with the widespread risk factors for chronic obstructive pulmonary disease (COPD) such as tobacco smoke, air pollution, and occupational exposure.,An assessment of COPD prevalence based on medical diagnosis statistics underestimates the true COPD prevalence.,This study aims to evaluate how medical examinations may increase the accuracy of estimates of COPD prevalence.,True COPD prevalence was estimated as a number of patients with the established disease diagnosis supplemented by the additional disease cases detected during medical examinations per 1,000 inhabitants of the region.,Official medical statistics data and the data collected from the Global Alliance against Chronic Respiratory Diseases program 2011 among 15,000 inhabitants of the region aged 18 years and older were analyzed.,This study revealed the COPD cases without official medical diagnosis.,The true prevalence of COPD is estimated to be two times higher than the prevalence estimates based on medical diagnosis statistics.,Undiagnosed and untreated cases of COPD result in severe COPD forms as well as addition of severe comorbidities.,Because of this, there is an increase in the index of potential years of life lost.,Conducting special medical examinations may increase the number of COPD cases detected at the early stages of the disease.,This, in turn, may reduce the overall burden of the disease for the population of the region.

Estimation suggests that at least 4 million people die, annually, as a result of chronic respiratory disease (CRD).,The Global Alliance against Chronic Respiratory Diseases (GARD) was formed following a mandate from the World Health Assembly to address this serious and growing health problem.,To investigate the prevalence of CRD in Russian symptomatic patients and to evaluate the frequency of major risk factors for CRD in Russia.,A cross-sectional, population-based epidemiological study using the GARD questionnaire on adults from 12 regions of the Russian Federation.,Common respiratory symptoms and risk factors were recorded.,Spirometry was performed in respondents with suspected CRD.,Allergic rhinitis (AR) and chronic bronchitis (CB) were defined by the presence of related symptoms according to the Allergic Rhinitis and its Impact on Asthma and the Global Initiative for Obstructive Lung Disease guidelines; asthma was defined based on disease symptoms; chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume per 1 second/forced vital capacity ratio <0.7 in symptomatic patients, following the Global Initiative for Obstructive Lung Disease guidelines.,The number of questionnaires completed was 7,164 (mean age 43.4 years; 57.2% female).,The prevalence of asthma symptoms was 25.7%, AR 18.2%, and CB 8.6%.,Based on patient self-reported diagnosis, 6.9% had asthma, 6.5% AR, and 22.2% CB.,The prevalence of COPD based on spirometry in patients with respiratory symptoms was estimated as 21.8%.,The prevalence of respiratory diseases and risk factors was high in Russia when compared to available data.,For bronchial asthma and AR, the prevalence for related symptoms was higher than self-reported previous diagnosis.

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.

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.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death by disease worldwide and has a 30-day readmission rate of 22.6%.,In 2015, COPD was added to the Medicare Hospital Readmission Reductions Program.,The objective of this paper was to survey the current medical technologies for remote patient monitoring (RPM) tools that forecast COPD exacerbations in order to reduce COPD readmissions.,We searched literature and digital health news to find commercially available RPM devices focused on predicting COPD exacerbations.,These technologies were reviewed and compared according to four criteria: forecasting ability, cost, ease of use, and appearance.,A rating system was developed to facilitate the evaluation process.,As of June 2019, a list of handheld and hands-free devices was compiled.,We compared features and found substantial variations.,Devices that ranked higher on all criteria tended to have a high or unlisted price.,Commonly mass-marketed devices like the pulse oximeter and spirometer surprisingly fulfilled the least criteria.,The COPD RPM technologies with most technological promise and compatibility with daily living appear to have high or unlisted prices.,Consumers and providers need better access to product information to make informed decisions.

The objective of this study was to identify the necessary features of pulmonary telerehabilitation (P-TR) from the perspectives of individuals living with chronic lung disease and health care professionals (HCPs) who deliver pulmonary rehabilitation (PR).,Focus groups were carried out with patients (n = 26) and HCPs (n = 26) to elicit and explore their opinions about the critical elements of in-person PR and ideas for how these elements could be supported using technology.,A questionnaire was used to assess technology use, PR experience, and general health status.,Four key elements of PR were identified as critical to P-TR: the social aspect of PR; communicating with HCPs for education and support; using biosensors for monitoring and promoting self-knowledge; and the evolution of support with progress over time.,A range of technology-enabled devices and programs were suggested as means to recreate aspects of these integral elements.,Consultations with patients and HCPs suggest that users are interested in technology and want to ensure it recreates the important aspects of PR.,Patients and HCPs identified similar key elements for P-TR.,The opinions and suggestions of patients and HCPs should be the driving force of innovation if P-TR is to succeed in improving health outcomes.

This study was undertaken to determine the association between cardiac function and therapy with beta2-adrenoceptor agonists (β2-agonists), β-blockers, or β-blocker-β-agonist combination therapy in elderly male patients with chronic obstructive pulmonary disease (COPD).,This was a retrospective cohort study of 220 elderly male COPD patients (mean age 84.1 ± 6.9 years).,The patients were divided into four groups on the basis of the use of β-blockers and β2-agonists.,N-terminal fragment pro-B-type natriuretic peptide (NT pro-BNP), left ventricular ejection fraction (LVEF), and other relevant parameters were measured and recorded.,At follow-up, the primary end point was all-cause mortality.,Multiple linear regression analysis revealed no significant associations between NT pro-BNP and the use of β2-agonists (β = 35.502, P = 0.905), β-blockers (β = 3.533, P = 0.989), or combination therapy (β = 298.635, P = 0.325).,LVEF was not significantly associated with the use of β2-agonists (β = −0.360, P = 0.475), β-blockers (β = −0.411, P = 0.284), or combination therapy (β = −0.397, P = 0.435).,Over the follow-up period, 52 patients died, but there was no significant difference in mortality among the four groups (P = 0.357).,Kaplan-Meier analysis showed no significant difference among the study groups (log-rank test, P = 0.362).,After further multivariate adjustment, use of β2-agonists (hazard ratio [HR] 0.711, 95% confidence interval [CI] 0.287-1.759; P = 0.460), β-blockers (HR 0.962, 95% CI 0.405-2.285; P = 0.930), or combination therapy (HR 0.638, 95% CI 0.241-1.689; P < 0.366) were likewise not correlated with mortality.,There was no association between the use of β2-agonists, β-blockers, or β-blocker-β2-agonist combination therapy with cardiac function and all-cause mortality in elderly male COPD patients, which indicated that they may be used safely in this population.

Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are elevated in patients with secondary pulmonary hypertension and chronic lung disease with right ventricular overload.,The aim of the present study was to investigate the use of plasma NT-proBNP levels as a prognostic marker of severe COPD with chronic respiratory failure and latent pulmonary hypertension.,Plasma NT-proBNP levels were measured in 61 patients with stable COPD.,Plasma NT-proBNP levels, pulmonary function, PaO2, and PaCO2 levels and systolic pulmonary artery pressure were compared according to COPD severity.,In addition, we examined correlations between plasma NT-proBNP levels and pulmonary function, PaO2, PaCO2, and systolic pulmonary artery pressure.,The levels of plasma NT-proBNP significantly increased in patients with stage IV and stage III COPD compared to individuals with stage II COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification.,The area under the receiver-operating characteristic curve of plasma NT-proBNP for severe to very severe COPD (FEV1 < 50%) was 0.707 (95% confidence interval [CI] 0.566-0.847, P = 0.008).,Plasma NT-proBNP levels significantly correlated with %FEV1 (r = −0.557; P < 0.001), arterial blood gas parameters such as PaCO2 (r = 0.476; P < 0.001) and PaO2 (r = −0.347; P = 0.031), and systolic pulmonary artery pressure (r = 0.435; P = 0.001).,Plasma NT-proBNP levels increased significantly with disease severity, progression of chronic respiratory failure, and secondary pulmonary hypertension in patients with stable COPD.,These results suggest that plasma NT-proBNP can be a useful prognostic marker to monitor COPD progression and identify cases of secondary pulmonary hypertension in patients with stable COPD.

The aim of this study was to assess health-related quality of life (HRQL) in patients with chronic obstructive pulmonary disease (COPD) and to discuss the different tools available for its assessment.,The most widely used assessments are the St.,George respiratory questionnaire (SGRQ) and the COPD assessment test (CAT) questionnaire.,Both have a different difficulty in exam completion, calculation, and scoring.,No studies exist that analyze the validity and internal consistency of using both questionnaires on patients admitted to the hospital for a COPD exacerbation.,A multicenter, cross-sectional analytic observational study of patients admitted to the hospital due to a COPD exacerbation (CIE 491.2).,During their hospital stay, they were administered the SGRQ and the CAT questionnaire within the framework of a therapeutic education program (APRENDEPOC).,Descriptive and comparative analysis, correlations between the scales (Pearson’s correlation index), consistency and reliability calculations (Cronbach’s α), and a forward stepwise multiple linear regression were performed, with significant correlations in both questionnaires considered p < 0.01 with the total scores.,A statistical significance of p < 0.05 was assumed.,Altogether, 231 patients were admitted for a COPD exacerbation (n = 77) at Hospital Clínic of Barcelona (HCB) and (n = 154) at Hospital Universitario General of Castellón (HUGC).,The sample profile was not homogeneous between both centers, with significant differences in HRQL between hospitals.,Correlation were noted between both scales (p < 0.01), along with high levels of internal consistency and reliability (CAT 0.836 vs.,SGRQ 0.827).,The HRQL is related to dyspnea, wheezing, daytime drowsiness, and edema, as well as to the need to sleep in a sitting position, anxiety, depression, and dependence on others in the execution of daily activities.,Our regression analysis showed that the SGRQ questionnaire could predict more changes in HRQL with a higher number of variables.

To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] level and history of community-acquired pneumonia (CAP).,We identified 16,975 individuals (≥17 years) from the third National Health and Nutrition Examination Survey (NHANES III) with documented 25(OH)D levels.,To investigate the association of 25(OH)D with history of CAP in these participants, we developed a multivariable logistic regression model, adjusting for demographic factors (age, sex, race, poverty-to-income ratio, and geographic location), clinical data (body mass index, smoking status, asthma, chronic obstructive pulmonary disease, congestive heart failure, diabetes mellitus, stroke, chronic kidney disease, neutropenia, and alcohol consumption), and season.,Locally weighted scatterplot smoothing (LOWESS) was used to depict the relationship between increasing 25(OH)D levels and the cumulative frequency of CAP in the study cohort.,The median [interquartile range (IQR)] serum 25(OH)D level was 24 (IQR 18-32) ng/mL.,2.1% [95% confidence interval (CI): 1.9-2.3] of participants reported experiencing a CAP within one year of their participation in the national survey.,After adjusting for demographic factors, clinical data, and season, 25(OH)D levels <30 ng/mL were associated with 56% higher odds of CAP [odds ratio 1.56; 95% confidence interval: 1.17-2.07] compared to levels ≥30 ng/mL.,LOWESS analysis revealed a near linear relationship between vitamin D status and the cumulative frequency of CAP up to 25(OH)D levels around 30 ng/mL.,Among 16,975 participants in NHANES III, 25(OH)D levels were inversely associated with history of CAP.,Randomized controlled trials are warranted to determine the effect of optimizing vitamin D status on the risk of CAP.

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

Olodaterol is a long-acting β2-agonist with a 24-hour bronchodilator profile.,Two replicate, randomized, double-blind, placebo-controlled, parallel-group, Phase III trials were performed as part of a comprehensive clinical program to investigate the long-term safety and efficacy of olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) receiving usual-care background therapy.,Patients received olodaterol 5 μg or 10 μg or placebo once daily for 48 weeks.,Coprimary end points were forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 3 hours (AUC0-3) response (change from baseline), and trough FEV1 response at 12 weeks.,Secondary end points included additional lung function assessments, use of rescue medications, FEV1 AUC response from 0 to 12 hours, and Patient Global Rating over 48 weeks.,Overall, 624 and 642 patients were evaluated in studies 1222.11 and 1222.12, respectively.,In both studies, olodaterol 5 μg and 10 μg significantly improved the FEV1 AUC0-3 response (P<0.0001) and trough FEV1 (study 1222.11, P<0.0001; study 1222.12, P<0.05, post hoc) at week 12, with an incidence of adverse events comparable with that of placebo.,Secondary end points supported the efficacy of olodaterol.,These studies demonstrate the long-term efficacy and safety of once-daily olodaterol 5 μg and 10 μg in patients with moderate to very severe COPD continuing with usual-care maintenance therapy.

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

GSK961081 is a bifunctional molecule demonstrating both muscarinic antagonist and β-agonist activities.,This was a 4-week, multicentre, randomised, double-blind, double-dummy, placebo and salmeterol controlled parallel group study.,Doses ranging across three twice-daily doses and three once-daily doses were assessed in moderate and severe chronic obstructive pulmonary disease (COPD) patients.,Trough forced expiratory volume in 1 s (FEV1) at day 29 was the primary end-point.,At days 1 and 28, 12-h FEV1 spirometry was performed in all patients.,A subset of patients underwent complete 24-h spirometry at day 28.,The study recruited 436 patients.,GSK961081 showed statistically and clinically significant differences from placebo in all doses and regimens for trough FEV1 on day 29 (155-277 mL).,The optimal total daily dose was 400 μg, either as 400 μg once daily or as 200 μg twice daily, with an improvement in day 29 trough FEV1 of 215 mL and 249 mL, respectively.,Other efficacy end-points also showed improvement.,No effects were observed on glucose, potassium, heart rate, blood pressure and no dose-response effect was seen on corrected QT elongation.,This study showed that GSK961081 is an effective bronchodilator in COPD and appeared to be safe and well tolerated.,Phase IIb study results showed the muscarinic antagonist-β-agonist GSK961081β is an effective bronchodilator in COPDhttp://ow.ly/lh7mU

Multiple factors can influence the severity of chronic obstructive pulmonary disease (COPD) and the functioning of patients with COPD, such as personal characteristics and systemic manifestations.,To evaluate the different factors that can influence the activity and psychosocial impact domains of the Saint George's Respiratory Questionnaire (SGRQ) in COPD patients.,Participants, recruited in a university-based hospital, responded to the SGRQ, and in addition, personal, anthropometric, and clinical data were collected.,The study was approved by the Institutional Ethics Committee.,Data were analyzed using multiple linear regression models, with the SGRQ activity and psychosocial impact scores as outcome variables, and 10 explanatory variables (age, gender, forced expiratory volume in the first second - FEV1, smoking load, body mass index, oxygen therapy, associated diseases, regular physical activity, participation in a formal rehabilitation program, and SGRQ symptoms score) were considered.,The best regression model for predicting the SGRQ activity score (r2=0.477) included gender, FEV1, and SGRQ symptoms.,In contrast, the predictive model with the highest proportion of explained variance in psychosocial impact score (r2=0.426) included the variables gender, oxygen therapy, and SGRQ symptoms.,The results indicate that the outcomes, while based on functioning parameters in COPD patients, could be partly explained by the personal and clinical factors analyzed, especially by the symptoms assessed by the SGRQ.,Thus, it appears that the health conditions of these patients cannot be described by isolated variables, including pulmonary function parameters.

Quadriceps muscle dysfunction is well confirmed in chronic obstructive pulmonary disease (COPD) and reported to be related to a higher risk of mortality.,Factors contributing to quadriceps dysfunction have been postulated, while not one alone could fully explain it and there are few reports on it in China.,This study was aimed to investigate the severity of quadriceps dysfunction in patients with COPD, and to compare quadriceps muscle function in COPD and the healthy elderly.,Quadriceps strength and endurance capabilities were investigated in 71 COPD patients and 60 age-matched controls; predicted values for quadriceps strength and endurance were calculated using regression equations (incorporating age, gender, anthropometric measurements and physical activities), based on the data from controls.,Potential parameters related to quadriceps dysfunction in COPD were identified by stepwise regression analysis.,Mean values of quadriceps strength was 46% and endurance was 38% lower, in patients with COPD relative to controls.,Gender, physical activities and anthropometric measurements were predictors to quadriceps function in the controls.,While in COPD, forced expiratory volume in 1 second percentage of predicted value (FEV1% pred), nutritional depletion, gender and physical inactivity were identified as independent factors to quadriceps strength (R2 = 0.72); FEV1%pred, thigh muscle mass, serum levels of tumor necrosis factor-alpha (TNF-α) and gender were correlated to quadriceps endurance variance, with each p<0.05.,Quadriceps strength and endurance capabilities are both substantially impaired in Chinese COPD patients, with strength most affected.,For the controls, physical activity is most important for quadriceps function.,While for COPD patients, quadriceps dysfunction is related to multiple factors, with airflow limitation, malnutrition and muscle disuse being the main ones.

The combination of the inhaled muscarinic antagonist umeclidinium (UMEC) with the long-acting β2-agonist vilanterol (VI) has been shown to provide significant improvements in lung function compared with UMEC, VI, or placebo (PBO) in patients with chronic obstructive pulmonary disease (COPD).,This study was specifically designed to support these findings by assessing health-related quality of life and symptomatic outcomes in a similar population.,This was a 12-week multicenter, randomized, double-blind, parallel-group, placebo-controlled study.,Eligible patients were randomized 1:1 to receive once-daily UMEC/VI 62.5/25 μg (via ELLIPTA® dry powder inhaler) or PBO for 12 weeks.,The primary endpoint was St George’s Respiratory Questionnaire (SGRQ) total score at day 84.,Secondary efficacy endpoints included rescue albuterol use (puffs/day) over weeks 1-12 and trough forced expiratory volume in 1 second on day 84.,Adverse events were also assessed.,A total of 496 patients were included in the intent-to-treat population in the UMEC/VI (n=248) and PBO (n=248) treatment groups.,UMEC/VI 62.5/25 μg provided a significant and clinically meaningful improvement in SGRQ total score at day 84 versus PBO (difference between treatments in SGRQ total score change from baseline: −4.03 [95% confidence interval {CI}: −6.28, −1.79]; P<0.001).,UMEC/VI 62.5/25 μg resulted in a statistically significant reduction in rescue albuterol use versus PBO (−0.7 puffs/day [95% CI: −1.1, −0.4]; P<0.001).,UMEC/VI 62.5/25 μg provided a significant and clinically meaningful improvement in trough forced expiratory volume in 1 second on day 84 versus PBO (122 mL [95% CI: 71, 172]; P<0.001).,The incidence of adverse events was similar between treatments (32% and 30% of patients in the UMEC/VI 62.5/25 μg and PBO groups, respectively).,The results of this study demonstrate that treatment with UMEC/VI 62.5/25 μg provides clinically important improvements in SGRQ and rescue medication use versus PBO in patients with moderate-to-very-severe COPD.

Sustained bronchodilation using inhaled medications in moderate to severe chronic obstructive pulmonary disease (COPD) grades 2 and 3 (Global Initiative for Chronic Obstructive Lung Disease guidelines) has been shown to have clinical benefits on long-term symptom control and quality of life, with possible additional benefits on disease progression and longevity.,Aggressive diagnosis and treatment of symptomatic COPD is an integral and pivotal part of COPD management, which usually begins with primary care physicians.,The current standard of care involves the use of one or more inhaled bronchodilators, and depending on COPD severity and phenotype, inhaled corticosteroids.,There is a wide range of inhaler devices available for delivery of inhaled medications, but suboptimal inhaler use is a common problem that can limit the clinical effectiveness of inhaled therapies in the real-world setting.,Patients’ comorbidities, other physical or mental limitations, and the level of inhaler technique instruction may limit proper inhaler use.,This paper presents information that can overcome barriers to proper inhaler use, including issues in device selection, steps in correct technique for various inhaler devices, and suggestions for assessing and monitoring inhaler techniques.,Ensuring proper inhaler technique can maximize drug effectiveness and aid clinical management at all grades of COPD.

Singing for lung health (SLH) is a popular arts-in-health activity for people with long-term respiratory conditions.,Participants report biopsychosocial benefits, however, research on impact is limited.,The ‘SLH: Improving Experiences of Lung Disease trial’, a randomised controlled, single (assessor) blind, trial of 12 weeks SLH versus usual care for people with chronic obstructive pulmonary disease (COPD) (n=120) was setup to help to address this.,The first group (n=18, nine singing and nine controls) started face-to-face (five sessions) before changing to online delivery (seven sessions) due to COVID-19-related physical distancing measures.,As such, the experience of this group is here reported as a pilot study to inform further research in this area.,We conducted semistructured interviews and thematic analysis regarding barriers, facilitators and key considerations for transitioning from face-to-face to online delivery.,Pilot quantitative outcomes include attendance, premeasures and postmeasures of quality of life and disease impact (Short Form 36 Health Survey, COPD Assessment Test score), breathlessness (Medical Research Council breathlessness scale, Dyspnoea-12), depression (Patient Health Questionnaire-9, PHQ-9), anxiety (Generalised Anxiety Disorder-7), balance confidence (Activity specific Balance Confidence, ABC scale) and physical activity (clinical visit PROactive physical activity in COPD tool, combining subjective rating and actigraphy).,Attendance was 69% overall, (90% of the face-to-face sessions, 53% online sessions).,Analysis of semistructured interviews identified three themes regarding participation in SLH delivered face to face and online, these where (1) perceived benefits; (2) digital barriers (online) and (3) digital facilitators (online).,Findings were summarised into key considerations for optimising transitioning singing groups from face-to-face to online delivery.,Pilot quantitative data suggested possible improvements in depression (treatment effect −4.78 PHQ-9 points, p<0.05, MCID 5) and balance confidence (treatment effect +17.21 ABC scale points, p=0.04, MCID 14.2).,This study identifies key considerations regarding the adaptation of SLH from face-to-face to online delivery.,Pilot data suggest online group singing for people with COPD may deliver benefits related to reducing depression and improved balance confidence.

This study was designed to investigate the effects of long-term home-based Liuzijue exercise combined with clinical guidance in elderly patients with chronic obstructive pulmonary disease (COPD).,Forty patients with COPD at stages II-III of the Global Initiative for Chronic Obstructive Lung Disease were enrolled.,The subjects were randomly allocated to the Liuzijue exercise group (LG) or control group (CG) in a 1:1 ratio.,Participants in the LG performed six Liuzijue training sessions, including 4 days at home and 2 days in the hospital with clinical guidance for 60 minutes/day for 6 months.,Participants in the CG conducted no exercise intervention.,In addition, lung function test, 6-minute walking test (6MWT), 30-second sit-to-stand test (30 s SST), and the St George’s Respiratory Questionnaire (SGRQ) were conducted at the baseline and at the end of the intervention.,Thirty-six patients completed the study.,The patients’ lung function improved significantly (p < 0.05) in the LG as well as the 6MWT, 30 s SST, and SGRQ score (p < 0.01).,While the SGRQ total score, activity, and impact scores increased significantly (p < 0.05) in the CG.,In addition, there were significant differences between the groups (p < 0.01) in regard to the values of forced expiratory volume in 1 second as a percentage of the predicted volume, 6MWT, 30 s SST, and SGRQ.,Long-term home-based Liuzijue exercise combined with clinical guidance can effectively improve the pulmonary function, exercise capacity, and quality of life of elderly patients with moderate to severe COPD.

The aim of this study is to quantify the burden of chronic obstructive pulmonary disease (COPD) - incidence, prevalence, and mortality - and identify trends in Australia, Canada, France, Germany, Italy, Japan, The Netherlands, Spain, Sweden, the United Kingdom, and the United States of America.,A structured literature search was performed (January 2000 to September 2010) of PubMed and EMBASE, identifying English-language articles reporting COPD prevalence, incidence, or mortality.,Of 2838 articles identified, 299 full-text articles were reviewed, and data were extracted from 133 publications.,Prevalence data were extracted from 80 articles, incidence data from 15 articles, and mortality data from 58 articles.,Prevalence ranged from 0.2%-37%, but varied widely across countries and populations, and by COPD diagnosis and classification methods.,Prevalence and incidence were greatest in men and those aged 75 years and older.,Mortality ranged from 3-111 deaths per 100,000 population.,Mortality increased in the last 30-40 years; more recently, mortality decreased in men in several countries, while increasing or stabilizing in women.,Although COPD mortality increased over time, rates declined more recently, likely indicating improvements in COPD management.,In many countries, COPD mortality has increased in women but decreased in men.,This may be explained by differences in smoking patterns and a greater vulnerability in women to the adverse effects of smoking.,Point your SmartPhone at the code above.,If you have a QR code reader the video abstract will appear.,Or use: http://dvpr.es/Nl3LKT

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.

With the limited reach of pulmonary rehabilitation (PR) and low levels of daily physical activity in chronic obstructive pulmonary disease (COPD), a need exists to increase daily exercise.,This study evaluated telephone health-mentoring targeting home-based walking (tele-rehab) compared to usual waiting time (usual care) followed by group PR.,People with COPD were randomized to tele-rehab (intervention) or usual care (controls).,Tele-rehab delivered by trained nurse health-mentors supported participants’ home-based walking over 8-12 weeks.,PR, delivered to both groups simultaneously, included 8 weeks of once-weekly education and self-management skills, with separate supervised exercise.,Data were collected at three time-points: baseline (TP1), before (TP2), and after (TP3) PR.,The primary outcome was change in physical capacity measured by 6-minute walk distance (6MWD) with two tests performed at each time-point.,Secondary outcomes included changes in self-reported home-based walking, health-related quality of life, and health behaviors.,Of 65 recruits, 25 withdrew before completing PR.,Forty attended a median of 6 (4) education sessions.,Seventeen attended supervised exercise (5±2 sessions).,Between TP1 and TP2, there was a statistically significant increase in the median 6MWD of 12 (39.1) m in controls, but no change in the tele-rehab group.,There were no significant changes in 6MWD between other time-points or groups, or significant change in any secondary outcomes.,Participants attending supervised exercise showed a nonsignificant improvement in 6MWD, 12.3 (71) m, while others showed no change, 0 (33) m.,The mean 6MWD was significantly greater, but not clinically meaningful, for the second test compared to the first at all time-points.,Telephone-mentoring for home-based walking demonstrated no benefit to exercise capacity.,Two 6-minute walking tests at each time-point may not be necessary.,Supervised exercise seems essential in PR.,The challenge of incorporating exercise into daily life in COPD is substantial.

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.

COPD exacerbations are commonly quantified as rate per year.,However, the total amount of time a patient suffers from exacerbations may be stronger related to his or her disease burden than just counting exacerbation episodes.,In this study, we examined the relationship between exacerbation frequency and exacerbation-free time, and their associations with baseline characteristics and health-related quality of life.,A total of 166 COPD patients reported symptom changes during 12 months.,Symptom-defined exacerbation episodes were correlated to the number of exacerbation-free weeks per year.,Analysis of covariance was used to examine the effects of baseline characteristics on annual exacerbation frequency and exacerbation-free weeks, Spearman’s rank correlations to examine associations between the two methods to express exacerbations and the Chronic Respiratory Questionnaire (CRQ).,The correlation between exacerbation frequency and exacerbation-free weeks was −0.71 (p < 0.001).,However, among frequent exacerbators (i.e., ≥3 exacerbations/year, n = 113) the correlation was weak (r = −0.25; p < 0.01).,Smokers had less exacerbation-free weeks than non-smokers (β = −5.709, p < 0.05).,More exacerbation-free weeks were related to better CRQ Total (r = 0.22, p < 0.05), Mastery (r = 0.22, p < 0.05), and Fatigue (r = 0.23, p < 0.05) scores, whereas no significant associations were found between exacerbation frequency and CRQ scores.,In COPD patients with frequent exacerbations, there is substantial variation in exacerbation-free time.,Exacerbation-free time may better reflect the burden of exacerbations in patients with COPD than exacerbation frequency does.,Time spent exacerbation-free may provide a stronger indication of disease burden than exacerbation frequency for patients with chronic lung disease.,Exacerbations in chronic obstructive pulmonary disease (COPD) are marked by a sudden decline in lung function, potential hospitalisation and a need to increase medication.,Exacerbation frequency is used as a marker in COPD management, but this does not consider the duration of exacerbations or the impact this has on patients’ lives.,Lonneke Boer at Radboud University Medical Center, the Netherlands, and co-workers questioned 166 patients every two weeks for a year about their experiences of exacerbation duration and frequency.,There was substantial variation in exacerbation-free time between patients, with smokers most likely to suffer longer periods of poorer health.,Exacerbation-free time was better correlated with health-related quality of life than exacerbation frequency.

Hospitalization for a severe exacerbation of COPD (eCOPD) is an important event in the natural history of COPD.,Identifying factors related to mortality 1 year after hospitalization could help determine interventions to reduce mortality.,In a prospective, observational, multicentre study, we evaluated data from two cohorts: the Spanish audit of hospital COPD exacerbation care (our derivation sample) and the Spanish cohort of the European audit of COPD exacerbation care (our validation sample).,The endpoint was all-cause mortality.,Mortality was determined by local research managers of the participating hospitals and matched the official national index records in Spain.,In the multivariate analysis, factors independently related to an increase in mortality were older age, cardio-cerebro-vascular and/or dementia comorbidities, PaCO2 > 55 mmHg measured at emergency department arrival, hospitalizations for COPD exacerbations in the previous year, and hospital characteristics.,The area under the receiver-operating curve for this model was 0.75 in the derivation cohort and 0.76 in the validation cohort.,One-year mortality following the index hospitalization for an exacerbation of COPD was related to clinical characteristics of the patient and of the index event, previous events of similar severity, and characteristics of the hospital where the patient was treated.

COPD is characterized by an ongoing inflammatory process of the airways that leads to obstruction or limitation of airflow.,It is mainly associated with exposure to cigarette smoke.,In addition, it is considered, at present, a serious public health problem, ranking fourth in mortality worldwide.,Many cells participate in the pathophysiology of COPD, the most important are neutrophils, macrophages and CD4+ and CD8+ T cells.,Neutrophil migration to the inflammation area could be mediated largely by cytokines related to CD4+ Th17 lymphocytes, because it has been shown that IL-17A, IL-17F and IL-22 act as inducers for CXCL8, CXCL1, CXCL5, G-CSF, and GM-CSF secretion by epithelial cells of the airways.,The aims of these molecules are differentiation, proliferation and recruitment of neutrophils.,Furthermore, it is believed that CD4+ lymphocytes Th17 may be involved in protection against pathogens for which Th1 and Th2 are not prepared to fight.,In COPD exacerbations, there is an increased cellularity in the lung region and respiratory tract.,Therefore, the increase in the number of neutrophils and macrophages in the airways and the increase in proinflammatory cytokines are directly related to the severity of exacerbations and that is the importance of the functions of Th17 profile in this entity.

Inflammatory biomarkers, including cytokines, are associated with COPD, but the association of particular circulating cytokines with systemic pathology remains equivocal.,To investigate this, we developed a protein microarray system to detect multiple cytokines in small volumes of serum.,Fourteen cytokines were measured in serum from never-smokers, ex-smokers, current smokers, and COPD patients (GOLD stages 1-3).,Certain individual circulating cytokines (particularly TNFα and IL-1β) were significantly elevated in concentration in the serum of particular COPD patients (and some current/ex-smokers without COPD) and may serve as markers of particularly significant systemic inflammation.,However, numerous circulating cytokines were raised such that their combined, but not individual, elevation was significantly associated with severity of disease, and these may be further indicators of, and contributors to, the systemic inflammatory manifestations of COPD.,The coelevation of numerous circulating cytokines in COPD is consistent with the insidious development, chronic nature, and systemic comorbidities of the disease.

A substantial proportion of chronic disease patients do not respond to self-management interventions, which suggests that one size interventions do not fit all, demanding more tailored interventions.,To compose more individualized strategies, we aim to increase our understanding of characteristics associated with patient activation for self-management and to evaluate whether these are disease-transcending.,A cross-sectional survey study was conducted in primary and secondary care in patients with type-2 Diabetes Mellitus (DM-II), Chronic Obstructive Pulmonary Disease (COPD), Chronic Heart Failure (CHF) and Chronic Renal Disease (CRD).,Using multiple linear regression analysis, we analyzed associations between self-management activation (13-item Patient Activation Measure; PAM-13) and a wide range of socio-demographic, clinical, and psychosocial determinants.,Furthermore, we assessed whether the associations between the determinants and the PAM were disease-transcending by testing whether disease was an effect modifier.,In addition, we identified determinants associated with low activation for self-management using logistic regression analysis.,We included 1154 patients (53% response rate); 422 DM-II patients, 290 COPD patients, 223 HF patients and 219 CRD patients.,Mean age was 69.6±10.9.,Multiple linear regression analysis revealed 9 explanatory determinants of activation for self-management: age, BMI, educational level, financial distress, physical health status, depression, illness perception, social support and underlying disease, explaining a variance of 16.3%.,All associations, except for social support, were disease transcending.,This study explored factors associated with varying levels of activation for self-management.,These results are a first step in supporting clinicians and researchers to identify subpopulations of chronic disease patients less likely to be engaged in self-management.,Increased scientific efforts are needed to explain the greater part of the factors that contribute to the complex nature of patient activation for self-management.

Although chronic obstructive pulmonary disease (COPD) is a major global health burden there is a lack of patient awareness of disease severity, particularly in relation to exacerbations.,We conducted a global patient survey using an innovative, internet-based methodology to gain insight into patient perceptions of COPD and exacerbations in a real-world sample typical of today’s working-age COPD population.,Two thousand patients with COPD (53%), chronic bronchitis (52%) and/or emphysema (22%) from 14 countries completed an online questionnaire developed by the authors.,The Medical Research Council (MRC) breathlessness scale was used to delineate symptom severity.,Over three quarters of patients (77%) had experienced an exacerbation, with 27% of MRC 1 and 2 patients and 52% of MRC 3, 4 and 5 patients requiring hospitalization as a result of an exacerbation.,While a majority of MRC 1 and 2 patients (51%) reported being back to normal within a few days of an exacerbation, 23% of MRC 3, 4 and 5 patients took several weeks to return to normal and 6% never fully recovered.,A high proportion of patients (39%) took a ‘wait and see’ approach to exacerbations.,Despite the high prevalence of exacerbations and their negative impact on quality of life, 73% of MRC 1 and 2 patients and 64% of MRC 3, 4 and 5 patients felt that they had control of their COPD.,However, 77% of all patients were worried about their long-term health, and 38% of MRC 1 and 2 patients and 59% of MRC 3, 4 and 5 patients feared premature death due to COPD.,To reduce the adverse effects of COPD on patients’ quality of life and address their fears for the future, we need better patient education and improved prevention and treatment of exacerbations.

Vitamin D is well known for its function in calcium homeostasis and bone mineralisation, but is increasingly studied for its potential immunomodulatory properties.,Vitamin D deficiency is a common problem in patients with COPD.,Previous studies have not demonstrated a beneficial effect of vitamin D on exacerbation rate in COPD patients.,However, subgroup analyses suggested protective effects in vitamin D deficient patients.,Our objective is to assess the effect of vitamin D supplementation on exacerbation rate specifically in vitamin D deficient COPD patients.,We will perform a randomised, multi-center, double-blind, placebo-controlled intervention study.,The study population consists of 240 COPD patients aged 40 years and older with vitamin D deficiency (25-hydroxyvitamin D concentration < 50 nmol/L).,Participants will be recruited after an exacerbation and will be randomly allocated in a 1:1 ratio to receive vitamin D3 16800 IU or placebo orally once a week during 1 year.,Participants will receive a diary card to register the incidence of exacerbations and changes in medication during the study period.,Visits will be performed at baseline, at 6 months and at 12 months after randomisation.,Participants will undergo spirometry, measurement of total lung capacity and assessment of maximal respiratory mouth pressure.,Several physical performance and hand grip strength tests will be performed, questionnaires on quality of life and physical activity will be filled in, a nasal secretion sample and swab will be obtained and blood samples will be taken.,The primary outcome will be exacerbation rate.,This study will be the first RCT aimed at the effects of vitamin D supplementation on exacerbation rate in vitamin D deficient COPD patients.,Also, in contrast to earlier studies that used infrequent dosing regimens, our trial will study effects of a weekly dose of vitamin D supplementation.,Secondly, the immunomodulatory effects of vitamin D on host immune response of COPD patients and underlying mechanisms will be studied.,Finally, the effects on physical functioning will be examined.,This trial is registered in ClinicalTrials.gov, ID number NCT02122627.,Date of Registration April 2014.

Objectives To understand the perspectives of people with severe chronic obstructive pulmonary disease (COPD) as their illness progresses, and of their informal and professional carers, to inform provision of care for people living and dying with COPD.,Design Up to four serial qualitative interviews were conducted with each patient and nominated carer over 18 months.,Interviews were transcribed and analysed both thematically and as narratives.,Participants 21 patients, and 13 informal carers (a family member, friend, or neighbour) and 18 professional carers (a key health or social care professional) nominated by the patients.,Setting Primary and secondary care in Lothian, Tayside, and Forth Valley, Scotland, during 2007-9.,Results Eleven patients died during the study period.,Our final dataset comprised 92 interviews (23 conducted with patient and informal carer together).,Severe symptoms that caused major disruption to normal life were described, often in terms implying acceptance of the situation as a “way of life” rather than an “illness.”,Patients and their informal carers adapted to and accepted the debilitating symptoms of a lifelong condition.,Professional carers’ familiarity with the patients’ condition, typically over many years, and prognostic uncertainty contributed to the difficulty of recognising and actively managing end stage disease.,Overall, patients told a “chaos narrative” of their illness that was indistinguishable from their life story, with no clear beginning and an unanticipated end described in terms comparable with attitudes to death in a normal elderly population.,Conclusions Our findings challenge current assumptions underpinning provision of end of life care for people with COPD.,The policy focus on identifying a time point for transition to palliative care has little resonance for people with COPD or their clinicians and is counter productive if it distracts from early phased introduction of supportive care.,Careful assessment of possible supportive and palliative care needs should be triggered at key disease milestones along a lifetime journey with COPD, in particular after hospital admission for an exacerbation.

With the current wealth of new inhalers available and insurance policy driven inhaler switching, the need for insights in optimal education on inhaler use is more evident than ever.,We aimed to systematically review educational inhalation technique interventions, to assess their overall effectiveness, and identify main drivers of success.,Medline, Embase and CINAHL databases were searched for randomised controlled trials on educational inhalation technique interventions.,Inclusion eligibility, quality appraisal (Cochrane’s risk of bias tool) and data extraction were performed by two independent reviewers.,Regression analyses were performed to identify characteristics contributing to inhaler technique improvement.,Thirty-seven of the 39 interventions included (95%) indicated statistically significant improvement of inhaler technique.,However, average follow-up time was relatively short (5 months), 28% lacked clinical relevant endpoints and all lacked cost-effectiveness estimates.,Poor initial technique, number of inhalation procedure steps, setting (outpatient clinics performing best), and time elapsed since intervention (all, p < 0.05), were shown to have an impact on effectiveness of the intervention, explaining up to 91% of the effectiveness variation.,Other factors, such as disease (asthma vs. chronic obstructive pulmonary disease), education group size (individual vs. group training) and inhaler type (dry powder inhalers vs. pressurised metered dose inhalers) did not play a significant role.,Notably, there was a trend (p = 0.06) towards interventions in adults being more effective than those in children and the intervention effect seemed to wane over time.,In conclusion, educational interventions to improve inhaler technique are effective on the short-term.,Periodical intervention reinforcement and longer follow-up studies, including clinical relevant endpoints and cost-effectiveness, are recommended.

To estimate patient- and episode-level direct costs of chronic obstructive pulmonary disease (COPD) among commercially insured patients in the US.,In this retrospective claims-based analysis, commercial enrollees with evidence of COPD were grouped into five mutually exclusive cohorts based on the most intensive level of COPD-related care they received in 2006, ie, outpatient, urgent outpatient (outpatient care in addition to a claim for an oral corticosteroid or antibiotic within seven days), emergency department (ED), standard inpatient admission, and intensive care unit (ICU) cohorts.,Patient- level COPD-related annual health care costs, including patient- and payer-paid costs, were compared among the cohorts.,Adjusted episode-level costs were calculated.,Of the 37,089 COPD patients included in the study, 53% were in the outpatient cohort, 37% were in the urgent outpatient cohort, 3% were in the ED cohort, and the standard admission and ICU cohorts together comprised 6%.,Mean (standard deviation, SD) annual COPD-related health care costs (2008 US$) increased across the cohorts (P < 0.001), ranging from $2003 ($3238) to $43,461 ($76,159) per patient.,Medical costs comprised 96% of health care costs for the ICU cohort.,Adjusted mean (SD) episode-level costs were $305 ($310) for an outpatient visit, $274 ($336) for an urgent outpatient visit, $327 ($65) for an ED visit, $9745 ($2968) for a standard admission, and $33,440 for an ICU stay.,Direct costs of COPD-related care for commercially insured patients are driven by hospital stays with or without ICU care.,Exacerbation prevention resulting in reduced need for inpatient care could lower costs.

The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality.

The landmark study of Fletcher and Peto on the natural history of tobacco smoke-related chronic airflow obstruction suggested that decline in the forced expiratory volume in the first second (FEV1) in chronic obstructive pulmonary disease (COPD) is slow at the beginning, becoming faster with more advanced disease.,The present authors reviewed spirometric data of COPD patients included in the placebo arms of recent clinical trials to assess the lung function decline of each stage, defined according to the severity of airflow obstruction as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,In large COPD populations the mean rate of FEV1 decline in GOLD stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year, respectively, and lower than 35 mL/year in GOLD stage IV.,Few data on FEV1 decline are available for GOLD stage I.,Hence, the loss of lung function, assessed as expiratory airflow reduction, seems more accelerated and therefore more relevant in the initial phases of COPD.,To have an impact on the natural history of COPD, it is logical to look at the effects of treatment in the earlier stages.

N-Acetylcysteine (NAC) demonstrates applications in the prevention of exacerbation of chronic obstructive pulmonary disease (COPD).,COPD is often characterized by fibrosis of the small airways.,This study aims at investigating the physiological mechanisms by which NAC might mediate the pulmonary fibrosis in COPD.,A total of 10 non-smokers without COPD and 10 smokers with COPD were recruited in this study, and COPD rat models were established.,Cigarette smoke extract (CSE) cell models were constructed.,The gain- or loss-of-function experiments were adopted to determine the expression of VWF and the extent of p38 MAPK phosphorylation, levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and immunoglobulins (IgG, IgM and IgA) in the serum of COPD rats and supernatant of alveolar epithelial cells and to detect cell invasion and migration and the ratio of CD3+, CD4+, CD8+ and CD4+/CD8+T lymphocytes.,Expression of VWF and the extent of p38 MAPK phosphorylation were increased in COPD.,NAC inhibited p38 MAPK phosphorylation by reducing the VWF expression.,NAC could inhibit cell migration and invasion, elevate E-cadherin expression, the ratio of CD3+, CD4+, CD8+ and CD4+/CD8+T lymphocytes, and levels of IgG, IgA, and IgM, and reduce N-cadherin expression and levels of IL-6 and TNF-α in CSE cells and serum of COPD rats.,NAC promoted immune response and suppressed epithelial-mesenchymal transformation (EMT) to relieve COPD-induced pulmonary fibrosis in vitro and in vivo by inhibiting the VWF/p38 MAPK axis.,Collectively, NAC could ameliorate COPD-induced pulmonary fibrosis by promoting immune response and inhibiting EMT process via the VWF/p38 MAPK axis, therefore providing us with a potential therapeutic target for treating COPD.,The online version contains supplementary material available at 10.1186/s10020-021-00342-y.

The reticular basement membrane (Rbm) in smokers and especially smokers with COPD is fragmented with "clefts" containing cells staining for the collagenase matrix-metalloproteinase-9 (MMP-9) and fibroblast protein, S100A4.,These cells are also present in the basal epithelium.,Such changes are likely hallmarks of epithelial mesenchymal transition (EMT).,We aimed to confirm the epithelial origin of these Rbm cells, and to exclude potential confounding by infiltrating inflammatory cells.,Endobronchial biopsy sections from 17 COPD current smokers, with documented Rbm splitting and cellularity were stained for neutrophil elastase (neutrophil marker), CD68 (macrophage/mature fibroblasts), CD4+/CD8+ T lymphocytes, CD19 (B-cells), CD11c (dendritic cells/inflammatory cells), and S100 (Langerhans cells).,The number of cells in the Rbm and epithelium staining for these "inflammatory" cell markers were then compared to numbers staining for S100A4, "a documented EMT epitope".,Slides were double stained for S100A4 and cytokeratin(s).,In the basal epithelium significantly more cells stained for S100A4 compared to infiltrating macrophages, fibroblasts or immune cells: median, 26 (21.3 - 37.3) versus 0 (0 - 9.6) per mm, p < 0.003.,Markedly more S100A4 staining cells were also observed in the Rbm compared to infiltrating macrophages, neutrophils, fibroblasts or immune cells or any sub-type: 58 (37.3 - 92.6) versus 0 (0 - 4.8) cells/mm Rbm, p < 0.003.,Cells in the basal epithelium 26 (21.3 - 37.3) per mm) and Rbm (5.9 (2.3 - 13.8) per mm) frequently double stained for both cytokeratin and S100A4.,These data provide additional support for active EMT in COPD airways.

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.

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.

Pulmonary emphysema is characterized by alveolar destruction and persistent inflammation of the airways.,Although IL-17A contributes to many chronic inflammatory diseases, it’s role in the inflammatory response of elastase-induced emphysema remains unclear.,In a model of elastase-induced pulmonary emphysema we examined the response of IL-17A-deficient mice, monitoring airway inflammation, static compliance, lung histology and levels of neutrophil-related chemokine and pro-inflammatory cytokines in bronchoalveolar lavage (BAL) fluid.,Wild-type mice developed emphysematous changes in the lung tissue on day 21 after elastase treatment, whereas emphysematous changes were decreased in IL-17A-deficient mice compared to wild-type mice.,Neutrophilia in BAL fluid, seen in elastase-treated wild-type mice, was reduced in elastase-treated IL-17A-deficient mice on day 4, associated with decreased levels of KC, MIP-2 and IL-1 beta.,Elastase-treated wild-type mice showed increased IL-17A levels as well as increased numbers of IL-17A+ CD4 T cells in the lung in the initial period following elastase treatment.,These data identify the important contribution of IL-17A in the development of elastase-induced pulmonary inflammation and emphysema.,Targeting IL-17A in emphysema may be a potential therapeutic strategy for delaying disease progression.

The Wnt pathway mediates differentiation of epithelial tissues; depending on the tissue types, Wnt can either drive or inhibit the differentiation process.,We hypothesized that key genes in the Wnt pathway are suppressed in the human airway epithelium under the stress of cigarette smoking, a stress associated with dysregulation of the epithelial differentiated state.,Microarrays were used to assess the expression of Wnt-related genes in the small airway epithelium (SAE) obtained via bronchoscopy and brushing of healthy nonsmokers, healthy smokers, and smokers with COPD.,Thirty-three of 56 known Wnt-related genes were expressed in the SAE.,Wnt pathway downstream mediators β-catenin and the transcription factor 7-like 1 were down-regulated in healthy smokers and smokers with COPD, as were many Wnt target genes.,Among the extracellular regulators that suppress the Wnt pathway, secreted frizzled-related protein 2 (SFRP2), was up-regulated 4.3-fold in healthy smokers and 4.9-fold in COPD smokers, an observation confirmed by TaqMan Real-time PCR, Western analysis and immunohistochemistry.,Finally, cigarette smoke extract mediated up-regulation of SFRP2 and down-regulation of Wnt target genes in airway epithelial cells in vitro.,Smoking down-regulates the Wnt pathway in the human airway epithelium.,In the context that Wnt pathway plays an important role in differentiation of epithelial tissues, the down-regulation of Wnt pathway may contribute to the dysregulation of airway epithelium differentiation observed in smoking-related airway disorders.

Current recommendations to consider initiation of palliative care (PC) in COPD patients are often based on an expected poor prognosis.,However, this approach is not evidence-based, and which and when COPD patients should start PC is controversial.,We aimed to assess whether current suggested recommendations for initiating PC were sufficiently reliable.,We identified prognostic variables proposed in the literature for initiating PC; then, we ascertained their relationship with 1-year mortality, and finally, we validated their utility in our cohort of 697 patients hospitalized for COPD exacerbation.,From 24 articles of 499 screened, we selected 20 variables and retrieved 48 original articles in which we were able to calculate the relationship between each of them and 1-year mortality.,The number of studies where 1-year mortality was detailed for these variables ranged from 9 for previous hospitalizations or FEV1 ≤30% to none for albumin ≤25 mg/dL.,The percentage of 1-year mortality in the literature for these variables ranged from 5% to 60%.,In the validation cohort study, the prevalence of these proposed variables ranged from 8% to 64%; only 10 of the 18 variables analyzed in our cohort reached statistical significance with Cox regression analysis, and none overcame an area under the curve ≥0.7.,We conclude that none of the suggested criteria for initiating PC based on an expected poor vital prognosis in COPD patients in the short or medium term offers sufficient reliability, and consequently, they should be avoided as exclusive criteria for considering PC or at least critically appraised.

Several composite markers have been proposed for risk assessment in chronic obstructive pulmonary disease (COPD).,However, choice of parameters and score complexity restrict clinical applicability.,Our aim was to provide and validate a simplified COPD risk index independent of lung function.,The PROMISE study (n=530) was used to develop a novel prognostic index.,Index performance was assessed regarding 2-year COPD-related mortality and all-cause mortality.,External validity was tested in stable and exacerbated COPD patients in the ProCOLD, COCOMICS and COMIC cohorts (total n=2988).,Using a mixed clinical and statistical approach, body mass index (B), severe acute exacerbations of COPD frequency (AE), modified Medical Research Council dyspnoea severity (D) and copeptin (C) were identified as the most suitable simplified marker combination. 0, 1 or 2 points were assigned to each parameter and totalled to B-AE-D or B-AE-D-C.,It was observed that B-AE-D and B-AE-D-C were at least as good as BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity), ADO (age, dyspnoea, airflow obstruction) and DOSE (dyspnoea, obstruction, smoking, exacerbation) indices for predicting 2-year all-cause mortality (c-statistic: 0.74, 0.77, 0.69, 0.72 and 0.63, respectively; Hosmer-Lemeshow test all p>0.05).,Both indices were COPD specific (c-statistic for predicting COPD-related 2-year mortality: 0.87 and 0.89, respectively).,External validation of B-AE-D was performed in COCOMICS and COMIC (c-statistic for 1-year all-cause mortality: 0.68 and 0.74; c-statistic for 2-year all-cause mortality: 0.65 and 0.67; Hosmer-Lemeshow test all p>0.05).,The B-AE-D index, plus copeptin if available, allows a simple and accurate assessment of COPD-related risk.,The B-AE-D indices allow a simple and accurate assessment of COPD-related risk in the absence of lung functionhttp://ow.ly/XFBox

Objective To test the effectiveness of telemonitoring integrated into existing clinical services such that intervention and control groups have access to the same clinical care.,Design Researcher blind, multicentre, randomised controlled trial.,Setting UK primary care (Lothian, Scotland).,Participants Adults with at least one admission for chronic obstructive pulmonary disease (COPD) in the year before randomisation.,We excluded people who had other significant lung disease, who were unable to provide informed consent or complete the study, or who had other significant social or clinical problems.,Interventions Participants were recruited between 21 May 2009 and 28 March 2011, and centrally randomised to receive telemonitoring or conventional self monitoring.,Using a touch screen, telemonitoring participants recorded a daily questionnaire about symptoms and treatment use, and monitored oxygen saturation using linked instruments.,Algorithms, based on the symptom score, generated alerts if readings were omitted or breached thresholds.,Both groups received similar care from existing clinical services.,Main outcome measures The primary outcome was time to hospital admission due to COPD exacerbation up to one year after randomisation.,Other outcomes included number and duration of admissions, and validated questionnaire assessments of health related quality of life (using St George’s respiratory questionnaire (SGRQ)), anxiety or depression (or both), self efficacy, knowledge, and adherence to treatment.,Analysis was intention to treat.,Results Of 256 patients completing the study, 128 patients were randomised to telemonitoring and 128 to usual care; baseline characteristics of each group were similar.,The number of days to admission did not differ significantly between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.66 to 1.44).,Over one year, the mean number of COPD admissions was similar in both groups (telemonitoring 1.2 admissions per person (standard deviation 1.9) v control 1.1 (1.6); P=0.59).,Mean duration of COPD admissions over one year was also similar between groups (9.5 days per person (standard deviation 19.1) v 8.8 days (15.9); P=0.88).,The intervention had no significant effect on SGRQ scores between groups (68.2 (standard deviation 16.3) v 67.3 (17.3); adjusted mean difference 1.39 (95% confidence interval −1.57 to 4.35)), or on other questionnaire outcomes.,Conclusions In participants with a history of admission for exacerbations of COPD, telemonitoring was not effective in postponing admissions and did not improve quality of life.,The positive effect of telemonitoring seen in previous trials could be due to enhancement of the underpinning clinical service rather than the telemonitoring communication.,Trial registration ISRCTN96634935.,Funding: The trial was funded by an NHS applied research programme grant from the Chief Scientist Office of the Scottish government (ARPG/07/03).,The funder had no role in study design and the collection, analysis, and interpretation of data and the writing of the article and the decision to submit it for publication.,NHS Lothian supported the telemonitoring service and the clinical services.

Pulmonary Rehabilitation for moderate Chronic Obstructive Pulmonary Disease in primary care could improve patients’ quality of life.,This study aimed to assess the efficacy of a 3-month Pulmonary Rehabilitation (PR) program with a further 9 months of maintenance (RHBM group) compared with both PR for 3 months without further maintenance (RHB group) and usual care in improving the quality of life of patients with moderate COPD.,We conducted a parallel-group, randomized clinical trial in Majorca primary health care in which 97 patients with moderate COPD were assigned to the 3 groups.,Health outcomes were quality of life, exercise capacity, pulmonary function and exacerbations.,We found statistically and clinically significant differences in the three groups at 3 months in the emotion dimension (0.53; 95%CI0.06-1.01) in the usual care group, (0.72; 95%CI0.26-1.18) the RHB group (0.87; 95%CI 0.44-1.30) and the RHBM group as well as in fatigue (0.47; 95%CI 0.17-0.78) in the RHBM group.,After 1 year, these differences favored the long-term rehabilitation group in the domains of fatigue (0.56; 95%CI 0.22-0.91), mastery (0.79; 95%CI 0.03-1.55) and emotion (0.75; 95%CI 0.17-1.33).,Between-group analysis only showed statistically and clinically significant differences between the RHB group and control group in the dyspnea dimension (0.79 95%CI 0.05-1.52).,No differences were found for exacerbations, pulmonary function or exercise capacity.,We found that patients with moderate COPD and low level of impairment did not show meaningful changes in QoL, exercise tolerance, pulmonary function or exacerbation after a one-year, community based rehabilitation program.,However, long-term improvements in the emotional, fatigue and mastery dimensions (within intervention groups) were identified.,ISRCTN94514482

Diseases of accelerated aging often occur together (multimorbidity), and their prevalence is increasing, with high societal and health care costs.,Chronic obstructive pulmonary disease (COPD) is one such condition, in which one half of patients exhibit ≥4 age-related diseases.,Diseases of accelerated aging share common molecular pathways, which lead to the detrimental accumulation of senescent cells.,These senescent cells no longer divide but release multiple inflammatory proteins, known as the senescence-associated secretory phenotype, which may perpetuate and speed disease.,Here, we show that inhibiting miR-570-3p, which is increased in COPD cells, reverses cellular senescence by restoring the antiaging molecule sirtuin-1.,MiR-570-3p is induced by oxidative stress in airway epithelial cells through p38 MAP kinase-c-Jun signaling and drives senescence by inhibiting sirtuin-1.,Inhibition of elevated miR-570-3p in COPD small airway epithelial cells, using an antagomir, restores sirtuin-1 and suppresses markers of cellular senescence (p16INK4a, p21Waf1, and p27Kip1), thereby restoring cellular growth by allowing progression through the cell cycle.,MiR-570-3p inhibition also suppresses the senescence-associated secretory phenotype (matrix metalloproteinases-2/9, C-X-C motif chemokine ligand 8, IL-1β, and IL-6).,Collectively, these data suggest that inhibiting miR-570-3p rejuvenates cells via restoration of sirtuin-1, reducing many of the abnormalities associated with cellular senescence.-Baker, J.,R., Vuppusetty, C., Colley, T., Hassibi, S., Fenwick, P.,S., Donnelly, L.,E., Ito, K., Barnes, P.,J.,MicroRNA-570 is a novel regulator of cellular senescence and inflammaging.

COPD is the third leading cause of death in the world and its global burden is predicted to increase further.,Even though the prevalence of COPD is well studied, only few studies examined the incidence of COPD in a prospective and standardized manner.,In a prospective population-based cohort study (Rotterdam Study) enrolling subjects aged ≥45, COPD was diagnosed based on a pre-bronchodilator obstructive spirometry (FEV1/FVC < 0.70).,In absence of an interpretable spirometry within the Rotterdam Study, cases were defined as having COPD diagnosed by a physician on the basis of clinical presentation and obstructive lung function measured by the general practitioner or respiratory physician.,Incidence rates were calculated by dividing the number of incident cases by the total number of person years of subjects at risk.,In this cohort of 14,619 participants, 1993 subjects with COPD were identified of whom 689 as prevalent ones and 1304 cases as incident ones.,The overall incidence rate (IR) of COPD was 8.9/1000 person-years (PY); 95 % Confidence Interval (CI) 8.4-9.4.,The IR was higher in males and in smokers.,The proportion of female COPD participants without a history of smoking was 27.2 %, while this proportion was 7.3 % in males.,The prevalence of COPD in the Rotterdam Study is 4.7 % and the overall incidence is approximately 9/1000 PY, with a higher incidence in males and in smokers.,The proportion of never-smokers among female COPD cases is substantial.,The online version of this article (doi:10.1007/s10654-016-0132-z) contains supplementary material, which is available to authorized users.

A high prevalence of bronchiectasis was found by chest computed tomography (CT) in patients with moderate-severe chronic obstructive pulmonary disease (COPD), and it was shown to be associated with more severe symptoms, higher frequency of exacerbations and mortality.,The risk factors for bronchiectasis in COPD are not yet clarified.,High-resolution computed tomography (HRCT) of chest was performed in patients with moderate-severe COPD, and the presence and the extent of bronchiectasis were evaluated by two radiologists.,Demographic data, respiratory symptoms, lung function, previous pulmonary tuberculosis, serum inflammatory markers, serum total immunoglobulin E (T-IgE), and sputum culture of Pseudomonas aeruginosa were compared between those with and without bronchiectasis.,Multivariate logistic regression analysis was used to determine the independent factors associated with bronchiectasis.,We enrolled 190 patients with stable COPD, of which 87 (87/190, 45.8%) had bronchiectasis on HRCT.,Compared with those without bronchiectasis, COPD patients with bronchiectasis were more likely to be males (P = 0.021), had a lower body mass index (BMI) (P = 0.019), a higher prevalence of previous tuberculosis (P = 0.005), longer history of dyspnea (P < 0.001), more severe dyspnea (P = 0.041), higher frequency of acute exacerbation (P = 0.002), higher serum concentrations of C-reactive protein (CRP) (P = 0.017), fibrinogen (P = 0.016), and T-IgE [P = 0.004; for log10(T-IgE), P <0.001].,COPD patients with bronchiectasis also showed poorer lung function (for FEV1/FVC, P = 0.013; for FEV1%predicted, P = 0.012; for global initiative for chronic obstructive lung disease (GOLD) grades, P = 0.035), and a higher positive rate of sputum P aeruginosa (P = 0.020).,Logistic regression analysis demonstrated that male gender (P = 0.021), previous tuberculosis (P = 0.021), and increased level of serum T-IgE [for log10(T-IgE), P < 0.001] were risk factors for coexistent bronchiectasis.,More notably, the level of serum T-IgE [log10(T-IgE)] was positively correlated with the extent of bronchiectasis in COPD patients (r = 0.208, P = 0.05).,Higher serum T-IgE, male gender, and previous tuberculosis are independent risk factors for coexistent bronchiectasis in COPD.,The association of T-IgE with the extent of bronchiectasis also suggests that further investigations are needed to explore the potential role of IgE in the pathogenesis of bronchiectasis in COPD.

Patients with severe chronic obstructive pulmonary disease (COPD) are at increased risk of infection by P. aeruginosa.,The specific role of bronchiectasis in both infection and chronic colonization by this microorganism in COPD, however, remains ill defined.,To evaluate the prevalence and risk factors for P. aeruginosa recovery from sputum in outpatients with severe COPD, characterizing P. aeruginosa isolates by pulsed-field gel electrophoresis (PFGE) and focusing on the influence of bronchiectasis on chronic colonization in these patients.,A case-cohort study of 118 patients with severe COPD attended at a Respiratory Day Unit for an acute infectious exacerbation and followed up over one year.,High-resolution CT scans were performed during stability for bronchiectasis assessment and sputum cultures were obtained during exacerbation and stability in all patients.,P. aeruginosa isolates were genotyped by PFGE.,Determinants of the recovery of P. aeruginosa in sputum and chronic colonization by this microorganism were assessed by multivariate analysis.,P. aeruginosa was isolated from 41 of the 118 patients studied (34.7%).,Five of these 41 patients (12.2%) with P. aeruginosa recovery fulfilled criteria for chronic colonization.,In the multivariate analysis, the extent of bronchiectasis (OR 9.8, 95% CI: 1.7 to 54.8) and the number of antibiotic courses (OR 1.7, 95% CI: 1.1 to 2.5) were independently associated with an increased risk of P. aeruginosa isolation.,Chronic colonization was unrelated to the presence of bronchiectasis (p=0.75).,In patients with chronic colonization the isolates of P. aeruginosa retrieved corresponded to the same clones during the follow-up, and most of the multidrug resistant isolates (19/21) were harbored by these patients.,The main risk factors for P. aeruginosa isolation in severe COPD were the extent of bronchiectasis and exposure to antibiotics.,Over 10% of these patients fulfilled criteria for chronic colonization by P. aeruginosa and showed clonal persistence, independently of the presence of bronchiectasis.

Chronic obstructive pulmonary disease (COPD) has been classically divided into blue bloaters and pink puffers.,The utility of these clinical subtypes is unclear.,However, the broader distinction between airway-predominant and emphysema-predominant COPD may be clinically relevant.,The objective was to define clinical features of emphysema-predominant and non-emphysematous COPD patients.,Current and former smokers from the Genetic Epidemiology of COPD Study (COPDGene) had chest computed tomography (CT) scans with quantitative image analysis.,Emphysema-predominant COPD was defined by low attenuation area at -950 Hounsfield Units (LAA-950) ≥10%.,Non-emphysematous COPD was defined by airflow obstruction with minimal to no emphysema (LAA-950 < 5%).,Out of 4197 COPD subjects, 1687 were classified as emphysema-predominant and 1817 as non-emphysematous; 693 had LAA-950 between 5-10% and were not categorized.,Subjects with emphysema-predominant COPD were older (65.6 vs 60.6 years, p < 0.0001) with more severe COPD based on airflow obstruction (FEV1 44.5 vs 68.4%, p < 0.0001), greater exercise limitation (6-minute walk distance 1138 vs 1331 ft, p < 0.0001) and reduced quality of life (St.,George’s Respiratory Questionnaire score 43 vs 31, p < 0.0001).,Self-reported diabetes was more frequent in non-emphysematous COPD (OR 2.13, p < 0.001), which was also confirmed using a strict definition of diabetes based on medication use.,The association between diabetes and non-emphysematous COPD was replicated in the ECLIPSE study.,Non-emphysematous COPD, defined by airflow obstruction with a paucity of emphysema on chest CT scan, is associated with an increased risk of diabetes.,COPD patients without emphysema may warrant closer monitoring for diabetes, hypertension, and hyperlipidemia and vice versa.,Clinicaltrials.gov identifiers: COPDGene NCT00608764, ECLIPSE NCT00292552.,The online version of this article (doi:10.1186/1471-2466-14-164) contains supplementary material, which is available to authorized users.

The prevalence of metabolic syndrome in COPD patients and its impact on patient related outcomes has been little studied.,We evaluated the prevalence of metabolic syndrome and clinical and functional characteristics in patients with COPD and healthy subjects.,228 COPD patients and 156 healthy subjects were included.,Metabolic syndrome was defined using criteria of the IDF.,In all patients spirometry, body composition, functional exercise performance, and mood and health status were assessed.,Groups were stratified for BMI and gender.,Metabolic syndrome was present in 57% of the COPD patients and 40% of the healthy subjects.,After stratification for BMI, presence of metabolic syndrome in patients with a BMI ≥25 kg/m2 was higher than in healthy peers.,Patients with metabolic syndrome and a BMI <25 kg/m2 had higher BMI, fat free mass index and bone mineral density, and a lower 6MWD than the BMI matched patients without metabolic syndrome.,Spirometry, maximal ergometry, mood and health status, and blood gases were not different between those groups.,In COPD patients with metabolic syndrome self-reported co-morbidities and medication use were higher than in those without.,Metabolic syndrome is more prevalent in overweight or obese COPD patients than in BMI matched healthy subjects.,Metabolic syndrome did not additionally impact patients' functional outcomes, but did impact the prevalence of co-morbidities.

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.

The Wnt pathway mediates differentiation of epithelial tissues; depending on the tissue types, Wnt can either drive or inhibit the differentiation process.,We hypothesized that key genes in the Wnt pathway are suppressed in the human airway epithelium under the stress of cigarette smoking, a stress associated with dysregulation of the epithelial differentiated state.,Microarrays were used to assess the expression of Wnt-related genes in the small airway epithelium (SAE) obtained via bronchoscopy and brushing of healthy nonsmokers, healthy smokers, and smokers with COPD.,Thirty-three of 56 known Wnt-related genes were expressed in the SAE.,Wnt pathway downstream mediators β-catenin and the transcription factor 7-like 1 were down-regulated in healthy smokers and smokers with COPD, as were many Wnt target genes.,Among the extracellular regulators that suppress the Wnt pathway, secreted frizzled-related protein 2 (SFRP2), was up-regulated 4.3-fold in healthy smokers and 4.9-fold in COPD smokers, an observation confirmed by TaqMan Real-time PCR, Western analysis and immunohistochemistry.,Finally, cigarette smoke extract mediated up-regulation of SFRP2 and down-regulation of Wnt target genes in airway epithelial cells in vitro.,Smoking down-regulates the Wnt pathway in the human airway epithelium.,In the context that Wnt pathway plays an important role in differentiation of epithelial tissues, the down-regulation of Wnt pathway may contribute to the dysregulation of airway epithelium differentiation observed in smoking-related airway disorders.

Respiratory viruses frequently are recovered in the upper-respiratory tract during acute exacerbations of COPD (AECOPD), but their role as contributing pathogens remains unclear.,The usefulness of procalcitonin and C-reactive protein as indicators of the presence or absence of viral infection in this setting also needs to be evaluated.,The study was of a prospective cohort of patients with COPD admitted to the ED for AECOPD.,Reverse transcriptase-polymerase chain reaction (RT-PCR) for 14 respiratory viruses was performed on nasopharyngeal swabs collected at admission and after recovery in stable condition.,Eighty-six patients (mean age, 72 years; male, 64%) were included.,During AECOPD, upper-respiratory viral infections were detected in 44 (51%) patients: picornavirus in 22, metapneumovirus in seven, coronavirus in eight, influenza A/B in two, parainfluenza in two, and respiratory syncytial virus in three.,A dual infection was present in three patients.,After recovery, viruses were detected in only eight (11%) of 71 patients (P < .001 compared with AECOPD phase).,In five of these patients, no virus had been identified during the initial exacerbation, thus suggesting a new viral infection acquired during follow-up.,During AECOPD, procalcitonin and C-reactive protein levels did not differ significantly between patients with or without a proven viral infection.,Prevalence of upper-respiratory viral infection, as detected from nasopharyngeal swab by RT-PCR, is high in AECOPD and low after clinical recovery, suggesting that AECOPD frequently are triggered by viral infections initiated in the upper-respiratory tract.,In our study, serum procalcitonin and C-reactive protein did not discriminate virus-associated exacerbations from others.,clinicaltrials.gov; Identifier: NCT00448604.

The aims of this systematic review were to determine which blood-based molecules have been evaluated as possible biomarkers to diagnose chronic obstructive pulmonary disease (COPD) exacerbations (AECOPD) and to ascertain the quality of these biomarker publications.,Patients of interest were those that have been diagnosed with COPD.,MEDLINE, EMBASE, and CINAHL databases were searched systematically through February 2015 for publications relating to AECOPD diagnostic biomarkers.,We used a modified guideline for the REporting of tumor MARKer Studies (mREMARK) to assess study quality.,Additional components of quality included the reporting of findings in a replication cohort and the use of receiver-operating characteristics area-under-the curve statistics in evaluating performance. 59 studies were included, in which the most studied biomarkers were C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α).,CRP showed consistent elevations in AECOPD compared to control subjects, while IL-6 and TNF-α had variable statistical significance and results. mREMARK scores ranged from 6 to 18 (median score of 13). 12 articles reported ROC analyses and only one study employed a replication cohort to confirm biomarker performance.,Studies of AECOPD diagnostic biomarkers remain inconsistent in their reporting, with few studies employing ROC analyses and even fewer demonstrating replication in independent cohorts.

COPD is characterized by an accelerated and progressive decline in forced expiratory volume in 1 second (FEV1) and lung hyperinflation.,Although lung hyperinflation is the hallmark of COPD, data on the longitudinal changes in lung hyperinflation and any association with the decline in FEV1 are lacking.,The aim of this study was to evaluate the longitudinal changes in lung hyperinflation and to investigate its relationship with FEV1 decline.,We conducted a prospective cohort study and studied 176 COPD patients with annual lung volume measurements over a period of 5 years or more.,We used a random coefficient model to calculate the annual changes in lung volumes and to evaluate the factors associated with changes in lung hyperinflation.,Additionally, the relationship between the change in lung hyperinflation and FEV1 was assessed.,Residual volume (RV), inspiratory capacity (IC), and total lung capacity (TLC) declined at a mean rate of 39.5, 49.6, and 63.8 mL/year, respectively.,While IC/TLC declined at 0.70%/year, RV/TLC also declined at 0.35%/year.,Changes in both IC/TLC and RV/TLC varied significantly.,Frequent exacerbations led to an increase in RV/TLC and faster decline in IC/TLC over time.,RV/TLC declined in 59.7% and increased in 40.3% of the patients.,A significant negative correlation was found between the rates of change in FEV1 and RV/TLC, and the rate of decline in FEV1 was greater in patients with an increase in RV/TLC than in those with a decline in RV/TLC (54.2 vs 10.7 mL/year, P<0.001).,The rate of change in lung hyperinflation varied greatly among COPD patients.,Progression of hyperinflation was associated with frequent exacerbations and a faster decline in FEV1.

We investigated whether a relationship between small airways dysfunction and bronchodilator responsiveness exists in patients with chronic obstructive pulmonary disease (COPD).,We studied 100 (20 female; mean age: 68±10 years) patients with COPD (forced expiratory volume in 1 second [FEV1]: 55% pred ±21%; FEV1/forced vital capacity [FVC]: 53%±10%) by impulse oscillometry system.,Resistance at 5 Hz and 20 Hz (R5 and R20, in kPa·s·L−1) and the fall in resistance from 5 Hz to 20 Hz (R5 - R20) were used as indices of total, proximal, and peripheral airway resistance; reactance at 5 Hz (X5, in kPa·s·L−1) was also measured.,Significant response to bronchodilator (salbutamol 400 μg) was expressed as absolute (≥0.2 L) and percentage (≥12%) change relative to the prebronchodilator value of FEV1 (flow responders, FRs) and FVC (volume responders, VRs).,Eighty out of 100 participants had R5 - R20 >0.03 kPa·s·L−1 (> upper normal limit) and, compared to patients with R5 - R20 ≤0.030 kPa·s·L−1, showed a poorer health status, lower values of FEV1, FVC, FEV1/FVC, and X5, along with higher values of residual volume/total lung capacity and R5 (P<0.05 for all comparisons).,Compared to the 69 nonresponders and the 8 FRs, the 16 VRs had significantly higher R5 and R5 - R20 values (P<0.05), lower X5 values (P<0.05), and greater airflow obstruction and lung hyperinflation.,This study shows that peripheral airway resistance is increased in the vast majority of patients with COPD, who showed worse respiratory reactance, worse spirometry results, more severe lung hyperinflation, and poorer health status.,Small airway dysfunction was also associated with the bronchodilator responsiveness in terms of FVC, but not in terms of FEV1.

Chronic obstructive pulmonary disease (COPD) is characterized by varying trajectories of decline.,Information regarding the prognostic value of preventing short-term clinically important deterioration (CID) in lung function, health status, or first moderate/severe exacerbation as a composite endpoint of worsening is needed.,We evaluated post hoc the link between early CID and long-term adverse outcomes.,CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1), ≥4-unit increase in St George’s Respiratory Questionnaire (SGRQ) score from baseline, and/or a moderate/severe exacerbation during enrollment in two 3-year studies.,Presence of CID was assessed at 6 months for the principal analysis (TORCH) and 12 months for the confirmatory analysis (ECLIPSE).,Association between presence (+) or absence (-) of CID and long-term deterioration in FEV1, SGRQ, future risk of exacerbations, and all-cause mortality was assessed.,In total, 2870 (54%; TORCH) and 1442 (73%; ECLIPSE) patients were CID+.,At 36 months, in TORCH, CID+ patients (vs CID-) had sustained clinically significant worsening of FEV1 (- 117 mL; 95% confidence interval [CI]: - 134, - 100 mL; P < 0.001) and SGRQ score (+ 6.42 units; 95% CI: 5.40, 7.45; P < 0.001), and had higher risk of exacerbations (hazard ratio [HR]: 1.61 [95% CI: 1.50, 1.72]; P < 0.001) and all-cause mortality (HR: 1.41 [95% CI: 1.15, 1.72]; P < 0.001).,Similar risks post-CID were observed in ECLIPSE.,A CID within 6-12 months of follow-up was consistently associated with increased long-term risk of exacerbations and all-cause mortality, and predicted sustained meaningful loss in FEV1 and health status amongst survivors.,NCT00268216; NCT00292552.,The online version of this article (10.1186/s12931-018-0928-3) contains supplementary material, which is available to authorized users.

Dual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits in lung function and health status versus monotherapy.,The aim of this study was to determine whether early initiation of a dual bronchodilator versus monotherapy reduced the risk of deterioration in COPD.,This post hoc pooled analysis investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared with tiotropium (TIO) 18 mcg/day in a maintenance-naïve (MN) subgroup of patients relative to the intent-to-treat (ITT) population from three 6-month active comparator studies (n = 1747).,Other treatment arms (UMEC/VI 125/25, VI 25 and UMEC 125) comprised 850 patients in total but were not included in this analysis.,The primary endpoint was trough forced expiratory volume in 1 s (FEV1).,St George’s Respiratory Questionnaire (SGRQ) score, rescue medication use, and a novel composite endpoint of short-term clinically important deterioration (CID; ≥100 ml decrease in trough FEV1, ≥4-unit increase in SGRQ score, or a COPD exacerbation) were also assessed.,UMEC/VI improved trough FEV1 versus TIO at day 169 [least squares mean (95% confidence interval): MN: 146 ml (102-189) and ITT: 95 ml (71-118); both P < 0.001].,Both UMEC/VI and TIO improved SGRQ and rescue use in the two populations, with greater improvements in rescue use with UMEC/VI versus TIO.,UMEC/VI reduced the risk of short-term clinically important deterioration versus TIO [hazard ratio; 95% confidence interval: MN: 0.66 (0.51-0.85); ITT: 0.62 (0.54-0.71), both P ≤ 0.001].,Adverse events were similar across both populations and treatments.,Early use of dual-bronchodilator therapy has superior efficacy on lung function and may reduce the risk of short-term deterioration compared to monotherapy in symptomatic patients with COPD.,Clinical trial registration: GSK analysis 202066 (NCT01316900/DB2113360, NCT01316913/DB2113374, NCT01777334/ZEP117115).,Funding: This study was funded by GSK.,The online version of this article (doi:10.1007/s12325-016-0430-6) contains supplementary material, which is available to authorized users.

Reduced physical activity (PA) in patients with COPD is associated with a poor prognosis.,Increasing PA is a key therapeutic target, but thus far few strategies have been found effective in this patient group.,To investigate the effectiveness of a 12-week semiautomated telecoaching intervention on PA in patients with COPD in a multicentre European randomised controlled trial.,343 patients from six centres, encompassing a wide spectrum of disease severity, were randomly allocated to either a usual care group (UCG) or a telecoaching intervention group (IG) between June and December 2014.,This 12-week intervention included an exercise booklet and a step counter providing feedback both directly and via a dedicated smartphone application.,The latter provided an individualised daily activity goal (steps) revised weekly and text messages as well as allowing occasional telephone contacts with investigators.,PA was measured using accelerometry during 1 week preceding randomisation and during week 12.,Secondary outcomes included exercise capacity and health status.,Analyses were based on modified intention to treat.,Both groups were comparable at baseline in terms of factors influencing PA.,At 12 weeks, the intervention yielded a between-group difference of mean, 95% CI (lower limit - upper limit; ll-ul) +1469, 95% CI (971 to 1965) steps/day and +10.4, 95% CI (6.1 to 14.7) min/day moderate PA; favouring the IG (all p≤0.001).,The change in 6-min walk distance was significantly different (13.4, 95% CI (3.40 to 23.5) m, p<0.01), favouring the IG.,In IG patients, an improvement could be observed in the functional state domain of the clinical COPD questionnaire (p=0.03) compared with UCG.,Other health status outcomes did not differ.,The amount and intensity of PA can be significantly increased in patients with COPD using a 12-week semiautomated telecoaching intervention including a step counter and an application installed on a smartphone.,NCT02158065.

Persons with Chronic Obstructive Pulmonary Disease (COPD), performing some level of regular physical activity, have a lower risk of both COPD-related hospital admissions and mortality.,COPD patients of all stages seem to benefit from exercise training programs, thereby improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue.,Physical inactivity, which becomes more severe with increasing age, is a point of concern in healthy older adults.,COPD might worsen this scenario, but it is unclear to what degree.,This literature review aims to present the extent of the impact of COPD on objectively-measured daily physical activity (DPA).,The focus is on the extent of the impact that COPD has on duration, intensity, and counts of DPA, as well as whether the severity of the disease has an additional influence on DPA.,A literature review was performed in the databases PubMed [MEDLINE], Picarta, PEDRO, ISI Web of Knowledge and Google scholar.,After screening, 11 studies were identified as being relevant for comparison between COPD patients and healthy controls with respect to duration, intensity, and counts of DPA.,Four more studies were found to be relevant to address the subject of the influence the severity of the disease may have on DPA.,The average percentage of DPA of COPD patients vs. healthy control subjects for duration was 57%, for intensity 75%, and for activity counts 56%.,Correlations of DPA and severity of the disease were low and/or not significant.,From the results of this review, it appears that patients with COPD have a significantly reduced duration, intensity, and counts of DPA when compared to healthy control subjects.,The intensity of DPA seems to be less affected by COPD than duration and counts.,Judging from the results, it seems that severity of COPD is not strongly correlated with level of DPA.,Future research should focus in more detail on the relation between COPD and duration, intensity, and counts of DPA, as well as the effect of disease severity on DPA, so that these relations become more understandable.

Little is known about the impact of exacerbations on COPD progression or whether inhaled corticosteroid (ICS) use and blood eosinophil count (BEC) affect progression.,We aimed to assess this in a prospective observational study.,The study population included patients with mild to moderate COPD, aged ≥35 years, with a smoking history, who were followed up for ≥3 years from first to last spirometry recording using two large UK electronic medical record databases: Clinical Practice Research Datalink (CPRD) and Optimum Patient Care Research Database (OPCRD).,Multilevel mixed-effects linear regression models were used to determine the relationship between annual exacerbation rate following initiation of therapy (ICS vs non-ICS) and FEV1 decline.,Effect modification by blood eosinophils was studied through interaction terms.,Of 12178 patients included (mean age 66 years; 48% female), 8981 (74%) received ICS.,In patients with BEC ≥350 cells/µL not on ICS, each exacerbation was associated with subsequent acceleration of FEV1 decline of 19.4 mL/year (95% CI 12.0 to 26.7, p<0.0001).,This excess decline was reduced by 15.1 mL/year (6.6 to 23.6) to 4.3 mL/year (1.9 to 6.7, p<0.0001) in those with BEC ≥350 cells/µL treated with ICS.,Exacerbations are associated with a more rapid loss of lung function among COPD patients with elevated blood eosinophils, defined as ≥350 cells/µL, not treated with ICS.,More aggressive prevention of exacerbations using ICS in such patients may prevent excess loss of lung function.

Chronic obstructive pulmonary disease (COPD) is one of the top five major causes of morbidity and mortality worldwide.,Despite worldwide health care efforts, costs, and medical research, COPD figures demonstrate a continuously increasing tendency in mortality.,This is contrary to other top causes of death, such as neoplasm, accidents, and cardiovascular disease.,A major factor affecting COPD-related mortality is the acute exacerbation of COPD (AECOPD).,Exacerbations and comorbidities contribute to the overall severity in individual patients.,Despite the underestimation by the physicians and the patients themselves, AECOPD is a really devastating event during the course of the disease, similar to acute myocardial infarction in patients suffering from coronary heart disease.,In this review, we focus on the evidence that supports the claim that AECOPD is the “stroke of the lungs”.,AECOPD can be viewed as: a Semicolon or disease’s full-stop period, Triggering a catastrophic cascade, usually a Relapsing and Overwhelming event, acting as a Killer, needing Emergent treatment.

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.

A combination of inhaled corticosteroid and long-acting beta2 agonist (ICS/LABA) is used frequently to treat chronic obstructive pulmonary disease (COPD) patients.,The aim of the study was to determine whether prescribing ICS/LABA to COPD patients in primary care in 2009/10 was within the GOLD guidelines and whether and to what degree patient characteristics were associated with prescription of these drugs by GPs.,This was a cross-sectional study in seven Norwegian GP practices.,Patients registered with a diagnosis of asthma or COPD in the previous five years were included.,Among the 376 patients included in the analysis, 149 patients had COPD, defined as a post-bronchodilator FEV1/FVC <0.7 and 55.6% of these patients were treated with ICS/LABA.,The rate of prescribing was significantly higher in the COPD patients also diagnosed with asthma than in those with COPD as the only diagnosis, 66.7%, and 39.0%, respectively (P = 0.001).,The prescribing rate in the latter subgroup would have been 18.6% if the 2007 GOLD guidelines had been followed.,One or more exacerbations in the previous year was the strongest predictor of ICS/LABA prescribing in the COPD patients who were not registered with a concomitant diagnosis of asthma (OR 3.2, 95% CI 1.0-10.0) but this association was limited to the patients with severe disease (FEV1% predicted <50) (OR 13.5, 95% CI 1.8-101.1).,Cardiovascular disease was associated with decreased ICS/LABA prescribing (OR 0.4, 95% CI 0.2-0.8) in the COPD group.,A Kappa coefficient of 0.32 was found between the actual prescribing rate and that recommended in the 2007 GOLD guidelines.,Overprescribing of ICS/LABA for the COPD patients was shown.,Previous exacerbation was a strong predictor of ICS/LABA prescribing only in patients with severe COPD.,Because of the low emphasis on previous exacerbation when prescribing for COPD patients with mild to moderate disease, the actual prescribing rate agreed more closely with the GOLD guidelines from 2007 than with those published in 2011.,Cardiovascular disease was associated with decreased prescribing, indicating that GPs adjust the treatment in cases with multimorbidity.

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

Chronic Obstructive Pulmonary Disease (COPD) is currently the fifth leading cause of death worldwide.,Neutrophilic inflammation is prominent, worsened during infective exacerbations and is refractory to glucocorticosteroids (GCs).,Deregulated neutrophilic inflammation can cause excessive matrix degradation through proteinase release.,Gelatinase and azurophilic granules within neutrophils are a major source of matrix metalloproteinase (MMP)-9 and neutrophil elastase (NE), respectively, which are elevated in COPD.,Secreted MMP-9 and NE activity in BALF were stratified according to GOLD severity stages.,The regulation of secreted NE and MMP-9 in isolated blood neutrophils was investigated using a pharmacological approach.,In vivo release of MMP-9 and NE in mice exposed to cigarette smoke (CS) and/or the TLR agonist lipopolysaccharide (LPS) in the presence of dexamethasone (Dex) was investigated.,Neutrophil activation as assessed by NE release was increased in severe COPD (36-fold, GOLD II vs.,IV).,MMP-9 levels (8-fold) and activity (21-fold) were also elevated in severe COPD, and this activity was strongly associated with BALF neutrophils (r = 0.92, p<0.001), but not macrophages (r = 0.48, p = 0.13).,In vitro, release of NE and MMP-9 from fMLP stimulated blood neutrophils was insensitive to Dex and attenuated by the PI3K inhibitor, wortmannin.,In vivo, GC resistant neutrophil activation (NE release) was only seen in mice exposed to CS and LPS.,In addition, GC refractory MMP-9 expression was only associated with neutrophil activation.,As neutrophils become activated with increasing COPD severity, they become an important source of NE and MMP-9 activity, which secrete proteinases independently of TIMPs.,Furthermore, as NE and MMP-9 release was resistant to GC, targeting of the PI3K pathway may offer an alternative pathway to combating this proteinase imbalance in severe COPD.

Noninvasive ventilation (NIV) is a well-established treatment for acute-on- chronic respiratory failure in hypercapnic COPD patients.,Less is known about the effects of a long-term treatment with NIV in hypercapnic COPD patients and about the factors that may predict response in terms of improved oxygenation and lowered CO2 retention.,In this study, we randomized 15 patients to a routine pharmacological treatment (n = 5, age 66 [standard deviation ± 6] years, FEV1 30.5 [±5.1] %pred, PaO2 65 [±6] mmHg, PaCO2 52.4 [±6.0] mmHg) or to a routine treatment and NIV (using the Synchrony BiPAP device [Respironics, Inc, Murrsville, PA]) (n = 10, age 65 [±7] years, FEV1 29.5 [±9.0] %pred, PaO2 59 [±13] mmHg, PaCO2 55.4 [±7.7] mmHg) for 6 months.,We looked at arterial blood gasses, lung function parameters and performed a low-dose computed tomography of the thorax, which was later used for segmentation (providing lobe and airway volumes, iVlobe and iVaw) and post-processing with computer methods (providing airway resistance, iRaw) giving overall a functional image of the separate airways and lobes.,In both groups there was a nonsignificant change in FEV1 (NIV group 29.5 [9.0] to 38.5 [14.6] %pred, control group 30.5 [5.1] to 36.8 [8.7] mmHg).,PaCO2 dropped significantly only in the NIV group (NIV: 55.4 [7.7] → 44.5 [4.70], P = 0.0076; control: 52.4 [6.0] → 47.6 [8.2], NS).,Patients actively treated with NIV developed a more inhomogeneous redistribution of mass flow than control patients.,Subsequent analysis indicated that in NIV-treated patients that improve their blood gases, mass flow was also redistributed towards areas with higher vessel density and less emphysema, indicating that flow was redistributed towards areas with better perfusion.,There was a highly significant correlation between the % increase in mass flow towards lobes with a blood vessel density of >9% and the increase in PaO2.,Improved ventilation-perfusion match and recruitment of previously occluded small airways can explain the improvement in blood gases.,We can conclude that in hypercapnic COPD patients treated with long-term NIV over 6 months, a mass flow redistribution occurs, providing a better ventilation-perfusion match and hence better blood gases and lung function.,Control patients improve homogeneously in iVaw and iRaw, without improvement in gas exchange since there is no improved ventilation/perfusion ratio or increased alveolar ventilation.,These differences in response can be detected through functional imaging, which gives a more detailed report on regional lung volumes and resistances than classical lung function tests do.,Possibly only patients with localized small airway disease are good candidates for long-term NIV treatment.,To confirm this and to see if better arterial blood gases also lead to better health related quality of life and longer survival, we have to study a larger population.

Noninvasive ventilation (NIV) improves gas-exchange and symptoms in selected chronic obstructive pulmonary disease (COPD) patients with hypercapnic respiratory failure.,We hypothesized NIV reverses respiratory failure by one or all of increased ventilatory response to carbon-dioxide, reduced respiratory muscle fatigue, or improved pulmonary mechanics.,Nineteen stable COPD patients (forced expiratory volume in one second 35% predicted) were studied at baseline (D0), 5-8 days (D5) and 3 months (3M) after starting NIV.,Ventilator use was 6.2 (3.7) hours per night at D5 and 3.4 (1.6) at 3M (p = 0.12).,Mean (SD) daytime arterial carbon-dioxide tension (PaCO2) was reduced from 7.4 (1.2) kPa to 7.0 (1.1) kPa at D5 and 6.5 (1.1) kPa at 3M (p = 0.001).,Total lung capacity decreased from 107 (28) % predicted to 103 (28) at D5 and 103 (27) % predicted at 3M (p = 0.035).,At D5 there was an increase in the hypercapnic ventilatory response and some volitional measures of inspiratory and expiratory muscle strength, but not isolated diaphragmatic strength whether assessed by volitional or nonvolitional methods.,These findings suggest decreased gas trapping and increased ventilatory sensitivity to CO2 are the principal mechanism underlying improvements in gas-exchange in patients with COPD following NIV.,Changes in some volitional but not nonvolitional muscle strength measures may reflect improved patient effort.

Changes in physical activity (PA) are difficult to interpret because no framework of minimal important difference (MID) exists.,We aimed to determine the minimal important difference (MID) in physical activity (PA) in patients with Chronic Obstructive Pulmonary Disease and to clinically validate this MID by evaluating its impact on time to first COPD-related hospitalization.,PA was objectively measured for one week in 74 patients before and after three months of rehabilitation (rehabilitation sample).,In addition the intraclass correlation coefficient was measured in 30 patients (test-retest sample), by measuring PA for two consecutive weeks.,Daily number of steps was chosen as outcome measurement.,Different distribution and anchor based methods were chosen to calculate the MID.,Time to first hospitalization due to an exacerbation was compared between patients exceeding the MID and those who did not.,Calculation of the MID resulted in 599 (Standard Error of Measurement), 1029 (empirical rule effect size), 1072 (Cohen's effect size) and 1131 (0.5SD) steps.day-1.,An anchor based estimation could not be obtained because of the lack of a sufficiently related anchor.,The time to the first hospital admission was significantly different between patients exceeding the MID and patients who did not, using the Standard Error of Measurement as cutoff.,The MID after pulmonary rehabilitation lies between 600 and 1100 steps.day-1.,The clinical importance of this change is supported by a reduced risk for hospital admission in those patients with more than 600 steps improvement.

Pulmonary rehabilitation (PR) provides benefit for patients with chronic obstructive pulmonary disease (COPD) in terms of quality of life (QoL) and exercise capacity; however, the effects diminish over time.,Our aim was to evaluate a maintenance programme for patients who had completed PR.,Primary and secondary care PR programmes in Norfolk.,148 patients with COPD who had completed at least 60% of a standard PR programme were randomised and data are available for 110 patients.,Patients had greater than 20 pack year smoking history and less than 80% predicted forced expiratory volume in 1 s but no other significant disease or recent respiratory tract infection.,Patients were randomised to receive a maintenance programme or standard care.,The maintenance programme consisted of 2 h (1 h individually tailored exercise training and 1 h education programme) every 3 months for 1 year.,The Chronic Respiratory Questionnaire (CRQ) (primary outcome), endurance shuttle walk test (ESWT), EuroQol (EQ5D), hospital anxiety and depression score (HADS), body mass index (BMI), body fat, activity levels (overall score and activity diary) and exacerbations were assessed before and after 12 months.,There was no statistically significant difference between the groups for the change in CRQ dyspnoea score (primary end point) at 12 months which amounted to 0.19 (−0.26 to 0.64) units or other domains of the CRQ.,There was no difference in the ESWT duration (−10.06 (−191.16 to 171.03) seconds), BMI, body fat, EQ5D, MET-minutes, activity rating, HADS, exacerbations or admissions.,A maintenance programme of three monthly 2 h sessions does not improve outcomes in patients with COPD after 12 months.,We do not recommend that our maintenance programme is adopted.,Other methods of sustaining the benefits of PR are required.,NCT00925171.

Umeclidinium (UMEC; long-acting muscarinic antagonist) plus vilanterol (VI; long-acting beta2 agonist [LABA]) and the LABA/inhaled corticosteroid fluticasone propionate/salmeterol (FP/SAL) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD).,This 12-week, multicentre, double-blind, parallel-group, double-dummy study compared the efficacy and safety of these treatments in symptomatic patients with moderate-to-severe COPD with no exacerbations in the year prior to enrolment.,Patients (n = 717) were randomised 1:1 to once-daily UMEC/VI 62.5/25 mcg or twice-daily FP/SAL 500/50 mcg.,Endpoints included 0-24 h weighted mean (wm) forced expiratory volume in 1 s (FEV1) (Day 84; primary), trough FEV1 (Day 85; secondary), other lung function endpoints, symptoms, quality of life (QoL) and safety.,Improvements with UMEC/VI versus FP/SAL were 0.080 L (95 % confidence interval: 0.046-0.113; wmFEV1) and 0.090 L (0.055-0.125; trough FEV1) (both p < 0.001).,UMEC/VI statistically significantly improved all other lung function measures versus FP/SAL.,Both treatments demonstrated a clinically meaningful improvement in symptoms (Transition Dyspnoea Index ≥1 unit) and QoL (St George’s Respiratory Questionnaire Total score ≥4 unit decrease from baseline) over 12 weeks.,The incidence of adverse events was 28 % (UMEC/VI) and 29 % (FP/SAL); nasopharyngitis and headache were most common.,Once-daily UMEC/VI 62.5/25 mcg over 12 weeks resulted in significant and sustained improvements in lung function versus twice-daily FP/SAL 500/50 mcg in patients with moderate-to-severe COPD and with no exacerbations in the year prior to enrolment.,NCT01822899 Registration date: March 28, 2013,The online version of this article (doi:10.1186/s12890-015-0092-1) contains supplementary material, which is available to authorized users.

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

In comparison to genome-wide association studies (GWAS), there has been poor replication of gene expression studies in chronic obstructive pulmonary disease (COPD).,We performed microarray gene expression profiling on a large sample of resected lung tissues from subjects with severe COPD.,Comparing 111 COPD cases and 40 control smokers, 204 genes were differentially expressed; none were at significant GWAS loci.,The top differentially expressed gene was HMGB1, which interacts with AGER, a known COPD GWAS gene.,Differentially expressed genes showed enrichment for putative interactors of the first three identified COPD GWAS genes IREB2, HHIP, and FAM13A, based on gene sets derived from protein and RNA binding studies, RNA-interference, a murine smoking model, and expression quantitative trait locus analyses.,The gene module most highly associated for COPD in Weighted Gene Co-Expression Network Analysis (WGCNA) was enriched for B cell pathways, and shared seventeen genes with a mouse smoking model and twenty genes with previous emphysema studies.,As in other common diseases, genes at COPD GWAS loci were not differentially expressed; however, using a combination of network methods, experimental studies and careful phenotype definition, we found differential expression of putative interactors of these genes, and we replicated previous human and mouse microarray results.

The Wnt pathway mediates differentiation of epithelial tissues; depending on the tissue types, Wnt can either drive or inhibit the differentiation process.,We hypothesized that key genes in the Wnt pathway are suppressed in the human airway epithelium under the stress of cigarette smoking, a stress associated with dysregulation of the epithelial differentiated state.,Microarrays were used to assess the expression of Wnt-related genes in the small airway epithelium (SAE) obtained via bronchoscopy and brushing of healthy nonsmokers, healthy smokers, and smokers with COPD.,Thirty-three of 56 known Wnt-related genes were expressed in the SAE.,Wnt pathway downstream mediators β-catenin and the transcription factor 7-like 1 were down-regulated in healthy smokers and smokers with COPD, as were many Wnt target genes.,Among the extracellular regulators that suppress the Wnt pathway, secreted frizzled-related protein 2 (SFRP2), was up-regulated 4.3-fold in healthy smokers and 4.9-fold in COPD smokers, an observation confirmed by TaqMan Real-time PCR, Western analysis and immunohistochemistry.,Finally, cigarette smoke extract mediated up-regulation of SFRP2 and down-regulation of Wnt target genes in airway epithelial cells in vitro.,Smoking down-regulates the Wnt pathway in the human airway epithelium.,In the context that Wnt pathway plays an important role in differentiation of epithelial tissues, the down-regulation of Wnt pathway may contribute to the dysregulation of airway epithelium differentiation observed in smoking-related airway disorders.

The fixed-dose dual bronchodilator combination (FDC) of tiotropium and olodaterol showed increased effectiveness regarding lung function and health-related quality of life in patients with chronic obstructive pulmonary disease (COPD) compared with the use of its mono-components.,Yet, while effectiveness and safety have been shown, the health economic implication of this treatment is still unknown.,The aim of this study was to assess the cost-utility and budget impact of tiotropium-olodaterol FDC in patients with moderate to very severe COPD in the Netherlands.,A cost-utility study was performed, using an individual-level Markov model.,To populate the model, individual patient-level data (age, height, sex, COPD duration, baseline forced expiratory volume in 1 second) were obtained from the tiotropium-olodaterol TOnado trial.,In the model, forced expiratory volume in 1 second and patient-level data were extrapolated to utility and survival, and treatment with tiotropium-olodaterol FDC was compared with tiotropium.,Cost-utility analysis was performed from the Dutch health care payer’s perspective using a 15-year time horizon in the base-case analysis.,The standard Dutch discount rates were applied (costs: 4.0%; effects: 1.5%).,Both univariate and probabilistic sensitivity analyses were performed.,Budget impact was annually assessed over a 5-year time horizon, taking into account different levels of medication adherence.,As a result of cost increases, combined with quality-adjusted life-year (QALY) gains, results showed that tiotropium-olodaterol FDC had an incremental cost-effectiveness ratio of €7,004/QALY.,Without discounting, the incremental cost-effectiveness ratio was €5,981/QALY.,Results were robust in univariate and probabilistic sensitivity analyses.,Budget impact was estimated at €4.3 million over 5 years assuming 100% medication adherence.,Scenarios with 40%, 60%, and 80% adherence resulted in lower 5-year incremental cost increases of €1.7, €2.6, and €3.4 million, respectively.,Tiotropium-olodaterol FDC can be considered a cost-effective treatment under current Dutch cost-effectiveness thresholds.

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

Inhaled corticosteroids (ICS) reduce exacerbation rates and the decline in lung function in people with chronic obstructive pulmonary disease (COPD).,There is evidence that smoking causes ‘steroid resistance’ and thus reduces the effect of ICS.,This systematic review aimed to investigate the effect of smoking on efficacy of ICS in COPD in terms of lung function and exacerbation rates.,Systematic review.,An electronic database search of PubMed, Ovid MEDLINE, Ovid Embase and Cochrane Library (January 2000 to January 2020).,Fully published randomised controlled trials (RCTs), in the English language, evaluating the use of ICS in COPD adults that stratified the participants by smoking status.,Trials that included participants with asthma, lung cancer and pneumonia were excluded.,The primary outcome measures were changes in lung function and yearly exacerbation rates.,Two independent reviewers extracted data and assessed risk of bias using the Cochrane Collaboration’s tool.,Seven studies were identified.,Four trials (17 892 participants) recorded change in forced expiratory volume in one second (FEV1) from baseline to up to 30 months after starting treatment.,Heavier smokers (>36 pack years) using ICS had a greater decline in FEV1 that ranged from −22 mL to −75 mL in comparison to lighter smokers.,Smokers using ICS had mixed results in FEV1 change: −8 mL to +77 mL in comparison to ex-smokers.,Four trials (21 270 participants) recorded difference in COPD exacerbation rates at 52 weeks.,The rate ratios favoured more exacerbations in ICS users who were current or heavier smokers than those who were ex-smokers or lighter smokers (0.81 to 0.99 vs 0.92 to 1.29).,In COPD, heavier or current smokers do not gain the same benefit from ICS use on lung function and exacerbation rates as lighter or ex-smokers do, however effects may not be clinically important.,CRD42019121833

Chronic obstructive pulmonary disease (COPD) imposes a substantial burden on individuals with the disease, which can include a range of symptoms (breathlessness, cough, sputum production, wheeze, chest tightness) of varying severities.,We present an overview of the biomedical literature describing reported relationships between COPD symptoms and disease burden in terms of quality of life, health status, daily activities, physical activity, sleep, comorbid anxiety, and depression, as well as risk of exacerbations and disease prognosis.,In addition, the substantial variability of COPD symptoms encountered (morning, daytime, and nighttime) is addressed and their implications for disease burden considered.,The findings from this narrative review, which mainly focuses on real-world and observational studies, demonstrate the impact of COPD symptoms on the burden of disease and that improved recognition and understanding of their impact is central to alleviating this burden.

Studies suggest that COPD prevalence may vary between countries.,We conducted an ecological study of data from COPD prevalence articles to assess the influence of differences in country-level risk factors on COPD prevalence.,Our study covered English language articles published during 2003-2014.,Qualified articles used spirometry to assess COPD prevalence and used representative samples from national or subnational populations.,Stepwise binomial regression was used to analyze associations between study- and country-level factors and COPD prevalence.,Eighty articles provided 1,583 measures of COPD prevalence for subjects in different sex, age, and smoking categories for 112 districts in 41 countries.,Adjusted prevalence rates for COPD were significantly lower for Australia/New Zealand and the Mediterranean and significantly higher for Latin America, compared to North America, Southeast Asia, and Northern Europe.,Country-level socioeconomic development variables had an uneven and mixed association with COPD prevalence.,High elevation above sea level was shown to be a protective factor for COPD.,Study-level variables for the established risk factors of sex, age, and smoking explained 64% of variability in COPD prevalence.,Country-level risk factors raised the explanatory power to 72%.,Approximately 28% of worldwide variability in COPD prevalence remained unexplained.,Our study suggests that COPD prevalence varies across world regions, even after adjustment for established risk factors.,Major country-level risk factors contributing to the worldwide epidemic of COPD remain to be investigated.

Chronic obstructive pulmonary disease (COPD) causes a high disease burden among the elderly worldwide.,In Taiwan, the long-term temporal trend of COPD mortality is declining, but the geographical disparity of the disease is not yet known.,Nationwide COPD age-adjusted mortality at the township level during 1999-2007 is used for elucidating the geographical distribution of the disease.,With an ordinary least squares (OLS) model and geographically weighted regression (GWR), the ecologic risk factors such as smoking rate, area deprivation index, tuberculosis exposure, percentage of aborigines, density of health care facilities, air pollution and altitude are all considered in both models to evaluate their effects on mortality.,Global and local Moran’s I are used for examining their spatial autocorrelation and identifying clusters.,During the study period, the COPD age-adjusted mortality rates in males declined from 26.83 to 19.67 per 100,000 population, and those in females declined from 8.98 to 5.70 per 100,000 population.,Overall, males’ COPD mortality rate was around three times higher than females’.,In the results of GWR, the median coefficients of smoking rate, the percentage of aborigines, PM10 and the altitude are positively correlated with COPD mortality in males and females.,The median value of density of health care facilities is negatively correlated with COPD mortality.,The overall adjusted R-squares are about 20% higher in the GWR model than in the OLS model.,The local Moran’s I of the GWR’s residuals reflected the consistent high-high cluster in southern Taiwan.,The findings indicate that geographical disparities in COPD mortality exist.,Future epidemiological investigation is required to understand the specific risk factors within the clustering areas.

This study aimed to generate real-world evidence to assess the burden of comorbidities in COPD patients, to effectively manage these patients and optimize the associated healthcare resource allocation.,ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients using electronic medical record data collected between 2000 and 2014.,These patients were studied for prevalence of various comorbidities and for association of these comorbidities with exacerbations, mortality, and healthcare costs compared with an age-, sex-, and comorbidities-matched non-COPD reference population.,A total of 17,479 patients with COPD were compared with 84,514 non-COPD reference population.,A significantly higher prevalence of various comorbidities was observed in COPD patients 2 years post-diagnosis vs. reference population, with the highest percentage increase observed for cardiovascular diseases (81.8% vs.,30.7%).,Among the selected comorbidities, lung cancer was relatively more prevalent in COPD patients vs. reference population (relative risk, RR = 5.97, p < 0.0001).,Ischemic heart disease, hypertension, depression, anxiety, sleep disorders, osteoporosis, osteoarthritis, and asthma caused increased mortality rates in COPD patients.,Comorbidities that were observed to be significantly associated with increased number of severe exacerbations in COPD patients included heart failure, ischemic heart disease, depression/anxiety, sleep disorders, osteoporosis, lung cancer, and stroke.,The cumulative healthcare costs associated with comorbidities over 2 years after the index date were observed to be significantly higher in COPD patients (€27,692) vs. reference population (€5141) (p < 0.0001).,The data support the need for patient-centered treatment strategies and targeted healthcare resource allocation to reduce the humanistic and economic burden associated with COPD comorbidities.,Co-existing conditions should be taken into consideration when treating patients with chronic lung disease to ensure coherent and cost-effective disease management.,In a large-scale study of the Swedish population, Björn Ställberg at Uppsala University and co-workers analyzed electronic medical records spanning fourteen years for 17,479 patients with chronic obstructive pulmonary disease (COPD) and compared their health status with 84,514 age-, sex- and comorbidity-matched non-COPD members of the population.,Patients with COPD were significantly more likely to suffer from co-morbidities two years after initial diagnosis than their non-COPD counterparts, with cardiovascular diseases being the most common comorbidities.,Lung cancer, hypertension, depression and sleep disorders were among other comorbidities more prevalent in the COPD population.,These data support the need for fully integrated, targeted healthcare to reduce mortality and the economic burden associated with COPD.

Exacerbations are important outcomes in COPD both from a clinical and an economic perspective.,Most studies investigating predictors of exacerbations were performed in COPD patients participating in pharmacological clinical trials who usually have moderate to severe airflow obstruction.,This study was aimed to investigate whether predictors of COPD exacerbations depend on the COPD population studied.,A network of COPD health economic modelers used data from five COPD data sources - two population-based studies (COPDGene® and The Obstructive Lung Disease in Norrbotten), one primary care study (RECODE), and two studies in secondary care (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoint and UPLIFT) - to estimate and validate several prediction models for total and severe exacerbations (= hospitalization).,The models differed in terms of predictors (depending on availability) and type of model.,FEV1% predicted and previous exacerbations were significant predictors of total exacerbations in all five data sources.,Disease-specific quality of life and gender were predictors in four out of four and three out of five data sources, respectively.,Age was significant only in the two studies including secondary care patients.,Other significant predictors of total exacerbations available in one database were: presence of cough and wheeze, pack-years, 6-min walking distance, inhaled corticosteroid use, and oxygen saturation.,Predictors of severe exacerbations were in general the same as for total exacerbations, but in addition low body mass index, cardiovascular disease, and emphysema were significant predictors of hospitalization for an exacerbation in secondary care patients.,FEV1% predicted, previous exacerbations, and disease-specific quality of life were predictors of exacerbations in patients regardless of their COPD severity, while age, low body mass index, cardiovascular disease, and emphysema seem to be predictors in secondary care patients only.

Mortality rate is high in patients with chronic obstructive pulmonary disease (COPD).,Our aim was to investigate long-term mortality and associated risk factors in COPD patients previously hospitalized for a COPD exacerbation.,A total of 256 patients from the Nordic countries were followed for 8.7 ± 0.4 years after the index hospitalization in 2000-2001.,Prior to discharge, the St George’s Respiratory Questionnaire was administered and data on therapy and comorbidities were obtained.,Information on long-term mortality was obtained from national registries in each of the Nordic countries.,In total, 202 patients (79%) died during the follow up period, whereas 54 (21%) were still alive.,Primary cause of death was respiratory (n = 116), cardiovascular (n = 43), malignancy (n = 28), other (n = 10), or unknown (n = 5).,Mortality was related to older age, with a hazard risk ratio (HRR) of 1.75 per 10 years, lower forced expiratory volume in 1 second (FEV1) (HRR 0.80), body mass index (BMI) <20 kg/m2 (HRR 3.21), and diabetes (HRR 3.02).,Older age, lower BMI, and diabetes were related to both respiratory and cardiovascular mortality.,An association was also found between lower FEV1 and respiratory mortality, whereas mortality was not significantly associated with therapy, anxiety, or depression.,Almost four out of five patients died within 9 years following an admission for COPD exacerbation.,Increased mortality was associated with older age, lower lung function, low BMI, and diabetes, and these factors should be taken into account when making clinical decisions about patients who have been admitted to hospital for a COPD exacerbation.

To evaluate the influence of heart disease on clinical characteristics, quality of life, use of health resources, and costs of patients with COPD followed at primary care settings under common clinical practice conditions.,Epidemiologic, observational, and descriptive study (EPIDEPOC study).,Patients ≥ 40 years of age with stable COPD attending primary care settings were included.,Demographic, clinical characteristics, quality of life (SF-12), seriousness of the disease, and treatment data were collected.,Results were compared between patients with or without associated heart disease.,A total of 9,390 patients with COPD were examined of whom 1,770 (18.8%) had heart disease and 78% were males.,When comparing both patient groups, significant differences were found in the socio-demographic characteristics, health profile, comorbidities, and severity of the airway obstruction, which was greater in patients with heart disease.,Differences were also found in both components of quality of life, physical and mental, with lower scores among those patients with heart disease.,Higher frequency of primary care and pneumologist visits, emergency-room visits and number of hospital admissions were observed among patients with heart diseases.,The annual total cost per patient was significantly higher in patients with heart disease; 2,937 ± 2,957 vs. 1,749 ± 2,120, p < 0.05.,Variables that were showed to be independently associated to COPD in subjects with hearth conditions were age, being inactive, ex-smokers, moderate physical exercise, body mass index, concomitant blood hypertension, diabetes, anxiety, the SF-12 physical and mental components and per patient per year total cost.,Patients with COPD plus heart disease had greater disease severity and worse quality of life, used more healthcare resources and were associated with greater costs compared to COPD patients without known hearth disease.

Chronic Obstructive Pulmonary Disease (COPD) is characterised by reduced lung function and is the third leading cause of death globally.,Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97.,A genetic risk score was associated with COPD susceptibility (odds ratios per standard deviation of the risk score (~6 alleles) (95% confidence interval) 1.24 (1.20-1.27), P=5.05x10-49) and we observed a 3.7 fold difference in COPD risk between highest and lowest genetic risk score deciles in UK Biobank.,The 97 signals show enrichment in development, elastic fibres and epigenetic regulation pathways.,We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.

A genetic contribution to develop chronic obstructive pulmonary disease (COPD) is well established.,However, the specific genes responsible for enhanced risk or host differences in susceptibility to smoke exposure remain poorly understood.,The goal of this review is to provide a comprehensive literature overview on the genetics of COPD, highlight the most promising findings during the last few years, and ultimately provide an updated COPD gene list.,Candidate gene studies on COPD and related phenotypes indexed in PubMed before January 5, 2012 are tabulated.,An exhaustive list of publications for any given gene was looked for.,This well-documented COPD candidate-gene list is expected to serve many purposes for future replication studies and meta-analyses as well as for reanalyzing collected genomic data in the field.,In addition, this review summarizes recent genetic loci identified by genome-wide association studies on COPD, lung function, and related complications.,Assembling resources, integrative genomic approaches, and large sample sizes of well-phenotyped subjects is part of the path forward to elucidate the genetic basis of this debilitating disease.

Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD.,To characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes.,We surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene.,We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes.,The stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies.,Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated.,We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events and bronchiectasis.,Subtypes of COPD have distinct bacterial compositions and stabilities over time.,Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future.,This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient.,Results, NCT01360398.

Sputum eosinophilia occurs in approximately one-third of stable chronic obstructive pulmonary disease (COPD) patients and can predict exacerbation risk and response to corticosteroid treatments.,Sputum induction, however, requires expertise, may not always be successful, and does not provide point-of-care results.,Easily applicable diagnostic markers that can predict sputum eosinophilia in stable COPD patients have the potential to progress COPD management.,This study investigated the correlation and predictive relationship between peripheral blood and sputum eosinophils.,It also examined the repeatability of blood eosinophil counts.,Stable COPD patients (n=141) were classified as eosinophilic or noneosinophilic based on their sputum cell counts (≥3%), and a cross-sectional analysis was conducted comparing their demographics, clinical characteristics, and blood cell counts.,Receiver operating characteristic curve analysis was used to assess the predictive ability of blood eosinophils for sputum eosinophilia.,Intraclass correlation coefficient was used to examine the repeatability of blood eosinophil counts.,Blood eosinophil counts were significantly higher in patients with sputum eosinophilia (n=45) compared to those without (0.3×109/L vs 0.15×109/L; P<0.0001).,Blood eosinophils correlated with both the percentage (ρ=0.535; P<0.0001) and number of sputum eosinophils (ρ=0.473; P<0.0001).,Absolute blood eosinophil count was predictive of sputum eosinophilia (area under the curve =0.76, 95% confidence interval [CI] =0.67-0.84; P<0.0001).,At a threshold of ≥0.3×109/L (specificity =76%, sensitivity =60%, and positive likelihood ratio =2.5), peripheral blood eosinophil counts enabled identification of the presence or absence of sputum eosinophilia in 71% of the cases.,A threshold of ≥0.4×109/L had similar classifying ability but better specificity (91.7%) and higher positive likelihood ratio (3.7).,In contrast, ≥0.2×109/L offered a better sensitivity (91.1%) for ruling out sputum eosinophilia.,There was a good agreement between two measurements of blood eosinophil count over a median of 28 days (intraclass correlation coefficient =0.8; 95% CI =0.66-0.88; P<0.0001).,Peripheral blood eosinophil counts can help identify the presence or absence of sputum eosinophilia in stable COPD patients with a reasonable degree of accuracy.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised many questions about the management of patients with chronic obstructive pulmonary disease (COPD) and whether modifications of their therapy are required.,It has raised questions about recognizing and differentiating coronavirus disease (COVID-19) from COPD given the similarity of the symptoms.,The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Science Committee used established methods for literature review to present an overview of the management of patients with COPD during the COVID-19 pandemic.,It is unclear whether patients with COPD are at increased risk of becoming infected with SARS-CoV-2.,During periods of high community prevalence of COVID-19, spirometry should only be used when it is essential for COPD diagnosis and/or to assess lung function status for interventional procedures or surgery.,Patients with COPD should follow basic infection control measures, including social distancing, hand washing, and wearing a mask or face covering.,Patients should remain up to date with appropriate vaccinations, particularly annual influenza vaccination.,Although data are limited, inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should continue to be used as indicated for stable COPD management.,Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications.,Differentiating symptoms of COVID-19 infection from chronic underlying symptoms or those of an acute COPD exacerbation may be challenging.,If there is suspicion for COVID-19, testing for SARS-CoV-2 should be considered.,Patients who developed moderate-to-severe COVID-19, including hospitalization and pneumonia, should be treated with evolving pharmacotherapeutic approaches as appropriate, including remdesivir, dexamethasone, and anticoagulation.,Managing acute respiratory failure should include appropriate oxygen supplementation, prone positioning, noninvasive ventilation, and protective lung strategy in patients with COPD and severe acute respiratory distress syndrome.,Patients who developed asymptomatic or mild COVID-19 should be followed with the usual COPD protocols.,Patients who developed moderate or worse COVID-19 should be monitored more frequently and accurately than the usual patients with COPD, with particular attention to the need for oxygen therapy.

Physicians do not routinely recommend smokers to undergo spirometry unless they are symptomatic.,To test the hypothesis that there are a significant number of asymptomatic smokers with chronic obstructive pulmonary disease (COPD), we estimated the prevalence of COPD in a group of asymptomatic smokers.,Two thousand nine hundred and sixty-one smokers with a cumulative consumption history of at least 10 pack-years, either smokers with symptoms or smokers without symptoms (WOS) were invited to perform a spirometry and complete a symptom questionnaire.,Six hundred and thirty-seven (21.5%) smokers had no symptoms, whereas 2,324 (78.5%) had at least one symptom.,The prevalence of COPD in subjects WOS was 1.5% when considering the whole group of smokers (45/2,961) and 7% when considering only the group WOS (45/637).,From 329 smokers with COPD, 13.7% were WOS.,Subjects WOS were younger, had better lung function and lower cumulative consumption of cigarettes, estimated as both cigarettes per day and pack-years.,According to severity of airflow limitation, 69% vs 87% of subjects were classified as Global Initiative for Chronic Obstructive Lung Disease stages I-II in the WOS and smokers with symptoms groups, respectively (P<0.001).,A multivariate analysis showed that forced expiratory volume in 1 second (mL) was the only predictive factor for COPD in asymptomatic smokers.,Prevalence of COPD in asymptomatic smokers is 1.5%.,This number of asymptomatic smokers may be excluded from the benefit of an “early” intervention, not just pharmacological but also from smoking cessation counseling.,The higher forced expiratory volume in 1 second may contribute to prevent early diagnosis.