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After the development of the COPD Strategy of the National Health Service in Spain, all scientific societies, patient organisations, and central and regional governments formed a partnership to enhance care and research in COPD.,At the same time, the Spanish Society of Pneumology and Thoracic Surgery (SEPAR) took the initiative to convene the various scientific societies involved in the National COPD Strategy and invited them to participate in the development of the new Spanish guidelines for COPD (Guía Española de la EPOC; GesEPOC).,Probably the more innovative approach of GesEPOC is to base treatment of stable COPD on clinical phenotypes, a term which has become increasingly used in recent years to refer to the different clinical forms of COPD with different prognostic implications.,The proposed phenotypes are: (A) infrequent exacerbators with either chronic bronchitis or emphysema; (B) overlap COPD-asthma; (C) frequent exacerbators with emphysema predominant; and (D) frequent exacerbators with chronic bronchitis predominant.,The assessment of severity has also been updated with the incorporation of multidimensional indices.,The severity of the obstruction, as measured by forced expiratory volume in 1 second, is essential but not sufficient.,Multidimensional indices such as the BODE index have shown excellent prognostic value.,If the 6-minute walking test is not performed routinely, its substitution by the frequency of exacerbations (BODEx index) provides similar prognostic properties.,This proposal aims to achieve a more personalised management of COPD according to the clinical characteristics and multidimensional assessment of severity. | 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 |
Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) released an updated document in 2017 that excluded the spirometric parameter in the classification of patients.,The validity of this new classification system in predicting mortality and respiratory hospitalization is still uncertain.,Methods: Outpatients (n=149) with chronic obstructive pulmonary disease (COPD) who underwent spirometry and six-minutes walking test from October 2011 to September 2013 were enrolled.,The overall mortality and rate of respiratory hospitalization over a median of 61 months were analyzed.,Kaplan-Meier survival analyses, receiver operaing curve analyses with areas under the curve (AUCs), and logistic regression analyses for GOLD 2007, GOLD 2011, GOLD 2017, and/or BODE index were performed to evaluate their abilities to predict mortality and respiratory hospitalization.,Results: Forty-two (53.2%) patients in 2011 GOLD C or D group were categorized into 2017 GOLD A or B group.,The odds ratios of GOLD 2017 group C and group D relative to group A were 7.55 (95% CI, 1.25-45.8) and 25.0 (95% CI, 6.01-102.9) for respiratory hospitalization.,Patients in GOLD 2017 group A and group B had significantly better survival (log-rank test, p<0.001) compared with patients in group D; however, survival among patients in GOLD 2007 groups and GOLD 2011 groups was comparable.,The AUC values for GOLD 2007, GOLD 2011, GOLD 2017, and BODE index were 0.573, 0.624, 0.691, 0.692 for mortality (p=0.013) and 0.697, 0.707, 0.741, and 0.754 for respiratory hospitalization (p=0.296), respectively.,Conclusion: The new GOLD classification may perform better than the previous classifications in terms of predicting mortality and respiratory hospitalization. | To investigate the correlation of miR-125a/b expression with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients and inflammatory cytokines.,Eighty-seven AECOPD patients, 93 stable chronic obstructive pulmonary disease (COPD) patients and 100 health volunteers (HCs) were recruited.,Plasma samples were collected from AECOPD patients at the day 1, day 7, day 14, and day 28 of admission and from stable COPD patients as well as HCs.,Total RNA was extracted from plasma, and miR-125a/b relative expressions were determined by quantitative real time-polymerase chain reaction.,MiR-125b had a great capacity for distinguishing AECOPD from stable COPD (AUC = 0.926, 95% CI: 0.884-0.967) and HCs (AUC = 0.923, 95% CI: 0.880-0.966), while miR-125a did not.,There were associations between miR-125b expression with TNF-α, IL-8, and LTB-4 in AECOPD patients (P = .012, P = .032, and P = .047, respectively), while no correlation of miR-125a with inflammatory cytokines was found.,MiR-125b expression gradually decreased at day 7, day 14, and day 28 compared with day 1 (all P < .05) on admission, while no difference in miR-125a was discovered between each visit compared to day 1.,Besides, TNF-α, IL-1β, IL-8, and LTB-4 were elevated in AECOPD patients compared with stable COPD patients (all P < .01).,MiR-125b, but not miR-125a, was positively associated with inflammatory cytokines and could be a novel biomarker for distincting AECOPD from stable COPD patients and HCs. | 1 |
Acute exacerbations (AE) affect the prognosis of hospitalized patients with chronic obstructive pulmonary disease (COPD).,Pneumonia further affects their prognosis and early diagnosis of pneumonia in AECOPD is important to initiate treatments.,This study aimed to examine the differences between hospitalized AECOPD patients with and without pneumonia in order to identify risk factors of pneumonia among hospitalized patients with AECOPD.,This was a retrospective case-control study of patients with COPD hospitalized at the respiratory ward of Beijing Shijitan Hospital, Capital Medical University, from October 2010 to October 2013.,Patients were divided into the pneumonia and nonpneumonia groups based on exudations or opacities on chest computed tomography (CT) at admission.,Data were analyzed using the chi-square test and independent 2-sample ANOVA in SPSS 20.0.,Logistic regression analysis was used to identify the factors independently associated with pneumonia.,P < .05 was considered statistically significant.,A total of 164 patients were included.,Smoking history (OR = 2.646, 95%CI 1.153-6.074, P = .022), use of drugs during the stable stage (OR = 0.435, 95%CI 0.216-0.877, P = .020), D-dimer levels (OR = 1.001, 95%CI 1.000-1.002, P = .049), percentage of neutrophils (OR = 0.271, 95%CI 0.078-0.940, P = .040), and magnitude of neutrophils increase (OR = 0.946, 95%CI 0.896-0.999, P = .046) were independently associated with pneumonia in patients with AECOPD.,For severe and very severe COPD patients, smoking history (OR = 4.426, 95%CI 1.458-13.435, P = .009), use of drugs during the stable stage (OR = 0.384, 95%CI 0.168-0.877, P = .042), and fever (OR = 0.426, 95%CI 0.187-0.969, P = .023) were independently associated with pneumonia.,Smoking history, use of drugs during the stable stage, and percentage of neutrophils are independently associated with CT-diagnosed pneumonia among hospitalized AECOPD patients. | In prognostic studies, the lasso technique is attractive since it improves the quality of predictions by shrinking regression coefficients, compared to predictions based on a model fitted via unpenalized maximum likelihood.,Since some coefficients are set to zero, parsimony is achieved as well.,It is unclear whether the performance of a model fitted using the lasso still shows some optimism.,Bootstrap methods have been advocated to quantify optimism and generalize model performance to new subjects.,It is unclear how resampling should be performed in the presence of multiply imputed data.,The data were based on a cohort of Chronic Obstructive Pulmonary Disease patients.,We constructed models to predict Chronic Respiratory Questionnaire dyspnea 6 months ahead.,Optimism of the lasso model was investigated by comparing 4 approaches of handling multiply imputed data in the bootstrap procedure, using the study data and simulated data sets.,In the first 3 approaches, data sets that had been completed via multiple imputation (MI) were resampled, while the fourth approach resampled the incomplete data set and then performed MI.,The discriminative model performance of the lasso was optimistic.,There was suboptimal calibration due to over-shrinkage.,The estimate of optimism was sensitive to the choice of handling imputed data in the bootstrap resampling procedure.,Resampling the completed data sets underestimates optimism, especially if, within a bootstrap step, selected individuals differ over the imputed data sets.,Incorporating the MI procedure in the validation yields estimates of optimism that are closer to the true value, albeit slightly too larger.,Performance of prognostic models constructed using the lasso technique can be optimistic as well.,Results of the internal validation are sensitive to how bootstrap resampling is performed.,The online version of this article (doi:10.1186/1471-2288-14-116) contains supplementary material, which is available to authorized users. | 1 |
Blood eosinophil count has been proposed as a predictor of response to inhaled corticosteroid (ICS) in the prevention of acute exacerbations of COPD.,An optimal threshold of blood eosinophil count for prescribing ICS has not been agreed.,Doubt has been cast on the role by observational studies.,The role of inhaled corticosteroids in this relationship, independent of long-acting bronchodilators, has not been examined.,We conducted a systematic review of post-hoc analyses of randomised controlled trials (RCTs) and observational studies examining three blood eosinophil thresholds and the independent role of ICS.,Included studies were categorised by the form (relative or absolute count) and cut point of eosinophil threshold used.,Thresholds assessed were relative eosinophil count of 2%, and absolute counts of 150 cells/μL and 300 cells/μL.,Three meta-analyses of the effect of ICS use in post-hoc analyses of RCTs based on these counts were carried out.,Initial analysis included all studies of ICS vs. any non-ICS regimen.,Further analysis examined the effect of ICS, independent of the effect of long-acting bronchodilators.,Sixteen studies examined the association between blood eosinophil count and response of exacerbation risk to ICS, in COPD patients.,Eleven studies (25,881 patients) were post-hoc analyses of RCTs.,Five studies (109,704 patients) were retrospective observational studies.,The independent effect of ICS on the reduction of exacerbation risk was 20% at ≥2% blood eosinophil threshold (RR, 0.80; 95% CI, 0.74-0.85), 35% at ≥150 cells/μL blood eosinophil threshold (RR, 0.65; 0.52-0.79), and 39% at ≥300 cells/μL blood eosinophil threshold (RR, 0.61; 0.44-0.78).,No association was found in four out of five observational studies.,This is the first systematic review to assess, in post-hoc analyses of RCTs, the independent effect of ICS in reducing the risk of COPD exacerbation across a range of blood eosinophil thresholds.,Association between ICS prescription and reduced exacerbation risk at these thresholds was confirmed.,The lack of association found in the observational studies questions the relevance of these observations to a “real world” COPD population.,To clarify the clinical utility of this biomarker, the association should be tested in prospective effectiveness studies. | Current evidence suggests that a higher blood eosinophil cell count at admission for acute exacerbation of COPD (AECOPD) is associated with a favorable response to systemic steroids.,However, the impact of blood eosinophil counts at admission on post-hospitalization outcomes is still unclear.,The main objective of this study is to investigate readmission outcomes associated with blood eosinophilia following severe COPD exacerbation in patients with infrequent COPD hospitalizations.,This is an observational cohort study design.,We retrospectively analyzed data of patients with a first hospitalization within 5 years for COPD exacerbation between April 2006 and March 2013.,Patients were stratified into the eosinophilic group if the blood eosinophil count on admission was ≥200 cells/µL and/or ≥2% of the total white blood cell (WBC) count.,The primary outcome was 1-year COPD-related readmission.,Secondary outcomes included 1-year all-cause mortality, 1-year all-cause readmission, length of stay, time to COPD-related readmission, and number of 1-year COPD-associated emergency department (ED) and ambulatory visits.,A total of 479 patients were included.,Of whom, 173 were stratified into the eosinophilic group.,Higher blood eosinophil cell count was associated with an increased risk of 1-year COPD-related readmission (OR, 1.83 [95% CI, 1.16-2.89]; P<0.01), a shorter time to first COPD-related readmission (HR, 1.64 [95% CI, 1.14-2.36]; P<0.01), and an increased number of 1-year COPD-related ED visits (incidence rate ratio, 1.78 [95% CI, 1.21-2.61]; P<0.01).,All-cause mortality, all-cause readmission, length of stay, and number of ambulatory visits did not differ between groups.,Higher blood eosinophil cell count at admission for a COPD exacerbation is associated with increased COPD readmission rates in patients with infrequent COPD hospitalizations. | 1 |
Patients with SCAD and concomitant COPD are at high risk of cardiovascular adverse events, due to chronic inflammation, responsible of endothelial dysfunction, oxidative stress and heightened platelet reactivity (PR).,The objective of this randomised clinical trial was to test if ticagrelor is superior to clopidogrel in improving endothelial function in patients with stable coronary artery disease (SCAD) and concomitant chronic obstructive pulmonary disease (COPD).,Forty-six patients with SCAD and COPD undergoing percutaneous coronary intervention (PCI) were randomly assigned to receive clopidogrel (n=23) or ticagrelor (n=23) on top of standard therapy with aspirin.,The following parameters were assessed at baseline and after 1 month: i) rate of apoptosis and ii) nitric oxide (NO) levels in human umbilical vein endothelial cells (HUVECs), iii) levels of reactive oxygen species (ROS) in peripheral blood mononuclear cell, iv) 29 cytokines/chemokines, v) on-treatment PR.,The primary endpoint of the study was the 1-month rate of HUVECs apoptosis.,The rate of apoptosis after 1 month was significantly lower in patients treated with ticagrelor (7.4 ± 1.3% vs 9.3 ± 1.5%, p<0.001), satisfying the pre-specified primary endpoint.,In the ticagrelor arm, levels of NO were higher (10.1 ± 2.2 AU vs 8.5 ± 2.6 AU, p=0.03) while those of ROS (4 ± 1.8 AU vs 5.7 ± 2.8 AU, p=0.02) and P2Y 12 reactivity units (52 ± 70 PRU vs 155 ± 62 PRU, p<0.001) were lower.,There were no differences in cytokines/chemokines levels and aspirin reactivity units between groups.,In patients with SCAD and COPD undergoing PCI, ticagrelor, as compared to clopidogrel is superior in improving surrogate markers of endothelial function and on-treatment PR (ClinicalTrials.gov, NCT02519608).,Supplementary Material to this article is available online at www.thrombosis-online.com. | Thrombocytosis has been associated with COPD prevalence and increased all-cause mortality in patients with acute exacerbation of COPD (AECOPD); but whether it is associated with morbidity in stable COPD is unknown.,This study aims to determine the association of thrombocytosis with COPD morbidity including reported AECOPD, respiratory symptoms and exercise capacity.,Participants with COPD were included from two multi-center observational studies (SPIROMICS and COPDGene).,Cross-sectional associations of thrombocytosis (platelet count ≥350 × 109/L) with AECOPD during prior year (none vs. any), exertional dyspnea (modified Medical Research Council (mMRC) score ≥ 2), COPD Assessment Test (CAT) score ≥ 10, six-minute-walk distance (6MWD), and St.,George Respiratory questionnaire (SGRQ) were modeled using multivariable logistic or linear regression.,A pooled effect estimate for thrombocytosis was produced using meta-analysis of data from both studies.,Thrombocytosis was present in 124/1820 (6.8%) SPIROMICS participants and 111/2185 (5.1%) COPDGene participants.,In meta-analysis thrombocytosis was associated with any AECOPD (adjusted odds ratio [aOR] 1.5; 95% confidence interval [95% CI]: 1.1-2.0), severe AECOPD (aOR 1.5; 95% CI: 1.1-2.2), dyspnea (mMRC ≥ 2 aOR 1.4; 95% CI: 1.0-1.9), respiratory symptoms (CAT ≥ 10 aOR 1.6; 95% CI: 1.1-2.4), and higher SGRQ score (β 2.7; 95% CI: 0.5, 5).,Thrombocytosis was also associated with classification into Global Initiative for Chronic Obstructive Lung Disease (GOLD) group D (aOR 1.7 95% CI: 1.2-2.4).,Thrombocytosis was associated with higher likelihood of prior exacerbation and worse symptoms.,Platelet count, a commonly measured clinical assay, may be a biomarker for moderate-severe COPD symptoms, guide disease classification and intensity of treatment.,Future longitudinal studies investigating the role of platelets in COPD progression may be warranted.,ClinicalTrials.gov: NCT01969344 (SPIROMICS) and NCT00608764 (COPDGene). | 1 |
Research on the association between chronic bronchitis and chronic obstructive pulmonary disease (COPD) exacerbations has led to discordant results.,Furthermore, the impact of chronic bronchitis on mortality in COPD subjects is unclear.,Within the Rotterdam Study, a population-based cohort study of subjects aged ≥45 years, chronic bronchitis was defined as having a productive cough for ≥3 months per year for two consecutive years.,Linear, logistic regression and Cox proportional hazard models were adjusted for age, sex and pack-years.,Out of 972 included COPD subjects, 752 had no chronic phlegm production (CB−) and 220 had chronic phlegm production, of whom 172 met the definition of chronic bronchitis (CB+).,CB+ subjects were older, more frequently current smokers and had more pack-years than CB− subjects.,During a median 6.5 years of follow-up, CB+ subjects had greater decline in lung function (−38 mL·year−1, 95% CI −61.7-−14.6; p=0.024).,CB+ subjects had an increased risk of frequent exacerbations (OR 4.0, 95% CI 2.7-5.9; p<0.001).,In females, survival was significantly worse in CB+ subjects compared to CB− subjects.,Regarding cause-specific mortality, CB+ subjects had an increased risk of respiratory mortality (hazard ratio 2.16, 95% CI 1.12-4.17; p=0.002).,COPD subjects with chronic bronchitis have an increased risk of exacerbations and respiratory mortality compared to COPD subjects without chronic phlegm production.,Chronic bronchitis increases the risk of exacerbations and mortality among patients with COPDhttp://ow.ly/o1fq30bFf9Q | 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 |
We investigated the association between cognitive impairment and chronic obstructive pulmonary disease (COPD), taking into account demographic and clinical variables evaluated during routine practice.,We performed a post hoc analysis of a cross-sectional study that included subjects with stable COPD.,Sociodemographic and clinical information was recorded using the Body mass index, airflow Obstruction, Dyspnea and Exacerbations index and the Charlson comorbidity index.,Cognitive performance was studied by the mini-mental state examination, with a score less than 27 indicating clinical impairment.,Depressive symptoms, physical activity, and quality of life (EuroQoL-5 dimensions and COPD Assessment Test) were also evaluated.,The analysis included 940 subjects.,The prevalence of cognitive impairment was 39.4%.,Multivariate logistic regression models revealed that cognitive impairment was associated with educational level (odds ratio [OR] =0.096, 95% confidence interval [CI] =0.011-0.447) and poorer quality of life measured by the EuroQoL-5 dimensions social tariff (OR =0.967, 95% CI =0.950-0.983).,When questionnaires were not included in the analysis, cognitive impairment was associated with educational level (OR =0.063, 95% CI =0.010-0.934), number of exacerbations (OR =11.070, 95% CI =1.450-84.534), Body mass index, airflow Obstruction, Dyspnea and Exacerbations index score (OR =1.261, 95% CI =1.049-1.515), and the Charlson comorbidity index (OR =1.412, 95% CI =1.118-1.783).,Cognitive impairment is common in COPD and is associated with low educational level, higher disease severity, and increased comorbidity.,This could have therapeutic implications for this population. | Cognitive impairment is increasingly being found to be a common comorbidity in chronic obstructive pulmonary disease (COPD).,This study sought to understand the relationship of comprehensively measured cognitive function with COPD severity, quality of life, living situation, health care utilization, and self-management abilities.,Subjects with COPD were recruited from the outpatient pulmonary clinic.,Cognitive function was assessed using the Montreal Cognitive Assessment (MOCA).,Self-management abilities were measured using the Self Management Ability Score 30.,Quality of life was measured using the Chronic Respiratory Disease Questionnaire.,Pearson correlation was used to assess the bivariate association of the MOCA with other study measures.,Multivariate analysis was completed to understand the interaction of the MOCA and living situation on COPD outcomes of hospitalization, quality of life, and self-management ability.,This study included 100 participants of mean age 70±9.4 years (63% male, 37% female) with COPD (mean FEV1 [forced expiratory volume in 1 second] percentage predicted 40.4±16.7).,Mean MOCA score was 23.8±3.9 with 63% of patients having mild cognitive impairment.,The MOCA was negatively correlated with age (r=−0.28, P=0.005) and positively correlated with education (r=+0.24, P=0.012).,There was no significant correlation between cognitive function and exacerbations, emergency room (ER) visits, or hospitalizations.,There was no association between the MOCA score and self-management abilities or quality of life.,We tested the interaction of living situation and the MOCA with self-management abilities and found statistical significance (P=0.017), indicating that individuals living alone with higher cognitive function report lower self-management abilities.,Cognitive impairment in COPD does not appear to be meaningfully associated with COPD severity, health outcomes, or self-management abilities.,The routine screening for cognitive impairment due to a diagnosis of COPD may not be indicated.,Living alone significantly affects the interaction between self-management abilities and cognitive function. | 1 |
Inhaled corticosteroid use is associated with increased rates of pneumonia in COPD patients.,The underlying mechanism is unknown, although recent data suggest that pneumonia is more frequent in patients treated with fluticasone propionate (FP) than budesonide.,Macrophages and neutrophils from COPD patients are deficient in clearing bacteria, and this might explain increased bacterial colonization in COPD.,Inhaled corticosteroid may further suppress this response; therefore, we examined the effect of FP and budesonide on phagocytosis of common respiratory pathogens by monocyte-derived macrophages (MDMs) and neutrophils.,MDMs from COPD patients (n=20-24) were preincubated with FP or budesonide for 1 or 18 hours, after which phagocytosis of fluorescently labeled inert beads or heat-killed Haemophilus influenzae/Streptococcus pneumoniae were measured fluorimetrically after 1 or 4 hours.,Additionally, CXCL8, IL6, and TNFα concentrations in supernatants by ELISA, MDM-scavenger-receptor expression by flow cytometry, and MDM ability to kill bacteria were measured.,Neutrophils from COPD patients (n=8) were preincubated with corticosteroids for 1 hour and bacteria phagocytosis measured by flow cytometry.,After 1 hour’s preincubation, neither corticosteroid altered MDM phagocytosis of beads or H. influenzae; however, budesonide (10−7 M) increased S. pneumoniae phagocytosis by 23% (P<0.05).,After 18 hours’ preincubation, neither corticosteroid altered MDM phagocytosis of any prey, although H. influenzae phagocytosis by budesonide was significantly greater compared to FP at 10−6 and 10−5 M (P<0.05).,The 1-hour preincubation with either corticosteroid inhibited bacteria-induced CXCL8 release (at 10−7 and 10−5 M, P<0.05); however, this effect was lost at 18-hour preincubation.,There was no change in receptor expression, bacterial killing, or neutrophil phagocytosis by either corticosteroid.,These data suggest that dissolved FP and budesonide do not have an overall effect on MDM or neutrophil phagocytosis of bacteria. | The cardiovascular (CV) safety of inhaled corticosteroids (ICSs) in chronic obstructive pulmonary disease (COPD) is controversial because different studies have suggested that ICSs either increase or reduce the risk of CV events in COPD patients.,In this meta-analysis, we assess the CV safety of ICS therapy in COPD.,A meta-analysis of randomized, double-blind, parallel-group, placebo-controlled trials of ICS treatment for COPD that include at least 4 weeks of follow-up was performed.,A random-effects model was used to evaluate the effects of ICS treatment on CV events.,CV events were documented in each trial, and the relative risk (RR) and 95% confidence intervals (CIs) for ICSs were estimated.,Thirty-one trials were included in this meta-analysis.,The risk of CV events was not different between ICS-treated and control groups (RR: 0.99; 95% CI: 0.93 to 1.06; P=0.801).,In a subgroup analysis, there were no significant differences in CV events between an ICS combined with long-acting β2 agonist (LABA) (ICS + LABA) group and an LABA-only group (RR: 1.00; 95% CI: 0.90 to 1.10; P=0.930), as well as between a combination group (ICS + LABA) and a long-acting muscarinic antagonist (LAMA) combined with LABA (LAMA + LABA) group (RR: 0.78; 95% CI: 0.39 to 1.55; P=0.473).,In addition, there was no difference in the risk of CV events between ICS treatment and control groups (RR: 0.99; 95% CI: 0.90 to 1.09; P=0.872).,These results demonstrate that ICSs do not increase the risk of CV events in COPD patients. | 1 |
The study aimed to investigate the demographic characteristics, clinical features, diagnoses, and treatments of hospitalized exacerbation COPD patients, as well as their disease prognoses and economic costs.,The study planned to enroll 7600 hospitalized patients (aged ≥18 years with main diagnosis as AECOPD).,Study patients were recruited since September 2017, followed up with a 3-year observing period.,In the baseline visit, information on demographic characteristics, clinical features, diagnoses, and treatments were collected.,In the following visits, treatments and examinations, recurrence of AECOPD, re-admission to hospital, complications, and mortality were recorded.,Several validated questionnaires were applied at specific visits.,This study included data from 1 September 2017 until 31 December 2022.,The data would be used to estimate all-cause mortality during hospital stay, AECOPD recurrence within 1 month after discharge, all-cause and cause-specific mortality, frequency of AECOPD recurrence, lung function, life quality, healthcare costs in the study period, etc. | COPD is a leading cause of morbidity and mortality worldwide.,Patients with COPD often require admission to intensive care units (ICU) during an acute exacerbation.,This study aimed to identify the factors independently associated with hospital mortality in patients requiring ICU admission for acute exacerbation of COPD.,Patients admitted to the ICU of Frankston Hospital between January 2005 and June 2016 with an admission diagnosis of COPD were retrospectively identified from ICU databases.,Patients’ comorbidities, arterial blood gas results, and in-patient interventions were retrieved from their medical records.,Outcomes analyzed included hospital and ICU length of stay (LOS) and mortality.,A total of 305 patients were included.,Mean age was 67.4 years.,A total of 77% of patients required non-invasive ventilation; and 38.7% required invasive mechanical ventilation (IMV) for a median of 127.2 hours (SD =179.5).,Mean ICU LOS was 4.5 days (SD =5.96), and hospital LOS was 11.6 days (SD =13).,In-hospital mortality was 18.7%.,Multivariate analysis revealed that patient age (odds ratio [OR] =1.06; 95% CI: 1.031-1.096), ICU LOS (OR =1.26; 95% CI: 1.017-1.571), Acute Physiology and Chronic Health Evaluation-II score (OR =1.07; 95% CI: 1.012-1.123), and requirement for IMV (OR =4.09; 95% CI: 1.791-9.324) to be significantly associated with in-hospital mortality.,Patient age, requirement for IMV, and illness severity were associated with poor patient outcomes. | 1 |
Dyspnea is a complex, prevalent, and distressing symptom of chronic obstructive pulmonary disease (COPD) associated with decreased quality of life, significant disability, and increased mortality.,It is a major reason for referral to pulmonary rehabilitation.,We reviewed 23 COPD studies to examine the evidence for the effectiveness of cognitive-behavioral strategies for relieving dyspnea in COPD.,Preliminary evidence from randomized controlled trials exists to support cognitive- behavioral strategies, used with or without exercise, for relieving sensory and affective components of dyspnea in COPD.,Small to moderate treatment effects for relieving dyspnea were noted for psychotherapy (effect size [ES] = 0.08-0.25 for intensity; 0.26-0.65 for mastery) and distractive auditory stimuli (ES = 0.08-0.33 for intensity; 0.09 to −0.61 for functional burden).,Small to large dyspnea improvements resulted from yoga (ES = 0.2-1.21 for intensity; 0.67 for distress; 0.07 for mastery; and −8.37 for functional burden); dyspnea self-management education with exercise (ES = −0.14 to −1.15 for intensity; −0.62 to −0.69 for distress; 1.04 for mastery; 0.14-0.35 for self-efficacy); and slow-breathing exercises (ES = −0.34 to −0.83 for intensity; −0.61 to −0.80 for distress; and 0.62 for self-efficacy).,Cognitive-behavioral interventions may relieve dyspnea in COPD by (1) decreasing sympathetic nerve activity, dynamic hyperinflation, and comorbid anxiety, and (2) promoting arterial oxygen saturation, myelinated vagus nerve activity, a greater exercise training effect, and neuroplasticity.,While evidence is increasing, additional randomized controlled trials are needed to evaluate the effectiveness of psychosocial and self-management interventions in relieving dyspnea, in order to make them more available to patients and to endorse them in official COPD, dyspnea, and pulmonary rehabilitation practice guidelines.,By relieving dyspnea and related anxiety, such interventions may promote adherence to exercise programs and adaptive lifestyle change. | Chronic obstructive pulmonary disease (COPD) is predicted to become a major cause of death worldwide.,Studies on the variability in the estimates of key epidemiological parameters of COPD may contribute to better assessment of the burden of this disease and to helpful guidance for future research and public policies.,In the present study, we examined differences in the main epidemiological characteristics of COPD derived from studies across countries of the European Union, focusing on prevalence, severity, frequency of exacerbations and mortality, as well as on differences between the studies' methods.,This systematic review was based on a search for the relevant literature in the Science Citation Index database via the Web of Science and on COPD mortality rates issued from national statistics.,Analysis was finally based on 65 articles and Eurostat COPD mortality data for 21 European countries.,Epidemiological characteristics of COPD varied widely from country to country.,For example, prevalence estimates ranged between 2.1% and 26.1%, depending on the country, the age group and the methods used.,Likewise, COPD mortality rates ranged from 7.2 to 36.1 per 105 inhabitants.,The methods used to estimate these epidemiological parameters were highly variable in terms of the definition of COPD, severity scales, methods of investigation and target populations.,Nevertheless, to a large extent, several recent international guidelines or research initiatives, such as GOLD, BOLD or PLATINO, have boosted a substantial standardization of methodology in data collection and have resulted in the availability of more comparable epidemiological estimates across countries.,On the basis of such standardization, severity estimates as well as prevalence estimates present much less variation across countries.,The contribution of these recent guidelines and initiatives is outlined, as are the problems remaining in arriving at more accurate COPD epidemiological estimates across European countries.,The accuracy of COPD epidemiological parameters is important for guiding decision making with regard to preventive measures, interventions and patient management in various health care systems.,Therefore, the recent initiatives for standardizing data collection should be enhanced to result in COPD epidemiological estimates of improved quality.,Moreover, establishing international guidelines for reporting research on COPD may also constitute a major contribution. | 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. | Acute exacerbations contribute to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD).,This proof-of-concept study evaluates whether intermittent pulsed moxifloxacin treatment could reduce the frequency of these exacerbations.,Stable patients with COPD were randomized in a double-blind, placebo-controlled trial to receive moxifloxacin 400 mg PO once daily (N = 573) or placebo (N = 584) once a day for 5 days.,Treatment was repeated every 8 weeks for a total of six courses.,Patients were repeatedly assessed clinically and microbiologically during the 48-week treatment period, and for a further 24 weeks' follow-up.,At 48 weeks the odds ratio (OR) for suffering an exacerbation favoured moxifloxacin: per-protocol (PP) population (N = 738, OR 0.75, 95% confidence interval (CI) 0.565-0.994, p = 0.046), intent-to-treat (ITT) population (N = 1149, OR 0.81, 95% CI 0.645-1.008, p = 0.059), and a post-hoc analysis of per-protocol (PP) patients with purulent/mucopurulent sputum production at baseline (N = 323, OR 0.55, 95% CI 0.36-0.84, p = 0.006).,There were no significant differences between moxifloxacin and placebo in any pre-specified efficacy subgroup analyses or in hospitalization rates, mortality rates, lung function or changes in St George's Respiratory Questionnaire (SGRQ) total scores.,There was, however, a significant difference in favour of moxifloxacin in the SGRQ symptom domain (ITT: -8.2 vs -3.8, p = 0.009; PP: -8.8 vs -4.4, p = 0.006).,Moxifloxacin treatment was not associated with consistent changes in moxifloxacin susceptibility.,There were more treatment-emergent, drug related adverse events with moxifloxacin vs placebo (p < 0.001) largely due to gastrointestinal events (4.7% vs 0.7%).,Intermittent pulsed therapy with moxifloxacin reduced the odds of exacerbation by 20% in the ITT population, by 25% among the PP population and by 45% in PP patients with purulent/mucopurulent sputum at baseline.,There were no unexpected adverse events and there was no evidence of resistance development.,ClinicalTrials.gov number, NCT00473460 (ClincalTrials.gov). | 1 |
Subjects with chronic respiratory symptoms and preserved pulmonary function (PPF) may have small airway dysfunction (SAD).,As the most common means to detect SAD, spirometry needs good cooperation and its reliability is controversial.,Impulse oscillometry (IOS) may complete the deficiency of spirometry and have higher sensitivity.,We aimed to explore the diagnostic value of IOS to detect SAD in symptomatic subjects with PPF.,The evaluation of symptoms, spirometry and IOS results in 209 subjects with chronic respiratory symptoms and PPF were assessed.,ROC curves of IOS to detect SAD were analyzed.,209 subjects with chronic respiratory symptoms and PPF were included.,Subjects who reported sputum had higher R5-R20 and Fres than those who didn’t.,Subjects with dyspnea had higher R5, R5-R20 and AX than those without.,CAT and mMRC scores correlated better with IOS parameters than with spirometry.,R5, R5-R20, AX and Fres in subjects with SAD (n = 42) significantly increased compared to those without.,Cutoff values for IOS parameters to detect SAD were 0.30 kPa/L s for R5, 0.015 kPa/L s for R5-R20, 0.30 kPa/L for AX and 11.23 Hz for Fres.,Fres has the largest AUC (0.665, P = 0.001) among these parameters.,Compared with spirometry, prevalence of SAD was higher when measured with IOS.,R5 could detect the most SAD subjects with a prevalence of 60.77% and a sensitivity of 81% (AUC = 0.659, P = 0.002).,IOS is more sensitive to detect SAD than spirometry in subjects with chronic respiratory symptoms and PPF, and it correlates better with symptoms.,IOS could be an additional method for SAD detection in the early stage of diseases. | We investigated whether a relationship between small airways dysfunction and bronchodilator responsiveness exists in patients with chronic obstructive pulmonary disease (COPD).,We studied 100 (20 female; mean age: 68±10 years) patients with COPD (forced expiratory volume in 1 second [FEV1]: 55% pred ±21%; FEV1/forced vital capacity [FVC]: 53%±10%) by impulse oscillometry system.,Resistance at 5 Hz and 20 Hz (R5 and R20, in kPa·s·L−1) and the fall in resistance from 5 Hz to 20 Hz (R5 - R20) were used as indices of total, proximal, and peripheral airway resistance; reactance at 5 Hz (X5, in kPa·s·L−1) was also measured.,Significant response to bronchodilator (salbutamol 400 μg) was expressed as absolute (≥0.2 L) and percentage (≥12%) change relative to the prebronchodilator value of FEV1 (flow responders, FRs) and FVC (volume responders, VRs).,Eighty out of 100 participants had R5 - R20 >0.03 kPa·s·L−1 (> upper normal limit) and, compared to patients with R5 - R20 ≤0.030 kPa·s·L−1, showed a poorer health status, lower values of FEV1, FVC, FEV1/FVC, and X5, along with higher values of residual volume/total lung capacity and R5 (P<0.05 for all comparisons).,Compared to the 69 nonresponders and the 8 FRs, the 16 VRs had significantly higher R5 and R5 - R20 values (P<0.05), lower X5 values (P<0.05), and greater airflow obstruction and lung hyperinflation.,This study shows that peripheral airway resistance is increased in the vast majority of patients with COPD, who showed worse respiratory reactance, worse spirometry results, more severe lung hyperinflation, and poorer health status.,Small airway dysfunction was also associated with the bronchodilator responsiveness in terms of FVC, but not in terms of FEV1. | 1 |
Goblet cell hyperplasia is a classic but variable pathologic finding in COPD.,Current literature shows that smoking is a risk factor for chronic bronchitis but the relationship of these clinical features to the presence and magnitude of large airway goblet cell hyperplasia has not been well described.,We hypothesized that current smokers and chronic bronchitics would have more goblet cells than nonsmokers or those without chronic bronchitis (CB), independent of airflow obstruction.,We recruited 15 subjects with moderate to severe COPD, 12 healthy smokers, and 11 healthy nonsmokers.,Six endobronchial mucosal biopsies per subject were obtained by bronchoscopy and stained with periodic acid Schiff-Alcian Blue.,Goblet cell density (GCD) was quantified as goblet cell number per millimeter of basement membrane.,Mucin volume density (MVD) was quantified as volume of mucin per unit area of basement membrane.,Healthy smokers had a greater GCD and MVD than nonsmokers and COPD subjects.,COPD subjects had a greater GCD than nonsmokers.,When current smokers (healthy smokers and COPD current smokers, n = 19) were compared with all nonsmokers (nonsmoking controls and COPD ex-smokers, n = 19), current smokers had a greater GCD and MVD.,When those with CB (n = 12) were compared to those without CB (n = 26), the CB group had greater GCD.,This finding was also seen in those with CB in the COPD group alone.,In multivariate analysis, current smoking and CB were significant predictors of GCD using demographics, lung function, and smoking pack years as covariates.,All other covariates were not significant predictors of GCD or MVD.,Current smoking is associated with a more goblet cell hyperplasia and number, and CB is associated with more goblet cells, independent of the presence of airflow obstruction.,This provides clinical and pathologic correlation for smokers with and without COPD. | Smoking and COPD are associated with decreased mucociliary clearance, and healthy smokers have shorter cilia in the large airway than nonsmokers.,We hypothesized that changes in cilia length are consistent throughout the airway, and we further hypothesized that smokers with COPD have shorter cilia than healthy smokers.,Because intraflagellar transport (IFT) is the process by which cilia of normal length are produced and maintained, and alterations in IFT lead to short cilia in model organisms, we also hypothesized that smoking induces changes in the expression of IFT-related genes in the airway epithelium of smokers and smokers with COPD.,To assess these hypotheses, airway epithelium was obtained via bronchoscopic brushing.,Cilia length was assessed by measuring 100 cilia (10 cilia on each of 10 cells) per subject and Affymetrix microarrays were used to evaluate IFT gene expression in nonsmokers and healthy smokers in 2 independent data sets from large and small airway as well as in COPD smokers in a data set from the small airway.,In the large and small airway epithelium, cilia were significantly shorter in healthy smokers than nonsmokers, and significantly shorter in COPD smokers than in both healthy smokers and nonsmokers.,The gene expression data confirmed that a set of 8 IFT genes were down-regulated in smokers in both data sets; however, no differences were seen in COPD smokers compared to healthy smokers.,These results support the concept that loss of cilia length contributes to defective mucociliary clearance in COPD, and that smoking-induced changes in expression of IFT genes may be one mechanism of abnormally short cilia in smokers.,Strategies to normalize cilia length may be an important avenue for novel COPD therapies. | 1 |
Cardiovascular disease is a primary cause of death in patients with chronic obstructive pulmonary disease (COPD).,Beta-blockers have been proved to reduce morbidity and improve survival in patients with cardiac diseases.,But the effects of beta-blockers on outcomes in patients with COPD remain controversial.,The objective of this meta-analysis was to assess the effect of beta-blockers on mortality and exacerbation in patients with COPD.,An extensive search of the EMBASE, MEDLINE and Cochrane was performed to retrieve the studies of beta-blockers treatment in patients with COPD.,The random effects model meta-analysis was used to evaluate effect on overall mortality and exacerbation of COPD.,Fifteen original observational cohort studies with a follow-up time from 1 to 7.2 years were included.,The results revealed that beta-blockers treatment significantly decreased the risk of overall mortality and exacerbation of COPD.,The relative risk (RR) for overall mortality was 0.72 (0.63 to 0.83), and for exacerbation of COPD was 0.63 (0.57 to 0.71).,In subgroup analysis of COPD patients with coronary heart disease or heart failure, the risk for overall mortality was 0.64 (0.54-0.76) and 0.74 (0.58-0.93), respectively.,The findings of this meta-analysis confirmed that beta-blocker use in patients with COPD may not only decrease the risk of overall mortality but also reduce the risk of exacerbation of COPD.,Beta-blocker prescription for cardiovascular diseases needs to improve in COPD patients. | The mortality and incidence of chronic obstructive pulmonary disease (COPD) and coronary heart disease increase with age.,Despite the clear evidence of beta blockers (BBs) effectiveness, there is a general reluctance to use them in patients with COPD due to a perceived contraindication and fear of inducing adverse reactions and bronchspasm.,BBs are well tolerated in patients with cardiac disease and concomitant COPD with no evidence of worsening of respiratory symptoms or FEV1, and the safety of BBs in patients with COPD has been demonstrated, but their use in this group of patients remains low.,The cumulative evidence from trials and meta-analysis indicates that cardioselective BBs should not be withheld in patients with reactive airway disease or COPD.,Patients with COPD have a high incidence of cardiac events necessitating careful consideration of prophylactic treatment.,The benefits of beta blockade in this group appear to outweigh any potential risk of side effects according to the available evidence.,In this article, we will discuss the use of BBs in patients with COPD and review the evidence for their use and safety in this group of patients. | 1 |
We conducted a randomized controlled trial of a digital health system supporting clinical care through monitoring and self-management support in community-based patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,The aim of this study was to determine the efficacy of a fully automated Internet-linked, tablet computer-based system of monitoring and self-management support (EDGE‚ sElf-management anD support proGrammE) in improving quality of life and clinical outcomes.,We compared daily use of EDGE with usual care for 12 months.,The primary outcome was COPD-specific health status measured with the St George’s Respiratory Questionnaire for COPD (SGRQ-C).,A total of 166 patients were randomized (110 EDGE, 56 usual care).,All patients were included in an intention to treat analysis.,The estimated difference in SGRQ-C at 12 months (EDGE−usual care) was −1.7 with a 95% CI of −6.6 to 3.2 (P=.49).,The relative risk of hospital admission for EDGE was 0.83 (0.56-1.24, P=.37) compared with usual care.,Generic health status (EQ-5D, EuroQol 5-Dimension Questionnaire) between the groups differed significantly with better health status for the EDGE group (0.076, 95% CI 0.008-0.14, P=.03).,The median number of visits to general practitioners for EDGE versus usual care were 4 versus 5.5 (P=.06) and to practice nurses were 1.5 versus 2.5 (P=.03), respectively.,The EDGE clinical trial does not provide evidence for an effect on COPD-specific health status in comparison with usual care, despite uptake of the intervention.,However, there appears to be an overall benefit in generic health status; and the effect sizes for improved depression score, reductions in hospital admissions, and general practice visits warrants further evaluation and could make an important contribution to supporting people with COPD.,International Standard Randomized Controlled Trial Number (ISRCTN): 40367841; http://www.isrctn.com/ISRCTN40367841 (Archived by WebCite at http://www.webcitation.org/6pmfIJ9KK) | To investigate the magnitude of barriers in access to health services for chronic patients and the socioeconomic and demographic characteristics that affect them.,A cross-sectional study was conducted in 1,594 chronic patients suffering from diabetes, hypertension, COPD and Alzheimer.,Logistic regression analyses were carried out in order to explore the factors related to economic and geographical barriers in access, as well as the determinants of barriers due to waiting lists.,A total of 25% of chronic patients face geographical barriers while 63.5% and 58.5% of them are in front of economic and waiting list barriers, respectively.,Unemployed, low-income and low-educated are more likely to face economic barriers in access.,Moreover, women, low-income patients, and patients with lower health status are more likely to be in front of geographical barriers.,In addition, the probability of waiting lists occurrence is greater for unemployed, employees and low income patients.,Barriers in access can be mainly attributed to income decrease and unemployment.,In this context, health policy measures are essential for removing barriers in access.,Otherwise, inequalities may increase and chronic patients’ health status will be deteriorated.,These consequences imply adverse effects on health expenditure. | 1 |
Chronic obstructive pulmonary disease (COPD) clinical trials aimed at evaluating treatment effects on exacerbations often suffer from early discontinuations of randomized treatment.,Treatment discontinuations imply a loss of information and should ideally be considered in the statistical analysis of trial results, particularly if the discontinuations are related to the disease or treatment itself.,Here, we explore this issue by investigating (1) whether there exists an association between the risks of exacerbation and treatment discontinuation in COPD clinical trials and (2) whether disregarding this association can cause bias in exacerbation treatment effect estimates.,We focus on the hypothetical estimand, i.e. the treatment effect that would have been observed had all subjects completed the trial as planned.,The association between exacerbation and discontinuation risks was analysed by applying a joint frailty (random effect) model - allowing for the simultaneous analysis of multiple types of correlated events - to data from five Phase III-IV COPD clinical trials.,Specifically, the impact of the association on exacerbation treatment effect estimates was assessed by comparing the treatment hazard ratios of the joint frailty model to the rate/hazard ratios of two related statistical models (the negative binomial and shared frailty models), which both assume discontinuations to be unrelated to the trial outcome.,The models were also compared using simulated data.,A statistically significant (p < 0.0001), positive association between exacerbation and discontinuation risks was found in all trials.,Importantly, simulations confirmed that - with such an association - models disregarding the association risk producing biased results (> 5 percentage point difference in hazard/rate ratio).,For some treatment comparisons in the clinical trials, the difference in treatment effect estimates between the joint frailty and the other models was as high as 10-15 percentage points.,The difference was affected by the strength of the exacerbation-discontinuation association, the population heterogeneity in exacerbation risk, and the difference in discontinuation rates between treatment arms.,We have identified an association between the risks of exacerbation and treatment discontinuation in five COPD clinical trials.,We recommend using the joint frailty model to account for this association when estimating exacerbation treatment effects, particularly when targeting the hypothetical estimand. | Large clinical trials have confirmed the long-term efficacy of inhaled corticosteroid/long-acting β2-agonist combinations in patients with chronic obstructive pulmonary disease (COPD).,It was hypothesized that significant treatment effects would already be present within 3 months after the initiation of treatment across a range of clinical outcomes, irrespective of COPD severity.,Post hoc analysis of 3-month post-randomization outcomes, including exacerbation rates, dropouts, symptoms, reliever use, and lung function, from three studies with similar inclusion criteria of moderate-to-very-severe COPD.,Patients (n=1,571) were treated with budesonide/formoterol (B/F) 320/9 μg or placebo, twice daily; in one study, tiotropium 18 μg once daily was also given.,Over the first 3 months of treatment, fewer patients randomized to B/F experienced exacerbations versus the placebo group (111 and 196 patients with ≥1 exacerbation, respectively).,This was true in each COPD severity group.,Compared with placebo, B/F treatment led to significantly lower 3-month exacerbation rates in the moderate and severe COPD severity groups (46% and 57% reduction, respectively), with a nonsignificant reduction (29%) in very severe COPD.,Fewer dropouts occurred among patients treated with B/F versus placebo, this effect being greater with increasing COPD severity.,B/F was associated with improved forced expiratory volume in 1 s, morning peak expiratory flow rate, total reliever use, and total symptom score versus placebo.,Treatment with B/F decreased exacerbations in patients with moderate-to-very-severe COPD within 3 months of commencing treatment.,This effect was paralleled by improved lung function, less reliever medication use, and fewer symptoms, irrespective of disease severity. | 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. | Chronic obstructive pulmonary disease (COPD) is a common disease that severely threatens human health.,Acute exacerbation of COPD (AECOPD) is a major cause of disease progression and death, and causes huge medical expenditures.,This consensus statement represents a description of clinical features of AECOPD in the People’s Republic of China and a set of recommendations.,It is intended to provide clinical guidelines for community physicians, pulmonologists and other health care providers for the prevention, diagnosis, and treatment of AECOPD. | 1 |
Although chronic obstructive pulmonary disease (COPD) and asthma are well-characterized diseases, they can coexist in a given patient.,The term asthma-COPD overlap (ACO) was introduced to describe patients that have clinical features of both diseases and may represent around 25% of COPD patients and around 20% of asthma patients.,Despite the increasing interest in ACO, there are still substantial controversies regarding its definition and its position within clinical guidelines for patients with obstructive lung disease.,In general, most definitions indicate that ACO patients must present with non-reversible airflow limitation, significant exposure to smoking or other noxious particles or gases, together with features of asthma.,In patients with a primary diagnosis of COPD, the identification of ACO has therapeutic implication because the asthmatic component should be treated with inhaled corticosteroids and some studies suggest that the most severe patients may respond to biological agents indicated for severe asthma.,This manuscript aims to summarize the current state-of-the-art of ACO.,The definitions, prevalence, and clinical manifestations will be reviewed and some innovative aspects, such as genetics, epigenetics, and biomarkers will be addressed.,Lastly, the management and prognosis will be outlined as well as the position of ACO in the COPD and asthma guidelines. | To evaluate the accuracy of inflammatory biomarkers in differentiating patients with asthma-COPD overlap (ACO) from those with COPD alone.,Clinical data of 134 patients with COPD and 48 patients with ACO admitted to the First Affiliated Hospital of Xi’an Jiaotong University from January 2016 to June 2019 were retrospectively analyzed.,Receiver operating characteristic (ROC) curve analysis was performed to determine the best cut-off values of fractional exhaled nitric oxide (FeNO), blood eosinophil counts (EOS), and neutrophil to lymphocyte ratio (NLR) for differentiating between ACO and COPD alone.,Spearman correlation analysis was conducted to evaluate the relationships between these inflammatory biomarkers and the forced expiratory volume in one second/prediction (FEV1%pred).,FeNO and EOS in the ACO patients were significantly higher than those in the COPD patients (FeNO: median 37.50 vs 24.50 ppb, P < 0.001; EOS: median 0.20 vs 0.10 ×109/L, P = 0.004).,FeNO was positively correlated with FEV1%pred (r = 0.314, P = 0.030), while NLR was negatively correlated with FEV1%pred (r = −0.372, P = 0.009) in patients with ACO.,In addition, a positive correlation between FeNO and EOS was also found in ACO, especially in patients without history of inhaled corticosteroids (ICS) use (r = 0.682, P < 0.001).,The optimal cut-off value of FeNO was 31.5 ppb (AUC = 0.758, 95% CI = 0.631-0.886) in patients with smoking history, with 70.0% sensitivity and 89.9% specificity for differentiating ACO from COPD.,In patients without history of ICS use, the best cut-off value of FeNO was 39.5 ppb (AUC = 0.740, 95% CI = 0.610-0.870), with 58.3% sensitivity and 84.9% specificity.,Among patients without history of ICS use and smoking, 27.5 ppb was optimal cut-off level for FeNO (AUC = 0.744, 95% CI = 0.579-0.908) to diagnose ACO, with 81.8% sensitivity and 60.7% specificity, and the sensitivity was improved to 91.7% when FeNO was combined with EOS.,The inflammatory biomarkers FeNO and EOS can be used as indicators for differentiating between ACO and COPD alone. | 1 |
Much of what is known about the Aryl Hydrocarbon Receptor (AhR) centers on its ability to mediate the deleterious effects of the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin).,However, the AhR is both ubiquitously-expressed and evolutionarily-conserved, suggesting that it evolved for purposes beyond strictly mediating responses to man-made environmental toxicants.,There is growing evidence that the AhR is required for the maintenance of health, as it is implicated in physiological processes such as xenobiotic metabolism, organ development and immunity.,Dysregulation of AhR expression and activity is also associated with a variety of disease states, particularly those at barrier organs such as the skin, gut and lungs.,The lungs are particularly vulnerable to inhaled toxicants such as cigarette smoke.,However, the role of the AhR in diseases such as chronic obstructive pulmonary disease (COPD)-a respiratory illness caused predominately by cigarette smoking-and lung cancer remains largely unexplored.,This review will discuss the growing body of literature that provides evidence that the AhR protects the lungs against the damaging effects of cigarette smoke. | Cigarette smoking is the major risk factor for COPD, leading to chronic airway inflammation.,We hypothesized that cigarette smoke induces structural and functional changes of airway epithelial mitochondria, with important implications for lung inflammation and COPD pathogenesis.,We studied changes in mitochondrial morphology and in expression of markers for mitochondrial capacity, damage/biogenesis and fission/fusion in the human bronchial epithelial cell line BEAS-2B upon 6-months from ex-smoking COPD GOLD stage IV patients to age-matched smoking and never-smoking controls.,We observed that long-term CSE exposure induces robust changes in mitochondrial structure, including fragmentation, branching and quantity of cristae.,The majority of these changes were persistent upon CSE depletion.,Furthermore, long-term CSE exposure significantly increased the expression of specific fission/fusion markers (Fis1, Mfn1, Mfn2, Drp1 and Opa1), oxidative phosphorylation (OXPHOS) proteins (Complex II, III and V), and oxidative stress (Mn-SOD) markers.,These changes were accompanied by increased levels of the pro-inflammatory mediators IL-6, IL-8, and IL-1β.,Importantly, COPD primary bronchial epithelial cells (PBECs) displayed similar changes in mitochondrial morphology as observed in long-term CSE-exposure BEAS-2B cells.,Moreover, expression of specific OXPHOS proteins was higher in PBECs from COPD patients than control smokers, as was the expression of mitochondrial stress marker PINK1.,The observed mitochondrial changes in COPD epithelium are potentially the consequence of long-term exposure to cigarette smoke, leading to impaired mitochondrial function and may play a role in the pathogenesis of COPD. | 1 |
Forced oscillation technique (FOT) has been reported to be useful in the evaluation and management of obstructive lung disease, including COPD.,To date, no data are available concerning long-term changes in respiratory system impedance measured by FOT.,Additionally, although exacerbations have been reported to be associated with excessive lung function decline in COPD, the impact of exacerbations on the results of FOT has not been demonstrated.,The aim of this study was to investigate the longitudinal changes in respiratory system impedance and the influence of exacerbations thereon.,Between March 2011 and March 2012, outpatients who attended Kobe City Medical Center West Hospital with a diagnosis of COPD were assessed for eligibility.,Baseline patient characteristics (age, sex, body mass index, smoking history, current smoking status, COPD stage), lung function (post-bronchodilator forced expiratory volume in 1 second [FEV1]), blood tests (neutrophils and eosinophils), FOT, and COPD assessment test results were collected at enrollment.,Lung function and FOT were examined every 6 months until March 2016.,Annual changes in FEV1 and FOT parameters were obtained from the slope of the linear regression curve.,The patients were divided into 2 groups based on exacerbation history.,Fifty-one of 58 patients with COPD were enrolled in this study.,The median follow-up period was 57 (52-59) months.,Twenty-five (49%) patients experienced exacerbations.,A significant annual decline in FEV1 and respiratory system impedance were shown.,Additionally, annual changes in FEV1, respiratory system resistance at 5 Hz, respiratory system reactance at 5 Hz, and resonant frequency were greater in patients with exacerbations than in those without exacerbations.,Exacerbations of COPD lead not only to a decline in lung function but also to an increase in respiratory system impedance. | The aims of the study were: (1) to compare numerical parameters of specific airway resistance (total, sRawtot, effective, sRaweff and at 0.5 L · s−1, sRaw0.5) and indices obtained from the forced oscillation technique (FOT: resistance extrapolated at 0 Hz [Rrs0 Hz], mean resistance [Rrsmean], and resistance/frequency slope [Rrsslope]) and (2) to assess their relationships with dyspnea in chronic obstructive pulmonary disease (COPD).,A specific statistical approach, principal component analysis that also allows graphic representation of all correlations between functional parameters was used.,A total of 108 patients (mean ± SD age: 65 ± 9 years, 31 women; GOLD stages: I, 14; II, 47; III, 39 and IV, 8) underwent spirometry, body plethysmography, FOT, and Medical Research Council (MRC) scale assessments.,Principal component analysis determined that the functional parameters were described by three independent dimensions (airway caliber, lung volumes and their combination, specific resistance) and that resistance parameters of the two techniques were not equivalent, obviously.,Correlative analyses further showed that Rawtot and Raweff (and their specific resistances) can be considered as equivalent and correlated with indices that are considered to explore peripheral airways (residual volume (RV), RV/ total lung capacity (TLC), Rrsslope), while Rrsmean and Raw0.5 explored more central airways.,Only specific resistances taking into account the specific resistance loop area (sRawtot and sRaweff) and Rrsslope were statistically linked to dyspnea.,Parameters obtained from both body plethysmography and FOT can explore peripheral airways, and some of these parameters (sRawtot, sRaweff, and Rrsslope) are linked to activity-related dyspnea in moderate to severe COPD patients. | 1 |
Chronic obstructive pulmonary disease (COPD) is a disease characterised by persistent airflow limitation that is not fully reversible and is currently the fourth leading cause of death globally.,It is now well established that cardiovascular-related comorbidities contribute to morbidity and mortality in COPD, with approximately 50% of deaths in COPD patients attributed to a cardiovascular event (e.g. myocardial infarction).,Cardiovascular disease (CVD) and COPD share various risk factors including hypertension, sedentarism, smoking and poor diet but the underlying mechanisms have not been fully established.,However, there is emerging and compelling experimental and clinical evidence to show that increased oxidative stress causes pulmonary inflammation and that the spill over of pro-inflammatory mediators from the lungs into the systemic circulation drives a persistent systemic inflammatory response that alters blood vessel structure, through vascular remodelling and arterial stiffness resulting in atherosclerosis.,In addition, regulation of endothelial-derived vasoactive substances (e.g. nitric oxide (NO)), which control blood vessel tone are altered by oxidative damage of vascular endothelial cells, thus promoting vascular dysfunction, a key driver of CVD.,In this review, the detrimental role of oxidative stress in COPD and comorbid CVD are discussed and we propose that targeting oxidant-dependent mechanisms represents a novel strategy in the treatment of COPD-associated CVD. | Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and loss of lung function, and is currently the third largest cause of death in the world.,It is now well established that cardiovascular-related comorbidities such as stroke contribute to morbidity and mortality in COPD.,The mechanisms linking COPD and stroke remain to be fully defined but are likely to be interconnected.,The association between COPD and stroke may be largely dependent on shared risk factors such as aging and smoking, or the association of COPD with traditional stroke risk factors.,In addition, we propose that COPD-related systemic inflammation and oxidative stress may play important roles by promoting cerebral vascular dysfunction and platelet hyperactivity.,In this review, we briefly discuss the pathogenesis of COPD, acute exacerbations of COPD (AECOPD) and cardiovascular comorbidities associated with COPD, in particular stroke.,We also highlight and discuss the potential mechanisms underpinning the link between COPD and stroke, with a particular focus on the roles of systemic inflammation and oxidative stress. | 1 |
Cough and sputum production are frequent in chronic obstructive pulmonary disease (COPD).,The objective of this study was to examine the relationship between cough and sputum production and health-related quality of life in COPD.,A cross-sectional study was conducted in the French Initiatives COPD cohort and assessed cough and sputum production within the past 7 days using the cough and sputum assessment questionnaire (CASA-Q), health-related quality of life, spirometry, smoking status, dyspnea, exacerbations, anxiety and depression, and comorbidities.,One hundred and seventy-eight stable COPD patients were included (age, 62 [56-69] years, 128 male, forced expiratory volume in 1 second [FEV1]: 57 [37-72] % predicted) (median [Q1-Q3]).,In univariate analyses, health-related quality of life (Saint George’s respiratory questionnaire total score) was associated with each CASA-Q domain and with chronic bronchitis, exacerbations, dyspnea, FEV1, depression, and anxiety.,All four domains introduced separately were independently associated with health-related quality of life.,When introduced together in multivariate analyses, only the cough impact domain remained independently associated with health-related quality of life (R2=0.60).,With chronic bronchitis (standard definition) instead of the CASA-Q, the R2 was lower (R2=0.54).,This study provides evidence that current cough in the previous 7 days is an important determinant of health-related quality of life impairment in stable COPD patients. | This randomized, double-blind, Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).,Methods: Patients received aclidinium 400 μg twice daily (morning and evening), tiotropium 18 μg once daily (morning), or placebo for 6 weeks.,The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose (FEV1 AUC0-24) at week 6.,Secondary and additional endpoints included FEV1 AUC12-24, COPD symptoms (EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [E-RS] total score and additional symptoms questionnaire), and safety.,Results: Overall, 414 patients were randomized and treated (FEV1 1.63 L [55.8% predicted]).,Compared with placebo, FEV1 AUC0-24 and FEV1 AUC12-24 were significantly increased from baseline with aclidinium (Δ = 150 mL and 160 mL, respectively; p < 0.0001) and tiotropium (Δ = 140 mL and 123 mL, respectively; p < 0.0001) at week 6.,Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium (p < 0.0001) than tiotropium (p < 0.05) versus placebo.,Only aclidinium significantly reduced the severity of early-morning cough, wheeze, shortness of breath, and phlegm, and of nighttime symptoms versus placebo (p < 0.05).,Adverse-event (AE) incidence (28%) was similar between treatments.,Few anticholinergic AEs (<1.5%) or serious AEs (<3%) occurred in any group.,Conclusions: Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks.,Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium.,Aclidinium was generally well tolerated. | 1 |
Beyond lung cancer, screening CT contains additional information on other smoking related diseases (e.g. chronic obstructive pulmonary disease, COPD).,Since pulmonary function testing is not regularly incorporated in lung cancer screening, imaging biomarkers for COPD are likely to provide important surrogate measures for disease evaluation.,Therefore, this study aims to determine the independent diagnostic value of CT emphysema, CT air trapping and CT bronchial wall thickness for COPD in low-dose screening CT scans.,Prebronchodilator spirometry and volumetric inspiratory and expiratory chest CT were obtained on the same day in 1140 male lung cancer screening participants.,Emphysema, air trapping and bronchial wall thickness were automatically quantified in the CT scans.,Logistic regression analysis was performed to derivate a model to diagnose COPD.,The model was internally validated using bootstrapping techniques.,Each of the three CT biomarkers independently contributed diagnostic value for COPD, additional to age, body mass index, smoking history and smoking status.,The diagnostic model that included all three CT biomarkers had a sensitivity and specificity of 73.2% and 88.%, respectively.,The positive and negative predictive value were 80.2% and 84.2%, respectively.,Of all participants, 82.8% was assigned the correct status.,The C-statistic was 0.87, and the Net Reclassification Index compared to a model without any CT biomarkers was 44.4%.,However, the added value of the expiratory CT data was limited, with an increase in Net Reclassification Index of 4.5% compared to a model with only inspiratory CT data.,Quantitatively assessed CT emphysema, air trapping and bronchial wall thickness each contain independent diagnostic information for COPD, and these imaging biomarkers might prove useful in the absence of lung function testing and may influence lung cancer screening strategy.,Inspiratory CT biomarkers alone may be sufficient to identify patients with COPD in lung cancer screening setting. | Socioeconomic status is likely an independent risk factor for Chronic Obstructive Pulmonary Disease (COPD), but little research has been done in China to study this association in a nationwide sample.,We used data from the 2007 China Chronic Disease Risk Factor Surveillance of 49,363 Chinese men and women aged 15-69 years to examine the association between the prevalence of self-reported physician diagnosed COPD and socioeconomic status defined by both educational level and annual household income.,Multivariable logistic regression modelling was performed with adjustement for potential confounders.,Both low educational attainment and low household income were independently associated with higher risk of physician-diagnosed COPD.,Compared to subjects with high educational level, subjects with low educational level had a significantly increased risk of COPD (OR 1.67, 95%CI 1.32-2.13, p for trend< 0.001 for urban, OR 1.76, 95%CI 1.34-2.30, p for trend < 0.001 for rural) after adjusting for age, sex, smoking status, passive smoking and geographic regions.,Similarly increased risk was observed for household income and COPD in urban (OR 1.64, 95%CI 1.28-2.09, P for trend< 0.001) but not rural areas.,Among never smokers, low educational level and household income were still associated with a significant higher prevalence of COPD (OR 1.77, 95%CI 1.40-2.25, OR 1.31, 95%CI 1.05-1.62).,Removal of those with asthma diagnosis did not alter the observed associations.,Socioeconomic status is a risk factor for self-reported physician-diagnosed COPD independently of current or passive smoking.,Prospective studies are needed in China to better understand the association between socioeconomic status and COPD. | 1 |
A genetic contribution to develop chronic obstructive pulmonary disease (COPD) is well established.,However, the specific genes responsible for enhanced risk or host differences in susceptibility to smoke exposure remain poorly understood.,The goal of this review is to provide a comprehensive literature overview on the genetics of COPD, highlight the most promising findings during the last few years, and ultimately provide an updated COPD gene list.,Candidate gene studies on COPD and related phenotypes indexed in PubMed before January 5, 2012 are tabulated.,An exhaustive list of publications for any given gene was looked for.,This well-documented COPD candidate-gene list is expected to serve many purposes for future replication studies and meta-analyses as well as for reanalyzing collected genomic data in the field.,In addition, this review summarizes recent genetic loci identified by genome-wide association studies on COPD, lung function, and related complications.,Assembling resources, integrative genomic approaches, and large sample sizes of well-phenotyped subjects is part of the path forward to elucidate the genetic basis of this debilitating disease. | Variation in ADAM33 has been shown to be important in the development of asthma and altered lung function.,This relationship however, has not been investigated in the population susceptible to COPD; long term tobacco smokers.,We evaluated the association between polymorphisms in ADAM33 gene with COPD and lung function in long term tobacco smokers.,Caucasian subjects, at least 50 year old, who smoked ≥ 20 pack-years (n = 880) were genotyped for 25 single nucleotide polymorphisms (SNPs) in ADAM33.,COPD was defined as an FEV1/FVC ratio < 70% and percent-predicted (pp)FEV1 < 75% (n = 287).,The control group had an FEV1/FVC ratio ≥ 70% and ppFEV1 ≥ 80% (n = 311) despite ≥ 20 pack years of smoking.,Logistic and linear regressions were used for the analysis.,Age, sex, and smoking status were considered as potential confounders.,Five SNPs in ADAM33 were associated with COPD (Q-1, intronic: p < 0.003; S1, Ile → Val: p < 0.003; S2, Gly → Gly: p < 0.04; V-1 intronic: p < 0.002; V4, in 3' untranslated region: p < 0.007).,Q-1, S1 and V-1 were also associated with ppFEV1, FEV1/FVC ratio and ppFEF25-75 (p values 0.001 - 0.02).,S2 was associated with FEV1/FVC ratio (p < 0.05).,The association between S1 and residual volume revealed a trend toward significance (p value < 0.07).,Linkage disequilibrium and haplotype analyses suggested that S1 had the strongest degree of association with COPD and pulmonary function abnormalities.,Five SNPs in ADAM33 were associated with COPD and lung function in long-term smokers.,Functional studies will be needed to evaluate the biologic significance of these polymorphisms in the pathogenesis of COPD. | 1 |
Development of adult respiratory disease is influenced by events in childhood.,The impact of childhood pneumonia on chronic obstructive pulmonary disease (COPD) is not well defined.,We hypothesize that childhood pneumonia is a risk factor for reduced lung function and COPD in adult smokers.,COPD cases and control smokers between 45-80 years old from the United States COPDGene Study were included.,Childhood pneumonia was defined by self-report of pneumonia at <16 years.,Subjects with lung disease other than COPD or asthma were excluded.,Smokers with and without childhood pneumonia were compared on measures of respiratory disease, lung function, and quantitative analysis of chest CT scans.,Of 10,192 adult smokers, 854 (8.4 %) reported pneumonia in childhood.,Childhood pneumonia was associated with COPD (OR 1.40; 95 % CI 1.17-1.66), chronic bronchitis, increased COPD exacerbations, and lower lung function: post-bronchodilator FEV1 (69.1 vs.,77.1 % predicted), FVC (82.7 vs.,87.4 % predicted), FEV1/FVC ratio (0.63 vs.,0.67; p < 0.001 for all comparisons).,Childhood pneumonia was associated with increased airway wall thickness on CT, without significant difference in emphysema.,Having both pneumonia and asthma in childhood further increased the risk of developing COPD (OR 1.85; 95 % CI 1.10-3.18).,Children with pneumonia are at increased risk for future smoking-related lung disease including COPD and decreased lung function.,This association is supported by airway changes on chest CT scans.,Childhood pneumonia may be an important factor in the early origins of COPD, and the combination of pneumonia and asthma in childhood may pose the greatest risk.,ClinicalTrials.gov, NCT00608764 (Active since January 28, 2008).,The online version of this article (doi:10.1186/s12931-015-0273-8) contains supplementary material, which is available to authorized users. | Cardiovascular disease (CVD) is a major cause of death in smokers, particularly in those with chronic obstructive pulmonary disease (COPD).,Circulating endothelial progenitor cells (EPC) are required for endothelial homeostasis, and their dysfunction contributes to CVD.,To investigate EPC dysfunction in smokers, we isolated and expanded blood outgrowth endothelial cells (BOEC) from peripheral blood samples from healthy nonsmokers, healthy smokers, and COPD patients.,BOEC from smokers and COPD patients showed increased DNA double-strand breaks and senescence compared to nonsmokers.,Senescence negatively correlated with the expression and activity of sirtuin-1 (SIRT1), a protein deacetylase that protects against DNA damage and cellular senescence.,Inhibition of DNA damage response by silencing of ataxia telangiectasia mutated (ATM) kinase resulted in upregulation of SIRT1 expression and decreased senescence.,Treatment of BOEC from COPD patients with the SIRT1 activator resveratrol or an ATM inhibitor (KU-55933) also rescued the senescent phenotype.,Using an in vivo mouse model of angiogenesis, we demonstrated that senescent BOEC from COPD patients are dysfunctional, displaying impaired angiogenic ability and increased apoptosis compared to cells from healthy nonsmokers.,Therefore, this study identifies epigenetic regulation of DNA damage and senescence as pathogenetic mechanisms linked to endothelial progenitors' dysfunction in smokers and COPD patients.,These defects may contribute to vascular disease and cardiovascular events in smokers and could therefore constitute therapeutic targets for intervention. | 1 |
A multitude of epidemiological studies have shown that ambient fine particulate matter 2.5 (diameter < 2.5um; PM2.5) was associated with increased morbidity and mortality of chronic obstructive pulmonary disease (COPD).,However, the underlying associated mechanisms have not yet been elucidated.,We conducted this study to investigate the role of PM2.5 in the development of COPD and associated mechanisms.,We firstly conducted a cross-sectional study in Chinese han population to observe PM2.5 effects on COPD morbidity.,Then, in vitro, we incubated human bronchial epithelial cells to different concentrations of PM2.5 for 24 h.,The expression levels of IL-6 and IL-8 were detected by ELISA and the levels of MMPs, TGF-β1, fibronectin and collagen was determined by immunoblotting.,In vivo, we subjected C57BL/6 mice to chronic prolonged exposure to PM2.5 for 48 weeks to study the influence of PM2.5 exposure on lung function, pulmonary structure and inflammation.,We found that the effect of PM2.5 on COPD morbidity was associated with its levels and that PM2.5 and cigarette smoke could have a synergistic impact on COPD development and progression.,Both vitro and vivo studies demonstrated that PM2.5 exposure could induce pulmonary inflammation, decrease lung function, and cause emphysematous changes.,Furthermore, PM2.5 could markedly aggravated cigarette smoke-induced changes.,In short, we found that prolonged chronic exposure to PM2.5 resulted in decreased lung function, emphysematous lesions and airway inflammation.,Most importantly, long-term PM2.5 exposure exacerbateed cigarette smoke-induced changes in 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 |
Potentially pathogenic microorganisms can be detected by quantitative real-time polymerase chain reaction (qPCR) in sputum from patients with COPD, although how this technique relates to culture and clinical measures of disease is unclear.,We used cross-sectional and longitudinal data to test the hypotheses that qPCR is a more sensitive measure of bacterial presence and is associated with neutrophilic airway inflammation and adverse clinical outcomes.,Sputum was collected from 174 stable COPD subjects longitudinally over 12 months.,Microbial sampling using culture and qPCR was performed.,Spirometry and sputum measures of airway inflammation were assessed.,Sputum was qPCR-positive (>106 copies/mL) in 77/152 samples (Haemophilus influenzae [n=52], Moraxella catarrhalis [n=24], Streptococcus pneumoniae [n=19], and Staphylococcus aureus [n=7]).,Sputum was culture-positive in 50/174 samples, with 49 out of 50 culture-positive samples having pathogen-specific qPCR bacterial loads >106 copies/mL.,Samples that had qPCR copy numbers >106/mL, whether culture-positive or not, had increased sputum neutrophil counts.,H. influenzae qPCR copy numbers correlated with sputum neutrophil counts (r=0.37, P<0.001), were repeatable within subjects, and were >106/mL three or more times in 19 patients, eight of whom were repeatedly sputum culture-positive.,Persistence, whether defined by culture, qPCR, or both, was associated with a higher sputum neutrophil count, lower forced expiratory volume in 1 second (FEV1), and worsened quality of life.,qPCR identifies a significant number of patients with potentially bacteria-associated neutrophilic airway inflammation and disease that are not identified by traditional culture-based methods. | Relationships between airway inflammation and respiratory potentially pathogenic microorganisms (PPMs) quantified using quantitative polymerase chain reaction (qPCR) in subjects with COPD are unclear.,Our aim was to evaluate mediators of airway inflammation and their association with PPMs in subjects with COPD at stable state and during exacerbations.,Sputum from 120 stable subjects with COPD was analyzed for bacteriology (colony-forming units; total 16S; and qPCR targeting Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae), differential cell counts, and inflammatory mediators using the Meso-Scale Discovery Platform.,Subjects were classified as colonized if any PPM was identified above the threshold of detection by qPCR.,Symptoms were quantified using the visual analog scale.,At stable state, 60% of subjects were qPCR positive for H influenzae, 48% for M catarrhalis, and 28% for S pneumoniae.,Elevated sputum concentrations of IL-1β, IL-10, and tumor necrosis factor (TNF)-α were detected in samples qPCR positive for either H influenzae or M catarrhalis.,Bacterial loads of H influenzae positively correlated with IL-1β, IL-8, IL-10, TNF-α, and symptoms; and M catarrhalis correlated with IL-10 and TNF-α.,H influenzae qPCR bacterial load was an independent predictor of sputum TNF-α and IL-1β.,In 55 subjects with paired exacerbation data, qPCR bacterial load fold change at exacerbation in M catarrhalis but not H influenzae correlated to changes in sputum TNF-α and IL-1β concentrations.,At stable state, H influenzae is associated with increased airway inflammation in COPD.,The relationship between bacterial load changes of specific pathogens and airway inflammation at exacerbation and recovery warrants further investigation. | 1 |
High fructose corn syrup (HFCS) sweetened soft drink intake has been linked with asthma in US high-schoolers.,Intake of beverages with excess free fructose (EFF), including apple juice, and HFCS sweetened fruit drinks and soft drinks, has been associated with asthma in children.,One hypothesis for this association is that underlying fructose malabsorption and fructose reactivity in the GI may contribute to in situ formation of enFruAGEs.,EnFruAGEs may be an overlooked source of advanced glycation end-products (AGE) that contribute to lung disease.,AGE/ RAGEs are elevated in COPD lungs.,EFF intake has increased in recent decades, and intakes may exceed dosages associated with adult fructose malabsorption in subsets of the population.,Intestinal dysfunction has been shown to be elevated in COPD patients.,The objective of this study was to investigate the association between HFCS sweetened soft drink intake and chronic bronchitis (CB), a common manifestation of COPD, in adults.,Design: In this cross sectional analysis, the outcome variable was self-reported existing chronic bronchitis or history of CB.,Exposure variable was non-diet soda.,Rao Scott Ҳ2 was used for prevalence differences and logistic regression for associations, adjusted for age, sex, race-ethnicity, BMI, smoking, exposure to in-home smoking, pre-diabetes, diabetes, SES, total energy and total fruits and beverages consumption.,Data are from the National Health and Nutrition Examination Survey 2003-2006.,2801 adults aged 20-55 y.,There was a statistically significant correlation between intake of non-diet soft drinks and greater prevalence and odds of chronic bronchitis (p < 0.05).,Independent of all covariates, intake of non-diet soda ≥5 times a week (vs. non/low non-diet soda) was associated with nearly twice the likelihood of having chronic bronchitis (OR = 1.80; p = 0.047; 95 % CI 1.01-3.20).,HFCS sweetened soft drink intake is correlated with chronic bronchitis in US adults aged 20-55 y, after adjusting for covariates, including smoking.,Results support the hypothesis that underlying fructose malabsorption and fructose reactivity in the GI may contribute to chronic bronchitis, perhaps through in situ formation of enFruAGEs, which may contribute to lung disease.,Longitudinal and biochemical research is needed to confirm and clarify the mechanisms involved. | Diet and nutrition may be important modifiable risk factors for the development, progression and management of obstructive lung diseases such as asthma and chronic obstructive pulmonary disease (COPD).,This review examines the relationship between dietary patterns, nutrient intake and weight status in obstructive lung diseases, at different life stages, from in-utero influences through childhood and into adulthood.,In vitro and animal studies suggest important roles for various nutrients, some of which are supported by epidemiological studies.,However, few well-designed human intervention trials are available to definitively assess the efficacy of different approaches to nutritional management of respiratory diseases.,Evidence for the impact of higher intakes of fruit and vegetables is amongst the strongest, yet other dietary nutrients and dietary patterns require evidence from human clinical studies before conclusions can be made about their effectiveness. | 1 |
Pulmonary rehabilitation is a highly effective treatment for people with chronic lung disease but remains underused across the world.,Recent years have seen the emergence of new program models that aim to improve access and uptake, including telerehabilitation and low-cost, home-based models.,This workshop was convened to achieve consensus on the essential components of pulmonary rehabilitation and to identify requirements for successful implementation of emerging program models.,A Delphi process involving experts from across the world identified 13 essential components of pulmonary rehabilitation that must be delivered in any program model, encompassing patient assessment, program content, method of delivery, and quality assurance, as well as 27 desirable components.,Only those models of pulmonary rehabilitation that have been tested in clinical trials are currently considered as ready for implementation.,The characteristics of patients most likely to succeed in each program model are not yet known, and research is needed in this area.,Health professionals should use clinical judgment to determine those patients who are best served by a center-based, multidisciplinary rehabilitation program.,A comprehensive patient assessment is critical for personalization of pulmonary rehabilitation and for effectively addressing individual patient goals.,Robust quality-assurance processes are important to ensure that any pulmonary rehabilitation service delivers optimal outcomes for patients and health services.,Workforce capacity-building and training should consider the skills necessary for emerging models, many of which are delivered remotely.,The success of all pulmonary rehabilitation models will be judged on whether the essential components are delivered and on whether the expected patient outcomes, including improved exercise capacity, reduced dyspnea, enhanced health-related quality of life, and reduced hospital admissions, are achieved. | Cachexia is associated with increased mortality risk among chronic obstructive pulmonary disease (COPD) patients.,However, low body mass index (BMI) as opposed to cachexia is often used, particularly when calculating the BODE (BMI, Obstruction, Dyspnea and Exercise) index.,For this reason, we examined mortality using a consensus definition and a weight-loss definition of cachexia among COPD cases and compared two new COPD severity indices with BODE.,In the current report, the consensus definition for cachexia incorporated weight-loss > 5% in 12-months or low BMI in addition to 3/5 of decreased muscle strength, fatigue, anorexia, low FFMI and inflammation.,The weight-loss definition incorporated weight-loss > 5% or weight-loss > 2% (if low BMI) in 12-months.,The low BMI component in BODE was replaced with the consensus definition to create the CODE (Consensus cachexia, Obstruction, Dyspnea and Exercise) index and the weight-loss definition to create the WODE (Weight loss, Obstruction, Dyspnea and Exercise) index.,Mortality was assessed using Kaplan-Meier survival and Cox Regression.,Performance of models was compared using C-statistics.,Among 1483 COPD cases, the prevalences of cachexia by the consensus and weight-loss definitions were 4.7 and 10.4%, respectively.,Cachectic patients had a greater than three-fold increased mortality by either the consensus or the weight-loss definition of cachexia independent of BMI and lung function.,The CODE index predicted mortality slightly more accurately than the BODE and WODE indices.,Cachexia is associated with increased mortality among COPD patients.,Monitoring cachexia using weight-loss criteria is relatively simple and predictive of mortality among COPD cases who may be missed if only low BMI is used.,The online version of this article (10.1186/s12931-019-1073-3) contains supplementary material, which is available to authorized users. | 1 |
In recent years, the so-called asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) has received much attention, not least because elderly individuals may present characteristics suggesting a diagnosis of both asthma and COPD.,At present, ACOS is described clinically as persistent airflow limitation combined with features of both asthma and COPD.,The aim of this paper is, therefore, to review the currently available literature focusing on symptoms and clinical characteristics of patients regarded as having ACOS.,Based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, a systematic literature review was performed.,A total of 11 studies met the inclusion criteria for the present review.,All studies dealing with dyspnea (self-reported or assessed by the Medical Research Council dyspnea scale) reported more dyspnea among patients classified as having ACOS compared to the COPD and asthma groups.,In line with this, ACOS patients have more concomitant wheezing and seem to have more cough and sputum production.,Compared to COPD-only patients, the ACOS patients were found to have lower FEV1% predicted and FEV1/FVC ratio in spite of lower mean life-time tobacco exposure.,Furthermore, studies have revealed that ACOS patients seem to have not only more frequent but also more severe exacerbations.,Comorbidity, not least diabetes, has also been reported in a few studies, with a higher prevalence among ACOS patients.,However, it should be acknowledged that only a limited number of studies have addressed the various comorbidities in patients with ACOS.,The available studies indicate that ACOS patients may have more symptoms and a higher exacerbation rate than patients with asthma and COPD only, and by that, probably a higher overall respiratory-related morbidity.,Similar to patients with COPD, ACOS patients seem to have a high occurrence of comorbidity, including diabetes.,Further research into the ACOS, not least from well-defined prospective studies, is clearly needed. | An association between chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) has been described, mainly due to smoking and corticosteroid use.,Whether inhaled corticosteroid (ICS) therapy is associated with an increased risk of TB remains unclear.,We selected COPD cases by using six diagnostic scenarios and control subjects from a nationwide health insurance database, and applied time-dependent Cox regression analysis to identify the risk factors for TB.,Among 1,000,000 beneficiaries, 23,594 COPD cases and 47,188 non-COPD control subjects were selected.,Cox regression analysis revealed that age, male gender, diabetes mellitus, end-stage renal disease, and cirrhosis, as well as COPD (hazard ratio = 2.468 [2.205-2.762]) were independent risk factors for TB.,Among the COPD cases, those who developed TB received more oral corticosteroids and oral β-agonists.,Time-dependent Cox regression analysis revealed that age, male gender, diabetes mellitus, low income, oral corticosteroid dose, and oral β-agonist dose, but not ICS dose, were independent risk factors for TB.,The identified risk factors and their hazard ratios were similar among the COPD cases selected using different scenarios.,Keeping a high suspicion and regularly monitoring for the development of pulmonary TB in COPD patients are necessary, especially for those receiving higher doses of oral corticosteroids and other COPD medications.,Although ICS therapy has been shown to predispose COPD patients to pneumonia in large randomized clinical trials, it does not increase the risk of TB in real world practice. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) exhibit poor sleep quality and consider morning as the worst time of day for their symptoms.,While work has been done to characterize nighttime (NT) and early morning (EM) symptoms in various populations, the impact and factors associated with NT/EM symptoms among patients with COPD in the United States is not well understood.,Commercially insured patients aged ≥40 years with one or more medical claim for COPD and one or more pharmacy claim for COPD maintenance medication were identified from the HealthCore Integrated Research Database between September 1, 2010 and August 31, 2011.,Consenting respondents were asked whether they had COPD symptoms on at least three nights or at least three mornings during the past week.,Respondents were then either assigned to one of three symptom groups to complete the survey or excluded if their predefined group quota limit had been met.,Survey completers completed the survey with questions about COPD symptoms and other commonly used patient-reported outcome measures.,Respondents with NT/EM symptoms were asked about the frequency, severity, and impact of the symptoms on sleep, morning activities, and anxiety levels.,Among respondents with symptoms, 73.1% of respondents with NT symptoms (N=376) and 83% of respondents with EM symptoms (N=506) experienced at least three distinct types of symptoms over the past week, with cough being the most frequently reported symptom.,Approximately half of respondents with NT or EM symptoms perceived their symptoms as moderate to very severe, with a majority reporting their symptoms affected their NT sleep and morning activities, and more than half felt anxious due to their symptoms.,Multinomial logistic regression showed COPD patients with both or either NT/EM symptoms were associated with poorer health status compared to those without.,Improved disease management may reduce NT/EM symptoms and improve health status in patients with COPD. | Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. | 1 |
Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.,For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler.,Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).,295 and 291 patients were treated in MORACTO 1 and 2, respectively.,Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001).,Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).,Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies.,Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.,T/O reduces lung hyperinflation in COPD versus T, O or placebo and increases exercise endurance versus placebohttp://ow.ly/ml3G307XW6a | Delivery of inhaled medications via an inhaler device underpins the effectiveness of treatment for patients with chronic obstructive pulmonary disease (COPD).,Correct inhaler technique among patients is also a predictor of achieving treatment compliance and adherence.,Reporting of patient satisfaction with inhalers is therefore gaining increasing attention and is now recognized as an important patient-reported outcome in clinical trials involving patients with COPD or asthma.,In this cross-sectional study, we use the validated Patient Satisfaction and Preference Questionnaire (PASAPQ) to assess the handling and satisfaction for Respimat® Soft Mist™ Inhaler (SMI) compared with the Breezhaler® dry powder inhaler (DPI) among patients with COPD in Spain.,Patients were already assigned to therapy with either SPIRIVA® (tiotropium) Respimat® or with Hirobriz®/Onbrez®/Oslif® (indacaterol) Breezhaler® for at least 3 but not more than 6 months before completing the PASAPQ at a single visit to the study site.,The primary endpoint of the trial was the mean total PASAPQ score.,Secondary endpoints were the performance score domain of the PASAPQ, the convenience score domain of the PASAPQ, and the overall satisfaction score of the PASAPQ.,For the primary endpoint, the mean PASAPQ total score in the Respimat® and Breezhaler® groups was 80.7 and 79.9, respectively (difference of 0.8, 95% confidence interval [CI] −2.9 to 4.5; P=0.67).,The mean total performance scores were 82.5 and 78.2 (difference of 4.3, 95% CI −0.3 to 8.9; P=0.06), and the mean total convenience scores were 78.6 and 81.9 (difference of −3.3, 95% CI −7.0 to 0.4; P=0.08) for the Respimat® and Breezhaler® groups, respectively.,Patients gave the Respimat® SMI and the Breezhaler® DPI overall satisfaction PASAPQ scores of 6.0 and 5.9, respectively, which shows that patients were satisfied with these inhalers. | 1 |
The combination of asthma and chronic obstructive pulmonary disease (COPD), or ACOS is a recently defined syndrome.,The epidemiology of the condition is poorly described and previous research has suggested ACOS is associated with worse outcomes than either condition alone.,We therefore decided to complete a systematic review of the published literature.,This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines.,A structured search was performed in the PubMed, Embase, and Medline databases up to Feb 2015 to identify studies reporting incidence, prevalence, health care utilization, morbidity, or mortality in COPD and asthma.,A total of 19 studies were included in the present study.,The pooled prevalence of overlap among COPD was 27% (95% CI: 0.16-0.38, p<0.0001) and 28% (95% CI: 0.09-0.47, p = 0.0032) in the population and hospital-based studies, respectively.,We found no significant difference between ACOS and COPD in terms of gender, smoking status, lung function and 6mWD.,However, in comparison to subject with only COPD, ACOS subjects were significantly younger, had higher BMI, healthcare utilization, and lower HRQoL.,ACOS is a common condition that exists in a substantial proportion of subjects with COPD.,ACOS represents a distinct clinical phenotype with more frequent exacerbations, hospitalization, worse health-related quality of life, and higher healthcare costs than either disease alone.,There is a critical need to better define the management and treatment of this syndrome. | The coexistence of COPD and asthma is widely recognized but has not been well described.,This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma.,We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study.,119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma.,These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001).,More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001).,Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001).,Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT.,There were no differences in spirometry or CT measurements of emphysema or airway wall thickness.,Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life.,They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history.,ClinicalTrials.gov: NCT00608764 | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by varying trajectories of decline.,Information regarding the prognostic value of preventing short-term clinically important deterioration (CID) in lung function, health status, or first moderate/severe exacerbation as a composite endpoint of worsening is needed.,We evaluated post hoc the link between early CID and long-term adverse outcomes.,CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1), ≥4-unit increase in St George’s Respiratory Questionnaire (SGRQ) score from baseline, and/or a moderate/severe exacerbation during enrollment in two 3-year studies.,Presence of CID was assessed at 6 months for the principal analysis (TORCH) and 12 months for the confirmatory analysis (ECLIPSE).,Association between presence (+) or absence (-) of CID and long-term deterioration in FEV1, SGRQ, future risk of exacerbations, and all-cause mortality was assessed.,In total, 2870 (54%; TORCH) and 1442 (73%; ECLIPSE) patients were CID+.,At 36 months, in TORCH, CID+ patients (vs CID-) had sustained clinically significant worsening of FEV1 (- 117 mL; 95% confidence interval [CI]: - 134, - 100 mL; P < 0.001) and SGRQ score (+ 6.42 units; 95% CI: 5.40, 7.45; P < 0.001), and had higher risk of exacerbations (hazard ratio [HR]: 1.61 [95% CI: 1.50, 1.72]; P < 0.001) and all-cause mortality (HR: 1.41 [95% CI: 1.15, 1.72]; P < 0.001).,Similar risks post-CID were observed in ECLIPSE.,A CID within 6-12 months of follow-up was consistently associated with increased long-term risk of exacerbations and all-cause mortality, and predicted sustained meaningful loss in FEV1 and health status amongst survivors.,NCT00268216; NCT00292552.,The online version of this article (10.1186/s12931-018-0928-3) contains supplementary material, which is available to authorized users. | Minimizing the risk of disease progression and exacerbations is the key goal of COPD management, as these are well-established indicators of poor COPD prognosis.,We developed a novel composite end point assessing three important aspects (lung function, health status, and exacerbations) of worsening in COPD.,The objective was to determine whether dual bronchodilation with umeclidinium/vilanterol (UMEC/VI) reduces clinically important deteriorations (CIDs) in COPD versus placebo or bronchodilator monotherapy.,This study is a post hoc analysis of two 24-week trials comparing UMEC/VI 62.5/25 µg with UMEC 62.5 µg, VI 25 µg, or placebo (Study A; NCT01313650), or UMEC/VI 62.5/25 µg with tiotropium (TIO) 18 µg (Study B; NCT01777334) in patients with symptomatic COPD, without a history of frequent exacerbations.,Deterioration was assessed as the time to a first CID, a composite measure defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 second or ≥4-unit increase in St George’s Respiratory Questionnaire total score or an on-treatment moderate-to-severe COPD exacerbation.,In Study A, fewer patients experienced a first CID with UMEC/VI (44%) versus UMEC (50%), VI (56%), and placebo (75%).,The risk of a first CID was reduced with UMEC/VI (hazard ratio [HR]: 0.37 [95% confidence interval, CI: 0.30, 0.45]), UMEC (HR: 0.46 [95% CI: 0.38, 0.56]), and VI (HR: 0.55 [95% CI: 0.45, 0.66]; all P<0.001) versus placebo, and with UMEC/VI versus UMEC (HR: 0.80 [95% CI: 0.65, 0.97]; P<0.05) and versus VI (HR: 0.67 [95% CI: 0.55, 0.81]; P<0.001).,In Study B, fewer patients experienced a first CID with UMEC/VI (41%) versus TIO (59%).,UMEC/VI reduced the risk of a first composite CID by 43% versus TIO (HR: 0.57 [95% CI: 0.47, 0.69]; P<0.001).,This exploratory analysis, using a new assessment of clinical deterioration in COPD, revealed that a majority of symptomatic patients with low exacerbation risk experienced a deterioration during the 24-week study periods.,UMEC/VI reduces the risk of a first CID versus placebo or bronchodilator monotherapy. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) often have poor health-related quality of life (HRQoL) that is disproportionate to their degree of airflow limitation.,This study evaluated the association between St George’s Respiratory Questionnaire for COPD (SGRQ-C) score and forced expiratory volume in one second and investigated the factors responsible for high SGRQ-C score according to severity of airflow limitation.,Data from 1,264 COPD patients were obtained from the Korean COPD Subgroup Study (KOCOSS) cohort.,Patients were categorized into two groups according to severity of airflow limitation: mild-to-moderate and severe-to-very severe COPD groups.,We evaluated the clinical factors associated with high SGRQ-C score (≥25) in each COPD patient group.,Of the 1,264 COPD patients, 902 (71.4%) had mild-to-moderate airflow limitation and 362 (28.6%) had severe-to-very severe airflow limitation.,Of the mild-to-moderate COPD patients, 59.2% (534/902) had high SGRQ-C score, while 80.4% (291/362) of the severe-to-very severe COPD patients had high SGRQ-C score.,The association between SGRQ-C score and post-bronchodilator forced expiratory volume in one second (% predicted) was very weak in the mild-to-moderate COPD patients (r=−0.103, p=0.002) and weak in the severe-to-very severe COPD patients (r=−0.219, p<0.001).,Multiple logistic regression analysis revealed that age, being an ex- or current smoker, lower level of education, cough, dyspnea, and number of comorbidities with congestive heart failure, hyperlipidemia, and depression were significantly associated with high SGRQ-C score in mild-to-moderate COPD patients.,In comparison, being an ex-smoker and having respiratory symptoms including sputum and dyspnea were significant factors associated with high SGRQ-C score in severe-to-very severe COPD patients.,In addition to the respiratory symptoms of dyspnea and cough, high SGRQ-C score was associated with extra-pulmonary comorbidities in mild-to-moderate COPD patients.,However, only respiratory symptoms such as sputum and dyspnea were significantly associated with high SGRQ-C score in severe-to-very severe COPD patients.,This indicates the need for an improved management strategy for relieving respiratory symptoms in COPD patients with poor HRQoL.,In addition, attention should be paid to extra-pulmonary comorbidities, especially in mild-to-moderate COPD patients with poor HRQoL. | Cardiovascular disease is a primary cause of death in patients with chronic obstructive pulmonary disease (COPD).,Beta-blockers have been proved to reduce morbidity and improve survival in patients with cardiac diseases.,But the effects of beta-blockers on outcomes in patients with COPD remain controversial.,The objective of this meta-analysis was to assess the effect of beta-blockers on mortality and exacerbation in patients with COPD.,An extensive search of the EMBASE, MEDLINE and Cochrane was performed to retrieve the studies of beta-blockers treatment in patients with COPD.,The random effects model meta-analysis was used to evaluate effect on overall mortality and exacerbation of COPD.,Fifteen original observational cohort studies with a follow-up time from 1 to 7.2 years were included.,The results revealed that beta-blockers treatment significantly decreased the risk of overall mortality and exacerbation of COPD.,The relative risk (RR) for overall mortality was 0.72 (0.63 to 0.83), and for exacerbation of COPD was 0.63 (0.57 to 0.71).,In subgroup analysis of COPD patients with coronary heart disease or heart failure, the risk for overall mortality was 0.64 (0.54-0.76) and 0.74 (0.58-0.93), respectively.,The findings of this meta-analysis confirmed that beta-blocker use in patients with COPD may not only decrease the risk of overall mortality but also reduce the risk of exacerbation of COPD.,Beta-blocker prescription for cardiovascular diseases needs to improve in COPD patients. | 1 |
COPD often coexists with chronic conditions that may influence disease prognosis.,We investigated associations between chronic (co)morbidities and exacerbations in primary care COPD patients.,Retrospective cohort study based on 2012-2013 electronic health records from 179 Dutch general practices.,Comorbidities from patients with physician-diagnosed COPD were categorized according to International Classification of Primary Care (ICPC) codes.,Chi-squared tests, uni- and multivariable logistic, and Cox regression analyses were used to study associations with exacerbations, defined as oral corticosteroid prescriptions.,Fourteen thousand six hundred three patients with COPD could be studied (mean age 67 (SD 12) years, 53% male) for two years.,At baseline 12,826 (88%) suffered from ≥1 comorbidities, 3263 (22%) from ≥5.,The most prevalent comorbidities were hypertension (35%), coronary heart disease (19%), and osteoarthritis (18%).,Several comorbidities showed statistically significant associations with frequent (i.e., ≥2/year) exacerbations: heart failure (odds ratio [OR], 95% confidence interval: 1.72; 1.38-2.14), blindness & low vision (OR 1.46; 1.21-1.75), pulmonary cancer (OR 1.85; 1.28-2.67), depression 1.48; 1.14-1.91), prostate disorders (OR 1.50; 1.13-1.98), asthma (OR 1.36; 1.11-1.70), osteoporosis (OR 1.41; 1.11-1.80), diabetes (OR 0.80; 0.66-0.97), dyspepsia (OR 1.25; 1.03-1.50), and peripheral vascular disease (OR 1.20; 1.00-1.45).,From all comorbidity categories, having another chronic respiratory disease beside COPD showed the highest risk for developing a new exacerbation (Cox hazard ratio 1.26; 1.17-1.36).,Chronic comorbidities are highly prevalent in primary care COPD patients.,Several chronic comorbidities were associated with having frequent exacerbations and increased exacerbation risk. | The aim of this study is to quantify the burden of chronic obstructive pulmonary disease (COPD) - incidence, prevalence, and mortality - and identify trends in Australia, Canada, France, Germany, Italy, Japan, The Netherlands, Spain, Sweden, the United Kingdom, and the United States of America.,A structured literature search was performed (January 2000 to September 2010) of PubMed and EMBASE, identifying English-language articles reporting COPD prevalence, incidence, or mortality.,Of 2838 articles identified, 299 full-text articles were reviewed, and data were extracted from 133 publications.,Prevalence data were extracted from 80 articles, incidence data from 15 articles, and mortality data from 58 articles.,Prevalence ranged from 0.2%-37%, but varied widely across countries and populations, and by COPD diagnosis and classification methods.,Prevalence and incidence were greatest in men and those aged 75 years and older.,Mortality ranged from 3-111 deaths per 100,000 population.,Mortality increased in the last 30-40 years; more recently, mortality decreased in men in several countries, while increasing or stabilizing in women.,Although COPD mortality increased over time, rates declined more recently, likely indicating improvements in COPD management.,In many countries, COPD mortality has increased in women but decreased in men.,This may be explained by differences in smoking patterns and a greater vulnerability in women to the adverse effects of smoking.,Point your SmartPhone at the code above.,If you have a QR code reader the video abstract will appear.,Or use: http://dvpr.es/Nl3LKT | 1 |
During most COPD exacerbations, patients continue to live in the community but there is little information on changes in activity during exacerbations due to the difficulties of obtaining recent, prospective baseline data.,Patients recorded on daily diary cards any worsening in respiratory symptoms, peak expiratory flow (PEF) and the number of steps taken per day measured with a Yamax Digi-walker pedometer.,Exacerbations were defined by increased respiratory symptoms and the number of exacerbations experienced in the 12 months preceding the recording of daily step count used to divide patients into frequent (> = 2/year) or infrequent exacerbators.,The 73 COPD patients (88% male) had a mean (±SD) age 71(±8) years and FEV1 53(±16)% predicted.,They recorded pedometer data on a median 198 days (IQR 134-353).,At exacerbation onset, symptom count rose by 1.9(±1.3) and PEF fell by 7(±13) l/min.,Mean daily step count fell from 4154(±2586) steps/day during a preceding baseline week to 3673(±2258) step/day during the initial 7 days of exacerbation (p = 0.045).,Patients with larger falls in activity at exacerbation took longer to recover to stable level (rho = −0.56; p < 0.001).,Recovery in daily step count was faster (median 3.5 days) than for exacerbation symptoms (median 11 days; p < 0.001).,Recovery in step count was also faster in untreated compared to treated exacerbation (p = 0.030).,Daily step count fell faster over time in the 40 frequent exacerbators, by 708 steps/year, compared to 338 steps/year in 33 infrequent exacerbators (p = 0.002).,COPD exacerbations reduced physical activity and frequent exacerbations accelerate decline in activity over time. | Chronic obstructive pulmonary disease (COPD) symptoms in the morning, including dyspnea and sputum production, affect patients’ quality of life and limit their ability to carry out even simple morning activities.,It is now emerging that these symptoms are associated with increased risk of exacerbations and work absenteeism, suggesting that they have a more profound impact on patients than previously thought.,The development of validated patient-reported outcome (PRO) questionnaires to capture patients’ experience of COPD symptoms in the morning is, therefore, vital for establishing effective and comprehensive management strategies.,Although it is well established that long-acting bronchodilators are effective in improving COPD symptoms, the limited available data on their impact on morning symptoms and activities have been obtained with non-validated PRO questionnaires.,In this review, we discuss the impact of COPD symptoms in the morning and available tools used to evaluate them, and highlight specific gaps that need to be addressed to develop standardized instruments able to meet regulatory requirement.,We also present available evidence on the effect of pharmacological therapies on morning symptoms. | 1 |
Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users. | 1 |
Many studies have reported the prevalence of chronic obstructive pulmonary disease (COPD) and its effects and prognosis in patients with lung cancer, but few have considered quality of life and survival of patients with lung cancer according to severity of airway obstruction.,This study investigated the presence of COPD and the severity of airway obstruction in patients with non-small cell lung cancer (NSCLC), and analyzed how these factors affected symptoms, quality of life, and prognosis.,We retrospectively reviewed the prospective lung cancer database of the Catholic Medical Centers at the Catholic University of Korea from 2014 to 2017.,We enrolled patients with advanced NSCLC and evaluated quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30.,We also estimated pulmonary function and analyzed survival data.,Of the 337 patients with advanced NSCLC, 170 (50.5%) had COPD and 167 (49.5%) did not.,Significant differences were observed in symptoms between the two groups.,The COPD group complained of more symptoms, such as cough, sputum, and dyspnea, than those in the non-COPD group.,The distribution according to the severity of obstruction in the COPD group was as follows: Grade 1 (FEV1 ≥ 80%) 35 patients (20.6%), Grade 2 (50% ≤ FEV1 < 80%) 103 patients (60.6%), Grade 3 (30% ≤ FEV1 < 50%) 24 patients (14.1%), and Grade 4 (FEV1 < 30%) 8 patients (4.7%).,The presence of COPD did not affect overall quality of life in patients with NSCLC, but as the airway obstruction increased, physical function decreased, and fatigue and dyspnea were more frequent.,The overall median survival of the COPD group was shorter than that of the non-COPD group (median survival, 224 vs. 339 days, p = 0.035).,In this study, a high prevalence of COPD was found among patients with advanced NSCLC, and COPD patients complained about various symptoms and had diminished quality of life in several sectors.,Therefore, it is necessary to actively evaluate quality of life, lung function, and symptoms in patients with lung cancer and reflect them in the treatment and management plans of these patients. | Supplemental Digital Content is available in the text,This study compares the prevalence rates of comorbidities between chronic obstructive pulmonary disease (COPD) and non-COPD control patients reported in literature.,Literature was searched in several electronic databases.,After the selection of studies by following précised eligibility criteria, meta-analyses of odds ratios (ORs) were carried out with subgroup and sensitivity analyses under random effects model.,Eleven studies (47,695,183 COPD and 47,924,876 non-COPD control patients’ data) were used for meta-analysis.,Average age of COPD patients was 66.66 ± 8.72 years of whom 55.4 ± 11.9% were males.,The prevalence of cardiovascular comorbidities [OR 1.90, 95% confidence interval (95% CI) 1.59-2.28; P < .00001], cerebrovascular comorbidities (OR 1.84, 95% CI 1.47-2.31; P < .00001), hypertension (OR 1.45, 95% CI 1.31-1.61; P < .00001), diabetes mellitus (OR 1.22, 95% CI 1.07-1.38; P = .003), neurological and psychiatric disorders (OR 1.78, 95% CI 1.48-2.14; P < .00001), gut and renal disorders (OR 1.96, 95% CI 1.43-2.68; P < .00001), musculoskeletal disorders (OR 1.51, 95% CI 1.27-1.78; P < .00001), non-COPD respiratory comorbidities (OR 2.81, 95% CI 2.52-3.14; P < .00001), and cancer (OR 1.67, 95% CI 1.25-2.23; P = .0005) were significantly higher in COPD patients than in non-COPD controls.,COPD is associated with significantly higher comorbidities than in other diseases that should be taken into consideration in COPD control strategies. | 1 |
Regular physical activity (PA) is recommended for persons with chronic obstructive pulmonary disease (COPD).,Interventions that promote PA and sustain long-term adherence to PA are needed.,We examined the effects of an Internet-mediated, pedometer-based walking intervention, called Taking Healthy Steps, at 12 months.,Veterans with COPD (N=239) were randomized in a 2:1 ratio to the intervention or wait-list control.,During the first 4 months, participants in the intervention group were instructed to wear the pedometer every day, upload daily step counts at least once a week, and were provided access to a website with four key components: individualized goal setting, iterative feedback, educational and motivational content, and an online community forum.,The subsequent 8-month maintenance phase was the same except that participants no longer received new educational content.,Participants randomized to the wait-list control group were instructed to wear the pedometer, but they did not receive step-count goals or instructions to increase PA.,The primary outcome was health-related quality of life (HRQL) assessed by the St George’s Respiratory Questionnaire Total Score (SGRQ-TS); the secondary outcome was daily step count.,Linear mixed-effect models assessed the effect of intervention over time.,One participant was excluded from the analysis because he was an outlier.,Within the intervention group, we assessed pedometer adherence and website engagement by examining percent of days with valid step-count data, number of log-ins to the website each month, use of the online community forum, and responses to a structured survey.,Participants were 93.7% male (223/238) with a mean age of 67 (SD 9) years.,At 12 months, there were no significant between-group differences in SGRQ-TS or daily step count.,Between-group difference in daily step count was maximal and statistically significant at month 4 (P<.001), but approached zero in months 8-12.,Within the intervention group, mean 76.7% (SD 29.5) of 366 days had valid step-count data, which decreased over the months of study (P<.001).,Mean number of log-ins to the website each month also significantly decreased over the months of study (P<.001).,The online community forum was used at least once during the study by 83.8% (129/154) of participants.,Responses to questions assessing participants’ goal commitment and intervention engagement were not significantly different at 12 months compared to 4 months.,An Internet-mediated, pedometer-based PA intervention, although efficacious at 4 months, does not maintain improvements in HRQL and daily step counts at 12 months.,Waning pedometer adherence and website engagement by the intervention group were observed.,Future efforts should focus on improving features of PA interventions to promote long-term behavior change and sustain engagement in PA.,Clinicaltrials.gov NCT01102777; https://clinicaltrials.gov/ct2/show/NCT01102777 (Archived by WebCite at http://www.webcitation.org/6iyNP9KUC) | Chronic obstructive pulmonary disease (COPD) is characterized by a persistent blockage of airflow, prompting episodes of shortness of breath, commonly leading to hospitalization.,Hospitalization may lead to a decline in physical activity following discharge.,Physical activity has been shown to improve symptoms of COPD and reduce readmissions, and to decrease morbidity and mortality.,This study aims to explore, from the perspectives of people with COPD, the barriers to and enablers of participation in physical activity following hospitalization for COPD.,This study had a qualitative descriptive design and included semistructured interviews with 28 adult COPD patients who had been admitted to hospital with a primary diagnosis of exacerbation of COPD.,A plethora of barriers to but fewer enablers of participation in physical activity and pulmonary rehabilitation were identified for this cohort of people.,The main barriers identified were health-related (comorbidities, COPD symptoms, and physical injury or illness) environment-related (weather, transport, and finance), and self-related.,The main enabling factors reported were access to health professionals and equipment, social support, routine and extracurricular activities, personal goals and motivation, and the effect of physical activity and “feeling better”.,This research provides a snapshot of the barriers to and enablers of physical activity and pulmonary rehabilitation in people with COPD.,It is evident that there are significant barriers which hinder the ability of people with COPD to undertake and continue participation in physical activity and pulmonary rehabilitation.,While there are some enablers that may counter these barriers, it is clear that health professionals dealing with people suffering from COPD need to actively recognize and address barriers to physical activity and pulmonary rehabilitation.,Hospital admission may create an opportunity for implementation of interventions promoting physical activity (such as referral to pulmonary rehabilitation), which may assist in reducing hospital readmission, as well as decreasing morbidity and mortality. | 1 |
The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood.,Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events.,In this prospective, observational cohort study (NCT01360398), patients with COPD aged 40-85 years underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses.,Results are presented for subjects in the full cohort, followed for 1 year.,Interactions between exacerbation occurrence and pathogens were investigated by generalised estimating equation and stratified conditional logistic regression analyses.,The mean exacerbation rate per patient-year was 3.04 (95% CI 2.63 to 3.50).,At AECOPD, the most common bacterial species were non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, and the most common virus was rhinovirus.,Logistic regression analyses (culture bacterial detection) showed significant OR for AECOPD occurrence when M. catarrhalis was detected regardless of season (5.09 (95% CI 2.76 to 9.41)).,When NTHi was detected, the increased risk of exacerbation was greater in high season (October-March, OR 3.04 (1.80 to 5.13)) than low season (OR 1.22 (0.68 to 2.22)).,Bacterial and viral coinfection was more frequent at exacerbation (24.9%) than stable state (8.6%).,A significant interaction was detected between NTHi and rhinovirus presence and AECOPD risk (OR 5.18 (1.92 to 13.99); p=0.031).,AECOPD aetiology varies with season.,Rises in incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effects of viral infection.,Results, NCT01360398. | It is reported that the iron-responsive element-binding protein 2 (IREB2) gene rs2568494 polymorphism might be associated with COPD risk.,The purpose of this meta-analysis was to collect all eligible studies to review the association between IREB2 gene rs2568494 polymorphism and susceptibility to COPD.,We carried out a comprehensive document search of electronic databases of PubMed, MEDLIN, Web of Science, and included 4 eligible studies that examined the association between IREB2 rs2568494 polymorphism and COPD susceptibility.,We performed a meta-analysis of these studies based on IREB2 rs2568494 genotypes.,After meta-analysis with fixed or random effects, no significant associations were found under the heterozygote model (GG/GA; OR=0.908, 95%CI: 0.790-1.043; P=0.172), homozygote model (GG/AA; OR=0.880, 95%CI: 0.497-1.557; P=0.661), dominant model (GG/AA+GA; OR=0.941, 95%CI: 0.748-1.182; P=0.599), or allelic model (G/A; OR=0.953, 95%CI: 0.770-1.179; P=0.655).,However, we found a significant correlation under the recessive model (AA/GA+GG; OR=1.384, 95%CI: 1.092-1.755; P=0.007).,The current results revealed that there was significant association between IREB2 gene rs2568494 polymorphism with susceptibility to COPD; the presence of allelic A might a genetic factor conferring susceptibility to COPD. | 1 |
Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.,For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler.,Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).,295 and 291 patients were treated in MORACTO 1 and 2, respectively.,Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001).,Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).,Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies.,Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.,T/O reduces lung hyperinflation in COPD versus T, O or placebo and increases exercise endurance versus placebohttp://ow.ly/ml3G307XW6a | The difference in efficacy of long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) for dynamic lung hyperinflation (DLH) in COPD is unclear.,The purpose of this study was to elucidate the difference in efficacy of LAMA and LABA alone and the combination thereof for DLH.,Thirty stable patients were enrolled and randomly divided into two groups following baseline measurements.,One group was treated with 5 μg tiotropium (Respimat inhaler) for 4 weeks following a 4-week treatment with 150 μg indacaterol, while the other group was treated with indacaterol for 4 weeks following a 4-week treatment with tiotropium.,For both groups, these treatments were followed by a combination of the two drugs for 4 weeks.,Pulmonary function tests, including DLH evaluated by metronome-paced incremental hyperventilation and exercise tolerance evaluated by the shuttle-walk test, were performed at the end of each treatment period.,In total, 23 patients completed this study.,Both tiotropium and indacaterol alone significantly increased forced expiratory volume in 1 second, exercise tolerance, and improved health status.,Tiotropium significantly improved DLH, but indacaterol did not.,The combination therapy resulted in further improvements in lung function and exercise tolerance, but not in DLH.,The efficacy of tiotropium in inhibiting DLH following metronome-paced incremental hyperventilation may be superior to that of 150 μg indacaterol, although the effects on airflow obstruction were the same, and the combination therapy showed further improvement in airflow obstruction, but not in DLH. | 1 |
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. | Genotoxic stress, such as by exposure to bromodeoxyuridine (BrdU) and cigarette smoke, induces premature cell senescence.,Recent evidence indicates that cellular senescence of various types of cells is accelerated in COPD patients.,However, whether the senescence of airway epithelial cells contributes to the development of airway diseases is unknown.,The present study was designed to test the hypothesis that premature senescence of airway epithelial cells (Clara cells) impairs repair processes and exacerbates inflammation after airway injury.,C57/BL6J mice were injected with the Clara-cell-specific toxicant naphthalene (NA) on days 0, 7, and 14, and each NA injection was followed by a daily dose of BrdU on each of the following 3 days, during which regenerating cells were allowed to incorporate BrdU into their DNA and to senesce.,The p38 MAPK inhibitor SB202190 was injected 30 minutes before each BrdU dose.,Mice were sacrificed at different times until day 28 and lungs of mice were obtained to investigate whether Clara cell senescence impairs airway epithelial regeneration and exacerbates airway inflammation.,NCI-H441 cells were induced to senesce by exposure to BrdU or the telomerase inhibitor MST-312.,Human lung tissue samples were obtained from COPD patients, asymptomatic smokers, and nonsmokers to investigate whether Clara cell senescence is accelerated in the airways of COPD patients, and if so, whether it is accompanied by p38 MAPK activation.,BrdU did not alter the intensity of the airway epithelial injury or inflammation after a single NA exposure.,However, after repeated NA exposure, BrdU induced epithelial cell (Clara cell) senescence, as demonstrated by a DNA damage response, p21 overexpression, increased senescence-associated β-galactosidase activity, and growth arrest, which resulted in impaired epithelial regeneration.,The epithelial senescence was accompanied by p38 MAPK-dependent airway inflammation.,Senescent NCI-H441 cells impaired epithelial wound repair and secreted increased amounts of pro-inflammatory cytokines in a p38 MAPK-dependent manner.,Clara cell senescence in COPD patients was accelerated and accompanied by p38 MAPK activation.,Senescence of airway epithelial cells impairs repair processes and exacerbates p38 MAPK-dependent inflammation after airway injury, and it may contribute to the pathogenesis of COPD. | 1 |
Maintenance treatment with macrolide antibiotics has shown to be effective in reducing exacerbations in COPD patients.,A major concern with prolonged treatment with antibiotics is the development of bacterial resistance.,In this study we determined the effect of azithromycin on the development and acquisition of resistance to macrolides in the nasopharyngeal flora in COPD patients.,This study was part of the COLUMBUS trial, a randomised, double-blind, placebo-controlled trial to measure the effect of maintenance treatment with azithromycin in 92 COPD patients on the exacerbation rates during a 12-month period.,In order to determine resistance to macrolides, we used a targeted metagenomic approach to measure the presence and relative abundance of specific macrolide resistance genes ermB, ermF and mefA in throat samples collected at different time-points during this 12-month period.,There was no increased risk for acquisition of macrolide resistance genes in the azithromycin group compared to the placebo group in COPD patients.,However, loss of the macrolide resistance gene ermB was increased overtime in the placebo treated group compared to the azithromycin group (n = 5 for the placebo group versus n = 0 for the azithromycin group at 12 months; p = 0.012).,The change in relative abundance of the three macrolide-resistance genes showed that all but one (ermF) increased during treatment with azithromycin.,The acquisition rate of macrolide resistance genes in COPD patients treated with azithromycin maintenance therapy was limited, but the relative abundance of macrolide resistance genes increased significantly over time compared to placebo.,This study was part of the COLUMBUS trial (Clinicaltrials.gov, NCT00985244). | Little is known about the microbiota shift induced by exacerbation in chronic obstructive pulmonary disease (COPD) patients.,The sputa microbiota of COPD patients was evaluated when clinically stable and during acute exacerbations of the disease.,Sputa microbiota was analyzed using 16S ribosomal RNA gene pyrosequencing and quantitative polymerase chain reaction-based pathogen detection.,Nine COPD patients were enrolled.,Pyrosequencing of 16S rRNA genes identified 2,267 unique bacterial operational taxonomic units.,Principal microbiota shifts during exacerbation were in either Proteobacteria, Firmicutes or Bacteroidetes.,Streptococcus and Moraxella levels were detected during exacerbation in severe (Global Initiative for Chronic Obstructive Lung Disease 3) COPD patients.,Most of the clinically-important genera found in the sputum with the pyrosequencing of 16S rRNA gene correlated with specific quantitative polymerase chain reactions for bacteria while respiratory viruses were nearly absent.,Sputum microbiotas of exacerbated COPD patients are complex.,This pilot study shows a clear shift in the microbiota of patients during exacerbation.,The nature of this shift varies from patient to patient in such a way that the treatment should be patient-specific.,Further studies are needed to establish the impact of microbial exacerbations on the pulmonary microbiota. | 1 |
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. | Chronic obstructive pulmonary disease (COPD) has been consistently associated with increased risk of lung cancer.,However, previous studies have had limited ability to determine whether the association is due to smoking.,The Environment And Genetics in Lung cancer Etiology (EAGLE) population-based case-control study recruited 2100 cases and 2120 controls, of whom 1934 cases and 2108 controls reported about diagnosis of chronic bronchitis, emphysema, COPD (chronic bronchitis and/or emphysema), or asthma more than 1 year before enrollment.,We estimated odds ratios (OR) and 95% confidence intervals (CI) using logistic regression.,After adjustment for smoking, other previous lung diseases, and study design variables, lung cancer risk was elevated among individuals with a history of chronic bronchitis (OR = 2.0, 95% CI = 1.5-2.5), emphysema (OR = 1.9, 95% CI = 1.4-2.8), or COPD (OR = 2.5, 95% CI = 2.0-3.1).,Among current smokers, association between chronic bronchitis and lung cancer was strongest among lighter smokers.,Asthma was associated with a decreased risk of lung cancer in males (OR = 0.48, 95% CI = 0.30-0.78).,These results suggest that the associations of personal history of chronic bronchitis, emphysema, and COPD with increased risk of lung cancer are not entirely due to smoking.,Inflammatory processes may both contribute to COPD and be important for lung carcinogenesis. | 1 |
The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood.,Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events.,In this prospective, observational cohort study (NCT01360398), patients with COPD aged 40-85 years underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses.,Results are presented for subjects in the full cohort, followed for 1 year.,Interactions between exacerbation occurrence and pathogens were investigated by generalised estimating equation and stratified conditional logistic regression analyses.,The mean exacerbation rate per patient-year was 3.04 (95% CI 2.63 to 3.50).,At AECOPD, the most common bacterial species were non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, and the most common virus was rhinovirus.,Logistic regression analyses (culture bacterial detection) showed significant OR for AECOPD occurrence when M. catarrhalis was detected regardless of season (5.09 (95% CI 2.76 to 9.41)).,When NTHi was detected, the increased risk of exacerbation was greater in high season (October-March, OR 3.04 (1.80 to 5.13)) than low season (OR 1.22 (0.68 to 2.22)).,Bacterial and viral coinfection was more frequent at exacerbation (24.9%) than stable state (8.6%).,A significant interaction was detected between NTHi and rhinovirus presence and AECOPD risk (OR 5.18 (1.92 to 13.99); p=0.031).,AECOPD aetiology varies with season.,Rises in incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effects of viral infection.,Results, NCT01360398. | Eosinophilic airway inflammation is observed in 10-30% of COPD subjects.,Whether increased eosinophils or impairment in their clearance by macrophages is associated with the severity and frequency of exacerbations is unknown.,We categorised 103 COPD subjects into 4 groups determined by the upper limit of normal for their cytoplasmic macrophage red hue (<6%), an indirect measure of macrophage efferocytosis of eosinophils, and area under the curve sputum eosinophil count (≥3%/year).,Eosinophil efferocytosis by monocyte-derived macrophages was studied in 17 COPD subjects and 8 normal controls.,There were no differences in baseline lung function, health status or exacerbation frequency between the groups: A-low red hue, high sputum eosinophils (n = 10), B-high red hue, high sputum eosinophils (n = 16), C-low red hue, low sputum eosinophils (n = 19) and D- high red hue, low sputum eosinophils (n = 58).,Positive bacterial culture was lower in groups A (10%) and B (6%) compared to C (44%) and D (21%) (p = 0.01).,The fall in FEV1 from stable to exacerbation was greatest in group A (ΔFEV1 [95 % CI] -0.41 L [-0.65 to -0.17]) versus group B (-0.16 L [-0.32 to -0.011]), C (-0.11 L [-0.23 to -0.002]) and D (-0.16 L [-0.22 to -0.10]; p = 0.02).,Macrophage efferocytosis of eosinophils was impaired in COPD versus controls (86 [75 to 92]% versus 93 [88 to 96]%; p = 0.028); was most marked in group A (71 [70 to 84]%; p = 0.0295) and was inversely correlated with exacerbation frequency (r = -0.63; p = 0.006).,Macrophage efferocytosis of eosinophils is impaired in COPD and is related to the severity and frequency of COPD exacerbations. | 1 |
Long-acting bronchodilators are the cornerstone of pharmacologic treatment of COPD.,The new combination of long-acting muscarinic antagonist (LAMA) tiotropium (TIO) and long acting beta-agonists (LABA) olodaterol (OLO) has been introduced as fist line therapy for COPD.,This article analyses the evidence of efficacy and safety of the TIO/OLO combination.,A systematic review and metaanalysis of randomized controlled trials (RCT) with a period of treatment of at least 6 weeks, in patients with COPD confirmed by spirometry, comparing combined treatment with TIO/OLO (approved doses only), with any of the mono-components or any other active comparator administered as an inhalator.,A total of 10 Randomized controlled trials (RCT) were identified (N = 10,918).,TIO/OLO significantly improved trough FEV1 from baseline to week 12 versus TIO, OLO and LABA/ICS (0.06 L, 0.09 L and between 0.04 and 0.05 L, respectively).,TIO/OLO improved transitional dyspnea index (TDI) and St.,George’s Respiratory Questionnaire (SGRQ) compared with mono-components, with patients more likely to achieve clinically important improvements in TDI (risk ratio [RR]: 1.17, 95% confidence interval [CI]: [1.07, 1.28] versus TIO and RR: 1.14, 95%CI: [1.01, 1.28] versus OLO) and in SGRQ (RR: 1.21, 95%CI: [1.12, 1.30] versus TIO and RR: 1.28, 95%CI: [1.18, 1.40] versus OLO).,Patients treated with TIO/OLO showed a significant reduction in the use of rescue medication and no significant differences in frequency of general and serious adverse events were observed between TIO/OLO and mono-components.,Treatment with TIO/OLO provided significant improvements in lung function versus mono-components and LABA/ICS with more patients achieving significant improvements in dyspnea and health status.,No differences in adverse events were observed compared with other active treatments.,PROSPERO register of systematic reviews (CRD42016040162).,The online version of this article (10.1186/s12931-017-0683-x) contains supplementary material, which is available to authorized users. | Randomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as β2-agonist (LABA)/muscarinic antagonist (LAMA), have favorable efficacy compared with commonly used COPD treatments.,The objective of this analysis was to compare the efficacy and safety of LABA/LAMA with LAMA or LABA/inhaled corticosteroid (ICS) in adults with stable moderate-to-very-severe COPD.,This systematic review and meta-analysis (PubMed/MEDLINE, Embase, Cochrane Library and clinical trial/manufacturer databases) included RCTs comparing ≥12 weeks’ LABA/LAMA treatment with LAMA and/or LABA/ICS (approved doses only).,Eligible studies were independently selected by two authors using predefined data fields; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.,Eighteen studies (23 trials) were eligible (N=20,185).,LABA/LAMA significantly improved trough forced expiratory volume in 1 second (FEV1) from baseline to week 12 versus both LAMA and LABA/ICS (0.07 L and 0.08 L, P<0.0001), with patients more likely to achieve clinically important improvements in FEV1 of >100 mL (risk ratio [RR]: 1.33, 95% confidence interval [CI]: [1.20, 1.46] and RR: 1.44, 95% CI: [1.33, 1.56], respectively, the number needed to treat being eight and six, respectively).,LABA/LAMA improved transitional dyspnea index and St George’s Respiratory Questionnaire scores at week 12 versus LAMA (both P<0.0001), but not versus LABA/ICS, and reduced rescue medication use versus both (P<0.0001 and P=0.001, respectively).,LABA/LAMA significantly reduced moderate/severe exacerbation rate compared with LABA/ICS (RR 0.82, 95% CI: [0.75, 0.91]).,Adverse event (AE) incidence was no different for LABA/LAMA versus LAMA treatment, but it was lower versus LABA/ICS (RR 0.94, 95% CI: [0.89, 0.99]), including a lower pneumonia risk (RR 0.59, 95% CI: [0.43, 0.81]).,LABA/LAMA presented a lower risk for withdrawals due to lack of efficacy versus LAMA (RR: 0.66, 95% CI: [0.51, 0.87]) and due to AEs versus LABA/ICS (RR: 0.83, 95% CI: [0.69, 0.99]).,The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD.,These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use. | 1 |
Statins have immunomodulatory properties that may provide beneficial effects in the treatment of COPD.,We investigated whether a statin improves the IL-17/IL-10 imbalance in patients with COPD, as has previously been demonstrated in patients with asthma.,Thirty patients with stable COPD were recruited to a double-blind, randomized, controlled, crossover trial comparing the effect of simvastatin, 20 mg po daily, with that of a matched placebo on sputum inflammatory markers and airway inflammation.,Each treatment was administered for 4 weeks separated by a 4-week washout period.,The primary outcome was the presence of T-helper 17 cytokines and indoleamine 2,3-dioxygenase (IDO) in induced sputum.,Secondary outcomes included sputum inflammatory cells, FEV1, and symptoms using the COPD Assessment Test (CAT).,At 4 weeks, there was a significant reduction in sputum IL-17A, IL-22, IL-6, and CXCL8 concentrations (mean difference, −16.4 pg/mL, P = .01; −48.6 pg/mL, P < .001; −45.3 pg/mL, P = .002; and −190.9 pg/mL, P = .007, respectively), whereas IL-10 concentrations, IDO messenger RNA expression (fold change), and IDO activity (kynurenine to tryptophan ratio) were markedly increased during simvastatin treatment compared with placebo treatment periods (mean difference, 24.7 pg/mL, P < .001; 1.02, P < .001; and 0.47, P < .001, respectively).,The absolute sputum macrophage count, proportion of macrophages, and CAT score were reduced after simvastatin compared with placebo (mean difference, −0.16 × 106, P = .004; −14.1%, P < .001; and −3.2, P = .02, respectively).,Values for other clinical outcomes were similar between the simvastatin and placebo treatments.,Simvastatin reversed the IL-17A/IL-10 imbalance in the airways and reduced sputum macrophage but not neutrophil counts in patients with COPD.,ClinicalTrials.gov; No.: NCT01944176; www.clinicaltrials.gov | 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 |
Many patients with chronic obstructive pulmonary disease (COPD) suffer from poor sleep quality.,We hypothesized that poor sleep quality in otherwise stable patients predicted exacerbations in these patients.,This is a secondary analysis of the results of a previously published randomized trial of azithromycin in 1,117 patients with moderate to severe COPD who were clinically stable on enrollment.,Sleep quality was measured using the Pittsburgh Sleep Quality Index.,Other quality of life indices included the Medical Outcome Study 36-item Short Form Health Survey and the St Georges Respiratory Questionnaire.,Outcomes included time to first exacerbation and exacerbation rate.,Sleep quality was “poor” (Pittsburgh Sleep Quality Index >5) in 53% of participants but was not related to age or severity of airflow obstruction.,Quality of life scores were worse in “poor” sleepers than in “good” sleepers.,Major classes of comorbid conditions, including psychiatric, neurologic, and musculoskeletal disease, were more prevalent in the “poor” sleepers.,Unadjusted time to first exacerbation was shorter (190 versus 239 days) and exacerbation rate (1.7 versus 1.37 per year) was greater in the poor sleepers, but no differences were observed after adjusting for medications and comorbid conditions associated with poor sleep.,Poor sleepers had greater exacerbation rates than did good sleepers.,This appeared to be due largely to them having more, or more severe, concomitant medical conditions and taking more medications. | 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 |
Tiotropium is prescribed for the treatment of chronic obstructive pulmonary disease (COPD) and delivered via HandiHaler® (18 μg once daily) or Respimat® Soft Mist™ inhaler (5 μg once daily).,The recent TIOtropium Safety and Performance In Respimat® (TIOSPIR™) study demonstrated that both exhibit similar safety profiles.,This analysis provides an updated comprehensive safety evaluation of tiotropium® using data from placebo-controlled HandiHaler® and Respimat® trials.,Pooled analysis of adverse event (AE) data from tiotropium HandiHaler® 18 μg and Respimat® 5 μg randomized, double-blind, parallel-group, placebo-controlled, clinical trials in patients with COPD (treatment duration ≥4 weeks).,Incidence rates, rate ratios (RRs), and 95% confidence intervals (CIs) were determined for HandiHaler® and Respimat® trials, both together and separately.,In the 28 HandiHaler® and 7 Respimat® trials included in this analysis, 11,626 patients were treated with placebo and 12,929 with tiotropium, totaling 14,909 (12,469 with HandiHaler®; 2,440 with Respimat®) patient-years of tiotropium exposure.,Mean age was 65 years, and mean prebronchodilator forced expiratory volume in 1 second (FEV1) was 1.16 L (41% predicted).,The risk (RR [95% CI]) of AEs (0.90 [0.87, 0.93]) and of serious AEs (SAEs) (0.94 [0.89, 0.99]) was significantly lower in the tiotropium than in the placebo group (HandiHaler® and Respimat® pooled results), and there was a numerically lower risk of fatal AEs (FAEs) (0.90 [0.79, 1.01]).,The risk of cardiac AEs (0.93 [0.85, 1.02]) was numerically lower in the tiotropium group.,Incidences of typical anticholinergic AEs, but not SAEs, were higher with tiotropium.,Analyzed separately by inhaler, the risks of AE and SAE in the tiotropium groups remained lower than in placebo and similarly for FAEs.,This analysis indicates that tiotropium is associated with lower rates of AEs, SAEs, and similar rates of FAEs than placebo when delivered via HandiHaler® or Respimat® (overall and separately) in patients with COPD. | Chronic obstructive pulmonary disease (COPD) is common in older people, with an estimated prevalence of 10% in the US population aged ≥75 years.,Inhaled medications are the cornerstone of treatment for COPD and are typically administered by one of three types of devices, ie, pressurized metered dose inhalers, dry powder inhalers, and nebulizers.,However, age-related pulmonary changes may negatively influence the delivery of inhaled medications to the small airways.,In addition, physical and cognitive impairment, which are common in elderly patients with COPD, pose special challenges to the use of handheld inhalers in the elderly.,Health care providers must take time to train patients to use handheld inhalers and must also check that patients are using them correctly on a regular basis.,Nebulizers should be considered for patients unable to use handheld inhalers properly.,What follows is a review of issues associated with COPD and its treatment in the elderly patient. | 1 |
BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease guidelines recommended a forced expiratory volume at one second per forced vital capacity as a standard diagnostic criterion of chronic obstructive pulmonary disease (COPD).,A few reports on the risk factors of COPD have used the standard diagnostic criteria.,In our study, the effects of age and smoking on COPD in Japan under the standard diagnosis criteria were evaluated.,METHODS: Subjects were 11,460 participants aged 25-74 years during health check-ups including spirometry at the Toyota Community Medical Center in Japan.,Logistic regression analyses with or without COPD as a dependent variable and age as an independent variable were conducted among non-smokers.,The ratio of the observed number of COPD cases in former and current smokers to the number expected for non-smokers with the same distribution of age (O/E) was calculated.,RESULTS: The proportion of males incurring COPD significantly increased with age, and the O/E for former and current male smokers was significantly higher than one, i.e., O/E (95% confidence interval) for current smokers with a Brinkman Index of <400, 400-799, and 800+ were 3.10 (2.00-4.81), 2.78 (2.05-3.73), and 4.76 (3.65-6.19), respectively.,Among females, the O/E for current smokers with a Brinkman Index of <400, and 400-799 were significantly higher than one.,CONCLUSION: Age and smoking were shown to constitute strong risk factors for COPD under the standard diagnostic criteria. | We investigated changes in the geography of Chronic Obstructuve Pulmonary Disease (COPD) hospitalization charges in California over the period of 1993 and 1999.,There is little information available at less than the county level for this increasingly costly disease in California.,We found, using a uniform grid unit method, (4X4 and 16X16 mile urban and rural grids respectively, using zip codes as the base source for information) positive relationships between COPD charges and age, percentage Hispanics, and number of tobacco outlets.,Further, inverse relationships were found between the incidence of COPD charges and income level and the percentage of the population with undergraduate degrees.,When examining “hotspot” grid units, we found that COPD was clearly associated with minority/immigrant status and depressed socio-economic measures, suggesting the need for better smoking interventions among persons of color and the poor.,In summary, the Los Angeles area had a marked increase in hotspots both in 1993 and 1999, and also experienced a significant increase in COPD hospitalization charges between 1993 and 1999.,Transforming zip code level data into a uniform grid allows for relatively simple comparisons across time, without such a transformation, such temporal comparisons are extremely difficult to implement.,This more, “fine grained” geographical analysis allows public health planners a better platform than is typically available to assess changes in COPD. | 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. | The integrated therapy of Bufei Yishen granule and acupoint sticking has been used in the treatment of stable chronic obstructive pulmonary disease (COPD) clinically, with remarkable benefits.,This study was initiated to observe the effects of the combination of Bufei Yishen granule and acupoint sticking on pulmonary function and morphormetry in a COPD rat model.,Rats were randomized into Control, Model, Bufei Yishen (BY), Acupoint sticking (AS), Bufei Yishen + Acupoint sticking (BY + AS) and aminophyline (APL) groups.,COPD rats were duplicated by repeated cigarette smoke and bacterial exposures.,The rats were treated with normal saline, Bufei Yishen granule, acupoint sticking, Bufei Yishen + Acupoint sticking and aminophylline, respectively, from week 9 through 20.,Pulmonary function was measured by using a whole body plethysmograph every 4 weeks.,The rats were sacrificed at the end of week 20, and lung tissue histology and ultrastructure was observed under light and electron microscopes.,The pulmonary function, including tidal volume (VT), peak expiratory flow (PEF) and expiratory flow at 50 % tidal volume (EF50), was markedly decreased from week 8 in COPD rats (P < 0.05).,At week 20, VT, PEF and EF50 were significantly lower in Model group (P < 0.05).,Compared with Model group, VT, PEF and EF50 were higher in BY and BY + AS groups (P < 0.05), and EF50 was higher in AS group, while VT was higher in APL group (P < 0.05).,Markedly histological and ultrastructural changes, including respiratory membrane thickening, volume density of lamellar corpuscle decreasing, mitochondria reducing in type II alveolar cell, were found in COPD rats and were alleviated in the treated groups, especially in BY and BY + AS groups.,Bufei Yishen granule and acupoint sticking can improve pulmonary function and lung pathological impairment in COPD rats, the curative effect of the combination is better than acupoint sticking or aminophylline only. | 1 |
Combination of the inhaled long-acting muscarinic antagonist umeclidinium (UMEC; GSK573719) with the long-acting β2-agonist vilanterol (VI) is an approved maintenance treatment for COPD in the US and EU.,We compared the efficacy and safety of UMEC/VI with placebo in patients with COPD of Asian ancestry.,In this 24-week, Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, patients were randomized 1:1:1 to UMEC/VI 125/25 μg, UMEC/VI 62.5/25 μg, or placebo.,The primary efficacy end point was trough forced expiratory volume in 1 second (FEV1) on day 169; secondary end points were Transition Dyspnea Index (TDI) focal score at week 24 and weighted mean (WM) FEV1 over 0-6 hours postdose on day 1.,Additional end points and safety were also assessed.,Both UMEC/VI 125/25 μg and UMEC/VI 62.5/25 μg statistically significantly improved trough FEV1 at day 169 versus placebo (UMEC/VI 125/25 μg, 0.216 L, [95% confidence interval [CI] 0.175-0.257]; UMEC/VI 62.5/25 μg, 0.151 L, 95% CI 0.110-0.191; both P<0.001).,Statistically significant improvements in TDI score were observed for both UMEC/VI groups versus placebo (UMEC/VI 125/25 μg, 0.9, 95% CI 0.3-1.4, P=0.002; UMEC/VI 62.5/25 μg, 0.7, 95% CI 0.1-1.2, P=0.016).,On day 1, both UMEC/VI groups improved 0-6-hour WM FEV1 versus placebo (UMEC/VI 125/25 μg, 0.182 L 95% CI 0.161-0.203; UMEC/VI 62.5/25 μg, 0.160 L, 95% CI 0.139-0.181; both P<0.001).,Statistically significant improvements for UMEC/VI groups versus placebo were observed for rescue albuterol use at weeks 1-24 (puffs/day, both P<0.001).,The incidence of adverse events was similar across groups.,In Asian patients with COPD, once-daily UMEC/VI 125/25 μg and UMEC 62.5/25 μg resulted in clinically meaningful and statistically significant improvements in lung-function end points versus placebo.,Symptomatic and quality of life measures also improved.,The safety profile of UMEC/VI was consistent with previous studies. | The benefits of pharmacotherapy with tiotropium HandiHaler 18 μg for patients with chronic obstructive pulmonary disease (COPD) have been previously demonstrated.,However, few data exist regarding the treatment of moderate disease (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II).,To determine whether tiotropium improves lung function/patient-reported outcomes in patients with GOLD stage II COPD naive to maintenance therapy.,A randomised 24-week double-blind placebo-controlled trial of tiotropium 18 μg once daily (via HandiHaler) was performed in maintenance therapy-naive patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7 and post-bronchodilator FEV1 ⩾50 and <80%.,A total of 457 patients were randomised (238 tiotropium, 219 placebo; mean age 62 years; FEV1 1.93 l (66% predicted)).,Tiotropium was superior to placebo in mean change from baseline in post-dose FEV1 area under the curve from 0 to 3 h (AUC0-3h) at week 24 (primary endpoint): 0.19 vs.,−0.03 l (least-squares mean difference 0.23 l, P<0.001).,FVC AUC0-3h, trough and peak FEV1 and FVC were significantly improved with tiotropium versus placebo (P<0.001).,Compared with placebo, tiotropium provided numerical improvements in physical activity (P=NS).,Physician’s Global Assessment (health status) improved (P=0.045) with less impairment on the Work Productivity and Activity Impairment questionnaire (P=0.043) at week 24.,The incidence of exacerbations, cough, bronchitis and dyspnoea was lower with tiotropium than placebo.,Tiotropium improved lung function and patient-reported outcomes in maintenance therapy-naive patients with GOLD stage II COPD, suggesting benefits in initiating maintenance therapy early. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is a common disease with significant health and economic consequences.,This study assesses the burden of COPD in the general population, and the influence of exacerbations (E-COPD) on disease progression and costs.,This is a secondary data analysis of healthcare administrative databases of the region of Lombardy, in northern Italy.,The study included ≥ 40 year-old patients hospitalized for a severe E-COPD (index event) during 2006.,Patients were classified in relation to the number and type of E-COPD experienced in a three-year pre-index period.,Subjects were followed up until December 31st, 2009, collecting data on healthcare resource use and vital status.,15857 patients were enrolled -9911 males, mean age: 76 years (SD 10).,Over a mean follow-up time of 2.4 years (1.36), 81% of patients had at least one E-COPD with an annual rate of 3.2 exacerbations per person-year and an all-cause mortality of 47%.,A history of exacerbation influenced the occurrence of new E-COPD and mortality after discharge for an E-COPD.,On average, the healthcare system spent 6725€ per year per person (95%CI 6590-6863).,Occurrence and type of exacerbations drove the direct healthcare cost.,Less than one quarter of patients presented claims for pulmonary function tests.,COPD imposes a substantial burden on healthcare systems, mainly attributable to the type and occurrence of E-COPD, or in other words, to the exacerbator phenotypes.,A more tailored approach to the management of COPD patients is required. | The economic burden of chronic obstructive pulmonary disease (COPD) exacerbations is significant, but the impact of other sources on the overall cost of COPD management is largely unknown.,We aimed to estimate overall costs for patients experiencing none, one, or two or more exacerbations per year in the UK.,A retrospective cohort of prevalent COPD patients was identified in the Clinical Practice Research Datalink UK database.,Patients with information recorded for at least 12 months before and after cohort entry date were included (first prevalent COPD diagnosis confirmed by spirometry on/after April 1, 2009).,Patients were categorized as having none, one, or two or more moderate-to-severe COPD exacerbations in the 12 months after cohort entry and further classified by the Global initiative for chronic Obstructive Lung Disease (GOLD) category of airflow obstruction and the Medical Research Council dyspnea scale.,Study outcomes included counts of general practitioner interactions, moderate-severe COPD exacerbations, and non-COPD hospitalizations.,Estimated resource use costs were calculated using National Health Service reference costs for 2010-2011.,The cohort comprised 58,589 patients (mean age 69.5 years, mean dyspnea grade 2.5, females 46.6%, current smokers 33.1%).,The average total annual per patient cost of COPD management, excluding medications, was £2,108 for all patients and £1,523, £2,405, and £3,396 for patients experiencing no, one, or two or more moderate-to-severe exacerbations, respectively.,General practitioner interactions contributed most to these annual costs, accounting for £1,062 (69.7%), £1,313 (54.6%), and £1,592 (46.9%) in patients with no, one, or two or more moderate-to-severe exacerbations, respectively.,Disease management strategies focused on reducing costs in primary care may help reduce total COPD costs significantly. | 1 |
Coronavirus disease 2019 (COVID‐19) caused by infection with severe acute respiratory syndrome coronavirus 2 was first detected in Wuhan, China, in late 2019 and continues to spread worldwide.,Persistent questions remain about the relationship between the severity of COVID‐19 and comorbid diseases, as well as other chronic pulmonary conditions.,In this systematic review and meta‐analysis, we aimed to examine in detail whether the underlying chronic obstructive pulmonary diseases (COPD), asthma and chronic respiratory diseases (CRDs) were associated with an increased risk of more severe COVID‐19.,A comprehensive literature search was performed using five international search engines.,In the initial search, 722 articles were identified.,After eliminating duplicate records and further consideration of eligibility criteria, 53 studies with 658,073 patients were included in the final analysis.,COPD was present in 5.2% (2191/42,373) of patients with severe COVID‐19 and in 1.4% (4203/306,151) of patients with non‐severe COVID‐19 (random‐effects model; OR = 2.58, 95% CI = 1.99-3.34, Z = 7.15, p < 0.001).,CRD was present in 8.6% (3780/44,041) of patients with severe COVID‐19 and in 5.7% (16,057/280,447) of patients with non‐severe COVID‐19 (random‐effects model; OR = 2.14, 95% CI = 1.74-2.64, Z = 7.1, p < 0.001).,Asthma was present in 2.3% (1873/81,319) of patients with severe COVID‐19 and in 2.2% (11,796/538,737) of patients with non‐severe COVID‐19 (random‐effects model; OR = 1.13, 95% CI = 0.79-1.60, Z = 0.66, p = 0.50).,In conclusion, comorbid COPD and CRD were clearly associated with a higher severity of COVID‐19; however, no association between asthma and severe COVID‐19 was identified.,See relatedEditorial | Chronic Obstructive Pulmonary Disease (COPD) is often caused by smoking and other stressors.,This causes oxidative stress, which induces numerous changes on both the transcriptome and proteome of the cell.,We aimed to examine if the endomembrane pathway, including the endoplasmic reticulum (ER), Golgi, and lysosomes, was disrupted in fibroblasts from COPD patients as opposed to healthy ever‐smokers or never‐smokers, and if the response to stress differed.,Different cellular compartments involved in the endomembrane pathway, as well as mRNA expression and apoptosis, were examined before and after the addition of stress in lung fibroblasts from never‐smokers, ever‐smokers, and patients with COPD.,We found that the ER, Golgi, and lysosomes were disorganized in fibroblasts from COPD patients under baseline conditions.,After a time course with ER stress inducing chemicals, changes to the phenotypes of cellular compartments in COPD patient fibroblasts were observed, and the expression of the ER stress‐induced gene ERP72 was upregulated more in the COPD patient's cells compared to ever‐smokers or never‐smokers.,Lastly, a tendency of increased active Caspase‐3 was observed in COPD fibroblasts.,Our results show that COPD patients have phenotypic changes in the lung fibroblasts endomembrane pathway, and respond differently to stress.,Furthermore, these fibroblasts were cultured for several weeks outside the body, but they were not able to regain proper ER structure, indicating that the internal changes to the endomembrane system are permanent in smokers.,This vulnerability to cellular stress might be a cause as to why some smokers develop COPD. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms that significantly impair health-related quality of life.,Despite this, COPD treatment and its management are mainly based on lung function assessments.,There is increasing evidence that conventional lung function measures alone do not correlate well with COPD symptoms and their associated impact on patients’ everyday lives.,Instead, symptoms should be assessed routinely, preferably by using patient-centered questionnaires that provide a more accurate guide to the actual burden of COPD.,Numerous questionnaires have been developed in an attempt to find a simple and reliable tool to use in everyday clinical practice.,In this paper, we review three such patient-reported questionnaires recommended by the latest Global Initiative for Chronic Obstructive Lung Disease guidelines, ie, the modified Medical Research Council questionnaire, the clinical COPD questionnaire, and the COPD Assessment Test, as well as other symptom-specific questionnaires that are currently being developed. | Exacerbations of chronic obstructive pulmonary disease (COPD) are a major burden to patients and to society.,Little is known about the possible role of day-to-day patient-reported outcomes during an exacerbation.,This study aims to describe the day-to-day course of patient-reported health status during exacerbations of COPD and to assess its value in predicting clinical outcomes.,Data from two randomized controlled COPD exacerbation trials (n = 210 and n = 45 patients) were used to describe both the feasibility of daily collection of and the day-to-day course of patient-reported outcomes during outpatient treatment or admission to hospital.,In addition to clinical parameters, the BORG dyspnea score, the Clinical COPD Questionnaire (CCQ), and the St George’s Respiratory Questionnaire were used in Cox regression models to predict treatment failure, time to next exacerbation, and mortality in the hospital study.,All patient-reported outcomes showed a distinct pattern of improvement.,In the multivariate models, absence of improvement in CCQ symptom score and impaired lung function were independent predictors of treatment failure.,Health status and gender predicted time to next exacerbation.,Five-year mortality was predicted by age, forced expiratory flow in one second % predicted, smoking status, and CCQ score.,In outpatient management of exacerbations, health status was found to be less impaired than in hospitalized patients, while the rate and pattern of recovery was remarkably similar.,Daily health status measurements were found to predict treatment failure, which could help decision-making for patients hospitalized due to an exacerbation of COPD. | 1 |
Chronic obstructive pulmonary disease is associated with a high healthcare resource and cost burden.,Healthcare resource utilization was analyzed in patients with symptomatic chronic obstructive pulmonary disease at risk of exacerbations in the FULFIL study.,Patients received either once-daily, single inhaler triple therapy (fluticasone furoate/umeclidinium/vilanterol) 100 µg/62.5 µg/25 µg or twice-daily dual inhaled corticosteroid/long-acting beta agonist therapy (budesonide/formoterol) 400 µg/12 µg.,FULFIL was a phase III, randomized, double-blind, double-dummy, multicenter study.,Unscheduled contacts with healthcare providers were recorded by patients in a daily electronic diary; the costs of healthcare resource utilization were calculated post hoc using UK reference costs.,Over 24 weeks, slightly fewer patients who received fluticasone furoate/umeclidinium/vilanterol (169/911; 18.6%) required contacts with healthcare providers compared with budesonide/formoterol (180/899; 20.0%).,Over 52 weeks in an extension population, fewer patients who received fluticasone furoate/umeclidinium/vilanterol required unscheduled contacts with healthcare providers compared with budesonide/formoterol (25.2% vs.,32.7%).,Non-drug costs per treated patient per year were lower in the fluticasone furoate/umeclidinium/vilanterol group than the budesonide/formoterol group over 24 and 52 weeks (£653.80 vs.,£763.32 and £749.22 vs.,£988.03, respectively), with the total annualized cost over 24 weeks being slightly greater for fluticasone furoate/umeclidinium/vilanterol than budesonide/formoterol (£1,289.35 vs.,£1,267.45).,This healthcare resource utilization evidence suggests that, in a clinical trial setting over a 24- or 52-week timeframe, non-drug costs associated with management of a single inhaler fluticasone furoate/umeclidinium/vilanterol are lower compared with twice-daily budesonide/formoterol.,ClinicalTrials.gov number: NCT02345161.,GSK,The online version of this article (doi:10.1007/s12325-017-0604-x) contains supplementary material, which is available to authorized users. | The coexistence of COPD and asthma is widely recognized but has not been well described.,This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma.,We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study.,119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma.,These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001).,More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001).,Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001).,Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT.,There were no differences in spirometry or CT measurements of emphysema or airway wall thickness.,Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life.,They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history.,ClinicalTrials.gov: NCT00608764 | 1 |
Umeclidinium (UMEC; long-acting muscarinic antagonist) plus vilanterol (VI; long-acting beta2 agonist [LABA]) and the LABA/inhaled corticosteroid fluticasone propionate/salmeterol (FP/SAL) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD).,This 12-week, multicentre, double-blind, parallel-group, double-dummy study compared the efficacy and safety of these treatments in symptomatic patients with moderate-to-severe COPD with no exacerbations in the year prior to enrolment.,Patients (n = 717) were randomised 1:1 to once-daily UMEC/VI 62.5/25 mcg or twice-daily FP/SAL 500/50 mcg.,Endpoints included 0-24 h weighted mean (wm) forced expiratory volume in 1 s (FEV1) (Day 84; primary), trough FEV1 (Day 85; secondary), other lung function endpoints, symptoms, quality of life (QoL) and safety.,Improvements with UMEC/VI versus FP/SAL were 0.080 L (95 % confidence interval: 0.046-0.113; wmFEV1) and 0.090 L (0.055-0.125; trough FEV1) (both p < 0.001).,UMEC/VI statistically significantly improved all other lung function measures versus FP/SAL.,Both treatments demonstrated a clinically meaningful improvement in symptoms (Transition Dyspnoea Index ≥1 unit) and QoL (St George’s Respiratory Questionnaire Total score ≥4 unit decrease from baseline) over 12 weeks.,The incidence of adverse events was 28 % (UMEC/VI) and 29 % (FP/SAL); nasopharyngitis and headache were most common.,Once-daily UMEC/VI 62.5/25 mcg over 12 weeks resulted in significant and sustained improvements in lung function versus twice-daily FP/SAL 500/50 mcg in patients with moderate-to-severe COPD and with no exacerbations in the year prior to enrolment.,NCT01822899 Registration date: March 28, 2013,The online version of this article (doi:10.1186/s12890-015-0092-1) contains supplementary material, which is available to authorized users. | Bronchodilator medications are central to the symptomatic management of chronic obstructive pulmonary disease (COPD).,Metered-dose inhalers (MDIs) are the most commonly used devices to deliver treatment to patients with COPD and asthma, comprising approximately 70% of bronchodilator prescriptions.,Proprietary porous-particle technology permits the formulation of long-acting muscarinic antagonists, long-acting β2-agonists, and a combination of both in hydrofluoroalkane (HFA) MDIs, providing a solution to formulation challenges inherent to the development of HFA MDIs, which have contributed to the development of dry-powder inhalers.,In this randomized, double-blind, 4-period, 6-treatment, placebo- and active-controlled, multicenter, crossover study, 4 ascending single doses of a proprietary glycopyrronium (GP) MDI were evaluated compared with Placebo MDI and open-label tiotropium (TIO) in study patients with COPD.,Thirty-three study patients were enrolled and received single-dose administration of 4 of the 6 treatments (Placebo MDI, TIO 18 μg, or GP MDI at 14.4, 28.8, 57.6, and 115.2 μg ex-actuator) with an interval of 1 to 3 weeks between doses.,The primary efficacy endpoint was peak change in forced expiratory volume in 1 second (FEV1).,All 4 doses of GP MDI showed statistically superior efficacy compared with Placebo MDI for peak FEV1 (differences of 146 to 248 mL; P < .001), with a clear dose ordering of the response.,Statistically significant differences compared with Placebo MDI were noted at almost all doses for the secondary FEV1 parameters (P ≤ .049) except 24-hour trough FEV1 at 28.8 μg.,All doses were safe and well tolerated in this study; the most frequently reported adverse event was dry mouth (0-14.3% across doses; 9.5% for Placebo MDI, and 9.1% for TIO).,This study demonstrated superior bronchodilatory efficacy of GP MDI compared with Placebo MDI at all doses tested, and no serious adverse events were reported.,This study supports the further evaluation of GP MDI in study patients with COPD.,In addition, these findings indicate that the correct dosage of glycopyrronium is no more than 115.2 μg total daily dose, or 57.6 μg twice daily based on comparisons with the active comparator.,This clinical trial was registered on ClinicalTrials.gov, Identifier:NCT00871182. | 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. | 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. | 1 |
Histone deacetylase 2 (HDAC2) is a class I histone deacetylase family member that plays a critical role in suppressing inflammatory gene expression in the airways, lung parenchyma, and alveolar macrophages in patients with chronic obstructive pulmonary disease (COPD).,However, the expression of HDAC2 in peripheral blood monocytes (PBMCs), nuclear factor kappa B (NF-κB) p65, and serum inflammatory cytokine levels in COPD patients, smokers, and non-smokers remains unclear.,PBMCs were obtained from COPD patients, healthy smokers, and healthy nonsmokers.,The HDAC2 and NF-κB p65 expression were quantified by Western Blot.,HDAC activity was assessed by an HDAC fluorometric immunoprecipitation activity assay kit.,Serum tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) levels were measured by ELISA.,HDAC2 expression and HDAC activity were decreased in PBMCs in COPD patients compared with smokers and non-smokers.,Increased NF-κB p65 expression, serum TNF-α and IL-8 levels were observed in COPD patients compared with nonsmokers.,The FEV1%pred was positively correlated with HDAC2 expression and HDAC activity in COPD patients.,Smokers had decreased HDAC activity, increased NF-κB p65 expression and serum TNF-α compared with nonsmokers.,HDAC2 expression was decreased in PBMCs of COPD patients and was correlated with disease severity.,The reduction of HDAC2 expression not only directly enhances the expression of inflammatory genes, but may account for the activation of NF-κB mediated inflammation.,Decreased HDAC2 may serve as a potential biomarker of COPD and predict the decline of lung function. | We sought to assess whether the effects of mesenchymal stromal cells (MSC) on lung inflammation and remodeling in experimental emphysema would differ according to MSC source and administration route.,Emphysema was induced in C57BL/6 mice by intratracheal (IT) administration of porcine pancreatic elastase (0.1 UI) weekly for 1 month.,After the last elastase instillation, saline or MSCs (1×105), isolated from either mouse bone marrow (BM), adipose tissue (AD) or lung tissue (L), were administered intravenously (IV) or IT.,After 1 week, mice were euthanized.,Regardless of administration route, MSCs from each source yielded: 1) decreased mean linear intercept, neutrophil infiltration, and cell apoptosis; 2) increased elastic fiber content; 3) reduced alveolar epithelial and endothelial cell damage; and 4) decreased keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8) and transforming growth factor-β levels in lung tissue.,In contrast with IV, IT MSC administration further reduced alveolar hyperinflation (BM-MSC) and collagen fiber content (BM-MSC and L-MSC).,Intravenous administration of BM- and AD-MSCs reduced the number of M1 macrophages and pulmonary hypertension on echocardiography, while increasing vascular endothelial growth factor.,Only BM-MSCs (IV > IT) increased the number of M2 macrophages.,In conclusion, different MSC sources and administration routes variably reduced elastase-induced lung damage, but IV administration of BM-MSCs resulted in better cardiovascular function and change of the macrophage phenotype from M1 to M2. | 1 |
There has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients.,We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort.,We prospectively collected sputum, serum and plasma samples for analysis of airway bacterial presence and load, and airway and systemic inflammation from 99 stable COPD patients between January 2011 and October 2012.,Health status was measured with St George’s Respiratory Questionnaire and COPD Assessment Test.,Airway inflammation and plasma fibrinogen, but not C-reactive protein, were greater in samples with PPM detection (p < 0.001, p = 0.049 and p = 0.261, respectively).,Increasing total bacterial load was associated with increasing airway (p < 0.01) but not systemic inflammation (p > 0.05).,Samples with high total bacterial loads had significantly higher airway inflammation than both samples without PPM detection and those with lower loads.,Haemophilus influenzae presence was associated with significantly higher levels of airway but not systemic inflammation for all given pathogen loads (p < 0.05), and was significantly greater than with other PPMs.,No association was observed between inflammation and health status (p > 0.05).,Airway and systemic inflammation, as measured by fibrinogen, is greater in stable COPD patients with PPMs detected using the culture-independent qPCR technique.,The airway, but not systemic inflammatory response, appears to have a total pathogen-load threshold and appears attributable to Haemophilus influenzae.,However, discordance between inflammation and health status was observed.,The online version of this article (doi:10.1186/s12931-014-0114-1) contains supplementary material, which is available to authorized users. | Nontypeable Haemophilus influenzae (NTHi) is the most common cause for bacterial exacerbations in chronic obstructive pulmonary disease (COPD).,Recent investigations suggest the participation of the inflammasome in the pathomechanism of airway inflammation.,The inflammasome is a cytosolic protein complex important for early inflammatory responses, by processing Interleukin-1β (IL-1β) to its active form.,Since inflammasome activation has been described for a variety of inflammatory diseases, we investigated whether this pathway plays a role in NTHi infection of the airways.,A murine macrophage cell line (RAW 264.7), human alveolar macrophages and human lung tissue (HLT) were stimulated with viable or non-viable NTHi and/or nigericin, a potassium ionophore.,Secreted cytokines were measured with ELISA and participating proteins detected via Western Blot or immunohistochemistry.,Western Blot analysis of cells and immunohistochemistry of lung tissue detected the inflammasome key components NLRP3 and caspase-1 after stimulation, leading to a significant induction of IL-1β expression (RAW: control at the lower detection limit vs.,NTHi 505±111pg/ml, p<0.01).,Inhibition of caspase-1 in human lung tissue led to a significant reduction of IL-1β and IL-18 levels (IL-1β: NTHi 24 h 17423±3198pg/ml vs.,NTHi+Z-YVAD-FMK 6961±1751pg/ml, p<0.01).,Our data demonstrate the upregulation of the NRLP3-inflammasome during NTHi-induced inflammation in respiratory cells and tissues.,Our findings concerning caspase-1 dependent IL-1β release suggest a role for the inflammasome in respiratory tract infections with NTHi which may be relevant for the pathogenesis of bacterial exacerbations in COPD. | 1 |
Pulmonary rehabilitation (PR) is an effective, key standard treatment for people with COPD.,Nevertheless, low participant uptake, insufficient attendance and high drop-out rates are reported.,Investigation is warranted of the benefits achieved through alternative approaches, such as pulmonary tele-rehabilitation (PTR).,To investigate whether PTR is superior to conventional PR on 6 min walk distance (6MWD) and secondarily on respiratory symptoms, quality of life, physical activity and lower limb muscle function in patients with COPD and FEV1 <50% eligible for routine hospital-based, outpatient PR.,In this single-blinded, multicentre, superiority randomised controlled trial, patients were assigned 1:1 to 10 weeks of groups-based PTR (60 min, three times weekly) or conventional PR (90 min, two times weekly).,Assessments were performed by blinded assessors at baseline, end of intervention and at 22 weeks’ follow-up from baseline.,The primary analysis was based on the intention-to-treat principle.,The primary outcome was change in 6MWD from baseline to 10 weeks; 134 participants (74 females, mean±SD age 68±9 years, FEV1 33%±9% predicted, 6MWD 327±103 metres) were included and randomised.,The analysis showed no between-group differences for changes in 6MWD after intervention (9.2 metres (95% CI: −6.6 to 24.9)) or at 22 weeks’ follow-up (−5.3 metres (95% CI: −28.9 to 18.3)).,More participants completed the PTR intervention (n=57) than conventional PR (n=43) (χ2 test p<0.01).,PTR was not superior to conventional PR on the 6MWD and we found no differences between groups.,As more participants completed PTR, supervised PTR would be relevant to compare with conventional PR in a non-inferiority design.,Trial registration number,ClinicalTrials.gov (NCT02667171), 28 January 2016. | Pulmonary rehabilitation is a cornerstone of care for COPD but uptake of traditional centre-based programmes is poor.,We assessed whether home-based pulmonary rehabilitation, delivered using minimal resources, had equivalent outcomes to centre-based pulmonary rehabilitation.,A randomised controlled equivalence trial with 12 months follow-up.,Participants with stable COPD were randomly assigned to receive 8 weeks of pulmonary rehabilitation by either the standard outpatient centre-based model, or a new home-based model including one home visit and seven once-weekly telephone calls from a physiotherapist.,The primary outcome was change in 6 min walk distance (6MWD).,We enrolled 166 participants to receive centre-based rehabilitation (n=86) or home-based rehabilitation (n=80).,Intention-to-treat analysis confirmed non-inferiority of home-based rehabilitation for 6MWD at end-rehabilitation and the confidence interval (CI) did not rule out superiority (mean difference favouring home group 18.6 m, 95% CI −3.3 to 40.7).,At 12 months the CI did not exclude inferiority (−5.1 m, −29.2 to 18.9).,Between-group differences for dyspnoea-related quality of life did not rule out superiority of home-based rehabilitation at programme completion (1.6 points, −0.3 to 3.5) and groups were equivalent at 12 months (0.05 points, −2.0 to 2.1).,The per-protocol analysis showed the same pattern of findings.,Neither group maintained postrehabilitation gains at 12 months.,This home-based pulmonary rehabilitation model, delivered with minimal resources, produced short-term clinical outcomes that were equivalent to centre-based pulmonary rehabilitation.,Neither model was effective in maintaining gains at 12 months.,Home-based pulmonary rehabilitation could be considered for people with COPD who cannot access centre-based pulmonary rehabilitation.,NCT01423227, clinicaltrials.gov. | 1 |
Chronic obstructive pulmonary disease (COPD) is underdiagnosed in general practice.,Our aim was to implement a population-based approach for the early detection of COPD and to assess its impact on primary care workload and costs, and the influence of socioeconomic status (SES).,An observational study with mixed methods was performed in 10 Dutch general practices of either low or moderate to high SES.,The Respiratory Health Screening Questionnaire was posted during a three-month period to all persons aged 45, 55, and 65 years (one age group per month).,The practices calculated the risk, and patients at high risk of COPD were invited for spirometry at the practice.,The general practitioner used the spirometric results and a consultation to establish a clinical diagnosis.,Qualitative and quantitative data on workload, cost, and barriers were evaluated.,Ten practices returned 293 (35.3%) COPD risk tests for the three age groups.,Participants from low SES practices responded better than those from moderate to high SES practices (40.8% vs.,30.5%).,In practices with low SES 17.9% of the tests indicated high risk compared with 16.1% in practices with moderate to high SES.,Nine patients (23%) were newly diagnosed with COPD.,The healthcare providers' extra workload averaged 18.5 hours during the three months for one standard practice.,The average cost of this survey programme (three age groups in three months) was 荤520 for low SES practices and 荤398 for moderate to high SES practices.,All healthcare providers affirmed that the extra workload in this survey model is acceptable and feasible when finances are compensated.,Early detection of COPD is feasible in daily life primary care.,In moderate to high SES practices the costs of detecting COPD were less than in low SES practices. | Guidelines on COPD diagnosis and management encourage primary care physicians to detect the disease at an early stage and to treat patients according to their condition and needs.,Problems in guideline implementation include difficulties in diagnosis, using spirometry and the disputed role of reversibility testing.,These lead to inaccurate diagnostic registers and inadequacy of administered treatments.,This study represents an audit of COPD diagnosis and management in primary care practices in Devon.,Six hundred and thirty two patients on COPD registers in primary care practices were seen by a visiting Respiratory Specialist Nurse.,Diagnoses were made according to the NICE guidelines.,Reversibility testing was carried out either routinely or based on clinical indication in two sub-samples.,Dyspnoea was assessed.,Data were entered into a novel IT-based software which computed guideline-based treatment recommendations.,Current and recommended treatments were compared.,Five hundred and eighty patients had spirometry.,Diagnoses of COPD were confirmed in 422 patients (73%).,Thirty nine patients were identified as asthma only, 94 had normal spirometry, 23 were restrictive and 2 had a cardiac disorder.,Reversibility testing changed diagnosis of 11% of patients with airflow obstruction, and severity grading in 18%.,Three quarters of patients with COPD had been offered practical help with smoking cessation.,Short and long-acting anticholinergics and long acting beta-2 agonists had been under-prescribed; in 15-18% of patients they were indicated but not received.,Inhaled steroids had been over-prescribed (recommended in 17%; taken by 60%), whereas only 4% of patients with a chronic productive cough were receiving mucolytics.,Pulmonary rehabilitation was not available in some areas and was under-used in other areas.,Diagnostic registers of COPD in primary care contain mistakes leading to inaccurate prevalence estimates and inappropriate treatment decisions.,Use of pre-bronchodilator readings for diagnosis overestimates the prevalence and severity in a significant minority, thus post bronchodilator readings should be used.,Management of stable COPD does often not correspond to guidelines.,The IT system used in this study has the potential to improve diagnosis and management of COPD in primary care. | 1 |
Among patients with chronic obstructive pulmonary disease (COPD), the frequency and severity of past exacerbations potentiates future events.,The impact of current therapies on exacerbation frequency and severity in patients with different exacerbation risks is not well known.,A post hoc analysis of patients at low (≤1 exacerbation [oral steroids/antibiotics requirement] and no COPD-related hospitalization in the year preceding trial entry) or high (≥2 exacerbations [oral steroids/antibiotics requirement] or ≥1 COPD-related hospitalization[s] in the year preceding trial entry) exacerbation risk, from the Prevention of Exacerbations with Tiotropium in Chronic Obstructive Pulmonary Disease (POET-COPD®) database.,Compared with salmeterol, tiotropium significantly increased time to first COPD exacerbation (hazard ratio 0.84; 95% confidence interval [CI] 0.76-0.92; p = 0.0002) and reduced the number of COPD exacerbations (rate ratio 0.90; 95% CI 0.81-0.99; p = 0.0383) in patients at high exacerbation risk.,With treatment, the risk of remaining in the high-risk exacerbator subgroup was statistically lower with tiotropium versus salmeterol (risk ratio [RR] 0.89; 95% CI 0.80-1.00; p = 0.0478).,For low-risk patients, time to first COPD exacerbation and number of COPD exacerbations were numerically lower with tiotropium versus salmeterol.,With treatment, the risk of transitioning from a low to a high exacerbation risk was lower with tiotropium versus salmeterol (RR 0.87; 95% CI 0.71-1.07; p = 0.1968).,This analysis confirms the higher efficacy of tiotropium versus salmeterol in prolonging time to first COPD exacerbation and reducing number of exacerbations in patients both at low and high exacerbation risk.,Boehringer Ingelheim and Pfizer.,Clinical trial registration number: ClinicalTrials.gov NCT00563381.,The online version of this article (doi:10.1007/s12325-015-0216-2) contains supplementary material, which is available to authorized users. | 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 |
Pulmonary rehabilitation (PR) is effective in reducing symptoms and improving health status, and exercise tolerance of patients with chronic obstructive pulmonary disease (COPD).,The coronavirus disease 19 (COVID-19) pandemic has greatly impacted PR programs and their delivery to patients.,Owing to fears of viral transmission and resultant outbreaks of COVID-19, institution-based PR programs have been forced to significantly reduce enrolment or in some cases completely shut down during the pandemic.,As a majority of COPD patients are elderly and have multiple co-morbidities including cardiovascular disease and diabetes, they are notably susceptible to severe complications of COVID-19.,As such, patients have been advised to stay at home and avoid social contact to the maximum extent possible.,This has increased patients’ vulnerability to physical deconditioning, depression, and social isolation.,To address this major gap in care, some traditional hospital or clinic-centered PR programs have converted some or all of their learning contents to home-based telerehabilitation during the pandemic.,There are, however, some significant barriers to this approach that have impeded its implementation in the community.,These include variable access and use of technology (by patients), a lack of standardization of methods and tools for evaluation of the program, and inadequate training and resources for health professionals in optimally delivering telerehabilitation to patients.,There is a pressing need for high-quality studies on these modalities of PR to enable the successful implementation of PR at home and via teleconferencing technologies.,Here, we highlight the importance of telerehabilitation of patients with COPD in the post-COVID world and discuss various strategies for clinical implementation. | Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease.,The aim of this systematic review was to quantify the disease burden of COPD in China and to determine the risk factors of the disease.,The number of studies included in the review was 47 with an average quality assessment score of 7.70 out of 10.,Reported COPD prevalence varied between 1.20% and 8.87% in different provinces/cities across China.,The prevalence rate of COPD was higher among men (7.76%) than women (4.07%).,The disease was more prevalent in rural areas (7.62%) than in urban areas (6.09%).,The diagnostic rate of COPD patients in China varied from 23.61% to 30.00%.,The percentage of COPD patients receiving outpatient treatment was around 50%, while the admission rate ranged between 8.78% and 35.60%.,Tobacco exposure and biomass fuel/solid fuel usage were documented as two important risk factors of COPD.,COPD ranked among the top three leading causes of death in China.,The direct medical cost of COPD ranged from 72 to 3,565 USD per capita per year, accounting for 33.33% to 118.09% of local average annual income.,The most commonly used scales for the assessment of quality of life (QoL) included Saint George Respiratory Questionnaire, Airways Questionnaire 20, SF-36, and their revised versions.,The status of QoL was worse among COPD patients than in non-COPD patients, and COPD patients were at higher risks of depression.,The COPD burden in China was high in terms of economic burden and QoL.,In view of the high smoking rate and considerable concerns related to air pollution and smog in China, countermeasures need to be taken to improve disease prevention and management to reduce disease burdens raised by COPD. | 1 |
Mitochondria contain their own DNA (MtDNA) that is very sensitive to oxidative stress and as a consequence could be damaged in quantity.,Oxidative stress is largely recognized to play a key role in the pathogenesis of asthma and COPD and might have a role in the new intermediate phenotype ACOS (asthma-COPD overlap syndrome).,The aim of this study was to investigate MtDNA alterations, as an expression of mitochondrial dysfunction, in ACOS and to verify whether they might help in the identification of this new phenotype and in its differentiation from asthma and COPD.,Ten (10) ACOS according to Spanish guidelines, 13 ACOS according to GINA guidelines, 13 COPD, 14 asthmatic patients and ten normal subjects were enrolled.,They further underwent a blood, induced sputum and exhaled nitric oxide collection.,Content of MtDNA and nuclear DNA (nDNA) were measured in the blood cells of patients by Real Time PCR.,ACOS patients showed an increase of MtDNA/nDNA ratio.,Dividing ACOS according to guidelines, those from the Spanish showed a higher value of MtDNA/nDNA compared to those from GINA/GOLD (92.69 ± 7.31 vs 80.68 ± 4.16).,Spanish ACOS presented MtDNA/nDNA ratio closer to COPD than asthma.,MtDNA was higher in asthmatic, COPD, GINA and Spanish ACOS patients compared to healthy subjects (73.30 ± 4.47-137.0 ± 19.45-80.68 ± 4.16-92.69 ± 7.31 vs 65.97 ± 20.56).,We found an increase of MtDNA/nDNA ratio in ACOS subjects that led us to conclude that there is presence of mitochondrial dysfunction in this disease, that makes it closer to COPD than to asthma.,Although the MtDNA/nDNA ratio results are a useful marker for differential diagnosis from asthma, COPD and ACOS, further studies are needed to confirm the potentiality of MtDNA/nDNA ratio and to a better characterization of ACOS.,The online version of this article (doi:10.1186/s12890-016-0192-6) contains supplementary material, which is available to authorized users. | Cigarette smoking is the major risk factor for COPD, leading to chronic airway inflammation.,We hypothesized that cigarette smoke induces structural and functional changes of airway epithelial mitochondria, with important implications for lung inflammation and COPD pathogenesis.,We studied changes in mitochondrial morphology and in expression of markers for mitochondrial capacity, damage/biogenesis and fission/fusion in the human bronchial epithelial cell line BEAS-2B upon 6-months from ex-smoking COPD GOLD stage IV patients to age-matched smoking and never-smoking controls.,We observed that long-term CSE exposure induces robust changes in mitochondrial structure, including fragmentation, branching and quantity of cristae.,The majority of these changes were persistent upon CSE depletion.,Furthermore, long-term CSE exposure significantly increased the expression of specific fission/fusion markers (Fis1, Mfn1, Mfn2, Drp1 and Opa1), oxidative phosphorylation (OXPHOS) proteins (Complex II, III and V), and oxidative stress (Mn-SOD) markers.,These changes were accompanied by increased levels of the pro-inflammatory mediators IL-6, IL-8, and IL-1β.,Importantly, COPD primary bronchial epithelial cells (PBECs) displayed similar changes in mitochondrial morphology as observed in long-term CSE-exposure BEAS-2B cells.,Moreover, expression of specific OXPHOS proteins was higher in PBECs from COPD patients than control smokers, as was the expression of mitochondrial stress marker PINK1.,The observed mitochondrial changes in COPD epithelium are potentially the consequence of long-term exposure to cigarette smoke, leading to impaired mitochondrial function and may play a role in the pathogenesis of COPD. | 1 |
Exercise intolerance is a common development in patients with chronic obstructive pulmonary disease (COPD).,There is little data on the use of an isolated program using vibration platform training on functional capacity in these patients, which is an area that deserves investigation.,To investigate the effect of training on a vibrating platform (whole-body vibration [WBV]) on functional performance and quality of life of subjects with COPD.,A randomized controlled crossover pilot study with eleven subjects with COPD (forced expiratory volume in 1 second [FEV1]% predicted =14.63±11.14; forced vital capacity [FVC]% predicted =48.84±15.21; FEV1/FVC =47.39±11.63) underwent a 12-week WBV training program.,Participants were randomized into the intervention group (IG) undergoing three sessions per week for a total of 12 weeks and control group (CG) without intervention.,We evaluated the 6-minute walk test (6MWT), distance walked (DW), duration of the walk (TW), and index of perceived exertion (IPE), quality of life using St George’s Respiratory Questionnaire (SGRQ) and developed a 12-week program of training on a vibrating platform.,The mean age was 62.91±8.82 years old (72.7% male).,The DW increased at the end of training with a difference between groups of 75 m; all domains of the SGRQ improved at the end of training.,The effect size Cohen’s d ranged from small to large for all the measured results.,These preliminary results suggest that WBV may potentially be a safe and feasible way to improve functional capacity in the 6MWT of patients with COPD undergoing a training program on the vibrating platform as well as in all domains of the SGRQ quality of life.,However, further studies with a larger number of patients are needed to establish the long-term effect on functional capacity and quality of life in these patients. | Patients with stable COPD show improvements in exercise capacity and muscular function after the application of whole body vibration.,We aimed to evaluate whether this modality added to conventional physiotherapy in exacerbated hospitalised COPD patients would be safe and would improve exercise capacity and quality of life.,49 hospitalised exacerbated COPD patients were randomized (1:1) to undergo physiotherapy alone or physiotherapy with the addition of whole body vibration.,The primary endpoint was the between-group difference of the 6-minute walking test (day of discharge - day of admission).,Secondary assessments included chair rising test, quality of life, and serum marker analysis.,Whole body vibration did not cause procedure-related adverse events.,Compared to physiotherapy alone, it led to significantly stronger improvements in 6-minute walking test (95.55 ± 76.29 m vs.,6.13 ± 81.65 m; p = 0.007) and St.,Georges Respiratory Questionnaire (-6.43 ± 14.25 vs.,5.59 ± 19.15, p = 0.049).,Whole body vibration increased the expression of the transcription factor peroxisome proliferator receptor gamma coactivator-1-α and serum levels of irisin, while it decreased serum interleukin-8.,Whole body vibration during hospitalised exacerbations did not cause procedure-related adverse events and induced clinically significant benefits regarding exercise capacity and health-related quality of life that were associated with increased serum levels of irisin, a marker of muscle activity.,German Clinical Trials Register DRKS00005979.,Registered 17 March 2014. | 1 |
Cigarette smoking is the major risk factor for COPD, leading to chronic airway inflammation.,We hypothesized that cigarette smoke induces structural and functional changes of airway epithelial mitochondria, with important implications for lung inflammation and COPD pathogenesis.,We studied changes in mitochondrial morphology and in expression of markers for mitochondrial capacity, damage/biogenesis and fission/fusion in the human bronchial epithelial cell line BEAS-2B upon 6-months from ex-smoking COPD GOLD stage IV patients to age-matched smoking and never-smoking controls.,We observed that long-term CSE exposure induces robust changes in mitochondrial structure, including fragmentation, branching and quantity of cristae.,The majority of these changes were persistent upon CSE depletion.,Furthermore, long-term CSE exposure significantly increased the expression of specific fission/fusion markers (Fis1, Mfn1, Mfn2, Drp1 and Opa1), oxidative phosphorylation (OXPHOS) proteins (Complex II, III and V), and oxidative stress (Mn-SOD) markers.,These changes were accompanied by increased levels of the pro-inflammatory mediators IL-6, IL-8, and IL-1β.,Importantly, COPD primary bronchial epithelial cells (PBECs) displayed similar changes in mitochondrial morphology as observed in long-term CSE-exposure BEAS-2B cells.,Moreover, expression of specific OXPHOS proteins was higher in PBECs from COPD patients than control smokers, as was the expression of mitochondrial stress marker PINK1.,The observed mitochondrial changes in COPD epithelium are potentially the consequence of long-term exposure to cigarette smoke, leading to impaired mitochondrial function and may play a role in the pathogenesis of COPD. | Chronic obstructive pulmonary disease (COPD) is characterised by irreversible airflow obstruction, neutrophilic airway inflammation and chronic bacterial colonisation, however the role of the innate immune response in the pathogenesis of COPD remains unclear.,Induced sputum was obtained from adults with COPD (n = 22), and healthy controls (n = 29) and was processed for differential cell counts.,The sputum supernatant was assayed for innate immune mediators using ELISA, whilst sputum gene expression was measured using real-time PCR.,Peripheral blood neutrophils were isolated and their response to lipopolysaccaride (LPS) stimulation was assessed in a subgroup of participants with COPD (n = 13) and healthy controls (n = 21).,Participants with COPD had significantly higher protein levels of interleukin (IL)-8, and neutrophil elastase (NE) and detection of oncostatin M (OSM) compared to healthy controls.,Gene expression for toll-like receptor (TLR) 2, IL-8 and OSM were also significantly higher in COPD participants.,The level of IL-1β, surfactant protein (SP)-A, matrix metalloproteinase (MMP)-9 and TLR4 mRNA was not significantly different between groups.,The level of innate immune response markers were highly associated with the presence of sputum neutrophils, each other and the degree of airflow limitation (FEV1/FVC).,Peripheral blood neutrophils from participants with COPD had an increased response to stimulation by LPS; with a greater fold increase in the production of IL-8 and MMP-9 protein, and gene expression of IL-8, TLR2 and TLR4.,The innate immune response is increased in the airways and circulating neutrophils in COPD, and may be an important mechanism involved in disease pathogenesis. | 1 |
Objectives.,To evaluate the sustaining effects of Tai Chi Qigong (TCQ) in improving the psychosocial health in chronic obstructive pulmonary disease (COPD) patients in the sixth month.,Background.,COPD affects both physical and emotional aspects of life.,Measures to minimize patients' suffering need to be implemented.,Methods.,206 COPD patients were randomly assigned into three groups: TCQ group, exercise group, and control group.,The TCQ group completed a three-month TCQ program, the exercise group practiced breathing and walking exercise, and the control group received usual care.,Results.,Significant group-by-time interactions in quality of life (QOL) using St.,George's respiratory questionnaire (P = 0.002) and the perceived social support from friends using multidimensional scale of perceived social support (P = 0.04) were noted.,Improvements were observed in the TCQ group only.,Conclusions.,TCQ has sustaining effects in improving psychosocial health; it is also a useful and appropriate exercise for COPD patients. | Approximately 210 million people are estimated to have chronic obstructive pulmonary disease [COPD] worldwide.,The burden of disease is known to be high, though less is known about those of a younger age.,The aim of this study was to investigate the wider personal, economic and societal burden of COPD on a cross country working-age cohort.,A cross-country [Brazil, China, Germany, Turkey, US, UK] cross-sectional survey methodology was utilised to answer the research questions. 2426 participants aged 45-67 recruited via a number of recruitment methods specific to each country completed the full survey.,Inclusion criteria were a recalled physician diagnosis of COPD, a smoking history of > 10 pack years and the use of COPD medications in the previous 3 months prior to questioning.,The survey included items from the validated Work Productivity and Activity Impairment [WPAI] scale and the EuroQoL 5 Dimension [EQ-5D] scale.,Disease severity was measured using the 5-point MRC [Medical Research Council] dyspnoea scale as a surrogate measure.,64% had either moderate [n = 1012] or severe [n = 521] COPD, although this varied by country. 75% of the cohort reported at least one comorbid condition.,Quality of life declined with severity of illness [mild, mean EQ-5D score = 0.84; moderate 0.58; severe 0.41].,The annual cost of healthcare utilisation [excluding treatment costs and diagnostic tests] per individual was estimated to be $2,364 [£1,500].,For those remaining in active employment [n: 677]: lost time from work cost the individual an average of $880 [£556] per annum and lifetime losses of $7,365 [£4,661] amounting to $596,000 [£377,000] for the cohort. 447 [~40%] of the working population had retired prematurely because of COPD incurring individual estimated lifetime income losses of $316,000 [£200,000] or a combined total of $141 m [£89.6 m].,As the mean age of retirees was 58.3 and average time since retirement was 4 years, this suggests the average age of retirement is around 54.,This would mean a high societal and economic impact in all study countries, particularly where typical state retirement ages are higher, for example in Brazil, Germany and the UK [65] and the US [65,66,67], compared to Turkey [58 for women, 60 for men] and China [60].,Although generalisation across a broader COPD population is limited due to the varied participant recruitment methods, these data nevertheless suggest that COPD has significant personal, economic and societal burden on working age people.,Further efforts to improve COPD diagnosis and management are required. | 1 |
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) was formed in the late 1990s to spread awareness of chronic obstructive pulmonary disease (COPD) as a major public health problem and facilitate its prevention and treatment.,GOLD has since become internationally recognized for the development of evidence-based strategy documents, most notably the annual GOLD Reports, for COPD diagnosis, management, and prevention.,The GOLD Reports incorporate the latest evidence and expert consensus to guide the management and prevention of COPD on a global level.,Since the first GOLD Report in 2001, profound innovations have taken place regarding inhaler device options, available pharmaceuticals, knowledge regarding effective dosages and potential side effects, and the various combinations of drugs used to relieve symptoms.,Concomitantly, an evolution of expert opinion on how best to apply these innovations to the care of patients with COPD has also taken place, an evolution that is nowhere more detailed or definitive than in the 20 years of annual GOLD Reports.,We summarize key features and trends in inhalation therapy for stable COPD in these Reports. | Chronic respiratory diseases (CRDs) are leading causes of morbidity worldwide.,However, the spatial and temporal trends in prevalence and incidence of CRDs have not been estimated.,Based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017, we analyzed the prevalence and incidence trends of CRDs from 1990 to 2017 according to age, sex, region and disease pattern.,Furthermore, the correlations between the incidence and the World Bank income levels, sociodemographic index (SDI), and human development index (HDI) levels were analyzed to assess the factors affecting incidence.,The total number of CRD cases increased by 39.5% from 1990 to 2017, nevertheless, the age-standardized prevalence rate (ASPR) and age-standardized incidence rate (ASIR) showed decreasing trends.,The ASIRs of CRD, chronic obstructive pulmonary disease (COPD), pneumoconiosis, and asthma decreased, whereas the ASIR of interstitial lung disease and pulmonary sarcoidosis increased during the past 27 years.,Significant differences between males and females in the incidence rates of pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis were observed.,Elderly people especially suffered from CRDs, except for asthma.,For COPD, the ASIR decreased from low-SDI regions to high-SDI regions.,The ASIR of interstitial lung disease and pulmonary sarcoidosis in the high-SDI region was highest and have increased mostly.,The ASIRs for pneumoconiosis and asthma were inversely related to the HDI.,In 2017, CRDs were still the leading causes of morbidity worldwide.,A large proportion of the disease burden was attributed to asthma and COPD.,The incidence rates of all four types of CRDs varied greatly across the world.,Statistically significant correlation was found between the ASIR and SDI/HDI. | 1 |
Remote patient monitoring should reduce mortality rates, improve care, and reduce costs.,We present an overview of the available technologies for the remote monitoring of chronic obstructive pulmonary disease (COPD) patients, together with the most important medical information regarding COPD in a language that is adapted for engineers.,Our aim is to bridge the gap between the technical and medical worlds and to facilitate and motivate future research in the field.,We also present a justification, motivation, and explanation of how to monitor the most important parameters for COPD patients, together with pointers for the challenges that remain.,Additionally, we propose and justify the importance of electrocardiograms (ECGs) and the arterial carbon dioxide partial pressure (PaCO2) as two crucial physiological parameters that have not been used so far to any great extent in the monitoring of COPD patients.,We cover four possibilities for the remote monitoring of COPD patients: continuous monitoring during normal daily activities for the prediction and early detection of exacerbations and life-threatening events, monitoring during the home treatment of mild exacerbations, monitoring oxygen therapy applications, and monitoring exercise.,We also present and discuss the current approaches to decision support at remote locations and list the normal and pathological values/ranges for all the relevant physiological parameters.,The paper concludes with our insights into the future developments and remaining challenges for improvements to continuous remote monitoring systems.,Graphical abstractᅟ,ᅟ | Chronic obstructive pulmonary disease (COPD) is a progressive, chronic respiratory disease with a significant socioeconomic burden.,Exacerbations, the sudden and sustained worsening of symptoms, can lead to hospitalization and reduce quality of life.,Major limitations of previous telemonitoring interventions for COPD include low compliance, lack of consensus on what constitutes an exacerbation, limited numbers of patients, and short monitoring periods.,We developed a telemonitoring system based on a digital health platform that was used to collect data from the 1-year EDGE (Self Management and Support Programme) COPD clinical trial aiming at daily monitoring in a heterogeneous group of patients with moderate to severe COPD.,The objectives of the study were as follows: first, to develop a systematic and reproducible approach to exacerbation identification and to track the progression of patient condition during remote monitoring; and second, to develop a robust algorithm able to predict COPD exacerbation, based on vital signs acquired from a pulse oximeter.,We used data from 110 patients, with a combined monitoring period of more than 35,000 days.,We propose a finite-state machine-based approach for modeling COPD exacerbation to gain a deeper insight into COPD patient condition during home monitoring to take account of the time course of symptoms.,A robust algorithm based on short-period trend analysis and logistic regression using vital signs derived from a pulse oximeter is also developed to predict exacerbations.,On the basis of 27,260 sessions recorded during the clinical trial (average usage of 5.3 times per week for 12 months), there were 361 exacerbation events.,There was considerable variation in the length of exacerbation events, with a mean length of 8.8 days.,The mean value of oxygen saturation was lower, and both the pulse rate and respiratory rate were higher before an impending exacerbation episode, compared with stable periods.,On the basis of the classifier developed in this work, prediction of COPD exacerbation episodes with 60%-80% sensitivity will result in 68%-36% specificity.,All 3 vital signs acquired from a pulse oximeter (pulse rate, oxygen saturation, and respiratory rate) are predictive of COPD exacerbation events, with oxygen saturation being the most predictive, followed by respiratory rate and pulse rate.,Combination of these vital signs with a robust algorithm based on machine learning leads to further improvement in positive predictive accuracy.,International Standard Randomized Controlled Trial Number (ISRCTN): 40367841; http://www.isrctn.com/ISRCTN40367841 (Archived by WebCite at http://www.webcitation.org/6olpMWNpc) | 1 |
The pathophysiology of chronic obstructive pulmonary disease (COPD) includes persistent airflow limitation, altered gas exchange, and enhanced chronic inflammatory response.,According to disease severity in individual patients, exacerbations and comorbidities frequently occur.,The overall nocturnal and daily symptoms have a strong impact on patient quality of life and clinical outcomes.,Bronchodilators, by targeting two important aspects of COPD pathophysiology, ie, bronchoconstriction and lung hyperinflation, are the mainstay of therapy for COPD.,Aclidinium bromide in particular is an anticholinergic molecule, approved for maintenance bronchodilator treatment of stable COPD, that combines high antimuscarinic activity with strong kinetic selectivity for the M3 receptor subtype.,Moreover, the elevated plasma clearance of aclidinium has been related to low systemic bioavailability and low incidence of anticholinergic adverse events, whereas the reduced residence time at M2 receptors provides good cardiovascular safety.,Altogether, these characteristics result in a high safety and tolerability profile.,This review aims to reappraise the contribution of symptoms and of the level of quality of life determinants on COPD severity and to evaluate how therapeutic strategies with aclidinium may positively impact on these specific determinants of disease severity. | This randomized, double-blind, Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).,Methods: Patients received aclidinium 400 μg twice daily (morning and evening), tiotropium 18 μg once daily (morning), or placebo for 6 weeks.,The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose (FEV1 AUC0-24) at week 6.,Secondary and additional endpoints included FEV1 AUC12-24, COPD symptoms (EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [E-RS] total score and additional symptoms questionnaire), and safety.,Results: Overall, 414 patients were randomized and treated (FEV1 1.63 L [55.8% predicted]).,Compared with placebo, FEV1 AUC0-24 and FEV1 AUC12-24 were significantly increased from baseline with aclidinium (Δ = 150 mL and 160 mL, respectively; p < 0.0001) and tiotropium (Δ = 140 mL and 123 mL, respectively; p < 0.0001) at week 6.,Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium (p < 0.0001) than tiotropium (p < 0.05) versus placebo.,Only aclidinium significantly reduced the severity of early-morning cough, wheeze, shortness of breath, and phlegm, and of nighttime symptoms versus placebo (p < 0.05).,Adverse-event (AE) incidence (28%) was similar between treatments.,Few anticholinergic AEs (<1.5%) or serious AEs (<3%) occurred in any group.,Conclusions: Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks.,Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium.,Aclidinium was generally well tolerated. | 1 |
A device called FeelBreathe (FB)® was designed, developed, and patented for inspiratory muscle training.,The main aim was to determine the acute responses on lung ventilation, gas exchange, and heart rate during exercise in patients with chronic obstructive pulmonary disease (COPD) with and without the use of FB.,In this study, a randomized cross-over trial was performed with 18 men diagnosed with COPD (FEV1 between 30% and 70% of its predicted value).,Each participant randomly conducted two trials with 30 min of rest between them with the same protocol on a treadmill for 10 min at a constant rate of 50% of VO2peak.,Each test was performed randomly and in a crossover randomized design in two different conditions: (1) oronasal breathing; and (2) nasal breathing with FB (nasal ventilatory flow restriction device).,It was observed that FB had positive effects on dynamic hyperinflation, breathing pattern, and breathing efficiency, with higher expiratory and inspiratory time.,Despite these differences, blood oxygen saturation percentage, oxygen uptake, and heart rate showed a similar response for both conditions during exercise.,The results suggest that exercise performed with FB improved ventilatory responses compared to the oronasal mode in COPD patients.,This new tool could be used during most daily tasks and exercise programs. | 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. | 1 |
Gastroesophageal reflux disease (GERD) is one of the most common causes of chronic cough and a potential risk factor for exacerbation of chronic obstructive pulmonary disease (COPD).,The aim of this study was to investigate the prevalence and risk factors of GERD in patients with COPD and association between GERD and COPD exacerbation.,Data were collected from the National Health Insurance Database of Korea.,The subjects were 40 years old and older, who had COPD as primary or secondary diagnosis codes and utilized health care resource to receive prescriptions of COPD medication at least twice in 2009.,Univariate logistic regression was performed to understand the relationship between COPD and GERD, and multiple logistic regression analysis was performed with adjustment for several confounding factors.,The prevalence of GERD in COPD patients was 28% (39,987/141,057).,Old age, female gender, medical aid insurance type, hospitalization, and emergency room (ER) visit were associated with GERD.,Most of COPD medications except inhaled muscarinic antagonists were associated with GERD.,The logistic regression analysis showed that the presence of GERD was associated with increased risk of hospitalization (OR 1.54, CI 1.50 to 1.58, p<0.001) and frequent ER visits (OR 1.55, CI 1.48 to 1.62, p<0.001).,The prevalence of GERD in patients with COPD was high.,Old age, female gender, medical aid insurance type, and many COPD medications except inhaled muscarinic antagonists were associated with GERD.,The presence of GERD was associated with COPD exacerbation. | Chronic obstructive lung disease (COPD) exacerbations are a significant cause of morbidity and mortality.,Data regarding factors which causes or prevents exacerbations is very limited.,The aim of this systematic review is to summarize the results from available studies to identify potential risk factors for hospital admission and/or re-admission among patients experiencing COPD exacerbations.,We undertook a systematic review of the literature.,Potential studies were identified by searching the electronic databases: PubMed, EMBASE, BIOSIS, CINAHL, PsycINFO, Cochrane library, reference lists in trial reports, and other relevant articles.,Seventeen articles that met the predefined inclusion criteria were identified.,Heterogeneity of study designs, risk factors and outcomes restrict the result to only a systematic review and precluded a formal meta-analysis.,In this review, three predictive factors: previous hospital admission, dyspnea and oral corticosteroids were all found to be significant risk factors of readmissions and variables including using long term oxygen therapy, having low health status or poor health related quality of life and not having routine physical activity were all associated with an increased risk of both admission and readmission to hospital.,There are a number of potential modifiable factors that are independently associated with a higher risk of COPD exacerbation requiring admission/readmission to the hospital.,Identifying these factors and the development of targeted interventions could potentially reduce the number and severity of such exacerbations. | 1 |
NVA237 (glycopyrronium bromide) is a once-daily long-acting muscarinic antagonist (LAMA) in development for chronic obstructive pulmonary disease (COPD).,The GLycopyrronium bromide in COPD airWays clinical Study 2 (GLOW2) evaluated the efficacy and safety of NVA237 in moderate-to-severe COPD over 52 weeks.,Patients were randomised 2:1:1 to NVA237 50 μg, placebo or open-label tiotropium 18 μg for 52 weeks.,Primary end-point was trough forced expiratory volume in 1 s (FEV1) at 12 weeks.,1,066 patients were randomised, 810 completed the study.,At week 12, trough FEV1 increased significantly by 97 mL with NVA237 (95% CI 64.6-130.2; p<0.001) and 83 mL with tiotropium (95% CI 45.6-121.4; p<0.001).,Compared with placebo, NVA237 produced significant improvements in dyspnoea (Transition Dyspnoea Index at week 26; p=0.002) and health status (St George's Respiratory Questionnaire at week 52; p<0.001).,NVA237 significantly reduced the risk of moderate-to-severe COPD exacerbations by 34% (p=0.001) and the use of rescue medication (p=0.039), versus placebo.,NVA237-placebo and tiotropium-placebo differences were comparable for all outcomes.,Safety profiles were similar across groups.,NVA237 50 μg provided significant improvements in lung function, dyspnoea, health status, exacerbations and rescue medication use, versus placebo, and was comparable to tiotropium.,NVA237 can potentially be an alternative choice of LAMA for COPD patients. | Asthma and chronic obstructive pulmonary disease (COPD) display features of overlap in airway physiology and airway inflammation.,Whether inflammatory phenotypes in airway disease describe similar mediator expression is unknown.,To explore the relationship of airway inflammation and cytokine and chemokine expression in asthma and COPD.,Subjects with asthma and COPD (n = 54 and n = 49) were studied.,Clinical characteristics and sputum were collected at entry into the study.,A 2-step sputum processing method was performed for supernatant and cytospin preparation.,Meso Scale Discovery and Luminex platforms were used to measure cytokines, chemokines and matrix metalloproteinase levels.,Analytes sensitive to dithiothreitol (DTT) that had increased recovery in the 2-step sputum process were IL-1β, 4, 5, 10, 13, IFN-γ, TNFRI, GM-CSF, CCL2, 3, 4, 5, 13 and 17.,There was a differential expression in IL-8, TNFRI and TNFRII between asthma and COPD [mean fold difference (95% CI): IL-8, 2.6 (1.3-5.4), p = 0.01; TNFRI, 2.1 (1.3-5.4), p = 0.03; TNFRII, 2.6 (1.2-5.6), p = 0.02].,In neutrophilic and eosinophilic airway inflammation, TNFα, TNFRI, TNFRII, IL-6, IL-8 and IL-5 could differentiate between these phenotypes.,However, these phenotypes were unrelated to the diagnosis of asthma or COPD.,Recovery of sputum mediators sensitive to DTT can be improved using the described sputum processing technique.,Within airway inflammatory sub-phenotypes there is a differential pattern of mediator expression that is independent of disease.,Whether these inflammatory phenotypes in asthma and COPD confer distinct pathogeneses, therapeutic responses and clinical phenotypes needs to be further evaluated. | 1 |
Chronic obstructive pulmonary disease (COPD) is a debilitating respiratory disease and one of the leading causes of morbidity and mortality worldwide.,It is characterized by persistent respiratory symptoms and airflow limitation due to abnormalities in the lower airway following consistent exposure to noxious particles or gases.,Acute exacerbations of COPD (AECOPD) are characterized by increased cough, purulent sputum production, and dyspnea.,The AECOPD is mostly associated with infection caused by common cold viruses or bacteria, or co-infections.,Chronic and persistent infection by non-typeable Haemophilus influenzae (NTHi), a Gram-negative coccobacillus, contributes to almost half of the infective exacerbations caused by bacteria.,This is supported by reports that NTHi is commonly isolated in the sputum from COPD patients during exacerbations.,Persistent colonization of NTHi in the lower airway requires a plethora of phenotypic adaptation and virulent mechanisms that are developed over time to cope with changing environmental pressures in the airway such as host immuno-inflammatory response.,Chronic inhalation of noxious irritants in COPD causes a changed balance in the lung microbiome, abnormal inflammatory response, and an impaired airway immune system.,These conditions significantly provide an opportunistic platform for NTHi colonization and infection resulting in a “vicious circle.”,Episodes of large inflammation as the consequences of multiple interactions between airway immune cells and NTHi, accumulatively contribute to COPD exacerbations and may result in worsening of the clinical status.,In this review, we discuss in detail the interplay and crosstalk between airway immune residents and NTHi, and their effect in AECOPD for better understanding of NTHi pathogenesis in COPD patients. | Despite the availability of guideline recommendations, diagnostic confusion between COPD and asthma appears common, and often it is very difficult to decide whether the obstruction is caused by asthma or COPD in a patient with airway obstruction.,However, there are well-defined features that help in differentiating asthma from COPD in the presence of fixed airflow obstruction.,Nonetheless, the presentations of asthma and COPD can converge and mimic each other, making it difficult to give these patients a diagnosis of either condition.,The association of asthma and COPD in the same patient has been designated mixed asthma-COPD phenotype or overlap syndrome.,However, since the absence of a clear definition and the inclusion of patients with different characteristics under this umbrella term, it may not facilitate treatment decisions, especially in the absence of clinical trials addressing this heterogeneous population.,We are realizing that neither asthma nor COPD are single diseases, but rather syndromes consisting of several endotypes and phenotypes, consequently comprising a spectrum of diseases that must be recognized and adequately treated with targeted therapy.,Therefore, we must treat patients by personalizing therapy on the basis of those treatable traits present in each subject. | 1 |
The gold standard for the diagnosis of chronic obstructive pulmonary disease (COPD) is spirometry, but there are barriers to its use in primary care.,To externally validate the COPD Diagnostic Questionnaire (CDQ) as a diagnostic tool in patients at increased risk in Australian general practice and to compare its performance with other CDQ validation studies.,Patients were recruited from 36 general practices in Sydney, Australia.,Former or current smokers aged 40-85 years with no prior COPD diagnosis were invited to a case-finding appointment with the practice nurse.,The CDQ was collected and pre- and postbronchodilator spirometry was performed.,Cases for whom complete CDQ data were present and the spirometry met quality standards were analysed.,Of 1,631 patients who attended case-finding recruitment, 1,054 (65%) could be analysed.,Spirometry showed 13% had COPD.,The ability of the CDQ to discriminate between patients with and without COPD was fair, represented by the area under the receiver operating characteristic curve of 0.713.,With a CDQ cut-off point value of 16.5 the sensitivity was 80% and specificity 47% and, at a cut-off point value of 19.5, the sensitivity was 63% and specificity 70%.,The CDQ did not discriminate between patients with and without COPD accurately enough to use as a diagnostic tool in patients at increased risk of COPD in Australian general practice.,Further research is needed on the value of the CDQ as a tool for selecting patients for spirometry. | 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. | Chronic obstructive pulmonary disease (COPD) is one of the most common causes of mortality and a major contributor to morbidity.,Longitudinal clinical practice data yielding information on the characteristics of the disease, its natural course, and management are limited.,To investigate and describe the COPD population from a nationwide perspective during an 11-year period (1999-2009) with a focus on management, co-morbidity, and mortality.,This observational retrospective epidemiological study linked electronic medical records data from patients with COPD in primary care to mandatory Swedish hospital, drug and Cause of Death registry data from 1999 to 2009 (PATHOS).,A total of 21,361 patients with a COPD diagnosis were included (mean age 68.0 years, 53% females).,The proportion of patients diagnosed in primary care increased from 59% in 1999 to 81% in 2009 and the mean age at diagnosis decreased from 73 to 66 years.,The number of exacerbations decreased from 3.0 to 1.3 and COPD-related hospitalisations decreased from 1.02 to 0.20 per patient per year.,Prescriptions of long-acting muscarinic antagonists and fixed combinations of inhaled corticosteroid/long-acting β2-agonist inhalers increased from 0% to 36% and 37%, respectively.,The most common co-morbidities were hypertension, heart failure, ischaemic heart disease, and diabetes.,Overall life expectancy was 8.3±6.8 years shorter in patients with COPD than in the general population, and all-cause mortality was 3.5 times higher.,Management of COPD in Sweden has improved during the 11-year study period.,Despite this, patients with COPD have a substantially reduced life expectancy than the general population. | 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. | Olodaterol is a long-acting β2-agonist with a 24-hour bronchodilator profile.,Two replicate, randomized, double-blind, placebo-controlled, parallel-group, Phase III trials were performed as part of a comprehensive clinical program to investigate the long-term safety and efficacy of olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) receiving usual-care background therapy.,Patients received olodaterol 5 μg or 10 μg or placebo once daily for 48 weeks.,Coprimary end points were forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 3 hours (AUC0-3) response (change from baseline), and trough FEV1 response at 12 weeks.,Secondary end points included additional lung function assessments, use of rescue medications, FEV1 AUC response from 0 to 12 hours, and Patient Global Rating over 48 weeks.,Overall, 624 and 642 patients were evaluated in studies 1222.11 and 1222.12, respectively.,In both studies, olodaterol 5 μg and 10 μg significantly improved the FEV1 AUC0-3 response (P<0.0001) and trough FEV1 (study 1222.11, P<0.0001; study 1222.12, P<0.05, post hoc) at week 12, with an incidence of adverse events comparable with that of placebo.,Secondary end points supported the efficacy of olodaterol.,These studies demonstrate the long-term efficacy and safety of once-daily olodaterol 5 μg and 10 μg in patients with moderate to very severe COPD continuing with usual-care maintenance therapy. | 1 |
Chronic obstructive pulmonary disease (COPD) is an illness characterized by progressive aggravation of airflow limitation, which seriously affects patients’ quality of life, and even life-threatening.,The lung function of COPD patients is chronically and progressively deteriorated.,Among them, the lung function of early COPD patients deteriorates rapidly, and forced expiratory volume in 1 second (FEV1) declines faster than other stages.,If diagnosed early and effectively treated in time, it can greatly affect the prognosis.,As a traditional exercise regimen, Baduanjin can improve lung function, exercise capacity, and quality of life of COPD patients.,However, high-quality evidence-based medical evidence is so far be lacking to confirm the effectiveness of Baduanjin in reducing or preventing mild COPD lung function decline.,This study is a randomized controlled trial, 192 patients with mild COPD were randomly divided into experimental group and control group.,Both of them will receive basic treatment (health education and Tiotropium bromide), the experimental group will receive Baduanjin exercise training, and the control group will be told to maintain the original lifestyle and control the exercise.,The Baduanjin exercise will last for 24 weeks and will be followed up for 72 weeks.,The primary outcome is the change in lung function, including FEV1, FEV1/forced vital capacity (FVC), and FEV1/predicted.,The secondary results included COPD assessment test, 6-minute walk test, St.,George Respiratory Questionnaire, and Dyspnea Scale.,Safety will also serve as assessing during the test.,The results of this trial will provide that traditional Baduanjin exercises can prevent COPD lung function deterioration, and provide a simple, inexpensive, and daily pulmonary rehabilitation measure for the patients with mild COPD. | Baduanjin exercise is a traditional Chinese health Qigong routine created by an ancient physician for health promotion.,Its mild-to-moderate exercise intensity is suitable for individuals with medical conditions.,Recently, a large number of trials have been conducted to investigate the effects of Baduanjin exercise in patients with chronic obstructive pulmonary disease (COPD).,It remains to be determined whether Baduanjin exercise prescription is beneficial for the management of COPD patients.,Thus, we conducted a systematic review to objectively evaluate the existing literature on this topic.,We searched six databases (PubMed, Web of Science, Cochrane Library, Scopus, China National Knowledge Infrastructure, and Wanfang) from inception until early May 2018.,The adapted Physical Therapy Evidence Database (PEDro) scale was used for study quality assessment of all randomized controlled trials (RCTs).,Based on 95% confidence interval (CI), the pooled effect size (Hedge’s g) of exercise capability (6-Minute Walking Test, 6-MWT), lung function parameters (forced expiratory volume in one second, FEV1; forced volume vital capacity, FVC; FEV1/FVC ratio), and quality of life were calculated based on the random-effects model.,Twenty RCTs (n = 1975 COPD patients) were included in this review, with sum scores of the adapted PEDro scale between 5 and 9.,Study results of the meta-analysis indicate that Baduanjin is effective in improving exercise capability (Hedge’s g = 0.69, CI 0.44 to 0.94, p < 0.001, I2 = 66%), FEV1 (Hedge’s g = 0.47, CI 0.22 to 0.73, p < 0.001, I2 = 68.01%), FEV1% (Hedge’s g = 0.38, CI 0.21 to 0.56, p < 0.001, I2 = 54.74%), FVC (Hedge’s g = 0.39, CI 0.22 to 0.56, p < 0.001, I2 = 14.57%), FEV1/FVC (Hedge’s g = 0.5, CI 0.33 to 0.68, p < 0.001, I2 = 53.49%), and the quality of life of COPD patients (Hedge’s g = −0.45, CI −0.77 to −0.12, p < 0.05, I2 = 77.02%), as compared to control groups.,Baduanjin exercise as an adjunctive treatment may potentially improve exercise capability and pulmonary function of COPD patients as well as quality of life.,Baduanjin exercise could be tentatively prescribed for COPD in combination with the conventional rehabilitation program to quicken the process of recovery.,To confirm the positive effects of Baduanjin exercise for COPD patients, future researchers need to consider our suggestions mentioned in this article. | 1 |
To assess the comparative efficacy of short-acting muscarinic antagonists (SAMAs), long-acting muscarinic antagonists (LAMAs), LAMA in combination with long-acting beta-agonists (LABAs; LAMA/LABAs) and inhaled corticosteroids (ICS) in combination with LABA (ICS/LABAs) for the maintenance treatment of COPD.,We systematically reviewed 74 randomized controlled trials (74,832 participants) published up to 15 November 2017, which compared any of the interventions (SAMA [ipratropium], LAMA [aclidinium, glycopyrronium, tiotropium, umeclidinium], LAMA/LABA [aclidinium/formoterol, indacaterol/glycopyrronium, tiotropium/olodaterol, umeclidinium/vilanterol] and ICS/LABA [fluticasone/vilanterol, budesonide/formoterol, salmeterol/fluticasone]) with each other or with placebo.,A random-effects network meta-analysis combining direct and indirect evidence was conducted to examine the change from baseline in trough FEV1, transition dyspnea index, St George’s Respiratory Questionnaire and frequency of adverse events at weeks 12 and 24.,Inconsistency models were not statistically significant for all outcomes.,LAMAs, LAMA/LABAs and ICS/LABAs led to a significantly greater improvement in trough FEV1 compared with placebo and SAMA monotherapy at weeks 12 and 24.,All LAMA/LABAs, except aclidinium/formoterol, were statistically significantly better than LAMA monotherapy and ICS/LABAs in improving trough FEV1.,Among the LAMAs, umeclidinium showed statistically significant improvement in trough FEV1 at week 12 compared to tiotropium and glycopyrronium, but the results were not clinically significant.,LAMA/LABAs had the highest probabilities of being ranked the best agents in FEV1 improvement.,Similar trends were observed for the transition dyspnea index and St George’s Respiratory Questionnaire outcomes.,There were no significant differences in the incidences of adverse events among all treatment options.,LAMA/LABA showed the greatest improvement in trough FEV1 at weeks 12 and 24 compared with the other inhaled drug classes, while SAMA showed the least improvement.,There were no significant differences among the LAMAs and LAMA/LABAs within their respective classes. | Combining bronchodilators with different mechanisms of action may improve efficacy and reduce risk of side effects compared to increasing the dose of a single agent in chronic obstructive pulmonary disease (COPD).,We investigated this by combining two long-acting bronchodilators: once-daily muscarinic antagonist tiotropium and once-daily β2-agonist olodaterol.,Two replicate, double-blind, randomized, 12-week studies (ANHELTO 1 [NCT01694771] and ANHELTO 2 [NCT01696058]) evaluated the efficacy and safety of olodaterol 5 μg once daily (via Respimat®) combined with tiotropium 18 μg once daily (via HandiHaler®) versus tiotropium 18 μg once daily (via HandiHaler®) combined with placebo (via Respimat®) in patients with moderate to severe COPD.,Primary efficacy end points were area under the curve from 0-3 hours of forced expiratory volume in 1 second (FEV1 AUC0-3) and trough FEV1 after 12 weeks (for the individual trials).,A key secondary end point was health status by St George’s Respiratory Questionnaire (SGRQ) total score (combined data set).,Olodaterol + tiotropium resulted in significant improvements over tiotropium + placebo in FEV1 AUC0-3 (treatment differences: 0.117 L [P<0.001], ANHELTO 1; 0.106 L [P<0.001], ANHELTO 2) and trough FEV1 (treatment differences: 0.062 L [P<0.001], ANHELTO 1; 0.040 L [P=0.0029], ANHELTO 2); these were supported by secondary end points.,These effects translated to improvements in SGRQ total scores (treatment difference −1.85; P<0.0001).,The tolerability profile of olodaterol + tiotropium was similar to tiotropium monotherapy.,These studies demonstrated that olodaterol (Respimat®) and tiotropium (HandiHaler®) provided bronchodilatory effects above tiotropium alone in patients with COPD.,In general, both treatments were well tolerated. | 1 |
Blood biomarkers are increasingly used to stratify high risk chronic obstructive pulmonary disease (COPD) patients; however, there are fewer studies that have investigated multiple biomarkers and replicated in multiple large well-characterized cohorts of susceptible current and former smokers.,We used two MSD multiplex panels to measure 9 cytokines and chemokines in 2123 subjects from COPDGene and 1117 subjects from SPIROMICS.,These biomarkers included: interleukin (IL)-2, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, eotaxin/CCL-11, eotaxin-3/CCL-26, and thymus and activation-regulated chemokine (TARC)/CCL-17.,Regression models adjusted for clinical covariates were used to determine which biomarkers were associated with the following COPD phenotypes: airflow obstruction (forced expiratory flow at 1 s (FEV1%) and FEV1/forced vital capacity (FEV1/FVC), chronic bronchitis, COPD exacerbations, and emphysema.,Biomarker-genotype associations were assessed by genome-wide association of single nucleotide polymorphisms (SNPs).,Eotaxin and IL-6 were strongly associated with airflow obstruction and accounted for 3-5% of the measurement variance on top of clinical variables.,IL-6 was associated with progressive airflow obstruction over 5 years and both IL-6 and IL-8 were associated with progressive emphysema over 5 years.,None of the biomarkers were consistently associated with chronic bronchitis or COPD exacerbations.,We identified one novel SNP (rs9302690 SNP) that was associated with CCL17 plasma measurements.,When assessing smoking related pulmonary disease, biomarkers of inflammation such as IL-2, IL-6, IL-8, and eotaxin may add additional modest predictive value on top of clinical variables alone.,COPDGene (ClinicalTrials.gov Identifier: NCT02445183).,Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) (ClinicalTrials.gov Identifier: NCT 01969344).,The online version of this article (10.1186/s12931-017-0662-2) contains supplementary material, which is available to authorized users. | Pulmonary surfactant protein D (SP-D) is considered as a candidate biomarker for the functional integrity of the lung and for disease progression, which can be detected in serum.,The origin of SP-D in serum and how serum concentrations are related to pulmonary concentrations under inflammatory conditions is still unclear.,In a cross-sectional study comprising non-smokers (n = 10), young - (n = 10), elderly smokers (n = 20), and smokers with COPD (n = 20) we simultaneously analysed pulmonary and serum SP-D levels with regard to pulmonary function, exercise, repeatability and its quaternary structure by native gel electrophoresis.,Statistical comparisons were conducted by ANOVA and post-hoc testing for multiple comparisons; repeatability was assessed by Bland-Altman analysis.,In COPD, median (IQR) pulmonary SP-D levels were lower (129(68) ng/ml) compared to smokers (young: 299(190), elderly: 296(158) ng/ml; p < 0.01) and non-smokers (967(708) ng/ml; p < 0.001).,The opposite was observed in serum, with higher concentrations in COPD (140(89) ng/ml) as compared to non-smokers (76(47) ng/ml; p < 0.01).,SP-D levels were reproducible and correlated with the degree of airway obstruction in all smokers.,In addition, smoking lead to disruption of the quaternary structure.,Pulmonary and serum SP-D levels are stable markers influenced by smoking and related to airflow obstruction and disease state.,Smaller subunits of pulmonary SP-D and the rapid increase of serum SP-D levels in COPD due to exercise support the translocation hypothesis and its use as a COPD biomarker.,no interventional trial | 1 |
This study was performed to examine acute exacerbation of COPD (AECOPD) during pulmonary rehabilitation (PR) and the usefulness of multidimensional indices (MIs) to predict AECOPD at enrolment in PR.,A 4-week PR program (PRP) was implemented for 125 consecutive patients with COPD.,At baseline and PRP completion, we recorded the FEV1, 6-minute walk test, peak work rate at cardiopulmonary testing, modified Medical Research Council score, and COPD Assessment Test (CAT) score.,The risk of AECOPDs at baseline was assessed using the body mass index, airway obstruction, dyspnea, Exercise capacity (BODE), dyspnea, obstruction, smoking, exacerbation (DOSE), and score to predict short-term risk of COPD exacerbations (SCOPEX) MIs.,Thirty-two episodes of AECOPD occurred.,The COPD status was worse in patients with than without AECOPD at baseline (lower FEV1, 6-minute walk test, and peak work rate; higher modified Medical Research Council and CAT scores).,The sensitivities of the BODE, DOSE, and SCOPEX MIs to predict the occurrence of AECOPD during PRP were 78.1%, 21.9%, and 84.4%, and the specificities were 73.6%, 87.1%, and 51.6%, respectively.,The BODE and SCOPEX MIs help to predict the exacerbation risk during PR. | The objective of the study is to develop a scoring system for predicting a 90-day re-exacerbation in hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,A total of 176 consecutive hospitalized patients with AECOPD were included.,The sociodemographic characteristics, status before acute exacerbation (AE), presentations of and treatment for the current AE, and the re-exacerbation in 90 days after discharge from hospital were collected.,The re-exacerbation rate in 90 days was 48.9% (86 out of 176).,It was associated with the degree of lung function impairment (Global initiative for chronic Obstructive Lung Disease [GOLD] grades), frequency of AE in the previous year, and parameters of the current AE, including pleural effusion, use of accessory respiratory muscles, inhaled long-acting β-2-agonists, inhaled corticosteroids, controlled oxygen therapy, noninvasive mechanical ventilation, and length of hospital stay, but was not associated with body mass index, modified Medical Research Council scale, or chronic obstructive pulmonary disease assessment test.,A subgroup of ten variables was selected and developed into the re-exacerbation index scoring system (age grades, GOLD grades, AE times in the previous year, pleural effusion, use of accessory respiratory muscles, noninvasive mechanical ventilation, controlled oxygen therapy, inhaled long-acting β-2-agonists and inhaled corticosteroids, and length of hospital stay).,The re-exacerbation index showed good discrimination for re-exacerbation, with a C-statistic of 0.750 (P<0.001).,A comprehensive assessment integrating parameters of stable chronic obstructive pulmonary disease, clinical presentations at exacerbation, and treatment showed a strong predictive capacity for short-term outcome in patients with AECOPD.,Further studies are required to verify these findings. | 1 |
Chronic obstructive pulmonary disease (COPD) has been classically divided into blue bloaters and pink puffers.,The utility of these clinical subtypes is unclear.,However, the broader distinction between airway-predominant and emphysema-predominant COPD may be clinically relevant.,The objective was to define clinical features of emphysema-predominant and non-emphysematous COPD patients.,Current and former smokers from the Genetic Epidemiology of COPD Study (COPDGene) had chest computed tomography (CT) scans with quantitative image analysis.,Emphysema-predominant COPD was defined by low attenuation area at -950 Hounsfield Units (LAA-950) ≥10%.,Non-emphysematous COPD was defined by airflow obstruction with minimal to no emphysema (LAA-950 < 5%).,Out of 4197 COPD subjects, 1687 were classified as emphysema-predominant and 1817 as non-emphysematous; 693 had LAA-950 between 5-10% and were not categorized.,Subjects with emphysema-predominant COPD were older (65.6 vs 60.6 years, p < 0.0001) with more severe COPD based on airflow obstruction (FEV1 44.5 vs 68.4%, p < 0.0001), greater exercise limitation (6-minute walk distance 1138 vs 1331 ft, p < 0.0001) and reduced quality of life (St.,George’s Respiratory Questionnaire score 43 vs 31, p < 0.0001).,Self-reported diabetes was more frequent in non-emphysematous COPD (OR 2.13, p < 0.001), which was also confirmed using a strict definition of diabetes based on medication use.,The association between diabetes and non-emphysematous COPD was replicated in the ECLIPSE study.,Non-emphysematous COPD, defined by airflow obstruction with a paucity of emphysema on chest CT scan, is associated with an increased risk of diabetes.,COPD patients without emphysema may warrant closer monitoring for diabetes, hypertension, and hyperlipidemia and vice versa.,Clinicaltrials.gov identifiers: COPDGene NCT00608764, ECLIPSE NCT00292552.,The online version of this article (doi:10.1186/1471-2466-14-164) contains supplementary material, which is available to authorized users. | Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies.,To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).,Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years.,We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation.,Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs.,0.9 (1.1) per year, p<0.001) compared to non-inflamed ones.,As a descriptive study our results show associations but do not prove causality.,Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.,Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment. | 1 |
Few studies have evaluated the coexistence of bronchiectasis (BE) and chronic obstructive pulmonary disease (COPD) in series of patients diagnosed primarily with BE.,The aim of this study was to analyse the characteristics of patients with BE associated with COPD included in the Spanish Bronchiectasis Historical Registry and compare them to the remaining patients with non-cystic fibrosis BE.,We conducted a multicentre observational study of historical cohorts, analysing the characteristics of 1,790 patients who had been included in the registry between 2002 and 2011.,Of these, 158 (8.8%) were registered as BE related to COPD and were compared to the remaining patients with BE of other aetiologies.,Patients with COPD were mostly male, older, had a poorer respiratory function and more frequent exacerbations.,There were no differences in the proportion of patients with chronic bronchial colonisation or in the isolated microorganisms.,A significantly larger proportion of patients with COPD received treatment with bronchodilators, inhaled steroids and intravenous antibiotics, but there was no difference in the use of long term oral or inhaled antibiotherapy.,During a follow-up period of 3.36 years, the overall proportion of deaths was 13.8%.,When compared to the remaining aetiologies, patients with BE associated with COPD presented the highest mortality rate.,The multivariate analysis showed that the diagnosis of COPD in a patient with BE as a primary diagnosis increased the risk of death by 1.77.,Patients with BE related to COPD have the same microbiological characteristics as patients with BE due to other aetiologies.,They receive treatment with long term oral and inhaled antibiotics aimed at controlling chronic bronchial colonisation, even though the current COPD treatment guidelines do not envisage this type of therapy.,These patients’ mortality is notably higher than that of remaining patients with non-cystic fibrosis BE. | Bronchiectasis revealed by chest computed tomography in COPD patients and its comorbid effect on prognosis have not been addressed by large-sized studies.,Understanding the presence of bronchiectasis in COPD is important for future intervention and preventing disease progression.,Observational studies were identified from electronic literature searches in Cochrane library, PubMed, ScienceDirect databases, American Thoracic Society and European Respiratory Society meeting abstracts.,A systematic review and meta-analysis of studies was performed to summarize the factors associated with bronchiectasis in COPD patients.,Primary outcomes included the risks for exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality.,Odds ratios (ORs) were pooled by random effects models.,Fourteen observational studies were eligible for the study.,Compared with COPD without bronchiectasis, comorbid bronchiectasis in COPD increased the risk of exacerbation (1.97, 95% CI, 1.29-3.00), isolation of a potentially pathogenic microorganism (4.11, 95%CI, 2.16-7.82), severe airway obstruction (1.31, 95% CI, 1.09-1.58) and mortality (1.96, 95% CI, 1.04-3.70).,The presence of bronchiectasis in patients with COPD was associated with exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality. | 1 |
Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020.,No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers.,We systematically searched electronic databases from inception to March 24, 2020.,Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.,Study quality was assessed using a modified version of the Newcastle-Ottawa Scale.,We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI).,In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed.,A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients.,All studies were included in the meta-analysis.,The crude case fatality rate of COVID-19 was 7.4%.,The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively.,COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)].,This was associated with higher mortality (60%).,Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications.,The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers.,Current smokers also had a higher mortality rate of 38.5%.,Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD.,Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate.,Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers. | Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms.,Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections.,Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations.,Exogenous interferon-β reverses these effects.,FP suppression of interferon may occur through inhibition of TLR3- and RIG-I virus-sensing pathways.,Mice deficient in the type I interferon-α/β receptor (IFNAR1−/−) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection.,This study identifies type I interferon as a central regulator of antibacterial immunity and mucus production.,Suppression of interferon by ICS during virus-induced COPD exacerbations likely mediates pneumonia risk and raises suggestion that inhaled interferon-β therapy may protect.,Corticosteroid therapy is frequently used for chronic obstructive pulmonary disease (COPD) but its use is associated with increased risk of pneumonia.,Here the authors show that corticosteroid use impairs innate and adaptive immunity to rhinovirus infection, which is restored by exogenous IFNβ. | 1 |
Chronic obstructive pulmonary disease (COPD) is the integrated form of chronic obstructive bronchitis and pulmonary emphysema, characterized by persistent small airway inflammation and progressive irreversible airflow limitation.,COPD is characterized by acute pulmonary exacerbations and associated accelerated lung function decline, hospitalization, readmission and an increased risk of mortality, leading to huge social-economic burdens.,Recent evidence suggests ~50% of COPD acute exacerbations are connected with a range of respiratory viral infections.,Nevertheless, respiratory viral infections have been linked to the severity and frequency of exacerbations and virus-induced secondary bacterial infections often result in a synergistic decline of lung function and longer hospitalization.,Here, we review current advances in understanding the cellular and molecular mechanisms underlying the pathogenesis of COPD and the increased susceptibility to virus-induced exacerbations and associated immune dysfunction in patients with COPD.,The multiple immune regulators and inflammatory signaling pathways known to be involved in host-virus responses are discussed.,As respiratory viruses primarily target airway epithelial cells, virus-induced inflammatory responses in airway epithelium are of particular focus.,Targeting virus-induced inflammatory pathways in airway epithelial cells such as Toll like receptors (TLRs), interferons, inflammasomes, or direct blockade of virus entry and replication may represent attractive future therapeutic targets with improved efficacy.,Elucidation of the cellular and molecular mechanisms of virus infections in COPD pathogenesis will undoubtedly facilitate the development of these potential novel therapies that may attenuate the relentless progression of this heterogeneous and complex disease and reduce morbidity and mortality. | Exacerbations of COPD are frequent and commonly triggered by respiratory tract infections.,The purpose of our study was to investigate innate immunity in stable COPD patients.,Induced sputum was collected from 51 stable consecutive COPD patients recruited from the COPD Clinic of CHU Liege and 35 healthy subjects.,Expression of interferons beta (IFN-β) and lambda1 (IL-29), IFN-stimulated genes (ISGs) MxA, OAS, and viperin were measured in total sputum cells by reverse transcription quantitative polymerase chain reaction (RT-qPCR).,The presence of Picornaviruses was assessed by RT-PCR, while potential pathogenic microorganisms (PPM) were identified by sputum bacteriology.,Expression of IL-29 was found in 16 of 51 COPD patients (31%) and in nine of 35 healthy subjects (26%), while IFN-β was detected in six of 51 COPD patients (12%) and in two of 35 healthy subjects (6%).,ISGs were easily detectable in both groups.,In the whole group of COPD patients, OAS expression was decreased (P<0.05), while that of viperin was increased (P<0.01) compared to healthy subjects.,No difference was found with respect to MxA.,COPD patients from group D of Global Initiative for Chronic Obstructive Lung Disease (GOLD) had reduced expression of all three ISGs (P<0.01 for MxA, P<0.05 for OAS, and P<0.01 for viperin) as compared to those of group B patients.,Picornaviruses were detected in eight of 51 (16%) COPD patients vs four of 33 (12%) healthy subjects, while PPM were detected in seven of 39 (18%) COPD patients and associated with raised sputum neutrophil counts.,IFN-β expression was raised when either picornavirus or PPM were detected (P=0.06), but no difference was seen regarding IL-29 or ISGs.,ISGs expression was reduced in severe COPD that may favor exacerbation and contribute to disease progress by altering response to infection. | 1 |
Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020.,No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers.,We systematically searched electronic databases from inception to March 24, 2020.,Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.,Study quality was assessed using a modified version of the Newcastle-Ottawa Scale.,We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI).,In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed.,A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients.,All studies were included in the meta-analysis.,The crude case fatality rate of COVID-19 was 7.4%.,The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively.,COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)].,This was associated with higher mortality (60%).,Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications.,The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers.,Current smokers also had a higher mortality rate of 38.5%.,Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD.,Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate.,Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers. | The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) a pandemic [1].,COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,COVID-19 displays symptoms ranging from mild to severe (pneumonia) that can lead to death in some individuals [2-4].,As of 18 April 2020, there have been 2 280 945 cases of COVID-19 worldwide and 156 354 deaths [5].,SARS-CoV-2 uses the angiotensin-converting enzyme II (ACE-2) as the cellular entry receptor [6].,While the virus can infect individuals of any age, to date, most of the severe cases have been described in those >55 years of age and with significant comorbidities, such as COPD [7].,Here, we determined whether patients with COPD have increased expression of ACE-2 in bronchial epithelial cells in the lower respiratory tract.,Smokers and those with COPD have increased airway expression of ACE-2, which is the entry receptor for the COVID-19 virus.,This may explain the increased risk of severe COVID-19 in these subpopulations and highlight the importance of smoking cessation.https://bit.ly/3bC29es | 1 |
Olodaterol is a long-acting β2-agonist with a 24-hour bronchodilator profile.,Two replicate, randomized, double-blind, placebo-controlled, parallel-group, Phase III trials were performed as part of a comprehensive clinical program to investigate the long-term safety and efficacy of olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) receiving usual-care background therapy.,Patients received olodaterol 5 μg or 10 μg or placebo once daily for 48 weeks.,Coprimary end points were forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 3 hours (AUC0-3) response (change from baseline), and trough FEV1 response at 12 weeks.,Secondary end points included additional lung function assessments, use of rescue medications, FEV1 AUC response from 0 to 12 hours, and Patient Global Rating over 48 weeks.,Overall, 624 and 642 patients were evaluated in studies 1222.11 and 1222.12, respectively.,In both studies, olodaterol 5 μg and 10 μg significantly improved the FEV1 AUC0-3 response (P<0.0001) and trough FEV1 (study 1222.11, P<0.0001; study 1222.12, P<0.05, post hoc) at week 12, with an incidence of adverse events comparable with that of placebo.,Secondary end points supported the efficacy of olodaterol.,These studies demonstrate the long-term efficacy and safety of once-daily olodaterol 5 μg and 10 μg in patients with moderate to very severe COPD continuing with usual-care maintenance therapy. | Indacaterol is a once-daily long-acting inhaled β2-agonist indicated for maintenance treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD).,The large inter-patient and inter-study variability in forced expiratory volume in 1 second (FEV1) with bronchodilators makes determination of optimal doses difficult in conventional dose-ranging studies.,We considered alternative methods of analysis.,We utilized a novel modelling approach to provide a robust analysis of the bronchodilatory dose response to indacaterol.,This involved pooled analysis of study-level data to characterize the bronchodilatory dose response, and nonlinear mixed-effects analysis of patient-level data to characterize the impact of baseline covariates.,The study-level analysis pooled summary statistics for each steady-state visit in 11 placebo-controlled studies.,These study-level summaries encompassed data from 7476 patients at indacaterol doses of 18.75-600 μg once daily, and showed that doses of 75 μg and above achieved clinically important improvements in predicted trough FEV1 response.,Indacaterol 75 μg achieved 74% of the maximum effect on trough FEV1, and exceeded the midpoint of the 100-140 mL range that represents the minimal clinically important difference (MCID; ≥120 mL vs placebo), with a 90% probability that the mean improvement vs placebo exceeded the MCID.,Indacaterol 150 μg achieved 85% of the model-predicted maximum effect on trough FEV1 and was numerically superior to all comparators (99.9% probability of exceeding MCID).,Indacaterol 300 μg was the lowest dose that achieved the model-predicted maximum trough response.,The patient-level analysis included data from 1835 patients from two dose-ranging studies of indacaterol 18.75-600 μg once daily.,This analysis provided a characterization of dose response consistent with the study-level analysis, and demonstrated that disease severity, as captured by baseline FEV1, significantly affects the dose response, indicating that patients with more severe COPD require higher doses to achieve optimal bronchodilation.,Comprehensive assessment of the bronchodilatory dose response of indacaterol in COPD patients provided a robust confirmation that 75 μg is the minimum effective dose, and that 150 and 300 μg are expected to provide optimal bronchodilation, particularly in patients with severe disease. | 1 |
To explore the existential significance of living with the risk of being infected with coronavirus in patients with COPD.,Distancing measures aim to break the coronavirus transmission chains.,Physical separation from social networks and social isolation are correlated with anxiety and depression.,People with a chronic obstructive lung disease are particularly vulnerable due to the increased risk of a serious course of illness, so therefore many of them choose self‐isolation to protect themselves from COVID‐19.,A qualitative exploratory study using individual semi‐structured interviews.,From June-September 2020, 13 participants were recruited through advertisements on Facebook as a convenience sample for semi‐structured individual interviews.,The interviews took place through virtual platforms or in physical meetings.,Data were analysed using Ricoeur's phenomenological approach, involving naïve reading, a structural analysis and a critical interpretation strategy.,The study has been reported in line with COREQ guidelines.,Living with the threat of being infected with coronavirus has greatly affected everyday life for patients with COPD.,The nagging fear of coronavirus as a death threat was a dominant feeling, together with anxiety, loneliness and hope.,With self‐isolation, followed concerns of being forgotten and thoughts of the future, balancing between fearing the worst, and hoping the best.,Patients with moderate to severe COPD feel compelled to self‐isolate, as they fear dying from COVID‐19.,The study revealed a need for proactive contact with health professionals to calm the patients' feelings of deprivation, loneliness, hopelessness and anxiety.,Information about the patient's perspective may be used to develop targeted interventions aimed at giving adequate information, supporting hope, implementing digital or virtual solutions to keep in contact and avoid the feeling of being alone and forgotten during a pandemic crisis. | As of 11 July, 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic has infected over 12.7 million people around the world and caused more than 560,000 deaths [1].,Given the devastating impact that COVID-19 can have on the lung, it is natural to fear for patients with underlying COPD.,Estimating their excess risk for contracting COVID-19 and, in particular, its more severe respiratory manifestations has been a challenging exercise in this pandemic for various reasons.,First, the reporting on cases has concentrated on hospitalised and intensive care unit (ICU) patients, rather than on mild, outpatient cases.,This is in part also due to the variability in testing strategies across the world, where some nations with stricter testing requirements and scarce testing resources have focused on testing only those requiring hospitalisation.,COPD patients have increased risk of severe pneumonia and poor outcomes when they develop COVID-19.,This may be related to poor underlying lung reserves or increased expression of ACE-2 receptor in small airways.https://bit.ly/37dSB8l | 1 |
Exercise tests are important to characterise chronic obstructive pulmonary disease patients and predict their prognosis, but are often not available outside of rehabilitation or research settings.,Our aim was to assess the predictive performance of the sit-to-stand and handgrip strength tests.,The prospective cohort study in Dutch and Swiss primary care settings included a broad spectrum of patients (n=409) with Global Initiative for Chronic Obstructive Lung Disease stages II to IV.,To assess the association of the tests with outcomes, we used Cox proportional hazards (mortality), negative binomial (centrally adjudicated exacerbations) and mixed linear regression models (longitudinal health-related quality of life) while adjusting for age, sex and severity of disease.,The sit-to-stand test was strongly (adjusted hazard ratio per five more repetitions of 0.58, 95% CI 0.40-0.85; p=0.004) and the handgrip strength test moderately strongly (0.84, 95% CI 0.72-1.00; p=0.04) associated with mortality.,Both tests were also significantly associated with health-related quality of life but not with exacerbations.,The sit-to-stand test alone was a stronger predictor of 2-year mortality (area under curve 0.78) than body mass index (0.52), forced expiratory volume in 1 s (0.61), dyspnoea (0.63) and handgrip strength (0.62).,The sit-to-stand test may close an important gap in the evaluation of exercise capacity and prognosis of chronic obstructive pulmonary disease patients across practice settings.,The 1-min sit-to-stand test predicts mortality in COPD patients and can easily be implemented across practice settingshttp://ow.ly/mxrPx | Persons with Chronic Obstructive Pulmonary Disease (COPD), performing some level of regular physical activity, have a lower risk of both COPD-related hospital admissions and mortality.,COPD patients of all stages seem to benefit from exercise training programs, thereby improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue.,Physical inactivity, which becomes more severe with increasing age, is a point of concern in healthy older adults.,COPD might worsen this scenario, but it is unclear to what degree.,This literature review aims to present the extent of the impact of COPD on objectively-measured daily physical activity (DPA).,The focus is on the extent of the impact that COPD has on duration, intensity, and counts of DPA, as well as whether the severity of the disease has an additional influence on DPA.,A literature review was performed in the databases PubMed [MEDLINE], Picarta, PEDRO, ISI Web of Knowledge and Google scholar.,After screening, 11 studies were identified as being relevant for comparison between COPD patients and healthy controls with respect to duration, intensity, and counts of DPA.,Four more studies were found to be relevant to address the subject of the influence the severity of the disease may have on DPA.,The average percentage of DPA of COPD patients vs. healthy control subjects for duration was 57%, for intensity 75%, and for activity counts 56%.,Correlations of DPA and severity of the disease were low and/or not significant.,From the results of this review, it appears that patients with COPD have a significantly reduced duration, intensity, and counts of DPA when compared to healthy control subjects.,The intensity of DPA seems to be less affected by COPD than duration and counts.,Judging from the results, it seems that severity of COPD is not strongly correlated with level of DPA.,Future research should focus in more detail on the relation between COPD and duration, intensity, and counts of DPA, as well as the effect of disease severity on DPA, so that these relations become more understandable. | 1 |
QVA149 is a once-daily (o.d.) inhaled dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium for the treatment of COPD.,The QUANTIFY study compared QVA149 with a free-dose bronchodilator combination of tiotropium plus formoterol (TIO+FOR) in improving health-related quality of life (HRQoL) of patients with COPD.,This multicentre, blinded, triple-dummy, parallel-group, non-inferiority study randomised patients aged ≥40 years with moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1 s (FEV1) ≥30% to <80% predicted) to QVA149 110/50 µg o.d. or TIO 18 µg o.d.,+ FOR 12 µg twice daily (1:1) for 26 weeks.,The primary endpoint was to demonstrate non-inferiority in HRQoL assessed using St George's Respiratory Questionnaire-COPD (SGRQ-C).,The prespecified non-inferiority margin was 4 units.,Secondary endpoints included Transition Dyspnoea Index (TDI) score, pre-dose FEV1, forced vital capacity (FVC) and safety.,Of the 934 patients randomised (QVA149=476 and TIO+FOR=458), 87.9% completed the study.,At week 26, non-inferiority was met for SGRQ-C (QVA149 vs TIO+FOR; difference: -0.69 units; 95% CI −2.31 to 0.92; p=0.399).,A significantly higher percentage of patients achieved a clinically relevant ≥1 point improvement in TDI total score with QVA149 (49.6%) versus TIO+FOR (42.4%; p=0.033).,QVA149 significantly increased pre-dose FEV1 (+68 mL, 95% CI 37 mL to 100 mL; p<0.001) and FVC (+74 mL, 95% CI 24 mL to 125 mL; p=0.004) compared with TIO+FOR at week 26.,The incidence of adverse events was comparable between both treatments (QVA149=43.7% and TIO+FOR=42.6%).,QVA149 is non-inferior to TIO+FOR in improving HRQoL, with clinically meaningful and significant improvements in breathlessness and lung function in patients with COPD.,NCT01120717. | Glycopyrronium bromide (NVA237) is an inhaled long-acting muscarinic antagonist in development for treatment of COPD.,This study compared the efficacy and safety of once-daily (OD) and twice-daily (BID) glycopyrronium bromide regimens, using a novel model-based approach, in patients with moderate-to-severe COPD.,Double-blind, randomized, dose-finding trial with an eight-treatment, two-period, balanced incomplete block design.,Patients (smoking history ≥10 pack-years, post-bronchodilator FEV1 ≥30% and <80% predicted, FEV1/FVC <0.7) were randomized to one of 16 independent sequences for 28 days.,Primary endpoint: mean trough FEV1 at Day 28.,385 patients (mean age 61.2 years; mean post-bronchodilator FEV1 53% predicted) were randomized; 88.6% completed.,All OD and BID dosing regimens produced dose-dependent bronchodilation; at Day 28, increases in mean trough FEV1 versus placebo were statistically significant for all regimens, ranging from 51 mL (glycopyrronium bromide 12.5 μg OD) to 160 mL (glycopyrronium bromide 50 μg BID).,Pharmacodynamic steady-state was reached by Day 7.,There was a small separation (≤37 mL) between BID and OD dose-response curves for mean trough FEV1 at steady-state in favour of BID dosing.,Over 24 hours, separation between OD and BID regimens was even smaller (FEV1 AUC0-24h maximum difference for equivalent daily dose regimens: 8 mL).,Dose-response results for FEV1 at 12 hours, FEV1 AUC0-12h and FEV1 AUC0-4h at steady-state showed OD regimens provided greater improvement over placebo than BID regimens for total daily doses of 25 μg, 50 μg and 100 μg, while the reverse was true for OD versus BID regimens from 12-24 hours.,The 12.5 μg BID dose produced a marginally higher improvement in trough FEV1 versus placebo than 50 μg OD, however, the response at 12 hours over placebo was suboptimal (74 mL).,Glycopyrronium bromide was safe and well tolerated at all doses.,Glycopyrronium bromide 50 μg OD provides significant bronchodilation over a 24 hour period, and in terms of FEV1 AUC0-24h is not significantly different than the same total daily dose administered BID.,Importantly, OD dosing may confer better patient adherence.,The results are consistent with previous glycopyrronium bromide studies and support once-daily dosing of glycopyrronium bromide 50 μg in patients with moderate-to-severe COPD.,ClinicalTrials.gov: NCT01119950 | 1 |
Lower risk of COPD has been reported in black and Asian people, raising questions of poorer recognition or reduced susceptibility.,We assessed prevalence and severity of COPD in ethnic groups, controlling for smoking.,A retrospective cross-sectional study using routinely collected primary care data in London.,COPD prevalence, severity (% predicted forced expiratory volume in 1 second [FEV1]), smoking status, and treatment were compared between ethnic groups, adjusting for age, sex, smoking, deprivation, and practice clustering.,Among 358,614 patients in 47 general practices, 47.6% were white, 20% black, and 5% Asian.,Prevalence of COPD was 1.01% overall, 1.55% in whites, 0.58% in blacks, and 0.78% in Asians.,COPD was less likely in blacks (adjusted odds ratio [OR], 0.44; 95% confidence interval [CI] 0.39-0.51) and Asians (0.82; CI, 0.68-0.98) than whites.,Black COPD patients were less likely to be current smokers (OR, 0.56; CI, 0.44-0.71) and more likely to be never-smokers (OR, 4.9; CI, 3.4-7.1).,Treatment of patients with similar disease severity was similar irrespective of ethnic origin, except that long-acting muscarinic antagonists were prescribed less in black COPD patients (OR, 0.53; CI, 0.42-0.68).,Black ethnicity was a predictor of poorer lung function (% predicted FEV1: B coefficient, −7.6; P<0.0001), an effect not seen when ethnic-specific predicted FEV1 values were used.,Black people in London were half as likely as whites to have COPD after adjusting for lower smoking rates in blacks.,It seems likely that the differences observed were due either to ethnic differences in the way cigarettes were smoked or to ethnic differences in susceptibility to COPD. | To determine the prevalence of COPD in Taiwan and to document the disease characteristics and associated risk factors.,We conducted a random cross-sectional national survey of adults older than 40 years in Taiwan.,Respiratory health screening questions identified subjects with diagnosed COPD or whose reported symptoms also fulfilled an epidemiological case definition; these were eligible to complete the survey, which also included indices of symptom severity and disability and questions on comorbidities, medical treatments, smoking habits, and occupations potentially harmful to respiratory health.,Subjects with diagnosed COPD were subdivided by smoking status.,Subjects who fulfilled the case definition of COPD and smoked were designated as “possible COPD”.,Participants who did not fit the case definition of COPD were asked only about their personal circumstances and smoking habits.,Data from these groups were analyzed and compared.,Of the 6,600 participants who completed the survey, 404 (6.1%) fulfilled the epidemiological case definition of COPD: 137 with diagnosed COPD and 267 possible COPD.,The most common comorbidities of COPD were hypertension or cardiovascular diseases (36.1%).,Subjects with definite COPD had significantly higher COPD Assessment Test scores than the possible COPD group (14.6±8.32 vs 12.6±6.49, P=0.01) and significantly more comorbid illnesses (P=0.01).,The main risk factors contributing to health care utilization in each COPD cohort were higher COPD Assessment Test scores (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.04-1.26), higher modified Medical Research Council Breathlessness Scale scores (OR 1.97, 95% CI 1.11-3.51), and having more than one comorbidity (OR 5.19, 95% CI 1.05-25.61).,With estimated prevalence of 6.1% in the general population, COPD in Taiwan has been underdiagnosed.,Symptoms and comorbidities were independent risk factors for health care utilization in subjects with definite or possible COPD.,There is an urgent need to raise awareness of the importance of early evaluation and prompt treatment for subjects with chronic airway symptoms. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with changes in the composition and function of peripheral and respiratory muscles, which can negatively impact quality of life.,Ultrasonography can provide a non-invasive evaluation of the integrity of both peripheral muscles and diaphragm, but its use in patients with COPD is still being investigated.,We aimed at evaluating the relationship between quadriceps size, using ultrasonography and symptoms, lung function and diaphragm contractility in a cohort of patients with COPD.,COPD patients were prospectively recruited and ultrasonography of the dominant quadriceps and of the diaphragm was performed.,Quadriceps size was evaluated using three measurements: 1) cross-sectional area of the rectus femoris (Qcsa), 2) thickness (Qthick) and 3) contractile index (Qci), defined as the ratio of quadriceps thickness/total anterior thigh thickness.,Diaphragm contractility was evaluated using thickening fraction (TFdi).,Clinical characteristics and number of moderate-to-severe exacerbations in the previous year were retrieved from medical files.,Dyspnea (mMRC scale) and disease impact on health status (COPD Assessment Test (CAT)) were measured at inclusion.,Fat-free mass index (FFMI) was assessed using bioelectrical impedance.,Forty patients were recruited (20 males, mean age and FEV1 66±6 years and 49±17%predicted, respectively).,Mean Qcsa, Qthick and Qci were 336±145 mm2, 1.55±0.53 cm and 64±16%, respectively, and mean TFdi was 91±36%.,Qci was significantly correlated with FFMI (rho=0.59, p=0.001), TFdi (rho=0.41, p=0.008), FEV1 (rho=0.43, p=0.001) but not with age (rho=0.18, p=0.28).,Qci was significantly correlated to CAT score (rho=−0.47, p=0.002), even when controlled for FEV1, and was lower in patients with an mMRC score ≥2 (55±15 vs 70±14%, p=0.002).,Qcsa and Qci were significantly lower in patients with frequent exacerbations.,In a multiple linear regression analysis that included age, gender, FFMI, FEV1 and TFdi, only FFMI and TFdi were found to be significantly related to lower Qci values.,In patients with COPD, ultrasound evaluation of the quadriceps contractile index is feasible and related to disease severity, clinical symptoms, exacerbation history and diaphragm contractility.,As such, it may provide a novel tool for the evaluation of the severity and burden of the disease in this population.,Further studies are required to better delineate its potential role as a prognostic marker in this population. | Pulmonary rehabilitation (PR) may improve respiratory symptoms and skeletal muscle strength in patients with COPD.,We aimed to evaluate changes in ultrasound (US) measurements of diaphragmatic mobility and thickness after PR in COPD patients and to test its correlation with PR outcomes.,Twenty-five COPD patients were enrolled and underwent a diaphragm US assessment before and after a 12-week PR program.,We found a correlation between the intraindividual percentage of change in the diaphragmatic length of zone of apposition at functional residual capacity (ΔLzapp%) and the change in 6-minute walking distance (6MWD) after PR (rho=0.49, P=0.02).,ΔLzapp% was significantly higher in patients with improved 6MWD and COPD Assessment Test (CAT) score (mean rank=12.03±2.57 vs 6.88±4.37; P=0.02).,A ΔLzapp% of ≥10% was able to discriminate among patients with improved 6MWD, with a sensitivity of 83% and a specificity of 74%.,The area under the receiver operating characteristic curve for ΔLzapp% was 0.83.,A cutoff value of ≥9% of ΔLzapp% had a positive predictive value in discriminating a reduction in ≥2 points of CAT score after PR, with a sensitivity and a specificity of 80% and 62%, respectively.,Diaphragm US assessment represents a useful prognostic marker of PR outcomes in COPD patients. | 1 |
In addition to clinical comorbidities, psychological and neuropsychological problems are frequent in COPD and may affect pulmonary rehabilitation delivery and outcome.,The aims of the study were to describe a COPD population in a rehabilitative setting as regards the patients depressive symptoms, anxiety, mild cognitive impairment (MCI) and self-reported adherence and to analyze their relationships; to compare the COPD sample MCI scores with normative data; and to investigate which factors might predict adherence to prescribed physical exercise.,This was a multicenter observational cross-sectional study.,Of the 117 eligible stable COPD inpatients, 84 were enrolled according to Global initiative for chronic Obstructive Lung Disease (GOLD) criteria (mainly in Stage III-IV).,The assessment included Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), anxiety, depression and self-reported pharmacological and nonpharmacological adherence.,From the MMSE, 3.6% of patients were found to be impaired, whereas from the MoCA 9.5% had a likely MCI.,Patients referred had mild-severe depression (46.7%), anxiety (40.5%), good pharmacological adherence (80.3%) and difficulties in following prescribed diet (24.1%) and exercise (51.8%); they struggled with disease acceptance (30.9%) and disease limitations acceptance (28.6%).,Most of them received good family (89%) or social (53%) support.,Nonpharmacological adherence, depression, anxiety and MCI showed significant relations with 6-minute walking test, body mass index (BMI) and GOLD.,Depression was related to autonomous long-term oxygen therapy modifications, disease perception, family support and MCI.,In the multivariate logistic regression analysis, higher BMI, higher depression and lower anxiety predicted lower adherence to exercise prescriptions (P=0.0004, odds ratio =0.796, 95% CI =0.701, 0.903; P=0.009, odds ratio =0.356, 95% CI =0.165, 0.770; and P=0.05, odds ratio =2.361, 95% CI =0.995, 5.627 respectively).,In COPD patients, focusing on pharmacological and nonpharmacological adherence enhance the possibility of tailored pulmonary rehabilitation programs. | Clinical care components for people with COPD are recommended in guidelines if high-level evidence exists.,However, there are gaps in their implementation, and factors which act as barriers or facilitators to their uptake are not well described.,The aim of this pilot study was to explore implementation of key high-evidence COPD guideline recommendations in patients admitted to hospital with a disease exacerbation, to inform the development of a larger observational study.,This study recruited consecutive COPD patients admitted to a tertiary hospital.,Patient demographic, disease and admission characteristics were recorded.,Information about implementation of target guideline recommendations (smoking cessation, pulmonary rehabilitation referral, influenza vaccination, medication use and long-term oxygen use if hypoxaemic) was gained from medical records and patient interviews.,Interviews with hospital-based doctors examined their perspectives on recommendation implementation.,Fifteen patients (aged 76(9) years, FEV1%pred 58(15), mean(SD)) and nine doctors participated.,Referral to pulmonary rehabilitation (5/15 patients) was underutilised by comparison with other high-evidence recommendations.,Low awareness of pulmonary rehabilitation was a key barrier for patients and doctors.,Other barriers for patients were access difficulties, low perceived health benefits, and co-morbidities.,Doctors reported they tended to refer patients with severe disease and frequent hospital attendance, a finding supported by the quantitative data.,This study provides justification for a larger observational study to test the hypothesis that pulmonary rehabilitation referral is low in suitable COPD patients, and closer investigation of the reasons for this evidence-practice gap. | 1 |
The benefits of pharmacotherapy with tiotropium HandiHaler 18 μg for patients with chronic obstructive pulmonary disease (COPD) have been previously demonstrated.,However, few data exist regarding the treatment of moderate disease (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II).,To determine whether tiotropium improves lung function/patient-reported outcomes in patients with GOLD stage II COPD naive to maintenance therapy.,A randomised 24-week double-blind placebo-controlled trial of tiotropium 18 μg once daily (via HandiHaler) was performed in maintenance therapy-naive patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7 and post-bronchodilator FEV1 ⩾50 and <80%.,A total of 457 patients were randomised (238 tiotropium, 219 placebo; mean age 62 years; FEV1 1.93 l (66% predicted)).,Tiotropium was superior to placebo in mean change from baseline in post-dose FEV1 area under the curve from 0 to 3 h (AUC0-3h) at week 24 (primary endpoint): 0.19 vs.,−0.03 l (least-squares mean difference 0.23 l, P<0.001).,FVC AUC0-3h, trough and peak FEV1 and FVC were significantly improved with tiotropium versus placebo (P<0.001).,Compared with placebo, tiotropium provided numerical improvements in physical activity (P=NS).,Physician’s Global Assessment (health status) improved (P=0.045) with less impairment on the Work Productivity and Activity Impairment questionnaire (P=0.043) at week 24.,The incidence of exacerbations, cough, bronchitis and dyspnoea was lower with tiotropium than placebo.,Tiotropium improved lung function and patient-reported outcomes in maintenance therapy-naive patients with GOLD stage II COPD, suggesting benefits in initiating maintenance therapy early. | Although chronic obstructive pulmonary disease (COPD) is a major global health burden there is a lack of patient awareness of disease severity, particularly in relation to exacerbations.,We conducted a global patient survey using an innovative, internet-based methodology to gain insight into patient perceptions of COPD and exacerbations in a real-world sample typical of today’s working-age COPD population.,Two thousand patients with COPD (53%), chronic bronchitis (52%) and/or emphysema (22%) from 14 countries completed an online questionnaire developed by the authors.,The Medical Research Council (MRC) breathlessness scale was used to delineate symptom severity.,Over three quarters of patients (77%) had experienced an exacerbation, with 27% of MRC 1 and 2 patients and 52% of MRC 3, 4 and 5 patients requiring hospitalization as a result of an exacerbation.,While a majority of MRC 1 and 2 patients (51%) reported being back to normal within a few days of an exacerbation, 23% of MRC 3, 4 and 5 patients took several weeks to return to normal and 6% never fully recovered.,A high proportion of patients (39%) took a ‘wait and see’ approach to exacerbations.,Despite the high prevalence of exacerbations and their negative impact on quality of life, 73% of MRC 1 and 2 patients and 64% of MRC 3, 4 and 5 patients felt that they had control of their COPD.,However, 77% of all patients were worried about their long-term health, and 38% of MRC 1 and 2 patients and 59% of MRC 3, 4 and 5 patients feared premature death due to COPD.,To reduce the adverse effects of COPD on patients’ quality of life and address their fears for the future, we need better patient education and improved prevention and treatment of exacerbations. | 1 |
While cross-national studies have documented rates of chronic obstructive pulmonary disease (COPD) misdiagnosis among patients in primary care, US studies are scarce.,Studies investigating diagnosis among uninsured patients are lacking.,The purpose of this study is to identify patients who are over diagnosed and thus, mistreated, for COPD in a federally qualified health center.,A descriptive study was conducted for a retrospective cohort from February 2011 to June 2012.,Spirometry was performed by trained personnel following American Thoracic Society recommendations.,Patients were referred for spirometry to confirm previous COPD diagnosis or to assess uncontrolled COPD symptoms.,Airway obstruction was defined as a forced expiratory volume in the first second of expiration (FEV1) to forced vital capacity ratio less than 0.7.,Reversibility was defined as a postbronchodilator increase in FEV1 greater than 200 mL and greater than 12%.,Eighty patients treated for a previous diagnosis of COPD (n = 72) or on anticholinergic inhalers (n = 8) with no COPD diagnosis were evaluated.,The average age was 52.9 years; 71% were uninsured.,Only 17.5% (14/80) of patients reported previous spirometry.,Spirometry revealed that 42.5% had no obstruction, 22.5% had reversible obstruction, and 35% had non-reversible obstruction.,Symptoms and smoking history are insufficient to diagnose COPD.,Prevalence of COPD over diagnosis among uninsured patient populations may be higher than previously reported.,Confirming previous COPD diagnosis with spirometry is essential to avoid unnecessary and potentially harmful treatment. | Objective measurement of airflow obstruction by spirometry is an essential part of the diagnosis of asthma or COPD.,During exacerbations, the feasibility and utility of spirometry to confirm the diagnosis of asthma or chronic obstructive pulmonary disease (COPD) are unclear.,Addressing these gaps in knowledge may help define the need for confirmatory testing in clinical care and quality improvement efforts.,This study was designed to determine the feasibility of spirometry and to determine its utility to confirm the diagnosis in patients hospitalized with a physician diagnosis of asthma or COPD exacerbation.,Multi-center study of four academic healthcare institutions.,Spirometry was performed in 113 adults admitted to general medicine wards with a physician diagnosis of asthma or COPD exacerbation.,Two board-certified pulmonologists evaluated the spirometry tracings to determine the proportion of patients able to produce adequate quality spirometry data.,Findings were interpreted to evaluate the utility of spirometry to confirm the presence of obstructive lung disease, according to the 2005 European Respiratory Society/American Thoracic Society recommendations.,There was an almost perfect agreement for acceptability (κ = 0.92) and reproducibility (κ =0.93) of spirometry tracings.,Three-quarters (73%) of the tests were interpreted by both pulmonologists as being of adequate quality.,Of these adequate quality tests, 22% did not present objective evidence of obstructive lung disease.,Obese patients (BMI ≥30 kg/m2) were more likely to produce spirometry tracings with no evidence of obstructive lung disease, compared to non-obese patients (33% vs. 8%, p = 0.007).,Adequate quality spirometry can be obtained in most hospitalized adults with a physician diagnosis of asthma or COPD exacerbation.,Confirmatory spirometry could be a useful tool to help reduce overdiagnosis of obstructive lung disease, especially among obese patients. | 1 |
Long-term oxygen therapy (LTOT) ≥ 15 h/day improves survival in hypoxemic chronic obstructive pulmonary disease (COPD).,LTOT 24 h/day is often recommended but may pose an unnecessary burden with no clear survival benefit compared with LTOT 15 h/day.,The aim was to test the hypothesis that LTOT 24 h/day decreases all-cause, respiratory, and cardiovascular mortality compared to LTOT 15 h/day in hypoxemic COPD.,This was a prospective, observational, population-based study of COPD patients starting LTOT between October 1, 2005 and June 30, 2009 in Sweden.,Overall and cause-specific mortality was analyzed using Cox and Fine-Gray regression, controlling for age, sex, prescribed oxygen dose, PaO2 (air), PaCO2 (air), Forced Expiratory Volume in one second (FEV1), WHO performance status, body mass index, comorbidity, and oral glucocorticoids.,A total of 2,249 included patients were included with a median follow-up of 1.1 years (interquartile range, 0.6-2.1). 1,129 (50%) patients died and no patient was lost to follow-up.,Higher LTOT duration analyzed as a continuous variable was not associated with any change in mortality rate (hazard ratio [HR] 1.00; (95% confidence interval [CI], 0.98 to 1.02) per 1 h/day increase above 15 h/day.,LTOT exactly 24 h/day was prescribed in 539 (24%) patients and LTOT 15-16 h/day in 1,231 (55%) patients.,Mortality was similar between the groups for all-cause, respiratory and cardiovascular mortality.,In hypoxemic COPD, LTOT 24 h/day was not associated with a survival benefit compared with treatment 15-16 h/day.,A design for a registry-based randomized trial (R-RCT) is proposed. | The prognostic role of the arterial blood gas tension of carbon dioxide (PaCO2) in severe Chronic Obstructive Pulmonary Disease (COPD) remains unknown.,The aim of this study was to estimate the association between PaCO2 and mortality in oxygen-dependent COPD.,National prospective study of patients starting long-term oxygen therapy (LTOT) for COPD in Sweden between October 1, 2005 and June 30, 2009, with all-cause mortality as endpoint.,The association between PaCO2 while breathing air, PaCO2 (air), and mortality was estimated using Cox regression adjusted for age, sex, arterial blood gas tension of oxygen (PaO2), World Health Organization performance status, body mass index, comorbidity, and medications.,Of 2,249 patients included, 1,129 (50%) died during a median 1.1 years (IQR 0.6-2.0 years) of observation.,No patient was lost to follow-up.,PaCO2 (air) independently predicted adjusted mortality (p < 0.001).,The association with mortality was U-shaped, with the lowest mortality at approximately PaCO2 (air) 6.5 kPa and increased mortality at PaCO2 (air) below 5.0 kPa and above 7.0 kPa.,In oxygen-dependent COPD, PaCO2 (air) is an independent prognostic factor with a U-shaped association with mortality. | 1 |
The aim of this study was to determine if an interactive web-based pulmonary rehabilitation (PR) programme is a feasible alternative to conventional PR.,Randomised controlled feasibility trial.,Participants with a diagnosis of chronic obstructive pulmonary disease were recruited from PR assessments, primary care and community rehabilitation programmes.,Patients randomised to conventional rehabilitation started the programme according to the standard care at their referred site on the next available date.,103 patients were recruited to the study and randomised: 52 to conventional rehabilitation (mean (±SD) age 66 (±8) years, Medical Research Council (MRC) 3 (IQR2-4)); 51 to the web arm (mean (±SD) age 66 (±10) years, MRC 3 (IQR2-4)).,Participants had to be willing to participate in either arm of the trial, have internet access and be web literate.,Patients randomised to the web-based programme worked through the website, exercising and recording their progress as well as reading educational material.,Conventional PR consisted of twice weekly, 2 hourly sessions (an hour for exercise training and an hour for education).,Recruitment rates, eligibility, patient preference and dropout and completion rates for both programmes were collected.,Standard outcomes for a PR assessment including measures of exercise capacity and quality of life questionnaires were also evaluated.,A statistically significant improvement (p≤0.01) was observed within each group in the endurance shuttle walk test (WEB: mean change 189±211.1; PR classes: mean change 184.5±247.4 s) and Chronic Respiratory disease Questionnaire-Dyspnoea (CRQ-D; WEB: mean change 0.7±1.2; PR classes: mean change 0.8±1.0).,However, there were no significant differences between the groups in any outcome.,Dropout rates were higher in the web-based programme (57% vs 23%).,An interactive web-based PR programme is feasible and acceptable when compared with conventional PR.,Future trials maybe around choice-based PR programmes for select patients enabling stratification of patient care.,ISRCTN03142263; Results. | Introduction of telehealth into the healthcare setting has been recognised as a service that might be experienced as disruptive.,This paper explores how this disruption is experienced.,In a longitudinal qualitative study, we conducted focus group discussions prior to and semi structured interviews post introduction of a telehealth service in Nottingham, U.K. with the community matrons, congestive heart failure nurses, chronic obstructive pulmonary disease nurses and community support workers that would be involved in order to elicit their preconceptions and reactions to the implementation.,Users experienced disruption due to the implementation of telehealth as threatening.,Three main factors add to the experience of threat and affect the decision to use the technology: change in clinical routines and increased workload; change in interactions with patients and fundamentals of face-to-face nursing work; and change in skills required with marginalisation of clinical expertise.,Since the introduction of telehealth can be experienced as threatening, managers and service providers should aim at minimising the disruption caused by taking the above factors on board.,This can be achieved by employing simple yet effective measures such as: providing timely, appropriate and context specific training; provision of adequate technical support; and procedures that allow a balance between the use of telehealth and personal visit by nurses delivering care to their patients. | 1 |
The immunopathology of chronic obstructive pulmonary disease (COPD) is based on the innate and adaptive inflammatory immune responses to the chronic inhalation of cigarette smoking.,In the last quarter of the century, the analysis of specimens obtained from the lower airways of COPD patients compared with those from a control group of age-matched smokers with normal lung function has provided novel insights on the potential pathogenetic role of the different cells of the innate and acquired immune responses and their pro/anti-inflammatory mediators and intracellular signalling pathways, contributing to a better knowledge of the immunopathology of COPD both during its stable phase and during its exacerbations.,This also has provided a scientific rationale for new drugs discovery and targeting to the lower airways.,This review summarises and discusses the immunopathology of COPD patients, of different severity, compared with control smokers with normal lung function. | Chronic obstructive pulmonary disease (COPD) is characterized by progressive worsening of airflow limitation associated with abnormally inflamed airways in older smokers.,Despite correlative evidence for a role for tumor necrosis factor-alpha in the pathogenesis of COPD, the anti-tumor necrosis factor-alpha, infliximab did not show clinical efficacy in a double-blind, placebo-controlled, phase II clinical trial.,This study sought to evaluate the systemic inflammatory profile associated with COPD and to assess the impact of tumor necrosis factor neutralization on systemic inflammation.,Serum samples (n = 234) from the phase II trial were collected at baseline and after 24 weeks of placebo or infliximab.,Additionally, baseline serum samples were obtained from an independent COPD cohort (n = 160) and 2 healthy control cohorts (n = 50; n = 109).,Serum concentrations of a broad panel of inflammation-associated analytes were measured using a 92-analyte multiplex assay.,Twenty-five proteins were significantly elevated and 2 were decreased in COPD, including highly elevated CD40 ligand, brain-derived neurotrophic factor, epidermal growth factor, acute-phase proteins, and neutrophil-associated proteins.,This profile was largely independent of smoking status, age, and clinical phenotype.,The majority of these associations of serum analytes with COPD are novel findings.,Increased serum creatine kinase-muscle/brain and myoglobin correlated modestly with decreased forced expiratory volume at 1 second, suggesting cardiac involvement.,Infliximab did not affect this systemic inflammatory profile.,A robust systemic inflammatory profile was associated with COPD.,This profile was generally independent of disease severity.,Because anti-tumor necrosis factor-alpha did not influence systemic inflammation, how to control the underlying pathology beyond symptom suppression remains unclear.,ClinicalTrials.gov, No.: NCT00056264. | 1 |
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