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A multidimensional assessment of COPD was recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) in 2013 and revised in 2017.,We examined the ability of the GOLD 2017 and the new 16 subgroup (1A-4D) classifications to predict clinical outcomes, including exacerbation and mortality, and compared them with the GOLD 2013 classifications.,Patients with COPD were recruited from January 2006 to December 2017.,The predictive abilities of grades 1-4 and groups A-D were examined through a logistic regression analysis with receiver operating curve estimations and area under the curve (AUC).,A total of 553 subjects with COPD were analyzed.,The mortality rate was 48.6% during a median follow-up period of 5.2 years.,Both the GOLD 2017 and the 2013 group A-D classifications had good predictive ability for total and severe exacerbations, for which the AUCs were 0.79 vs 0.77 and 0.79 vs 0.78, respectively.,The AUCs for the GOLD 2017 groups A-D, grades 1-4, and the GOLD 2013 group A-D classifications were 0.70, 0.66, and 0.70 for all-cause mortality and 0.73, 0.71, and 0.74 for respiratory cause mortality, respectively.,Combining the spirometric staging with the grouping for the GOLD 2017 subgroups (1A-4D), the all-cause mortality rate for group B and D patients was significantly increased from subgroups 1B-4B (27.7%, 50.6%, 53.3%, and 69.2%, respectively) and groups 1D-4D (55.0%, 68.8%, 82.1%, and 90.5%, respectively).,The AUCs of subgroups (1A-4D) were 0.73 and 0.77 for all-cause and respiratory mortality, respectively; the new classification was determined more accurate than the GOLD 2017 for predicting mortality (P<0.0001).,The GOLD 2017 classification performed well by identifying individuals at risk of exacerbation, but its predictive ability for mortality was poor among COPD patients.,Combining the spirometric staging with the grouping increased the predictive ability for all-cause and respiratory mortality.,We validate the ability of the GOLD 2017 and 16 subgroup (1A-4D) classifications to predict clinical outcome for COPD patients.,The GOLD 2017 classification performed well by identifying individuals at risk of exacerbation, but its predictive ability for mortality was poor.,The new 16 subgroup (1A-4D) classification combining the spirometric 1-4 staging and the A-D grouping increased the predictive ability for mortality and was better than the GOLD 2017 for predicting all-cause and respiratory mortality among COPD patients. | 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. | 1 |
To examine the relationship between gastroesophageal reflux (GER) and COPD exacerbations.,We conducted a systematic search of various electronic databases for articles published up through December of 2012.,Studies considered eligible for inclusion were those dealing with COPD, COPD exacerbations, and GER; comparing at least two groups (COPD vs. controls or GER vs. controls); and describing relative risks (RRs) and prevalence ratios-or ORs and their respective 95% CIs (or presenting enough data to allow further calculations) for the association between GER and COPD-as well as exacerbation rates.,Using a standardized form, we extracted data related to the study design; criteria for GER diagnosis; age, gender, and number of participants; randomization method; severity scores; methods of evaluating GER symptoms; criteria for defining exacerbations; exacerbation rates (hospitalizations, ER visits, unscheduled clinic visits, prednisone use, and antibiotic use); GER symptoms in COPD group vs. controls; mean number of COPD exacerbations (with symptoms vs. without symptoms); annual frequency of exacerbations; GER treatment; and severity of airflow obstruction.,Overall, GER was clearly identified as a risk factor for COPD exacerbations (RR = 7.57; 95% CI: 3.84-14.94), with an increased mean number of exacerbations per year (mean difference: 0.79; 95% CI: 0.22-1.36).,The prevalence of GER was significantly higher in patients with COPD than in those without (RR = 13.06; 95% CI: 3.64-46.87; p < 0.001).,GER is a risk factor for COPD exacerbations.,The role of GER in COPD management should be studied in greater detail. | Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death. | 1 |
According to the American Thorasic Society (ATS)/European Respiratory Society (ERS) Statement, chronic obstructive pulmonary disease (COPD) is defined as a preventable and treatable disease with a strong genetic component, characterized by airflow limitation that is not fully reversible, but is usually progressive and associated with an enhanced inflammatory response of the lung to noxious particles or gases.,The main features of COPD are chronic inflammation of the airways and progressive destruction of lung parenchyma and alveolar structure.,The pathogenesis of COPD is complex due to the interactions of several mechanisms, such as inflammation, proteolytic/antiproteolytic imbalance, oxidative stress, DNA damage, apoptosis, enhanced senescence of the structural cells and defective repair processes.,This review focuses on the effects of oxidative DNA damage and the consequent immune responses in COPD.,In susceptible individuals, cigarette smoke injures the airway epithelium generating the release of endogenous intracellular molecules or danger-associated molecular patterns from stressed or dying cells.,These signals are captured by antigen presenting cells and are transferred to the lymphoid tissue, generating an adaptive immune response and enhancing chronic inflammation. | Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease caused by the interaction of genetic susceptibility and environmental influences.,There is increasing evidence that genes link to disease pathogenesis and heterogeneity by causing variation in protease anti-protease systems, defence against oxidative stress and inflammation.,The main methods of genomic research for complex disease traits are described, together with the genes implicated in COPD thus far, their roles in disease causation and the future for this area of investigation. | 1 |
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 | There is an ongoing debate on whether patients with chronic obstructive pulmonary disease (COPD) seen in real-life clinical settings are represented in randomized controlled trials (RCTs) of COPD.,It is thought that the stringent inclusion and exclusion criteria of RCTs may prevent the participation of patients with specific characteristics or risk factors.,We surveyed a database of patients recruited into 35 placebo-controlled tiotropium RCTs and also conducted a systematic literature review of large-scale observational studies conducted in patients with a documented diagnosis of COPD between 1990 and 2013.,Patient demographics and comorbidities with a high prevalence in patients with COPD were compared between the two patient populations at baseline.,Using the Medical Dictionary for Regulatory Activities (MedDRA; v 14.0), patient comorbidities in the pooled tiotropium RCTs were classified according to system organ class, pharmacovigilance (PV) endpoints, and Standardised MedDRA Queries to enable comparison with the observational studies.,We identified 24,555 patients in the pooled tiotropium RCTs and 61,361 patients among the 13 observational studies that met our search criteria.,The Global initiative for chronic Obstructive Lung Disease (GOLD) staging of patients in the RCTs differed from that in observational studies: the proportion of patients with GOLD stages I+II disease ranged from 40.0% to 51.5% in the RCTs but 24.5% to 44.1% in the observational studies; for GOLD stage III or IV disease these ranges were 7.2%-45.8% (RCTs) and 13.7-42.1% (observational studies).,The comorbidities with the highest prevalence reported in the RCTs and observational studies were: hypertension (39.4%-40.0% vs 40.1%-60.6%), other ischemic heart disease (12.3%-14.2% vs 12.5%-41.0%), diabetes (10.3%-10.9% vs 4.0%-38.9%), depression (8.5%-9.5% vs 17.0%-20.6%), and cardiac arrhythmia (7.8%-11.4% vs 11.3%-15.8%).,The clinical profile of COPD patients treated in the tiotropium trial program appears to be largely in the range of clinical characteristics, including cardiovascular comorbidities, reported for “real-life patients.”,The tiotropium RCTs tended to include patients with more severe disease than the observational studies. | 1 |
COPD is a progressive condition involving chronic inflammation and parenchymal destruction with resulting airflow limitation.,COPD is associated with worsening airflow limitation over time and increased frequency of COPD exacerbations, leading to increased mortality and morbidity.,The effects of COPD extend beyond the lungs, as multiple comorbidities may occur with COPD, including cardiovascular disease, diabetes mellitus, osteoporosis, depression, and pneumonia.,COPD exacerbations are associated with a rapid worsening of baseline symptoms that requires prompt management and may necessitate hospitalization in the case of a severe episode.,Patients with COPD exacerbations require urgent management of symptoms to prevent further worsening, and preventative steps may be taken to help reduce the number and frequency of future exacerbations.,Roflumilast is a potent and selective inhibitor of the enzyme phosphodiesterase-4 that targets the systemic inflammation associated with COPD.,Roflumilast has a variety of anti-inflammatory effects including decreasing inflammatory mediators and the expression of cell surface markers and inhibition of apoptosis.,Several clinical trials evaluating roflumilast in the treatment of COPD have demonstrated significant improvements from baseline versus placebo in lung function, including increases in mean pre- and postbronchodilator forced expiratory volume in 1 second and forced vital capacity.,Data suggest that roflumilast reduces moderate to severe exacerbations with the benefit most well established in patients with severe disease.,Given this evidence, roflumilast, as part of a combination regimen with long-acting bronchodilators, appears to be a reasonable treatment option for patients with severe to very severe COPD associated with chronic bronchitis and a history of exacerbations. | Exacerbation-associated health-related quality of life (HRQoL) in patients with severe and very severe chronic obstructive pulmonary disease (COPD) is ill-defined.,This study describes patterns, HRQoL, and the work productivity impact of COPD-related moderate and SEV exacerbations in patients with SEV/VSEV COPD, focusing on the chronic bronchitis subtype.,A US sample of SEV and VSEV COPD patients with recent moderate or SEV exacerbation was recruited.,Along with the demographic and clinical data collected from medical records, patients reported on exacerbation frequency, health-related quality of life (HRQoL) (using the St George’s Respiratory Questionnaire for COPD [SGRQ-C] and the European Quality of Life-5 Dimensions [EQ-5D]™ index), and work productivity and activity impairment (using the Work Productivity and Activity Impairment Questionnaire - Specific Health Problem [WPAI-SHP]).,The HRQoL-related impacts of exacerbation frequency, time since exacerbation, and last exacerbation severity were evaluated via linear regressions.,A total of 314 patients (190 SEV/124 VSEV, mean age =68.0 years, 51% male, 28% current smokers) were included.,In the previous 12 months, patients reported an average of 1.8 moderate exacerbations and 0.9 SEV exacerbations.,Overall, 16% of patients were employed and reported a high percentage of overall work impairment (42.4% ± 31.1%).,Activity impairment was positively associated with recent exacerbation severity (SEV 64.6% ± 26.8% versus moderate 55.6% ± 28.2%) (P=0.006).,The HRQoL was significantly worse for SEV versus VSEV COPD (EQ-5D: 0.62 ± 0.23 versus 0.70 ± 0.17, respectively, and SGRQ-C: 70.1 ± 21.3 versus 61.1 ± 19.0, respectively) (P<0.001).,Worse current HRQoL was reported by patients with a SEV versus moderate recent exacerbation (EQ-5D: 0.63 ± 0.21 versus 0.70 ± 0.20, respectively) (P=0.003); SGRQ-C: 70.3 ± 19.9 versus 61.7 ± 20.1, respectively (P<0.001).,One additional exacerbation in the previous 12 months was associated with a 2.4-point SGRQ-C increase and a 0.02-point EQ-5D index decrease.,The severity and frequency of COPD-related moderate/SEV exacerbations in SEV and VSEV COPD patients were positively associated with poor HRQoL and work productivity and activity impairment. | 1 |
The purpose of this study was to assess the relationship of smoking duration with respiratory symptoms and history of chronic obstructive pulmonary disease (COPD) in the South Carolina Behavioral Risk Factor Surveillance System survey in 2012.,Data from 4,135 adults aged ≥45 years with a smoking history were analyzed using multivariable logistic regression that accounted for sex, age, race/ethnicity, education, and current smoking status, as well as the complex sampling design.,The distribution of smoking duration ranged from 19.2% (1-9 years) to 36.2% (≥30 years).,Among 1,454 respondents who had smoked for ≥30 years, 58.3% were current smokers, 25.0% had frequent productive cough, 11.2% had frequent shortness of breath, 16.7% strongly agreed that shortness of breath affected physical activity, and 25.6% had been diagnosed with COPD.,Prevalence of COPD and each respiratory symptom was lower among former smokers who quit ≥10 years earlier compared with current smokers.,Smoking duration had a linear relationship with COPD (P<0.001) and all three respiratory symptoms (P<0.001) after adjusting for smoking status and other covariates.,While COPD prevalence increased with prolonged smoking duration in both men and women, women had a higher age-adjusted prevalence of COPD in the 1-9 years, 20-29 years, and ≥30 years duration periods.,These state population data confirm that prolonged tobacco use is associated with respiratory symptoms and COPD after controlling for current smoking behavior. | Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD).,It is unclear whether the risk of pneumonia varies for different inhaled agents, particularly fluticasone and budesonide, and increases with the dose and long-term duration of use.,We formed a new-user cohort of patients with COPD treated during 1990-2005.,Subjects were identified using the Quebec health insurance databases and followed through 2007 or until a serious pneumonia event, defined as a first hospitalisation for or death from pneumonia.,A nested case-control analysis was used to estimate the rate ratio (RR) of serious pneumonia associated with current ICS use, adjusted for age, sex, respiratory disease severity and comorbidity.,The cohort included 163 514 patients, of which 20 344 had a serious pneumonia event during the 5.4 years of follow-up (incidence rate 2.4/100/year).,Current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63 to 1.75).,The risk was sustained with long-term use and declined gradually after stopping ICS use, disappearing after 6 months (RR 1.08; 95% CI 0.99 to 1.17).,The rate of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93 to 2.10), increasing with the daily dose, but was much lower with budesonide (RR 1.17; 95% CI 1.09 to 1.26).,ICS use by patients with COPD increases the risk of serious pneumonia.,The risk is particularly elevated and dose related with fluticasone.,While residual confounding cannot be ruled out, the results are consistent with those from recent randomised trials. | 1 |
COPD is prevalent in Western society and its incidence is rising in the developing world.,Acute exacerbations of COPD, about 50% of which are unreported, lead to deterioration in quality of life and contribute significantly to disease burden.,Quality of life deteriorates with time; thus, most of the health burden occurs in more severe disease.,COPD severity and frequent and more severe exacerbations are all related to an increased risk of mortality.,Inhaled corticosteroids (ICS) have similar effects on quality of life but ICS/long-acting bronchodilator combinations and the long-acting antimuscarinic tiotropium all improve health status and exacerbation rates and are likely to have an effect on mortality but perhaps only with prolonged use.,Erythromycin has been shown to decrease the rate of COPD exacerbations.,Pulmonary rehabilitation and regular physical activity are indicated in all severities of COPD and improve quality of life.,Noninvasive ventilation is associated with improved quality of life.,Long-term oxygen therapy improves mortality but only in hypoxic COPD patients.,The choice of an inhaler device is a key component of COPD therapy and this requires more attention from physicians than perhaps we are aware of.,Disease management programs, characterized as they are by patient centeredness, improve quality of life and decrease hospitalization rates.,Most outcomes in COPD can be modified by interventions and these are well tolerated and have acceptable safety profiles. | To review published evidence regarding the cost effectiveness of multi-component COPD programs and to illustrate how potentially cost effective programs can be identified.,Systematic search of Medline and Cochrane databases for evaluations of multi-component disease management or chronic care programs for adults with COPD, describing process, intermediate, and end results of care.,Data were independently extracted by two reviewers and descriptively summarized.,Twenty articles describing 17 unique COPD programs were included.,There is little evidence for significant improvements in process and intermediate outcomes, except for increased provision of patient self-management education and improved disease-specific knowledge.,Overall, the COPD programs generate end results equivalent to usual care, but programs containing ≥3 components show lower relative risks for hospitalization.,There is limited scope for programs to break-even or save money.,Identifying cost effective multi-component COPD programs remains a challenge due to scarce methodologically sound studies that demonstrate significant improvements on process, intermediate and end results of care.,Estimations of potential cost effectiveness of specific programs illustrated in this paper can, in the absence of ‘perfect data’, support timely decision-making regarding these programs.,Nevertheless, well-designed health economic studies are needed to decrease the current decision uncertainty. | 1 |
Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide.,Genetic risk loci provide novel insights into disease pathogenesis.,We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium.,We identified 82 loci with P-value < 5 × 10−8; 47 were previously described in association with either COPD or population-based lung function.,Of the remaining 35 novel loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium.,Using gene expression and regulation data, we identified enrichment for loci in lung tissue, smooth muscle and several lung cell types.,We found 14 COPD loci shared with either asthma or pulmonary fibrosis.,COPD genetic risk loci clustered into groups of quantitative imaging features and comorbidity associations.,Our analyses provide further support to the genetic susceptibility and heterogeneity of COPD. | Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD).,In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new.,In combination, these variants strongly predict COPD in independent patient populations.,Furthermore, the combined effect of these variants showed generalizability across smokers and never-smokers, and across ancestral groups.,We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function associated variants.,This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD. | 1 |
Fluticasone furoate/vilanterol (FF/VI) is a novel, once-daily, inhaled corticosteroid/long-acting β2-agonist combination approved for the treatment of COPD and asthma.,We compared the safety and efficacy of FF/VI and tiotropium (TIO) in subjects with moderate-to-severe COPD with greater risk for comorbid cardiovascular disease (CVD).,This randomized, blinded, double-dummy, parallel-group study compared a once-daily morning dose of FF/VI 100/25 mcg delivered via ELLIPTA™ with TIO 18 mcg via HandiHaler® for 12 weeks in subjects with diagnosed COPD, forced expiratory volume in 1 second (FEV1) 30%-70% predicted, and CVD or CVD risk.,The primary endpoint was change from baseline in 24-hour weighted mean FEV1 on Day 84.,Other efficacy endpoints included time to onset of bronchodilation, trough FEV1, other spirometry measures, rescue medication use, symptoms, quality of life (St George’s Respiratory Questionnaire-COPD [SGRQ-C]), and health status (COPD Assessment Tests [CAT]) measures.,Safety endpoints included cardiovascular monitoring, cortisol excretion, COPD exacerbations, and adverse events, including prespecified drug effects.,Both FF/VI and TIO improved the 24-hour weighted mean FEV1 from baseline after 12 weeks with no significant difference between treatments.,Other endpoints favored FF/VI for time to onset of bronchodilation, rescue medication use, dyspnea, SGRQ-C and CAT scores, or favored TIO for change from baseline in forced vital capacity and inspiratory capacity.,Pneumonia occurred more frequently in the FF/VI group, and two TIO-treated subjects died following cardiovascular events.,Other safety measures were similar between groups, and cardiovascular monitoring did not reveal increased CVD risk.,Both FF/VI and TIO were efficacious in improving lung function in subjects with COPD and comorbid CVD or CVD risk factors, with minor differences in efficacy and safety profiles. | Exercise training improves exercise tolerance in chronic obstructive pulmonary disease (COPD).,Tiotropium 18 μg once daily induces sustained bronchodilation throughout the day and reduces hyperinflation, one of the pathophysiological factors contributing to exertional dyspnea in COPD patients.,To determine whether tiotropium enhances the effects of exercise training in patients with COPD.,Multicenter, 25 week randomized, double-blind, placebo-controlled, parallel-group study.,Twelve Italian Pulmonary Units practicing pulmonary rehabilitation.,Two hundred thirty four COPD patients (196 males; mean age: 67.4 ± 7.6; forced expiratory volume at 1 second (FEV1): 41.4 ± 13.0% predicted) were randomised to tiotropium 18 μg or placebo inhalation capsules taken once daily.,Both groups underwent a 8 week pulmonary rehabilitation program (PR) consisting of 3 exercise training session per week.,Baseline, at the end of PR and after 12 weeks, patients completed pulmonary function testing, six minute walking test (6MWT), the Baseline and Transition Dyspnea Index (BDI and TDI), and the St.,George’s Respiratory Questionnaire (SGRQ).,Relative to placebo, tiotropium had larger trough and post-study drug FEV1 responses on all test days.,At the end of and 12 weeks following PR, patients on tiotropium showed no statistically significant differences in 6MWT compared to patients on placebo.,Compared to the period immediately prior to PR, the mean improvement in 6MWT was only 29.7 meters (7.1%) for the combined cohort.,Mean TDI focal scores at the end of PR were 3.60 for tiotropium and 2.25 for placebo (p < 0.01).,At 12 weeks after PR, TDI focal scores were 2.71 for tiotropium and 2.11 for placebo (p = 0.16).,Reduction in all four SGRQ component scores, indicating an improvement in health-related quality of life, was observed for the tiotropium group over the duration of the study compared to placebo but the differences were not statistically significant.,During the study period, there were fewer exacerbations and exacerbation days in the tiotropium group.,Although significant improvements were observed with perceived dyspnea, compared to placebo, the addition of tiotropium to pulmonary rehabilitation did not improve the 6MWT. | 1 |
Triple therapy versus dual therapy for chronic pulmonary obstructive disease (COPD) can reduce symptoms, limit the risk of acute exacerbations (AEs) as well as improve lung function.,Currently, studies that feature clinically important deterioration (CID) as a composite endpoint to assess the need for treatment intensification for patients maintained on dual therapy remained to be scarce.,This study is a retrospective analysis (January 2014 to January 2018) of COPD patients that presented with moderate to severe AEs during the previous year with blood eosinophil counts ≥ 100 cells/μL.,The first line of therapy included a combination of inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA).,Composite CID was used in assessing the response to treatment after 24 weeks of therapy.,This study included 110 patients, of which 49 patients reportedly experienced CID.,The most common events of CID include a decline in forced expiratory volume in 1 second (FEV1) ≥ 100 mL from baseline (25/49, 51%) and an increase in COPD Assessment Test (CAT) scores ≥ 2 (13/49, 26.5%); many of these patients respond to the addition of a long-acting muscarinic antagonist (LAMA).,Seven patients (7/110, 6.3%) experienced moderate to severe exacerbations while undergoing treatment with ICS/LABA.,Univariate and multivariate analyses have identified low baseline FEV1 (OR = 0.81, p = 0.004), high CAT score (OR = 1.89, p = 0.004), and the frequency of AE (OR = 19.86, p = 0.021) as independent predictors of CID.,A baseline FEV1 of ≤42%, an initial CAT score ≥ 18, and AE ≥ 2 last year were considered the optimal cut-off values, which were identified via receiver operating characteristics (ROC) curve analysis.,Triple therapy (ICS/LABAs/LAMAs) may be considered as first-line treatment in patients experiencing more than 2 times moderate to severe AEs of COPD in the previous year and who have blood eosinophil counts ≥100 cells/μL, reduced lung function (FEV1 ≤ 42%), and more symptoms (CAT score ≥ 18). | Objective: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is of increasing interest because ACO patients have significantly worse outcomes, leading to greater social and economic burdens compared with asthma or COPD alone.,Some guidelines for ACO recommend triple therapy with inhaled corticosteroids, long-acting β2 agonists, and long-acting muscarinic antagonists.,However, this approach is based on extrapolating data from patients with asthma or COPD alone.,Therapeutic studies for ACO have not previously been conducted.,Materials and methods: A 12-week, randomized, open-label cross-over pilot study was conducted in 17 ACO patients to evaluate the effect of umeclidinium (UMEC) 62.5 µg once-daily added to fluticasone furoate/vilanterol (FF/VI) 200/25 µg once-daily.,A 4-week run-in, a first and a second 4-week treatment period were included.,Respiratory function, respiratory impedance, fractional exhaled nitric oxide, COPD assessment test, and asthma control test scores were evaluated 0, 4, and 8 weeks after randomization.,Results: Mean values of post-bronchodilator forced expiratory volume in 1 second as a percentage of the predicted value (%FEV1), after UMEC was added to FF/VI, were significantly higher than after the run-in (p < 0.01).,Mean values of resonant frequency during inspiration (Fres), after UMEC was added to FF/VI, were significantly lower than after the run-in (p < 0.01).,Conclusion: Adding UMEC to FF/VI provides greater improvement in lung function, indicating that triple therapy is a suitable regular treatment for ACO. | 1 |
Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century.,The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD.,Our understanding of the key molecular mechanisms which drive the pathological changes are not complete.,In this article we will provide a historical overview of key histopathological studies which have helped shape our understanding of SAD and discuss the hallmark features of airway remodelling, mucous plugging and inflammation.,We focus on the relationship between SAD and emphysema, SAD in the early stages of COPD, and the mechanisms which cause SAD progression, including bacterial colonization and exacerbations.,We discuss the need to specifically target SAD to attenuate the progression of COPD. | Never smokers comprise a substantial proportion of patients with COPD.,Their characteristics and possible risk factors in this population are not yet well defined.,We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study.,Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors.,A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines.,In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio.,Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD.,Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD.,This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio.,Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations.,This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD.,Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers. | 1 |
Purpose: Assess the clinical and economic consequences associated with an early versus late diagnosis in patients with COPD.,Patients and methods: In a retrospective, observational cohort study, electronic medical record data (2000-2014) were collected from Swedish primary care patients with COPD.,COPD indicators (pneumonia, other respiratory diseases, oral corticosteroids, antibiotics for respiratory infections, prescribed drugs for respiratory symptoms, lung function measurement) registered prior to diagnosis were applied to categorize patients into those receiving early (2 or less indicators) or late diagnosis (3 or more indicators registered >90 days preceding a COPD diagnosis).,Outcome measures included annual rate of and time to first exacerbation, mortality risk, prevalence of comorbidities and health care utilization.,Results: More patients with late diagnosis (n=8827) than with early diagnosis (n=3870) had a recent comorbid diagnosis of asthma (22.0% vs 3.9%; P<0.0001).,Compared with early diagnosis, patients with late diagnosis had a higher exacerbation rate (hazard ratio [HR] 1.89, 95% confidence interval [CI]: 1.83-1.96; P<0.0001) and shorter time to first exacerbation (HR 1.61, 95% CI: 1.54-1.69; P<0.0001).,Mortality was not different between groups overall but higher for late versus early diagnosis, after excluding patients with past asthma diagnosis (HR 1.10, 95% CI: 1.02-1.18; P=0.0095).,Late diagnosis was also associated with higher direct costs than early diagnosis.,Conclusion: Late COPD diagnosis is associated with higher exacerbation rate and increased comorbidities and costs compared with early diagnosis.,The study highlights the need for accurate diagnosis of COPD in primary care in order to reduce exacerbations and the economic burden of COPD. | Multimorbidity has already become common in primary care and will be a challenge in the future.,Primary care in Sweden participates to a great extent in the care of patients with two severe, chronic conditions: chronic obstructive pulmonary disease (COPD) and heart failure.,Both conditions are characterized by high mortality and often coexist.,Age, sex, heart failure and other comorbidities are considered to be the major predictors of mortality in patients with COPD.,We aimed to study the impact of heart failure, other comorbidities, age and sex on mortality in patients with COPD.,A register-based, prospective cohort study conducted in Blekinge County in Sweden with about 150,000 inhabitants.,The study population was comprised of people aged ≥35 years.,The data about diagnoses of COPD and heart failure came from the 2007 health care register, in which we found 984 individuals with a diagnosis of COPD.,Date of death was collected from January 1st, 2008 -August 31st, 2015.,The diagnosis-based Adjusted Clinical Groups (ACG) Case-Mix System 7.1 was used to describe comorbidity.,Each individual was assigned one of six comorbidity levels called resource utilization bands (RUB) graded from 0 to 5.,Estimated eight year mortality in patients with COPD and coexisting heart failure was seven times higher than in patients with COPD alone - odds ratio 7.06 (95% CI 3.88-12.84).,Adjusting for age and male sex resulted in odds ratio 3.75 (95% CI 1.97-7.15).,Further adjusting for other comorbidities resulted in odds ratio 3.26 (95% CI 1.70-6.25).,The mortality was strongly associated with the highest comorbidity level - RUB 5 where the odds ratio was 5.19 (95% CI 2.59-10.38).,Heart failure has an important impact on mortality in patients with COPD.,The mortality in patients with COPD and coexisting heart failure was strongly associated with age, male sex and other comorbidities.,Of those three predictors, only other comorbidities can be influenced.,Heart failure and other comorbidities should be recognized early and properly treated in order to improve survival in patients with coexisting COPD and heart failure. | 1 |
Although chronic obstructive pulmonary disease (COPD) is regarded as a chronic inflammatory lung disease, the disease mechanism is still not known.,Intriguingly, aging lungs are quite similar to COPD-affected lungs in many ways, and COPD has been viewed as a disease of accelerated premature aging of the lungs.,In this paper, based on a literature review, we would like to propose immunosenescence, age-associated decline in immunity, as a critical mechanism for the development of COPD.,Immunosenescence can cause a low-grade, systemic inflammation described as inflammaging.,This inflammaging may be directly involved in the COPD pathogenesis.,The potential contributors to the development of inflammaging in the lungs possibly leading to COPD are discussed in the review paper.,A notable fact about COPD is that only 15% to 20% of smokers develop clinically significant COPD.,Given that there is a substantial inter-individual variation in inflammaging susceptibility, which is genetically determined and significantly affected by the history of the individual's exposure to pathogens, immunosenescence and inflammaging may also provide the answer for this unexpectedly low susceptibility of smokers to clinically significant COPD. | Among patients with chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM) is a common comorbidity and is probably associated with increased systemic inflammation and worse prognosis.,Metformin, with its pleiotropic anti-inflammatory and antioxidant actions, may offer theoretical benefits in COPD patients with DM.,Thus, this study aimed to investigate the effects of DM and metformin use on mortality in the clinical trajectory of COPD.,This was a retrospective cohort study comprising patients with spirometry-confirmed COPD and an age of ≥40 years from 2008 to 2014.,The primary outcome of interest was all-cause mortality.,We evaluated the effects of DM on mortality through the clinical course of COPD and we also assessed the impact of metformin use on survival of the COPD population.,Among 4231 COPD patients, 556 (13%) had DM, and these patients had 1.62 times higher hazards of 2-year mortality than those without DM (95% confidence interval [CI], 1.15-2.28) after adjusting for age, gender, COPD stage, comorbidities and prior COPD hospitalization.,Over a 2-year period, metformin users had a significantly lower risk of death (hazard ratio, 0.46; 95% CI, 0.23-0.92) compared with non-metformin users in patients with coexistent COPD and DM.,Moreover, metformin users had similar survival to COPD patients without DM.,This study shows that DM is associated with an increased risk of death in COPD patients and metformin use seems to mitigate the hazard.,Our findings suggest a potential role of metformin in the management of DM in COPD.,The online version of this article (10.1186/s12931-019-1035-9) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide with a substantial and increasing social and economic burden.,Liuzijue Qigong is a kind of traditional Chinese Qigong exercises that Traditional Chinese Medicine practitioners prescribe to individuals with COPD to strengthen the internal organs’ function.,Liuzijue Qigong was recommended for use in COPD rehabilitation, and some clinical trials indicate that Liuzijue Qigong would produce better functional capacity and quality of life of individuals with COPD.,The objective of this study is to conduct a systematic review of the existing studies to assess effectiveness and safety of Liuzijue Qigong for the prevention or treatment of COPD in patients.,We will perform the comprehensive literature search in English and Chinese electronic database.,The publication period will be from inception to the search date.,In addition, the clinical trial registries, dissertations, informal publication, grey literature, reference lists of studies, systematic reviews, and conference abstracts will also be collected.,Two reviewers will identify relevant studies, extract data information, and then assess the methodical quality by the Cochrane risk of bias assessment tool.,Only randomized controlled trials comparing Liuzijue Qigong against other intervention or nonintervention will be included.,Data will be synthesized by either fixed-effect or random-effect model regarding to a heterogeneity test.,The routine lung function, arterial blood gas tensions, partial pressure of carbon dioxide, functional capacity, 30 seconds sit-to-stand test, respiratory function, maximal inspiration pressure, maximal expiratory pressure, airway resistance, and specific airway conductance will be assessed as primary outcomes.,The secondary outcomes involved dyspnea, and fatigue levels, respiratory muscle strength, upper and lower limb muscle strength, handgrip strength test, and health-related quality of life and safety.,Meta-analysis will be performed by using Cochrane's Review Manager software (version 5.3.5).,This systematic review and meta-analysis will provide a high-quality synthesis and evaluate the efficacy and safety based on current relevant literature evidence of Liuzijue Qigong intervention for COPD patient.,Our systematic review will provide evidence to determine whether Liuzijue Qigong is an effective and safe approach to prevention and treatment of COPD patients. | Pulmonary rehabilitation (PR) is able to improve dyspnea, endurance capacity, and health-related quality of life in chronic obstructive pulmonary disease (COPD) patients, but it is rarely used in China.,This study aimed to assess the effectiveness and safety of PR after exacerbation of COPD.,Patients admitted to hospital due to an exacerbation of COPD were randomized to receive either PR or routine care (control group).,The PR program was performed from the second day of admission until discharge.,The pre-post changes in 6-minute walk distance (6MWD), self-reported quality of life (QOL) assessed by CAT score and CRQ-SAS score, and activity of daily life assessed by ADL-D score were determined.,The perceived end-effort dyspnea (Borg scale) was measured throughout the study.,A total of 101 patients were enrolled, of whom 7 withdrew after randomization, and 94 completed this study.,There were 66 patients in the PR group and 28 in the control group.,The 6MWD, resting SpO2, and exercise Borg dyspnea score were significantly improved in the PR group.,In addition, the PR group had greater improvement in the total CRQ-SAS score and had a lower CAT score.,Significant improvements were also found in the ADL-D and BODE index in the PR group.,No adverse events were recorded during exercise.,Our study provides evidence that it is safe and feasible to apply an early PR in patients with acute exacerbation of COPD. | 1 |
Cognitive impairment has been found in chronic obstructive pulmonary disease (COPD) patients.,However, the structural alteration of the brain and underlying mechanisms are poorly understood.,Thirty-seven mild-to-moderate COPD patients, forty-eight severe COPD patients, and thirty-one control subjects were recruited for cognitive test and neuroimaging studies.,Serum levels of S100B,pulmonary function and arterial blood gas levels were also evaluated in each subject.,The hippocampal volume was significantly smaller in COPD patients compared to the control group.,It is positively correlated with a mini mental state examination (MMSE) score, SaO2 in mild-to-moderate COPD patients, the levels of PaO2 in both mild-to-moderate and severe COPD patients.,Higher S100B concentrations were observed in mild-to-moderate COPD patients, while the highest S100B level was found in severe COPD patients when compared to the control subjects.,S100B levels are negatively associated with MMSE in both mild-to-moderate and severe COPD patients and also negatively associated with the hippocampal volume in the total COPD patients.,Hippocampal atrophy based on quantitative assessment by magnetic resonance imaging does occur in COPD patients, which may be associated with cognitive dysfunction and the most prevalent mechanism accountable for hippocampal atrophy is chronic hypoxemia in COPD.,Higher serum S100B levels may be peripheral biochemical marker for cognitive impairment in COPD. | Previous studies have shown that COPD adversely affects distant organs and body systems, including the brain.,This pilot study aims to model the relationships between respiratory insufficiency and domains related to brain function, including low mood, subtly impaired cognition, systemic inflammation, and brain structural and neurochemical abnormalities.,Nine healthy controls were compared with 18 age- and education-matched medically stable COPD patients, half of whom were oxygen-dependent.,Measures included depression, anxiety, cognition, health status, spirometry, oximetry at rest and during 6-minute walk, and resting plasma cytokines and soluble receptors, brain MRI, and MR spectroscopy in regions relevant to mood and cognition.,ANOVA was used to compare controls with patients and with COPD subgroups (oxygen users [n = 9] and nonusers [n = 9]), and only variables showing group differences at p ≤ 0.05 were included in multiple regressions controlling for age, gender, and education to develop the final model.,Controls and COPD patients differed significantly in global cognition and memory, mood, and soluble TNFR1 levels but not brain structural or neurochemical measures.,Multiple regressions identified pathways linking disease severity with impaired performance on sensitive cognitive processing measures, mediated through oxygen dependence, and with systemic inflammation (TNFR1), related through poor 6-minute walk performance.,Oxygen desaturation with activity was related to indicators of brain tissue damage (increased frontal choline, which in turn was associated with subcortical white matter attenuation).,This empirically derived model provides a conceptual framework for future studies of clinical interventions to protect the brain in patients with COPD, such as earlier oxygen supplementation for patients with desaturation during everyday activities. | 1 |
There is much description in the literature of how patients with chronic obstructive pulmonary disease (COPD) manage their breathlessness and engage in self-care activities; however, little of this is from the perspective of those with less severe disease, who are primarily managed in primary care.,This study aimed to understand the self-care experiences of patients with COPD who are primarily managed in primary care, and to examine the challenges of engaging in such behaviors.,Semistructured interviews were carried out with 15 patients with COPD as part of a larger project evaluating a self-management intervention.,Thematic analysis was supported by NVivo software (version 8, QSR International, Melbourne, Australia).,Three main themes are described, ie, experiencing and understanding symptoms of COPD, current self-care activities, and the importance of family perceptions in managing COPD.,Self-care activities evolved spontaneously as participants experienced symptoms of COPD.,However, there was a lack of awareness about whether these strategies would impact upon symptoms.,Perceptions of COPD by family members posed a challenge to self-care for some participants.,Health care professionals should elicit patients’ prior disease experiences and utilize spontaneous attempts at disease management in future self-management.,These findings have implications for promoting self-management and enhancing quality of life. | The management of COPD is complex and patient adherence to treatment recommendations is known to be poor.,In this paper the methods used for evaluating adherence in COPD are compared.,Self-reporting has satisfactory reliability and offers a cheap, simple and easy method for assessing adherent behaviors.,Unlike the objective measures of adherence such as electronic monitoring, self-reporting helps in identifying the reasons for nonadherence, which in turn would be useful in addressing adherence issues.,Patients do not follow their treatment recommendations either intentionally or unintentionally.,Intentional deviations are driven by patient beliefs and experiences about illness and treatment, which are in turn influenced by social and cultural factors.,Unintentional deviations are often due to cognitive impairment and lack of routines.,Factors associated with adherence in COPD have been explained using the Becker-Maiman model.,Strategies for overcoming nonadherence have to be formulated based on the nature and reasons for nonadherence.,In the event of unintentional nonadherence, the use of adherence aids like Dosette boxes, calendar packs and reminders should be promoted.,Understanding patient beliefs and experiences, patient education focusing on the pathology of COPD and the role of treatment, periodic monitoring and reinforcement are critical for overcoming the barriers of intentional nonadherence. | 1 |
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 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. | 1 |
Patients with chronic airway lung diseases often experience depression and anxiety, but little information is available regarding Koreans with these conditions.,We thus assessed depression and anxiety in Korean patients with chronic airway lung diseases.,The degree of depression and anxiety in 84 outpatients with chronic obstructive pulmonary disease (COPD), 37 with asthma, 33 with bronchiectasis, and 73 healthy controls were evaluated by the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI).,The patients with COPD and bronchiectasis had higher BDI scores and were more likely than controls to experience depression ([COPD, 17; range, 0 to 42; prevalence, 55%], [bronchiectasis, 16; range, 3 to 51; prevalence, 55%], [controls, 13; range, 0 to 31; prevalence, 30%], p < 0.05).,The state-anxiety scores of the patients were higher than those of the controls, but only the bronchiectasis group demonstrated a higher frequency of state-anxiety compared with the controls (39 vs. 16%, patients vs. controls, p = 0.015).,Among all patients, 22% presented with concomitant depression and state-anxiety, and 25% demonstrated depression and trait-anxiety.,Depression was positively correlated with both state-anxiety (r = 0.644) and trait-anxiety (r = 0.597, p < 0.0001).,Irrespective of individual diagnosis, post-bronchodilator FEV1 (odds ratio [OR], 0.972; p = 0.027) and smoking history (OR, 3.894; p = 0.018) were independent risk factors for depression in patients with chronic airway lung diseases.,Chronic airway lung diseases are associated with depression and/or anxiety, particularly in those with a higher airflow limitation and/or history of smoking. | Recent reports indicate that over the next decade rates of chronic obstructive pulmonary disease (COPD) in women will exceed those in men in the western world, though in most jurisdictions, women continue to smoke less compared with men.,Whether female adult smokers are biologically more susceptible to COPD is unknown.,This study reviewed the available evidence to determine whether female adult smokers have a faster decline in forced expiratory volume in one second (FEV1) compared with male adult smokers and whether age modifies the relationship between cigarette smoke and lung function decline.,A systematic review and a meta-analysis was performed of population-based cohort studies that had a follow-up period of at least 3 years, measured FEV1 on at least two different time points, and presented FEV1 data stratified by gender and smoking status in adults.,Of the 646 potentially relevant articles, 11 studies met these criteria and were included in the analyses (N = 55 709 participants).,There was heterogeneity in gender-related results across the studies.,However, on average current smokers had a faster annual decline rate in FEV1% predicted compared with never and former smokers.,Female current smokers had with increasing age a significantly faster annual decline in FEV1% predicted than male current smokers (linear regression analysis, R2 = 0.56; p = 0.008).,Age did not materially affect the rate of decline in FEV1% predicted in male and female former and never smokers (p = 0.775 and p = 0.326, respectively).,As female smokers age, they appear to experience an accelerated decline in FEV1% predicted compared with male smokers.,Future research powered specifically on gender-related changes in lung function is needed to confirm these early findings. | 1 |
It has recently been proposed that the concept of clinical control in COPD may be useful for deciding treatment in COPD, but the original control criteria (OCC) were considered too restrictive.,Define and subsequently validate “modified” control criteria (MCC) of COPD.,Prospective observational study in COPD patients with a 1-year follow-up.,Control was defined as the presence of low clinical impact and clinical stability.,To evaluate clinical impact, the following clinical parameters were assessed: the degree of dyspnea, use of rescue medication, physical activity, and sputum color.,Stability was assessed by clinical changes and exacerbations in the last 3 months.,The COPD assessment test score and their changes were also evaluated as alternative control criteria.,To define the MCC, adjustment for disease severity using BODEx index (MCC-B) or FEV1 (MCC-F) was evaluated, and the best cutoff point was established.,Time to first combined event (emergency visit, hospitalization, or death) was analyzed to evaluate the predictive capacity of risk of the OCC, MCC-B, and MCC-F.,We included 265 patients, 224 (83.9%) men, with a mean age (±SD) of 68±9 years and FEV1 of 58%±17%.,The proportion of controlled patients was higher using clinical MCC-B or MCC-F (61.5% and 59.6%) than OCC (27.5%).,Similar percentages were found using COPD assessment test scores.,The time to the first combined event was significantly greater in controlled patients using MCC criteria (P<0.001, all cases).,The predictive capacity of risk was similar in MCC-B (c-statistic [C]=0.639) and MCC-F (C=0.637) and higher than OCC (C=0.589).,The new MCC identified a higher number of controlled COPD patients.,These patients have a better quality of life and lower risk of poor outcomes.,The concept of control and the new MCC could be a useful tool to optimize therapy. | Chronic obstructive pulmonary disease (COPD) exacerbations are associated with systemic consequences.,Data from a 4-year trial (Understanding Potential Long-term Impacts on Function with Tiotropium [UPLIFT®], n = 5,992) were used to determine risk for nonlower respiratory serious adverse events (NRSAEs) following an exacerbation.,Patients with ≥1 exacerbation were analyzed.,NRSAE incidence rates (incidence rate [IR], per 100 patient-years) were calculated for the 30 and 180 days before and after the first exacerbation.,NRSAEs were classified by diagnostic terms and organ classes.,Maentel-Haenszel rate ratios (RR) (pre- and postexacerbation onset) along with 95% confidence intervals (CI) were computed.,A total of 3,960 patients had an exacerbation.,The mean age was 65 years, forced expiratory volume in 1 s (FEV1) was 38% predicted, and 74% were men.,For all NRSAEs, the IRs 30 days before and after an exacerbation were 20.2 and 65.2 with RR (95% CI) = 3.22 (2.40-4.33).,The IRs for the 180-day periods were 13.2 and 31.0 with RR (95% CI) = 2.36 (1.93-2.87).,The most common NRSAEs by organ class for both time periods were cardiac, respiratory system (other), and gastrointestinal.,All NRSAEs as well as cardiac events were more common after the first exacerbation, irrespective of whether the patient had cardiac disease at baseline.,The findings confirm that, after exacerbations, serious adverse events in other organ systems are more frequent, particularly those that are cardiac in nature. | 1 |
Patient: Female, 69,Final Diagnosis: Chronic cavitation pulmonary aspergillosis,Symptoms: Shortness of breath • weight loss,Medication: -,Clinical Procedure: -,Specialty: Pulmonology,Challenging differential diagnosis,Aspergillus spores have the ability to affect patients with or without intact immune systems; because of this disease’s wide patient involvement it deserves a place on the differential diagnosis list, with endocarditis and tuberculosis, for those presenting with new pulmonary nodules or cavitation.,This case report involves the presentation, diagnosis, and treatment of a 69-year-old female who presented with new rapidly progressing cavitary lung lesions in the setting of copious administration of systemic steroid use.,Given the patient’s past history of alcoholism and environmental exposure, her case was not straight forward in regard to a diagnosis.,Ultimately, she was diagnosed with chronic cavity pulmonary aspergillosis in the setting of chronic immunosuppression secondary to systemic steroid administration.,Due to her convoluted medical history and the poor differential diagnosis list, there was a delay in final diagnosis.,This case report and clinical review aims to prevent anchoring when the patient’s presentation is not straight forward and aims to remind the clinician of the importance of a differential diagnosis. | The objective of the study was to determine whether the cadmium-derived materials induce intracellular protein citrullination.,Human A549 lung epithelial cells were exposed to cadmium in soluble and nanoparticulate forms represented by cadmium chloride (CdCl2) and cadmium oxide (CdO), respectively, and their combinations with ultrafine carbon black (ufCB) produced by high temperature combustion, imitating cigarette burning.,Protein citrullination in cell lysates was analyzed by Western immunoblotting and verified by immunofluorescent confocal microscopy.,Target citrullinated proteins were identified by proteomic analysis.,CdO, ufCB and its combination with CdCl2 and CdO after high temperature combustion induced protein citrullination in cultured human lung epithelial cells, as detected by immunoblotting with anti-citrullinated protein antibody.,Cytokeratins of type II (1, 2, 5, 6A, 6B and 77) and type I (9, 10) were identified as major intracellular citrullination targets.,Immunofluorescent staining confirmed the localization of citrullinated proteins both in the cytoplasm and cell nuclei.,Cadmium oxide nanoparticle exposure facilitated post-translational citrullination of proteins. | 1 |
Lung hyperinflation and exercise intolerance are hallmarks of chronic obstructive pulmonary disease (COPD).,However, their relationship remains uncertain.,A combined analysis of two placebo-controlled, randomized studies examined the effects of the long-acting muscarinic antagonist umeclidinium (UMEC) and long-acting β2-agonist vilanterol (VI) separately and in combination on static hyperinflation, exercise endurance time (EET), and their relationship in patients with COPD.,Patients with moderate-to-severe stable COPD and resting functional residual capacity >120% predicted were randomized to UMEC/VI 62.5/25 μg, UMEC 62.5 μg, VI 25 μg, or placebo for 12 weeks.,Inspiratory capacity (IC), residual volume (RV), total lung capacity (TLC), and EET in an endurance shuttle-walk test were measured.,In this post hoc analysis, IC/TLC, RV/TLC, and IC were used as hyperinflation markers.,After 12 weeks, UMEC/VI and UMEC and VI showed significant improvements in hyperinflation versus placebo when measured by absolute change from baseline in IC/TLC (trough and 3 hours postdose [P≤0.011]).,UMEC/VI showed significant improvements versus UMEC and VI in absolute changes in IC/TLC (trough and 3 hours postdose [P≤0.001]).,Statistical significance for comparisons with placebo and between treatments for absolute changes in IC and percentage changes in RV/TLC followed similar patterns to those for absolute changes in IC/TLC.,UMEC/VI showed significant improvements in EET versus placebo at day 2 and week 12, measured as change from baseline in seconds (P≤0.002) and as a percentage from baseline (P≤0.005).,There was a lack of evidence to suggest a correlation between improvements in static hyperinflation and EET at any time point.,Although the dual bronchodilator UMEC/VI demonstrated greater improvements in static hyperinflation markers than UMEC or VI and significant improvements in exercise endurance, no direct relationship was observed between static hyperinflation and exercise endurance. | Reducing rescue medication use is a guideline-defined goal of asthma treatment, however, little is known about the validity of rescue medicine use as a marker of symptoms in chronic obstructive pulmonary disease (COPD).,To improve patient outcomes, greater insight is needed into the relationship between rescue medication use and alternative COPD outcomes.,A systematic search of electronic databases (Embase®, MEDLINE® and Cochrane CENTRAL) was conducted from database start to 26 May, 2015.,Studies of bronchodilator therapy with a duration of ≥24 weeks were included if they reported either mean change from baseline (CFB) in rescue medication use in puffs/day or % rescue-free days (%RFD), and at least one other COPD endpoint.,Correlation and meta-regression analyses were undertaken to test the association between rescue medication use and other COPD outcomes using weighted means (weights proportional to the sample size of the treatment group) and unweighted means (equal weight for each treatment group).,Each association was assessed at 6 months and study end.,Forty-six studies involving 46,531 patients provided mean data from 145 treatment groups for evaluation.,Changes in both measures of rescue medication use were correlated with changes in trough forced expiratory volume in one second ([FEV1]; Pearson correlation coefficients |r| ≥ 0.63; p < 0.0001) and with St George’s Respiratory Questionnaire (SGRQ) score (|r| ≥ 0.70; p < 0.0001) at study end.,Change in rescue medication use in puffs/day during the study correlated with annualized rates of moderate/severe exacerbations at 6 months and study end (both r = 0.66; p ≤ 0.0028).,CFB in puffs/day was not well correlated with Transition Dyspnoea Index (TDI), but %RFD did correlate with TDI score at 6 months and study end (both r = 0.69; p < 0.0001).,The values for CFB in puffs/day corresponding to the proposed minimal clinically important differences for trough FEV1 and SGRQ score were -1.3 and -0.6 puffs/day, respectively.,A -1.0 puffs/day CFB in rescue use corresponded to a change of 0.26 events/patient-year in moderate/severe exacerbations.,This analysis provides clear evidence of associations at a patient group level between rescue medication use and other clinically important COPD outcomes.,The online version of this article (doi:10.1186/s12931-017-0566-1) contains supplementary material, which is available to authorized users. | 1 |
Comorbidities are associated with the severity of coronavirus disease 2019 (COVID‐19).,This meta‐analysis aimed to explore the risk of severe COVID‐19 in patients with pre‐existing chronic obstructive pulmonary disease (COPD) and ongoing smoking history.,A comprehensive systematic literature search was carried out to find studies published from December 2019 to 22 March 2020 from five databases.,The languages of literature included English and Chinese.,The point prevalence of severe COVID‐19 in patients with pre‐existing COPD and those with ongoing smoking was evaluated with this meta‐analysis.,Overall 11 case series, published either in Chinese or English language with a total of 2002 cases, were included in this study.,The pooled OR of COPD and the development of severe COVID‐19 was 4.38 (fixed‐effects model; 95% CI: 2.34‐8.20), while the OR of ongoing smoking was 1.98 (fixed‐effects model; 95% CI: 1.29‐3.05).,There was no publication bias as examined by the funnel plot and Egger's test (P = not significant).,The heterogeneity of included studies was moderate for both COPD and ongoing smoking history on the severity of COVID‐19.,COPD and ongoing smoking history attribute to the worse progression and outcome of COVID‐19. | Hospitalisation due to acute exacerbations of COPD (AECOPD) is common, and subsequent mortality high.,The DECAF score was derived for accurate prediction of mortality and risk stratification to inform patient care.,We aimed to validate the DECAF score, internally and externally, and to compare its performance to other predictive tools.,The study took place in the two hospitals within the derivation study (internal validation) and in four additional hospitals (external validation) between January 2012 and May 2014.,Consecutive admissions were identified by screening admissions and searching coding records.,Admission clinical data, including DECAF indices, and mortality were recorded.,The prognostic value of DECAF and other scores were assessed by the area under the receiver operator characteristic (AUROC) curve.,In the internal and external validation cohorts, 880 and 845 patients were recruited.,Mean age was 73.1 (SD 10.3) years, 54.3% were female, and mean (SD) FEV1 45.5 (18.3) per cent predicted.,Overall mortality was 7.7%.,The DECAF AUROC curve for inhospital mortality was 0.83 (95% CI 0.78 to 0.87) in the internal cohort and 0.82 (95% CI 0.77 to 0.87) in the external cohort, and was superior to other prognostic scores for inhospital or 30-day mortality.,DECAF is a robust predictor of mortality, using indices routinely available on admission.,Its generalisability is supported by consistent strong performance; it can identify low-risk patients (DECAF 0-1) potentially suitable for Hospital at Home or early supported discharge services, and high-risk patients (DECAF 3-6) for escalation planning or appropriate early palliation.,UKCRN ID 14214. | 1 |
Randomized, controlled trials comparing long-acting muscarinic antagonist (LAMA) efficacy in COPD are limited.,This network meta-analysis (NMA) assessed the relative efficacy of tiotropium 18 µg once-daily (OD) and newer agents (aclidinium 400 µg twice-daily, glycopyrronium 50 µg OD, and umeclidinium 62.5 µg OD).,A systematic literature review identified randomized, controlled trials of adult COPD patients receiving LAMAs.,A NMA within a Bayesian framework examined change from baseline in trough forced expiratory volume in 1 second (FEV1), transitional dyspnea index focal score, St George’s Respiratory Questionnaire score, and rescue medication use.,Twenty-four studies (n=21,311) compared LAMAs with placebo/each other.,Aclidinium, glycopyrronium, tiotropium, and umeclidinium, respectively, demonstrated favorable results versus placebo, for change from baseline (95% credible interval) in 12-week trough FEV1 (primary endpoint: 101.40 mL [77.06-125.60]; 117.20 mL [104.50-129.90]; 114.10 mL [103.10-125.20]; 136.70 mL [104.20-169.20]); 24-week trough FEV1 (128.10 mL [84.10-172.00]; 135.80 mL [123.10-148.30]; 106.40 mL [95.45-117.30]; 115.00 mL [74.51-155.30]); 24-week St George’s Respiratory Questionnaire score (−4.60 [−6.76 to −2.54]; −3.14 [−3.83 to −2.45]; −2.43 [−2.92 to −1.93]; −4.69 [−7.05 to −2.31]); 24-week transitional dyspnea index score (1.00 [0.41-1.59]; 1.01 [0.79-1.22]; 0.82 [0.62-1.02]; 1.00 [0.49-1.51]); and 24-week rescue medication use (data not available; −0.41 puffs/day [−0.62 to −0.20]; −0.52 puffs/day [−0.74 to −0.30]; −0.30 puffs/day [−0.81 to 0.21]).,For 12-week trough FEV1, differences in change from baseline (95% credible interval) were −12.8 mL (−39.39 to 13.93), aclidinium versus tiotropium; 3.08 mL (−7.58 to 13.69), glycopyrronium versus tiotropium; 22.58 mL (−11.58 to 56.97), umeclidinium versus tiotropium; 15.90 mL (−11.60 to 43.15), glycopyrronium versus aclidinium; 35.40 mL (−5.06 to 76.07), umeclidinium versus aclidinium; and 19.50 mL (−15.30 to 54.38), umeclidinium versus glycopyrronium.,Limitations included inhaler-related factors and safety; longer-term outcomes were not considered.,The new LAMAs studied had at least comparable efficacy to tiotropium, the established class standard.,Choice should depend on physician’s and patient’s preference. | The aims of this study were: (1) to compare the discriminative ability of a disease-specific instrument, the St.,George's Respiratory Questionnaire (SGRQ) to generic instruments (i.e., EQ-5D and SF-36); and (2), to evaluate the strength of associations among clinical and health-related quality of life (HRQL) measures in chronic obstructive pulmonary disease (COPD).,We analyzed data collected from 120 COPD patients in a Veterans Affairs hospital.,Patients self-completed two generic HRQL measures (EQ-5D and SF-36) and the disease-specific SGRQ.,The ability of the summary scores of these HRQL measures to discriminate COPD disease severity based on Global Obstructive Lung Disease (GOLD) stage was assessed using relative efficiency ratios (REs).,Strength of correlation was used to further evaluate associations between clinical and HRQL measures.,Mean total scores for PCS-36, EQ-VAS and SGRQ were significantly lower for the more severe stages of COPD (p < 0.05).,Using SGRQ total score as reference, the summary scores of the generic measures (PCS-36, MCS-36, EQ index, and EQ-VAS) all had REs of <1.,SGRQ exhibited a stronger correlation with clinical measures than the generic summary scores.,For instance, SGRQ was moderately correlated with FEV1 (r = 0.43), while generic summary scores had trivial levels of correlation with FEV1 (r < 0.2).,The SGRQ demonstrated greater ability to discriminate among different levels of severity stages of COPD than generic measures of health, suggestive that SGRQ may provide COPD studies with greater statistical power than EQ-5D and SF-36 summary scores to capture meaningful differences in clinical severity. | 1 |
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. | Chronic obstructive pulmonary disease (COPD) is a multicomponent disorder that leads to substantial disability, impaired quality of life, and increased mortality.,Although the majority of COPD patients are first diagnosed and treated in primary care practices, there is comparatively little information on the management of COPD patients in primary care.,A web-based pilot survey was conducted to evaluate the primary care physician’s, or general practitioner’s (GP’s), knowledge, understanding, and management of COPD in twelve territories across the Asia-Pacific region, Africa, eastern Europe, and Latin America, using a 10-minute questionnaire comprising 20 questions and translated into the native language of each participating territory.,The questionnaire was administered to a total of 600 GPs (50 from each territory) involved in the management of COPD patients and all data were collated and analyzed by an independent health care research consultant.,This survey demonstrated that the GPs’ understanding of COPD was variable across the territories, with large numbers of GPs having very limited knowledge of COPD and its management.,A consistent finding across all territories was the underutilization of spirometry (median 26%; range 10%-48%) and reliance on X-rays (median 14%; range 5%-22%) for COPD diagnosis, whereas overuse of blood tests (unspecified) was particularly high in Russia and South Africa.,Similarly, there was considerable underrecognition of the importance of exacerbation history as an important factor of COPD and its initial management in most territories (median 4%; range 0%-22%).,Management of COPD was well below guideline-recommended levels in most of the regions investigated.,The findings of this survey suggest there is a need for more ongoing education and information, specifically directed towards GPs outside of Europe and North America, and that global COPD guidelines appear to have limited reach and application in most of the areas studied. | 1 |
The morphologic alterations of pulmonary small vessels measured by computed tomography (CT) have been used to evaluate chronic obstructive pulmonary disease (COPD).,However, the relationship between small pulmonary vascular alteration and acute exacerbations of COPD (AECOPD) is not well understood.,The aim of this study was to evaluate the cross-sectional area (CSA) of small pulmonary vessel alterations measured on CT images and investigate its relationship with the COPD severity staged by the degree of airflow limitation and the occurrence of AECOPD.,We retrospectively reviewed CT scans, clinical characteristics, and pulmonary function test results of 153 patients with COPD.,All the patients were divided into AECOPD and non-AECOPD group according to the COPD staging and pulmonary function test results.,The percentages of the total CSA less than 5 mm2 and equal to 5-10 mm2 over the lung area (%CSA<5 and %CSA5-10, respectively) were measured.,The %CSA<5 steadily decreased in relation to the increase of COPD severity.,In addition, %CSA<5 of the AECOPD group was significantly lower than that of the non-AECOPD group (0.41±0.13 versus 0.68±0.18, P<0.001), and the optimal cutoff value was 0.56 (sensitivity, 0.863; specificity, 0.731).,Therefore, small pulmonary vascular alteration, as measured by %CSA<5, could indicate not only the degree of COPD severity, but also the occurrence of AECOPD. | There is controversy regarding the significance of radiological consolidation in the context of COPD exacerbation (eCOPD).,While some studies into eCOPD exclude these cases, consolidation is a common feature of eCOPD admissions in real practice.,This study aims to address the question of whether consolidation in eCOPD is a distinct clinical phenotype with implications for management decisions and outcomes.,The European COPD Audit was carried out in 384 hospitals from 13 European countries between 2010 and 2011 to analyze guideline adherence in eCOPD.,In this analysis, admissions were split according to the presence or not of consolidation on the admission chest radiograph.,Groups were compared in terms of clinical and epidemiological features, existing treatment, clinical care utilized and mortality.,14,111 cases were included comprising 2,714 (19.2%) with consolidation and 11,397 (80.8%) without.,The risk of radiographic consolidation increased with age, female gender, cardiovascular diseases, having had two or more admissions in the previous year, and sputum color change.,Previous treatment with inhaled steroids was not associated.,Patients with radiographic consolidation were significantly more likely to receive antibiotics, oxygen and non-invasive ventilation during the admission and had a lower survival from admission to 90-day follow-up.,Patients admitted for COPD exacerbation who have radiological consolidation have a more severe illness course, are treated more intensively by clinicians and have a poorer prognosis.,We recommend that these patients be considered a distinct subset in COPD exacerbation. | 1 |
Background: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in China.,Although numerous studies have been conducted to determine the risk factors for COPD mortality such as ambient air pollution, the results are not fully consistent.,Methods: This study included mortality analysis and a case-control design by using the data extracted from the Mortality Registration System in Jiading District, Shanghai.,Traditional logistic regression, geographically weighted logistic regression (GWLR), and spatial scan statistical analysis were performed to explore the geographic variation of COPD mortality and the possible influencing factors.,Results: Traditional logistic regression showed that extreme lower temperature in the month prior to death, shorter distance to highway, lower GDP level were associated with increased COPD mortality.,GWRL model further demonstrated obvious geographical discrepancies for the above associations.,We additionally identified a significant cluster of low COPD mortality (OR = 0.36, P = 0.002) in the southwest region of Jiading District with a radius of 3.55 km by using the Bernoulli model.,The geographical variation in age-standardized mortality rate for COPD in Jiading District was explained to a certain degree by these factors.,Conclusion: The risk of COPD mortality in Jiading District showed obvious geographical variation, which were partially explained by the geographical variations in effects of the extreme low temperature in the month prior to death, residential proximity to highway, and GDP level. | 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. | 1 |
Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | 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. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality.,COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation.,They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation.,Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations.,Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations.,Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials.,The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD. | Bacteria are isolated in more than 50% of exacerbations of chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD).,The most prevalent respiratory pathogens include Gram-positive (Streptococcus pneumoniae) and Gram-negative (Haemophilus influenzae, Moraxella catarrhalis) microorganims.,Moxifloxacin is a fourth-generation fluoroquinolone that has been shown to be effective against respiratory pathogens, including atypicals and those resistant to most common antibiotics.,The bioavailability and half-life of moxifloxacin provides potent bactericidal effects at a dose of 400 mg once daily.,Among the fluoroquinolones, the ratio of the area under the concentration-time curve (AUC) to minimal inhibitory concentration of moxifloxacin is the highest against S. pneumoniae.,Moxifloxacin has demonstrated better eradication in exacerbations of CB and COPD compared with standard therapy, in particular, with macrolides.,Patients treated with moxifloxacin showed a prolonged time to the next exacerbation and observational studies suggest that moxifloxacin induces a faster release of symptoms of exacerbation.,Some guidelines recommend the use of moxifloxacin as first-line therapy in bacterial exacerbations in patients with moderate to severe COPD and in patients with mild COPD with risk factors.,The current article reviews the use of moxifloxacin in bacterial exacerbations of CB and COPD. | 1 |
Acute COPD exacerbations account for much of the rising disability and costs associated with COPD, but data on predictive risk factors are limited.,The goal of the current study was to develop a robust, clinically based model to predict frequent exacerbation risk.,Patients identified from the Optimum Patient Care Research Database (OPCRD) with a diagnostic code for COPD and a forced expiratory volume in 1 second/forced vital capacity ratio <0.7 were included in this historical follow-up study if they were ≥40 years old and had data encompassing the year before (predictor year) and year after (outcome year) study index date.,The data set contained potential risk factors including demographic, clinical, and comorbid variables.,Following univariable analysis, predictors of two or more exacerbations were fed into a stepwise multivariable logistic regression.,Sensitivity analyses were conducted for subpopulations of patients without any asthma diagnosis ever and those with questionnaire data on symptoms and smoking pack-years.,The full predictive model was validated against 1 year of prospective OPCRD data.,The full data set contained 16,565 patients (53% male, median age 70 years), including 9,393 patients without any recorded asthma and 3,713 patients with questionnaire data.,The full model retained eleven variables that significantly predicted two or more exacerbations, of which the number of exacerbations in the preceding year had the strongest association; others included height, age, forced expiratory volume in 1 second, and several comorbid conditions.,Significant predictors not previously identified included eosinophilia and COPD Assessment Test score.,The predictive ability of the full model (C statistic 0.751) changed little when applied to the validation data set (n=2,713; C statistic 0.735).,Results of the sensitivity analyses supported the main findings.,Patients at risk of exacerbation can be identified from routinely available, computerized primary care data.,Further study is needed to validate the model in other patient populations. | Data examining the characteristics of patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD) and associated hospitalisations and mortality are scarce.,Post-hoc analysis of the Prevention Of Exacerbations with Tiotropium in COPD (POET-COPD) trial, targeting exacerbations as the primary endpoint.,Patients were classified as non-, infrequent, and frequent exacerbators (0, 1, or ≥ 2 exacerbations during study treatment), irrespective of study treatment.,A multivariate Cox regression model assessed the effect of covariates on time to first exacerbation.,In total, 7376 patients were included in the analysis: 63.5% non-exacerbators, 22.9% infrequent, 13.6% frequent exacerbators.,Factors significantly associated with exacerbation risk were age, sex, body mass index, COPD duration and severity, smoking history, baseline inhaled corticosteroid use, and preceding antibiotic or systemic corticosteroid courses.,Frequent exacerbators had greater severity and duration of COPD, received more pulmonary medication, and ≥ 2 systemic corticosteroid or antibiotic courses in the preceding year, and were more likely to be female and ex-smokers.,The small proportion of frequent exacerbators (13.6%) accounted for 56.6% of exacerbation-related hospitalisations, which, overall, were associated with a three-fold increase in mortality.,The frequent exacerbator phenotype was closely associated with exacerbation-related hospitalisations, and exacerbation-related hospitalisations were associated with poorer survival.,NCT00563381; Study identifier: BI 205.389. | 1 |
Skeletal muscle weakness in chronic obstructive pulmonary disease (COPD) carries a poor prognosis, therefore a non-invasive marker of this process could be useful.,Reduced expression of muscle-specific microRNA (myomiRs) in quadriceps muscle in patients with COPD is associated with skeletal muscle weakness and changes in muscle fibre composition.,Circulating exosomal miRNAs can be measured in blood, making them candidate biomarkers of biopsy phenotype.,To determine whether plasma myomiR levels were associated with fibre size or fibre proportion, we measured myomiRs in plasma from patients with COPD and healthy controls.,103 patients with COPD and 25 age-matched controls were studied.,Muscle-specific miRNA was elevated in the plasma of patients with COPD and showed distinct patterns.,Specifically, miR-1 was inversely associated with fat-free mass in the cohort, whereas levels of miR-499 were more directly associated with strength and quadriceps type I fibre proportion.,Two miRs not restricted to muscle in origin (miR-16 and miR-122) did not differ between patients and controls.,Plasma miR-499 was also associated with muscle nuclear factor κB p50 but not p65 in patients with early COPD whereas plasma inflammatory cytokines were associated with miR-206 in patients with more advanced disease.,Plasma levels of individual myomiRs are altered in patients with COPD but alone do not predict muscle fibre size or proportion.,Our findings are consistent with an increase in muscle wasting and turnover associated with the development of skeletal muscle dysfunction and fibre-type shift in patients with stable COPD. | Muscle atrophy confers a poor prognosis in patients with chronic obstructive pulmonary disease (COPD), yet the molecular pathways responsible are poorly characterised.,Muscle-specific microRNAs and serum response factor (SRF) are important regulators of muscle phenotype that contribute to a feedback system to regulate muscle gene expression.,The role of these factors in the skeletal muscle dysfunction that accompanies COPD is unknown.,31 patients with COPD and 14 healthy age-matched controls underwent lung and quadriceps function assessments, measurement of daily activity and a percutaneous quadriceps muscle biopsy.,The expression of muscle-specific microRNAs, myosin heavy chains and components of the serum response factor signalling pathway were determined by qPCR.,A reduction in expression of miR-1 (2.5-fold, p=0.01) and the myocardin-related transcription factors (MRTFs) A and B was observed in patients compared with controls (MRTF-A mRNA: twofold, p=0.028; MRTF-B mRNA: fourfold, p=0.011). miR-1 expression was associated with smoking history, lung function, fat-free mass index, 6 min walk distance and percentage of type 1 fibres. miR-133 and miR-206 were negatively correlated with daily physical activity.,Insulin-like growth factor 1 mRNA was increased in the patients and miR-1 was negatively correlated with phosphorylation of the kinase Akt.,Furthermore, the protein levels of histone deacetylase 4, another miR-1 target, were increased in the patients.,Downregulation of the activity of the MRTF-SRF axis and the expression of muscle-specific microRNAs, particularly miR-1, may contribute to COPD-associated skeletal muscle dysfunction. | 1 |
Childhood asthma is strongly influenced by genetics and is a risk factor for reduced lung function and chronic obstructive pulmonary disease (COPD) in adults.,This study investigates self-reported childhood asthma in adult smokers from the COPDGene Study.,We hypothesize that childhood asthma is associated with decreased lung function, increased risk for COPD, and that a genome-wide association study (GWAS) will show association with established asthma variants.,We evaluated current and former smokers ages 45-80 of non-Hispanic white (NHW) or African American (AA) race.,Childhood asthma was defined by self-report of asthma, diagnosed by a medical professional, with onset at < 16 years or during childhood.,Subjects with a history of childhood asthma were compared to those who never had asthma based on lung function, development of COPD, and genetic variation.,GWAS was performed in NHW and AA populations, and combined in meta-analysis.,Two sets of established asthma SNPs from published literature were examined for association with childhood asthma.,Among 10,199 adult smokers, 730 (7%) reported childhood asthma and 7493 (73%) reported no history of asthma.,Childhood asthmatics had reduced lung function and increased risk for COPD (OR 3.42, 95% CI 2.81-4.18).,Genotype data was assessed for 8031 subjects.,Among NHWs, 391(7%) had childhood asthma, and GWAS identified one genome-wide significant association in KIAA1958 (rs59289606, p = 4.82 × 10− 8).,Among AAs, 339 (12%) had childhood asthma.,No SNPs reached genome-wide significance in the AAs or in the meta-analysis combining NHW and AA subjects; however, potential regions of interest were identified.,Established asthma SNPs were examined, seven from the NHGRI-EBI database and five with genome-wide significance in the largest pediatric asthma GWAS.,Associations were found in the current childhood asthma GWAS with known asthma loci in IL1RL1, IL13, LINC01149, near GSDMB, and in the C11orf30-LRRC32 region (Bonferroni adjusted p < 0.05 for all comparisons).,Childhood asthmatics are at increased risk for COPD.,Defining asthma by self-report is valid in populations at risk for COPD, identifying subjects with clinical and genetic characteristics known to associate with childhood asthma.,This has potential to improve clinical understanding of asthma-COPD overlap (ACO) and enhance future research into ACO-specific treatment regimens.,ClinicalTrials.gov, NCT00608764 (Active since January 28, 2008).,The online version of this article (10.1186/s12931-018-0890-0) contains supplementary material, which is available to authorized users. | Pulmonary inflammation, oxidants-antioxidants imbalance, as well as innate and adaptive immunity have been proposed as playing a key role in the development of COPD.,The role of vitamins, as assessed either by food frequency questionnaires or measured in serum levels, have been reported to improve pulmonary function, reduce exacerbations and improve symptoms.,Vitamin supplements have therefore been proposed to be a potentially useful additive to COPD therapy.,A systematic literature review was performed on the association of vitamins and COPD.,The role of vitamin supplements in COPD was then evaluated.,The results of this review showed that various vitamins (vitamin C, D, E, A, beta and alpha carotene) are associated with improvement in features of COPD such as symptoms, exacerbations and pulmonary function.,High vitamin intake would probably reduce the annual decline of FEV1.,There were no studies that showed benefit from vitamin supplementation in improved symptoms, decreased hospitalization or pulmonary function. | 1 |
The tradition classification of the severity of COPD, based on spirometry, fails to encompass the heterogeneity of the disease.,The COPD assessment test (CAT), a multi-dimensional, patient-filled questionnaire, assesses the overall health status of patients, and is recommended as part of the assessment of individuals with COPD.,However, information regarding the range of values for the test in a non-COPD population (normative values) is limited, and consequently, knowledge regarding the optimal cut-off, and the minimum clinically important difference (MCID) for the test remain largely empirical.,CanCOLD is a population-based multi-center cohort study conducted across Canada, the methodology of which is based on the international BOLD initiative.,The study includes subjects with COPD, at-risk individuals who smoke, and healthy control subjects.,CAT questionnaires were administered at baseline to all subjects.,Among non-COPD subjects, normative values for the CAT questionnaire, and psychometric properties of the test were characterized.,Predictors of high CAT scores were identified using multivariable logistic regression.,Of the 525 non-COPD subjects enrolled, 500 were included in the analysis.,Mean FEV1/FVC ratio among the 500 included subjects was 0.77 (SD 0.49); the mean predicted FEV1 was 99.38% (SD 16.88%).,The overall mean CAT score was 6 (SD 5.09); scores were higher among females (6.43, SD 5.59), and subjects over 80 years of age (mean 7.58, SD 6.82).,Cronbach alpha for the CAT was 0.79, suggesting a high internal consistency for the test.,A score of 16 was the 95th percentile for the population, and 27 subjects (5.4%) were found to have a CAT score > =16.,Current smoking (aOR 3.41, 95% CI 1.05, 11.02), subject-reported physician-diagnosed asthma (aOR 7.59, 95% CI 2.71, 21.25) and musculoskeletal disease (aOR 4.09, 95% CI 1.72, 9.71) were found to be significantly associated with a score ≥16.,The characterization of CAT scores in the general population will be useful for norm-based comparisons.,Longitudinal follow-up of these subjects will help in the optimization of cut-offs for the test. | Chronic obstructive pulmonary disease (COPD) is a health problem that is becoming increasingly attended-to in Primary Care (PC).,However, there is a scarcity of health-care programs and studies exploring the implementation of Clinical Practice Guidelines (CPG).,The principal objective of the present study is to evaluate the effectiveness of a combined strategy directed towards health-care professionals and patients to improve the grade of clinical control and the quality-of-life (QoL) of the patients via a feedback on their state-of-health.,A training plan for the health-care professionals is based on CPG and health education.,Multi-centred, before-after, quasi experimental, prospective study involving an intervention group and a control group of individuals followed-up for 12 months.,The patients receive attention from urban and semi-urban Primary Care Centres (PCC) within the administrative area of the Costa de Ponent (near Barcelona).,All the pacients corresponding to the PCC of one sub-area were assigned to the intervention group and patients from the rest of sub-areas to the group control.,The intervention includes providing data to the health-care professionals (clinician/nurse) derived from a clinical history and an interview.,A course of training focused on aspects of CPG, motivational interview and health education (tobacco, inhalers, diet, physical exercise, physiotherapy).,The sample random includes a total of 801 patients (≥ 40 years of age), recorded as having COPD, receiving attention in the PCC or at home, who have had at least one clinical visit, and who provided written informed consent to participation in the study.,Data collected include socio-demographic characteristics, drug treatment, exacerbations and hospital admissions, evaluation of inhaler use, tobacco consumption and life-style and health-care resources consumed.,The main endpoints are dyspnoea, according to the modified scale of the Medical Research Council (MRC) and the QoL, evaluated with the St George's Respiratory Questionnaire (SGRQ).,The variables are obtained at the start and the end of the intervention.,Information from follow-up visits focuses on the changes in life-style activities of the patient.,This study is conducted with the objective of generating evidence that shows that implementation of awareness programs directed towards health-care professionals as well as patients in the context of PC can produce an increase in the QoL and a decrease in the disease exacerbation, compared to standard clinical practice.,Clinical Trials.gov Identifier: NCT00922545; | 1 |
Drug development in chronic obstructive pulmonary disease (COPD) has been characterised by unacceptably high failure rates.,In addition to the poor sensitivity in forced expiratory volume in one second (FEV1), numerous causes are known to contribute to this phenomenon, which can be clustered into drug-, disease- and design-related factors.,Here we present a model-based approach to describe disease progression, treatment response and dropout in clinical trials with COPD patients.,Data from six phase II trials lasting up to 6 months were used.,Disease progression (trough FEV1 measurements) was modelled by a time-varying function, whilst the treatment effect was described by an indirect response model.,A time-to-event model was used for dropout,All relevant parameters were characterised with acceptable precision.,Two parameters were necessary to model the dropout patterns, which was found to be partly linked to the treatment failure.,Disease severity at baseline, previous use of corticosteroids, gender and height were significant covariates on disease baseline whereas disease severity and reversibility to salbutamol/salmeterol were significant covariates on Emax for salmeterol active arm.,Incorporation of the various interacting factors into a single model will offer the basis for patient enrichment and improved dose rationale in COPD.,The online version of this article (doi:10.1007/s11095-014-1490-4) contains supplementary material, which is available to authorized users. | Patients with chronic obstructive pulmonary disease (COPD) can experience 'exacerbations' of their conditions.,An exacerbation is an event defined in terms of subjective descriptors or symptoms, namely dyspnoea, cough and sputum that worsen sufficiently to warrant a change in medical management.,There is a need for reliable markers that reflect the pathological mechanisms that underlie exacerbation severity and that can be used as a surrogate to assess treatment effects in clinical studies.,Little is known as to how existing study variables and suggested markers change in both the stable and exacerbation phases of COPD.,In an attempt to find the best surrogates for exacerbations, we have reviewed the literature to identify which of these markers change in a consistent manner with the severity of the exacerbation event.,We have searched standard databases between 1966 to July 2004 using major keywords and terms.,Studies that provided demographics, spirometry, potential markers, and clear eligibility criteria were included in this study.,Central tendencies and dispersions for all the variables and markers reported and collected by us were first tabulated according to sample size and ATS/ERS 2004 Exacerbation Severity Levels I to III criteria.,Due to the possible similarity of patients in Levels II and III, the data was also redefined into categories of exacerbations, namely out-patient (Level I) and in-patient (Levels II & III combined).,For both approaches, we performed a fixed effect meta-analysis on each of the reported variables.,We included a total of 268 studies reported between 1979 to July 2004.,These studies investigated 142,407 patients with COPD.,Arterial carbon dioxide tension and breathing rate were statistically different between all levels of exacerbation severity and between in out- and in-patient settings.,Most other measures showed weak relationships with either level or setting, or they had insufficient data to permit meta-analysis.,Arterial carbon dioxide and breathing rate varied in a consistent manner with exacerbation severity and patient setting.,Many other measures showed weak correlations that should be further explored in future longitudinal studies or assessed using suggested mathematical modelling techniques.,The online version of this article (doi:10.1186/1465-9921-7-74) contains supplementary material, which is available to authorized users. | 1 |
The study aimed to explore the correlations of long non‐coding RNA MALAT1 (lncRNA MALAT1) and its targets microRNA (miR)‐125b, miR‐133, miR‐146a, and miR‐203 with acute exacerbation risk, inflammation, and disease severity of chronic obstructive pulmonary disease (COPD).,Plasma samples were obtained from 120 acute exacerbation COPD (AECOPD) patients, 120 stable COPD patients, and 120 healthy controls (HCs).,RT‐qPCR was conducted to detect lncRNA MALAT1 expression and its target miRNAs, and ELISA was performed to detect the inflammatory cytokines.,LncRNA MALAT1 was highest in AECOPD patients followed by stable COPD patients and then HCs, which distinguished AECOPD patients from HCs (AUC: 0.969, 95% CI: 0.951‐0.987) and stable COPD patients (AUC: 0.846, 95% CI: 0.798‐0.894).,Furthermore, lncRNA MALAT1 positively correlated with GOLD stage in both AECOPD and stable COPD patients.,Regarding inflammatory cytokines, lncRNA MALAT1 positively correlated with tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1β, IL‐6, IL‐8, IL‐17, and IL‐23 in both AECOPD and stable COPD patients.,Besides, lncRNA MALAT1 negatively correlated with miR‐125b, miR‐146a, and miR‐203 in AECOPD patients and reversely correlated with miR‐125b and miR‐146a in stable COPD patients.,Notably, miR‐125b, miR‐133, miR‐146a, and miR‐203 were the lowest in AECOPD patients, followed by stable COPD patients, and then HCs; miR‐125b, miR‐133, miR‐146a, and miR‐203 negatively correlated with inflammation and GOLD stage in AECOPD and stable COPD patients.,LncRNA MALAT1 exhibits clinical implications in acute exacerbation risk prediction and management of COPD via the inner‐correlation with its targets miR‐125b, miR‐146a, and miR‐203. | Chronic obstructive pulmonary disease (COPD) significantly increases the risk of developing cancer.,Biomarker studies frequently follow a case-control set-up in which patients diagnosed with a disease are compared to controls.,Longitudinal cohort studies such as the COPD-centered German COPD and SYstemic consequences-COmorbidities NETwork (COSYCONET) study provide the patient and biomaterial base for discovering predictive molecular markers.,We asked whether microRNA (miRNA) profiles in blood collected from COPD patients prior to a tumor diagnosis could support an early diagnosis of tumor development independent of the tumor type.,From 2741 participants of COSYCONET diagnosed with COPD, we selected 534 individuals including 33 patients who developed cancer during the follow-up period of 54 months and 501 patients who did not develop cancer, but had similar age, gender and smoking history.,Genome-wide miRNA profiles were generated and evaluated using machine learning techniques.,For patients developing cancer we identified nine miRNAs with significantly decreased abundance (two-tailed unpaired t-test adjusted for multiple testing P < 0.05), including members of the miR-320 family.,The identified miRNAs regulate different cancer-related pathways including the MAPK pathway (P = 2.3 × 10−5).,We also observed the impact of confounding factors on the generated miRNA profiles, underlining the value of our matched analysis.,For selected miRNAs, qRT-PCR analysis was applied to validate the results.,In conclusion, we identified several miRNAs in blood of COPD patients, which could serve as candidates for biomarkers to help identify COPD patients at risk of developing cancer. | 1 |
Eosinophils in blood and sputum in chronic obstructive pulmonary disease (COPD) have been associated with more frequent exacerbations, lower lung function, and corticosteroid responsiveness.,We hypothesized increased eosinophils are associated with a severe COPD phenotype, including exacerbation frequency, and tested whether blood eosinophils reliably predict sputum eosinophils.,Comprehensive baseline data on SPIROMICS subjects, recruited for a range of COPD severity for smokers with ≥20 pack year history, included demographics, questionnaires, clinical assessments, quantitative computed tomography (QCT), blood and induced sputum.,Significantly, stratification by mean sputum eosinophils ≥1·25% (N=827) was associated with reduced FEV1 % predicted (differences: 10% pre-bronchodilator, 4·7% post-bronchodilator), QCT density measures for emphysema and air trapping, and exacerbations treated with corticosteroids (p=0·002).,In contrast, stratification by mean blood eosinophils ≥200/µL (N=2499) showed that FEV1 % predicted was significant between low and high blood subgroups, but less than observed between sputum subgroups (blood eosinophil group differences: 4·2% pre-bronchodilator, 2·7% post-bronchodilator), slightly increased airway wall thickness (0·02 mm, p=0·032), greater symptoms (p=0·037), and wheezing (p=0·018), but no evidence of association with COPD exacerbations or other indices of severity.,Blood eosinophils showed weak although significant association with sputum eosinophils (ROC AUC=0·64, p<0·001), but with a high false discovery rate (72%).,Elevated sputum eosinophils, with or without blood eosinophils, were associated with lower lung function.,Elevated blood eosinophils only in combination with elevated sputum eosinophils were associated with COPD exacerbations.,Stratification of SPIROMICS subjects by blood eosinophils alone showed minimal clinical differences and no association with exacerbations, whereas stratification by sputum eosinophils was associated with larger phenotypic differences and COPD exacerbations.,Importantly, increased blood eosinophils did not reliably predict airway eosinophils in induced sputum. | Chronic obstructive pulmonary disease is a common condition and a major cause of mortality.,COPD is characterized by irreversible airflow obstruction.,The physiological abnormalities observed in COPD are due to a combination of emphysema and obliteration of the small airways in association with airway inflammation.,The predominant cells involved in this inflammatory response are CD8+ lymphocytes, neutrophils, and macrophages.,Although eosinophilic airway inflammation is usually considered a feature of asthma, it has been demonstrated in large and small airway tissue samples and in 20%-40% of induced sputum samples from patients with stable COPD.,This airway eosinophilia is increased in exacerbations.,Thus, modifying eosinophilic inflammation may be a potential therapeutic target in COPD.,Eosinophilic airway inflammation is resistant to inhaled corticosteroid therapy, but does respond to systemic corticosteroid therapy, and the degree of response is related to the intensity of the eosinophilic inflammation.,In COPD, targeting treatment to normalize the sputum eosinophilia reduced the number of hospital admissions.,Whether controlling eosinophilic inflammation in COPD patients with an airway eosinophilia will modify disease progression and possibly alter mortality is unknown, but warrants further investigation. | 1 |
Adherence to inhaled medications by COPD patients is a challenging issue, but relatively understudied.,The aim of this study is the characterization of adherence to inhaled medications by COPD patients, with a focus on patient-related determinants.,Stable COPD outpatients ≥40 years of age from a respiratory unit and diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease criteria were included in a cross-sectional study.,The Measure of Treatment Adherence (MTA), the Beliefs about Medications Questionnaire (BMQ) and demographic, clinical, and COPD questionnaires were used.,After completing these questionnaires, semi-structured interviews were carried out and participants were encouraged to justify their opinions and behaviors.,Field notes were made during the interviews and each interview was analyzed before the next one.,Quantitative and qualitative analyses of the variables were then performed.,A total of 300 out of 319 participants (mean age =67.7 years, 78.1% males) completed the MTA questionnaire.,Of these, 31.3% were considered poorly adherent and 16.7% as non-adherent to the inhaled therapy.,A statistically significant negative association was found between adherence and current smoking status (P=0.044), and between adherence and FEV1% (P=0.000).,The mean BMQ Necessity score was higher in adherent patients (P=0.000), but the the mean Concern score was similar for both (P=0.877).,We found nine patterns of poor-adherence, six reasons given for poor-adherence behaviors, five reasons for good-adherence behaviors and three patient-related domains on adherence to medications.,Adherence is related to need perception and to the functional severity of the disease.,A non-adherent patient is usually a current smoker with lower degree of airflow limitation and lower perception of medication necessity.,New information obtained was related to the patterns and reasons for different adherence behaviors, which are based on three major groups of patient related-determinants: health-related experiences, health-related behaviors and health-related beliefs. | This study assessed the adherence profiles to inhaled therapies and the agreement between two patient self-report adherence methods in stable COPD lpatients from seven Latin American countries.,This observational, cross-sectional, multinational, multicenter study involved 795 COPD patients (post-bronchodilator forced expiratory volume in 1 second/forced vital capacity [FEV1/FVC] <0.70).,Adherence to inhaled therapy was assessed using the specific Test of Adherence to Inhalers (10-item TAI) and the generic 8-item Morisky Medication Adherence Scale (MMAS-8) questionnaires.,The percentage agreement and the kappa index were used to compare findings.,59.6% of patients were male (69.5±8.7 years); post-bronchodilator FEV1 percent predicted was 50.0±18.6%.,Mean values for 10-item TAI and MMAS-8 questionnaires were 47.4±4.9 and 6.8±1.6, respectively.,Based on the TAI questionnaire, 54.1% of patients had good, 26.5% intermediate, and 19.4% poor adherence.,Using the MMAS-8 questionnaire, 51% had high, 29.1% medium, and 19.9% low adherence.,According to both questionnaires, patients with poor adherence had lower smoking history, schooling but higher COPD Assessment Test score, exacerbations in the past-year and post-bronchodilator FEV1.,The agreement between 10-item TAI and MMAS-8 questionnaires was moderate (Kappa index: 0.42; agreement: 64.7%).,Suboptimal adherence to medication was frequent in COPD patients from Latin America.,Low adherence was associated with worse health status impairment and more exacerbations.,There was inadequate agreement between the two questionnaires.,Greater effort should be made to improve COPD patients’ adherence to treatment, and assessment of adherence with more specific instruments, such as the TAI questionnaire, would be more convenient in these patients.,NCT02789540 | 1 |
In clinical practice, some patients with asthma show incompletely reversible airflow obstruction, resembling chronic obstructive pulmonary disease (COPD).,The aim of this study was to analyze this overlap phenotype of asthma with COPD feature.,A total of 256 patients, over the age of 40 years or more with a diagnosis of asthma, based on either 1) positive response to bronchodilator: >200 mL forced expiratory volume in 1 s (FEV1) and >12% baseline or 2) positive methacholine or mannitol provocation test, were enrolled.,Among the asthma patients, we defined the overlap group with incompletely reversible airflow obstruction [postbronchodilator FEV1/forced vital capacity (FVC) <70] at the initial time of admission and continuing airflow obstruction after at least 3 months follow up.,We evaluated clinical features, serum eosinophil counts, serum total immunoglobulin (Ig) E with allergy skin prick test, spirometry, methacholine or mannitol provocation challenges and bronchodilator responses, based on their retrospective medical record data.,All of the tests mentioned above were performed within one week.,The study population was divided into two groups: asthma only (62%, n=159, postbronchodilator FEV1/FVC ≥70) and overlap group (38%, n=97, postbronchodilator FEV1/FVC <70).,The overlap group was older, and contained more males and a higher percentage of current or ex-smokers than the asthma only group.,Significantly lower FEV1 and higher total lung capacity, functional residual capacity, and residual volume were observed in the overlap group.,Finally, significantly lower serum eosinophil count and higher IgE were seen in the overlap group.,Our results showed that the overlap phenotype was older, male asthmatic patients who have a higher lifetime smoking intensity, more atopy and generally worse lung function. | The joint distribution of asthma and chronic obstructive pulmonary disease (COPD) has not been well described.,This study aims at determining the prevalence of self-reported physician diagnoses of asthma, COPD and of the asthma-COPD overlap syndrome and to assess whether these conditions share a common set of risk factors.,A screening questionnaire on respiratory symptoms, diagnoses and risk factors was administered by mail or phone to random samples of the general Italian population aged 20-44 (n = 5163) 45-64 (n = 2167) and 65-84 (n = 1030) in the frame of the multicentre Gene Environment Interactions in Respiratory Diseases (GEIRD) study.,A physician diagnosis of asthma or COPD (emphysema/chronic bronchitis/COPD) was reported by 13% and 21% of subjects aged <65 and 65-84 years respectively.,Aging was associated with a marked decrease in the prevalence of diagnosed asthma (from 8.2% to 1.6%) and with a marked increase in the prevalence of diagnosed COPD (from 3.3% to 13.3%).,The prevalence of the overlap of asthma and COPD was 1.6% (1.3%-2.0%), 2.1% (1.5%-2.8%) and 4.5% (3.2%-5.9%) in the 20-44, 45-64 and 65-84 age groups.,Subjects with both asthma and COPD diagnoses were more likely to have respiratory symptoms, physical impairment, and to report hospital admissions compared to asthma or COPD alone (p<0.01).,Age, sex, education and smoking showed different and sometimes opposite associations with the three conditions.,Asthma and COPD are common in the general population, and they coexist in a substantial proportion of subjects.,The asthma-COPD overlap syndrome represents an important clinical phenotype that deserves more medical attention and further research. | 1 |
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. | Events of the past decade have stimulated development of new drug formulations and delivery devices that have improved the efficiency, ease of use, and environmental impact of inhaled drug therapy.,Respimat® Soft Mist™ Inhaler is a novel, multidose, propellant-free, hand-held, liquid inhaler that represents a new category of inhaler devices.,The aerosol cloud generated by Respimat contains a higher fraction of fine particles than most pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs), and the aerosol spray exits the inhaler more slowly and for a longer duration than with pMDIs.,This translates into higher lung drug deposition and lower oropharyngeal deposition, making it possible to give lower nominal doses of delivered drugs without lowering efficacy.,In clinical trials in patients with COPD, bronchodilator drugs delivered from Respimat were equally effective at half of the dose delivered from a pMDI.,In one study of inhaler preference, Respimat was preferred over the pMDI by patients with COPD and other obstructive lung diseases.,Respimat is a valuable addition to the range of inhaler devices available to the patient with COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure (ARF) frequently require admission to the intensive care unit (ICU) for application of mechanical ventilation (MV).,We aimed to determine whether comorbidities and clinical variables present at ICU admission are predictive of ICU mortality.,A retrospective, observational cohort study was performed in a tertiary teaching hospital’s respiratory ICU using data collected between January 2008 and December 2012.,Previously diagnosed COPD patients who were admitted to the ICU with ARF were included.,Patients’ demographics, comorbidities, body mass index (BMI), ICU admission data, application of noninvasive and invasive MV (NIV and IMV, respectively), cause of ARF, length of ICU and hospital stay, and mortality were recorded from their files.,Patients were grouped according to mortality (survival versus non-survival), and all the variables were compared between the two groups.,During the study period, a total of 1,013 COPD patients (749 male) with a mean age (standard deviation) of 70±10 years met the inclusion criteria.,Comorbidities of the non-survival group (female/male, 40/131) were significantly higher compared with the survival group (female/male, 224/618): arrhythmia (24% vs 11%), hypertension (42% vs 34%), coronary artery disease (28% vs 11%), and depression (7% vs 3%) (P<0.001, P<0.035, P<0.001, and P<0.007, respectively).,Logistic regression revealed the following mortality risk factors: need of IMV, BMI <20 kg/m2, pneumonia, coronary artery disease, arrhythmia, hypertension, chronic hypoxia, and higher acute physiology and chronic health evaluation II (APACHE II) scores.,The respective odds ratios, confidence intervals, and P-values for each of these were as follows: 27.7, 15.7-49.0, P<0.001; 6.6, 3.5-412.7, P<0.001; 5.1, 2.9-8.8, P<0.001; 2.9, 1.5-5.6, P<0.001; 2.7, 1.4-5.2, P<0.003; 2.6, 1.5-4.4, P<0.001; 2.2, 1.2-3.9, P<0.008; and 1.1, 1.03-1.11, P<0.001.,Patients with severe COPD and cardiac comorbidities and cachexia should be closely monitored in ICU due to their high risk of ICU mortality. | Chronic obstructive pulmonary disease (COPD) and asthma may overlap and converge in older people (overlap syndrome).,It was hypothesized that patients with overlap syndrome may have different clinical characteristics such as sputum eosinophilia, and better responsiveness to treatment with inhaled corticosteroid (ICS).,Sixty-three patients with stable COPD (forced expiratory volume in 1 second [FEV1] ≤80%) underwent pulmonary function tests, including reversibility of airflow limitation, arterial blood gas analysis, analysis of inflammatory cells in induced sputum, and chest high-resolution computed tomography.,The inclusion criteria for COPD patients with asthmatic symptoms included having asthmatic symptoms such as episodic breathlessness, wheezing, cough, and chest tightness worsening at night or in the early morning (COPD with asthma group).,The clinical features of COPD patients with asthmatic symptoms were compared with those of COPD patients without asthmatic symptoms (COPD without asthma group).,The increases in FEV1 in response to treatment with ICS were significantly higher in the COPD with asthma group.,The peripheral eosinophil counts and sputum eosinophil counts were significantly higher.,The prevalence of patients with bronchial wall thickening on chest high-resolution computed tomography was significantly higher.,A significant correlation was observed between the increases in FEV1 in response to treatment with ICS and sputum eosinophil counts, and between the increases in FEV1 in response to treatment with ICS and the grade of bronchial wall thickening.,Receiver operating characteristic curve analysis revealed 82.4% sensitivity and 84.8% specificity of sputum eosinophil count for detecting COPD with asthma, using 2.5% as the cutoff value.,COPD patients with asthmatic symptoms had some clinical features.,ICS should be considered earlier as a potential treatment in such patients.,High sputum eosinophil counts and bronchial wall thickening on chest high-resolution computed tomography might therefore be a good predictor of response to ICS. | 1 |
Chronic obstructive pulmonary disease (COPD) was the fourth leading cause of death worldwide in 2015.,Current treatments for patients ease discomfort and help decrease disease progression; however, none improve lung function or change mortality.,COPD is heterogeneous in its molecular and clinical presentation, making it difficult to understand disease aetiology and define robust therapeutic strategies.,Given the complexity of the disease we propose a precision medicine approach to understanding and better treating COPD.,It is possible that multiOMICs can be used as a tool to integrate data from multiple fields.,Moreover, analysis of electronic medical records could aid in the treatment of patients and in the predictions of outcomes.,The Precision Medicine Initiative created in 2015 has made precision medicine approaches to treat disease a reality; one of these diseases being COPD. | The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | 1 |
COPD presents with an array of extra-pulmonary symptoms of which skeletal muscle dysfunction, particularly of the quadriceps, is well recognized.,This contributes to impaired quality of life and increased health care utilization.,Work on the quadriceps originated from the observation that a good proportion of COPD patients stop exercise due to the feeling of leg fatigue rather than breathlessness.,This study was carried out with the aim of finding the prevalence of quadriceps weakness in a population set and correlate it with severity of COPD.,This cross-sectional study was conducted in 75 subjects suffering from COPD aged 45 years or above.,COPD severity in the subjects was graded based on the GOLD staging system.,A digital hand held dynamometer (HHD) was used to measure quadriceps muscle strength.,Descriptive statistics were done, and Pearson’s Correlation Coefficient and ANOVA analysis was used for expressing the results.,Ninety two percent of subjects were suffering from quadriceps muscle weakness.,Quadriceps weakness was present in significantly high proportions even in those suffering from mild disease and belonging to a younger age group.,The mean quadriceps muscle force value decreased with disease severity and this relation was found to be significant (P<0.01).,Majority of the COPD patients were found to be suffering from quadriceps weakness, which was also present in significant proportions in subjects belonging to younger age groups and suffering from mild disease.,These findings indicate that onset of muscle weakness in COPD may precede the onset of symptoms.,These findings suggest need for early remedial measure to prevent occurrence of associated systemic diseases. | The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed.,Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD.,We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012.,Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence.,86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both.,Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence.,Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low.,As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence.,Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence.,Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment. | 1 |
Pulse oximetry could potentially contribute to self-monitoring.,NHS Lothian’s ‘Light Touch’ service provided COPD patients with a self-management plan based on symptoms and oximetry.,The service was overseen (though not actively monitored) by respiratory-trained community teams who were contactable by a telephone helpline.,We aimed to assess the feasibility, perceived utility and impact of the ‘Light Touch’ service.,A before-and-after assessment of St George’s Respiratory Questionnaire (SGRQ), Hospital Anxiety and Depression Scale (HADS) and use of healthcare resources during the 6-month feasibility study compared to the previous corresponding 6-months.,Paired semi-structured interviews with patients at baseline and 6-months, interviews with managers and a focus group of professionals explored perceptions of the service and self-management.,Transcripts were coded, and analysed thematically.,We recruited 51 participants (mean age 69.7 years (SD 8.4); 21 (46 %) male). 46 participants completed quantitative follow up (2 died, 2 were unwell, 1 refused).,SGRQ: 21 (46 %) participants improved by 4 or more (the minimum important difference); 12 (26 %) deteriorated by 4 or more.,HADS: more participants had normal scores for anxiety (65 %) and depression (80 %) at 6-months than at baseline (51 and 64 %).,More emergency therapy was prescribed during the study period compared to the previous year.,Only 18 participants (39 %) contacted the Light Touch Helpline during the 6-month study.,Twenty patients provided a total of 36 interviews, 8 clinicians contributed to a focus group and 6 managers were interviewed.,Patients considered that the oximetry readings heightened awareness of their condition and gave them confidence to make self-management decisions.,Healthcare professionals valued oximetry as a tool for teaching people self-management skills, but were concerned that patients rarely contacted the teams for help or advice during the study.,‘Light Touch’ shows promise as a low-cost strategy for empowering patients’ self-management skills and reducing reliance on clinical supervision.,The online version of this article (doi:10.1186/s12913-015-1135-2) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is a highly prevalent condition associated with a high health care resource consumption and health care expenditures, driven mainly by exacerbations-related hospitalizations.,Telemedicine has been proposed as a mean for timely detection of exacerbation, but the available evidence is inadequate to provide conclusive information on its efficacy.,The aim of this study is to evaluate the efficacy of a telemonitoring system in reducing COPD-related hospitalizations in an elderly population with COPD.,This is a parallel arms, randomized trial including patients aged 65 or older with COPD in GOLD stages II and III enrolled in a Pulmonary Medicine outpatient facility.,Patients were randomly assigned to receive a non-invasive system able to telemonitor vital signs (oxygen saturation, heart rate, near-body temperature, overall physical activity) or standard care, and were followed up for 9 months.,The outcome measures were the number of exacerbations and exacerbation-related hospitalization.,Fifty patients were included in the telemonitoring group and 49 in the control group.,The incidence rate of respiratory events was 28/100 person/years in the telemonitoring group vs. 42/100 person/years in the control group (incidence rate ratio: 0.67, 95% CI: 0.32 - 1.36).,The corresponding figures for hospital admissions where 13/100 person/years and 20/100 person/years, respectively (IRR: 0.66, 95% CI: 0.21 - 1.86).,In our study, COPD patients followed up with the aid of a multiparametric remote monitoring system experienced a lower rate of exacerbations and COPD-related hospitalizations compared to patients followed up using the standard model of care.,These results need to be replicated in larger studies before they can be applied to the general COPD population.,Trial registration number: NCT01481506 (clinicaltrials.gov).,Funding: co-financed by Lazio Region and Intersistemi Inc. | 1 |
We compared the clinical characteristics and treatment outcomes of patients with eosinophilic and neutrophilic COPD exacerbations requiring hospital admission.,This was a retrospective multicenter study performed between January 2010 and December 2014.,In all, 1,688 COPD patients admitted via the outpatient clinics or emergency departments of six university hospitals were enrolled.,The patients were grouped by complete blood counts: eosinophilic group, >2% peripheral blood eosinophils, and neutrophilic group, >65% peripheral blood neutrophils or >11,000 leukocytes/mL.,The patients with radiographic evidence of pneumonia at the time of admission, those with lung cancer, those admitted for treatment of other medical problems, and those who chronically used steroids were excluded.,A total of 605 patients hospitalized with COPD exacerbations (177 eosinophilic and 380 neutrophilic) were included.,Pulmonary functions, including the forced expiratory volume in 1 second and forced vital capacity, were better in patients with eosinophilic exacerbations.,Treatment outcomes, including the rate of admission to the intensive care unit and mortality, were poorer in patients with neutrophilic exacerbations (4.5% vs 12.4%, P=0.004; 1.1% vs 4.5%, P=0.043, respectively).,Congestive heart failure (odds ratio [OR] =3.40, 95% confidence interval [CI]: 1.28-9.01) and neutrophilic exacerbation (OR = 2.81, 95% CI: 1.21-6.52) were independent risk factors for intensive care unit admission.,COPD patients with neutrophilic exacerbations experienced worse clinical outcomes than did those with eosinophilic exacerbations.,The peripheral blood eosinophil count may be a useful predictor of clinical progress during hospitalization of COPD patients with acute exacerbations. | There is little data surrounding the survival of patients with chronic obstructive pulmonary disease (COPD) who are admitted to the critical care unit with exacerbation of symptoms.,We conducted a study to measure the in-hospital and intensive care unit (ICU) outcomes of patients admitted with COPD exacerbation, and identified the related prognostic factors.,We performed a retrospective cohort study of patients who were admitted to the adult ICU between January 2006 and July 2011 for COPD exacerbation in King Abdulaziz National Guard Hospital, Al-Hasa, Saudi Arabia.,During the study period, a total of 119 patients were admitted to the ICU with acute respiratory failure attributed to COPD exacerbation.,The mean age was 72 ± 13 years, and 44 (37%) were females.,The main cause of respiratory failure was infection, which occurred in 102 (86%) patients.,Thirty-nine (33%) of the admitted patients were mechanically ventilated, and the median duration was 2.6 (1-42) days.,The median lengths of the ICU and hospital stays were 3 (1-40) and 9 (2-43) days, respectively.,The ICU mortality was 6%, and hospital mortality was 11%.,Low Glasgow Coma Scale on admission, intubation, duration of mechanical ventilation, current smoking, tracheostomy, cardiopulmonary arrest, and the development of acute renal failure were associated with higher hospital mortality.,Early ICU and hospital mortality is low for COPD patients who have been admitted to the ICU with exacerbation.,Low Glasgow Coma Scale scores on admission, intubation, prolonged use of mechanical ventilation, and the development of acute renal failure were identified as risk factors associated with increased hospital mortality. | 1 |
Wood smoke exposure is a risk factor for COPD.,For a given degree of airway obstruction, the reduction in DLCO is smaller in individuals with wood smoke-related COPD than in those with smoking-related COPD, suggesting that there is less emphysema in the former.,The objective of this study was to compare HRCT findings between women with wood smoke-related COPD and women with smoking-related COPD.,Twenty-two women with severe COPD (FEV1/FVC ratio < 70% and FEV1 < 50%) were divided into two groups: those with wood smoke-related COPD (n = 12) and those with smoking-related COPD (n = 10).,The two groups were compared regarding emphysema scores and airway involvement (as determined by HRCT); and functional abnormalities-spirometry results, DLCO, alveolar volume (VA), the DLCO/VA ratio, lung volumes, and specific airway resistance (sRaw).,There were no significant differences between the two groups in terms of FEV1, sRaw, or lung hyperinflation.,Decreases in DLCO and in the DLCO/VA ratio were greater in the smoking-related COPD group subjects, who also had higher emphysema scores, in comparison with the wood smoke-related COPD group subjects.,In the wood smoke-related COPD group, HRCT scans showed no significant emphysema, the main findings being peribronchial thickening, bronchial dilation, and subsegmental atelectasis.,Female patients with severe wood smoke-related COPD do not appear to develop emphysema, although they do show severe airway involvement.,The reduction in DLCO and VA, with a normal DLCO/VA ratio, is probably due to severe bronchial obstruction and incomplete mixing of inspired gas during the determination of single-breath DLCO. | More than two-fifths of the world’s population uses solid fuels, mostly biomass, for cooking.,The resulting biomass smoke exposure is a major cause of chronic obstructive pulmonary disease (COPD) among women in developing countries.,To assess whether lower woodsmoke exposure from use of a stove with a chimney, compared to open fires, is associated with lower markers of airway inflammation in young women.,We carried out a cross-sectional analysis on a sub-cohort of participants enrolled in a randomized controlled trial in rural Guatemala, RESPIRE.,We recruited 45 indigenous women at the end of the 18-month trial; 19 women who had been using the chimney stove for 18-24 months and 26 women still using open fires.,We obtained spirometry and induced sputum for cell counts, gene expression of IL-8, TNF-α, MMP-9 and 12, and protein concentrations of IL-8, myeloperoxidase and fibronectin.,Exhaled carbon monoxide (CO) and 48-hr personal CO tubes were measured to assess smoke exposure.,MMP-9 gene expression was significantly lower in women using chimney stoves.,Higher exhaled CO concentrations were significantly associated with higher gene expression of IL-8, TNF-α, and MMP-9.,Higher 48-hr personal CO concentrations were associated with higher gene expression of IL-8, TNF- α, MMP-9 and MMP-12; reaching statistical significance for MMP-9 and MMP-12.,Compared to using an open wood fire for cooking, use of a chimney stove was associated with lower gene expression of MMP-9, a potential mediator of airway remodeling.,Among all participants, indoor biomass smoke exposure was associated with higher gene expression of multiple mediators of airway inflammation and remodeling; these mechanisms may explain some of the observed association between prolonged biomass smoke exposure and COPD. | 1 |
Currently, chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide.,The determination of immune mechanisms of inflammation in the disease presents an important challenge for fundamental medical research.,According to modern views, Toll-like receptors (TLRs), among which TLR2 and TLR4 play a key role, are one of the essential components of inflammatory process in COPD.,This review focuses on following aspects: the role of TLR2 and TLR4 in the initiation of inflammatory process in COPD; the mechanisms of influence of various exogenous factors (cigarette smoke, suspended particulate matter, and bacteria) on the expression of TLR2 and TLR4; the contribution of these TLRs to the T-helper (Th) immune response development in COPD, in particular to the Th17 immune response, which contributes to the progression of the disease and therapeutic implications of TLR2 and TLR4 in COPD. | Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterized by a progressive and irreversible deterioration of lung function.,Exacerbations of COPD have prolonged negative effects on pulmonary function and a major impact on health status and outcomes.,NLRP3 inflammasome is a cardinal component of the inflammatory response, with marked evidence in stable and exacerbations of COPD.,The aim of our study was to evaluate the NLRP3 inflammasome activity during COPD exacerbation by using an in vitro model.,A549 cells were stimulated with different concentrations (10%, 4%, 2%) of cigarette smoke extract (CSE) with or without LPS (0.1μg/ml) for 24 hours.,Cell viability was assessed by using XTT test.,Levels of inflammatory cytokines (IL-8, MCP-1, and IL-1β) were measured by ELISA and the activity level of NLRP-3 was evaluated by flow cytometry.,Cells exposed to CSE present an increase in inflammatory cytokines (IL-8 and MCP-1) production in a dose-dependent manner.,Incubation with LPS to these cells results in higher levels of IL-8 and MCP-1 compared to stimulation of CSE alone.,NLRP3 inflammasome activity and IL-1β levels were significantly increased in cells exposed to both CSE and LPS compared to CSE alone.,NLRP3 inflammasome is upregulated in an in-vitro model of COPD and COPD exacerbation.,Our findings provide novel biomarkers for COPD exacerbation and may present new targets for future research. | 1 |
The influence of peak inspiratory flow (PIF) on dose delivery from dry powder inhalers (DPIs) and association with treatment efficacy in patients with chronic obstructive pulmonary disease (COPD) has not been fully determined.,In vitro studies have demonstrated adequate dose delivery through ELLIPTA DPI at PIF ≥30 L/min.,This analysis of two clinical trials and a real-world population of COPD patients determined spirometric PIF distribution, and explored the relationship between PIF and outcomes in the trials.,The replicate Phase IV, 12-week, randomized, double-blind 207608/207609 (NCT03478683/NCT03478696) trials evaluated fluticasone furoate/umeclidinium/vilanterol via ELLIPTA DPI versus budesonide/formoterol+tiotropium in COPD patients.,This post hoc analysis assessed spirometric PIF distribution at screening and relationship between PIF and lung function outcomes in the pooled 207608/207609 population.,Spirometric PIF distributions in a real-world population of COPD patients were evaluated by retrospective analysis of the Kaiser Permanente Northwest (KPNW) database to assess similarities between clinical trial and real-world populations.,A total of 1460 (207608/207609) and 3282 (KPNW) patients were included.,There was considerable overlap between spirometric PIF distributions for both populations.,Overall, 99.7% and 99.8% of the 207608/207609 and KPNW populations, respectively, reported spirometric PIF ≥50 L/min, estimated as equivalent to ELLIPTA PIFR ≥30 L/min.,In the 207608/207609 combined analysis, there was no significant interaction between spirometric PIF and treatment for lung function endpoints, indicating treatment effect is independent of PIF.,Nearly all COPD patients in the 207608/207609 and KPNW populations achieved spirometric PIF values estimated as equivalent to PIFR of ≥30 L/min through the ELLIPTA DPI.,Lack of correlation between spirometric PIF at screening and treatment efficacy aligns with consistent dose performance from the ELLIPTA DPI across a wide range of PIFs, achieved by patients with COPD of all severities. | 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. | 1 |
Asthma-COPD overlap (ACO) is a term that encompasses patients with characteristics of two conditions, smoking asthmatics or COPD patients with asthma-like features such as high bronchodilator response or blood eosinophil count ≥300 cells/μL.,The aim of this study was to compare the different phenotypes inside the ACO definition in a real-life population cohort.,We analyzed patients from the MAJORICA cohort who had a diagnosis of asthma and/or COPD based on current guidelines, laboratory data in 2014 and follow-up until 2015.,Prevalence of ACO according to the different criteria, demographic, clinical and functional characteristics, prescriptions and use of health resources data were compared between three groups.,We included 603 patients.,Prevalence of smoking asthmatics was 14%, COPD patients with high bronchodilator response 1.5% and eosinophilic COPD patients 12%.,Smoking asthmatics were younger and used more rescue inhalers, corticosteroids and health resources.,Conversely, eosinophilic COPD patients were older than the other groups, often treated with corticosteroids and had lower use of health resources.,Most of the COPD patients with high bronchodilator response were included in the eosinophilic COPD group.,ACO includes two conditions (smoking asthmatics and eosinophilic COPD patients) with different medication requirement and prognosis that should not be pooled together.,Use of ≥300 blood eosinophils/μL as a treatable trait should be recommended. | The term Asthma and COPD Overlap (ACO) describes a condition where asthma and COPD overlap.,We aimed to investigate associations between ACO and insomnia and respiratory symptoms, and to investigate the prevalence of ACO and the characteristics of subjects with ACO in two Northern European population studies.,The study comprised 25 429 subjects aged ≥ 40 years who participated in one of two Northern European general population surveys.,Both surveys included questions on asthma, COPD, respiratory and sleep-related symptoms, including difficulty initiating sleep, difficulty maintaining sleep, early-morning awakening, and excessive daytime sleepiness.,ACO was defined as having both self-reported asthma and COPD.,The prevalence of ACO was 1.0%.,The group with ACO had a higher prevalence of both insomnia and respiratory symptoms than subjects with only asthma or COPD.,Having ACO was independently associated with a 2-3 times higher probability of having sleep-related symptoms as compared with the group without asthma or COPD, after adjustment for age, sex, BMI, smoking history and educational level (adjusted odds ratio 2.14-3.36, 95% CI).,Subjects with ACO have a high prevalence of insomnia and respiratory symptoms.,To our knowledge, this is the first study to assess the association between sleep-related symptoms and ACO. | 1 |
Triple therapy using salmeterol/fluticasone propionate (FP) and tiotropium bromide is commonly used to treat chronic obstructive pulmonary disease (COPD), but sparse efficacy data exist in COPD patients with fewer symptoms and with a lower dose of inhaled corticosteroid in Japanese patients.,The effects of of salmeterol/fluticasone propionate 50/250 μg (SFC250) twice daily plus tiotropium 18 μg (TIO) once daily and individual treatments on lung function were compared.,Fifty three Japanese COPD patients participated in this randomized, double-blind, double-dummy, Williams square design crossover study.,Lung function was assessed by plethysmography and spirometry.,The primary endpoint of postdose specific airway conductance area under the curve (AUC0-4h) on day 28 was significantly higher following SFC250 + TIO (0.854) compared with TIO (0.737, 15.8%) and SFC250 (0.663, 28.8%) alone.,SFC250 + TIO significantly improved trough forced expiratory volume in 1 second from baseline versus TIO (0.161 L, P<0.001) and SFC250 (0.103 L, P=0.008).,SFC250 + TIO significantly improved residual volume compared with TIO (P<0.001) and SFC250 (P=0.003) on day 28.,Nonsignificant improvements were seen in trough inspiratory capacity, total lung capacity, and thoracic gas volume.,There was no mean change seen in rescue medication.,Triple therapy using SFC250 + TIO was well tolerated and gave a greater improvement in bronchodilation compared with TIO and SFC250 alone in Japanese patients with COPD.,There was improvement in few symptoms, but no mean change was seen in patient-reported outcomes measured by rescue medication use. | Real-world prescription pathways leading to triple therapy (TT) (inhaled corticosteroid [ICS] plus long-acting β2-agonist bronchodilator [LABA] plus long-acting muscarinic antagonist) differ from Global initiative for chronic Obstructive Lung Disease [GOLD] and National Institute for Health and Care Excellence treatment recommendations.,This study sets out to identify COPD patients without asthma receiving TT, and determine the pathways taken from diagnosis to the first prescription of TT.,This was a historical analysis of COPD patients without asthma from the Optimum Patient Care Research Database (387 primary-care practices across the UK) from 2002 to 2010.,Patient disease severity was classified using GOLD 2013 criteria.,Data were analyzed to determine prescribing of TT before, at, and after COPD diagnosis; the average time taken to receive TT; and the impact of lung function grade, modified Medical Research Council dyspnea score, and exacerbation history on the pathway to TT.,During the study period, 32% of patients received TT.,Of these, 19%, 28%, 37%, and 46% of patients classified as GOLD A, B, C, and D, respectively, progressed to TT after diagnosis (P<0.001).,Of all patients prescribed TT, 25% were prescribed TT within 1 year of diagnosis, irrespective of GOLD classification (P=0.065).,The most common prescription pathway to TT was LABA plus ICS.,It was observed that exacerbation history did influence the pathway of LABA plus ICS to TT.,Real life UK prescription data demonstrates the inappropriate prescribing of TT and confirms that starting patients on ICS plus LABA results in the inevitable drift to overuse of TT.,This study highlights the need for dissemination and implementation of COPD guidelines to physicians, ensuring that patients receive the recommended therapy. | 1 |
COPD is among the major causes of death, and it is associated with several comorbid conditions.,Chronic kidney disease (CKD) is frequently diagnosed in older people living in Western societies and could impact COPD patients’ mortality.,We evaluated the relationship between burden of comorbidities, CKD, and mortality in a population-based cohort of patients discharged with a diagnosis of COPD.,A longitudinal cohort study was conducted evaluating 27,272 COPD patients.,Recruitment of COPD subjects and identification of CKD and other comorbidities summarized by the Charlson comorbidity index (CCI) were based on claims data coded according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM).,Severity of COPD was classified by hospital diagnosis or exemption from medical charges due to respiratory failure or previous hospitalizations for COPD.,The impact of comorbidities on survival was assessed by Cox regression.,Less than 40% of patients were still alive at the end of a median follow-up of 37 months (17 months for patients who died and 56 months for those alive at the end of follow-up).,After adjustment for age, gender, and severity score of COPD, CKD (hazard ratio =1.36, 95% confidence interval 1.30-1.42) independently from comorbidities summarized by the CCI was a significant risk factor for mortality.,In spite of limitations due to the use of claims data, long-term survival of COPD patients was heavily affected by the presence of CKD and other comorbidities. | The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | 1 |
The purpose of this study was to investigate the clinical efficacy and safety of a fixed-dose combination of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate-to-very severe chronic obstructive pulmonary disease (COPD).,This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension.,Subjects (n = 1196), at least 40 years old, were current or ex-smokers randomized to twice-daily inhaled MF/F 400/10 μg, MF/F 200/10 μg, MF 400 μg, F 10 μg, or placebo.,The trial’s co-primary endpoints were mean changes from baseline, as area under the curve (AUC), in forced expiratory volume (FEV1) over 0-12 hours (AUC0-12 h FEV1) with MF/F versus MF, and in morning (AM) pre-dose (trough) FEV1 with MF/F versus F after 13 weeks of treatment.,Key secondary endpoints were the effects of MF/F on respiratory health status using the Saint George’s Respiratory Questionnaire (SGRQ), symptom-free nights, partly stable COPD at 26 weeks, and time to first COPD exacerbation.,The largest improvements in AUC0-12 h FEV1 were observed with MF/F 400/10 μg and MF/F 200/10 μg.,Serial spirometry results demonstrated that bronchodilator effects with MF/F occurred rapidly (within 5 minutes), persisted for 12 hours after dosing, and were sustained over the 26-week treatment period.,Similar findings were observed for AM pre-dose FEV1, for which effects were further investigated, excluding subjects whose AM FEV1 data were incorrectly collected after 2 days from the last dose of study treatment.,Improvements in SGRQ scores surpassed the minimum clinically important difference of more than four units with both MF/F treatments.,At 26 weeks, no notable between-treatment differences in the occurrence and nature of adverse events (AEs) were reported.,No unexpected AEs were observed.,Overall, 90 subjects reported AEs considered to be treatment-related, the most common of which were lenticular opacities, dysphonia, and oral candidiasis.,In conclusion, MF/F treatments improved lung function and respiratory health status, reduced exacerbations, and were well tolerated in subjects with moderate-to-very severe COPD. | Some large population-based studies have reported a dose-related increased risk of cataracts and glaucoma associated with use of inhaled corticosteroids (ICS) in patients with asthma or chronic obstructive pulmonary disease (COPD).,We evaluated the association between use of ICS-containing products, specifically fluticasone propionate/salmeterol fixed-dose combination (FSC), and incidence of cataracts and glaucoma among patients with COPD in a large electronic medical record database in the United Kingdom.,We identified a cohort of patients aged 45 years and over with COPD in the General Practice Research Database (GPRD) between 2003 and 2006.,Cases of incident cataracts or glaucoma were defined based on diagnosis and procedure codes and matched to controls from the risk set to estimate odds ratios (OR) and 95% confidence intervals (CI).,The association with FSC or ICS exposure was modeled using conditional logistic regression.,Medication exposure was assessed with respect to recency, duration, and number of prescriptions prior to the index date.,Average daily dose was defined as none, low (1-250 mcg), medium (251-500 mcg), high (501-1000 mcg), or very high (1001+ mcg) using fluticasone propionate (FP) equivalents.,We identified 2941 incident cataract cases and 327 incident glaucoma cases in the COPD cohort (n = 53,191).,FSC or ICS prescriptions were not associated with risk of incident cataracts or glaucoma for any exposure category, after adjusting for confounders.,We observed a lack of a dose response in all analyses, where low dose was the reference group.,The odds of cataracts associated with FSC dose were medium OR: 1.1 (95% CI: 0.9-1.4); high OR: 1.2 (95% CI: 0.9-1.5); and very high OR: 1.2 (95% CI: 0.9-1.7).,The odds of glaucoma associated with FSC dose: medium OR: 1.0 (95% CI: 0.5-2.1); high OR: 1.0 (95% CI: 0.5-2.0); and very high OR: 1.0 (95% CI: 0.4-2.8).,FSC or other ICS exposure was not associated with an increased odds of cataracts or glaucoma, nor was a dose-response relationship observed in this population-based nested case-control study of COPD patients in the United Kingdom. | 1 |
This study was conducted to investigate the association between the chronic obstructive pulmonary disease (COPD) assessment test (CAT) and depression in COPD patients.,The Korean versions of the CAT and patient health questionnaire-9 (PHQ-9) were used to assess COPD symptoms and depressive disorder, respectively.,In total, 803 patients with COPD were enrolled from 32 hospitals and the prevalence of depression was 23.8%.,The CAT score correlated well with the PHQ-9 score (r=0.631; P<0.001) and was significantly associated with the presence of depression (β±standard error, 0.452±0.020; P<0.001).,There was a tendency toward increasing severity of depression in patients with higher CAT scores.,By assessment groups based on the 2011 Global Initiative for Chronic Obstructive Lung Disease guidelines, the prevalence of depression was affected more by current symptoms than by airway limitation.,The area under the receiver operating characteristic curve for the CAT was 0.849 for predicting depression, and CAT scores ≥21 had the highest accuracy rate (80.6%).,Among the eight CAT items, energy score showed the best correlation and highest power of discrimination.,CAT scores are significantly associated with the presence of depression and have good performance for predicting depression in COPD patients. | It has been debated whether treatment should be started early in subjects with mild to moderate COPD.,An impaired health status score was associated with a higher probability of being diagnosed with COPD as compared with undiagnosed COPD.,To investigate the health status in a healthy working population, to determine reference scores for healthy non-smoking subjects, and to investigate the relationship between their health status and airflow limitation.,A total of 1333 healthy industrial workers aged ≥40 years performed spirometry and completed the St.,George’s Respiratory Questionnaire (SGRQ) and the COPD Assessment Test (CAT).,The prevalence of COPD defined by the fixed ratio of the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) was 10.9%, and the prevalence defined by the Lower Limit of Normal was 5.0%.,All SGRQ and CAT scores were skewed to the milder end.,In 512 non-smoking subjects with normal spirometry, the mean SGRQ score was 5.7, and the mean CAT score was 5.8.,In 145 people with COPD defined by the fixed ratio, the mean SGRQ score was 7.9, with a zero score in 6.9% of the subjects.,Using the CAT, the mean score was 7.3, with 7.6% of the scores being zero.,The scores in patients identified using the Lower Limit of Normal approach were: SGRQ 8.4 (13.4% had a score of zero) and CAT 7.4 (13.4% had a score of zero).,Although the 95th percentiles of the Total, Symptoms, Activity, and Impact scores of the SGRQ and CAT sores were 13.8, 34.0, 23.4, 7.2 and 13.6 in the 512 healthy non-smoking subjects, respectively, they were also distributed under their upper limits in over 80% of the COPD subjects.,The COPD-specific health status scores in a working population were good, even in those with spirometrically diagnosed COPD.,All scores were widely distributed in both healthy non-smoking subjects and in subjects with COPD, and the score distribution overlapped remarkably between these two groups.,This suggests that symptom-based methods are not suitable screening tools in a healthy general population. | 1 |
Rationale: Individuals eligible for lung cancer screening (LCS) by low-dose computed tomography (LDCT) are also at risk of chronic obstructive pulmonary disease (COPD) due to age and smoking exposure.,Whether the LCS episode is useful for early detection of COPD is not well established.,Objectives: To explore associations between symptoms, comorbidities, spirometry, and emphysema in participants enrolled in the Lung Screen Uptake Trial.,Methods: This cross-sectional study was a prespecified analysis nested within Lung Screen Uptake Trial, which was a randomized study testing the impact of differing invitation materials on attendance of 60- to 75-year-old smokers and ex-smokers to a “lung health check” between November 2015 and July 2017.,Participants with a smoking history ≥30 pack-years and who quit ≤15 years ago, or meeting a lung cancer risk of ≥1.51% via the Prostate Lung Colorectal Ovarian model or ≥2.5% via the Liverpool Lung Project model, were offered LDCT.,COPD was defined and classified according to the GOLD (Global Initiative for Obstructive Lung Disease) criteria using prebronchodilator spirometry.,Analyses included the use of descriptive statistics, chi-square tests to examine group differences, and univariable and multivariable logistic regression to explore associations between symptom prevalence, airflow limitation, and visually graded emphysema.,Results: A total of 560 of 986 individuals included in the analysis (57%) had prebronchodilator spirometry consistent with COPD; 67% did not have a prior history of COPD and were termed “undiagnosed.”,Emphysema prevalence in those with known and “undiagnosed” COPD was 73% and 68%, respectively.,A total of 32% of those with “undiagnosed COPD” had no emphysema on LDCT.,Inhaler use and symptoms were more common in the “known” than the “undiagnosed” COPD group (63% vs. 33% with persistent cough [P < 0.001]; 73% vs. 33% with dyspnea [P < 0.001]).,Comorbidities were common in all groups.,Adjusted odds ratio (aOR) of respiratory symptoms were more significant for airflow obstruction (aOR GOLD 1 and 2, 1.57; confidence interval [CI], 1.14-2.17; aOR GOLD 3 and 4, 4.6; CI, 2.17-9.77) than emphysema (aOR mild, 1.12; CI, 0.81-1.55; aOR moderate, 1.33; CI, 0.85-2.09; aOR severe, 4.00; CI, 1.57-10.2).,Conclusions: There is high burden of “undiagnosed COPD” and emphysema in LCS participants.,Adding spirometry findings to the LDCT enhances identification of individuals with COPD.,Clinical trial registered with www.clinicaltrials.gov (NCT02558101). | Oxidative stress is a major driving mechanism in the pathogenesis of COPD.,There is increased oxidative stress in the lungs of COPD patients due to exogenous oxidants in cigarette smoke and air pollution and due to endogenous generation of reactive oxygen species by inflammatory and structural cells in the lung.,Mitochondrial oxidative stress may be particularly important in COPD.,There is also a reduction in antioxidant defences, with inactivation of several antioxidant enzymes and the transcription factors Nrf2 and FOXO that regulate multiple antioxidant genes.,Increased systemic oxidative stress may exacerbate comorbidities and contribute to skeletal muscle weakness.,Oxidative stress amplifies chronic inflammation, stimulates fibrosis and emphysema, causes corticosteroid resistance, accelerates lung aging, causes DNA damage and stimulates formation of autoantibodies.,This suggests that treating oxidative stress by antioxidants or enhancing endogenous antioxidants should be an effective strategy to treat the underlying pathogenetic mechanisms of COPD.,Most clinical studies in COPD have been conducted using glutathione-generating antioxidants such as N-acetylcysteine, carbocysteine and erdosteine, which reduce exacerbations in COPD patients, but it is not certain whether this is due to their antioxidant or mucolytic properties.,Dietary antioxidants have so far not shown to be clinically effective in COPD.,There is a search for more effective antioxidants, which include superoxide dismutase mimetics, NADPH oxidase inhibitors, mitochondria-targeted antioxidants and Nrf2 activators. | 1 |
Oxidative stress is recognized to be one of predisposing factor in the pathogenesis of COPD.,The oxidant/antioxidant imbalance is significantly pronounced in patients with COPD exacerbation.,N-acetylcysteine (NAC) seems to be able to reduce COPD exacerbations by modulating the oxidative stress in addition to its well-known mucolytic activity, but there are discordant findings on the actual anti-oxidant activity of NAC.,The anti-oxidant effect of NAC and its impact on the inflammatory response have been pharmacologically characterized on a human ex vivo model of COPD exacerbation induced by lipopolysaccharide (LPS).,NAC prevented the desensitization induced by LPS incubation on the contractile tone in linear concentration-response manner.,Concentrations of NAC ≥1 μM reduced the pro-oxidant response (peroxidase activity, hydrogen peroxide, malondialdehyde, nitric oxide), and improved the anti-oxidant response (total anti-oxidant capacity, glutathione, superoxide dismutase) induced by LPS.,Lower concentrations of NAC (<1 μM) did not modulate the bronchial oxidative imbalance.,Concentrations of NAC ≥300 μM inhibited the inflammatory response (release of IL-1β, IL-8, and TNF-α) of human airways induced by the overnight stimulation with LPS, whereas lower concentrations of NAC (≥1 μM) were sufficient to reduce the release of IL-6 elicited by LPS.,Both the anti-oxidant effect and the anti-inflammatory effect of NAC were inversely correlated with the release of NKA.,The findings of this study suggest that NAC may have a role in modulating the detrimental effect induced by LPS in course of COPD exacerbation.,It may elicit both anti-oxidant and anti-inflammatory effects when administered at high concentrations. | 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. | 1 |
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. | 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. | 1 |
COPD is characterized by chronic bronchitis, chronic airway obstruction, and emphysema, leading to a progressive and irreversible decline in lung function.,Inflammation is central for the development of COPD.,Chronic inflammation in COPD mainly involves the infiltration of neutrophils, macrophages, lymphocytes, and other inflammatory cells into the small airways.,The contribution of resident airway structural cells to the inflammatory process is also important in COPD.,Airway remodeling consists of detrimental changes in structural tissues and cells including airway wall thickening, epithelial metaplasia, goblet cell hypertrophy, and smooth muscle hyperplasia.,Persistent airway inflammation might contribute to airway remodeling and small airway obstruction.,However, the underlying mechanisms remain unclear.,In this review, we will provide an overview of recent insights into the role of major immunoinflammatory cells in COPD airway remodeling. | A new phenotype with overlapping characteristics between asthma and chronic obstructive pulmonary disease (COPD) called asthma-COPD overlap syndrome (ACOS) is emerging among inflammation diseases.,To date, there is no agreement on specific criteria to define this syndrome, and the current guidelines are insufficient to classify the analogy and differences between overlap and COPD or asthma phenotypes.,It would be necessary to identify new biomarkers able to identify these diseases clearly.,Thus, the aim of this study was to identify a serum and supernatant of sputum microRNA (miRNA) expression profile of miRNA-145 and miRNA-338 in patients with asthma (n=13), COPD (n=31), and ACOS (n=8) and controls (n=7).,The expression was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR).,For statistical analysis, the ANOVA test, Kruskal-Wallis test, Mann-Whitney U-test, and Spearman’s rank correlation were used.,The main finding of this work is that the expression of miRNA-338 is higher in the supernatant of different obstructive diseases than in peripheral blood, while miRNA-145 is higher only in the supernatant of asthma patients.,The expression of both selected miRNAs is higher in the supernatant of asthma and COPD patients than in controls.,Differences in sputum miRNA expression profile were observed between patients with ACOS and asthma or COPD, which underline the potential role of miRNA as a biomarker that is able to discriminate patients with ACOS, asthma, and COPD. | 1 |
To investigate the association of the GOLD ABCD groups classification with costs and health-related quality of life (HR-QoL) and to compare this with the GOLD 1234 grades classification that was primarily based on lung function only.,In a cross-sectional study, we selected patients diagnosed with chronic obstructive pulmonary disease (COPD) from electronic medical records of general practices.,Multi-level analysis was used with costs (medication, primary care, healthcare, societal), disease-specific and generic HR-QoL as independent variables.,Either the new or the old GOLD stages were included in the analysis together with several covariates (age, gender, living situation, co-morbidity, self-efficacy, smoking, education, employment).,611 patients from 28 general practices were categorised as GOLD-A (n=333), GOLD-B (n=110), GOLD-C (n=80) and GOLD-D (n=88).,Patients in the GOLD-B and GOLD-D groups had the highest prevalence of co-morbidities and the lowest level of physical activity, self-efficacy, and employment.,The models with GOLD ABCD groups were more strongly related to and explained more variance in costs and in disease-specific and generic HR-QoL than the models with GOLD 1234 grades.,The mean Clinical COPD Questionnaire score worsened significantly, with scores 1.04 (GOLD-B), 0.4 (GOLD-C) and 1.21 (GOLD-D) worse than for patients in GOLD-A.,Healthcare costs per patient were significantly higher in GOLD-B (72%), GOLD-C (74%) and GOLD-D (131%) patients than in GOLD-A patients.,The GOLD ABCD groups classification is more closely associated with costs and HR-QoL than the GOLD 1234 grades classification.,Furthermore, patients with GOLD-C had a better HR-QoL than those with GOLD-B but the costs of the two groups did not differ. | Favorable effects of formal pulmonary rehabilitation in selected moderate to severe COPD patients are well established.,Few data are available on the effects and costs of integrated disease management (IDM) programs on quality of care and health status of COPD patients in primary care, representing a much larger group of COPD patients.,Therefore, the RECODE trial assesses the long-term clinical and cost-effectiveness of IDM in primary care.,RECODE is a cluster randomized trial with two years of follow-up, during which 40 clusters of primary care teams (including 1086 COPD patients) are randomized to IDM or usual care.,The intervention started with a 2-day multidisciplinary course in which healthcare providers are trained as a team in essential components of effective COPD IDM in primary care.,During the course, the team redesigns the care process and defines responsibilities of different caregivers.,They are trained in how to use feedback on process and outcome data to guide implement guideline-driven integrated healthcare.,Practice-tailored feedback reports are provided at baseline, and at 6 and 12 months.,The team learns the details of an ICT program that supports recording of process and outcome measures.,Afterwards, the team designs a time-contingent individual practice plan, agreeing on steps to be taken in order to integrate a COPD IDM program into daily practice.,After 6 and 12 months, there is a refresher course for all teams simultaneously to enable them to learn from each other’s experience.,Health status of patients at 12 months is the primary outcome, measured by the Clinical COPD Questionnaire (CCQ).,Secondary outcomes include effects on quality of care, disease-specific and generic health-related quality of life, COPD exacerbations, dyspnea, costs of healthcare utilization, and productivity loss.,This article presents the protocol and baseline results of the RECODE trial.,This study will allow to evaluate whether IDM implemented in primary care can positively influence quality of life and quality of care in mild to moderate COPD patients, thereby making the benefits of multidisciplinary rehabilitation applicable to a substantial part of the COPD population.,Netherlands Trial Register (NTR): NTR2268 | 1 |
Dyspnea is a distressing, debilitating, and near-ubiquitous symptom affecting patients with COPD.,In addition to the functional consequences of dyspnea, which include activity limitation and reduced exercise tolerance, it is important to consider its psychological impact on patients with COPD, such as onset of depression or anxiety.,Moreover, the anticipation of dyspnea itself can have a significant effect on patients’ emotions and behavior, with patients frequently self-limiting physical activity to avoid what has become the hallmark symptom of COPD.,Dyspnea is, therefore, a key target for COPD treatments.,Pharmacologic treatments can optimize respiratory mechanics, provide symptom relief, and reduce patients’ increased inspiratory neural drive to breathe.,However, it is important to acknowledge the value of non-pharmacologic interventions, such as pulmonary rehabilitation and patient self-management education, which have proven to be invaluable tools for targeting the affective components of dyspnea.,Furthermore, it is important to encourage maintenance of physical activity to optimize long-term patient outcomes.,Here, we review the physiological and psychological consequences of activity-related dyspnea in COPD, assess the efficacy of modern management strategies in improving this common respiratory symptom, and discuss key unmet clinical and research needs that warrant further immediate attention. | Asthma and chronic obstructive pulmonary disease (COPD) are both highly prevalent conditions that can coexist in the same individual: the so-called ‘asthma -COPD overlap’ (ACO).,Its prevalence and prognosis vary widely depending on how ACO is defined in each publication, the severity of bronchial obstruction of patients included and the treatment they are receiving.,Although there is a lack of evidence about the biology of ACO, the overlap of both diseases should express a mixture of a Th1 inflammatory pattern (characteristic of COPD) and a Th2 signature (characteristic of asthma).,In this review we support a novel algorithm for ACO diagnosis proposed by the Spanish Respiratory Society (SEPAR), based on a sequential evaluation that considers: (a) the presence of chronic airflow limitation in a smoker or ex-smoker patient ⩾35 years old; (b) a current diagnosis of asthma; and (c) the existence of a very positive bronchodilator test (PBT; ⩾15% and ⩾400 ml) or the presence of eosinophilia in blood (⩾300 eosinophils/μl).,This algorithm can identify those patients who may benefit from a treatment with inhaled corticosteroids (ICSs) and maybe from biological drugs in a near future.,In addition, it is easily applicable in clinical practice.,The major disadvantage is that it groups patients with very different characteristics under the ACO’s umbrella.,In view of this heterogeneity, we recommend a strategy of defining specific and measurable therapeutic objectives for every single patient and identifying the traits that can be treated to achieve those objectives. | 1 |
Bodyweight and fat distribution may be related to COPD risk.,Limited prospective evidence linked COPD to abdominal adiposity.,We investigated the association of body mass index (BMI) and measures of abdominal adiposity with COPD risk in a prospective cohort study.,The China Kadoorie Biobank recruited participants aged 30-79 years from 10 areas across China.,Anthropometric indexes were objectively measured at the baseline survey during 2004-2008.,After exclusion of participants with prevalent COPD and major chronic diseases, 452 259 participants were included and followed-up until the end of 2016.,We used Cox models to estimate adjusted hazard ratios relating adiposity to risk of COPD hospitalisation or death.,Over an average of 10.1 years of follow-up, 10 739 COPD hospitalisation events and deaths were reported.,Compared with subjects with normal BMI (18.5-<24.0 kg·m−2), underweight (BMI <18.5 kg·m−2) individuals had increased risk of COPD, with adjusted hazard ratio 1.78 (95% CI 1.66-1.89).,Overweight (BMI 24.0-<28.0 kg·m−2) and obesity (BMI ≥28.0 kg·m−2) were not associated with an increased risk after adjustment for waist circumference.,A higher waist circumference (≥85 cm for males and ≥80 cm for females) was positively associated with COPD risk after adjustment for BMI.,Additionally, waist-to-hip ratio and waist-to-height ratio were positively related to COPD risk.,Abdominal adiposity and underweight were risk factors for COPD in Chinese adults.,Both BMI and measures of abdominal adiposity should be considered in the prevention of COPD.,Abdominal adiposity and underweight were risk factors for COPD in Chinese adults.,Both BMI and measures of abdominal adiposity should be considered in the prevention of COPD.http://bit.ly/36To4fk | Chronic obstructive pulmonary disease is one of the leading causes of morbidity and mortality worldwide and a growing healthcare problem.,Identification of modifiable risk factors for prevention and treatment of COPD is urgent, and the scientific community has begun to pay close attention to diet as an integral part of COPD management, from prevention to treatment.,This review summarizes the evidence from observational and clinical studies regarding the impact of nutrients and dietary patterns on lung function and COPD development, progression, and outcomes, with highlights on potential mechanisms of action.,Several dietary options can be considered in terms of COPD prevention and/or progression.,Although definitive data are lacking, the available scientific evidence indicates that some foods and nutrients, especially those nutraceuticals endowed with antioxidant and anti-inflammatory properties and when consumed in combinations in the form of balanced dietary patterns, are associated with better pulmonary function, less lung function decline, and reduced risk of COPD.,Knowledge of dietary influences on COPD may provide health professionals with an evidence-based lifestyle approach to better counsel patients toward improved pulmonary health. | 1 |
To identify COPD associated gene susceptibility and lung function in a longitudinal cohort including COPD and subjects who were at risk for developing COPD, and to replicate this in two cross-sectional and longitudinal populations in Chinese Han population.,Three cohorts were recruited in this study, including an 18-year follow-up population (306 COPD and 743 control subjects) in one village in 1992 and it changed to 409 COPD and 611 controls in 2010, a 2 year follow-up study in another village (374 COPD and 377 controls) and another 2 year follow-up one in a city (541 COPD and 560 controls) in 2010.,Sixteen candidate single nucleotide polymorphisms (SNPs) were selected for genotyping.,Among them, 5SNPs in or near HHIP, 1SNP in IREB2 and 1SNP in FAM13A were previously reported to be associated with COPD susceptibility or lung function decline.,And another 9SNPs were selected from HapMap website as HHIP tags.,In 2010, totaling 1,324 COPD patients and 1,548 healthy controls were finally included in our genetic susceptibility analyses.,We identified two new regions showing an association with COPD susceptibility in the Human Hedgehog interacting protein (HHIP) rs11100865 and rs7654947, and we confirmed that the family with sequence similarity 13 member A gene (FAM13A) rs7671167 was associated with the development of COPD in Chinese Han population.,And the HHIP rs7654947 and FAM13A rs7671167 were associated with lung function decline, and this result was replicated in other two populations.,These results suggest an important role of the HHIP and FAM13A regions as genetic risk factors for COPD development and lung function decline in Chinese Han population.,Future research on these genes should focus on the molecular mechanisms of these genes on developing COPD and creating therapies to alleviate reduced lung function.,The online version of this article (doi:10.1186/s12931-015-0209-3) contains supplementary material, which is available to authorized users. | Substantial evidence suggests that there is genetic susceptibility to chronic obstructive pulmonary disease (COPD).,To identify common genetic risk variants, we performed a genome-wide association study in 2940 cases and 1380 smoking controls with normal lung function.,We demonstrate a novel susceptibility locus at 4q22.1 in FAM13A (rs7671167, OR=0.76, P=8.6×10−8) and provide evidence of replication in one case-control and two family-based cohorts (for all studies, combined P=1.2×10−11). | 1 |
The use of information and communication technologies to manage chronic diseases allows the application of integrated care pathways, and the optimization and standardization of care processes.,Decision support tools can assist in the adherence to best-practice medicine in critical decision points during the execution of a care pathway.,The objectives are to design, develop, and assess a clinical decision support system (CDSS) offering a suite of services for the early detection and assessment of chronic obstructive pulmonary disease (COPD), which can be easily integrated into a healthcare providers' work-flow.,The software architecture model for the CDSS, interoperable clinical-knowledge representation, and inference engine were designed and implemented to form a base CDSS framework.,The CDSS functionalities were iteratively developed through requirement-adjustment/development/validation cycles using enterprise-grade software-engineering methodologies and technologies.,Within each cycle, clinical-knowledge acquisition was performed by a health-informatics engineer and a clinical-expert team.,A suite of decision-support web services for (i) COPD early detection and diagnosis, (ii) spirometry quality-control support, (iii) patient stratification, was deployed in a secured environment on-line.,The CDSS diagnostic performance was assessed using a validation set of 323 cases with 90% specificity, and 96% sensitivity.,Web services were integrated in existing health information system platforms.,Specialized decision support can be offered as a complementary service to existing policies of integrated care for chronic-disease management.,The CDSS was able to issue recommendations that have a high degree of accuracy to support COPD case-finding.,Integration into healthcare providers' work-flow can be achieved seamlessly through the use of a modular design and service-oriented architecture that connect to existing health information systems. | Chronic Obstructive Pulmonary Disease (COPD) patients are characterized by heterogeneous clinical manifestations and patterns of disease progression.,Two major factors that can be used to identify COPD subtypes are muscle dysfunction/wasting and co-morbidity patterns.,We hypothesized that COPD heterogeneity is in part the result of complex interactions between several genes and pathways.,We explored the possibility of using a Systems Medicine approach to identify such pathways, as well as to generate predictive computational models that may be used in clinic practice.,Our overarching goal is to generate clinically applicable predictive models that characterize COPD heterogeneity through a Systems Medicine approach.,To this end we have developed a general framework, consisting of three steps/objectives: (1) feature identification, (2) model generation and statistical validation, and (3) application and validation of the predictive models in the clinical scenario.,We used muscle dysfunction and co-morbidity as test cases for this framework.,In the study of muscle wasting we identified relevant features (genes) by a network analysis and generated predictive models that integrate mechanistic and probabilistic models.,This allowed us to characterize muscle wasting as a general de-regulation of pathway interactions.,In the co-morbidity analysis we identified relevant features (genes/pathways) by the integration of gene-disease and disease-disease associations.,We further present a detailed characterization of co-morbidities in COPD patients that was implemented into a predictive model.,In both use cases we were able to achieve predictive modeling but we also identified several key challenges, the most pressing being the validation and implementation into actual clinical practice.,The results confirm the potential of the Systems Medicine approach to study complex diseases and generate clinically relevant predictive models.,Our study also highlights important obstacles and bottlenecks for such approaches (e.g. data availability and normalization of frameworks among others) and suggests specific proposals to overcome them. | 1 |
Pulmonary emphysema is characterized by the irreversible loss of pulmonary alveoli.,Despite recent advances in the understanding this disease, its treatment remains palliative.,In this review, we will successively review the data suggesting (1) that alveolar regeneration systems are functional in the mammalian lung and have the potential to regrow lost alveoli, (2) that cigarette smoke, the main etiologic factor of emphysema, inhibits those systems under experimental conditions, and (3) that alveolar regeneration systems are dysfunctional in the human emphysematous lung and may be a target for therapeutic intervention in this disease.,Special emphasis will be put on the role of alveolar fibroblasts in those processes. | Emphysema is mainly caused by cigarette smoking and is characterized by the loss of alveolar integrity and an enlargement of the alveolar space.,However, mechanisms involved in its development are not fully understood.,Alveolar cell apoptosis has been previously investigated in the lung of emphysematous subjects as a potential contributor to the loss of alveolar cell and has been found abnormally elevated.,Though, mechanisms involved in the increased alveolar apoptosis that occurs in emphysema have now become a prolific field of research.,Those mechanisms are reviewed here with special focus on how they affect cell viability and how they may be implicated in emphysema.,Moreover, we suggest a model that integrates all those mechanisms to explain the increased alveolar apoptosis observed in emphysema.,This review also includes some reflections and suggestions on the research to come. | 1 |
Patients with COPD experience respiratory symptoms, impairments of daily living and recurrent exacerbations.,The aim of integrated disease management (IDM) is to establish a programme of different components of care (ie, self-management, exercise, nutrition) in which several healthcare providers (ie, nurses, general practitioners, physiotherapists, pulmonologists) collaborate to provide efficient and good quality of care.,The aim of this Cochrane systematic review was to evaluate the effectiveness of IDM on quality of life, exercise tolerance and exacerbation related outcomes.,Searches for all available evidence were carried out in various databases.,Included randomised controlled trials (RCTs) consisted of interventions with multidisciplinary (≥2 healthcare providers) and multitreatment (≥2 components) IDM interventions with duration of at least 3 months.,Two reviewers independently searched, assessed and extracted data of all RCTs.,A total of 26 RCTs were included, involving 2997 patients from 11 different countries with a follow-up varying from 3 to 24 months.,In all 68% of the patients were men, with a mean age of 68 years and a mean forced expiratory volume in 1 s (FEV1) predicted value of 44.3%.,Patients treated with an IDM programme improved significantly on quality of life scores and reported a clinically relevant improvement of 44 m on 6 min walking distance, compared to controls.,Furthermore, the number of patients with ≥1 respiratory related hospital admission reduced from 27 to 20 per 100 patients.,Duration of hospitalisation decreased significantly by nearly 4 days. | Pulmonary rehabilitation (PR) is an important treatment option for chronic obstructive pulmonary disease (COPD) patients and might contribute to a reduction in exacerbation and exacerbation-related hospitalization rate.,In this prospective study, all COPD patients that completed a comprehensive pulmonary rehabilitation program (PRP) between June 2006 and December 2012 were included.,Self-reported exacerbation and hospitalization frequency 1 year before PR was retrospectively recorded.,During the year following PR, exacerbation and hospitalization frequency was recorded with questionnaires.,For 343 patients, complete information on exacerbation and hospitalization rate was obtained.,The mean number of exacerbations decreased significantly after participating in a PRP by 1.37 exacerbations/year (95% confidence interval 1.029 to 1.717) from 4.56±3.26 exacerbations in the year preceding PR to 3.18±2.53 in the year following PR (P<0.0005).,The number of hospitalizations due to exacerbations decreased significantly by 0.68 hospitalizations/year (95% confidence interval 0.467 to 0.903) from 1.48±1.84 in the year preceding PR to 0.80±1.31 hospitalizations/year in the year following PR (P<0.0005).,The proportion of patients with a frequent exacerbation type (more than two exacerbations/year) was reduced by 24%.,Multivariate regression analysis to explore determinants that might predict reduction in exacerbation frequency or change in exacerbation pattern did not reveal clinically useful predictors, although patients with more exacerbations before PR had the highest potential for reduction.,In a large population of severely impaired COPD patients with high exacerbation rates, a significant reduction in exacerbation and hospitalization frequency was observed after participation in a comprehensive PRP. | 1 |
Conventional measures to evaluate COPD may fail to capture systemic problems, particularly musculoskeletal weakness and cardiovascular disease.,Identifying these manifestations and assessing their association with clinical outcomes (ie, mortality, exacerbation and COPD hospital admission) is of increasing clinical importance.,To assess associations between 6 min walk distance (6MWD), heart rate, fibrinogen, C reactive protein (CRP), white cell count (WCC), interleukins 6 and 8 (IL-6 and IL-8), tumour necrosis factor-alpha, quadriceps maximum voluntary contraction, sniff nasal inspiratory pressure, short physical performance battery, pulse wave velocity, carotid intima-media thickness and augmentation index and clinical outcomes in patients with stable COPD.,We systematically searched electronic databases (August 2018) and identified 61 studies, which were synthesised, including meta-analyses to estimate pooled HRs, following Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.,Shorter 6MWD and elevated heart rate, fibrinogen, CRP and WCC were associated with higher risk of mortality.,Pooled HRs were 0.80 (95% CI 0.73 to 0.89) per 50 m longer 6MWD, 1.10 (95% CI 1.02 to 1.18) per 10 bpm higher heart rate, 3.13 (95% CI 2.14 to 4.57) per twofold increase in fibrinogen, 1.17 (95% CI 1.06 to 1.28) per twofold increase in CRP and 2.07 (95% CI 1.29 to 3.31) per twofold increase in WCC.,Shorter 6MWD and elevated fibrinogen and CRP were associated with exacerbation, and shorter 6MWD, higher heart rate, CRP and IL-6 were associated with hospitalisation.,Few studies examined associations with musculoskeletal measures.,Findings suggest 6MWD, heart rate, CRP, fibrinogen and WCC are associated with clinical outcomes in patients with stable COPD.,Use of musculoskeletal measures to assess outcomes in patients with COPD requires further investigation.,CRD42016052075. | Reduced physical activity is an important feature of Chronic Obstructive Pulmonary Disease (COPD).,Various activity monitors are available but their validity is poorly established.,The aim was to evaluate the validity of six monitors in patients with COPD.,We hypothesized triaxial monitors to be more valid compared to uniaxial monitors.,Thirty-nine patients (age 68±7years, FEV1 54±18%predicted) performed a one-hour standardized activity protocol.,Patients wore 6 monitors (Kenz Lifecorder (Kenz), Actiwatch, RT3, Actigraph GT3X (Actigraph), Dynaport MiniMod (MiniMod), and SenseWear Armband (SenseWear)) as well as a portable metabolic system (Oxycon Mobile).,Validity was evaluated by correlation analysis between indirect calorimetry (VO2) and the monitor outputs: Metabolic Equivalent of Task [METs] (SenseWear, MiniMod), activity counts (Actiwatch), vector magnitude units (Actigraph, RT3) and arbitrary units (Kenz) over the whole protocol and slow versus fast walking.,Minute-by-minute correlations were highest for the MiniMod (r = 0.82), Actigraph (r = 0.79), SenseWear (r = 0.73) and RT3 (r = 0.73).,Over the whole protocol, the mean correlations were best for the SenseWear (r = 0.76), Kenz (r = 0.52), Actigraph (r = 0.49) and MiniMod (r = 0.45).,The MiniMod (r = 0.94) and Actigraph (r = 0.88) performed better in detecting different walking speeds.,The Dynaport MiniMod, Actigraph GT3X and SenseWear Armband (all triaxial monitors) are the most valid monitors during standardized physical activities.,The Dynaport MiniMod and Actigraph GT3X discriminate best between different walking speeds. | 1 |
Endpoints that evaluate deterioration rather than improvement of disease may have clinical utility in COPD.,In this analysis, we compared the effects of different maintenance treatments on the prevention of clinically important deterioration (CID) in moderate-to-severe COPD patients.,Data were analyzed from three 26-week studies comparing indacaterol/glycopyrronium (IND/GLY) with tiotropium (TIO) or salmeterol/fluticasone (SFC).,Two definitions of CID were used; each was a composite of three outcome measures typically associated with COPD.,Definition 1 (D1) comprised a ≥100 mL decrease in forced expiratory volume in 1 second (FEV1), a ≥4-unit increase in St George’s Respiratory Questionnaire, and a moderate-to-severe COPD exacerbation.,In Definition 2 (D2), a ≥1-unit decrease in transition dyspnea index replaced FEV1.,Using D1, IND/GLY significantly reduced the risk of first or sustained CID versus either TIO (hazard ratio 0.72 [0.61, 0.86], P=0.0003 and 0.73 [0.61, 0.89], P=0.001) or SFC (0.67 [0.57, 0.80] and 0.63 [0.52, 0.77], both P<0.0001).,With D2, IND/GLY significantly reduced the risk of first, but not sustained, CID versus TIO (0.80 [0.64 to 0.99], P=0.0359 and 0.85 [0.66, 1.10], P=0.2208) and both first and sustained CID versus SFC (0.73 [0.61, 0.88], P=0.001 and 0.72 [0.58, 0.90], P=0.0036).,These data confirm the utility of the CID endpoint as a means of monitoring COPD worsening in patients with moderate-to-severe COPD.,Using the CID measure, we demonstrated that dual bronchodilation with IND/GLY significantly reduced the risk of CID versus either long-acting muscarinic antagonist or long-acting β2-agonist/inhaled corticosteroid treatment, providing further evidence for the benefit of dual bronchodilation in this patient population. | 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. | 1 |
We have previously shown that NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells are reduced in both numbers and cytotoxicity in peripheral blood.,The aim of the present study was to investigate their numbers and function within induced sputum.,Induced sputum cell numbers and intracellular granzyme B and perforin were analysed by flow cytometry.,Immunomagnetically selected CD56+ cells (NK and NKT-like cells) were used in an LDH release assay to determine cytotoxicity.,The proportion of NK cells and NKT-like cells in smokers with COPD (COPD subjects) was significantly higher (12.7% and 3%, respectively) than in healthy smokers (smokers) (5.7%, p < 0.01; 1%, p < 0.001) and non-smoking healthy subjects (HNS) (4.2%, p < 0.001; 0.8%, p < 0.01).,The proportions of NK cells and NKT-like cells expressing both perforin and granzyme B were also significantly higher in COPD subjects compared to smokers and HNS.,CD56+ cells from COPD subjects were significantly more cytotoxic (1414 biological lytic activity) than those from smokers (142.5; p < 0.01) and HNS (3.8; p < 0.001) and were inversely correlated to FEV1. (r = -0.75; p = 0.0098).,We have shown an increased proportion of NK and NKT-like cells in the induced sputum of COPD subjects and have demonstrated that these cells are significantly more cytotoxic in COPD subjects than smokers and HNS. | There is mounting evidence that perforin and granzymes are important mediators in the lung destruction seen in COPD.,We investigated the characteristics of the three main perforin and granzyme containing peripheral cells, namely CD8+ T lymphocytes, natural killer (NK; CD56+CD3-) cells and NKT-like (CD56+CD3+) cells.,Peripheral blood mononuclear cells (PBMCs) were isolated and cell numbers and intracellular granzyme B and perforin were analysed by flow cytometry.,Immunomagnetically selected CD8+ T lymphocytes, NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells were used in an LDH release assay to determine cytotoxicity and cytotoxic mechanisms were investigated by blocking perforin and granzyme B with relevant antibodies.,The proportion of peripheral blood NKT-like (CD56+CD3+) cells in smokers with COPD (COPD subjects) was significantly lower (0.6%) than in healthy smokers (smokers) (2.8%, p < 0.001) and non-smoking healthy participants (HNS) (3.3%, p < 0.001).,NK (CD56+CD3-) cells from COPD subjects were significantly less cytotoxic than in smokers (16.8% vs 51.9% specific lysis, p < 0.001) as were NKT-like (CD56+CD3+) cells (16.7% vs 52.4% specific lysis, p < 0.001).,Both cell types had lower proportions expressing both perforin and granzyme B.,Blocking the action of perforin and granzyme B reduced the cytotoxic activity of NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells from smokers and HNS.,In this study, we show that the relative numbers of peripheral blood NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells in COPD subjects are reduced and that their cytotoxic effector function is defective. | 1 |
Self-management interventions for chronic obstructive pulmonary disease (COPD) can improve quality of life, reduce hospital admissions, and improve symptoms.,However, many factors impede engagement for patients and practitioners.,Qualitative research, with its focus on subjective experience, can provide invaluable insights into such factors.,Therefore, a systematic review and synthesis of qualitative evidence on COPD self-management from the perspective of patients, carers, and practitioners was conducted.,Following a systematic search and screening, 31 studies were appraised and data extracted for analysis.,This review found that patients can adapt to COPD; however, learning to self-manage is often a protracted process.,Emotional needs are considerable; frustration, depression, and anxiety are common.,In addition, patients can face an assortment of losses and limitations on their lifestyle and social interaction.,Over time, COPD can consume their existence, reducing motivation.,Support from family can prove vital, yet tinged with ambivalence and burden.,Practitioners may not have sufficient time, resources, or appropriate skills or confidence to provide effective self-management support, particularly in regard to patients’ psychosocial needs.,This can compound patients’ capability to engage in self-management.,For COPD self-management to be effective, patients’ psychosocial needs must be prioritised alongside medication and exacerbation management.,In addition, patients’ personal beliefs regarding COPD and its management should be reviewed periodically to avoid problematic behaviours and enhance positive adaptions to the disease.,Patients with COPD are not a homogenous group and no one intervention will prove effective for all.,Finally, practitioners require greater education, training, and support to successfully assist patients. | Chronic obstructive pulmonary disease (COPD) has traditionally been considered an inexorably progressive disease, associated with a constant increase of symptoms that occur as the forced expiratory volume in 1 second (FEV1) worsens, only intermittently interrupted by exacerbations.,However, this paradigm has been challenged in recent decades by the available evidence.,Recent studies have pointed out that COPD-related symptoms are not consistently perceived by patients in the same way, showing not only seasonal variation, but also changes in symptom perception during a week or even within a single day.,According to the available data, patients experience the biggest increase in respiratory symptoms during the first hours of the early morning, followed by the nighttime.,This variation over time is of considerable importance, since it impacts on daily life activities and health-related quality of life, as measured by a recently developed ad hoc questionnaire.,Additionally, recent clinical trials have suggested that the use of rapid-onset long-acting bronchodilators may have an impact on morning symptoms, despite their current use as maintenance treatment for a determined period.,Although this hypothesis is to be validated in future long-term clinical trials comparing fast-onset versus slow-onset inhaled drugs in COPD, it may bring forward a new concept of long-term bronchodilator therapy.,At the present time, the two available long-acting, fast-onset bronchodilators used in the treatment of COPD are formoterol and the recently marketed indacaterol.,Newer drugs have also been shown to have a rapid onset of action in preclinical studies.,Health care professionals caring for COPD patients should consider this variation in the perception of symptoms during their clinical interview as a potential new target in the long-term treatment plan. | 1 |
“Physical inactivity” and “sedentary lifestyles” are phrases often used when describing lifestyles of people with chronic obstructive pulmonary disease (COPD).,Evidence suggests activity types, independent of energy expenditure, influence health outcomes, so understanding patterns of time use is important, particularly in chronic disease.,We aimed to identify reports of time use in people with COPD.,Predefined search strategies were used with six electronic databases to identify individual activity reports (including frequencies and/or durations) in which community-dwelling people with COPD engaged.,Eligible studies were assessed independently against predefined criteria and data were extracted by two reviewers.,Data synthesis was achieved by aggregating activity reports into activity domains (sports/exercise, screen time, transport, quiet time, self-care, sociocultural, work/study, chores, and sleep).,Twenty-six publications reported 37 specific daily activities.,People with COPD were found to spend extended periods in sedentary behaviors (eg, standing [194 min/day]; sitting [359 min/day]; lying [88 min/day]), have limited engagement in physical activity (eg, walking [51 min/day]; exercising [1.2 episodes per week {ep/w}, 13 min/day]), have high health care needs (medical appointments [1.0 ep/w]), and experience difficulties associated with activities of daily living (eg, showering [2.5 ep/w, 60 minutes per episode]; preparing meals [4.7 ep/w]).,Little data could be found describing how people with COPD use their time, and data synthesis was problematic because of variations in methodologies, population differences, and research emphases.,Identified data largely referred to posture and were skewed according to country, assessment methods, and disease severity.,Comparisons with age-matched population data showed people with COPD spent less time engaged in personal-care activities (self-care and sleeping) and chores than people in similar age groups.,The incorporation of time-use outcomes in future research designs should be encouraged.,Ideally, these tools should use consistent frameworks and comparable outcome measures in order to provide clearer descriptions of time use in chronic disease. | The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed.,Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD.,We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012.,Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence.,86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both.,Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence.,Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low.,As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence.,Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence.,Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment. | 1 |
Patients with COPD have frequent exacerbations.,The role of respiratory viral infection is just emerging.,We wished to determine prospectively the incidence of viral infection in exacerbated and stable COPD patients as well as smokers who do not have airways obstruction.,Stable and exacerbated COPD patients were recruited along with a group of patients who had smoked but who did not have any airways obstruction.,Spirometry was performed and sputum specimens were tested for a range of 12 different respiratory viruses using PCR.,One hundred and thirty-six patients with exacerbations of COPD, 68 stable COPD patients and 16 non-obstructed smokers were recruited.,A respiratory virus was detected in 37% of exacerbations, 12% of stable COPD patients and 12% of non-obstructed smokers, p < 0.0005.,Rhinovirus was most frequently detected.,The symptom of fever was associated with virus detection, p < 0.05.,Infection with more than one virus was only found in the exacerbated COPD patients.,Respiratory viral infection is associated with exacerbations of COPD.,Rhinovirus was the most common infecting agent identified and in two cases human metapneumovirus was also detected.,Dual infections were only seen amongst those patients admitted to hospital with acute exacerbations of COPD.,Viruses were more commonly detected in those with more severe airways disease. | Moraxella catarrhalis causes approximately 10% of exacerbations in chronic obstructive pulmonary disease (COPD) and also colonizes the lower airway in stable patients.,Little is known about the effects of colonization by M. catarrhalis on airway inflammation and protease-antiprotease balance, and how these changes compare to those seen during exacerbations.,Since COPD is a progressive inflammatory disease, elucidating the effects of bacterial colonization and exacerbation on airway inflammation is relevant to understanding disease progression in COPD.,Our aims were (1) Analyze changes in airway inflammation in colonization and exacerbation of COPD due to M. catarrhalis; (2) Explore protease-antiprotease balance in colonization and exacerbation due to M. catarrhalis.,Our hypothesis were (1) Acquisition of a new strain of M. catarrhalis in COPD increases airway inflammation from baseline and alters the protease-antiprotease balance towards a more proteolytic environment; (2) These changes are greater during exacerbations associated with M. catarrhalis as compared to colonization.,Thirty-nine consecutive COPD patients with 76 acquisitions of a new strain of M. catarrhalis over a 6-year period were identified in a prospective study.,Seventy-six pre-acquisition sputum supernatant samples, obtained just before acquisition of M catarrhalis, and 76 acquisition samples (34 were associated with exacerbation, 42 with colonization) were analyzed for IL-8, TNF-α, Neutrophil Elastase (NE) and Secretory leukocyte protease inhibitor (SLPI).,Changes were compared in paired samples from each patient.,IL-8, TNF-α and NE were significantly elevated after acquisition of M. catarrhalis, compared to pre-acquisition samples (p =< 0.001 for all three).,These changes were present in colonization (p = 0.015 for IL-8; p =< 0.001 for TNF-α and NE) as well as in exacerbation (p =< 0.001 for all three), compared to pre-acquisition levels.,SLPI was significantly lower after acquisition (p =< 0.001), in colonization (p =< 0.001) as well as in exacerbation (p = 0.004), compared to pre-acquisition levels.,SLPI levels correlated negatively with NE levels (R2 = 0.07; p = 0.001).,Acquisition of M. catarrhalis in COPD causes increased airway inflammation and worsening protease-antiprotease imbalance during exacerbations and also in colonization, even in the absence of increased symptoms.,These effects could contribute to progression of airway disease in COPD. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD), characterized by acute deterioration in symptoms, may be due to bacterial or viral infections, environmental exposures, or unknown factors.,Exacerbation frequency may be a stable trait in COPD patients, which could imply genetic susceptibility.,Observing the genes, networks, and pathways that are up- and down-regulated in COPD patients with differing susceptibility to exacerbations will help to elucidate the molecular signature and pathogenesis of COPD exacerbations.,Gene expression array and plasma biomarker data were obtained using whole-blood samples from subjects enrolled in the Treatment of Emphysema With a Gamma-Selective Retinoid Agonist (TESRA) study.,Linear regression, weighted gene co-expression network analysis (WGCNA), and pathway analysis were used to identify signatures and network sub-modules associated with the number of exacerbations within the previous year; other COPD-related phenotypes were also investigated.,Individual genes were not found to be significantly associated with the number of exacerbations.,However using network methods, a statistically significant gene module was identified, along with other modules showing moderate association.,A diverse signature was observed across these modules using pathway analysis, marked by differences in B cell and NK cell activity, as well as cellular markers of viral infection.,Within two modules, gene set enrichment analysis recapitulated the molecular signatures of two gene expression experiments; one involving sputum from asthma exacerbations and another involving viral lung infections.,The plasma biomarker myeloperoxidase (MPO) was associated with the number of recent exacerbations.,A distinct signature of COPD exacerbations may be observed in peripheral blood months following the acute illness.,While not predictive in this cross-sectional analysis, these results will be useful in uncovering the molecular pathogenesis of COPD exacerbations.,The online version of this article (doi:10.1186/s12920-014-0072-y) contains supplementary material, which is available to authorized users. | Patients with chronic obstructive pulmonary disease (COPD) who are defined as frequent exacerbators suffer with 2 or more exacerbations every year.,The molecular mechanisms responsible for this phenotype are poorly understood.,We investigated gene expression profile patterns associated with frequent exacerbations in sputum and blood cells in a well-characterised cohort.,Samples from subjects from the ECLIPSE COPD cohort were used; sputum and blood samples from 138 subjects were used for microarray gene expression analysis, while blood samples from 438 subjects were used for polymerase chain reaction (PCR) testing.,Using microarray, 150 genes were differentially expressed in blood (>±1.5 fold change, p≤0.01) between frequent compared to non-exacerbators.,In sputum cells, only 6 genes were differentially expressed.,The differentially regulated genes in blood included downregulation of those involved in lymphocyte signalling and upregulation of pro-apoptotic signalling genes.,Multivariate analysis of the microarray data followed by confirmatory PCR analysis identified 3 genes that predicted frequent exacerbations; B3GNT, LAF4 and ARHGEF10.,The sensitivity and specificity of these 3 genes to predict the frequent exacerbator phenotype was 88% and 33% respectively.,There are alterations in systemic immune function associated with frequent exacerbations; down-regulation of lymphocyte function and a shift towards pro-apoptosis mechanisms are apparent in patients with frequent exacerbations. | 1 |
Chronic obstructive pulmonary disease (COPD), a prevalent obstructive airway disease, has become the third most common cause of death globally.,Xuanbai Chengqi decoction (XBCQ) is a traditional Chinese medicine prescription for the acute exacerbation of COPD.,Here, we aimed to reveal the therapeutic effects of XBCQ administration and its molecular mechanisms mediated by Th17/Treg balance and gut microbiota.,We determined the counts of Th17 and Treg cells in the serum of 15 COPD and 10 healthy subjects.,Then, cigarette smoke extract-induced COPD mice were gavaged with low, middle, and high doses of XBCQ, respectively.,Weight loss, pulmonary function and inflammation, Th17/Treg ratio, and gut microbiota were measured to evaluate the efficacy of XBCQ on COPD.,COPD patients had a higher Th17/Treg ratio in the serum than healthy controls, which was consistent with the results in the lung and colon of COPD mice.,The middle dose of XBCQ (M-XBCQ) significantly decreased the weight loss and improved the pulmonary function (FEV0.2/FVC) in COPD mice.,Moreover, M-XBCQ alleviated lung inflammation by rectifying the Th17/Treg imbalance, reducing the expressions of TNF-α, IL-1β, and MMP-9, and suppressing inflammatory cells infiltration.,Meanwhile, M-XBCQ greatly improved the microbial homeostasis in COPD mice by accumulating probiotic Gordonibacter and Akkermansia but inhibiting the growth of pathogenic Streptococcus, which showed significant correlations with pulmonary injury.,Oral M-XBCQ could alleviate COPD exacerbations by reshaping the gut microbiota and improving the Th17/Treg balance, which aids in elucidating the mechanism through which XBCQ as a therapy for COPD. | The Chinese herbal Bufei Jianpi formula (BJF) provides an effective treatment option for chronic obstructive pulmonary disease (COPD).,However, the systems-level mechanism underlying the clinical effects of BJF on COPD remains unknown.,In this study, a systems pharmacology model based on absorption filtering, network targeting, and systems analyses was applied specifically to clarify the active compounds and therapeutic mechanisms of BJF.,Then, a rat model of cigarette smoke- and bacterial infection-induced COPD was used to investigate the therapeutic mechanisms of BJF on COPD and its comorbidity.,The pharmacological system successfully identified 145 bioactive ingredients from BJF and revealed 175 potential targets.,There was a significant target overlap between the herbal constituents of BJF.,These results suggested that each herb of BJF connected with similar multitargets, indicating potential synergistic effects among them.,The integrated target-disease network showed that BJF probably was efficient for the treatment of not only respiratory tract diseases but also other diseases, such as nervous system and cardiovascular diseases.,The possible mechanisms of action of BJF were related to activation of inflammatory response, immune responses, and matrix metalloproteinases, among others.,Furthermore, we demonstrated that BJF treatment could effectively prevent COPD and its comorbidities, such as ventricular hypertrophy, by inhibition of inflammatory cytokine production, matrix metalloproteinases expression, and other cytokine production in vivo.,This study using the systems pharmacology method, in combination with in vivo experiments, helped us successfully dissect the molecular mechanism of BJF for the treatment of COPD and predict the potential targets of the multicomponent BJF, which provides a new approach to illustrate the synergetic mechanism of the complex prescription and discover more effective drugs against COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality.,The cornerstone of pharmacological treatment for COPD is bronchodilation.,Inhaled glycopyrronium bromide is a long-acting muscarinic antagonist developed as a maintenance treatment for patients with COPD.,Phase III trials have shown that glycopyrronium produces rapid and sustained bronchodilation with an efficacy similar to tiotropium and is well tolerated, with a low incidence of muscarinic side effects in patients with moderate to severe COPD.,A combination of glycopyrronium bromide with indacaterol maleate (QVA149) has recently been approved as a once-daily maintenance therapy in adult patients with COPD.,Phase III trials (the IGNITE program) with QVA149 have demonstrated significant improvements in lung function versus placebo, glycopyrronium, and tiotropium in patients with moderate to severe COPD, with no safety concerns of note.,Hence QVA149 is a safe treatment option for moderate to severe COPD patients in whom long-acting muscarinic antagonist monotherapy is inadequate. | Exercise limitation, dynamic hyperinflation, and exertional dyspnea are key features of symptomatic chronic obstructive pulmonary disease (COPD).,We assessed the effects of glycopyrronium bromide (NVA237), a once-daily, long-acting muscarinic antagonist, on exercise tolerance in patients with moderate to severe COPD.,Patients were randomized to a cross-over design of once-daily NVA237 50 μg or placebo for 3 weeks, with a 14-day washout.,Exercise endurance, inspiratory capacity (IC) during exercise, IC and expiratory volumes from spirometry, plethysmographic lung volumes, leg discomfort and dyspnea under exercise (Borg scales), and transition dyspnea index were measured on Days 1 and 21 of treatment.,The primary endpoint was endurance time during a submaximal constant-load cycle ergometry test on Day 21.,A total of 108 patients were randomized to different treatment groups (mean age, 60.5 years; mean post-bronchodilator, forced expiratory volume in 1 second [FEV1] 57.1% predicted).,Ninety-five patients completed the study.,On Day 21, a 21% difference in endurance time was observed between patients treated with NVA237 and those treated with placebo (P < 0.001); the effect was also significant from Day 1, with an increase of 10%.,Dynamic IC at exercise isotime and trough FEV1 showed significant and clinically relevant improvements from Day 1 of treatment that were maintained throughout the study.,This was accompanied by inverse decreases in residual volume and functional residual capacity.,NVA237 was superior to placebo (P < 0.05) in decreasing leg discomfort (Borg CR10 scale) on Day 21 and exertional dyspnea on Days 1 and 21 (transition dyspnea index and Borg CR10 scale at isotime).,The safety profile of NVA237 was similar to that of the placebo.,NVA237 50 μg once daily produced immediate and significant improvement in exercise tolerance from Day 1.,This was accompanied by sustained reductions in lung hyperinflation (indicated by sustained and significant improvements in IC at isotime), and meaningful improvements in trough FEV1 and dyspnea.,Improvements in exercise endurance increased over time, suggesting that mechanisms beyond improved lung function may be involved in enhanced exercise tolerance.,(ClinicalTrials.gov Identifier: NCT01154127). | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are natural events in the progression of the disease, and are characterised by acute worsening of symptoms, especially dyspnoea.,These heterogeneous events follow increased airway inflammation, often due to infection, and lead to decreased airflow and increased lung hyperinflation relative to stable COPD.,Although exacerbation frequency generally increases as COPD progresses, some patients experience frequent exacerbations (≥2 per year) independently of disease severity.,Exacerbations, especially frequent exacerbations, are associated with impaired health-related quality of life, reduced physical activity and poor disease prognosis.,The cornerstone of pharmacotherapy for stable COPD is long-acting bronchodilators, including the long-acting β2-agonists (LABAs) and long-acting anti-muscarinic agents (LAMAs) alone or combined with inhaled corticosteroids (ICS).,While ICS treatment can potentially reduce the risk of exacerbations, clinical studies have demonstrated the efficacy of LABAs and LAMAs in reducing COPD symptoms, primarily by reducing lung hyperinflation secondary to reduced airway resistance.,Sustained reduction in lung hyperinflation may in turn lessen dyspnoea during an exacerbation.,Indeed, recent studies suggest that bronchodilators may also reduce the incidence of, or prevent, exacerbations.,Using data from recent studies, this review explores the evidence and possible mechanisms through which bronchodilators may prevent exacerbations. | 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. | 1 |
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. | To compare the Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE) index scores and its individual components between COPD patients with and without severe physical inactivity, as well as to correlate the number of steps/day with scores of physical activity questionnaires, age, and the BODE index (including its components).,We included 30 patients, who were evaluated for body composition, pulmonary function (FEV1), perception of dyspnea (modified Medical Research Council scale), and exercise capacity (six-minute walk distance [6MWD]).,The patients also completed the International Physical Activity Questionnaire (IPAQ), short version, and the modified Baecke questionnaire (mBQ).,The level of physical activity was assessed by the number of steps/day (as determined by pedometer), using the cut-off of 4,580 steps/day to form two groups: no severe physical inactivity (SPI−) and severe physical inactivity (SPI+).,We used the Mann-Whitney test or t-test, as well as Pearson's or Spearman's correlation tests, in the statistical analysis.,In comparison with the SPI− group, the SPI+ group showed more advanced age, higher mBQ scores (leisure domain), lower 6MWD (in m and % of predicted), and lower IPAQ scores (metabolic equivalent-walk/week domain and total).,The IPAQ scores showed weak correlations with steps/day (r = 0.399), age (r = −0.459), and 6MWD-in m (r = 0.446) and in % of predicted (r = 0.422).,In our sample, the cut-off of 4,580 steps/day was not sensitive enough to identify differences between the groups when compared with the predictors of mortality.,The IPAQ, short version score correlated with steps/day.,Comparar a pontuação do índice Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE) e seus componentes individuais em pacientes com DPOC com grave inatividade física ou não, assim como correlacionar o número de passos diários com pontuações de questionários de atividade física, idade, índice BODE e seus componentes.,Foram incluídos 30 pacientes, os quais foram avaliados quanto a sua composição corporal, função pulmonar (VEF1), percepção de dispneia (escala modified Medical Research Council) e capacidade de exercício distância percorrida no teste de caminhada de seis minutos (DTC6).,Além disso, os participantes responderam ao International Physical Activity Questionnaire (IPAQ) versão curta e questionário de Baecke modificado (QBm).,O nível de atividade desses pacientes foi avaliado pelo número de passos diários por pedômetro, utilizando-se o ponto de corte de 4.580 passos para a formação de dois grupos: grupo sem grave inatividade física (GIF−) e grupo com grave inatividade física (GIF+).,Foram utilizados os testes de Mann-Whitney ou t não pareado, assim como os testes de correlação de Spearman ou de Pearson, na análise estatística.,Idade mais avançada, maiores escores no QBm (domínio lazer), menor DTC6 (em m e em % do previsto) e menores escores no IPAQ (domínios equivalentes metabólicos em caminhada e total por semana) foram encontrados no grupo GIF+ do que no grupo GIF−.,Houve correlações fracas dos escores do IPAQ com o número de passos diários (r =0,399), idade (r = -0,459), DTC6 em m (r = 0,446) e em % do previsto (r = 0,422).,Na amostra estudada, o ponto de corte de 4.580 passos diários não foi sensível para identificar diferenças entre os grupos estudados quando comparado com os preditores de mortalidade.,O questionário IPAQ versão curta correlacionou-se com o número de passos diários. | 1 |
Inhaled drug delivery is the cornerstone treatment for asthma and chronic obstructive pulmonary disease (COPD).,However, use of inhaler devices can be challenging, potentially leading to critical errors in handling that can significantly reduce drug delivery to the lungs and effectiveness of treatment.,A systematic review was conducted to define ‘critical’ errors and their impact on health outcomes and resource use between 2004 and 2016, using key search terms for inhaler errors in asthma and COPD (Search-1) and associated health-economic and patient burden (Search-2).,Search-1 identified 62 manuscripts, 47 abstracts, and 5 conference proceedings (n = 114 total).,Search-2 identified 9 studies.,We observed 299 descriptions of critical error.,Age, education status, previous inhaler instruction, comorbidities and socioeconomic status were associated with worse handling error frequency.,A significant association was found between inhaler errors and poor disease outcomes (exacerbations), and greater health-economic burden.,We have shown wide variations in how critical errors are defined, and the evidence shows an important association between inhaler errors and worsened health outcomes.,Given the negative impact diminished disease outcomes impose on resource use, our findings highlight the importance of achieving optimal inhaler technique, and a need for a consensus on defining critical and non-critical errors.,The online version of this article (10.1186/s12931-017-0710-y) contains supplementary material, which is available to authorized users. | Different inhalation devices are characterized by different techniques of use.,The untrained switching of device in chronic obstructive pulmonary disease (COPD) and asthma patients may be associated with inadequate inhalation technique and, consequently, could lead to a reduction in adherence to treatment and limit control of the disease.,The aim of this analysis was to estimate the potential economic impact related to errors in inhalation in patients switching device without adequate training.,An Italian real-practice study conducted in patients affected by COPD and asthma has shown an increase in health care resource consumption associated with misuse of inhalers.,Particularly, significantly higher rates of hospitalizations, emergency room visits (ER), and pharmacological treatments (steroids and antimicrobials) were observed.,In this analysis, those differences in resource consumption were monetized considering the Italian National Health Service (INHS) perspective.,Comparing a hypothetical cohort of 100 COPD patients with at least a critical error in inhalation vs 100 COPD patients without errors in inhalation, a yearly excess of 11.5 hospitalizations, 13 ER visits, 19.5 antimicrobial courses, and 47 corticosteroid courses for the first population were revealed.,In the same way, considering 100 asthma patients with at least a critical error in inhalation vs 100 asthma patients without errors in inhalation, the first population is associated with a yearly excess of 19 hospitalizations, 26.5 ER visits, 4.5 antimicrobial courses, and 21.5 corticosteroid courses.,These differences in resource consumption could be associated with an increase in health care expenditure for INHS, due to inhalation errors, of €23,444/yr in COPD and €44,104/yr in asthma for the considered cohorts of 100 patients.,This evaluation highlights that misuse of inhaler devices, due to inadequate training or nonconsented switch of inhaled medications, is associated with a decrease in disease control and an increase in health care resource consumption and costs. | 1 |
Classification of COPD is usually based on the severity of airflow, which may not sensitively differentiate subpopulations.,Using a multiscale imaging-based cluster analysis (MICA), we aim to identify subpopulations for current smokers with COPD.,Among the SPIROMICS subjects, we analyzed computed tomography images at total lung capacity (TLC) and residual volume (RV) of 284 current smokers.,Functional variables were derived from registration of TLC and RV images, e.g. functional small airways disease (fSAD%).,Structural variables were assessed at TLC images, e.g. emphysema and airway wall thickness and diameter.,We employed an unsupervised method for clustering.,Four clusters were identified.,Cluster 1 had relatively normal airway structures; Cluster 2 had an increase of fSAD% and wall thickness; Cluster 3 exhibited a further increase of fSAD% but a decrease of wall thickness and airway diameter; Cluster 4 had a significant increase of fSAD% and emphysema.,Clinically, Cluster 1 showed normal FEV1/FVC and low exacerbations.,Cluster 4 showed relatively low FEV1/FVC and high exacerbations.,While Cluster 2 and Cluster 3 showed similar exacerbations, Cluster 2 had the highest BMI among all clusters.,Association of imaging-based clusters with existing clinical metrics suggests the sensitivity of MICA in differentiating subpopulations.,The online version of this article (10.1186/s12931-018-0888-7) contains supplementary material, which is available to authorized users. | COPD is a significant cause of morbidity and mortality.,In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation.,Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy.,In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention.,In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13.,The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions.,We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity. | The performance of daily activities is a major challenge for people with chronic obstructive pulmonary disease (COPD).,The Functional Performance Inventory (FPI) was developed based on an analytical framework of functional status and qualitative interviews with COPD patients describing these difficulties.,The 65-item FPI was reduced to a 32-item short form (SF) through a systematic process of qualitative and quantitative item reduction and formatted for greater clarity and ease of use.,This study examined the content validity of the reduced, reformatted form of the instrument, the FPI-SF.,Qualitative cognitive interviews were conducted with COPD patients recruited from three geographically diverse pulmonary clinics in the United States.,Interviews were designed to assess respondent interpretation of the instrument, evaluate clarity and ease of completion, and identify any new activities participants found important and difficult to perform that were not represented by the existing items.,Twenty subjects comprised the sample; 12 (60%) were male, 14 (70%) were Caucasian, the mean age was 63.0 ± 11.3 years, 12 (60%) were retired, the mean forced expiratory volume in 1 second (FEV1) was 1.5 ± 0.5 L, and the mean percent predicted FEV1 was 48.4% ± 13.1%.,Participants understood the FPI-SF as intended, including instructions, items, and response options.,Two minor formatting changes were suggested to improve clarity of presentation.,Participants found the content of the FPI-SF to be comprehensive, with items covering activities they felt were important and often difficult to perform.,These results, together with its development history and previously tested quantitative properties, suggest that the FPI-SF is content valid for use in clinical studies of COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Comorbidities are often reported in patients with COPD and may influence the cost of care.,Yet, the extent by which comorbidities affect costs remains to be determined.,To review, quantify and evaluate excess costs of comorbidities in COPD.,Using a systematic review approach, Pubmed and Embase were searched for studies analyzing excess costs of comorbidities in COPD.,Resulting studies were evaluated according to study characteristics, comorbidity measurement and cost indicators.,Mark-up factors were calculated for respective excess costs.,Furthermore, a checklist of quality criteria was applied.,Twelve studies were included.,Nine evaluated comorbidity specific costs; three examined index-based results.,Pneumonia, cardiovascular disease and diabetes were associated with the highest excess costs.,The mark-up factors for respective excess costs ranged between 1.5 and 2.5 in the majority of cases.,On average the factors constituted a doubling of respective costs in the comorbid case.,The main cost driver, among all studies, was inpatient cost.,Indirect costs were not accounted for by the majority of studies.,Study heterogeneity was high.,The reviewed studies clearly show that comorbidities are associated with significant excess costs in COPD.,The inclusion of comorbid costs and effects in future health economic evaluations of preventive or therapeutic COPD interventions seems highly advisable. | Several studies investigated the association of anemia with health related quality of life (HRQL) in patients with chronic disease.,However, there is little evidence regarding the association of anemia with HRQL in patients with chronic obstructive pulmonary disease (COPD).,This is a post-hoc analysis of a study which enrolled a population of adults aged 35-79 randomly selected from residents of Erie and Niagara Counties, NY, between 1996 and 2000.,In addition to demographic information and physical measurements, we obtained spirometry data and hemoglobin levels.,We used modified Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria to define COPD, and World Health Organization (WHO) criteria to define anemia.,To assess HRQL we used the Short Form-36 (SF-36) to assess physical functioning (PF), physical component summary (PCS) measures and mental component summary (MCS) measures.,In the entire study population (n = 2704), respondents with anemia had lower scores on the physical functioning domain [45.4 (SD10.9) vs.,49.2 (SD 9.1); p < 0.0001].,Among patients with COPD (n = 495) the PF scores (39.9 vs.,45.4) and the PCS (41.9 vs.,45.9) were significantly lower in individuals with anemia compared to those without.,In multiple regression analysis, the association between hemoglobin and PCS was positive (regression coefficient 0.02, p = 0.003).,There was no significant association of hemoglobin with PF scores or the mental component summary measure after adjusting for covariates in patients with COPD.,In patients with moderate to very severe COPD anemia may be associated with worse HRQL.,However, co-morbidities may explain part or all of this association in these patients. | 1 |
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. | Recent studies have provided evidence for a link between leptin and tumor necrosis factor-alpha (TNF-α).,Insulin-like growth factor I (IGF-I) mediates the metabolic effects of growth hormone (GH).,The GH axis is believed to be suppressed in chronic obstructive pulmonary disease (COPD).,The aim of this study is to find out whether acute exacerbations of COPD are followed by changes in plasma leptin and insulin-like growth factor I (IGF-I) levels and furthermore, whether these changes are related to systemic inflammation.,We measured serum leptin, IGF-I, TNF-α, interleukin 1β (IL-1β), interleukin 6 (IL-6) and interleukin 8 (IL-8) levels in 52 COPD patients with acute exacerbation on admission to hospital (Day 1) and two weeks later (Day 15). 25 healthy age-matched subjects served as controls.,COPD patients were also divided into two subgroups (29 with chronic bronchitis and 23 with emphysema).,Serum leptin and IGF-I were measured by radioimmunoassay and TNF-α, IL-1β, IL-6 and IL-8 were measured by ELISA.,Serum leptin levels were significantly higher and serum IGF-I levels significantly lower in COPD patients on Day 1 than in healthy controls (p < 0.001).,A positive correlation was observed between leptin and TNF-α on Day 1 (r = 0.620, p < 0.001).,Emphysematous patients had significantly lower IGF-I levels compared to those with chronic bronchitis both on Day 1 and Day 15 (p = 0.003 and p < 0.001 respectively).,Inappropriately increased circulating leptin levels along with decreased IGF-I levels occured during acute exacerbations of COPD.,Compared to chronic bronchitis, patients with emphysema had lower circulating IGF-I levels both at the onset of the exacerbation and two weeks later. | 1 |
COPD-OSA (chronic obstructive pulmonary disease-obstructive sleep apnea) overlap syndrome is associated with more frequent COPD acute exacerbations than COPD without OSA.,With the application of high-resolution computed tomography (HRCT) in COPD, bronchiectasis is commonly detected and is associated with disease severity.,Sleep respiratory disease is also associated with bronchiectasis; however, the correlation between OSA and coexisted bronchiectasis in COPD (COPD-Bx) has not been reported yet.,A total of 124 consecutive patients with stable COPD were enrolled.,All subjects completed the chest HRCT and nocturnal polysomnography (PSG).,The scores of extent and severity in bronchiectasis were assessed based on the Smith method and the Bhalla scoring system.,Clinical data, questionnaire, routine blood test data, blood levels of C-reactive protein (CRP) and Immunoglobulin E, and the lymphocyte subtype were collected.,Among all enrolled patients, 56.45% (70/124) were diagnosed as COPD-OSA based on the results of PSG screening.,Bronchiectasis was detected in 42.86% (30/70) of the patients with COPD-OSA, but in 18.52% (10/54) of the patients without OSA (χ2=8.264, p=0.004).,PSG screening revealed that COPD with OSA had a significantly higher apnea-hypopnea index and percent of time spent with oxygen saturation below 90% (T90).,Higher values of CRP, T90, and lower CD4/CD8 in the COPD-Bx with OSA were detected compared to COPD-Bx without OSA.,Correlation analysis showed that the Bhalla severity score was related to CD8 cell count (r=0.446, p<0.05) and CD4/CD8 (r=−0.357, p<0.05) in all the COPD-Bx patients.,The Smith extent score was also associated with the values of CD8 count (r=0.388, p<0.05) and CD4/CD8 (r=−0.381, p<0.05).,The comorbid bronchiectasis was more common in COPD-OSA overlap syndrome patient and may be related to more severe hypoxia and increased systemic inflammation. | It is unknown whether aggressive medication strategies should be used for early COPD with or without lung hyperinflation.,We aimed to explore the characteristics and bronchodilator responsiveness of early COPD patients (stages I and II) with/without lung hyperinflation.,Four hundred and six patients with COPD who performed both lung volume and bronchodilation tests were retrospectively analyzed.,Residual volume to total lung capacity >120% of predicted values indicated lung hyperinflation.,The characteristics and bronchodilator responsiveness were compared between the patients with and without lung hyperinflation across all stages of COPD.,The percentages of patients with lung hyperinflation were 72.7% in the entire cohort, 19.4% in stage I, 68.5% in stage II, 95.3% in stage III, and 100.0% in stage IV.,The patients with lung hyperinflation exhibited poorer lung function but better bronchodilator responsiveness of both forced expiratory volume in 1 second and forced vital capacity than those without lung hyperinflation during early COPD (t=2.21-5.70, P=0.000-0.029), especially in stage I, while age, body mass index, smoking status, smoking history, and disease duration were similar between the two subgroups in the same stages.,From stages I to IV of subgroups with lung hyperinflation, stage I patients had the best bronchodilator responsiveness.,Use of bronchodilator responsiveness of forced vital capacity to detect the presence of lung hyperinflation in COPD patients showed relatively high sensitivities (69.5%-75.3%) and specificities (70.3%-75.7%).,We demonstrated the novel finding that early COPD patients with lung hyperinflation are associated with poorer lung function but better bronchodilator responsiveness and established a simple method for detecting lung hyperinflation. | 1 |
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. | Self-treatment of acute exacerbations of COPD with antibiotics and/or oral corticosteroids has emerged as a promising strategy to reduce hospitalization rates, mortality and health costs.,However, for reasons little understood, the effect of self-treatment, particularly when not part of comprehensive self-management programs, remains unclear.,Therefore, this study aims to get insight into the patients’ perspective on self-treatment of acute exacerbations of COPD, focusing specifically on how patients decide for the right moment to start treatment with antibiotics and/or oral corticosteroids, what they consider important when making this decision and aspects which might interfere with successful implementation.,We interviewed 19 patients with chronic obstructive pulmonary disease using qualitative semi-structured interviews, and applied thematic analysis for data analysis.,Patients were well equipped with experiential knowledge to recognize and promptly respond to worsening COPD symptoms.,Worries regarding potential adverse effects of antibiotics and oral corticosteroids played an important role in the decision to start treatment and could result in hesitation to start treatment.,Although self-treatment represented a practical and appreciated option for some patients with predictable symptom patterns and treatment effect, all patients favoured assistance from a medical professional when their perceived competence reached its limits.,However, a feeling of obligation to succeed with self-treatment or distrust in their doctors or the health care system could keep patients from timely help seeking.,COPD patients regard self-treatment of exacerbations with antibiotics and/or oral corticosteroids as a valuable alternative.,How they engage in self-treatment depends on their concerns regarding the medications’ adverse effects as well as on their understanding of and preferences for self-treatment as a means of health care.,Caregivers should address these perspectives in a collaborative approach when offering COPD patients the opportunity for self-treatment of exacerbations.,The online version of this article (doi:10.1186/s12875-017-0582-8) contains supplementary material, which is available to authorized users. | 1 |
Acknowledgement of COPD underdiagnosis and misdiagnosis in primary care can contribute to improved disease diagnosis.,PUMA is an international primary care study in Argentina, Colombia, Venezuela and Uruguay.,To assess COPD underdiagnosis and misdiagnosis in primary care and identify factors associated with COPD underdiagnosis in this setting.,COPD was defined as post-bronchodilator (post-BD) forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) <0.70 and the lower limit of normal (LLN).,Prior diagnosis was self-reported physician diagnosis of emphysema, chronic bronchitis, or COPD.,Those patients with spirometric COPD were considered to have correct prior diagnosis, while those without spirometric criteria had misdiagnosis.,Individuals with spirometric criteria without previous diagnosis were considered as underdiagnosed.,1,743 patients were interviewed, 1,540 completed spirometry, 309 (post-BD FEV1/FVC <0.70) and 226 (LLN) had COPD.,Underdiagnosis using post-BD FEV1/FVC <0.70 was 77% and 73% by LLN.,Overall, 102 patients had a prior COPD diagnosis, 71/102 patients (69.6%) had a prior correct diagnosis and 31/102 (30.4%) had a misdiagnosis defined by post-BD FEV1/FVC ≥0.70.,Underdiagnosis was associated with higher body mass index (≥30 kg/m2), milder airway obstruction (GOLD I-II), black skin color, absence of dyspnea, wheezing, no history of exacerbations or hospitalizations in the past-year.,Those not visiting a doctor in the last year or only visiting a GP had more risk of underdiagnosis.,COPD underdiagnosis (65.8%) and misdiagnosis (26.4%) were less prevalent in those with previous spirometry.,COPD underdiagnosis is a major problem in primary care.,Availability of spirometry should be a priority in this setting. | COPD has a profound impact on daily life, yet remains underdiagnosed and undertreated.,We set out to develop a brief, reliable, self-scored questionnaire to identify individuals likely to have COPD.,COPD-PS™ development began with a list of concepts identified for inclusion using expert opinion from a clinician working group comprised of pulmonologists (n = 5) and primary care clinicians (n = 5).,A national survey of 697 patients was conducted at 12 practitioner sites.,Logistic regression identified items discriminating between patients with and without fixed airflow obstruction (AO, postbronchodilator FEV1/FVC < 70%).,ROC analyses evaluated screening accuracy, compared scoring options, and assessed concurrent validity.,Convergent and discriminant validity were assessed via COPD-PS and SF-12v2 score correlations.,For known-groups validation, COPD-PS differences between clinical groups were tested.,Test-retest reliability was evaluated in a 20% sample.,Of 697 patients surveyed, 295 patients met expert review criteria for spirometry performance; 38% of these (n = 113) had results indicating AO.,Five items positively predicted AO (p < 0.0001): breathlessness, productive cough, activity limitation, smoking history, and age.,COPD-PS scores accurately classified AO status (area under ROC curve = 0.81) and reliable (r = 0.91).,Patients with spirometry indicative of AO scored significantly higher (6.8, SD = 1.9; p < 0.0001) than patients without AO (4.0, SD = 2.3).,Higher scores were associated with more severe AO, bronchodilator use, and overnight hospitalization for breathing problems.,With the prevalence of COPD in the studied cohort, a score on the COPD-PS of greater than five was associated with a positive predictive value of 56.8% and negative predictive value of 86.4%.,The COPD-PS accurately classified physician-reported COPD (AUC = 0.89).,The COPD-PS is a brief, accurate questionnaire that can identify individuals likely to have COPD. | 1 |
The benefit of pulmonary rehabilitation (PR) in symptomatic chronic obstructive pulmonary disease (COPD) is well known.,However, advanced patients with chronic respiratory failure (CRF), a category excluded from most studies, are frequently unable to sustain a work-load sufficiently high to obtain the full benefit of PR on exercise tolerance.,Recent studies involving heated and humidified high flow oxygen therapy (HFOT) showed positive effects on breathing pattern and ventilatory efficiency during effort.,We thus plan to compare, in COPD patients with CRF undergoing a high-intensity exercise programme, the effect of using HFOT versus standard oxygen delivery via Venturi Mask (V-mask), at the same inspiratory oxygen fraction, on improving exercise endurance.,This is a multicentre randomised controlled trial that will involve 156 COPD inpatients with CRF recruited from seven PR hospitals.,Patients will be randomised to one of two groups - V-mask versus HFOT.,All patients will undergo the same high-intensity exercise programme using either of the oxygen delivery devices as per their group allocation.,Training will consist of 20 sessions, over 1 month (5 sessions per week) within the hospitalisation period.,Anthropometric and clinical data, including body mass index, diagnosis, spirometry and comorbidities (Cumulative Rating Scale) will be collected at baseline.,At baseline and at the end of the exercise programme (primary assessment time) evaluation will include exercise tolerance (Constant Work Rate Exercise Test) (primary outcome), functional capacity (6-min walk test), maximal inspiratory pressure/maximal expiratory pressure, peripheral muscle strength (biceps and quadriceps) by manual dynamometer, respiratory exchanges (blood gases analysis), disability (Barthel Index and Barthel Dyspnoea Index), impact of disease (COPD Assessment test), and quality of life (Maugeri Respiratory Failure Scale-26).,At the end of the training period, patient satisfaction will be evaluated.,This study will add knowledge about the exercise response in advanced COPD with CRF and verify if an alternative tool, namely HFOT, can increase the benefit obtained from PR.,ClinicalTrials.gov ID NET03322787,Registered: 6 November 2017,The online version of this article (10.1186/s13063-019-3440-2) contains supplementary material, which is available to authorized users. | Rehabilitation of patients with chronic obstructive pulmonary disease (COPD) is a key treatment in COPD.,However, despite the existing evidence and a strong recommendation from lung associations worldwide, 50% of patients with COPD decline to participate in COPD rehabilitation program and 30-50% drop-out before completion.,The main reasons are severe symptoms, inflexible accessibility and necessity for transportation.,Currently there are no well-established and evident rehabilitation alternatives.,Supervised online screen rehabilitation could be a useful approach to increase accessibility and compliance.,The aim of this multicenter RCT study is to compare the potential benefits of a 10-week online COPD rehabilitation program (CORe) with conventional outpatient COPD rehabilitation (CCRe).,This study is a randomized assessor- and statistician blinded superiority multicenter trial with two parallel groups, employing 1:1 allocation to the intervention and the comparison group.On the basis of a sample size calculation, 134 patients with severe or very severe COPD and eligible to conventional hospital based outpatient COPD rehabilitation will be included and randomized from eight different hospitals.,The CORe intervention group receives group supervised resistance- and endurance training and patient education, 60 min, three times/week for 10 weeks at home via online-screen.,The CCRe comparison group receives group based supervised resistance- and endurance training and patient education, 90 min, two times/week for 10 weeks (two hospitals) or 12 weeks (six hospitals) in groups at the local hospital.,The primary outcome is change in the 6-min walking distance after 10/12 weeks; the secondary outcomes are changes in 30 s sit-to-stand chair test, physical activity level, symptoms, anxiety and depression symptoms, disease specific and generic quality of life.,Primary endpoint is 10/12 weeks from baseline, while secondary endpoints are 22, 36, 62 weeks from baseline assessments.,The study will likely contribute to knowledge regarding COPD tele-rehabilitation and to which extent it is more feasible and thereby more efficient than conventional COPD rehabilitation in patients with severe and very severe COPD.,Clinicaltrials.gov Identifier: NCT02667171.,Registration data: January 28th 2016. | 1 |
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. | A nebulized formulation of formoterol, Perforomist®, 20 μg/2 ml, has been available since 2007 for the maintenance treatment of chronic obstructive pulmonary disease (COPD).,We review the safety and efficacy data obtained during its development.,In a dose-finding study, formoterol inhalation solution (FFIS) was similar to the formoterol originator, Foradil® 12 μg DPI (FA) in patients with COPD.,In a 12-week efficacy study, FFIS manifested a rapid onset of action and FEV1 peak, AUC0-12, and trough levels similar to FA.,No loss of efficacy, tachyphylaxis, was observed over 12 weeks of regular administration.,In placebo-controlled studies in COPD patients receiving maintenance tiotropium, the addition of FFIS significantly augmented bronchodilation over the 6-week treatment duration, signifying that nebulized formoterol can further improve lung function in patients who are receiving tiotropium without an observed increase in adverse reactions.,The safety profile of FFIS during 12-week and 1-year studies revealed adverse events that were similar to those of placebo and FA.,Cardiac rhythm studies, including frequent ECGs and Holter monitoring, did not indicate any increase in rate or rhythm disturbances greater than placebo or FA.,We conclude that maintenance use of Perforomist® is appropriate for patients with COPD who require or prefer a nebulizer for management of their disease. | 1 |
Chronic obstructive pulmonary disease (COPD) is a progressive disease and a composite endpoint could be an indicator of treatment effect on disease worsening.,This post-hoc analysis assessed whether indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily reduced the risk of clinically important deterioration (CID) versus salmeterol/fluticasone (SFC) 50/500 μg twice daily in moderate-to-very severe COPD patients from the FLAME study.,CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1) or ≥ 4-unit increase in St.,George’s Respiratory Questionnaire (SGRQ) total score or a moderate-to-severe COPD exacerbation.,Changes from baseline in the rate of moderate and severe exacerbations, time to first moderate-to-severe exacerbation, and change from baseline in the SGRQ score, measured after Week 12 up to Week 52, were assessed by presence of early CID (CID+) or absence of CID (CID−) at Week 12.,IND/GLY significantly delayed the time to CID (hazard ratio [HR] (95% confidence interval [CI]), 0.72 [0.67-0.78]; P < 0.0001), and reduced the incidences of CID versus SFC.,Additionally, IND/GLY delayed the time to CID in all patient subgroups.,After 12 weeks until 52 weeks, CID+ patients had a significantly higher rate of moderate-to-severe exacerbations versus CID− patients (P < 0.0001); moreover, CID+ patients experienced moderate-to-severe exacerbations significantly earlier versus CID− patients (P < 0.0001).,CID+ patients had a comparable change in the SGRQ total score versus CID− patients.,IND/GLY reduced the risk of CID versus SFC.,CID had a significant impact on long-term exacerbation outcomes in patients with moderate-to-very severe COPD and a history of ≥1 exacerbations in the previous year.,Clinicaltrials.gov NCT01782326.,The online version of this article (10.1186/s12931-018-0830-z) contains supplementary material, which is available to authorized users. | Lung hyperinflation and exercise intolerance are hallmarks of chronic obstructive pulmonary disease (COPD).,However, their relationship remains uncertain.,A combined analysis of two placebo-controlled, randomized studies examined the effects of the long-acting muscarinic antagonist umeclidinium (UMEC) and long-acting β2-agonist vilanterol (VI) separately and in combination on static hyperinflation, exercise endurance time (EET), and their relationship in patients with COPD.,Patients with moderate-to-severe stable COPD and resting functional residual capacity >120% predicted were randomized to UMEC/VI 62.5/25 μg, UMEC 62.5 μg, VI 25 μg, or placebo for 12 weeks.,Inspiratory capacity (IC), residual volume (RV), total lung capacity (TLC), and EET in an endurance shuttle-walk test were measured.,In this post hoc analysis, IC/TLC, RV/TLC, and IC were used as hyperinflation markers.,After 12 weeks, UMEC/VI and UMEC and VI showed significant improvements in hyperinflation versus placebo when measured by absolute change from baseline in IC/TLC (trough and 3 hours postdose [P≤0.011]).,UMEC/VI showed significant improvements versus UMEC and VI in absolute changes in IC/TLC (trough and 3 hours postdose [P≤0.001]).,Statistical significance for comparisons with placebo and between treatments for absolute changes in IC and percentage changes in RV/TLC followed similar patterns to those for absolute changes in IC/TLC.,UMEC/VI showed significant improvements in EET versus placebo at day 2 and week 12, measured as change from baseline in seconds (P≤0.002) and as a percentage from baseline (P≤0.005).,There was a lack of evidence to suggest a correlation between improvements in static hyperinflation and EET at any time point.,Although the dual bronchodilator UMEC/VI demonstrated greater improvements in static hyperinflation markers than UMEC or VI and significant improvements in exercise endurance, no direct relationship was observed between static hyperinflation and exercise endurance. | 1 |
Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/FVC).,Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV1 and FEV1/FVC across 19 studies (total N = 50,047).,We identified three novel loci not previously associated with pulmonary function.,SNPs in or near DNER (smallest P JMA = 5.00×10−11), HLA-DQB1 and HLA-DQA2 (smallest P JMA = 4.35×10−9), and KCNJ2 and SOX9 (smallest P JMA = 1.28×10−8) were associated with FEV1/FVC or FEV1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction.,The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated.,We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue.,DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers.,Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects. | Since the discovery of alpha-1 antitrypsin in the early 1960s, several new genes have been suggested to play a role in chronic obstructive pulmonary disease (COPD) pathogenesis.,Yet, in spite of those advances, much about the genetic basis of COPD still remains to be discovered.,Unbiased approaches, such as genome-wide association (GWA) studies, are critical to identify genes and pathways and to verify suggested genetic variants.,Indeed, most of our current understanding about COPD candidate genes originates from GWA studies.,Experiments in form of cross-study replications and advanced meta-analyses have propelled the field towards unravelling details about COPD's pathogenesis.,Here, we review the discovery of genetic variants in association with COPD phenotypes by discussing the available approaches and current findings.,Limitations of current studies are considered and future directions provided. | 1 |
Few studies investigated the respiratory outcomes of metformin use in patients with coexistent type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD).,We want to compare the long-term respiratory endpoints of metformin use and nonuse in patients with T2DM and COPD.,This retrospective cohort study enrolled patients with T2DM and COPD from Taiwan’s National Health Insurance Program between January 1, 2000, and December 31, 2012.,Main outcomes were hospitalized bacterial pneumonia, hospitalization for COPD, noninvasive positive pressure ventilation (NIPPV), invasive mechanical ventilation (IMV), and lung cancer.,In total, 20,644 propensity score-matched metformin users and nonusers were assessed.,The adjusted hazard ratios (95% confidence intervals) of metformin use relative to nonuse for bacterial pneumonia, hospitalization for COPD, NIPPV, IMV, and lung cancer were 1.17 (1.11-1.23), 1.34 (1.26-1.43), 0.99 (0.89-1.10), 1.10 (1.03-1.17), and 1.12 (0.96-1.30).,Metformin use also exhibited significant dose-response relationship with respect to the risks of bacterial pneumonia, hospitalization for COPD and IMV.,Consistent results were found in the sensitivity test.,This nationwide cohort study demonstrated that in patients with T2DM and COPD, metformin use was associated with higher risks of pneumonia, hospitalization for COPD, and IMV.,If patients with COPD use metformin, vigilance with regard to their pulmonary condition may be required. | Respiratory syncytial viral (RSV) infections are a frequent cause of chronic obstructive pulmonary disease (COPD) exacerbations, which are a major factor in disease progression and mortality.,RSV is able to evade antiviral defenses to persist in the lungs of COPD patients.,Though RSV infection has been identified in COPD, its contribution to cigarette smoke-induced airway inflammation and lung tissue destruction has not been established.,Here we examine the long-term effects of cigarette smoke exposure, in combination with monthly RSV infections, on pulmonary inflammation, protease production and remodeling in mice.,RSV exposures enhanced the influx of macrophages, neutrophils and lymphocytes to the airways of cigarette smoke exposed C57BL/6J mice.,This infiltration of cells was most pronounced around the vasculature and bronchial airways.,By itself, RSV caused significant airspace enlargement and fibrosis in mice and these effects were accentuated with concomitant smoke exposure.,Combined stimulation with both smoke and RSV synergistically induced cytokine (IL-1α, IL-17, IFN-γ, KC, IL-13, CXCL9, RANTES, MIF and GM-CSF) and protease (MMP-2, -8, -12, -13, -16 and cathepsins E, S, W and Z) expression.,In addition, RSV exposure caused marked apoptosis within the airways of infected mice, which was augmented by cigarette smoke exposure.,RSV and smoke exposure also reduced protein phosphatase 2A (PP2A) and protein tyrosine phosphates (PTP1B) expression and activity.,This is significant as these phosphatases counter smoke-induced inflammation and protease expression.,Together, these findings show for the first time that recurrent RSV infection markedly enhances inflammation, apoptosis and tissue destruction in smoke-exposed mice.,Indeed, these results indicate that preventing RSV transmission and infection has the potential to significantly impact on COPD severity and progression. | 1 |
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. | COPD prevalence and consequent burden are expected to rapidly increase worldwide.,Until now, there has been no community-based study of COPD in Thailand.,We aimed to compare the prevalence, clinical characteristics, disease severity, previous diagnosis, and management of COPD between urban and rural communities.,A population-based cross-sectional study was designed to compare COPD prevalence and burden in rural and urban communities in Chiang Mai Province, Thailand.,The COPD subjects were diagnosed and severity categories assigned using Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.,The prevalence between the groups was compared using risk regression analysis.,Unpaired t-test and chi-square were used to compare differences between the groups.,There were 574 and 293 enrolled subjects with acceptable spirometry, in rural and urban communities respectively.,The prevalence of COPD in general and COPD in females was higher in the rural group (6.8% vs 3.7% and 4.4% vs 0.9%, respectively) across all independent variables.,However, after adjustment for age, sex, and smoking status, no significant differences were demonstrated.,Although the pulmonary function and disease severity between the two groups were not significantly different, the tendency was more pronounced in the rural group (COPD stage III-IV: 65.0% vs 33.3%).,Most of the COPD patients in both groups were underdiagnosed (80.0% vs 77.2%) and undertreated (85.0% vs 81.9%).,None of the patients in the study had participated in exercise training programs.,The prevalence of COPD in general and particularly COPD in females tended to be higher, with more severe disease in the rural community.,However, both groups were similarly underdiagnosed and undertreated. | 1 |
Cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) commonly coexist and share common risk factors.,The prevalence of COPD in outpatients with a smoking history and CVD in Japan is unknown.,The aim of this study was to determine the proportion of Japanese patients with a smoking history being treated for CVD who have concurrent airflow limitation compatible with COPD.,A secondary objective was to test whether the usage of lung function tests performed in the clinic influenced the diagnosis rate of COPD in the patients identified with airflow limitation.,In a multicenter observational prospective study conducted at 17 centers across Japan, the prevalence of airflow limitation compatible with COPD (defined as forced expiratory volume (FEV)1/FEV6 <0.73, by handheld spirometry) was investigated in cardiac outpatients ≥40 years old with a smoking history who routinely visited the clinic for their CVD.,Each patient completed the COPD Assessment Test prior to spirometry testing.,Data were available for 995 patients with a mean age of 66.6±10.0 years, of whom 95.5% were male.,The prevalence of airflow limitation compatible with COPD was 27.0% (n=269), and 87.7% of those patients (n=236) did not have a prior diagnosis of COPD.,The prevalence of previously diagnosed airflow limitation was higher in sites with higher usage of lung function testing (14.0%, 15.2% respectively) compared against sites where it is performed seldom (11.1%), but was still low.,The prevalence of airflow limitation in this study indicates that a quarter of outpatients with CVD have COPD, almost all of whom are undiagnosed.,This suggests that it is important to look routinely for COPD in CVD outpatients. | It has been debated whether treatment should be started early in subjects with mild to moderate COPD.,An impaired health status score was associated with a higher probability of being diagnosed with COPD as compared with undiagnosed COPD.,To investigate the health status in a healthy working population, to determine reference scores for healthy non-smoking subjects, and to investigate the relationship between their health status and airflow limitation.,A total of 1333 healthy industrial workers aged ≥40 years performed spirometry and completed the St.,George’s Respiratory Questionnaire (SGRQ) and the COPD Assessment Test (CAT).,The prevalence of COPD defined by the fixed ratio of the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) was 10.9%, and the prevalence defined by the Lower Limit of Normal was 5.0%.,All SGRQ and CAT scores were skewed to the milder end.,In 512 non-smoking subjects with normal spirometry, the mean SGRQ score was 5.7, and the mean CAT score was 5.8.,In 145 people with COPD defined by the fixed ratio, the mean SGRQ score was 7.9, with a zero score in 6.9% of the subjects.,Using the CAT, the mean score was 7.3, with 7.6% of the scores being zero.,The scores in patients identified using the Lower Limit of Normal approach were: SGRQ 8.4 (13.4% had a score of zero) and CAT 7.4 (13.4% had a score of zero).,Although the 95th percentiles of the Total, Symptoms, Activity, and Impact scores of the SGRQ and CAT sores were 13.8, 34.0, 23.4, 7.2 and 13.6 in the 512 healthy non-smoking subjects, respectively, they were also distributed under their upper limits in over 80% of the COPD subjects.,The COPD-specific health status scores in a working population were good, even in those with spirometrically diagnosed COPD.,All scores were widely distributed in both healthy non-smoking subjects and in subjects with COPD, and the score distribution overlapped remarkably between these two groups.,This suggests that symptom-based methods are not suitable screening tools in a healthy general population. | 1 |
Pulmonary function measures obtained by spirometry are used to diagnose chronic obstructive pulmonary disease (COPD) and are highly heritable.,We conducted genome-wide association (GWA) analyses (Affymetrix 100K SNP GeneChip) for measures of lung function in the Framingham Heart Study.,Ten spirometry phenotypes including percent of predicted measures, mean spirometry measures over two examinations, and rates of change based on forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory flow from the 25th to 75th percentile (FEF25-75), the FEV1/FVC ratio, and the FEF25-75/FVC ratio were examined.,Percent predicted phenotypes were created using each participant's latest exam with spirometry.,Predicted lung function was estimated using models defined in the set of healthy never-smokers, and standardized residuals of percent predicted measures were created adjusting for smoking status, pack-years, and body mass index (BMI).,All modeling was performed stratified by sex and cohort.,Mean spirometry phenotypes were created using data from two examinations and adjusting for age, BMI, height, smoking and pack-years.,Change in pulmonary function over time was studied using two to four examinations with spirometry to calculate slopes, which were then adjusted for age, height, smoking and pack-years.,Analyses were restricted to 70,987 autosomal SNPs with minor allele frequency ≥ 10%, genotype call rate ≥ 80%, and Hardy-Weinberg equilibrium p-value ≥ 0.001.,A SNP in the interleukin 6 receptor (IL6R) on chromosome 1 was among the best results for percent predicted FEF25-75.,A non-synonymous coding SNP in glutathione S-transferase omega 2 (GSTO2) on chromosome 10 had top-ranked results studying the mean FEV1 and FVC measurements from two examinations.,SNPs nearby the SOD3 and vitamin D binding protein genes, candidate genes for COPD, exhibited association to percent predicted phenotypes.,GSTO2 and IL6R are credible candidate genes for association to pulmonary function identified by GWA.,These and other observed associations warrant replication studies.,This resource of GWA results for pulmonary function measures is publicly available at . | Chronic obstructive pulmonary disease (COPD) is associated with increased oxidative and nitrosative stress.,The aim of our study was to assess the importance of these factors in the airways of healthy smokers and symptomatic smokers without airway obstruction, i.e. individuals with GOLD stage 0 COPD.,Exhaled NO (FENO) and induced sputum samples were collected from 22 current smokers (13 healthy smokers without any respiratory symptoms and 9 with symptoms i.e. stage 0 COPD) and 22 healthy age-matched non-smokers (11 never smokers and 11 ex-smokers).,Sputum cell differential counts, and expressions of inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE) were analysed from cytospins by immunocytochemistry.,Eosinophil cationic protein (ECP) and lactoferrin were measured from sputum supernatants by ELISA.,FENO was significantly decreased in smokers, mean (SD) 11.0 (6.7) ppb, compared to non-smokers, 22.9 (10.0), p < 0.0001.,Induced sputum showed increased levels of neutrophils (p = 0.01) and elevated numbers of iNOS (p = 0.004), MPO (p = 0.003), nitrotyrosine (p = 0.003), and 4-HNE (p = 0.03) positive cells in smokers when compared to non-smokers.,Sputum lactoferrin levels were also higher in smokers than in non-smokers (p = 0.02).,Furthermore, we noted four negative correlations between FENO and 1) total neutrophils (r = -0.367, p = 0.02), 2) positive cells for iNOS (r = -0.503, p = 0.005), 3) MPO (r = -0.547, p = 0.008), and 4) nitrotyrosine (r = -0.424, p = 0.03).,However, no major differences were found between never smokers and ex-smokers or between healthy smokers and stage 0 COPD patients.,Our results clearly indicate that several markers of oxidative/nitrosative stress are increased in current cigarette smokers compared to non-smokers and no major differences can be observed in these biomarkers between non-symptomatic smokers and subjects with GOLD stage 0 COPD. | 1 |
The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | Sleep quality is often poor in patients with chronic obstructive pulmonary disease (COPD).,A cross-sectional European survey investigated the prevalence of night-time symptoms in COPD to evaluate the level of disconnect between physician and patient perceptions of the presence of night-time symptoms, and to compare the characteristics of patients with and without night-time symptoms.,A total of 251 primary care physicians and 251 respiratory specialists completed record forms on 2,807 patients with COPD.,The forms captured information on patient demographics, lung function, COPD severity, and symptoms.,Patients completed questionnaires on the time of day when their COPD symptoms bothered them, and the impact of COPD on their ability to get up in the morning and on sleep.,Data were compared between groups (those with and without night-time symptoms) using t-tests or Wilcoxon signed rank tests.,The kappa statistic was used to assess the level of disconnect between physician and patient perceptions of the impact of night-time symptoms.,Most patients (78%) reported night-time disturbance.,Patients with night-time symptoms experienced more daytime breathlessness (mean modified Medical Research Council dyspnea scale score 2.4 versus 1.1) and exacerbations in the previous 12 months (mean 1.7 versus 0.4), and received more maintenance therapy (mean of 2.8 versus 2.3 products) than those without.,Concordance between the frequency of physician-reported (67.9% of patients) and patient-reported (68.5% of patients) night-time symptoms was good.,Physicians significantly underestimated the impact of COPD on the patient’s ability to get up in the morning and on sleep (fair-moderate agreement).,Physician-reported night-time symptoms were present for 41.2% of patients who could be categorized by Global initiative for chronic Obstructive Lung Disease (GOLD) group (n=937), increasing from 20.9% of those in the low-risk group to 77.4% of those in the high-riskgroup.,Patients with COPD experience night-time symptoms regardless of GOLD group, that impact on their ability to get up in the morning and on their sleep quality. | 1 |
Studies examining the cellular mechanisms of inflammation and protease production in the lung tissue and airways of COPD patients have shed light on the important role of kinase-based signaling cascades.,These pathways can be activated by environmental stimuli such as tobacco smoke, and by endogenous signals such as cytokines, growth factors, and inflammation-derived oxidants.,The three most widely characterized cascades are those directed by the classical mitogen activated protein (MAP) kinase (ERK1/2), stress activated protein kinase/c-Jun N-terminal protein kinase, and p38 enzymes.,These phosphorylation cascades transmit and amplify extracellular, receptor-mediated signals through the cytoplasm of the cell to activate nuclear transcription factors which bind and induce expression of target genes.,The result is tight control of diverse cellular events, and rapid responses to external stimuli.,However, recent research suggests that constitutive or aberrant activation of MAP kinases contributes to several COPD-associated phenotypes, including mucus overproduction and secretion, inflammation, cytokine expression, apoptosis, T cell activation, matrix metalloproteinase production, and fibrosis.,This review explores the biological functions of the MAP kinase pathways in the pathogenesis of COPD, their activation by cigarette smoke, and discusses the potential role of MAP kinase inhibitors in COPD therapy. | Despite the status of chronic obstructive pulmonary disease (COPD) as a major global health problem, no currently available therapies can limit COPD progression.,Therefore, an urgent need exists for the development of new and effective treatments for COPD.,An improved understanding in the molecular pathogenesis of COPD can potentially identify molecular targets to facilitate the development of new therapeutic modalities.,Among the best approaches for understanding the molecular basis of COPD include gene expression profiling techniques, such as serial analysis of gene expression or microarrays.,Using these methods, recent studies have mapped comparative gene expression profiles of lung tissues from patients with different stages of COPD relative to healthy smokers or non-smokers.,Such studies have revealed a number of differentially-regulated genes associated with COPD progression, which include genes involved in the regulation of inflammation, extracellular matrix, cytokines, chemokines, apoptosis, and stress responses.,These studies have shed new light on the molecular mechanisms of COPD, and suggest novel targets for clinical treatments. | 1 |
Guidelines are critical for facilitating cost-effective COPD care.,Development and implementation in low-and middle-income countries (LMICs) is challenging.,To guide future strategy, an overview of current global COPD guidelines is required.,We systematically reviewed national COPD guidelines, focusing on worldwide availability and identification of potential development, content, context, and quality gaps that may hamper effective implementation.,Scoping review of national COPD management guidelines.,We assessed: (1) global guideline coverage; (2) guideline information (authors, target audience, dissemination plans); (3) content (prevention, diagnosis, treatments); (4) ethical, legal, and socio-economic aspects; and (5) compliance with the eight Institute of Medicine (IOM) guideline standards.,LMICs guidelines were compared with those from high-income countries (HICs).,Of the 61 national COPD guidelines identified, 30 were from LMICs.,Guidelines did not cover 1.93 billion (30.2%) people living in LMICs, whereas only 0.02 billion (1.9%) in HICs were without national guidelines.,Compared with HICs, LMIC guidelines targeted fewer health-care professional groups and less often addressed case finding and co-morbidities.,More than 90% of all guidelines included smoking cessation advice.,Air pollution reduction strategies were less frequently mentioned in both LMICs (47%) and HICs (42%).,LMIC guidelines fulfilled on average 3.37 (42%) of IOM standards, compared with 5.29 (66%) in HICs (P < .05).,LMICs scored significantly lower compared with HICs regarding conflicts of interest management, updates, articulation of recommendations, and funding transparency (all, P < .05).,Several development, content, context, and quality gaps exist in COPD guidelines from LMICs that may hamper effective implementation.,Overall, COPD guidelines in LMICs should be more widely available and should be transparently developed and updated.,Guidelines may be further enhanced by better inclusion of local risk factors, case findings, and co-morbidity management, preferably tailored to available financial and staff resources. | Although cardiovascular disease (CVD) is a common comorbidity associated with chronic obstructive pulmonary disease (COPD), it is unknown how to improve prediction of cardiovascular (CV) risk in individuals with COPD.,Traditional CV risk scores have been tested in different populations but not uniquely in COPD.,The potential of alternative markers to improve CV risk prediction in individuals with COPD is unknown.,We aimed to determine the predictive value of conventional CVD risk factors in COPD and to determine if additional markers improve prediction beyond conventional factors.,Data from the Evaluation of the Role of Inflammation in Chronic Airways disease cohort, which enrolled 729 individuals with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II-IV COPD were used.,Linked hospital episode statistics and survival data were prospectively collected for a median 4.6 years of follow-up.,Five UK centres interested in COPD.,Population-based sample including 714 individuals with spirometry-defined COPD, smoked at least 10 pack years and who were clinically stable for >4 weeks.,Baseline measurements included aortic pulse wave velocity (aPWV), carotid intima-media thickness (CIMT), C reactive protein (CRP), fibrinogen, spirometry and Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) Index, 6 min walk test (6MWT) and 4 m gait speed (4MGS) test.,New occurrence (first event) of fatal or non-fatal hospitalised CVD, and all-cause and cause-specific mortality.,Out of 714 participants, 192 (27%) had CV hospitalisation and 6 died due to CVD.,The overall CV risk model C-statistic was 0.689 (95% CI 0.688 to 0.691). aPWV and CIMT neither had an association with study outcome nor improved model prediction.,CRP, fibrinogen, GOLD stage, BODE Index, 4MGS and 6MWT were associated with the outcome, independently of conventional risk factors (p<0.05 for all).,However, only 6MWT improved model discrimination (C=0.727, 95% CI 0.726 to 0.728).,Poor physical performance defined by the 6MWT improves prediction of CV hospitalisation in individuals with COPD.,ID 11101. | 1 |
Favorable effects of formal pulmonary rehabilitation in selected moderate to severe COPD patients are well established.,Few data are available on the effects and costs of integrated disease management (IDM) programs on quality of care and health status of COPD patients in primary care, representing a much larger group of COPD patients.,Therefore, the RECODE trial assesses the long-term clinical and cost-effectiveness of IDM in primary care.,RECODE is a cluster randomized trial with two years of follow-up, during which 40 clusters of primary care teams (including 1086 COPD patients) are randomized to IDM or usual care.,The intervention started with a 2-day multidisciplinary course in which healthcare providers are trained as a team in essential components of effective COPD IDM in primary care.,During the course, the team redesigns the care process and defines responsibilities of different caregivers.,They are trained in how to use feedback on process and outcome data to guide implement guideline-driven integrated healthcare.,Practice-tailored feedback reports are provided at baseline, and at 6 and 12 months.,The team learns the details of an ICT program that supports recording of process and outcome measures.,Afterwards, the team designs a time-contingent individual practice plan, agreeing on steps to be taken in order to integrate a COPD IDM program into daily practice.,After 6 and 12 months, there is a refresher course for all teams simultaneously to enable them to learn from each other’s experience.,Health status of patients at 12 months is the primary outcome, measured by the Clinical COPD Questionnaire (CCQ).,Secondary outcomes include effects on quality of care, disease-specific and generic health-related quality of life, COPD exacerbations, dyspnea, costs of healthcare utilization, and productivity loss.,This article presents the protocol and baseline results of the RECODE trial.,This study will allow to evaluate whether IDM implemented in primary care can positively influence quality of life and quality of care in mild to moderate COPD patients, thereby making the benefits of multidisciplinary rehabilitation applicable to a substantial part of the COPD population.,Netherlands Trial Register (NTR): NTR2268 | 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 | 1 |
Coronavirus disease 2019 (COVID-19) was rapidly expanded worldwide within a short period.,Its relationship with chronic comorbidities is still unclear.,We aimed to determine the effects of chronic comorbidities on clinical outcomes of patients with and without COVID-19.,This was an analysis of 65,535 patients with suspicion of viral respiratory disease (38,324 SARS-CoV-2 positive and 27,211 SARS-CoV-2 negative) from January 01 to May 12, 2020 using the national administrative healthcare open data of Mexico.,SARS-CoV-2 infection was confirmed by reverse-transcriptase-polymerase-chain-reaction.,General characteristics and chronic comorbidities were explored.,Clinical outcomes of interest were hospital admission, pneumonia, intensive care unit admission, endotracheal intubation and mortality.,Prevalence of chronic comorbidities was 49.4%.,Multivariate logistic regression analysis showed that the effect of age, male sex, bronchial asthma, diabetes mellitus and chronic kidney disease on clinical outcomes was similar for both SARS-CoV-2 positive and negative patients.,Adverse clinical outcomes were associated with the time from symptoms onset to medical contact, chronic obstructive pulmonary disease, hypertension and obesity in SARS-CoV-2 positive patients, but with cardiovascular disease in SARS-CoV-2 negative patients (p value < 0.01 for all comparisons).,Chronic comorbidities are commonly found in patients with suspicion of viral respiratory disease.,The knowledge of the impact of comorbidities on adverse clinical outcomes can better define those COVID-19 patients at higher risk.,The different impact of the specific type of chronic comorbidity on clinical outcomes in patients with and without SARS-CoV-2 infection requires further researches.,These findings need confirmation using other data sources.,The online version contains supplementary material available at 10.1007/s11739-020-02597-5. | The potential detrimental effects of steroids on the immune system to fight viral infections had always been a concern for patients on long term steroids in chronic conditions.,A recent warning from WHO on systemic corticosteroid use amid COVID-19 raised suspicion among public and healthcare professionals regarding the safety of steroid use during the SARS-CoV-2 pandemic.,The corticosteroids (inhaled and oral) are commonly prescribed in the management of asthma and COPD patients and any unsolicited changes in medications use may lead to potentially severe exacerbations and may risk patient lives.,This article provides a critical review of clinical evidence and offers a detailed discussion on the safety and efficacy of corticosteroids in asthma and COPD patients, both with and without COVID-19. | 1 |
An incremental approach using open-triple therapy may improve outcomes in patients with chronic obstructive pulmonary disease (COPD).,However, there is little sufficient, real-world evidence available identifying time to open-triple initiation.,This retrospective study of patients with COPD, newly initiated on long-acting muscarinic antagonist (LAMA) monotherapy or inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) combination therapy, assessed baseline demographics, clinical characteristics, and exacerbations during 12 months prior to first LAMA or ICS/LABA use.,Time to initiation of open-triple therapy was assessed for 12 months post-index date.,Post hoc analyses were performed to assess the subsets of patients with pulmonary-function test (PFT) information and patients with and without comorbid asthma.,Demographics and clinical characteristics were similar between cohorts in the pre-specified and post hoc analyses.,In total, 283 (19.3%) and 160 (10.9%) patients had moderate and severe exacerbations at baseline, respectively, in the LAMA cohort, compared with 482 (21.3%) and 289 (12.8%) patients in the ICS/LABA cohort.,Significantly more patients initiated open-triple therapy in the LAMA cohort compared with the ICS/LABA cohort (226 [15.4%] versus 174 [7.7%]; P<0.001); results were similar in the post hoc analyses.,Mean (standard deviation) time to open-triple therapy was 79.8 (89.0) days in the LAMA cohort and 122.9 (105.4) days in the ICS/LABA cohort (P<0.001).,This trend was also observed in the post hoc analyses, though the difference between cohorts was nonsignificant in the subset of patients with PFT information.,In this population, patients with COPD are more likely to initiate open-triple therapy following LAMA therapy, compared with ICS/LABA therapy.,Further research is required to identify factors associated with the need for treatment augmentation among patients with COPD. | Because additive effects of inhaled corticosteroids and long-acting anticholinergics are unclear, we undertook this study to compare the efficacy of tiotropium alone and tiotropium plus budesonide in patients with chronic obstructive pulmonary disease.,The study subjects were randomized to receive either tiotropium 18 µg once daily with or without budesonide 200 µg twice daily for 6 weeks.,The efficacy variables were changes in trough forced expiratory volume in one second (FEV1), St.,George's Respiratory Questionnaire (SGRQ), 6-minute walk distance (6MWD), and use of rescue medication.,One hundred patients were randomized and 81 completed the study.,The mean age was 64.0 yr, and the mean FEV1 was 39.7% predicted.,Compared with tiotropium alone (N=40), the tiotropium/budesonide combination (N=41) was related to an improvement in the SGRQ total score (tiotropium -2.8 units and tiotropium/budesonide -5.6 units, p=0.003).,6MWD was improved by 13.5 m in the tiotropium group and by 22.5 m in the tiotropium/budesonide group (p=0.031).,Changes in trough FEV1 and the use of rescue medication were similar between two groups.,In conclusion, compared with tiotropium alone, the tiotropium/budesonide combination was related to an improved health-related quality of life.,These data support that low-dose budesonide may enhance the efficacy of tiotropium. | 1 |
Life expectancy is significantly shorter for patients with chronic obstructive pulmonary disease (COPD) than the general population.,Concurrent diseases are known to infer an increased mortality risk in those with COPD, but the effects of pharmacological treatments on survival are less established.,This study aimed to examine any associations between commonly used drugs, comorbidities and mortality in Swedish real-world primary care COPD patients.,Patients with physician-diagnosed COPD from a large primary care population were observed retrospectively, utilizing primary care records and mandatory Swedish national registers.,The time to all-cause death was assessed in a stepwise multiple Cox proportional hazards regression model including demography, socioeconomic factors, exacerbations, comorbidities and medication.,During the observation period (1999-2009) 5776 (32.5%) of 17,745 included COPD patients died.,Heart failure (hazard ratio [HR]: 1.88, 95% confidence interval [CI]: 1.74-2.04), stroke (HR: 1.52, 95% CI: 1.40-1.64) and myocardial infarction (HR: 1.40, 95% CI: 1.24-1.58) were associated with an increased risk of death.,Use of inhaled corticosteroids (ICS; HR: 0.79, 95% CI: 0.66-0.94), beta-blockers (HR: 0.86, 95% CI: 0.76-0.97) and acetylsalicylic acid (ASA; HR: 0.87, 95% CI: 0.77-0.98) was dose-dependently associated with a decreased risk of death, whereas use of long-acting muscarinic antagonists (LAMA; HR: 1.33, 95% CI: 1.14-1.55) and N-acetylcysteine (NAC; HR: 1.26, 95% CI: 1.08-1.48) were dose-dependently associated with an increased risk of death in COPD patients.,This large, retrospective, observational study of Swedish real-world primary care COPD patients indicates that coexisting heart failure, stroke and myocardial infarction were the strongest predictors of death, underscoring the importance of timely recognition and treatment of comorbidities.,A decreased risk of death associated with the use of ICS, beta-blockers and ASA, and an increased risk associated with the use of LAMA and NAC, was also found. | Chronic obstructive pulmonary disease (COPD) exacerbations are associated with systemic consequences.,Data from a 4-year trial (Understanding Potential Long-term Impacts on Function with Tiotropium [UPLIFT®], n = 5,992) were used to determine risk for nonlower respiratory serious adverse events (NRSAEs) following an exacerbation.,Patients with ≥1 exacerbation were analyzed.,NRSAE incidence rates (incidence rate [IR], per 100 patient-years) were calculated for the 30 and 180 days before and after the first exacerbation.,NRSAEs were classified by diagnostic terms and organ classes.,Maentel-Haenszel rate ratios (RR) (pre- and postexacerbation onset) along with 95% confidence intervals (CI) were computed.,A total of 3,960 patients had an exacerbation.,The mean age was 65 years, forced expiratory volume in 1 s (FEV1) was 38% predicted, and 74% were men.,For all NRSAEs, the IRs 30 days before and after an exacerbation were 20.2 and 65.2 with RR (95% CI) = 3.22 (2.40-4.33).,The IRs for the 180-day periods were 13.2 and 31.0 with RR (95% CI) = 2.36 (1.93-2.87).,The most common NRSAEs by organ class for both time periods were cardiac, respiratory system (other), and gastrointestinal.,All NRSAEs as well as cardiac events were more common after the first exacerbation, irrespective of whether the patient had cardiac disease at baseline.,The findings confirm that, after exacerbations, serious adverse events in other organ systems are more frequent, particularly those that are cardiac in nature. | 1 |
H. haemolyticus is often misidentified as NTHi due to their close phylogenetic relationship.,Differentiating between the two is important for correct identification and appropriate treatment of infective organism and to ensure any role of H. haemolyticus in disease is not being overlooked.,Speciation however is not completely reliable by culture and PCR methods due to the loss of haemolysis by H. haemolyticus and the heterogeneity of NTHi.,Haemophilus isolates from COPD as part of the AERIS study (ClinicalTrials - NCT01360398) were speciated by analysing sequence data for the presence of molecular markers.,Further investigation into the genomic relationship was carried out using average nucleotide identity and phylogeny of allelic and genome alignments.,Only 6.3% were identified as H. haemolyticus.,Multiple in silico methods were able to distinguish H. haemolyticus from NTHi.,However, no single gene target was found to be 100% accurate.,A group of omp2 negative NTHi were observed to be phylogenetically divergent from H. haemolyticus and remaining NTHi.,The presence of an atypical group from a geographically and disease limited set of isolates supports the theory that the heterogeneity of NTHi may provide a genetic continuum between NTHi and H. haemolyticus. | Emphysema is characterised by distinct pathological sub-types, but little is known about the divergent underlying aetiology.,Matrix-metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and have been identified as potentially important in the development of emphysema.,However, the relationship between MMPs and emphysema sub-type is unknown.,We investigated the role of MMPs and their inhibitors in the development of emphysema sub-types by quantifying levels and determining relationships with these sub-types in mild-moderate COPD patients and ex/current smokers with preserved lung function.,Twenty-four mild-moderate COPD and 8 ex/current smokers with preserved lung function underwent high resolution CT and distinct emphysema sub-types were quantified using novel local histogram-based assessment of lung density.,We analysed levels of MMPs and tissue inhibitors of MMPs (TIMPs) in bronchoalveolar lavage (BAL) and assessed their relationship with these emphysema sub-types.,The most prevalent emphysema subtypes in COPD subjects were mild and moderate centrilobular (CLE) emphysema, while only small amounts of severe centrilobular emphysema, paraseptal emphysema (PSE) and panlobular emphysema (PLE) were present.,MMP-3, and -10 associated with all emphysema sub-types other than mild CLE, while MMP-7 and -8 had associations with moderate and severe CLE and PSE.,MMP-9 also had associations with moderate CLE and paraseptal emphysema.,Mild CLE occurred in substantial quantities irrespective of whether airflow obstruction was present and did not show any associations with MMPs.,Multiple MMPs are directly associated with emphysema sub-types identified by CT imaging, apart from mild CLE.,This suggests that MMPs play a significant role in the tissue destruction seen in the more severe sub-types of emphysema, whereas early emphysematous change may be driven by a different mechanism.,Trial registration number NCT01701869.,The online version of this article (doi:10.1186/s12931-016-0402-z) contains supplementary material, which is available to authorized users. | 1 |
Exacerbations of COPD (ECOPD) are a frequent cause of hospitalization that seemed to ameliorate during the COVID outbreak.,We aimed to evaluate the clinical characteristics of COPD-related hospital admissions and mortality in relation to the presence of COVID-19.,We conducted a case-control study of patients admitted in four teaching hospitals throughout Spain between March 15 and April 30, 2020.,Hospital admissions of respiratory cause with and without PCR-proven SARS-CoV-2 infection in patients with COPD were evaluated.,Baseline and episode-related clinical characteristics were analyzed.,Logistic regression analysis was performed to evaluate the risk for mortality.,During the study period, 2101 patients were admitted for respiratory worsening, 1200 (57.1%) with COVID-19.,A total of 228 (10.8%) were admitted due to COPD worsening, of whom 52 (22.8%) tested positive for COVID-19.,COPD patients with COVID-19, when compared to those without COVID-19, were more frequently males with better lung function (FEV1 postbronchodilator 71% vs 46% respectively, p<0.001) and had higher mortality (44.9% vs 13.6% respectively, p<0.001) despite similar age, comorbidities, total days of hospitalization and admission to intensive care unit.,COVID-19 and eosinopenia were the strongest risk factors for mortality in the multivariate analysis in the overall COPD population.,Inhaled corticosteroid use was not associated to mortality.,Hospitalizations for ECOPD without COVID-19 were more frequent than COPD with COVID-19 during the first outbreak, but the latter were associated with higher mortality and low eosinophil counts that warrant further analysis. | To evaluate whether the initial chest X-ray (CXR) severity assessed by an AI system may have prognostic utility in patients with COVID-19.,This retrospective single-center study included adult patients presenting to the emergency department (ED) between February 25 and April 9, 2020, with SARS-CoV-2 infection confirmed on real-time reverse transcriptase polymerase chain reaction (RT-PCR).,Initial CXRs obtained on ED presentation were evaluated by a deep learning artificial intelligence (AI) system and compared with the Radiographic Assessment of Lung Edema (RALE) score, calculated by two experienced radiologists.,Death and critical COVID-19 (admission to intensive care unit (ICU) or deaths occurring before ICU admission) were identified as clinical outcomes.,Independent predictors of adverse outcomes were evaluated by multivariate analyses.,Six hundred ninety-seven 697 patients were included in the study: 465 males (66.7%), median age of 62 years (IQR 52-75).,Multivariate analyses adjusting for demographics and comorbidities showed that an AI system-based score ≥ 30 on the initial CXR was an independent predictor both for mortality (HR 2.60 (95% CI 1.69 − 3.99; p < 0.001)) and critical COVID-19 (HR 3.40 (95% CI 2.35-4.94; p < 0.001)).,Other independent predictors were RALE score, older age, male sex, coronary artery disease, COPD, and neurodegenerative disease.,AI- and radiologist-assessed disease severity scores on CXRs obtained on ED presentation were independent and comparable predictors of adverse outcomes in patients with COVID-19.,ClinicalTrials.gov NCT04318366 (https://clinicaltrials.gov/ct2/show/NCT04318366).,• AI system-based score ≥ 30 and a RALE score ≥ 12 at CXRs performed at ED presentation are independent and comparable predictors of death and/or ICU admission in COVID-19 patients.,• Other independent predictors are older age, male sex, coronary artery disease, COPD, and neurodegenerative disease.,• The comparable performance of the AI system in relation to a radiologist-assessed score in predicting adverse outcomes may represent a game-changer in resource-constrained settings. | 1 |
Low-attenuation muscle area (LAMA) and normal-attenuation muscle area (NAMA) indicate lipid-rich and lipid-poor skeletal muscle areas, respectively.,Additionally, intermuscular adipose tissue (IMAT) indicates localized fat between muscle groups.,In this study, we aimed to evaluate the intramuscular and intermuscular fat infiltration in individuals with chronic obstructive pulmonary disease (COPD) by performing quantitative assessment of the LAMA, NAMA, and IMAT observed on abdominopelvic computed tomography (APCT) images.,We performed a cross-sectional study using data of subjects who underwent a general health examination with APCT at Ulsan University Hospital between March 2014 and June 2019.,We classified the subjects into control and COPD groups based on age, smoking history, and pulmonary function results.,We compared the attenuation and body mass index adjusted area of intra-abdominal components between the two groups using propensity score matching.,We also evaluated these outcomes in COPD subgroups (mild and moderate stage subjects).,Overall, 6,965 subjects were initially enrolled, and 250 pairs of control and COPD subjects were selected after propensity score matching.,The NAMA attenuation (unstandardized β=−1.168, P<0.001) was lower, and the IMAT (unstandardized β=0.042, P=0.006) and LAMA (unstandardized β=0.120, P<0.001) indexes were greater in the COPD group than in the control group.,In subgroup analysis, those with mild and moderate COPD also had high IMAT (unstandardized β=0.037, P=0.009 and unstandardized β=0.045, P<0.001) and LAMA (unstandardized β=0.089, P=0.002 and unstandardized β=0.147, P<0.001) indexes compared to the control subjects.,However, the NAMA attenuation (unstandardized β=−1.075, P<0.001) and NAMA index (unstandardized β=−0.133, P=0.015) were significantly lower in moderate COPD subjects only.,Our study showed that intramuscular and intermuscular abdominal fat infiltration could be present in subjects with mild COPD, and it might be exacerbated in those with moderate COPD. | Physical activity (PA) is considered as one of the most important prognostic predictors in chronic obstructive pulmonary disease (COPD) patients.,Longevity gene, SIRT1, is reported to be involved in the pathogenesis of COPD by regulating the signaling pathways of oxidative stress, inflammation, and aging.,We hypothesize that SIRT1 and related genes are also associated with the benefits of PA in COPD patients.,Eighteen COPD outpatients were enrolled in this study, and their PA level was assessed with an accelerometer.,We assessed the SIRT1 and related genes mRNA expression levels in the peripheral blood mononuclear cells (PBMCs) of the subjects.,We carried out respiratory function testing, blood gas analysis, the 6-minute walk test, and measurement of the cross-sectional area of the erector spinae muscles (ESMCSA) by chest computed tomography.,We analyzed the association of PA with the results of each of the examinations.,The mean age was 72±9 years, and the mean forced expiratory volume in 1 second was 1.4±0.56 L (52%±19% predicted).,Our findings revealed a correlation between the daily PA and ESMCSA.,The SIRT1 and Forkhead box O (FOXO)1 mRNA expression levels in PBMCs were positively correlated with moderate-PA time (r=0.60, p=0.008 for SIRT1 and r=0.59, p=0.01 for FOXO1). | 1 |
The introduction of microCT has made it possible to show that the terminal bronchioles are narrowed and destroyed before the onset of emphysematous destruction in COPD.,This report extends those observations to the cellular and molecular level in the centrilobular phenotype of emphysematous destruction in lungs donated by persons with very severe COPD (n = 4) treated by lung transplantation with unused donor lungs (n = 4) serving as controls.,These lung specimens provided companion samples to those previously examined by microCT (n = 61) that we examined using quantitative histology (n = 61) and gene expression profiling (n = 48).,The histological analysis showed that remodeling and destruction of the bronchiolar and alveolar tissue is associated with macrophage, CD4, CD8, and B cell infiltration with increased formation of tertiary lymphoid organs.,Moreover, gene set enrichment analysis showed that genes known to be expressed by natural killer (NK), lymphoid tissue inducer (LTi), and innate lymphoid cell 1 (ILC1) cells, but not ILC2 or ILC3 cells, were enriched in the expression profiles associated with CD4, CD8, and B cell infiltration.,Based on these findings, we postulate that the centrilobular phenotype of emphysematous destruction COPD is driven by a Th1 response activated by infiltrating ILC1, NK, and LTi cells. | A suggested role for T cells in COPD pathogenesis is based on associations between increased lung cytotoxic T lymphocyte (CD8+) numbers and airflow limitation.,CD69 is an early T cell activation marker.,Natural Killer cell group 2 D (NKG2D) receptors are co-stimulatory molecules induced on CD8+ T cells upon activation.,The activating function of NKG2 D is triggered by binding to MHC class 1 chain-related (MIC) molecules A and B, expressed on surface of stressed epithelial cells.,The aim of this study was to evaluate the expression of MIC A and B in the bronchial epithelium and NKG2 D and CD69 on BAL lymphocytes in subjects with COPD, compared to smokers with normal lung function and healthy never-smokers.,Bronchoscopy with airway lavages and endobronchial mucosal biopsy sampling was performed in 35 patients with COPD, 21 healthy never-smokers and 16 smokers with normal lung function.,Biopsies were immunohistochemically stained and BAL lymphocyte subsets were determined using flow cytometry.,Epithelial CD3+ lymphocytes in bronchial biopsies were increased in both smokers with normal lung function and in COPD patients, compared to never-smokers.,Epithelial CD8+ lymphocyte numbers were higher in the COPD group compared to never-smoking controls.,Among gated CD3+cells in BAL, the percentage of CD8+ NKG2D+ cells was enhanced in patients with COPD and smokers with normal lung function, compared to never-smokers.,The percentage of CD8+ CD69+ cells and cell surface expression of CD69 were enhanced in patients with COPD and smokers with normal lung function, compared to never-smokers.,No changes in the expression of MIC A or MIC B in the airway epithelium could be detected between the groups, whereas significantly decreased soluble MICB was detected in bronchial wash from smokers with normal lung function, compared to never-smokers.,In COPD, we found increased numbers of cytotoxic T cells in both bronchial epithelium and airway lumen.,Further, the proportions of CD69- and NKG2D-expressing cytotoxic T cells in BAL fluid were enhanced in both subjects with COPD and smokers with normal lung function and increased expression of CD69 was found on CD8+ cells, indicating the cigarette smoke exposure-induced expansion of activated cytotoxic T cells, which potentially can respond to stressed epithelial cells. | 1 |
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