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Acute COPD exacerbations account for much of the rising disability and costs associated with COPD, but data on predictive risk factors are limited.,The goal of the current study was to develop a robust, clinically based model to predict frequent exacerbation risk.,Patients identified from the Optimum Patient Care Research Database (OPCRD) with a diagnostic code for COPD and a forced expiratory volume in 1 second/forced vital capacity ratio <0.7 were included in this historical follow-up study if they were ≥40 years old and had data encompassing the year before (predictor year) and year after (outcome year) study index date.,The data set contained potential risk factors including demographic, clinical, and comorbid variables.,Following univariable analysis, predictors of two or more exacerbations were fed into a stepwise multivariable logistic regression.,Sensitivity analyses were conducted for subpopulations of patients without any asthma diagnosis ever and those with questionnaire data on symptoms and smoking pack-years.,The full predictive model was validated against 1 year of prospective OPCRD data.,The full data set contained 16,565 patients (53% male, median age 70 years), including 9,393 patients without any recorded asthma and 3,713 patients with questionnaire data.,The full model retained eleven variables that significantly predicted two or more exacerbations, of which the number of exacerbations in the preceding year had the strongest association; others included height, age, forced expiratory volume in 1 second, and several comorbid conditions.,Significant predictors not previously identified included eosinophilia and COPD Assessment Test score.,The predictive ability of the full model (C statistic 0.751) changed little when applied to the validation data set (n=2,713; C statistic 0.735).,Results of the sensitivity analyses supported the main findings.,Patients at risk of exacerbation can be identified from routinely available, computerized primary care data.,Further study is needed to validate the model in other patient populations. | 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 |
Most pulmonary rehabilitation programmes currently involve 2-3 sessions per week as recommended by international guidelines.,We aimed to investigate whether relevant improvements in physical capabilities and quality of life in patients with chronic obstructive pulmonary disease (COPD) could be achieved by a long-term, low intensity, once weekly rehabilitation programme using limited resources.,100 patients with moderate to severe COPD were randomised to a continuous outpatient interdisciplinary rehabilitation programme or standard care.,Physiotherapy-led supervised outpatient training sessions were performed once weekly in addition to educational elements.,Outcome measures at baseline and after 26 weeks were 6-minute-walk-test, cycle ergometry, and health-related quality of life.,37 patients in the training group and 44 patients in the control group completed the study.,After 26 weeks there were clinically significant differences between the groups for 6 minute-walk-distance (+59 m, 95% CI 28-89 m), maximum work load (+7.4 Watt, 95% CI 0.5-13.4 Watt) and St.,George’s Respiratory Questionnaire score (−5 points, 95% CI −10 to −1 points).,Total staff costs of the programme per participant were ≤ €625.,Clinically meaningful improvements in physical capabilities and health-related quality of life may be achieved using long-term pulmonary rehabilitation programmes of lower intensity than currently recommended.,Trial registration: clinicaltrials.gov NCT01195402. | Asthma and chronic obstructive pulmonary disease (COPD) are characterized by different patterns of airway remodeling, which all include an increased mass of bronchial smooth muscle (BSM).,A remaining major question concerns the mechanisms underlying such a remodeling of BSM.,Because mitochondria play a major role in both cell proliferation and apoptosis, we hypothesized that mitochondrial activation in BSM could play a role in this remodeling.,We describe that both the mitochondrial mass and oxygen consumption were higher in the BSM from asthmatic subjects than in that from both COPD and controls.,This feature, which is specific to asthma, was related to an enhanced mitochondrial biogenesis through up-regulation of peroxisome proliferator-activated receptor γ coactivator (PGC)-1α, nuclear respiratory factor-1, and mitochondrial transcription factor A.,The priming event of such activation was an alteration in BSM calcium homeostasis.,BSM cell apoptosis was not different in the three groups of subjects.,Asthmatic BSM was, however, characterized by increased cell growth and proliferation.,Both characteristics were completely abrogated in mitochondria-deficient asthmatic BSM cells.,Conversely, in both COPD and control BSM cells, induction of mitochondrial biogenesis reproduced these characteristics.,Thus, BSM in asthmatic patients is characterized by an altered calcium homeostasis that increases mitochondrial biogenesis, which, in turn, enhances cell proliferation, leading to airway remodeling. | 1 |
Metabolic adaptation in immune cells is necessary to modulate immune cell function as it is intricately coupled with intracellular metabolism.,We aimed to characterize the metabolic state of human peripheral blood mononuclear cells (PBMCs) after long-term exposure to tobacco smoke in smokers with preserved lung function and COPD subjects.,PBMCs were isolated from healthy non-smokers (HNS), healthy smokers (HS) and COPD subjects, cultured and the mitochondrial respiration while utilizing glucose (glycolysis), fatty acids (β-oxidation) or pyruvate (direct Krebs’ cycle substrate) was measured using the XFp Extracellular Flux Analyzer.,Plasma levels of inflammatory cytokines IFN-γ, IL-17, TNF-α, IL-5, IL-9 and IFN-α were measured using flow cytometry.,RAW264.7 cells were exposed to cigarette smoke condensate (CSC) for 1 h and its effect on cell viability, cellular metabolism and phagocytosis ability were also studied.,Patient’s data was analyzed using the Mann Whitney U test, whereas Student’s t test was performed to analyze the in-vitro data.,PBMCs from COPD subjects showed a significant decrease in extracellular acidification rate (ECAR) while utilizing glucose as compared to HNS (151.9 Vs 215%).,Mitochondrial oxygen consumption rate (OCR) on palmitate or pyruvate was also found to be significantly lower in COPD subjects as compared to HS and a strong positive correlation between palmitate OCR in PBMCs and FEV1 (r = 0.74, p < 0.05) and FVC (r = 0.79, p < 0.05) values in HS was observed.,The metabolic shift towards fatty acid metabolism in healthy smokers promoted an inflammatory cytokine response with a greater increase in the levels of IL-5, IL-9 and IFN-α as compared to IFN-γ, IL-17 and TNF-α.,In-vitro experiments with RAW 264.7 cells showed similar metabolic alterations and a reduced ability to phagocytose Streptococcus pneumonia and Haemophilus influenza after cigarette smoke exposure in the presence of glucose or palmitate.,These findings indicate a metabolic basis for the inflammatory response in COPD and could suggest a new therapeutic target for controlling the immune response and delaying the onset of disease.,This observational study was retrospectively registered in the Clinical Trails Registry - India (ICMR - NIMS) on 19th January 2018 with the registration number CTRI/2018/01/011441.,The online version of this article (10.1186/s12931-019-1139-2) contains supplementary material, which is available to authorized users. | COPD is underdiagnosed and its early assessment is problematic.,It has been suggested that symptomatic smokers with normal FEV1/FVC (Stage 0 COPD, GOLD criteria) can develop COPD in the future.,Potential early biomarkers in COPD include the matrix metallo-proteinases (MMPs).,It is not yet known, whether alterations in MMP expression are associated with smoking alone or with the risk of developing COPD.,In this cross-sectional study MMP-8, MMP-9 and MMP-12 were determined from induced sputum and plasma by ELISA, immunocytochemistry, zymography, and/or Western blot in non-smokers (n = 32), smokers with symptoms (Stage 0, GOLD criteria) (n = 23) or without symptoms (n = 23).,Only MMP-8 differentiated Stage 0 COPD from non-symptomatic smokers (p = 0.02).,MMP-9 levels were significantly elevated in the induced sputum of non-symptomatic smokers and Stage 0 COPD (p = 0.01, p < 0.001) compared to non-smokers, but did not differ between the two subgroups of smokers.,MMP-12 was higher only at Stage 0 compared to non-smokers (p = 0.04).,MMP-8, MMP-9 and MMP-12 immunoreactivity was localized in macrophages and neutrophils, especially in smokers.,MMP-8 levels correlated significantly with the small airway flow parameters (MEF50, MEF25) (p = 0.005 and p = 0.0004) and markers of neutrophil activation (myeloperoxidase, lactoferrin).,In conclusion MMP-8 may differentiate Stage 0 from healthy smokers. | 1 |
Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with high morbidity and mortality.,The most important pathophysiological change of COPD is airway obstruction.,Airway obstruction can cause airflow restriction and obstructive ventilation dysfunction.,Currently, many studies have shown that there is EMT phenomenon in the process of airway remodeling of COPD.,Cullin4A (CUL4A) is an E3 ubiquitin ligase that interacts with other factors to form the E3 complex.,Studies have shown that CLU4A is associated with EMT in non-small cell lung cancer and other cancers.,However, its relationship with EMT in COPD has not been reported systematically.,In this study, we detected the expression of CUL4A in lung epithelium of COPD patients.,In addition, the regulatory effect and mechanism of CUL4A on EMT in COPD were clarified in small airway epithelial cells.,The expression of CUL4A was assessed by immunohistochemistry in lung epithelium specimens from smokers, non-smokers and patients with chronic obstructive pulmonary disease.,The role of CUL4A on cigarette smoke extract (CSE)-induced epithelial-mesenchymal transition (EMT) in human small airway epithelial cells (HSAEpiCs) was assessed by silencing or overexpression CUL4A in vitro.,Cigarette smoke is recognized as a high-risk factor in the induction of COPD, and its damage to the airway involves airway damage, airway inflammation and airway remodeling.,The results shown that CUL4A expression in small airway epithelium was significantly increased in patients with COPD.,We also observed a significant negative association between CUL4A and FEV1%, a useful clinical marker for the diagnosis and evaluation of COPD severity, in small airway epithelial cells.,In vitro, CSE-induced EMT is associated with high expression of CUL4A, and targeted silencing of CUL4A with shRNA inhibits CSE-induced EMT in human small airway epithelial cells.,Our results showed that CUL4A was overexpressed in lung epithelium of COPD patients, and CUL4A could regulate EMT of human small airway epithelium, which revealed a new mechanism of remodeling of small airway epithelium of COPD patients.,The online version of this article (10.1186/s12931-019-1048-4) contains supplementary material, which is available to authorized users. | Chronic airway inflammation and airway remodeling are the major pathophysiological characteristics of chronic obstructive pulmonary disease (COPD).,Resveratrol and genistein have been previously demonstrated to have anti-inflammatory and antioxidative properties.,The present study aimed to measure the inhibitory effects of resveratrol and genistein on tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMP)-9 concentration in patients with COPD.,Lymphocytes were isolated from the blood of 34 patients with COPD and 30 healthy subjects, then randomly divided into the following four treatment groups: Control, dexamethasone (0.5 µmol/l), resveratrol (12.5 µmol/l) and genistein (25 µmol/l) groups.,After 1 h of treatment, 100 µl lymphocytes were collected for nuclear factor (NF)-κB immunocytochemical staining.,After 48 h treatment, the supernatant of the lymphocytes was collected for analysis of TNF-α and MMP-9 concentration levels.,The percentage of lymphocytes with positive nuclear NF-κB expression was analyzed by immunocytochemical staining.,The concentration levels of TNF-α and MMP-9 were measured using radioimmunoassay and enzyme-linked immunosorbent assay, respectively.,The present study demonstrated that the percentage of NF-κB-positive cells, and the levels of TNF-α and MMP-9 in lymphocytes from patients with COPD patients were significantly higher compared with healthy subjects.,Additionally, there were positive correlations between the percentage of NF-κB-positive cells, and the concentration levels of TNF-α and MMP-9 in patients with COPD.,All three factors were significantly reduced in lymphocytes treated with resveratrol and genistein, and the inhibitory effects of resveratrol on NF-κB, TNF-α and MMP-9 were more potent than the effects of genistein.,In conclusion, resveratrol and genistein may inhibit the NF-κB, TNF-α and MMP-9-associated pathways in patients with COPD.,It is suggested that resveratrol and genistein may be potential drugs candidates for use in the treatment of COPD. | 1 |
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. | 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. | 1 |
Chronic obstructive pulmonary disease (COPD) affects over 250 million people globally, carrying a notable economic burden.,This systematic literature review aimed to highlight the economic burden associated with moderate-to-very severe COPD and to investigate key drivers of healthcare resource utilization (HRU), direct costs and indirect costs for this patient population.,Relevant publications published between January 1, 2006 and November 14, 2016 were captured from the Embase, MEDLINE and MEDLINE In-Process databases.,Supplemental searches from relevant 2015-2016 conferences were also performed.,Titles and abstracts were reviewed by two independent researchers against pre-defined inclusion and exclusion criteria.,Studies were grouped by the type of economic outcome presented (HRU or costs).,Where possible, data were also grouped according to COPD severity and/or patient exacerbation history.,In total, 73 primary publications were included in this review: 66 reported HRU, 22 reported direct costs and one reported indirect costs.,Most of the studies (94%) reported on data from either Europe or North America.,Trends were noted across multiple studies for higher direct costs (including mean costs per patient per year and mean costs per exacerbation) being associated with increasingly severe COPD and/or a history of more frequent or severe exacerbations.,Similar trends were noted according to COPD severity and/or exacerbation history for rate of hospitalization and primary care visits.,Multivariate analyses were reported by 29 studies and demonstrated the statistical significance of these associations.,Several other drivers of increased costs and HRU were highlighted for patients with moderate-to-very severe COPD, including comorbidities, and treatment history.,Moderate-to-very severe COPD represents a considerable economic burden for healthcare providers despite the availability of efficacious treatments and comprehensive guidelines on their use.,Further research is warranted to ensure cost-efficient COPD management, to improve treatments and ease budgetary pressures. | Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients.,Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype.,This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.,These patients are therefore a priority for research and treatment.,The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection.,Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment.,Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.,This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.,The online version of this article (doi:10.1186/1741-7015-11-181) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is a major respiratory disorder, largely caused by smoking that has been linked with large health inequalities worldwide.,There are important gaps in our knowledge about how COPD affects Aboriginal peoples.,This retrospective cohort study assessed the epidemiology of COPD in a cohort of Aboriginal peoples relative to a non-Aboriginal cohort.,We used linkage of administrative health databases in Alberta (Canada) from April 1, 2002 to March 31, 2010 to compare the annual prevalence, and the incidence rates of COPD between Aboriginal and non-Aboriginal cohorts aged 35 years and older.,Poisson regression models adjusted the analysis for important sociodemographic factors.,Compared to a non-Aboriginal cohort, prevalence estimates of COPD from 2002 to 2010 were 2.3 to 2.4 times greater among Registered First Nations peoples, followed by the Inuit (1.86 to 2.10 times higher) and the Métis (1.59 to 1.67 times higher).,All Aboriginal peoples had significantly higher COPD incidence rates than the non-Aboriginal group (incidence rate ratio [IRR]: 2.1; 95% confidence interval [CI]: 1.97, 2.27).,COPD incidence rates were higher in First Nation peoples (IRR: 2.37; 95% CI: 2.19, 2.56) followed by Inuit (IRR: 1.92; 95% CI: 1.64, 2.25) and Métis (IRR: 1.49; 95% CI: 1.32, 1.69) groups.,We found a high burden of COPD among Aboriginal peoples living in Alberta; a province with the third largest Aboriginal population in Canada.,Altogether, the three Aboriginal peoples groups have higher prevalence and incidence of COPD compared to a non-Aboriginal cohort.,The condition affects the three Aboriginal groups differently; Registered First Nations and Inuit have the highest burden of COPD.,Reasons for these differences should be further explored within a framework of social determinants of health to help designing interventions that effectively influence modifiable COPD risk factors in each of the Aboriginal groups. | Chronic obstructive pulmonary disease (COPD) causes a high disease burden among the elderly worldwide.,In Taiwan, the long-term temporal trend of COPD mortality is declining, but the geographical disparity of the disease is not yet known.,Nationwide COPD age-adjusted mortality at the township level during 1999-2007 is used for elucidating the geographical distribution of the disease.,With an ordinary least squares (OLS) model and geographically weighted regression (GWR), the ecologic risk factors such as smoking rate, area deprivation index, tuberculosis exposure, percentage of aborigines, density of health care facilities, air pollution and altitude are all considered in both models to evaluate their effects on mortality.,Global and local Moran’s I are used for examining their spatial autocorrelation and identifying clusters.,During the study period, the COPD age-adjusted mortality rates in males declined from 26.83 to 19.67 per 100,000 population, and those in females declined from 8.98 to 5.70 per 100,000 population.,Overall, males’ COPD mortality rate was around three times higher than females’.,In the results of GWR, the median coefficients of smoking rate, the percentage of aborigines, PM10 and the altitude are positively correlated with COPD mortality in males and females.,The median value of density of health care facilities is negatively correlated with COPD mortality.,The overall adjusted R-squares are about 20% higher in the GWR model than in the OLS model.,The local Moran’s I of the GWR’s residuals reflected the consistent high-high cluster in southern Taiwan.,The findings indicate that geographical disparities in COPD mortality exist.,Future epidemiological investigation is required to understand the specific risk factors within the clustering areas. | 1 |
To identify clusters of patients who may benefit from treatment with an inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) versus LABA alone, in terms of exacerbation reduction, and to validate previously identified clusters of patients with chronic obstructive pulmonary disease (COPD) (based on diuretic use and reversibility).,Post hoc supervised cluster analysis using a modified recursive partitioning algorithm of two 1-year randomised, controlled trials of fluticasone furoate (FF)/vilanterol (VI) versus VI alone, with the primary end points of the annual rate of moderate-to-severe exacerbations.,Global.,3255 patients with COPD (intent-to-treat populations) with a history of exacerbations in the past year.,FF/VI 50/25 µg, 100/25 µg or 200/25 µg, or VI 25 µg; all one time per day.,Mean annual COPD exacerbation rate to identify clusters of patients who benefit from adding an ICS (FF) to VI bronchodilator therapy.,Three clusters were identified, including two groups that benefit from FF/VI versus VI: patients with blood eosinophils >2.4% (RR=0.68, 95% CI 0.58 to 0.79), or blood eosinophils ≤2.4% and smoking history ≤46 pack-years, experienced a reduced rate of exacerbations with FF/VI versus VI (RR=0.78, 95% CI 0.63 to 0.96), whereas those with blood eosinophils ≤2.4% and smoking history >46 pack-years were identified as non-responders (RR=1.22, 95% CI 0.94 to 1.58).,Clusters of patients previously identified in the fluticasone propionate/salmeterol (SAL) versus SAL trials of similar design were not validated; all clusters of patients tended to benefit from FF/VI versus VI alone irrespective of diuretic use and reversibility.,In patients with COPD with a history of exacerbations, those with greater blood eosinophils or a lower smoking history may benefit more from ICS/LABA versus LABA alone as measured by a reduced rate of exacerbations.,In terms of eosinophils, this finding is consistent with findings from other studies; however, the validity of the 2.4% cut-off and the impact of smoking history require further investigation.,NCT01009463; NCT01017952; Post-results. | Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD.,Despite guideline recommendations that combined long-acting β2-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk.,This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens.,The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD.,This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 µg and 2.5/5 µg) via Respimat® and twice-daily salmeterol + fluticasone propionate (50/500 µg and 50/250 µg) via Accuhaler® for 6 weeks.,The primary end point was change in forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 12 hours (AUC0-12) relative to the baseline after 6 weeks.,Tiotropium + olodaterol 5/5 µg and 2.5/5 µg demonstrated statistically significant improvements in FEV1 AUC0-12 compared to salmeterol + fluticasone propionate (improvements from baseline were 317 mL and 295 mL with tiotropium + olodaterol 5/5 µg and 2.5/5 µg, and 188 mL and 192 mL with salmeterol + fluticasone propionate 50/500 µg and 50/250 µg, respectively).,Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV1 area under the curve from 0 hour to 24 hours (AUC0-24).,Once-daily tiotropium + olodaterol in participants with moderate-to-severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate.,Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD. | 1 |
Suitable tools for assessing the severity of chronic obstructive pulmonary disease (COPD) include multi-component indices and the global initiative for chronic obstructive lung disease (GOLD) categories.,The aim of this study was to evaluate the dyspnoea, obstruction, smoking, exacerbation (DOSE) and the age, dyspnoea, obstruction (ADO) indices and GOLD categories as measures of current health status and future outcomes in COPD patients.,This was an observational cohort study comprising 5,114 primary care COPD patients across three databases from UK, Sweden and Holland.,The associations of DOSE and ADO indices with (i) health status using the Clinical COPD Questionnaire (CCQ) and St George’s Respiratory Questionnaire (SGRQ) and COPD Assessment test (CAT) and with (ii) current and future exacerbations, admissions and mortality were assessed in GOLD categories and DOSE and ADO indices.,DOSE and ADO indices were significant predictors of future exacerbations: incident rate ratio was 1.52 (95% confidence intervals 1.46-1.57) for DOSE, 1.16 (1.12-1.20) for ADO index and 1.50 (1.33-1.68) and 1.23 (1.10-1.39), respectively, for hospitalisations.,Negative binomial regression showed that the DOSE index was a better predictor of future admissions than were its component items.,The hazard ratios for mortality were generally higher for ADO index groups than for DOSE index groups.,The GOLD categories produced widely differing assessments for future exacerbation risk or for hospitalisation depending on the methods used to calculate them.,None of the assessment systems were excellent at predicting future risk in COPD; the DOSE index appears better than the ADO index for predicting many outcomes, but not mortality.,The GOLD categories predict future risk inconsistently.,The DOSE index and the GOLD categories using exacerbation frequency may be used to identify those at high risk for exacerbations and admissions. | 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 accounts for the highest rate of hospital admissions among major chronic diseases.,COPD hospitalizations are associated with impaired quality of life, high health care utilization, and poor prognosis and result in an economic and a social burden that is both substantial and increasing.,The aim of this study is to determine the efficacy of a comprehensive case management program (CCMP) in reducing length of stay (LOS) and risk of hospital admissions and readmissions in patients with COPD.,We retrospectively compared outcomes across five large hospitals in Vancouver, BC, Canada, following the implementation of a systems approach to the management of COPD patients who were identified in the hospital and followed up in the community for 90 days.,We compared numbers, rates, and intervals of readmission and LOS during 2 years of active program delivery compared to 1 year prior to program implementation.,A total of 1,564 patients with a clinical diagnosis of COPD were identified from 2,719 hospital admissions during the 3 years of study.,The disease management program reduced COPD-related hospitalizations by 30% and hospitalizations for all causes by 13.6%.,Similarly, the rate of readmission for all causes showed a significant decline, with hazard ratios (HRs) of 0.55 (year 1) and 0.51 (year 2) of intervention (P<0.001).,In addition, patients’ mean LOS (days) for COPD-related admissions declined significantly from 10.8 to 6.8 (P<0.05).,A comprehensive disease management program for COPD patients, including education, case management, and follow-up, was associated with significant reduction in hospital admissions and LOS. | COPD is the third leading cause of death in the world.,Utilizing care bundles during acute COPD exacerbations results in fewer complications and lower costs.,Our aim was to construct a COPD exacerbation care bundle and evaluate the effects on patient care.,We conducted a prospective analysis of 44 patients admitted with a COPD exacerbation to a single tertiary care facility.,Primary outcomes included length of stay, readmission rates, and hospital costs.,Secondary outcomes included patient education, pulmonologist follow-up, and timeliness of medication administration.,Two cohorts were analyzed: those treated with an electronic COPD care bundle (cases; N=22) versus those treated without the care bundle (controls; N=22).,Mean length of stay (51.2 vs 101.1 hours in controls; P-value =0.001), 30-day readmission rates (9.1% vs 54.4% in controls; P-value =0.001), and 60-day readmission rates (22.7% vs 77% in controls; P-value =0.0003) decreased in the care bundle group.,Ninety-day hospital costs had a significant difference in the care bundle group (US$7,652 vs US$19,954 in controls; P-value =0.044).,Secondary outcomes included a 100% rate of COPD inhaler teaching (vs 27.3% in controls; P-value <0.001), 59.1% rate of pulmonologist follow-up after discharge (vs 18.2% in controls; P-value =0.005), and a mean reduction in time to steroid administration (7.0 hours; P-value =0.015) seen in the care bundle cases.,Our significant findings coupled with the recent success of standardized algorithms in managing COPD exacerbations stress the importance of enforcing clinical guidelines that can enhance patient care.,We demonstrated improved care for COPD exacerbation patients during hospitalizations, thereby decreasing morbidity and the financial burden hospitals face in regard to this increasingly prevalent disease. | 1 |
Recently, two “fixed triple” single-inhaler combinations of an inhaled corticosteroid (ICS), a long-acting β2-agonist (LABA), and a long-acting muscarinic antagonist (LAMA) have become available for patients with COPD.,This review presents the clinical evidence that led to the approval of these triple therapies, discusses the role of ICS in patients with COPD, and presents data on the relative efficacy of “fixed triple” (ICS/LAMA/LABA) therapy vs LAMA, ICS/LABA, and LAMA/LABA combinations, and summarizes studies in which ICS/LABAs were combined with LAMAs to form “open triple” combinations.,Of the five main fixed triple studies completed so far, three evaluated the efficacy and safety of an extrafine formulation of beclometasone dipropionate, formoterol fumarate, and glycopyrronium; the other two studies evaluated fluticasone furoate, vilanterol, and umeclidinium.,Overall, compared to LAMA, ICS/LABA, or LAMA/LABA, triple therapy decreased the risk of exacerbations and improved lung function and health status, with a favorable benefit-to-harm ratio.,Furthermore, triple therapy showed a promising signal in terms of improved survival.,The evidence suggests that triple therapy is the most effective treatment in moderate/severe symptomatic patients with COPD at risk of exacerbations, with marginal if any risk of side effects including pneumonia.,Ongoing studies are examining the role of triple therapy in less severe symptomatic patients with COPD and asthma-COPD overlap. | A single inhaler containing inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA)/long-acting muscarinic antagonist (LAMA) is a more convenient way of delivering triple therapy in patients with COPD.,Single triple therapy has been shown to be superior at reducing exacerbations and improving quality of life compared to LABA/LAMA, especially in patients with a prior history of frequent exacerbations and blood eosinophilia, who have ICS responsive disease.,The corollary is that patients with infrequent exacerbations who are noneosinophilic may be safely de-escalated from triple therapy to LABA/LAMA without loss of control.,Pointedly, there is a substantially increased risk of pneumonia associated with the triple therapy containing fluticasone furoate but not beclometasone dipropionate or budesonide.,Since triple therapy is also better than ICS/LABA at reducing exacerbations and improving lung function, symptoms, and quality of life, this brings into question the rationale for using ICS/LABA.,Hence, we propose a simplified pragmatic decision process based on symptoms, prior to exacerbation history, and blood eosinophils to select which patients should be given a single triple inhaler or LABA/LAMA.,Differences in patient preference of inhaler device, formulations and drugs will also determine which triple inhaler prescribers elect to use. | 1 |
Not all patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) benefit from treatment with systemic corticosteroids and antibiotics.,The aim of the study was to identify criteria recommended in current COPD guidelines for treating acute exacerbations with systemic corticosteroids and antibiotics and to assess the underlying evidence.,Current COPD guidelines were identified by a systematic literature search.,The most recent guidelines as per country/organisation containing recommendations about treating acute exacerbations of COPD were included.,Guideline development and criteria for treating acute exacerbations with systemic corticosteroids and antibiotics were appraised.,Randomised controlled trials directly referred to in context with the recommendations were evaluated in terms of study design, setting, and study population.,A total of 19 COPD guidelines were included.,Systemic corticosteroids were often universally recommended to all patients with acute exacerbations.,Criteria for treatment with antibiotics were mainly an increase in respiratory symptoms.,Objective diagnostic tests or clinical examination were only rarely recommended.,Only few criteria were directly linked to underlying evidence, and the trial patients represented a highly specific group of COPD patients.,Current COPD guidelines are of little help in primary care to identify patients with acute exacerbations probably benefitting from treatment with systemic corticosteroids and antibiotics in primary care, and might contribute to overuse or inappropriate use of either treatment. | The bronchial microbiome in severe COPD during stability and exacerbation in patients chronically colonised by Pseudomonas aeruginosa (PA), has not been defined.,Our objective was to determine the characteristics of the bronchial microbiome of severe COPD patients colonised and not colonised by P. aeruginosa and its changes during exacerbation.,COPD patients with severe disease and frequent exacerbations were categorised according to chronic colonisation by P. aeruginosa.,Sputum samples were obtained in stability and exacerbation, cultured, and analysed by 16S rRNA gene amplification and pyrosequencing.,Sixteen patients were included, 5 of them showing chronic colonisation by P. aeruginosa.,Pseudomonas genus had significantly higher relative abundance in stable colonised patients (p = 0.019), but no significant differences in biodiversity parameters were found between the two groups (Shannon, 3 (2-4) vs 3 (2-3), p = 0.699; Chao1, 124 (77-159) vs 140 (115-163), p = 0.364).,In PA-colonised patients bronchial microbiome changed to a microbiome similar to non-PA-colonised patients during exacerbations.,An increase in the relative abundance over 20 % during exacerbation was found for Streptococcus, Pseudomonas, Moraxella, Haemophilus, Neisseria, Achromobacter and Corynebacterium genera, which include recognised potentially pathogenic microorganisms, in 13 patients colonised and not colonised by P. aeruginosa with paired samples.,These increases were not identified by culture in 5 out of 13 participants (38.5 %).,Stable COPD patients with severe disease and PA-colonised showed a similar biodiversity to non-PA-colonised patients, with a higher relative abundance of Pseudomonas genus in bronchial secretions.,Exacerbation in severe COPD patients showed the same microbial pattern, independently of previous colonisation by P. aeruginosa.,The online version of this article (doi:10.1007/s10096-013-2044-0) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by abnormal inflammation, persistent and progressive lung function decline.,The anti-inflammatory actions of tanshinone IIA, which is the most important active component from Chinese herbal medicine Danshen, have been well studied.,However, it remains unknown whether sodium tanshinone IIA sulfonate (STS) protects against the development of COPD.,Here we found that STS inhalation (5 mg/kg, 30 min per session, twice a day) significantly attenuated lung function decline, airspace enlargement, mucus production, bronchial collagen deposition, inflammatory responses and oxidative stress caused by cigarette smoke (CS) and lipopolysaccharide (LPS) exposures in mice.,Moreover, treatment with STS (10 μg/ml) reduced CS extract (CSE)-induced IL-6 and IL-8 secretion in human bronchial epithelial (16HBE) cells.,The anti-inflammatory actions of STS were associated with inhibition of ERK1/2 and NF-κB activations.,Interestingly, STS inhibited CS-induced reduction of cystic fibrosis transmembrane conductance regulator (CFTR) in mouse lungs and in 16HBE cells.,Treatment with a specific CFTR inhibitor CFTR-Inh172 augmented CSE-induced ERK1/2 and NF-κB-dependent inflammatory responses, but abolished the inhibitory action of STS on IL-6 and IL-8 secretion in 16HBE cells.,These results demonstrate that CS-induced COPD and down-regulation of CFTR are prevented by STS. | 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 |
Chronic obstructive pulmonary disease (COPD) includes chronic bronchitis and emphysema.,Environmental exposure, primarily cigarette smoking, can cause high oxidative stress and is the main factor of COPD development.,Cigarette smoke also contributes to the imbalance of oxidant/antioxidant due to exogenous reactive oxygen species (ROS).,Moreover, endogenously released ROS during the inflammatory process and mitochondrial dysfunction may contribute to this disease progression.,ROS and reactive nitrogen species (RNS) can oxidize different biomolecules such as DNA, proteins, and lipids leading to epithelial cell injury and death.,Various detoxifying enzymes and antioxidant defense systems can be involved in ROS removal.,In this review, we summarize the main findings regarding the biological role of ROS, which may contribute to COPD development, and cytoprotective mechanisms against this disease progression. | Circulating markers of inflammation in chronic obstructive pulmonary disease (COPD) may correlate to disease progression and extrapulmonary complications such as malnourishment.,However, surprisingly little is known about gender-related differences for circulating inflammatory markers in COPD.,To characterize differences in circulating markers of inflammation in malnourished female and male patients with COPD.,Thirty female and 11 male patients with a clinical diagnosis of COPD and malnourishment were examined.,A group of control subjects without evidence of COPD was recruited for comparison of some variables.,Blood samples were drawn, and the following parameters were studied: leukocytes and differential counts, C-reactive protein (CRP), tumor necrosis factor-α, interleukin (IL)-6 and IL-8, myeloperoxidase (MPO), neutrophil elastase (NE), intracellular adhesion molecule-1, vascular endothelial adhesion molecule-1, and E-selectin.,The mean neutrophil concentration was significantly (P = 0.019) higher in female (4.5 × 109/L) than in male patients with COPD (3.5 × 109/L) and significantly higher than in female control subjects (3.1 × 109/L) (P < 0.01, n = 85).,The mean CRP values were considerably higher in female (4.9 mg/mL) than in male patients with COPD (1.5 mg/mL), but the difference was not statistically significant (P = 0.20).,The mean concentrations of IL-6 and IL-8 tended to be higher in female than in male patients with COPD, but these differences did not reach statistical significance either (P > 0.05).,Confounding factors (smoking, medication) could not explain the gender differences noted.,The concentrations of MPO and NE displayed a strong correlation (r = 0.89; P < 0.01, n = 41) but revealed no gender differences.,The latter was true for concentrations of adhesion molecules as well.,Our study puts forward evidence of a gender-related difference in systemic inflammation in malnourished patients with COPD in terms of circulating neutrophils being more abundant in female patients.,Among these female patients, there was also a trend toward an increase in two neutrophil-mobilizing cytokines.,New and better-powered studies are warranted to confirm and characterize this potentially important phenomenon in greater detail. | 1 |
COPD is characterized by variability in exercise capacity and physical activity (PA), and acute exacerbations (AEs).,Little is known about the relationship between daily step count, a direct measure of PA, and the risk of AEs, including hospitalizations.,In an observational cohort study of 169 persons with COPD, we directly assessed PA with the StepWatch Activity Monitor, an ankle-worn accelerometer that measures daily step count.,We also assessed exercise capacity with the 6-minute walk test (6MWT) and patient-reported PA with the St.,George's Respiratory Questionnaire Activity Score (SGRQ-AS).,AEs and COPD-related hospitalizations were assessed and validated prospectively over a median of 16 months.,Mean daily step count was 5804±3141 steps.,Over 209 person-years of observation, there were 263 AEs (incidence rate 1.3±1.6 per person-year) and 116 COPD-related hospitalizations (incidence rate 0.56±1.09 per person-year).,Adjusting for FEV1 % predicted and prednisone use for AE in previous year, for each 1000 fewer steps per day walked at baseline, there was an increased rate of AEs (rate ratio 1.07; 95%CI = 1.003-1.15) and COPD-related hospitalizations (rate ratio 1.24; 95%CI = 1.08-1.42).,There was a significant linear trend of decreasing daily step count by quartiles and increasing rate ratios for AEs (P = 0.008) and COPD-related hospitalizations (P = 0.003).,Each 30-meter decrease in 6MWT distance was associated with an increased rate ratio of 1.07 (95%CI = 1.01-1.14) for AEs and 1.18 (95%CI = 1.07-1.30) for COPD-related hospitalizations.,Worsening of SGRQ-AS by 4 points was associated with an increased rate ratio of 1.05 (95%CI = 1.01-1.09) for AEs and 1.10 (95%CI = 1.02-1.17) for COPD-related hospitalizations.,Lower daily step count, lower 6MWT distance, and worse SGRQ-AS predict future AEs and COPD-related hospitalizations, independent of pulmonary function and previous AE history.,These results support the importance of assessing PA in patients with COPD, and provide the rationale to promote PA as part of exacerbation-prevention strategies. | 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. | 1 |
Cardiovascular disease (CVD) is remarkably frequent in patients with chronic obstructive pulmonary disease (COPD).,Albuminuria is a marker of vascular endothelial dysfunction and predictor of CVD events.,Albuminuria is prevalent in patients with COPD as it has been shown in Caucasian and Oriental populations with COPD.,The objective of this study was to determine the prevalence of Albuminuria and COPD severity correlates among black patients with chronic obstructive pulmonary disease in order to see whether a similar trend of albuminuria is also prevalent in this population.,A total of 104 COPD patients were enrolled in the study.,Lung functions were assessed by means of the Easy One™ spirometer.,Albuminuria defined by urine albumin to creatinine ratio (ACR) was tested using CYBOW 12MAC microalbumin strips in a random spot urine collection.,SPSS version 20 was used for data analysis.,In the studied population, 25/104 (24%) patients had albuminuria and 16/104 (15.4%) patients had CVD.,Abnormal urine albumin (Albuminuria and Proteinuria) was present in all patients with CVD.,In the subset of 46 COPD patients assessed for severity, 60.9% (95%CIs 46.1-73.9) had moderate COPD and 30.4% (95% CIs, 17.9-49.0) severe COPD.,Albuminuria was moderately significantly associated with COPD severity, p = 0.049; (0.049 < p < 0.05).,Participants who ever smoked cigarettes had significantly likelihood of severe and very severe COPD (OR 11.5; 95% CIs, 1.3, 98.4) however, the significance was lost when adjusted for age and gender.,Albuminuria was prevalent in patients with COPD and it had a significant association with COPD severity. | Acute respiratory failure (ARF) is a life-threatening event, which is frequently associated with the severe exacerbations of chronic obstructive pulmonary disease (COPD).,Hypoalbuminemia is associated with increased mortality in patients with COPD.,However, to date, little is known regarding whether or not hypoalbuminemia is a risk factor for developing ARF in COPD.,We conducted a retrospective cohort study using data from the National Health Insurance system of Taiwan.,A total of 42,732 newly diagnosed COPD patients (age ≥40 years) from 1997 to 2011 were enrolled.,Among them, 1,861 (4.36%) patients who had received albumin supplementation were defined as hypoalbuminemia, and 40,871 (95.6%) patients who had not received albumin supplementation were defined as no hypoalbuminemia.,Of 42,732 newly diagnosed COPD patients, 5,248 patients (12.3%) developed ARF during the 6 years follow-up period.,Patients with hypoalbuminemia were older, predominantly male, had more comorbidities, and required more steroid treatment and blood transfusions than patients without hypoalbuminemia.,In a multivariable Cox regression analysis model, being elderly was the strongest independent risk factor for ARF (adjusted hazard ratio [HR]: 4.63, P<0.001), followed by hypoalbuminemia (adjusted HR: 2.87, P<0.001).,However, as the annual average dose of albumin supplementation was higher than 13.8 g per year, the risk for ARF was the highest (adjusted HR: 11.13, 95% CI: 10.35-11.98, P<0.001).,Hypoalbuminemia is a strong risk factor for ARF in patients with COPD.,Therefore, further prospective studies are required to verify whether or not albumin supplementation or nutritional support may help to reduce the risk of ARF in patients with COPD. | 1 |
This study assessed the effects of inhaled corticosteroid (ICS) on airway vascular remodeling in chronic obstructive pulmonary disease (COPD).,Thirty-four subjects with mild-to-moderate COPD were randomly allocated 2:1 to ICS or placebo treatment in a double-blinded clinical trial over 6 months.,Available tissue was compared before and after treatment for vessel density, and expression of VEGF, TGF-β1, and TGF-β1-related phosphorylated transcription factors p-SMAD 2/3.,This clinical trial has been registered and allocated with the Australian New Zealand Clinical Trials Registry (ANZCTR) on 17/10/2012 with reference number ACTRN12612001111864.,There were no significant baseline differences between treatment groups.,With ICS, vessels and angiogenic factors did not change in hypervascular reticular basement membrane, but in the hypovascular lamina propria (LP), vessels increased and this had a proportionate effect on lung air trapping.,There was modest evidence for a reduction in LP vessels staining for VEGF with ICS treatment, but a marked and significant reduction in p-SMAD 2/3 expression.,Six-month high-dose ICS treatment had little effect on hypervascularity or angiogenic growth factors in the reticular basement membrane in COPD, but normalized hypovascularity in the LP, and this was physiologically relevant, though accompanied by a paradoxical reduction in growth factor expression. | Chronic obstructive pulmonary disease (COPD) is characterized by inflammation and remodeling of the lungs.,This results in alterations in extracellular matrix (ECM) and structural changes leading to airflow obstruction.,We studied the expression of tenascin-C (Tn-C) and alpha smooth muscle actin (α-SMA), which act as a marker of myofibroblasts, in large airways from COPD patients.,Our aim was to elucidate whether this expression correlated with smoking or with disease development.,Bronchoscopy was performed on 20 COPD patients (mean age 56 years; range 39-61; FEV1/FVC < 70% and FEV1 median 53% (range 33-69) of predicted).,Age and smoking matched smokers (S) without COPD (n = 13) and age matched non-smokers (NS) (n = 14) served as controls.,Bronchial mucosal biopsies were analyzed by immunohistochemistry.,The distribution of Tn-C expression was assessed and graded in three levels, and the number of spindle shaped cells staining positive for α-SMA were counted.,Biopsies from COPD patients had more (P < 0.001) Tn-C expression than the two control groups.,A significantly (P < 0.05) increased number of spindle shaped cells expressing α-SMA was observed in COPD patients compared with the controls.,Smokers and nonsmokers did not differ in this respect.,The expression of Tn-C correlated positively (P < 0.001) to the number of α-SMA positive cells.,We demonstrate increased expression of Tn-C and α-SMA positive cells in the large airways in COPD.,This was not associated to smoking per se, but to the presence of airway obstruction.,Our findings add new information regarding remodeling characteristics and highlight the large airways as a potential site for airways obstruction in COPD. | 1 |
COPD is a significant cause of morbidity and mortality.,In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation.,Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy.,In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention.,In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13.,The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions.,We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD. | Computed tomography scan images have been used to identify different radiological COPD phenotypes based on the presence and severity of emphysema, bronchial wall thickening, and bronchiectasis.,Bronchiectasis is defined as an abnormal dilation of the bronchi, usually as a result of chronic airway inflammation and/or infection.,The prevalence of bronchiectasis in patients with COPD is high, especially in advanced stages.,The identification of bronchiectasis in COPD has been defined as a different clinical COPD phenotype with greater symptomatic severity, more frequent chronic bronchial infection and exacerbations, and poor prognosis.,A causal association has not yet been proven, but it is biologically plausible that COPD, and particularly the infective and exacerbator COPD phenotypes, could be the cause of bronchiectasis without any other known etiology, beyond any mere association or comorbidity.,The study of the relationship between COPD and bronchiectasis could have important clinical implications, since both diseases have different and complementary therapeutic approaches.,Longitudinal studies are needed to investigate the development of bronchiectasis in COPD, and clinical trials with treatments aimed at reducing bacterial loads should be conducted to investigate their impact on the reduction of exacerbations and improvements in the long-term evolution of the disease. | 1 |
Discrepancy exists amongst studies investigating the effect of comorbid heart failure (HF) on the morbidity and mortality of chronic obstructive pulmonary disease (COPD) patients.,MEDLINE and Embase were searched using a pre-specified search strategy for studies comparing hospitalisation, rehospitalisation, and mortality of COPD patients with and without HF.,Studies must have reported crude and/or adjusted rate ratios, risk ratios, odds ratios (OR), or hazard ratios (HR).,Twenty-eight publications, reporting 55 effect estimates, were identified that compared COPD patients with HF with those without HF.,One study reported on all-cause hospitalisation (1 rate ratio).,Two studies reported on COPD-related hospitalisation (1 rate ratio, 2 OR).,One study reported on COPD- or cardiovascular-related hospitalisation (4 HR).,One study reported on 90-day all-cause rehospitalisation (1 risk ratio).,One study reported on 3-year all-cause rehospitalisation (2 HR).,Four studies reported on 30-day COPD-related rehospitalisation (1 risk ratio; 5 OR).,Two studies reported on 1-year COPD-related rehospitalisation (1 risk ratio; 1 HR).,One study reported on 3-year COPD-related rehospitalisation (2 HR).,Eighteen studies reported on all-cause mortality (1 risk ratio; 4 OR; 24 HR).,Five studies reported on all-cause inpatient mortality (1 risk ratio; 4 OR).,Meta-analyses of hospitalisation and rehospitalisation were not possible due to insufficient data for all individual effect measures.,Meta-analysis of studies requiring spirometry for the diagnosis of COPD found that risk of all-cause mortality was 1.61 (pooled HR; 95%CI: 1.38, 1.83) higher in patients with HF than in those without HF.,In this systematic review, we investigated the effect of HF comorbidity on hospitalisation and mortality of COPD patients.,There is substantial evidence that HF comorbidity increases COPD-related rehospitalisation and all-cause mortality of COPD patients.,The effect of HF comorbidity may differ depending on COPD phenotype, HF type, or HF severity and should be the topic of future research. | Asthma and chronic obstructive pulmonary disease (COPD) share many characteristics and symptoms, and the differential diagnosis between the two diseases can be difficult in primary care.,This study explored potential overlap between both diseases in a primary care environment.,To quantify how commonly patients with COPD have a concomitant diagnosis of asthma, and how commonly patients with asthma have a concomitant diagnosis of COPD in UK primary care.,Additionally, the study aimed to determine the extent of possible misdiagnosis and missed opportunities for diagnosis.,Patients with validated asthma and patients with validated COPD in primary care were identified from the UK Clinical Practice Research Datalink (CPRD) in separate validation studies, and the diseases were confirmed by review of GP questionnaires.,The prevalence of concurrent asthma and COPD in validated cases of either disease was examined based on CPRD coding, GP questionnaires, and requested additional information.,In total, 400 patients with COPD and 351 patients with asthma in primary care were identified.,Of the patients with validated asthma, 15% (n = 52) had previously received a diagnostic COPD Read code, although COPD was only likely in 14.8% (95% confidence interval [CI] = 11.3 to 19.0) of patients with validated asthma.,More than half (52.5%, n = 210) of patients with validated COPD had previously received a diagnostic asthma Read code.,However, when considering additional evidence to support a diagnosis of asthma, concurrent asthma was only likely in 14.5% (95% CI = 11.2 to 18.3) of patients with validated COPD.,A concurrent asthma and COPD diagnosis appears to affect a relative minority of patients with COPD (14.5%) or asthma (14.8%).,Asthma diagnosis may be over-recorded in people with COPD. | 1 |
Viruses are a common cause of exacerbations in chronic obstructive pulmonary disease (COPD).,They activate toll-like receptors (TLRs) 3, 7, and 8, leading to a pro-inflammatory response.,We have characterized the responses of TLR3 and TLR7/8 in lung tissue explants from COPD patients and control smokers.,We prepared lung whole tissue explants (WTEs) from patients undergoing surgery for confirmed or suspected lung cancer.,In order to mimic the conditions of viral infection, we used poly(I:C) for TLR3 stimulation and R848 for TLR7/8 stimulation.,These TLR ligands were used alone and in combination.,The effects of tumor necrosis factor α (TNFα) neutralization and dexamethasone on TLR responses were examined.,Inflammatory cytokine release was measured by enzyme-linked immunosorbent assay and gene expression by quantitative real-time polymerase chain reaction.,WTEs from COPD patients released higher levels of pro-inflammatory cytokines compared with WTEs from smokers.,Activation of multiple TLRs led to a greater than additive release of TNFα and CCL5.,TNFα neutralization and dexamethasone treatment decreased cytokine release.,This WTE model shows an enhanced response of COPD compared with controls, suggesting an increased response to viral infection.,There was amplification of innate immune responses with multiple TLR stimulation. | Oxidative stress occurs when free radicals and other reactive species overwhelm the availability of antioxidants.,Reactive oxygen species (ROS), reactive nitrogen species, and their counterpart antioxidant agents are essential for physiological signaling and host defense, as well as for the evolution and persistence of inflammation.,When their normal steady state is disturbed, imbalances between oxidants and antioxidants may provoke pathological reactions causing a range of nonrespiratory and respiratory diseases, particularly chronic obstructive pulmonary disease (COPD).,In the respiratory system, ROS may be either exogenous from more or less inhalative gaseous or particulate agents such as air pollutants, cigarette smoke, ambient high-altitude hypoxia, and some occupational dusts, or endogenously generated in the context of defense mechanisms against such infectious pathogens as bacteria, viruses, or fungi.,ROS may also damage body tissues depending on the amount and duration of exposure and may further act as triggers for enzymatically generated ROS released from respiratory, immune, and inflammatory cells.,This paper focuses on the general relevance of free radicals for the development and progression of both COPD and pulmonary emphysema as well as novel perspectives on therapeutic options.,Unfortunately, current treatment options do not suffice to prevent chronic airway inflammation and are not yet able to substantially alter the course of COPD.,Effective therapeutic antioxidant measures are urgently needed to control and mitigate local as well as systemic oxygen bursts in COPD and other respiratory diseases.,In addition to current therapeutic prospects and aspects of genomic medicine, trending research topics in COPD are presented. | 1 |
COPD is the most frequent chronic respiratory disease and a leading cause of morbidity and mortality.,The major risk factor for COPD development is cigarette smoke, and the most efficient treatment for COPD is smoking cessation.,However, even after smoking cessation, inflammation, apoptosis, and oxidative stress may persist and continue contributing to disease progression.,Although current therapies for COPD (primarily based on anti-inflammatory agents) contribute to the reduction of airway obstruction and minimize COPD exacerbations, none can avoid disease progression or reduce mortality.,Within this context, recent advances in mesenchymal stromal cell (MSC) therapy have made this approach a strong candidate for clinical use in the treatment of several pulmonary diseases.,MSCs can be readily harvested from diverse tissues and expanded with high efficiency, and have strong immunosuppressive properties.,Preclinical studies have demonstrated encouraging outcomes of MSCs therapy for lung disorders, including emphysema.,These findings instigated research groups to assess the impact of MSCs in human COPD/emphysema, but clinical results have fallen short of expectations.,However, MSCs have demonstrated a good adjuvant role in the clinical scenario.,Trials that used MSCs combined with another, primary treatment (eg, endobronchial valves) found that patients derived greater benefit in pulmonary function tests and/or quality of life reports, as well as reductions in systemic markers of inflammation.,The present review summarizes and describes the more recent preclinical studies that have been published about MSC therapy for COPD/emphysema and discusses what has already been applied about MSCs treatment in COPD patients in the clinical setting. | Transforming growth factor-beta1 (TGF-β1) is a multipotential cytokine with angiogenic activity.,There are only limited data about its role in airway remodeling in COPD.,We have previously shown that the reticular basement membrane (Rbm) is hypervascular in the airways of current smokers either with or without chronic obstructive pulmonary disease (COPD).,This study evaluated TGF-β1 immunostaining in the Rbm and its relationship to vascularity in smokers with or without COPD.,Bronchial biopsies from 15 smokers with normal lung function, 19 current and 14 ex-smokers with COPD were immunostained for TGF-β1 antibody and compared to 17 healthy controls.,The percentage area of tissue and also number and area of vessels staining positively for TGF-β1 were measured and compared between groups.,Some bronchial biopsies from current smoking COPD subjects were also stained for phosphorylated (active) Smad2/3.,Epithelial TGF- β1 staining was not different between COPD current smokers and normal controls.,TGF-β1 stained vessels in the Rbm were increased in smokers with normal lung function, current smoking COPD and ex-smokers with COPD compared to controls [median (range) for number of vessels/mm Rbm 2.5 (0.0-12.7), 3.4 (0.0-8.1) and 1.0 (0.0-6.3) vs.,0.0 (0.0-7.0), p<0.05].,Percentage of vessels stained was also increased in these clinical groups.,Preliminary data suggest that in current smoking COPD subjects endothelial cells and cells in the Rbm stain positively for phosphorylated Smad2/3 suggesting TGF-β1 is functionally active in this situation.,Vessel-associated TGF-β1 activity is increased in the bronchial Rbm in smokers and especially those with COPD. | 1 |
Little is known about iron deficiency (ID) and anemia in Chronic Obstructive Pulmonary Disease (COPD).,The purposes of this study were: (i) To study the prevalence and treatment of anemia and ID in patients hospitalized with an exacerbation of COPD. (ii) to study the hematological responses and degree of dyspnea before and after correction of anemia with subcutaneous Erythropoiesis Stimulating Agents (ESAs) and intravenous (IV) iron therapy, in ambulatory anemic patients with both COPD and chronic kidney disease.,(i) We examined the hospital records of all patients with an acute exacerbation of COPD (AECOPD) to assess the investigation, prevalence, and treatment of anemia and ID. (ii) We treated 12 anemic COPD outpatients with the combination of ESAs and IV-iron, given once weekly for 5 weeks.,One week later we measured the hematological response and the severity of dyspnea by Visual Analogue Scale (VAS).,(i) Anemia and iron deficiency in hospitalized COPD patients: Of 107 consecutive patients hospitalized with an AECOPD, 47 (43.9%) were found to be anemic on admission.,Two (3.3%) of the 60 non-anemic patients and 18 (38.3%) of the 47 anemic patients had serum iron, percent transferrin saturation (%Tsat) and serum ferritin measured.,All 18 (100%) anemic patients had ID, yet none had oral or IV iron subscribed before or during hospitalization, or at discharge. (ii) Intervention outpatient study: ID was found in 11 (91.7%) of the 12 anemic ambulatory patients.,Hemoglobin (Hb), Hematocrit (Hct) and the VAS scale scores increased significantly with the ESAs and IV-iron treatment.,There was a highly significant correlation between the ∆Hb and ∆VAS; rs = 0.71 p = 0.009 and between the ∆Hct and ∆VAS; rs = 0.8 p = 0.0014.,ID is common in COPD patients but is rarely looked for or treated.,Yet correction of the ID in COPD patients with ESAs and IV iron can improve the anemia, the ID, and may improve the dyspnea. | Recent literature has suggested that emphysema and chronic bronchitis, traditionally considered to be entities overlapping within chronic obstructive pulmonary disease (COPD), may be distinct disorders.,Few studies have examined the differences in patient characteristics and health outcomes between these conditions.,This study examined whether COPD phenotypes represent distinct patient populations, in a large nationally representative US sample.,Data were obtained from the 2010 US National Health and Wellness Survey (NHWS).,NHWS respondents (n = 75,000) were categorized as a COPD phenotype based on their self-reported diagnosis of COPD only (n = 970), emphysema only (n = 399), or chronic bronchitis only (n = 2071).,Phenotypes were compared on demographics, health characteristics, treatment patterns, health outcomes, work productivity, and resource use.,Variables were compared using Chi-square and analysis of variance tests for categorical and continuous outcomes, respectively.,Health outcomes were also examined using regression modeling, controlling for demographic and health characteristic covariates.,Patients with chronic bronchitis were significantly younger (51.38 years versus 63.24 years for COPD versus 63.30 years for emphysema, P < 0.05) and more likely to be employed (46.98% versus 23.81% for COPD versus 28.33% for emphysema, P < 0.05).,Relative to the other phenotypes, patients with chronic bronchitis were also significantly more likely to be female, nonwhite, and to exercise currently (all P < 0.05), and were significantly less likely to be a current or former smoker (P < 0.05).,Controlling for demographic and health characteristics, patients self-identified as having COPD only reported significantly worse physical quality of life (adjusted mean 36.69) and health utilities (adjusted mean 0.65) and significantly more absenteeism (adjusted mean 7.08%), presenteeism (adjusted mean 30.73%), overall work impairment (adjusted mean 34.06%), and activity impairment (adjusted mean 46.59%) than the other phenotypes (all P < 0.05).,These results suggest considerable heterogeneity among different COPD phenotypes with respect to demographics, health characteristics, disease characteristics, treatment patterns, and health outcomes.,Research aimed at understanding the differences in patient characteristics and disease presentation of these phenotypes could be used to guide treatment recommendations. | 1 |
Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a leading cause of hospitalizations and readmissions in the US.,Reducing the frequency of hospital readmission is a high priority of US health care organizations and government agencies.,This study evaluated the risk factors associated with readmissions among commercially insured adults aged 40-65 years in the US who were hospitalized for COPD.,This retrospective cohort study used anonymized claims data from the Truven Health MarketScan® Commercial Claims and Encounters database.,The patients included were aged 40-65 years, had an index hospitalization with a primary diagnosis of COPD between July 1, 2008 and June 30, 2010 (continuously enrolled 12 months before and after), and were alive at hospital discharge.,Patients with cystic fibrosis or tuberculosis or who were transferred to another inpatient facility after hospital discharge were excluded.,All readmissions regardless of diagnosis, and separately a subset of all readmissions that had COPD as a primary or secondary diagnosis (COPD-related), were examined.,Univariate descriptive statistics and multivariable regression methods were used.,Of the 18,568 patients with index COPD hospitalizations, 6,095 (32.83%) met the eligibility criteria.,Of those, 503 (8.25%) were readmitted within the first 30 days post-index hospitalization and 2,527 (41.46%) within the first year (COPD-related 340 [5.58%] and 1,681 [27.58%], respectively).,The median time to the first readmission post initial discharge was 4.0 months, with a mean of 5.0 ± 3.4 months.,Multivariable regression analyses showed that comorbid conditions and health care utilization in the pre-index period were significant predictors for readmission both 30 and 90 days following index hospitalization.,A relatively high readmission rate was observed for patients aged 40-65 years.,The results suggest that attention to patient comorbidities and pre-index/index health care service utilization may help identify hospitalized COPD patients at higher risk for readmission. | To investigate the incidence of asthma and chronic obstructive pulmonary disease (COPD) exacerbations in primary care during one year and to identify risk factors for such events.,The study was carried out at seven general practice offices in Norway.,Patients aged 40 years or more registered with a diagnosis of asthma and/or COPD the previous 5 years were included.,After a baseline examination, the participants consulted their GP during exacerbations for the following 12 months.,A questionnaire on exacerbations during the follow-up year was distributed to all.,Univariable and multivariable logistic regression was performed to determine predictors of future exacerbations.,Three hundred and eighty patients attended the baseline examination and complete follow-up data were retrieved from 340 patients.,COPD as defined by forced expiratory volume in the first second of expiration/forced vital capacity (FEV1/FVC) < 0.7, was found in 132 (38.8%) patients.,One hundred and fifty-nine patients (46.8%) experienced one exacerbation or more and 101 (29.7%) two exacerbations or more.,Patients who had an exacerbation treated with antibiotics or systemic corticosteroids or leading to hospitalization the year before baseline (N = 88) had the highest risk of getting an exacerbation during the subsequent year (odds ratio 9.2), whether the FEV1/FVC was below 0.7 or not.,Increased risk of future exacerbations was also related to age ≥ 65 years and limitations in social activities, but not to the FEV1.,The study confirms that previous exacerbations strongly predict future exacerbations in patients with COPD or asthma.,Identification and a closer follow-up of patients at risk of such events could promote earlier treatment when necessary and prevent a rapid deterioration of their condition. | 1 |
The pathogenesis of chronic obstructive pulmonary disease (COPD) is characterized by an interaction of environmental influences, particularly cigarette smoking, and genetic determinants.,Given the global increase in COPD, research on the genomic variants that affect susceptibility to this complex disorder is reviving.,In the present study, we investigated whether single nucleotide polymorphisms in 'a disinter-grin and metalloprotease' 33 (ADAM33) are associated with the development and course of COPD.,We genotyped 150 German COPD patients and 152 healthy controls for the presence of the F+1 and S_2 SNPs in ADAM 33 that lead to the base pair exchange G to A and C to G, respectively.,To assess whether these genetic variants are influential in the course of COPD, we subdivided the cohort into two subgroups comprising 60 patients with a stable and 90 patients with an unstable course of disease.,In ADAM33, the frequency of the F+1 A allele was 35.0% among stable and 43.9% among unstable COPD subjects, which was not significantly different from the 35.5% found in the controls (P = 0.92 and P = 0.07, respectively).,The frequency of the S_2 mutant allele in subjects with a stable COPD was 23.3% (P = 0.32), in subjects with an unstable course 30.6% (P = 0.47).,The study shows that there is no significant difference in the distribution of the tested SNPs between subjects with and without COPD.,Furthermore, these polymorphisms appear to have no consequences for the stability of the disease course. | Multidrug resistance-associated protein-1 (MRP1) protects against oxidative stress and toxic compounds generated by cigarette smoking, which is the main risk factor for chronic obstructive pulmonary disease (COPD).,We have previously shown that single nucleotide polymorphisms (SNPs) in MRP1 significantly associate with level of FEV1 in two independent population based cohorts.,The aim of our study was to assess the associations of MRP1 SNPs with FEV1 level, MRP1 protein levels and inflammatory markers in bronchial biopsies and sputum of COPD patients.,Five SNPs (rs212093, rs4148382, rs504348, rs4781699, rs35621) in MRP1 were genotyped in 110 COPD patients.,The effects of MRP1 SNPs were analyzed using linear regression models.,One SNP, rs212093 was significantly associated with a higher FEV1 level and less airway wall inflammation.,Another SNP, rs4148382 was significantly associated with a lower FEV1 level, higher number of inflammatory cells in induced sputum and with a higher MRP1 protein level in bronchial biopsies.,This is the first study linking MRP1 SNPs with lung function and inflammatory markers in COPD patients, suggesting a role of MRP1 SNPs in the severity of COPD in addition to their association with MRP1 protein level in bronchial biopsies. | 1 |
To describe the characteristics and prognosis of patients with COPD admitted to the hospital due to SARS-CoV-2 infection.,The SEMI-COVID registry is an ongoing retrospective cohort comprising consecutive COVID-19 patients hospitalized in Spain since the beginning of the pandemic in March 2020.,Data on demographics, clinical characteristics, comorbidities, laboratory tests, radiology, treatment, and progress are collected.,Patients with COPD were selected and compared to patients without COPD.,Factors associated with a poor prognosis were analyzed.,Of the 10,420 patients included in the SEMI-COVID registry as of May 21, 2020, 746 (7.16%) had a diagnosis of COPD.,Patients with COPD are older than those without COPD (77 years vs 68 years) and more frequently male.,They have more comorbidities (hypertension, hyperlipidemia, diabetes mellitus, atrial fibrillation, heart failure, ischemic heart disease, peripheral vascular disease, kidney failure) and a higher Charlson Comorbidity Index (2 vs 1, p<0.001).,The mortality rate in COPD patients was 38.3% compared to 19.2% in patients without COPD (p<0.001).,Male sex, a history of hypertension, heart failure, moderate-severe chronic kidney disease, presence of cerebrovascular disease with sequelae, degenerative neurological disease, dementia, functional dependence, and a higher Charlson Comorbidity Index have been associated with increased mortality due to COVID-19 in COPD patients.,Survival was higher among patients with COPD who were treated with hydroxychloroquine (87.1% vs 74.9%, p<0.001) and with macrolides (57.9% vs 50%, p<0.037).,Neither prone positioning nor non-invasive mechanical ventilation, high-flow nasal cannula, or invasive mechanical ventilation were associated with a better prognosis.,COPD patients admitted to the hospital with SARS-CoV-2 infection have more severe disease and a worse prognosis than non-COPD patients. | Background: The comorbidities and clinical signs of coronavirus disease 2019 (COVID-19) patients have been reported mainly as descriptive statistics, rather than quantitative analysis even in very large investigations.,The aim of this study was to identify specific patients’ characteristics that may modulate COVID-19 hospitalization risk.,Research design and methods: A pooled analysis was performed on high-quality epidemiological studies to quantify the prevalence (%) of comorbidities and clinical signs in hospitalized COVID-19 patients.,Pooled data were used to calculate the relative risk (RR) of specific comorbidities by matching the frequency of comorbidities in hospitalized COVID-19 patients with those of general population.,Results: The most frequent comorbidities were hypertension, diabetes mellitus, and cardiovascular and/or cerebrovascular diseases.,The RR of COVID-19 hospitalization was significantly (P < 0.05) reduced in patients with asthma (0.86, 0.77-0.97) or chronic obstructive pulmonary disease (COPD) (0.46, 0.40-0.52).,The most frequent clinical signs were fever and cough.,Conclusion: The clinical signs of hospitalized COVID-19 patients are similar to those of other infective diseases.,Patients with asthma or COPD were at lower hospitalization risk.,This paradoxical evidence could be related with the protective effect of inhaled corticosteroids that are administered worldwide to most asthmatic and COPD patients. | 1 |
Acute Exacerbations of COPD (AECOPD) identified from electronic healthcare records (EHR) are important for research, public health and to inform healthcare utilisation and service provision.,However, there is no standardised method of identifying AECOPD in UK EHR.,We aimed to validate the recording of AECOPD in UK EHR.,We randomly selected 1385 patients with COPD from the Clinical Practice Research Datalink.,We selected dates of possible AECOPD based on 15 different algorithms between January 2004 and August 2013.,Questionnaires were sent to GPs asking for confirmation of their patients’ AECOPD on the dates identified and for any additional relevant information.,Responses were reviewed independently by two respiratory physicians.,Positive predictive value (PPV) and sensitivity were calculated.,The response rate was 71.3%.,AECOPD diagnostic codes, lower respiratory tract infection (LRTI) codes, and prescriptions of antibiotics and oral corticosteroids (OCS) together for 5-14 days had a high PPV (>75%) for identifying AECOPD.,Symptom-based algorithms and prescription of antibiotics or OCS alone had lower PPVs (60-75%).,A combined strategy of antibiotic and OCS prescriptions for 5-14 days, or LRTI or AECOPD code resulted in a PPV of 85.5% (95% CI, 82.7-88.3%) and a sensitivity of 62.9% (55.4-70.4%).,Using a combination of diagnostic and therapy codes, the validity of AECOPD identified from EHR can be high.,These strategies are useful for understanding health-care utilisation for AECOPD, informing service provision and for researchers.,These results highlight the need for common coding strategies to be adopted in primary care to allow easy and accurate identification of events. | COPD exerts a substantial burden on health and health care systems globally and will continue to do so for the foreseeable future.,Treatment however can be costly and health care providers are interested in both whether treatments can offer improvements in disease burden and whether they represent value for money.,Economic evaluations seek to resolve this issue by producing results that can be used to inform and assist the decision maker in allocating scarce health care resources.,In this paper we introduce economic evaluation and then use these themes to review and critically appraise the existing COPD economic evaluations, in order to assess quality in light of today’s standards.,The use of existing economic evaluations in informing the decision maker is then discussed.,Ten out of the fifteen studies were clinical trial or observational study based, and the remaining five on a decision analytic model.,Study design, interventions, outcome measures and the use of uncertainty varied considerably; consequentially the results are difficult to compare in any consistent manner.,Efforts for future studies to harmonize study design and methodology, particularly towards adopting a modeling framework, using current treatment as comparator and adopting a common effectiveness measure, such as the QALY, should be made in order to produce results that are comparable and useful to a decision maker. | 1 |
To identify differentially methylated probes (DMPs) and regions (DMRs) in relation to chronic obstructive pulmonary disease (COPD) and lung function traits.,We performed an epigenome-wide association study of COPD and spirometric parameters, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC, in blood DNA using the Infinium HumanMethylation450 (n = 100, a Korean COPD cohort).,We found one significant DMP (cg03559389, DIP2C) and 104 significant DMRs after multiple-testing correction.,Of these, 34 DMRs mapped to genes differential expressed with respect to the same trait.,Five of the genes were associated with more than two traits: CTU2, USP36, ZNF516, KLK10 and CPT1B.,We identified novel differential methylation loci related to COPD and lung function in blood DNA in Koreans and confirmed previous findings in non-Asians.,Epigenetic modification could contribute to the etiology of these phenotypes. | Smoking is the leading cause of COPD.,Exploring molecular markers and understanding the pathogenic mechanisms of smoking-related COPD are helpful for early clinical diagnosis and treatment of the disease.,This study aims to identify specific circulating microRNAs (miRNAs) from the blood of COPD patients with a long history of smoking.,Blood samples from four different groups were collected, and miRNA microarray was performed.,Differential expression of miRNAs was verified by quantitative polymerase chain reaction.,In vitro, THP-1 cells were cultured and stimulated with cigarette smoke extract (CSE) or transfected with miR-149-3p inhibitor/mimics.,Protein levels of Toll-like receptor 4 (TLR-4) and nuclear factor κB (NF-κB) were detected using Western blot and immunofluorescence.,Interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels were determined by an enzyme-linked immunosorbent assay.,miRNA profiling revealed that the expression of 56 miRNAs was changed between the four groups.,Expression of miR-149-3p in group C (non-smoker non-COPD) was higher than in group S (smoker non-COPD), S-COPD (smoker with stable COPD) and AE-COPD (smoker with acute exacerbation COPD).,CSE stimulation down-regulated the expression of miR-149-3p and up-regulated the TLR-4 and NF-κB levels in THP-1 cells.,Transfecting miR-149-3p inhibitors in THP-1 cells also increased the expression of its target genes.,Furthermore, overexpression of miR-149-3p inhibited the TLR-4/NF-κB signaling pathways and reduced the secretion of IL-1β and TNF-α.,This study found that smoking can induce differential expression of circulating miR-NAs, such as down-regulation of miR-149-3p.,Reducing miR-149-3p may increase the inflammatory response in COPD patients through the regulation of the TLR-4/NF-κB signaling pathway. | 1 |
Exercise intolerance, exertional dyspnea, reduced health-related quality of life, and acute exacerbations are features characteristic of chronic obstructive pulmonary disease (COPD).,Patients with a primary diagnosis of COPD often report comorbidities and other secondary manifestations, which diversifies the clinical presentation.,Pulmonary rehabilitation that includes whole body exercise training is a critical part of management, and core programs involve endurance and resistance training for the upper and lower limbs.,Improvement in maximal and submaximal exercise capacity, dyspnea, fatigue, health-related quality of life, and psychological symptoms are outcomes associated with exercise training in pulmonary rehabilitation, irrespective of the clinical state in which it is commenced.,There may be benefits for the health care system as well as the individual patient, with fewer exacerbations and subsequent hospitalization reported with exercise training.,The varying clinical profile of COPD may direct the need for modification to traditional training strategies for some patients.,Interval training, one-legged cycling (partitioning) and non-linear periodized training appear to be equally or more effective than continuous training.,Inspiratory muscle training may have a role as an adjunct to whole body training in selected patients.,The benefits of balance training are also emerging.,Strategies to ensure that health enhancing behaviors are adopted and maintained are essential.,These may include training for an extended duration, alternative environments to undertake the initial program, maintenance programs following initial exercise training, program repetition, and incorporation of approaches to address behavioral change.,This may be complemented by methods designed to maximize uptake and completion of a pulmonary rehabilitation program. | In patients with COPD progressive dyspnoea leads to a sedentary lifestyle.,To date, no studies exist investigating the effects of Nordic Walking in patients with COPD.,Therefore, the aim was to determine the feasibility of Nordic Walking in COPD patients at different disease stages.,Furthermore we aimed to determine the short- and long-term effects of Nordic Walking on COPD patients' daily physical activity pattern as well as on patients exercise capacity.,Sixty COPD patients were randomised to either Nordic Walking or to a control group.,Patients of the Nordic Walking group (n = 30; age: 62 ± 9 years; FEV1: 48 ± 19% predicted) underwent a three-month outdoor Nordic Walking exercise program consisting of one hour walking at 75% of their initial maximum heart rate three times per week, whereas controls had no exercise intervention.,Primary endpoint: daily physical activities (measured by a validated tri-axial accelerometer); secondary endpoint: functional exercise capacity (measured by the six-minute walking distance; 6MWD).,Assessment time points in both groups: baseline, after three, six and nine months.,After three month training period, in the Nordic Walking group time spent walking and standing as well as intensity of walking increased (Δ walking time: +14.9 ± 1.9 min/day; Δ standing time: +129 ± 26 min/day; Δ movement intensity: +0.40 ± 0.14 m/s2) while time spent sitting decreased (Δ sitting time: -128 ± 15 min/day) compared to baseline (all: p < 0.01) as well as compared to controls (all: p < 0.01).,Furthermore, 6MWD significantly increased compared to baseline (Δ 6MWD: +79 ± 28 meters) as well as compared to controls (both: p < 0.01).,These significant improvements were sustained six and nine months after baseline.,In contrast, controls showed unchanged daily physical activities and 6MWD compared to baseline for all time points.,Nordic Walking is a feasible, simple and effective physical training modality in COPD.,In addition, Nordic Walking has proven to positively impact the daily physical activity pattern of COPD patients under short- and long-term observation.,Nordic Walking improves daily physical activities in COPD: a randomised controlled trial - ISRCTN31525632 | 1 |
Rationale: Aberrant bronchial epithelium-fibroblast communication is essential for the airway remodeling that contributes to chronic obstructive pulmonary disease (COPD).,Exosomes have emerged as novel mediators of intercellular communication, but their role in cigarette smoke (CS)-induced COPD is unknown.,Here, we investigated the role of exosomal miR-21 in the dysfunctional epithelium-fibroblast cross-talk caused by CS.,Methods: Normal or CS extract (CSE)-treated human bronchial epithelial (HBE) cells were co-cultured with bronchial fibroblasts (MRC-5 cells).,Exosomes were obtained from culture media or serum by use of commercial kits.,The size distribution and concentration of exosomes were analyzed by nanoparticle tracking analysis using a ZetaView particle tracker from ParticleMetrix.,Inhibition of miR-21 levels by tail vein injection of antagomir-21 into mice exposed to CS was used to demonstrate the role of miR-21 in airway remodeling leading to COPD in animals.,Results: For MRC-5 cells, co-culture with CSE-treated HBE cells or with exosomes derived from CSE-treated HBE cells resulted in the myofibroblast differentiation phenotype.,Exosomal miR-21 was responsible for myofibroblast differentiation through hypoxia-inducible factor 1α (HIF-1α) signaling by targeting the von Hippel-Lindau protein (pVHL); HIF-1α transcriptionally regulated the α-SMA gene.,For mice, downregulation of miR-21 prevented CS-induced airway remodeling.,The levels of exosomal miR-21 were high in sera of smokers and COPD patients and inversely correlated with FEV1/FVC.,Conclusion: We demonstrate that CS triggers the modification of exosome components and identify miR-21 derived from bronchial epithelial cells as a mediator of myofibroblast differentiation through the pVHL/HIF-1α signaling pathway, which has potential value for diagnosis and treatment of COPD. | Circulating endothelial microparticles (EMPs) and progenitor cells (PCs) are biological markers of endothelial function and endogenous repair capacity.,The study was aimed to investigate whether COPD patients have an imbalance between EMPs to PCs compared to controls and to evaluate the effect of cigarette smoke on these circulating markers.,Circulating EMPs and PCs were determined by flow cytometry in 27 nonsmokers, 20 smokers and 61 COPD patients with moderate to severe airflow obstruction.,We compared total EMPs (CD31+CD42b-), apoptotic if they co-expressed Annexin-V+ or activated if they co-expressed CD62E+, circulating PCs (CD34+CD133+CD45+) and the EMPs/PCs ratio between groups.,COPD patients presented increased levels of total and apoptotic circulating EMPs, and an increased EMPs/PCs ratio, compared with nonsmokers.,Women had less circulating PCs than men through all groups and those with COPD showed lower levels of PCs than both control groups.,In smokers, circulating EMPs and PCs did not differ from nonsmokers, being the EMPs/PCs ratio in an intermediate position between COPD and nonsmokers.,We conclude that COPD patients present an imbalance between endothelial damage and repair capacity that might explain the frequent concurrence of cardiovascular disorders.,Factors related to the disease itself and gender, rather than cigarette smoking, may account for this imbalance. | 1 |
Pulmonary rehabilitation (PR) is recommended in the management of people with chronic obstructive pulmonary disease (COPD), but referral to this service is low.,To identify barriers to, and facilitators for, referral to PR programmes from the perspective of Australian general practitioners.,Semi-structured interviews were conducted with general practitioners involved in the care of people with COPD.,Interview questions were informed by a validated behavioural framework and asked about participants’ experience of referring people with COPD for PR, and barriers to, or facilitators of, this behaviour.,Interviews were audiotaped, transcribed verbatim, and analysed using content analysis.,Twelve general practitioners participated in this study, 10 of whom had never referred a patient to a PR programme.,Four major categories relating to barriers to referral were identified: low knowledge of PR for COPD; low knowledge of how to refer; actual or anticipated access difficulties for patients; and questioning the need to do more to promote exercise behaviour change.,Awareness of benefit was the only current facilitator.,Three major categories of potential facilitators were identified: making PR part of standard COPD care through financial incentive; improving information flow with regard to referrals and services; and informing patients and public.,Significant barriers to referral exist, but opportunities to change the organisation of practice and information management were identified.,Behaviour change strategies which directly target these barriers and incorporate facilitators should make up the key components of interventions to improve referral to PR by general practitioners who care for people with COPD. | Objective To assess the effect of second generation, home based telehealth on health related quality of life, anxiety, and depressive symptoms over 12 months in patients with long term conditions.,Design A study of patient reported outcomes (the Whole Systems Demonstrator telehealth questionnaire study; baseline n=1573) was nested in a pragmatic, cluster randomised trial of telehealth (the Whole Systems Demonstrator telehealth trial, n=3230).,General practice was the unit of randomisation, and telehealth was compared with usual care.,Data were collected at baseline, four months (short term), and 12 months (long term).,Primary intention to treat analyses tested treatment effectiveness; multilevel models controlled for clustering by general practice and a range of covariates.,Analyses were conducted for 759 participants who completed questionnaire measures at all three time points (complete case cohort) and 1201 who completed the baseline assessment plus at least one other assessment (available case cohort).,Secondary per protocol analyses tested treatment efficacy and included 633 and 1108 participants in the complete case and available case cohorts, respectively.,Setting Provision of primary and secondary care via general practices, specialist nurses, and hospital clinics in three diverse regions of England (Cornwall, Kent, and Newham), with established integrated health and social care systems.,Participants Patients with chronic obstructive pulmonary disease (COPD), diabetes, or heart failure recruited between May 2008 and December 2009.,Main outcome measures Generic, health related quality of life (assessed by physical and mental health component scores of the SF-12, and the EQ-5D), anxiety (assessed by the six item Brief State-Trait Anxiety Inventory), and depressive symptoms (assessed by the 10 item Centre for Epidemiological Studies Depression Scale).,Results In the intention to treat analyses, differences between treatment groups were small and non-significant for all outcomes in the complete case (0.480≤P≤0.904) or available case (0.181≤P≤0.905) cohorts.,The magnitude of differences between trial arms did not reach the trial defined, minimal clinically important difference (0.3 standardised mean difference) for any outcome in either cohort at four or 12 months.,Per protocol analyses replicated the primary analyses; the main effect of trial arm (telehealth v usual care) was non-significant for any outcome (complete case cohort 0.273≤P≤0.761; available case cohort 0.145≤P≤0.696).,Conclusions Second generation, home based telehealth as implemented in the Whole Systems Demonstrator Evaluation was not effective or efficacious compared with usual care only.,Telehealth did not improve quality of life or psychological outcomes for patients with chronic obstructive pulmonary disease, diabetes, or heart failure over 12 months.,The findings suggest that concerns about potentially deleterious effect of telehealth are unfounded for most patients.,Trial Registration ISRCTN43002091. | 1 |
Dual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits in lung function and health status versus monotherapy.,The aim of this study was to determine whether early initiation of a dual bronchodilator versus monotherapy reduced the risk of deterioration in COPD.,This post hoc pooled analysis investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared with tiotropium (TIO) 18 mcg/day in a maintenance-naïve (MN) subgroup of patients relative to the intent-to-treat (ITT) population from three 6-month active comparator studies (n = 1747).,Other treatment arms (UMEC/VI 125/25, VI 25 and UMEC 125) comprised 850 patients in total but were not included in this analysis.,The primary endpoint was trough forced expiratory volume in 1 s (FEV1).,St George’s Respiratory Questionnaire (SGRQ) score, rescue medication use, and a novel composite endpoint of short-term clinically important deterioration (CID; ≥100 ml decrease in trough FEV1, ≥4-unit increase in SGRQ score, or a COPD exacerbation) were also assessed.,UMEC/VI improved trough FEV1 versus TIO at day 169 [least squares mean (95% confidence interval): MN: 146 ml (102-189) and ITT: 95 ml (71-118); both P < 0.001].,Both UMEC/VI and TIO improved SGRQ and rescue use in the two populations, with greater improvements in rescue use with UMEC/VI versus TIO.,UMEC/VI reduced the risk of short-term clinically important deterioration versus TIO [hazard ratio; 95% confidence interval: MN: 0.66 (0.51-0.85); ITT: 0.62 (0.54-0.71), both P ≤ 0.001].,Adverse events were similar across both populations and treatments.,Early use of dual-bronchodilator therapy has superior efficacy on lung function and may reduce the risk of short-term deterioration compared to monotherapy in symptomatic patients with COPD.,Clinical trial registration: GSK analysis 202066 (NCT01316900/DB2113360, NCT01316913/DB2113374, NCT01777334/ZEP117115).,Funding: This study was funded by GSK.,The online version of this article (doi:10.1007/s12325-016-0430-6) contains supplementary material, which is available to authorized users. | Current methods for assessing clinical outcomes in COPD mainly rely on physiological tests combined with the use of questionnaires.,The present review considers commonly used outcome measures such as lung function, health status, exercise capacity and physical activity, dyspnoea, exacerbations, the multi-dimensional BODE score, and mortality.,Based on current published data, we provide a concise overview of the principles, strengths and weaknesses, and discuss open questions related to each methodology.,Reviewed is the current set of markers for measuring clinically relevant outcomes with particular emphasis on their limitations and opportunities that should be recognized when assessing and interpreting their use in clinical trials of COPD. | 1 |
We have previously identified Urokinase Plasminogen Activator Receptor (PLAUR) as an asthma susceptibility gene.,In the current study we tested the hypothesis that PLAUR single nucleotide polymorphisms (SNPs) determine baseline lung function and contribute to the development of Chronic Obstructive Pulmonary Disease (COPD) in smokers.,25 PLAUR SNPs were genotyped in COPD subjects and individuals with smoking history (n = 992).,Linear regression was used to determine the effects of polymorphism on baseline lung function (FEV1, FEV1/FVC) in all smokers.,Genotype frequencies were compared in spirometry defined smoking controls (n = 176) versus COPD cases (n = 599) and COPD severity (GOLD stratification) using logistic regression.,Five SNPs showed a significant association (p < 0.01) with baseline lung function; rs2302524(Lys220Arg) and rs2283628(intron 3) were associated with lower and higher FEV1 respectively. rs740587(-22346), rs11668247(-20040) and rs344779(-3666) in the 5'region were associated with increased FEV1/FVC ratio. rs740587 was also protective for COPD susceptibility and rs11668247 was protective for COPD severity although no allele dose relationship was apparent.,Interestingly, several of these associations were driven by male smokers not females.,This study provides tentative evidence that the asthma associated gene PLAUR also influences baseline lung function in smokers.,However the case-control analyses do not support the conclusion that PLAUR is a major COPD susceptibility gene in smokers.,PLAUR is a key serine protease receptor involved in the generation of plasmin and has been implicated in airway remodelling. | The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease.,Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and Nfe2l2-deficient mice develop tobacco-induced emphysema.,We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second (FEV1) in the general population.,Five NFE2L2 and three KEAP1 tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390).,On average 3 FEV1 measurements during 3 surveys, respectively 7 FEV1 measurements during 8 surveys were present.,Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated FEV1 measurements.,In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in KEAP1 was associated with a higher FEV1 level (p = 0.02 for an additive effect), and SNP rs2364723 in NFE2L2 was associated with a lower FEV1 level (p = 0.06).,The associations were even more significant in the pooled cohort analysis.,No significant association of KEAP1 or NFE2L2 SNPs with FEV1 decline was observed.,This is the first genetic study on variations in key antioxidant transcriptional regulators KEAP1 and NFE2L2 and lung function in a general population.,It identified 2 SNPs in NFE2L2 and KEAP1 which affect the level of FEV1 in the general population.,It additionally shows that NFE2L2 and KEAP1 variations are unlikely to play a role in the longitudinal course of FEV1 in the general population. | 1 |
Circulating endothelial microparticles (EMPs) are emerging as biomarkers of chronic obstructive pulmonary disease (COPD) in individuals exposed to cigarette smoke (CS), but their mechanism of release and function remain unknown.,We assessed biochemical and functional characteristics of EMPs and circulating microparticles (cMPs) released by CS.,CS exposure was sufficient to increase microparticle levels in plasma of humans and mice, and in supernatants of primary human lung microvascular endothelial cells.,CS-released EMPs contained predominantly exosomes that were significantly enriched in let-7d, miR-191; miR-126; and miR125a, microRNAs that reciprocally decreased intracellular in CS-exposed endothelium.,CS-released EMPs and cMPs were ceramide-rich and required the ceramide-synthesis enzyme acid sphingomyelinase (aSMase) for their release, an enzyme which was found to exhibit significantly higher activity in plasma of COPD patients or of CS-exposed mice.,The ex vivo or in vivo engulfment of EMPs or cMPs by peripheral blood monocytes-derived macrophages was associated with significant inhibition of efferocytosis.,Our results indicate that CS, via aSMase, releases circulating EMPs with distinct microRNA cargo and that EMPs affect the clearance of apoptotic cells by specialized macrophages.,These targetable effects may be important in the pathogenesis of diseases linked to endothelial injury and inflammation in smokers. | Infection-related exacerbations of respiratory diseases are a major health concern; thus understanding the mechanisms driving them is of paramount importance.,Despite distinct inflammatory profiles and pathological differences, asthma and COPD share a common clinical facet: raised airway ATP levels.,Furthermore, evidence is growing to suggest that infective agents can cause the release of extracellular vesicle (EVs) in vitro and in bodily fluids.,ATP can evoke the P2X7/caspase 1 dependent release of IL-1β/IL-18 from EVs; these cytokines are associated with neutrophilia and are increased during exacerbations.,Thus we hypothesized that respiratory infections causes the release of EVs in the airway and that the raised ATP levels, present in respiratory disease, triggers the release of IL-1β/IL-18, neutrophilia and subsequent disease exacerbations.,To begin to test this hypothesis we utilised human cell-based assays, ex vivo murine BALF, in vivo pre-clinical models and human samples to test this hypothesis.,Data showed that in a murine model of COPD, known to have increased airway ATP levels, infective challenge causes exacerbated inflammation.,Using cell-based systems, murine models and samples collected from challenged healthy subjects, we showed that infection can trigger the release of EVs.,When exposed to ATP the EVs release IL-1β/IL-18 via a P2X7/caspase-dependent mechanism.,Furthermore ATP challenge can cause a P2X7 dependent increase in LPS-driven neutrophilia.,This preliminary data suggests a possible mechanism for how infections could exacerbate respiratory diseases and may highlight a possible signalling pathway for drug discovery efforts in this area. | 1 |
Health-related quality of life (HRQL) is an important patient-reported outcome measure used to describe the burden of chronic obstructive pulmonary disease (COPD) which is often accompanied by comorbid conditions.,Data from 2275 participants in the COPD cohort COSYCONET and from 4505 lung-healthy control subjects from the population-based KORA and SHIP studies were pooled.,Main outcomes were the five dimensions of the generic EQ-5D-3 L questionnaire and two EQ-5D index scores using a tariff based on valuations from the general population and an experience-based tariff.,The association of COPD in GOLD grades 1-4 and of several comorbid conditions with the EQ-5D index scores was quantified by multiple linear regression models while adjusting for age, sex, education, body mass index (BMI), and smoking status.,For all dimensions of the EQ-5D, the proportion of participants reporting problems was higher in the COPD group than in control subjects.,COPD was associated with significant reductions in the EQ-5D index scores (-0.05 points for COPD grades 1/2, -0.09 for COPD grade 3, -0.18 for COPD grade 4 according to the preference-based utility tariff, all p < 0.0001).,Adjusted mean index scores were 0.89 in control subjects and 0.85, 0.84, 0.81, and 0.72 in COPD grades 1-4 according to the preference-based utility tariff and 0.76, 0.71, 0.68, 0.64, and 0.58 for control subjects and COPD grades 1-4 for the experience-based tariff respectively.,Comorbidities had additive negative effects on the index scores; the effect sizes for comorbidities were comparable to or smaller than the effects of COPD grade 3.,No statistically significant interactions between COPD and comorbidities were observed.,Score differences between COPD patients and control subjects were most pronounced in younger age groups.,Compared with control subjects, the considerable reduction of HRQL in patients with COPD was mainly due to respiratory limitations, but observed comorbidities added linearly to this effect.,Younger COPD patients showed a greater loss of HRQL and may therefore be in specific need of comprehensive disease management.,NCT01245933 | This study was conducted to investigate the association between the chronic obstructive pulmonary disease (COPD) assessment test (CAT) and depression in COPD patients.,The Korean versions of the CAT and patient health questionnaire-9 (PHQ-9) were used to assess COPD symptoms and depressive disorder, respectively.,In total, 803 patients with COPD were enrolled from 32 hospitals and the prevalence of depression was 23.8%.,The CAT score correlated well with the PHQ-9 score (r=0.631; P<0.001) and was significantly associated with the presence of depression (β±standard error, 0.452±0.020; P<0.001).,There was a tendency toward increasing severity of depression in patients with higher CAT scores.,By assessment groups based on the 2011 Global Initiative for Chronic Obstructive Lung Disease guidelines, the prevalence of depression was affected more by current symptoms than by airway limitation.,The area under the receiver operating characteristic curve for the CAT was 0.849 for predicting depression, and CAT scores ≥21 had the highest accuracy rate (80.6%).,Among the eight CAT items, energy score showed the best correlation and highest power of discrimination.,CAT scores are significantly associated with the presence of depression and have good performance for predicting depression in COPD patients. | 1 |
Pulmonary hypertension (PH) in COPD is associated with a higher mortality and an increased risk on exacerbations compared to COPD patients without PH.,The aim was to evaluate the diagnostic value of pulmonary artery (PA) measurements on chest computed tomography (CT) for PH in end-stage COPD.,COPD patients evaluated for eligibility for lung transplantation between 2004 and 2015 were retrospectively analyzed.,Clinical characteristics, chest CTs, spirometry, and right-sided heart catheterizations (RHC) were studied.,Diameters of PA and ascending aorta (A) were measured on CT.,Diagnostic properties of different cut-offs of PA diameter and PA:A ratio in diagnosing PH were calculated.,Of 92 included COPD patients, 30 (32.6 %) had PH at RHC (meanPAP > 25 mm Hg).,PA:A > 1 had a negative predictive value (NPV) of 77.9 % and a positive predictive value (PPV) of 63.1 % with an odds ratio (OR (CI 95 %)) of 5.60 (2.00-15.63).,PA diameter ≥30 mm had a NPV of 78 % and PPV of 64 % with an OR (CI 95 %) of 6.95 (2.51-19.24).,A small PA diameter and PA:A make the presence of PH unlikely but cannot exclude its presence in end-stage COPD.,A large PA diameter and PA:A maybe used to detect PH early. | Pulmonary hypertension is a frequent complication of chronic obstructive pulmonary disease (COPD) and associated with a worse survival and increased risk of hospitalization for exacerbation of COPD.,However, little information exists regarding the potential role of systemic inflammation in pulmonary hypertension of COPD.,The purpose of the present study was to investigate the degree of C-reactive protein (CRP) and endothelin-1 (ET-1) levels in COPD patient with and without pulmonary hypertension.,The levels of CRP and ET-1 were investigated in 58 COPD patient with pulmonary hypertension and 50 patients without pulmonary hypertension.,Pulmonary hypertension was defined as a systolic pulmonary artery pressure (Ppa) ≥35 mmHg assessed by Doppler echocardiography.,Plasma CRP and ET-1 levels were significantly higher in patients with pulmonary hypertension than in patients without hypertension.,There were significant positive correlations between the plasma ET-1 level and CRP level in the whole study groups.,For COPD patients, systolic Ppa correlated significantly with plasma CRP levels and plasma ET-1 levels.,These findings support a possibility that CRP and ET-1 correlate to pulmonary hypertension in COPD patients. | 1 |
Chronic obstructive pulmonary disease (COPD) outpatients account for a large burden of usual care by respirologists.,EPOCONSUL is the first national clinical audit conducted in Spain on the medical care for COPD patients delivered in outpatient respiratory clinics.,We aimed to evaluate the clinical interventions and the degree of adherence to recommendations in outpatients of current COPD clinical practice guidelines.,This is an observational study with prospective recruitment (May 2014-May 2015) of patients with a COPD diagnosis as seen in outpatient respiratory clinics.,The information collected was historical in nature as for the clinical data of the last and previous consultations, and the information concerning hospital resources was concurrent.,A total of 17,893 clinical records of COPD patients in outpatient respiratory clinics from 59 Spanish hospitals were evaluated.,Of the 5,726 patients selected, 4,508 (78.7%) were eligible.,Overall, 12.1% of COPD patients did not fulfill a diagnostic spirometry criteria.,Considerable variability existed in the available resources and work organization of the hospitals, although the majority were university hospitals with respiratory inpatient units.,There was insufficient implementation of clinical guidelines in preventive and educational matters.,In contrast, quantitative evaluation of dyspnea grade (81.9%) and exacerbation history (70.9%) were more frequently performed.,Only 12.4% had COPD severity calculated according to the Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) index.,Phenotype characteristics according to Spanish National Guideline for COPD were determined in 46.3% of the audited patients, and the risk evaluation according to Global initiative for chronic Obstructive Lung Disease was estimated only in 21.9%.,The EPOCONSUL study reports the current situation of medical care for COPD patients in outpatient clinics in Spain, revealing its variability, strengths, and weaknesses.,This information has to be accounted for by health managers to define corrective strategies and maximize good clinical practice. | Chronic obstructive pulmonary disease (COPD) exacerbations have a negative impact on the quality of life of patients and the evolution of the disease.,We have investigated the prognostic value of several health-related quality of life questionnaires to predict the appearance of a composite event (new ambulatory or emergency exacerbation, hospitalization, or death) over a 1-year follow-up.,This was a multicenter, prospective, observational study.,Patients completed four questionnaires after recovering from an exacerbation (COPD Assessment Test [CAT], a Clinical COPD Questionnaire [CCQ], COPD Severity Score [COPDSS], and Airways Questionnaire [AQ20]).,Patients were followed-up until the appearance of the composite event or for 1 year, whichever came first.,A total of 497 patients were included in the study.,The majority of them were men (89.7%), with a mean age of 68.7 (SD 9.2) years, and a forced expiratory volume in 1 second of 47.1% (SD 17.5%).,A total of 303 (61%) patients experienced a composite event.,Patients with an event had worse mean scores of all questionnaires at baseline compared to patients without event: CAT=12.5 vs 11.3 (P=0.028); CCQ=2.2 vs 1.9 (P=0.013); COPDSS=12.3 vs 10.9 (P=0.001); AQ20=8.3 vs 7.5 (P=0.048).,In the multivariate analysis, only previous history of exacerbations and CAT score ≥13.5 were significant risk factors for the composite event.,A CAT score ≥13.5 increased the predictive value of previous exacerbations with an area under the receiver operating characteristic curve of 0.864 (95% CI: 0.829-0.899; P=0.001).,The predictive value of previous exacerbations significantly increased only in one of the four trialled questionnaires, namely in the CAT questionnaire.,However, previous history of exacerbations was the strongest predictor of the composite event. | 1 |
Multi-morbidity is common in patients with chronic obstructive pulmonary disease and low levels of physical activity are hypothesized to be an important risk factor.,The current study aimed to assess the longitudinal association between physical activity and risk of seven categories of comorbidity in chronic obstructive pulmonary disease patients.,The study included 409 patients from primary care practice in the Netherlands and Switzerland.,We assessed physical activity using the Longitudinal Ageing Study Amsterdam Physical Activity Questionnaire at baseline and followed patients for up to 5 years.,During follow-up, patients reported their comorbidities (cardiovascular, neurological, endocrine, musculoskeletal, malignant, and infectious diseases) and completed the Hospital Anxiety and Depression Scale questionnaire for mental health assessment.,We implemented multinomial logistic regression (an approximation to discrete time survival model using death as a competing risk) for our analysis.,Study results did not suggest a statistically significant association of baseline physical activity with the development of seven categories of comorbidity.,However, when we focused on depression and anxiety symptoms, we found that higher levels of physical activity at baseline were associated with a lower risk for depression (adjusted hazard ratio, 0.85; 0.75-0.95; p = 0.005) and anxiety (adjusted hazard ratio, 0.89; 0.79-1.00; p = 0.045).,In chronic obstructive pulmonary disease patients, those with high physical activity are less likely to develop depression or anxiety symptoms over time.,Increasing physical activity in chronic obstructive pulmonary disease patients may be an approach for testing to lower the burden from incident depression and anxiety.,Patients with chronic lung disease who stay physically active could reduce their chances of depression and anxiety.,Milo Puhan at the University of Zurich, Switzerland, and co-workers assessed the association between physical activity and the risk of developing various co-existing diseases in 409 patients with chronic obstructive pulmonary disease (COPD).,Co-morbidities such as cardiovascular diseases, diabetes and depression are prevalent in patients with COPD, but the reasons why are not clear.,Puhan’s team assessed patients’ activity levels using an existing questionnaire, and administered another questionnaire to assess mental health.,They followed the cohort for 5 years.,Results indicated weak associations between physical activity levels and most physical illnesses, but there were significant links between higher levels of physical activity and a reduced risk of depression and anxiety.,The results could inform novel COPD treatment programs. | Physical inactivity is associated with poor outcomes in COPD, and as a result, interventions to improve physical activity (PA) are a current research focus.,However, many trials have been small and inconclusive.,The aim of this systematic review and meta-analysis was to study the effects of randomized controlled trials (RCTs) targeting PA in COPD.,Databases (Physiotherapy Evidence Database [PEDro], Embase, MEDLINE, CINAHL and the Cochrane Central Register for Controlled Trials) were searched using the following keywords: “COPD”, “intervention” and “physical activity” from inception to May 20, 2016; published RCTs that aimed to increase PA in individuals with COPD were included.,The PEDro scale was used to rate study quality.,Standardized mean differences (effect sizes, ESs) with 95% confidence intervals (CIs) were determined.,Effects of included interventions were also measured according to the minimal important difference (MID) in daily steps for COPD (599 daily steps).,A total of 37 RCTs with 4,314 participants (mean forced expiratory volume in one second (FEV1) % predicted 50.5 [SD=10.4]) were identified.,Interventions including exercise training (ET; n=3 studies, 103 participants) significantly increased PA levels in COPD compared to standard care (ES [95% CI]; 0.84 [0.44-1.25]).,The addition of activity counseling to pulmonary rehabilitation (PR; n=4 studies, 140 participants) showed important effects on PA levels compared to PR alone (0.47 [0.02-0.92]), achieving significant increases that exceeded the MID for daily steps in COPD (mean difference [95% CI], 1,452 daily steps [549-2,356]).,Reporting of methodological quality was poor in most included RCTs.,Interventions that included ET and PA counseling during PR were effective strategies to improve PA in COPD. | 1 |
Hospitalization for a severe exacerbation of COPD (eCOPD) is an important event in the natural history of COPD.,Identifying factors related to mortality 1 year after hospitalization could help determine interventions to reduce mortality.,In a prospective, observational, multicentre study, we evaluated data from two cohorts: the Spanish audit of hospital COPD exacerbation care (our derivation sample) and the Spanish cohort of the European audit of COPD exacerbation care (our validation sample).,The endpoint was all-cause mortality.,Mortality was determined by local research managers of the participating hospitals and matched the official national index records in Spain.,In the multivariate analysis, factors independently related to an increase in mortality were older age, cardio-cerebro-vascular and/or dementia comorbidities, PaCO2 > 55 mmHg measured at emergency department arrival, hospitalizations for COPD exacerbations in the previous year, and hospital characteristics.,The area under the receiver-operating curve for this model was 0.75 in the derivation cohort and 0.76 in the validation cohort.,One-year mortality following the index hospitalization for an exacerbation of COPD was related to clinical characteristics of the patient and of the index event, previous events of similar severity, and characteristics of the hospital where the patient was treated. | 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. | 1 |
Prevention of chronic obstructive pulmonary disease hospital readmissions is an international priority aimed to slow disease progression and limit costs.,Evidence of the risk of readmission and of interventions that might prevent it is lacking.,We aimed to determine readmission risk for chronic obstructive pulmonary disease, factors influencing that risk, and variation in readmission risk between hospitals across 7.5 million people in London.,This retrospective longitudinal observational study included all chronic obstructive pulmonary disease admissions to any hospital in the United Kingdom among patients registered at London general practices who had emergency National Health Service chronic obstructive pulmonary disease hospital admissions between April 2006 and March 2010.,Influence of patient characteristics, geographical deprivation score, length of stay, day of week of admission or of discharge, and admitting hospital, were assessed using multiple logistic regression. 38,894 chronic obstructive pulmonary disease admissions of 20,932 patients aged ≥ 45 years registered with London general practices were recorded. 6295 patients (32.2%) had at least one chronic obstructive pulmonary disease readmission within 1 year. 1993 patients (10.2%) were readmitted within 30 days and 3471 patients (17.8%) were readmitted within 90 days.,Age and patient geographical deprivation score were very weak predictors of readmission.,Rates of chronic obstructive pulmonary disease readmissions within 30 days and within 90 days did not vary among the majority of hospitals.,The finding of lower chronic obstructive pulmonary disease readmission rates than was previously estimated and the limited variation in these rates between hospitals suggests that the opportunity to reduce chronic obstructive pulmonary disease readmission risk is small.,A managed reduction of hospital readmissions for London-based chronic lung disease patients may not be needed.,Preventing hospital readmissions for patients with chronic obstructive pulmonary disease (COPD) is a key priority to improve patient care and limit costs.,However, few data are available to determine and ultimately reduce the risk of readmission.,Timothy Harries at King’s College, London, and co-workers conducted a longitudinal study incorporating all COPD admissions into UK hospitals for 20,932 patients registered at London general practitioners between 2006 and 2010.,They found that 32% of patients were readmitted within a year, 17.8% within 90 days and 10% within 30 days.,Neither age nor geographical deprivation were useful predictors of readmission.,These represent lower than estimated levels of readmission, suggesting there may be fewer opportunities to reduce the risk of readmission further. | Chronic obstructive pulmonary disease (COPD) is characterised by high morbidity and mortality.,It remains unknown which aspect of lung function carries the most prognostic information and if simple spirometry is sufficient.,Survival was assessed in COPD outpatients whose data had been added prospectively to a clinical audit database from the point of first full lung function testing including spirometry, lung volumes, gas transfer and arterial blood gases.,Variables univariately associated with survival were entered into a multivariate Cox proportional hazard model.,604 patients were included (mean±sd age 61.9±9.7 years; forced expiratory volume in 1 s 37±18.1% predicted; 62.9% males); 229 (37.9%) died during a median follow-up of 83 months.,Median survival was 91.9 (95% CI 80.8-103) months with survival rates at 3 and 5 years 0.83 and 0.66, respectively.,Carbon monoxide transfer factor % pred quartiles (best quartile (>51%): HR 0.33, 95% CI 0.172-0.639; and second quartile (51-37.3%): HR 0.52, 95% CI 0.322-0.825; versus lowest quartile (<27.9%)), age (HR 1.04, 95% CI 1.02-1.06) and arterial oxygen partial pressure (HR 0.85, 95% CI 0.77-0.94) were the only parameters independently associated with mortality.,Measurement of gas transfer provides additional prognostic information compared to spirometry in patients under hospital follow-up and could be considered routinely.,Transfer factor not GOLD stage is the most powerful predictor of survival in patients with COPDhttp://ow.ly/mGmjG | 1 |
Patients with COPD often experience severe exacerbations involving hospitalization, which accelerate lung function decline and reduce quality of life.,This study aimed to develop and validate a predictive model to identify patients at risk of developing severe COPD exacerbations using administrative claims data, to facilitate appropriate disease management programs.,A predictive model was developed using a retrospective cohort of COPD patients aged 55-89 years identified between July 1, 2010 and June 30, 2013 using Humana’s claims data.,The baseline period was 12 months postdiagnosis, and the prediction period covered months 12-24.,Patients with and without severe exacerbations in the prediction period were compared to identify characteristics associated with severe COPD exacerbations.,Models were developed using stepwise logistic regression, and a final model was chosen to optimize sensitivity, specificity, positive predictive value (PPV), and negative PV (NPV).,Of 45,722 patients, 5,317 had severe exacerbations in the prediction period.,Patients with severe exacerbations had significantly higher comorbidity burden, use of respiratory medications, and tobacco-cessation counseling compared to those without severe exacerbations in the baseline period.,The predictive model included 29 variables that were significantly associated with severe exacerbations.,The strongest predictors were prior severe exacerbations and higher Deyo-Charlson comorbidity score (OR 1.50 and 1.47, respectively).,The best-performing predictive model had an area under the curve of 0.77.,A receiver operating characteristic cutoff of 0.4 was chosen to optimize PPV, and the model had sensitivity of 17%, specificity of 98%, PPV of 48%, and NPV of 90%.,This study found that of every two patients identified by the predictive model to be at risk of severe exacerbation, one patient may have a severe exacerbation.,Once at-risk patients are identified, appropriate maintenance medication, implementation of disease-management programs, and education may prevent future exacerbations. | The objectives of this study were to estimate the impact of recruitment source and outcome definition on the incidence of acute exacerbations of COPD (AECOPD) and explore possible predictors of AECOPD.,During a 1-year follow-up, we performed a baseline visit and four telephone interviews of 81 COPD patients and 132 controls recruited from a population-based survey and 205 hospital-recruited COPD patients.,Both a definition based on health care utilization and a symptom-based definition of AECOPD were applied.,For multivariate analyses, we chose a negative binomial regression model.,COPD patients from the population- and hospital-based samples experienced on average 0.4 utilization-defined and 2.9 symptom-defined versus 1.0 and 5.9 annual exacerbations, respectively.,The incidence rate ratios for utilization-defined AECOPD were 2.45 (95% CI 1.22-4.95), 3.43 (95% CI 1.59-7.38), and 5.67 (95% CI 2.58-12.48) with Global Initiative on Obstructive Lung Disease spirometric stages II, III, and IV, respectively.,The corresponding incidence rate ratios for the symptom-based definition were 3.08 (95% CI 1.96-4.84), 3.45 (95% CI 1.92-6.18), and 4.00 (95% CI 2.09-7.66).,Maintenance therapy (regular long-acting muscarinic antagonists, long-acting beta-2 agonists, inhaled corticosteroids, or theophylline) also increased the risk of AECOPD with both exacerbation definitions (incidence rate ratios 1.65 and 1.73, respectively).,The risk of AECOPD was 59%-78% higher in the hospital sample than in the population sample.,If externally valid conclusions are to be made regarding incidence and predictors of AECOPD, studies should be based on general population samples or adjustments should be made on account of a likely higher incidence in other samples.,Likewise, the effect of different AECOPD definitions should be taken into consideration. | 1 |
Limited evidence links air pollution exposure to chronic cough and sputum production.,Few reports have investigated the association between long-term exposure to air pollution and classically defined chronic bronchitis.,Our objective was to estimate the association between long-term exposure to particulate matter (diameter <10 μm, PM10; <2.5μm, PM2.5), nitrogen dioxide (NO2), and both incident and prevalent chronic bronchitis.,We estimated annual average PM2.5, PM10, and NO2 concentrations using a national land-use regression model with spatial smoothing at home addresses of participants in a prospective nationwide U.S. cohort study of sisters of women with breast cancer.,Incident chronic bronchitis and prevalent chronic bronchitis, cough and phlegm, were assessed by questionnaires.,Among 47,357 individuals with complete data, 1,383 had prevalent chronic bronchitis at baseline, and 647 incident cases occurred over 5.7-y average follow-up.,No associations with incident chronic bronchitis were observed.,Prevalent chronic bronchitis was associated with PM10 [adjusted odds ratio (aOR) per interquartile range (IQR) difference (5.8 μg/m3)=1.07; 95% confidence interval (CI): 1.01, 1.13].,In never-smokers, PM2.5 was associated with prevalent chronic bronchitis (aOR=1.18 per IQR difference; 95% CI: 1.04, 1.34), and NO2 was associated with prevalent chronic bronchitis (aOR=1.10; 95% CI=1.01, 1.20), cough (aOR=1.10; 95% CI: 1.05, 1.16), and phlegm (aOR=1.07; 95% CI: 1.01, 1.14); interaction p-values (nonsmokers vs. smokers) <0.05.,PM10 exposure was related to chronic bronchitis prevalence.,Among never-smokers, PM2.5 and NO2 exposure was associated with chronic bronchitis and component symptoms.,Results may have policy ramifications for PM10 regulation by providing evidence for respiratory health effects related to long-term PM10 exposure. https://doi.org/10.1289/EHP2199 | Ambient particulate matter (PM) can trigger adverse reactions in the respiratory system, but less is known about the effect of indoor PM.,In this longitudinal study, we investigated the relationships between indoor PM and clinical parameters in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,Indoor air quality (PM2.5 and PM10 levels) was monitored in the patients’ bedroom, kitchen, living room, and front door at baseline and every two months for one year.,At each home visit, the patients were asked to complete spirometry and questionnaire testing.,Exacerbations were assessed by chart review and questionnaires during home visits.,Generalized estimating equation (GEE) analysis (n = 83) showed that the level of wheezing was significantly higher in patients whose living room and kitchen had abnormal (higher than ambient air quality standards in Taiwan) PM2.5 and PM10 levels.,Patients who lived in houses with abnormal outdoor PM2.5 levels had higher COPD Assessment Test scores (physical domain), and those who lived in houses with abnormal PM10 levels in the living room and kitchen had higher London Chest Activity of Daily Living scores.,Increased PM levels were associated with worse respiratory symptoms and increased risk of exacerbation in patients with moderate to very severe COPD. | 1 |
Phase III studies demonstrated efficacy and safety of nebulized glycopyrrolate inhalation solution (GLY) in subjects with COPD.,Secondary analyses were performed to examine the effect of background long-acting beta2-agonist (LABA) use on the efficacy and safety of nebulized GLY.,In two 12-week placebo-controlled studies (GOLDEN 3 and GOLDEN 4) and one 48-week, open-label active-controlled study (GOLDEN 5), a total of 2,379 subjects were stratified by background LABA use (LABA-yes: n=861; LABA-no: n=1,518) and randomized to placebo vs GLY 25 or 50 µg twice daily, or GLY 50 µg twice daily vs tiotropium (TIO) 18 µg once daily.,Lung function, patient-reported outcomes, exacerbations, and safety were assessed.,Compared with placebo, pooled data from the 12-week studies showed significant improvements from baseline with GLY 25 and 50 µg across LABA subgroups in trough FEV1 (LABA-yes: 0.101 and 0.110 L; LABA-no: 0.092 and 0.101 L, respectively; P<0.001) and St George’s Respiratory Questionnaire total score (SGRQ; LABA-yes: −2.957 and −3.888; LABA-no: −3.301 and −2.073, respectively; P<0.05).,Incidence of treatment-emergent adverse events (TEAEs) was similar in LABA subgroups, and lower in GLY 25 µg vs placebo.,In the 48-week active-controlled study, GLY and TIO both showed improvement from baseline across LABA subgroups in FEV1 (LABA-yes: 0.106 and 0.092 L; LABA-no: 0.096 and 0.096 L, respectively) and in SGRQ total score (LABA-yes: −5.190 and −3.094; LABA-no: −4.368 and −4.821, respectively).,Incidence of TEAEs was similar between GLY and TIO, and across LABA subgroups.,Exacerbation rates were similar across treatments and LABA subgroups, and cardiovascular events of special interest were more frequent in the LABA-no subgroup.,Nebulized GLY, combined with LABA, did not generate any additional safety signals.,Nebulized GLY demonstrated efficacy and was well tolerated up to 48 weeks in subjects with COPD with/without background LABA. | 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 |
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 | Physical inactivity is a cardinal feature of chronic obstructive pulmonary disease (COPD), and is associated with increased morbidity and mortality.,Pedometers, which have been used in healthy populations, might also increase physical activity in patients with COPD.,COPD patients taking part in a 3-month individualised programme to promote an increase in their daily physical activity were randomised to either a standard programme of physical activity encouragement alone, or a pedometer-based programme.,Assessments were performed by investigators blinded to treatment allocation.,Change in average 1-week daily step count, 6-min walking distance (6MWD), modified Medical Research Council scale, St George’s respiratory questionnaire (SGRQ) and COPD assessment test (CAT) were compared between groups.,102 patients were recruited, of whom 97 completed the programme (pedometer group: n=50; control group: n=47); 60.8% were male with a mean±sd age of 68.7±8.5 years, and forced expiratory volume in 1 s (FEV1) 66.1±19.4% and FEV1/forced vital capacity 55.2±9.5%.,Both groups had comparable characteristics at baseline.,The pedometer group had significantly greater improvements in: physical activity 3080±3254 steps·day−1versus 138.3±1950 steps·day−1 (p<0.001); SGRQ −8.8±12.2 versus −3.8±10.9 (p=0.01); CAT score −3.5±5.5 versus −0.6±6.6 (p=0.001); and 6MWD 12.4±34.6 versus −0.7±24.4 m (p=0.02) than patients receiving activity encouragement only.,A simple physical activity enhancement programme using pedometers can effectively improve physical activity level and quality of life in COPD patients.,Pedometer-based programme produced clinically important improvements in physical activity and health status in COPDhttp://ow.ly/AmcCO | 1 |
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. | Chronic obstructive pulmonary disease is a common condition and a major cause of mortality.,COPD is characterized by irreversible airflow obstruction.,The physiological abnormalities observed in COPD are due to a combination of emphysema and obliteration of the small airways in association with airway inflammation.,The predominant cells involved in this inflammatory response are CD8+ lymphocytes, neutrophils, and macrophages.,Although eosinophilic airway inflammation is usually considered a feature of asthma, it has been demonstrated in large and small airway tissue samples and in 20%-40% of induced sputum samples from patients with stable COPD.,This airway eosinophilia is increased in exacerbations.,Thus, modifying eosinophilic inflammation may be a potential therapeutic target in COPD.,Eosinophilic airway inflammation is resistant to inhaled corticosteroid therapy, but does respond to systemic corticosteroid therapy, and the degree of response is related to the intensity of the eosinophilic inflammation.,In COPD, targeting treatment to normalize the sputum eosinophilia reduced the number of hospital admissions.,Whether controlling eosinophilic inflammation in COPD patients with an airway eosinophilia will modify disease progression and possibly alter mortality is unknown, but warrants further investigation. | 1 |
The use of inhaled corticosteroids in patients with chronic obstructive pulmonary disease (COPD) has been associated with an increased risk of pneumonia in controlled clinical trials and case-control analyses.,Using claims databases as a research model of real-world diagnosis and treatment, to determine if the use and dose of inhaled corticosteroids (ICS) among patients with newly diagnosed COPD are associated with increased risk of pneumonia.,This was a retrospective cohort analysis of patients diagnosed with COPD between January 01, 2006 and September 30, 2010, drawn from databases (years 2006-2010).,Patients (aged ≥45 years) were followed until first pneumonia diagnosis, end of benefit enrollment, or December 31, 2010, whichever was earliest.,A Cox proportional hazard model was used to assess the association of ICS use and risk of pneumonia, controlling for baseline characteristics.,Daily ICS use was classified into low, medium, and high doses (1 μg-499 μg, 500 μg-999 μg, and ≥1000 μg fluticasone equivalents daily) and was modeled as a time-dependent variable.,Among 135,445 qualifying patients with a total of 243,097 person-years, there were 1020 pneumonia incidences out of 5677 person-years on ICS (crude incidence rate, 0.180 per person-year), and 27,730 pneumonia incidences out of 237,420 person-years not on ICS (crude incidence rate, 0.117 per person-year).,ICS use was associated with a dose-related increase in risk of pneumonia, with adjusted hazard ratios (versus no use; (95% confidence interval) of 1.38 (1.27-1.49) for low-dose users, 1.69 (1.52-1.88) for medium-dose users, and 2.57 (1.98-3.33) for high-dose users (P < 0.01 versus no use and between doses).,The use of ICS in newly diagnosed patients with COPD is potentially associated with a dose-related increase in the risk of pneumonia. | The relationship between prior health care utilization and respiratory medication prescriptions in an unselected population of patients with COPD is not known.,We determined the prescribed respiratory medications and respiratory and nonrespiratory health care encounters in 523 Veterans with COPD at the Cincinnati Veterans Affairs Medical Center between 2000 and 2005.,Prescribed treatments were compared with the GOLD guidelines and each patient was classified as receiving less medications than recommended in the guidelines (<G), medications according to the guidelines (=G), or more medications than recommended (>G).,Respiratory medications were <G for 54%, =G in 33%, and >G for 14% of the patients studied.,For GOLD stages 1 and 2, <G patients had the fewest and >G patients the most prior respiratory encounters during a 12 month period (0.31 ± 0.073 (0.21, 0.47), 0.75 ± 0.5 (0.37, 1.5), 1.1 ± 0.27 (0.74, 1.6) visits/person/year, <G, =G, >G, respectively, mean + standard error of mean (SEM) (95% confidence limits) 2 degrees of freedom (df) ANOVA P < 0.001 for prescription effect).,For GOLD stages 3 and 4, <G was associated with significantly fewer prior respiratory visits than was =G (0.78 ± 0.11 (0.6, 1.0) and 2.4 ± 0.47 (1.9, 3.1) visits/person/year, respectively, P < 0.001).,There were no differences in nonrespiratory health care visits for GOLD stages 1 and 2 by prescription level (3.1 ± 0.24 (2.6, 3.5), 3.1 ± 0.46 (2.1, 4.6) and 4.1 ± 0.55 (3.3, 5.1) visits/person/year, <G, =G, >G respectively, 2 df ANOVA P = 0.096) or for GOLD stages 3 and 4 (3.6 ± 0.25 (3.2, 4.1) and 4.0 ± 0.44 (3.3, 4.9) visits/person/year, <G and =G, respectively, P = 0.36).,Respiratory medications prescribed for an unselected population with a broad range of COPD severity complied poorly with the GOLD pharmacologic treatment guidelines but correlated with the number of prior respiratory health care visits. | 1 |
Co-morbidities are common in chronic obstructive pulmonary disease (COPD).,We assessed the contribution of common co-morbidities on health related quality of life (HRQoL) among COPD patients.,Using both generic (15D) and respiratory-specific (AQ20) instruments, HRQoL was assessed in a hospital based COPD population (N = 739, 64% males, mean age 64 years, SD 7 years) in this observational study with inferential analysis.,The prevalence of their co-morbidities was compared with those of 5000 population controls.,The patients represented all severity stages of COPD and the patterns of common concomitant disorders differed between patients.,Co-morbidities such as psychiatric conditions, alcohol abuse, cardiovascular diseases, and diabetes were more common among COPD patients than in age and gender matched controls.,Psychiatric conditions and alcohol abuse were the strongest determinants of HRQoL in COPD and could be detected by both 15D (Odds Ratio 4.7 and 2.3 respectively) and AQ20 (OR 2.0 and 3.0) instruments.,Compared to respiratory specific AQ20, generic 15D was more sensitive to the effects of comorbidities while AQ20 was slightly more sensitive for the low FEV1.,FEV1 was a strong determinant of HRQoL only at more severe stages of disease (FEV1 < 40% of predicted).,Poor HRQoL also predicted death during the next five years.,The results suggest that co-morbidities may impair HRQoL at an early stage of the disease, while bronchial obstruction becomes a significant determinant of HRQoL only in severe COPD. | To systematically investigate the prevalence of pain, factors related with pain and pain management interventions in patients with chronic obstructive pulmonary disease (COPD).,Systematic review and meta-analysis.,PubMed (MEDLINE), EMBASE, CINAHL and PsychINFO from 1966 to December 2013.,Studies were included if they presented clinical data on pain or symptom burden in patients with COPD, or pain as a domain of quality of life (QoL).,All types of study designs were included.,Of the 1571 articles that were identified, 39 met the inclusion criteria and were included in this review.,Fourteen studies focused on pain and symptom burden (including pain) in patients with COPD and 25 studies focused on QoL using a questionnaire that included a separate pain domain.,Reported pain prevalence in high-quality studies ranged from 32 to 60%.,Included studies report that pain is more prevalent in patients with COPD compared to participants from the general population.,Comorbidity, nutritional status, QoL and several symptoms were related to pain.,None of the included studies reported a significant relationship between lung function and pain prevalence or severity.,However, studies investigating pain in patients with moderate COPD reported higher pain prevalence compared to studies in patients with severe of very severe COPD.,Although literature on this topic is limited and shows substantial heterogeneity, pain seems to be a significant problem in patients with COPD and is related to several other symptoms, comorbidity and QoL.,Data synthesis suggests that pain is more prevalent in patients with moderate COPD compared to patients with severe or very severe COPD.,Further research is needed and should focus on determining a more accurate pain prevalence, investigating the relationship between pain prevalence, disease severity and comorbidity and explore implementation and efficacy of pain management interventions in patients with COPD. | 1 |
We recently reported that epithelial-mesenchymal transition (EMT) is active in the airways in chronic obstructive pulmonary disease (COPD), suggesting presence of an active profibrotic and promalignant stroma.,With no data available on potential treatment effects, we undertook a blinded analysis of inhaled corticosteroids (ICS) effects versus placebo on EMT markers in previously obtained endobronchial biopsies in COPD patients, as a “proof of concept” study.,Assessment of the effects of inhaled fluticasone propionate (FP; 500 μg twice daily for 6 months) versus placebo in 34 COPD patients (23 on fluticasone propionate and eleven on placebo).,The end points were epidermal growth factor receptor (EGFR; marker of epithelial activation) and the biomarkers of EMT: reticular basement membrane (Rbm) fragmentation (“hallmark” structural marker), matrix metalloproteinase-9 (MMP-9) cell expression, and S100A4 expression in basal epithelial and Rbm cells (mesenchymal transition markers).,Epithelial activation, “clefts/fragmentation” in the Rbm, and changes in the other biomarkers all regressed on ICS, at or close to conventional levels of statistical significance.,From these data, we have been able to nominate primary and secondary end points and develop power calculations that would be applicable to a definitive prospective study.,Although only a pilot “proof of concept” study, this trial provided strong suggestive support for an anti-EMT effect of ICS in COPD airways.,A larger and fully powered prospective study is now indicated as this issue is likely to be extremely important.,Such studies may clarify the links between ICS use and better clinical outcomes and protection against lung cancer in COPD. | The reticular basement membrane (Rbm) in smokers and especially smokers with COPD is fragmented with "clefts" containing cells staining for the collagenase matrix-metalloproteinase-9 (MMP-9) and fibroblast protein, S100A4.,These cells are also present in the basal epithelium.,Such changes are likely hallmarks of epithelial mesenchymal transition (EMT).,We aimed to confirm the epithelial origin of these Rbm cells, and to exclude potential confounding by infiltrating inflammatory cells.,Endobronchial biopsy sections from 17 COPD current smokers, with documented Rbm splitting and cellularity were stained for neutrophil elastase (neutrophil marker), CD68 (macrophage/mature fibroblasts), CD4+/CD8+ T lymphocytes, CD19 (B-cells), CD11c (dendritic cells/inflammatory cells), and S100 (Langerhans cells).,The number of cells in the Rbm and epithelium staining for these "inflammatory" cell markers were then compared to numbers staining for S100A4, "a documented EMT epitope".,Slides were double stained for S100A4 and cytokeratin(s).,In the basal epithelium significantly more cells stained for S100A4 compared to infiltrating macrophages, fibroblasts or immune cells: median, 26 (21.3 - 37.3) versus 0 (0 - 9.6) per mm, p < 0.003.,Markedly more S100A4 staining cells were also observed in the Rbm compared to infiltrating macrophages, neutrophils, fibroblasts or immune cells or any sub-type: 58 (37.3 - 92.6) versus 0 (0 - 4.8) cells/mm Rbm, p < 0.003.,Cells in the basal epithelium 26 (21.3 - 37.3) per mm) and Rbm (5.9 (2.3 - 13.8) per mm) frequently double stained for both cytokeratin and S100A4.,These data provide additional support for active EMT in COPD airways. | 1 |
Acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with a significant mortality, health and economic burden.,Their diagnosis, assessment and management remain suboptimal and unchanged for decades.,Recent clinical and translational studies revealed that the significant heterogeneity in mechanisms and outcomes of exacerbations could be resolved by grouping them etiologically.,This is anticipated to lead to a better understanding of the biological processes that underlie each type of exacerbation and to allow the introduction of precision medicine interventions that could improve outcomes.,This review summarises novel data on the diagnosis, phenotyping, targeted treatment and prevention of COPD exacerbations. | Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide.,Genetic risk loci provide novel insights into disease pathogenesis.,We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium.,We identified 82 loci with P-value < 5 × 10−8; 47 were previously described in association with either COPD or population-based lung function.,Of the remaining 35 novel loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium.,Using gene expression and regulation data, we identified enrichment for loci in lung tissue, smooth muscle and several lung cell types.,We found 14 COPD loci shared with either asthma or pulmonary fibrosis.,COPD genetic risk loci clustered into groups of quantitative imaging features and comorbidity associations.,Our analyses provide further support to the genetic susceptibility and heterogeneity of COPD. | 1 |
Oxidative stress is a major driving mechanism in the pathogenesis of COPD.,There is increased oxidative stress in the lungs of COPD patients due to exogenous oxidants in cigarette smoke and air pollution and due to endogenous generation of reactive oxygen species by inflammatory and structural cells in the lung.,Mitochondrial oxidative stress may be particularly important in COPD.,There is also a reduction in antioxidant defences, with inactivation of several antioxidant enzymes and the transcription factors Nrf2 and FOXO that regulate multiple antioxidant genes.,Increased systemic oxidative stress may exacerbate comorbidities and contribute to skeletal muscle weakness.,Oxidative stress amplifies chronic inflammation, stimulates fibrosis and emphysema, causes corticosteroid resistance, accelerates lung aging, causes DNA damage and stimulates formation of autoantibodies.,This suggests that treating oxidative stress by antioxidants or enhancing endogenous antioxidants should be an effective strategy to treat the underlying pathogenetic mechanisms of COPD.,Most clinical studies in COPD have been conducted using glutathione-generating antioxidants such as N-acetylcysteine, carbocysteine and erdosteine, which reduce exacerbations in COPD patients, but it is not certain whether this is due to their antioxidant or mucolytic properties.,Dietary antioxidants have so far not shown to be clinically effective in COPD.,There is a search for more effective antioxidants, which include superoxide dismutase mimetics, NADPH oxidase inhibitors, mitochondria-targeted antioxidants and Nrf2 activators. | Clinical outcomes are worse in patients with COPD and chronic bronchitis.,N-acetylcysteine (NAC) is commonly prescribed for such patients but with uncertain clinical benefits.,We postulated that oral NAC, at much larger doses than those ordinarily prescribed, would improve clinical outcomes in a subset of patients with COPD and chronic bronchitis.,The aim of this study was to determine whether very high-dose NAC would improve respiratory health status in patients with COPD and chronic bronchitis.,Patients with COPD and chronic bronchitis were enrolled in a randomized, controlled, double-blinded trial.,Patients received oral NAC (1,800 mg) or matching placebo twice daily for 8 weeks in addition to their usual respiratory medications.,The primary outcome, respiratory health status, was assessed by changes in the St George’s Respiratory Questionnaire.,The effects of NAC on lung function and circulating markers of oxidative stress and inflammation were also evaluated.,We terminated the study prematurely because new external information suggested the possibility of a safety issue.,Of the planned 130 patients, 51 were randomized and 45 (22 in the placebo arm and 23 in the NAC arm) completed the study.,There was no statistically significant difference between changes in the St George’s Respiratory Questionnaire total score, comparing NAC to placebo (adjusted mean difference, 0.1 U; 95% CI, −7.8 to 8.18 U; P=0.97).,There were also no significant NAC-related improvements in any of the secondary outcomes.,In this 8-week trial, we were unable to show any clinical benefit from a very high dose of NAC in patients with COPD and chronic bronchitis. | 1 |
Two replicate, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase III studies investigated the long-term efficacy and safety of once-daily olodaterol via Respimat® versus placebo and formoterol over 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease receiving usual-care background therapy.,Patients received once-daily olodaterol 5 or 10 μg, twice-daily formoterol 12 μg, or placebo.,Co-primary end points were forced expiratory volume in 1 second (FEV1) area under the curve from 0-3 hours response, FEV1 trough response, and Mahler transition dyspnea index total score after 24 weeks; secondary end points included St George’s Respiratory Questionnaire.,Overall, 904 (Study 1222.13) and 934 (Study 1222.14) patients received treatment.,Olodaterol significantly improved FEV1 area under the curve from 0-3 hours versus placebo in both studies (with olodaterol 5 μg, 0.151 L and 0.129 L; with olodaterol 10 μg, 0.165 L and 0.154 L; for all comparisons P<0.0001) and FEV1 trough responses versus placebo (0.053-0.085 L; P<0.01), as did formoterol.,Primary analysis revealed no significant difference in transition dyspnea index focal score for any active treatment versus placebo.,Post hoc analysis using pattern mixture modeling (accounting for discontinuations) demonstrated statistical significance for olodaterol versus placebo.,St George’s Respiratory Questionnaire total score was significantly improved with olodaterol, but not formoterol, versus placebo.,No safety signals were identified from adverse-event or other safety data.,Once-daily olodaterol 5 μg and 10 μg is efficacious in patients with moderate to very severe chronic obstructive pulmonary disease on usual-care maintenance therapy, with a satisfactory safety profile. | 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 |
Underdiagnosis of chronic obstructive pulmonary disease (COPD) in primary care can be improved by a more efficient screening strategy.,To evaluate a three-step method of screening for COPD consisting of an initial short questionnaire followed by measurement of forced expiratory volume in 1s/forced expiratory volume in 6s (FEV1/FEV6) using an inexpensive pocket spirometer in those with high risk, and diagnostic quality spirometry in those with a low FEV1/FEV6.,We analysed two related Mexico City cross-sectional samples.,The 2003 Mexico City PLATINO survey (n=542) was used to develop a short questionnaire to determine the risk of COPD and a 2010 survey (n=737) additionally used a pocket spirometer.,The discriminatory power of the two instruments was assessed with receiver operator characteristic (ROC) curves using three COPD definitions.,The developed COPD scale included two variables from a simple questionnaire and, in ROC analysis, an area under the curve (AUC) between 0.64 and 0.77 was found to detect COPD.,The pocket spirometer had an AUC between 0.85 and 0.88 to detect COPD.,Using the COPD scale as a first screening step excluded 35-48% of the total population from further testing at the cost of not detecting 8-18% of those with COPD.,Using the pocket spirometer and sending those with a FEV1/FEV6<0.80 for diagnostic quality spirometry is very efficient, and substantially improved the positive predictive value at the cost of not detecting one-third of COPD cases.,A three-step screening strategy for COPD substantially reduces the need for spirometry testing when only a COPD scale is used for screening. | The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999-2000.,Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples.,Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments.,Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis.,The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale.,Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey.,COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%-9%.,In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%-14%) than among women (range 5%-11%).,A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries.,Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment.,This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey.,A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities.,The main cause is smoking tobacco, but other factors have been identified.,Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli.,The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both.,Comorbidities include ischaemic heart disease, diabetes, and lung cancer.,Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids).,Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification.,Future research should be directed towards the development of agents that notably affect the course of disease. | Associations between Vitamin D3 [25(OH)D], vitamin D binding protein (VDBP) and chronic obstructive pulmonary disease (COPD) are previously reported.,We aimed to further investigate these associations on longitudinal outcomes.,426 COPD patients from western Norway, GOLD stage II-IV, aged 40-76, were followed every six-month from 2006 through 2009 with spirometry, bioelectrical impedance measurements and registration of exacerbation frequency.,Serum 25(OH)D and VDBP levels were determined at study-entry by high-performance liquid chromatography coupled with mass spectrometry and enzyme immunoassays respectively.,Yearly change in lung function and body composition was assessed by generalized estimating equations (GEE), yearly exacerbation rate by negative binomial regression models, and 5 years all-cause mortality by Cox proportional-hazard regression.,1/3 of the patients had vitamin D deficiency (<20ng/mL) and a greater decline in both FEV1 and FVC, compared to patients with normal levels; for FEV1 this difference only reached statistical significance in the 28 patients with the lowest levels (<10ng/mL, p = 0.01).,Neither 25(OH)D nor VDBP levels predicted exacerbation rate, change in fat free mass index or risk of death.,Severe vitamin D deficiency may affect decline in lung function parameters in COPD.,Neither 25(OH)D nor VDBP levels did otherwise predict markers of disease progression. | 1 |
Mechanisms driving persistent airway inflammation in chronic obstructive pulmonary disease (COPD) are incompletely understood.,As secretory immunoglobulin A (SIgA) deficiency in small airways has been reported in COPD patients, we hypothesized that immunobarrier dysfunction resulting from reduced SIgA contributes to chronic airway inflammation and disease progression.,Here we show that polymeric immunoglobulin receptor-deficient (pIgR−/−) mice, which lack SIgA, spontaneously develop COPD-like pathology as they age.,Progressive airway wall remodelling and emphysema in pIgR−/− mice are associated with an altered lung microbiome, bacterial invasion of the airway epithelium, NF-κB activation, leukocyte infiltration and increased expression of matrix metalloproteinase-12 and neutrophil elastase.,Re-derivation of pIgR−/− mice in germ-free conditions or treatment with the anti-inflammatory phosphodiesterase-4 inhibitor roflumilast prevents COPD-like lung inflammation and remodelling.,These findings show that pIgR/SIgA deficiency in the airways leads to persistent activation of innate immune responses to resident lung microbiota, driving progressive small airway remodelling and emphysema.,The mechanisms driving lung inflammation and remodelling in chronic obstructive pulmonary disease (COPD) are incompletely understood.,Here the authors show that lack of secretory IgA promotes bacterial invasion in small airways, resulting in leukocyte recruitment and a COPD-like phenotype. | Chronic Obstructive Pulmonary Disease (COPD) is associated with bronchial epithelial changes, including squamous cell metaplasia and goblet cell hyperplasia.,These features are partially attributed to activation of the epidermal growth factor receptor (EGFR).,Whereas smoking cessation reduces respiratory symptoms and lung function decline in COPD, inflammation persists.,We determined epithelial proliferation and composition in bronchial biopsies from current and ex-smokers with COPD, and its relation to duration of smoking cessation.,114 COPD patients were studied cross-sectionally: 99 males/15 females, age 62 ± 8 years, median 42 pack-years, no corticosteroids, current (n = 72) or ex-smokers (n = 42, median cessation duration 3.5 years), postbronchodilator FEV1 63 ± 9% predicted.,Squamous cell metaplasia (%), goblet cell (PAS/Alcian Blue+) area (%), proliferating (Ki-67+) cell numbers (/mm basement membrane), and EGFR expression (%) were measured in intact epithelium of bronchial biopsies.,Ex-smokers with COPD had significantly less epithelial squamous cell metaplasia, proliferating cell numbers, and a trend towards reduced goblet cell area than current smokers with COPD (p = 0.025, p = 0.001, p = 0.081, respectively), but no significant difference in EGFR expression.,Epithelial features were not different between short-term quitters (<3.5 years) and current smokers.,Long-term quitters (≥3.5 years) had less goblet cell area than both current smokers and short-term quitters (medians: 7.9% vs.,14.4%, p = 0.005; 7.9% vs.,13.5%, p = 0.008; respectively), and less proliferating cell numbers than current smokers (2.8% vs.,18.6%, p < 0.001).,Ex-smokers with COPD had less bronchial epithelial remodelling than current smokers, which was only observed after long-term smoking cessation (>3.5 years).,NCT00158847 | 1 |
Clinical audits have reported considerable variability in COPD medical care and frequent inconsistencies with recommendations.,The objectives of this study were to identify factors associated with a better adherence to clinical practice guidelines and to explore determinants of this variability at the the hospital level.,EPOCONSUL is a Spanish nationwide clinical audit that evaluates the outpatient management of COPD.,Multilevel logistic regression with two levels was performed to assess the relationships between individual and disease-related factors, as well as hospital characteristics.,A total of 4508 clinical records of COPD patients from 59 Spanish hospitals were evaluated.,High variability was observed among hospitals in terms of medical care.,Some of the patient’s characteristics (airflow obstruction, degree of dyspnea, exacerbation risk, presence of comorbidities), the hospital factors (size and respiratory nurses available) and treatment at a specialized COPD outpatient clinic were identified as factors associated with a better adherence to recommendations, although this only explains a small proportion of the total variance.,To be treated at a specialized COPD outpatient clinic and some intrinsic patient characteristics were factors associated with a better adherence to guideline recommendations, although these variables were only explaining part of the high variability observed among hospitals in terms of COPD medical care. | Daily diaries are often used to collect data on disease activity, but are burdensome and compliance may be poor.,Their use in chronic obstructive pulmonary disease (COPD) and impact on the prevention and treatment of exacerbations is poorly researched.,We investigated diary-keeping in COPD and ascertained items that best predicted emergency attendances for exacerbations.,Participants in the active limb of a clinical trial in COPD kept daily diaries rating breathlessness, cough, sputum, physical activity, and use of reliever medication.,Data on 55 participants, 67% of whom were female, showed that overall compliance with diary-keeping was 62%.,Participants educated to primary school level only had lower compliance (P = 0.05).,Twenty patients had at least one emergency attendance, in whom the relative risk of an acute exacerbation for an increase in item score rose from six days prior to hospitalization, most sharply in the last two days.,Even for optimal combinations of items, the positive predictive value was poor, the best combination being cough, activity level, and inhaler use.,Good compliance can be achieved using daily diaries in COPD, although this is worse in those with a poor educational level.,Diary-keeping is not accurate in predicting acute exacerbations, but could be substantially simplified without loss of efficiency. | 1 |
Previous models of Hospital at Home (HAH) for COPD exacerbation (ECOPD) were limited by the lack of a reliable prognostic score to guide patient selection.,Approximately 50% of hospitalised patients have a low mortality risk by DECAF, thus are potentially suitable.,In a non-inferiority randomised controlled trial, 118 patients admitted with a low-risk ECOPD (DECAF 0 or 1) were recruited to HAH or usual care (UC).,The primary outcome was health and social costs at 90 days.,Mean 90-day costs were £1016 lower in HAH, but the one-sided 95% CI crossed the non-inferiority limit of £150 (CI −2343 to 312).,Savings were primarily due to reduced hospital bed days: HAH=1 (IQR 1-7), UC=5 (IQR 2-12) (P=0.001).,Length of stay during the index admission in UC was only 3 days, which was 2 days shorter than expected.,Based on quality-adjusted life years, the probability of HAH being cost-effective was 90%.,There was one death within 90 days in each arm, readmission rates were similar and 90% of patients preferred HAH for subsequent ECOPD.,HAH selected by low-risk DECAF score was safe, clinically effective, cost-effective, and preferred by most patients.,Compared with earlier models, selection is simpler and approximately twice as many patients are eligible.,The introduction of DECAF was associated with a fall in UC length of stay without adverse outcome, supporting use of DECAF to direct early discharge.,Registered prospectively ISRCTN29082260. | Exacerbations of COPD are clinically relevant events with therapeutic and prognostic implications.,Yet, significant heterogeneity of clinical presentation and disease progression exists within acute exacerbations of COPD (AECOPD).,Currently, different phenotypes have been widely used to describe the characteristics among patients with AECOPD.,This has proved to be significant in the treatment and prediction of the outcomes of the disease.,In this review of published literature, the phenotypes of AECOPD were classified according to etiology, inflammatory biomarkers, clinical manifestation, comorbidity, the frequency of exacerbations, and so on.,This review concentrates on advancements in the use of phenotypes of AECOPD. | 1 |
The landmark study of Fletcher and Peto on the natural history of tobacco smoke-related chronic airflow obstruction suggested that decline in the forced expiratory volume in the first second (FEV1) in chronic obstructive pulmonary disease (COPD) is slow at the beginning, becoming faster with more advanced disease.,The present authors reviewed spirometric data of COPD patients included in the placebo arms of recent clinical trials to assess the lung function decline of each stage, defined according to the severity of airflow obstruction as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,In large COPD populations the mean rate of FEV1 decline in GOLD stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year, respectively, and lower than 35 mL/year in GOLD stage IV.,Few data on FEV1 decline are available for GOLD stage I.,Hence, the loss of lung function, assessed as expiratory airflow reduction, seems more accelerated and therefore more relevant in the initial phases of COPD.,To have an impact on the natural history of COPD, it is logical to look at the effects of treatment in the earlier stages. | Although personal cigarette smoking is the most important cause and modulator of chronic obstructive pulmonary disease (COPD), secondhand smoke (SHS) exposure could influence the course of the disease.,Despite the importance of this question, the impact of SHS exposure on COPD health outcomes remains unknown.,We used data from two waves of a population-based multiwave U.S. cohort study of adults with COPD. 77 non-smoking respondents with a diagnosis of COPD completed direct SHS monitoring based on urine cotinine and a personal badge that measures nicotine.,We evaluated the longitudinal impact of SHS exposure on validated measures of COPD severity, physical health status, quality of life (QOL), and dyspnea measured at one year follow-up.,The highest level of SHS exposure, as measured by urine cotinine, was cross-sectionally associated with poorer COPD severity (mean score increment 4.7 pts; 95% CI 0.6 to 8.9) and dyspnea (1.0 pts; 95% CI 0.4 to 1.7) after controlling for covariates.,In longitudinal analysis, the highest level of baseline cotinine was associated with worse COPD severity (4.7 points; 95% CI -0.1 to 9.4; p = 0.054), disease-specific QOL (2.9 pts; -0.16 to 5.9; p = 0.063), and dyspnea (0.9 pts; 95% CI 0.2 to 1.6 pts; p < 0.05), although the confidence intervals did not always exclude the no effect level.,Directly measured SHS exposure appears to adversely influence health outcomes in COPD, independent of personal smoking.,Because SHS is a modifiable risk factor, clinicians should assess SHS exposure in their patients and counsel its avoidance.,In public health terms, the effects of SHS exposure on this vulnerable subpopulation provide a further rationale for laws prohibiting public smoking. | 1 |
Airway bacterial dysbiosis is a feature of chronic obstructive pulmonary disease (COPD).,However, there is limited comparative data of the lung microbiome between healthy smokers, non-smokers and COPD.,We compared the 16S rRNA gene-based sputum microbiome generated from pair-ended Illumina sequencing of 124 healthy subjects (28 smokers and 96 non-smokers with normal lung function), with single stable samples from 218 COPD subjects collected from three UK clinical centres as part of the COPDMAP consortium.,In healthy subjects Firmicutes, Bacteroidetes and Actinobacteria were the major phyla constituting 88% of the total reads, and Streptococcus, Veillonella, Prevotella, Actinomyces and Rothia were the dominant genera.,Haemophilus formed only 3% of the healthy microbiome.,In contrast, Proteobacteria was the most dominant phylum accounting for 50% of the microbiome in COPD subjects, with Haemophilus and Moraxella at genus level contributing 25 and 3% respectively.,There were no differences in the microbiome profile within healthy and COPD subgroups when stratified based on smoking history.,Principal coordinate analysis on operational taxonomic units showed two distinct clusters, representative of healthy and COPD subjects (PERMANOVA, p = 0·001).,The healthy and COPD sputum microbiomes are distinct and independent of smoking history.,Our results underline the important role for Gammaproteobacteria in COPD. | 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 |
Rationale: Although clinical trials have found that pulmonary rehabilitation (PR) can reduce the risk of readmissions after hospitalization for a chronic obstructive pulmonary disease (COPD) exacerbation, less is known about PR’s impact in routine clinical practice.,Objectives: To evaluate the association between initiation of PR within 90 days of discharge and rehospitalization(s).,Methods: We analyzed a retrospective cohort of Medicare beneficiaries (66 years of age or older) hospitalized for COPD in 2014 who survived at least 30 days after discharge.,Measurements and Main Results: We used propensity score matching and estimated the risk of recurrent all-cause rehospitalizations at 1 year using a multistate model to account for the competing risk of death.,Of 197,376 total patients hospitalized in 4,446 hospitals, 2,721 patients (1.5%) initiated PR within 90 days of discharge.,Overall, 1,534 (56.4%) patients who initiated PR and 125,720 (64.6%) who did not were rehospitalized one or more times within 1 year of discharge.,In the propensity-score-matched analysis, PR initiation was associated with a lower risk of readmission in the year after PR initiation (hazard ratio, 0.83; 95% confidence interval, 0.77-0.90).,The mean cumulative number of rehospitalizations at 1 year was 0.95 for those who initiated PR within 90 days and 1.15 for those who did not (P < 0.001).,Conclusions: After hospitalization for COPD, Medicare beneficiaries who initiated PR within 90 days of discharge experienced fewer rehospitalizations over 1 year.,These results support findings from randomized controlled clinical trials and highlight the need to identify effective strategies to increase PR participation. | The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality. | 1 |
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 | 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 |
To understand and predict chronic obstructive pulmonary disease (COPD), a biomarker that reflects disease severity is needed.,Data from 10269 adults aged over 40 years of age were retrieved from the Korea National Health and Nutrition Examination Survey (KNHANES), and 1302 patients met the criteria for COPD.,The association between values of vitamin D and parathyroid hormone (PTH), and COPD severity including lung function and quality of life, were analyzed.,In COPD patients, lung function was inversely related to PTH values (P = 0.02 for FVC [% predicted]; P < 0.001 for FEV1 [% predicted]); however, the association of lung function with vitamin D levels was not statistically significant in a multivariable analysis.,Value of PTH was independently associated with EQ5D-index (P = 0.04), but vitamin D level showed no significant relationship with EQ5D-index (P = 0.59) or EQ5D-VAS (P = 0.81).,Elevation of PTH, unlike vitamin D, is independently associated with COPD severity, and may be a better biomarker for COPD. | Low 25-hydroxyvitamin D (25[OH]D) levels, commonly observed in chronic obstructive pulmonary disease (COPD), are associated with muscle weakness in elderly populations, and vitamin D supplementation appears to improve muscle strength and decrease falls in older individuals.,We tested the effect of vitamin D supplementation on physical performance in patients with COPD.,Patients were randomized to daily cholecalciferol (2000 IU) or placebo for 6 weeks.,The primary outcome was the 6-week change in Short Physical Performance Battery (SPPB) score.,Secondary outcomes included changes in the St George’s Respiratory Questionnaire (SGRQ) score, and serum 25(OH)D.,Thirty-six participants (mean age 68 years, all Caucasian males, mean forced expiratory volume in one second 33% of predicted) completed the study.,Despite an increase in 25(OH)D levels in the intervention arm to a mean of 32.6 ng/mL (versus 22.1 ng/mL in the placebo arm), there was no difference in improvements in either SPPB scores (0.3 point difference; 95% confidence interval −0.8 to 1.5; P = 0.56) or SGRQ scores (2.3 point difference; 95% confidence interval −2.3 to 6.9; P = 0.32).,Among patients with severe COPD, 2000 IU of daily vitamin D for 6 weeks increased 25(OH)D to a level widely considered as normal.,However, compared with placebo, short-term vitamin D supplementation had no discernible effect on a simple measure of physical performance. | 1 |
COPD affects over 13 million Americans, and accounts for over half a million hospitalizations annually.,The Hospital Readmission Reduction Program, established by the Affordable Care Act requires the Centers for Medicare and Medicaid Services to reduce payments to hospitals with excess readmissions for COPD as of 2015.,This study sought to develop a predictive readmission scale to identify COPD patients at higher readmission risk.,Demographic and clinical data on 339,389 patients from New York and California (derivation cohort) and 258,113 patients from Washington and Florida (validation cohort) were abstracted from the State Inpatient Database (2006-2011), and the Readmission After COPD Exacerbation (RACE) Scale was developed to predict 30-day readmission risk.,Thirty-day COPD readmission rates were 7.54% for the derivation cohort and 6.70% for the validation cohort.,Factors including age 40-65 years (odds ratio [OR] 1.17; 95% CI, 1.12-1.21), male gender (OR 1.16; 95% CI, 1.13-1.19), African American (OR 1.11; 95% CI, 1.06-1.16), 1st income quartile (OR 1.10; 95% CI, 1.06-1.15), 2nd income quartile (OR 1.06; 95% CI, 1.02-1.10), Medicaid insured (OR 1.83; 95% CI, 1.73-1.93), Medicare insured (OR 1.45; 95% CI, 1.38-1.52), anemia (OR 1.05; 95% CI, 1.02-1.09), congestive heart failure (OR 1.06; 95% CI, 1.02-1.09), depression (OR 1.18; 95% CI, 1.14-1.23), drug abuse (OR 1.17; 95% CI, 1.09-1.25), and psychoses (OR 1.19; 95% CI, 1.13-1.25) were independently associated with increased readmission rates, P<0.01.,When the devised RACE scale was applied to both cohorts together, it explained 92.3% of readmission variability.,The RACE Scale reliably predicts an individual patient’s 30-day COPD readmission risk based on specific factors present at initial admission.,By identifying these patients at high risk of readmission with the RACE Scale, patient-specific readmission-reduction strategies can be implemented to improve patient care as well as reduce readmissions and health care expenditures. | We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.,Three studies of ≥1-year duration met the inclusion criteria.,Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%).,At baseline, 57-75% of patients had ≥2% blood eosinophils.,Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.,For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001).,No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively).,In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo).,No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.,Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. | 1 |
Natural history of chronic obstructive pulmonary disease (COPD) is punctuated by exacerbations; however, little is known about prognosis of the first-ever COPD exacerbation and variables predicting its outcomes.,A population-based cohort study among COPD patients with their first-ever exacerbations requiring hospitalizations was conducted.,Main outcomes were in-hospital mortality and one-year mortality after discharge.,Demographics, comorbidities, medications and in-hospital events were obtained to explore outcome predictors.,The cohort comprised 4204 hospitalized COPD patients, of whom 175 (4%) died during the hospitalization.,In-hospital mortality was related to higher age (odds ratio [OR]: 1.05 per year; 95% confidence interval [CI]: 1.03-1.06) and Charlson comorbidity index score (OR: 1.08 per point; 95% CI: 1.01-1.15); angiotensin II receptor blockers (OR: 0.61; 95% CI: 0.38-0.98) and β blockers (OR: 0.63; 95% CI: 0.41-0.95) conferred a survival benefit.,At one year after discharge, 22% (871/4029) of hospital survivors were dead.,On multivariate Cox regression analysis, age and Charlson comorbidity index remained independent predictors of one-year mortality.,Longer hospital stay (hazard ratio [HR] 1.01 per day; 95% CI: 1.01-1.01) and ICU admission (HR: 1.33; 95% CI: 1.03-1.73) during the hospitalization were associated with higher mortality risks.,Prescription of β blockers (HR: 0.79; 95% CI: 0.67-0.93) and statins (HR: 0.66; 95% CI: 0.47-0.91) on hospital discharge were protective against one-year mortality.,Even the first-ever severe COPD exacerbation signifies poor prognosis in COPD patients.,Comorbidities play a crucial role in determining outcomes and should be carefully assessed.,Angiotensin II receptor blockers, β blockers and statins may, in theory, have dual cardiopulmonary protective properties and probably alter prognosis of COPD patients.,Nevertheless, the limitations inherent to a claims database study, such as the diagnostic accuracy of COPD and its exacerbation, should be born in mind. | The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality. | 1 |
The causal association between depression, anxiety, and health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD) is unclear.,We therefore conducted a systematic review of prospective cohort studies that measured depression, anxiety, and HRQoL in COPD.,Electronic databases (Medline, Embase, Cumulative Index to Nursing and Allied Health Literature [CINAHL], British Nursing Index and Archive, PsycINFO and Cochrane database) were searched from inception to June 18, 2013.,Studies were eligible for inclusion if they: used a nonexperimental prospective cohort design; included patients with a diagnosis of COPD confirmed by spirometry; and used validated measures of depression, anxiety, and HRQoL.,Data were extracted and pooled using random effects models.,Six studies were included in the systematic review; of these, three were included in the meta-analysis for depression and two were included for the meta-analysis for anxiety.,Depression was significantly correlated with HRQoL at 1-year follow-up (pooled r=0.48, 95% confidence interval 0.37-0.57, P<0.001).,Anxiety was also significantly correlated with HRQoL at 1-year follow-up (pooled r=0.36, 95% confidence interval 0.23-0.48, P<0.001).,Anxiety and depression predict HRQoL in COPD.,However, this longitudinal analysis does not show cause and effect relationships between depression and anxiety and future HRQoL.,Future studies should identify psychological predictors of poor HRQoL in well designed prospective cohorts with a view to isolating the mediating role played by anxiety disorder and depression. | Many people with COPD report difficulties falling asleep or staying asleep, insufficient sleep duration, or nonrestorative sleep.,Cognitive behavioral therapy for insomnia (CBT-I) has proved effective not only in people with primary insomnia but also in people with insomnia comorbid with psychiatric and medical illness (eg, depression, cancer, and chronic pain).,However, CBT-I has rarely been tested in those with COPD who have disease-related features that interfere with sleep and may lessen the effectiveness of such therapies.,The purpose of this study was to determine the feasibility of applying a CBT-I intervention for people with COPD and to assess the impact of CBT-I on insomnia severity and sleep-related outcomes, fatigue, mood, and daytime functioning.,The study had two phases.,In Phase 1, a 6-weekly session CBT-I intervention protocol in participants with COPD was assessed to examine feasibility and acceptability.,Phase 2 was a small trial utilizing a prospective two-group pre- and post-test design with random assignment to the six-session CBT-I or a six-session wellness education (WE) program to determine the effects of each intervention, with both interventions being provided by a nurse behavioral sleep medicine specialist.,Fourteen participants (five in Phase 1 and nine in Phase 2) completed six sessions of CBT-I and nine participants completed six sessions of WE.,Participants indicated that both interventions were acceptable.,Significant positive treatment-related effects of the CBT-I intervention were noted for insomnia severity (P = 0.000), global sleep quality (P = 0.002), wake after sleep onset (P = 0.03), sleep efficiency (P = 0.02), fatigue (P = 0.005), and beliefs and attitudes about sleep (P = 0.000).,Significant positive effects were noted for depressed mood after WE (P = 0.005).,Results suggest that using CBT-I in COPD is feasible and the outcomes compare favorably with those obtained in older adults with insomnia in the context of other chronic illnesses. | 1 |
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Comorbidities are often reported in patients with COPD and may influence the cost of care.,Yet, the extent by which comorbidities affect costs remains to be determined.,To review, quantify and evaluate excess costs of comorbidities in COPD.,Using a systematic review approach, Pubmed and Embase were searched for studies analyzing excess costs of comorbidities in COPD.,Resulting studies were evaluated according to study characteristics, comorbidity measurement and cost indicators.,Mark-up factors were calculated for respective excess costs.,Furthermore, a checklist of quality criteria was applied.,Twelve studies were included.,Nine evaluated comorbidity specific costs; three examined index-based results.,Pneumonia, cardiovascular disease and diabetes were associated with the highest excess costs.,The mark-up factors for respective excess costs ranged between 1.5 and 2.5 in the majority of cases.,On average the factors constituted a doubling of respective costs in the comorbid case.,The main cost driver, among all studies, was inpatient cost.,Indirect costs were not accounted for by the majority of studies.,Study heterogeneity was high.,The reviewed studies clearly show that comorbidities are associated with significant excess costs in COPD.,The inclusion of comorbid costs and effects in future health economic evaluations of preventive or therapeutic COPD interventions seems highly advisable. | Early identification of patients with a prolonged stay due to acute exacerbation of chronic obstructive pulmonary disease (COPD) may reduce risk of adverse event and treatment costs.,This study aimed to identify predictors of prolonged stay after acute exacerbation of COPD based on variables on admission; the study also looked to establish a prediction model for length of stay (LOS).,We extracted demographic and clinical data from the medical records of 599 patients discharged after an acute exacerbation of COPD between March 2006 and December 2008 at Oslo University Hospital, Aker.,We used logistic regression analyses to assess predictors of a length of stay above the 75th percentile and assessed the area under the receiving operating characteristic curve to evaluate the model’s performance.,We included 590 patients (54% women) aged 73.2±10.8 years (mean ± standard deviation) in the analyses.,Median LOS was 6.0 days (interquartile range [IQR] 3.5-11.0).,In multivariate analysis, admission between Thursday and Saturday (odds ratio [OR] 2.24 [95% CI 1.60-3.51], P<0.001), heart failure (OR 2.26, 95% CI 1.34-3.80), diabetes (OR 1.90, 95% CI 1.07-3.37), stroke (OR 1.83, 95% CI 1.04-3.21), high arterial PCO2 (OR 1.26 [95% CI 1.13-1.41], P<0.001), and low serum albumin level (OR 0.92 [95% CI 0.87-0.97], P=0.001) were associated with a LOS >11 days.,The statistical model had an area under the receiver operating characteristic curve of 0.73.,Admission between Thursday and Saturday, heart failure, diabetes, stroke, high arterial PCO2, and low serum albumin level were associated with a prolonged LOS.,These findings may help physicians to identify patients that will need a prolonged LOS in the early stages of admission.,However, the predictive model exhibited suboptimal performance and hence is not ready for clinical use. | 1 |
Frailty is a state of increased vulnerability that has a significant risk of unfavorable outcomes such as increased dependency and/or death, but little is known about frailty in people with chronic obstructive pulmonary disease (COPD).,We aimed to determine the prevalence of frailty in COPD patients and to identify the associated risk factors.,Two hundred fifty-seven COPD patients enrolled from primary care in Greece between 2015 and 2016.,Physicians used structured interviews to collect cross-sectional data including demographics, medical history, symptoms and COPD Assessment Tool (CAT) or modified Medical Research Council Dyspnea scale (mMRC) score.,Patients were classified into severity groups according to GOLD 2017 guidelines.,Participants completed the The Frail Non-Disabled (FiND) questionnaire, exploring the frailty and disability domains.,In the present analyses, frail patients with and without mobility disability were pooled and were compared to non-frail patients.,Factors associated with frailty were analyzed using univariate and multivariate logistic regression.,Mean (SD) age was 65 (12.3) with 79% males.,The majority of patients suffered with frailty (82%) of which 76.8% had mobility disability.,84.2% were married/with partner and 55.4% retired.,55.6% were current smokers.,Uncontrolled disease (≥10 CAT score) was reported in 91.1% and 37.2% of patients had ≥2 exacerbations in the past year.,Dyspnea (38%) and cough (53.4%) were the main symptoms.,Main comorbidities were hypertension (72.9%), hyperlipidaemia (24.6%) and diabetes (11%).,Risk of frailty was significantly increased with age (OR; 95%CI: 1.05; 1.02-1.08), hypertension (2.25; 1.14-4.45), uncontrolled disease (≥10 CAT score 4.65; 1.86-11.63, ≥2 mMRC score 5.75 (2.79-11.85) or ≥ 2 exacerbations 1.73; 1.07-2.78), smoking cessation (ex compared to current smokers: 2.37; 1.10-5.28) and GOLD status (B&D compared to A&C groups: CAT-based 4.65; 1.86-11.63; mMRC-based: 5.75; 2.79-11.85).,In multivariate regression smoking cessation and GOLD status remained significant.,Gender, body mass index, occupational or marital status, symptoms and other comorbidities were not significant.,Frailty with mobility disability is common in COPD patients and severity of disease increases the risk.,It is possible that frail patients are more likely to quit smoking perhaps because of their disability and uncontolled disease.,Routine assessment of frailty in addition to COPD control may allow early interventions for preventing or delaying progression of frailty and improvement in COPD disease. | The physical frailty status affects the health status of patients with chronic obstructive pulmonary disease (COPD).,The objective was to determine if the individual physical frailty characteristics have a differential impact on the CAT score.,This observational study included 137 patients with stable COPD.,Physical frailty was measured with unintentional weight loss, low physical activity, exhaustion, slow walking speed and low grip strength and health status assessed with the COPD Assessment test (CAT).,The following variables were evaluated as potential determinants of CAT: sex, age, body mass index, smoking, dyspnea, exacerbations, comorbidities, %FEV1, %FVC, anxiety and depression.,The prevalence of characteristics for individual frailty was as follows: low grip strength, 60.6%; low physical activity, 27.0%; exhaustion, 19.7%; slow walking speed, 9.5%; and unintentional weight loss, 7.3%.,A total of 17.5% of the patients were non-frail, 73.7% were pre-frail and only 8.7% were frail.,One of the five frailty characteristics, exhaustion (adjusted β coefficient 5.12 [standard error = 1.27], p = 0.001) was an independent determinant of CAT score in the final regression model which was adjusted by other independent determinants of CAT (dyspnea, exacerbations and anxiety).,Due to the fact that exhaustion is a frequent and relevant psychological symptom on CAT score of patients with COPD, interventions should reduce that stress.,Future research should explore how exhaustion persists or remits over time. | 1 |
Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY | Chronic obstructive pulmonary disease (COPD) represents a significant cause of global morbidity and mortality, with a substantial economic impact.,Recent changes in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidance refined the classification of patients for treatment using a combination of spirometry, assessment of symptoms, and/or frequency of exacerbations.,The aim of treatment remains to reduce existing symptoms while decreasing the risk of future adverse health events.,Long-acting bronchodilators are the mainstay of therapy due to their proven efficacy.,GOLD guidelines recommend combining long-acting bronchodilators with differing mechanisms of action if the control of COPD is insufficient with monotherapy, and recent years have seen growing interest in the additional benefits that combination of long-acting muscarinic antagonists (LAMAs), typified by tiotropium, with long-acting β2-agonists (LABAs), such as formoterol and salmeterol.,Most studies have examined free combinations of currently available LAMAs and LABAs, broadly showing a benefit in terms of lung function and other patient-reported outcomes, although evidence is limited at present.,Several once- or twice-daily fixed-dose LAMA/LABA combinations are under development, most involving newly developed monotherapy components.,This review outlines the existing data for LAMA/LABA combinations in the treatment of COPD, summarizes the ongoing trials, and considers the evidence required to inform the role of LAMA/LABA combinations in treatment of this 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. | Intact cognitive functioning is necessary for patients with chronic obstructive pulmonary disease (COPD) to understand the value of healthy lifestyle guidelines, to make informed decisions and subsequently act on it.,Nevertheless, brain abnormalities and cognitive impairment have been found in patients with COPD.,To date, it remains unknown which cognitive domains are affected and what the possible consequences are of cognitive impairment.,Therefore, objectives of the study described are to determine neuropsychological functioning in patients with COPD, and its influence on health status, daily functioning and pulmonary rehabilitation outcome.,Furthermore, structural and functional brain abnormalities and the relationship with cognitive and daily functioning will be explored.,A longitudinal observational comparative study will be performed in 183 patients with COPD referred for pulmonary rehabilitation and in 90 healthy control participants.,Demographic and clinical characteristics, activities of daily living and knowledge about COPD will be assessed.,Baseline cognitive functioning will be compared between patients and controls using a detailed neuropsychological testing battery.,An MRI substudy will be performed to compare brain abnormalities between 35 patients with COPD with cognitive impairment and 35 patients with COPD without cognitive impairment.,Patients will be recruited between November 2013 and November 2015.,The study has been approved by the Medical Ethics Committee of the University Hospital Maastricht and Maastricht University (NL45127.068.13/METC 13-3-035) and is registered in the Dutch trial register.,All participants will provide written informed consent and can withdraw from the study at any point in time.,Assessment and home visit data material will be managed anonymously.,The results obtained can be used to optimise patient-oriented treatment for cognitively impaired patients with COPD.,The findings will be disseminated in international peer-reviewed journals and through research conferences. | 1 |
A large body of evidence suggests that self-management interventions (SMIs) may improve outcomes in chronic obstructive pulmonary disease (COPD).,However, accurate comparisons of the relative effectiveness of SMIs are challenging, partly due to heterogeneity of outcomes across trials and uncertainty about the importance of these outcomes for patients.,We aimed to develop a core set of patient-relevant outcomes (COS) for SMIs trials to enhance comparability of interventions and ensure person-centred care.,We undertook an innovative approach consisting of four interlinked stages: i) Development of an initial catalogue of outcomes from previous EU-funded projects and/or published studies, ii) Scoping review of reviews on patients and caregivers’ perspectives to identify outcomes of interest, iii) Two-round Delphi online survey with patients and patient representatives to rate the importance of outcomes, and iv) Face-to-face consensus workshop with patients, patient representatives, health professionals and researchers to develop the COS.,From an initial list of 79 potential outcomes, 16 were included in the COS plus one supplementary outcome relevant to all participants.,These were related to patient and caregiver knowledge/competence, self-efficacy, patient activation, self-monitoring, adherence, smoking cessation, COPD symptoms, physical activity, sleep quality, caregiver quality of life, activities of daily living, coping with the disease, participation and decision-making, emergency room visits/admissions and cost effectiveness.,The development of the COPD COS for the evaluation of SMIs will increase consistency in the measurement and reporting of outcomes across trials.,It will also contribute to more personalized health care and more informed health decisions in clinical practice as patients’ preferences regarding COPD outcomes are more systematically included. | In chronic obstructive pulmonary disease (COPD), the problem of poor patient participation in studies of self-management (SM) and pulmonary rehabilitation (PR) programmes (together referred to as COPD support programmes) is established.,Understanding this problem beyond the previously reported socio-demographics and clinical factors is critical.,The aim of this study was to explore factors that explain patient participation in studies of COPD support programmes.,Thematic ‘framework’ synthesis was conducted on literature published from 1984 to 1 February 2015.,Emergent themes and subthemes were mapped onto the adapted ‘attitude-social influence-external barriers’ and the ‘self-regulation’ models to produce analytical themes.,Ten out of 12 studies were included: PR (n=9) and SM (n=1).,Three descriptive themes with 38 subthemes were mapped onto the models' constructs, and it generated four analytical themes: ‘attitude’, ‘social influences’ and ‘illness’ and ‘intervention representations’.,The following factors influenced (1) attendance-helping oneself through health improvements, perceived control of worsening condition, perceived benefits and positive past experience of the programme, as well as perceived positive influence of professionals; (2) non-attendance-perceived negative effects and negative past experience of the programme, perceived physical/practical concerns related to attendance, perceived severity of condition/symptoms and perceived negative influence of professionals/friends; (3) dropout-no health improvements perceived after attending a few sessions of the programme, perceived severity of the condition and perceived physical/practical concerns related to attendance.,Psychosocial factors including perceived practical/physical concerns related to attendance influenced patients’ participation in COPD support programmes.,Addressing the negative beliefs/perceptions via behaviour change interventions may help improve participation in COPD support programmes and, ultimately, patient outcomes. | 1 |
To investigate how the changes of definition in assessment of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stratification 2017 lead to changes of chronic obstructive pulmonary disease (COPD) patient clinical characteristics across categories in China.,COPD patients from 11 medical centers in China were stratified into old and new groups A-D twice according to the GOLD 2011 and 2017 comprehensive assessment.,Demography and clinical characteristics were compared between old and new groups A-D.,In 1,532 COPD patients, the distribution from group A to D was 330 (21.5%), 132 (8.6%), 411 (26.8%), 659 (43.0%) and 557 (36.4%), 405 (26.4%), 184 (12.0%), 386 (25.2%), respectively according to GOLD 2011 and 2017.,46.7% (500/1,070) patients in high-risk groups were regrouped to low-risk groups.,Compared to the old groups A and B, the new groups A and B had a higher proportion of males, lower body mass index, higher modified Medical Research Council (mMRC) grade, poor pulmonary function, more patients with chronic bronchitis, and fewer patients with coronary heart disease and hypertension disease.,Compared to the old groups C and D, the new groups C and D had older patients, fewer men, better pulmonary functions, frequent acute exacerbations in the previous year, and more patients with chronic bronchitis, coronary heart disease, or diabetes mellitus.,The new group D had more patients with stroke than the old group D.,In China, GOLD 2017 shifted the overall COPD comprehensive assessments distribution to more low-risk groups.,The new high-risk groups had more characteristics associated with high risk of acute exacerbation and mortality.,Some of the changes in demography and clinical characteristics of the new low-risk groups were associated with high risk of acute exacerbation and/or mortality. | COPD exerts a substantial burden on health and health care systems globally and will continue to do so for the foreseeable future.,Treatment however can be costly and health care providers are interested in both whether treatments can offer improvements in disease burden and whether they represent value for money.,Economic evaluations seek to resolve this issue by producing results that can be used to inform and assist the decision maker in allocating scarce health care resources.,In this paper we introduce economic evaluation and then use these themes to review and critically appraise the existing COPD economic evaluations, in order to assess quality in light of today’s standards.,The use of existing economic evaluations in informing the decision maker is then discussed.,Ten out of the fifteen studies were clinical trial or observational study based, and the remaining five on a decision analytic model.,Study design, interventions, outcome measures and the use of uncertainty varied considerably; consequentially the results are difficult to compare in any consistent manner.,Efforts for future studies to harmonize study design and methodology, particularly towards adopting a modeling framework, using current treatment as comparator and adopting a common effectiveness measure, such as the QALY, should be made in order to produce results that are comparable and useful to a decision maker. | 1 |
We studied the prevalence, burden and potential risk factors for chronic bronchitis symptoms in the Burden of Obstructive Lung Disease study.,Representative population-based samples of adults aged ≥40 years were selected in participating sites.,Participants completed questionnaires and spirometry.,Chronic bronchitis symptoms were defined as chronic cough and phlegm on most days for ≥3 months each year for ≥2 years.,Data from 24 855 subjects from 33 sites in 29 countries were analysed.,There were significant differences in the prevalence of self-reported symptoms meeting our definition of chronic bronchitis across sites, from 10.8% in Lexington (KY, USA), to 0% in Ile-Ife (Nigeria) and Blantyre (Malawi).,Older age, less education, current smoking, occupational exposure to fumes, self-reported diagnosis of asthma or lung cancer and family history of chronic lung disease were all associated with increased risk of chronic bronchitis.,Chronic bronchitis symptoms were associated with worse lung function, more dyspnoea, increased risk of respiratory exacerbations and reduced quality of life, independent of the presence of other lung diseases.,The prevalence of chronic bronchitis symptoms varied widely across the studied sites.,Chronic bronchitis symptoms were associated with significant burden both in individuals with chronic airflow obstruction and those with normal lung function.,Chronic bronchitis symptoms are associated with significant burden regardless of the presence of airflow obstructionhttp://ow.ly/kP9P30eFELK | Incidental CT findings may provide an opportunity for early detection of chronic obstructive pulmonary disease (COPD), which may prove important in CT-based lung cancer screening setting.,We aimed to determine the diagnostic performance of human observers to visually evaluate COPD presence on CT images, in comparison to automated evaluation using quantitative CT measures.,This study was approved by the Dutch Ministry of Health and the institutional review board.,All participants provided written informed consent.,We studied 266 heavy smokers enrolled in a lung cancer screening trial.,All subjects underwent volumetric inspiratory and expiratory chest computed tomography (CT).,Pulmonary function testing was used as the reference standard for COPD.,We evaluated the diagnostic performance of eight observers and one automated model based on quantitative CT measures.,The prevalence of COPD in the study population was 44% (118/266), of whom 62% (73/118) had mild disease.,The diagnostic accuracy was 74.1% in the automated evaluation, and ranged between 58.3% and 74.3% for the visual evaluation of CT images.,The positive predictive value was 74.3% in the automated evaluation, and ranged between 52.9% and 74.7% for the visual evaluation.,Interobserver variation was substantial, even within the subgroup of experienced observers.,Agreement within observers yielded kappa values between 0.28 and 0.68, regardless of the level of expertise.,The agreement between the observers and the automated CT model showed kappa values of 0.12-0.35.,Visual evaluation of COPD presence on chest CT images provides at best modest accuracy and is associated with substantial interobserver variation.,Automated evaluation of COPD subjects using quantitative CT measures appears superior to visual evaluation by human observers. | 1 |
The objective of the study is to explore the role of respiratory syncytial virus Toll-like receptor 3 (TLR3)-mediated immune response in the pathogenesis of acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,A total of 20 AECOPD patients and 10 normal volunteers were studied.,TLR3 was detected by RT-PCR, and respiratory syncytial virus (RSV) was detected by nested RT-PCR.,Then, A549 cells were infected by RSV at different time points and at different viral titers.,TLR3 mRNA was detected by RT-PCR, the protein of TLR3 and interferon regulatory factor 3 (IRF3) were detected by western blot, and IRF3 protein localization was detected by immunofluorescence.,Interferon-β (IFN-β) and interleukin-6 (IL-6) were detected by ELISA.,A total of 4 (20%) of the 20 AECOPD patients sampled were infected with RSV.,The forced expiratory volume in 1 second (FEV1) percentage was lower in the AECOPD patients infected with RSV compared to those not infected (P = 0.03).,The expression of IL-6 in the two groups was diametrically opposite (P = 0.04).,The AECOPD group (n = 20) showed an increase in TLR3 mRNA compared with that of the control group (n = 10) (P = 0.02).,The RSV-infected AECOPD group (n = 4) showed an obvious increase in TLR3 mRNA compared with that of the control group (P = 0.03).,There was a significant correlation between severity of reduction in lung function at exacerbation and the increasing expression of TLR3 in AECOPD patients.,The TLR3 signaling pathway was activated in lung epithelial cells.,TLR3 mRNA/protein levels were increased in A549 infected with RSV compared with those of the control group.,IRF3 protein also increased along with the occurrence of nuclear transfer in A549 infected with RSV.,IFN-β and IL-6 were also increased in the RSV-infected A549 cells compared with those of the control (P = 0.00 and 0.00, respectively).,Increased TLR3 expression in AECOPD patients is associated with declining lung function.,TLR3 may be a risk factor for RSV-infected AECOPD patients. | Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a significant cause of mortality of COPD patients, and pose a huge burden on healthcare.,One of the major causes of AECOPD is airway bacterial (e.g. nontypeable Haemophilus influenzae [NTHi]) infection.,However, the mechanisms underlying bacterial infections during AECOPD remain poorly understood.,As neutrophilic inflammation including increased release of human neutrophil elastase (HNE) is a salient feature of AECOPD, we hypothesized that HNE impairs airway epithelial defense against NTHi by degrading airway epithelial host defense proteins such as short palate, lung, and nasal epithelium clone 1 (SPLUNC1).,Recombinant human SPLUNC1 protein was incubated with HNE to confirm SPLUNC1 degradation by HNE.,To determine if HNE-mediated impairment of host defense against NTHi was SPLUNC1-dependent, SPLUNC1 protein was added to HNE-treated primary normal human airway epithelial cells.,The in vivo function of SPLUNC1 in NTHi defense was investigated by infecting SPLUNC1 knockout and wild-type mice intranasally with NTHi.,We found that: (1) HNE directly increased NTHi load in human airway epithelial cells; (2) HNE degraded human SPLUNC1 protein; (3) Recombinant SPLUNC1 protein reduced NTHi levels in HNE-treated human airway epithelial cells; (4) NTHi levels in lungs of SPLUNC1 knockout mice were increased compared to wild-type mice; and (5) SPLUNC1 was reduced in lungs of COPD patients.,Our findings suggest that SPLUNC1 degradation by neutrophil elastase may increase airway susceptibility to bacterial infections.,SPLUNC1 therapy likely attenuates bacterial infections during AECOPD. | 1 |
Current treatment strategies to stratify exacerbation risk rely on history of ≥2 events in the previous year.,To understand year-to-year variability and factors associated with consistent exacerbations over time, we present a prospective analysis of the SPIROMICS cohort.,We analyzed SPIROMICS participants with COPD and three years of prospective data (n=1,105).,We classified participants according to yearly exacerbation frequency.,Stepwise logistic regression compared factors associated with individuals experiencing ≥1 AECOPD in every year for three years versus none.,During three years follow-up, 48·7% of participants experienced at least one AECOPD, while the majority (51·3%) experienced none.,Only 2·1% had ≥2 AECOPD in each year.,An inconsistent pattern (both years with and years without AECOPD) was common (41·3% of the group), particularly among GOLD stages 3 and 4 subjects (56·1%).,In logistic regression, consistent AECOPD (≥1 event per year for three years) as compared to no AECOPD were associated with higher baseline symptom burden assessed with the COPD Assessment Test, previous exacerbations, greater evidence of small airway abnormality by computed tomography, lower Interleukin-15 (IL-15) and elevated Interleukin-8 (IL-8).,Although AECOPD are common, the exacerbation status of most individuals varies markedly from year to year.,Among participants who experienced any AECOPD over three years, very few repeatedly experienced ≥2 events/year.,In addition to symptoms and history of exacerbations in the prior year, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, IL-15 and IL-8. | Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with accelerated disease progression and are important drivers of health care resource utilization.,The study aimed to quantify the rates of COPD exacerbations in England and assess health care resource utilization by severity categories according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013.,Data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics were used to identify patients with a COPD diagnosis aged ≥40 years.,Those with complete spirometric, modified Medical Research Council Dyspnea Scale information, and exacerbation history 12 months prior to January 1, 2011 (index date) were classified into GOLD severity groups.,Study outcomes over follow-up (up to December 31, 2013) were exacerbation rates and resource utilization (general practitioner visits, hospital admissions).,From the 44,201 patients in the study cohort, 83.5% were classified into severity levels GOLD A: 33.8%, GOLD B: 21.0%, GOLD C: 18.1%, and GOLD D: 27.0%.,Mean age at diagnosis was 66 years and 52.0% were male.,Annual exacerbation rates per person-year increased with severity, from 0.83 (95% confidence interval [CI]: 0.81-0.85) for GOLD A to 2.51 (95% CI: 2.47-2.55) for GOLD D.,General practitioner visit rates per person-year also increased with severity, from 4.82 (95% CI: 4.74-4.93) for GOLD A to 7.44 (95% CI: 7.31-7.61) for GOLD D.,COPD-related hospitalization rates per person-year increased from less symptoms (GOLD A: 0.28, GOLD C: 0.39) to more symptoms (GOLD B: 0.52, GOLD D: 0.84).,Patients in the most severe category (GOLD D) experienced nearly three times the number of exacerbations and COPD-related hospitalizations as those in the least severe category (GOLD A), in addition to increased general practitioner visits.,Better patient management to stabilize the disease progression could allow for an improvement in exacerbation frequency and a reduction in health care resource utilization. | 1 |
To compare the safety and effectiveness of long-acting β-antagonists (LABA), long-acting antimuscarinic agents (LAMA) and inhaled corticosteroids (ICS) for managing chronic obstructive pulmonary disease (COPD).,Systematic review and network meta-analysis (NMA).,208 randomised clinical trials (RCTs) including 134 692 adults with COPD.,LABA, LAMA and/or ICS, alone or in combination, versus each other or placebo.,The proportion of patients with moderate-to-severe exacerbations.,The number of patients experiencing mortality, pneumonia, serious arrhythmia and cardiovascular-related mortality (CVM) were secondary outcomes.,NMA was conducted including 20 RCTs for moderate-to-severe exacerbations for 26 141 patients with an exacerbation in the past year. 32 treatments were effective versus placebo including: tiotropium, budesonide/formoterol, salmeterol, indacaterol, fluticasone/salmeterol, indacaterol/glycopyrronium, tiotropium/fluticasone/salmeterol and tiotropium/budesonide/formoterol.,Tiotropium/budesonide/formoterol was most effective (99.2% probability of being the most effective according to the Surface Under the Cumulative RAnking (SUCRA) curve).,NMA was conducted on mortality (88 RCTs, 97 526 patients); fluticasone/salmeterol was more effective in reducing mortality than placebo, formoterol and fluticasone alone, and was the most effective (SUCRA=71%).,NMA was conducted on CVM (37 RCTs, 55 156 patients) and the following were safest: salmeterol versus each OF placebo, tiotropium and tiotropium (Soft Mist Inhaler (SMR)); fluticasone versus tiotropium (SMR); and salmeterol/fluticasone versus tiotropium and tiotropium (SMR).,Triamcinolone acetonide was the most harmful (SUCRA=81%).,NMA was conducted on pneumonia occurrence (54 RCTs, 61 551 patients). 24 treatments were more harmful, including 2 that increased risk of pneumonia versus placebo; fluticasone and fluticasone/salmeterol.,The most harmful agent was fluticasone/salmeterol (SUCRA=89%).,NMA was conducted for arrhythmia; no statistically significant differences between agents were identified.,Many inhaled agents are available for COPD, some are safer and more effective than others.,Our results can be used by patients and physicians to tailor administration of these agents.,PROSPERO # CRD42013006725. | Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY | 1 |
To map and assess prognostic models for outcome prediction in patients with chronic obstructive pulmonary disease (COPD).,Systematic review.,PubMed until November 2018 and hand searched references from eligible articles.,Studies developing, validating, or updating a prediction model in COPD patients and focusing on any potential clinical outcome.,The systematic search yielded 228 eligible articles, describing the development of 408 prognostic models, the external validation of 38 models, and the validation of 20 prognostic models derived for diseases other than COPD.,The 408 prognostic models were developed in three clinical settings: outpatients (n=239; 59%), patients admitted to hospital (n=155; 38%), and patients attending the emergency department (n=14; 3%).,Among the 408 prognostic models, the most prevalent endpoints were mortality (n=209; 51%), risk for acute exacerbation of COPD (n=42; 10%), and risk for readmission after the index hospital admission (n=36; 9%).,Overall, the most commonly used predictors were age (n=166; 41%), forced expiratory volume in one second (n=85; 21%), sex (n=74; 18%), body mass index (n=66; 16%), and smoking (n=65; 16%).,Of the 408 prognostic models, 100 (25%) were internally validated and 91 (23%) examined the calibration of the developed model.,For 286 (70%) models a model presentation was not available, and only 56 (14%) models were presented through the full equation.,Model discrimination using the C statistic was available for 311 (76%) models. 38 models were externally validated, but in only 12 of these was the validation performed by a fully independent team.,Only seven prognostic models with an overall low risk of bias according to PROBAST were identified.,These models were ADO, B-AE-D, B-AE-D-C, extended ADO, updated ADO, updated BODE, and a model developed by Bertens et al.,A meta-analysis of C statistics was performed for 12 prognostic models, and the summary estimates ranged from 0.611 to 0.769.,This study constitutes a detailed mapping and assessment of the prognostic models for outcome prediction in COPD patients.,The findings indicate several methodological pitfalls in their development and a low rate of external validation.,Future research should focus on the improvement of existing models through update and external validation, as well as the assessment of the safety, clinical effectiveness, and cost effectiveness of the application of these prognostic models in clinical practice through impact studies.,PROSPERO CRD42017069247 | Our understanding of how comorbid diseases influence health-related quality of life (HRQL) in patients with chronic obstructive pulmonary disease (COPD) is limited and in need of improvement.,The aim of this study was to examine the associations between comorbidities and HRQL as measured by the instruments EuroQol-5 dimension (EQ-5D) and the COPD Assessment Test (CAT).,Information on patient characteristics, chronic bronchitis, cardiovascular disease, diabetes, renal impairment, musculoskeletal symptoms, osteoporosis, depression, and EQ-5D and CAT questionnaire results was collected from 373 patients with Forced Expiratory Volume in one second (FEV1) <50% of predicted value from 27 secondary care respiratory units in Sweden.,Correlation analyses and multiple linear regression models were performed using EQ-5D index, EQ-5D visual analog scale (VAS), and CAT scores as response variables.,Having more comorbid conditions was associated with a worse HRQL as assessed by all instruments.,Chronic bronchitis was significantly associated with a worse HRQL as assessed by EQ-5D index (adjusted regression coefficient [95% confidence interval] −0.07 [−0.13 to −0.02]), EQ-5D VAS (−5.17 [−9.42 to −0.92]), and CAT (3.78 [2.35 to 5.20]).,Musculoskeletal symptoms were significantly associated with worse EQ-5D index (−0.08 [−0.14 to −0.02]), osteoporosis with worse EQ-5D VAS (−4.65 [−9.27 to −0.03]), and depression with worse EQ-5D index (−0.10 [−0.17 to −0.04]).,In stratification analyses, the associations of musculoskeletal symptoms, osteoporosis, and depression with HRQL were limited to female patients.,The instruments EQ-5D and CAT complement each other and emerge as useful for assessing HRQL in patients with COPD.,Chronic bronchitis, musculoskeletal symptoms, osteoporosis, and depression were associated with worse HRQL.,We conclude that comorbid conditions, in particular chronic bronchitis, depression, osteoporosis, and musculoskeletal symptoms, should be taken into account in the clinical management of patients with severe COPD. | 1 |
Forced expiratory volume in 1s/forced expiratory volume in 6 s ( FEV1/FEV6) assessment with a microspirometer may be useful in the diagnostic work up of subjects who are suspected of having COPD in primary care.,To determine the diagnostic accuracy of a negative pre-bronchodilator (BD) microspirometry test relative to a full diagnostic spirometry test in subjects in whom general practitioners (GPs) suspect airflow obstruction.,Cross-sectional study in which the order of microspirometry and diagnostic spirometry tests was randomised.,Study subjects were (ex-)smokers aged ⩾50 years referred for diagnostic spirometry to a primary care diagnostic centre by their GPs.,A pre-BD FEV1/FEV6 value <0.73 as measured with the PiKo-6 microspirometer was compared with a post-BD FEV1/FVC (forced vital capacity) <0.70 and FEV1/FVC<lower limit of normal (LLN) from diagnostic spirometry.,One hundred and four subjects were analysed (59.6% males, 42.3% current smokers).,Negative predictive values from microspirometry for airflow obstruction based on the fixed and LLN cut-off points were 94.4% (95% confidence interval (CI), 86.4-98.5) and 96.3% (95% CI, 88.2-99.3), respectively.,In all, 18% of positive microspirometry results were not confirmed by a post-BD FEV1/FVC <0.70 and 44% of tests were false positive compared with the LLN criterion for airflow obstruction.,Pre-bronchodilator microspirometry seems to be able to reliably preselect patients for further assessment of airflow obstruction by means of regular diagnostic spirometry.,However, use of microspirometry alone would result in overestimation of airflow obstruction and should not replace regular spirometry when diagnosing COPD in primary care. | A 6-second spirometry test is easier than full exhalations.,We compared the reliability of the ratio of the Forced expiratory volume in 1 second/Forced expiratory volume in 6 seconds (FEV1/FEV6) to the ratio of the FEV1/Forced vital capacity (FEV1/FVC) for the detection of airway obstruction.,The PLATINO population-based survey in individuals aged 40 years and over designed to estimate the prevalence of post-Bronchodilator airway obstruction repeated for the same study participants after 5-9 years in three Latin-American cities.,Using the FEV1/FVC<Lower limit of normal (LLN) index, COPD prevalence apparently changed from 9.8 to 13.2% in Montevideo, from 9.7 to 6.0% in São Paulo and from 8.5 to 6.6% in Santiago, despite only slight declines in smoking prevalence (from 30.8% to 24.3%).,These changes were associated with differences in Forced expiratory time (FET) between the two surveys.,In contrast, by using the FEV1/FEV6 to define airway obstruction, the changes in prevalence were smaller: 9.7 to 10.6% in Montevideo, 8.6 to 9.0% in São Paulo, and 7.5 to 7.9% in Santiago.,Changes in the prevalence of COPD with criteria based on FEV1/FVC correlated strongly with changes in the FET of the tests (R2 0.92) unlike the prevalence based on a low FEV1/FEV6 (R2 = 0.40).,The FEV1/FEV6 is a more reliable index than FEV1/FVC because FVC varies with the duration of the forced exhalation.,Reporting FET and FEV1/FEV6<LLN helps to understand differences in prevalence of COPD obtained from FEV1/FVC-derived indices. | 1 |
Alpha-1-Antitrypsin Deficiency (AATD) is an economically unexplored genetic disease.,Direct and indirect costs (based on self-reported information on healthcare utilization) and health-related quality of life (HRQL, as assessed by SGRQ, CAT, and EQ-5D-3 L) were compared between 131 AATD patients (106 with, 25 without augmentation therapy (AT)) and 2,049 COPD patients without AATD participating in the COSYCONET COPD cohort.,The medication costs of AT were excluded from all analyses to reveal differences associated with morbidity profiles.,The association of AATD (with/without AT) with costs or HRQL was examined using generalized linear regression modelling (GLM) adjusting for age, sex, GOLD grade, BMI, smoking status, education and comorbidities.,Adjusted mean direct annual costs were €6,099 in AATD patients without AT, €7,117 in AATD patients with AT (excluding costs for AT), and €7,460 in COPD patients without AATD.,AATD with AT was significantly associated with higher outpatient (+273%) but lower inpatient (−35%) and medication costs (−10%, disregarding AT) compared with COPD patients without AATD.,There were no significant differences between groups regarding indirect costs and HRQL.,Apart from AT costs, AATD patients tended to have lower, though not significant, overall costs and similar HRQL compared to COPD patients without AATD.,AT was not associated with lower costs or higher HRQL.,NCT01245933,The online version of this article (doi:10.1186/s12931-017-0543-8) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible disease responsible for the deaths of 3 million people worldwide in 2005, and predicted to be the third leading cause of death worldwide by 2030.,Many COPD models developed to date have followed a Markov structure, in which patients or populations can move between defined health states over successive time periods or cycles.,In COPD, health states are typically based on disease severity defined solely by lung function, as described by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,These current modelling methods may restrict the ability to reflect the disease progression/clinical pathway or clinical practice.,Given these limitations in previous COPD models, the authors aimed to develop a more flexible model that could improve on the description of the clinical disease pathway.,The overall objective of this model was to inform the development of policies, guidelines or cost-effectiveness analyses.,A second objective was to validate the model in relation to existing epidemiology studies of COPD.,A patient simulation model was developed in Microsoft Excel™.,The predictability of the model was tested by populating it with data from natural history of disease studies as well as with clinical trial data.,Each patient moves through the model with demographic characteristics randomly generated from a set distribution.,These characteristics determine the risk of clinical events occurring in the model.,The validation with these studies found the model to have generally good predictive ability, yielding in this way a good degree of external validity.,The micro-simulation model is a flexible approach for modelling COPD that allows consideration of complex COPD treatment pathways.,The model was found to be generally robust in terms of predicting clinical outcomes of published studies when tested against other studies.,It has significant potential as a tool for supporting future COPD treatment positioning decisions as well as to inform the development of policies, guidelines or cost-effectiveness analyses. | 1 |
Benralizumab, a humanized, afucosylated, monoclonal antibody that targets interleukin-5 receptor α, depletes eosinophils and basophils by enhanced antibody-dependent cell-mediated cytotoxicity.,It demonstrated efficacy for patients with moderate to severe asthma and, in a Phase IIa trial, for chronic obstructive pulmonary disease (COPD) with eosinophilic inflammation.,We investigated effects of benralizumab 100 mg every 8 weeks (first three doses every 4 weeks) subcutaneous on blood inflammatory markers through proteomic and gene-expression analyses collected during two Phase II studies of patients with eosinophilic asthma and eosinophilic COPD.,Serum samples for proteomic analysis and whole blood for gene expression analysis were collected at baseline and 52 weeks (asthma study) or 32 weeks (COPD study) post-treatment.,Proteomic analyses were conducted on a custom set of 90 and 147 Rules-Based Medicine analytes for asthma and COPD, respectively.,Gene expression was profiled by Affymetrix Human Genome U133 plus 2 arrays (~ 54 K probes).,Gene set variation analysis (GSVA) was used to determine transcriptomic activity of immune signatures.,Treatment-related differences between analytes, genes, and gene signatures were analyzed for the overall population and for patient subgroups stratified by baseline blood eosinophil count (eosinophil-high [≥300 cells/μL] and eosinophil-low [< 300 cells/μL]) via t-test and repeated measures analysis of variance.,Eosinophil chemokines eotaxin-1 and eotaxin-2 were significantly upregulated (false discovery rate [FDR] < 0.05) by approximately 2.1- and 1.4-fold in the asthma study and by 2.3- and 1.7-fold in the COPD study following benralizumab treatment.,Magnitude of upregulation of these two chemokines was greater for eosinophil-high patients than eosinophil-low patients in both studies.,Benralizumab was associated with significant reductions (FDR < 0.05) in expression of genes associated with eosinophils and basophils, such as CLC, IL-5Rα, and PRSS33; immune-signaling complex genes (FCER1A); G-protein-coupled receptor genes (HRH4, ADORA3, P2RY14); and further immune-related genes (ALOX15 and OLIG2).,The magnitude of downregulation of gene expression was greater for eosinophil-high than eosinophil-low patients.,GSVA on immune signatures indicated significant treatment reductions (FDR < 0.05) in eosinophil-associated signatures.,Benralizumab is highly selective, modulating blood proteins or genes associated with eosinophils or basophils.,Modulated protein and gene expression patterns are most prominently altered in eosinophil-high vs. eosinophil-low patients.,NCT01227278 and NCT01238861.,The online version of this article (10.1186/s12931-018-0968-8) contains supplementary material, which is available to authorized users. | Growing evidence suggests that blood eosinophil count is associated with patient responsiveness to inhaled corticosteroids (ICS).,We performed post hoc predictive modeling on data from the FORWARD study and two replicate studies by Dransfield, to evaluate the relationships between baseline eosinophil count and the effect of ICS on exacerbations and lung function in patients with COPD.,The studies assessed ICS/long-acting β2 agonist (LABA) combinations vs LABA alone.,Using data from each study, we modeled COPD exacerbation rates, predose FEV1, and St George’s Respiratory Questionnaire score ([FORWARD only]) over a continuous range of eosinophils (0-1,000 eosinophils/µL in FORWARD, 0-993 eosinophils/µL in Dransfield).,In all studies, ICS/LABA reduced exacerbations versus LABA alone across all eosinophil levels, with progressively greater reductions at increasing baseline blood eosinophil counts.,In FORWARD, annual exacerbation rates ranged from 0.78 to 0.83 per year between 0 and 1,000 eosinophils/µL in the ICS/LABA arm, and from 0.81 to 1.54 per year in the LABA-only arm.,In the Dransfield studies, exacerbation rates ranged from 0.54 to 1.02 per year in the ICS/LABA arm between 0 and 993 eosinophils/µL, and from 0.56 to 1.75 per year in the LABA-only arm.,Change in FEV1 was not associated with eosinophil count in ICS-treated patients in FORWARD, whereas an increased treatment benefit in terms of FEV1 was observed at higher eosinophil levels in the Dransfield studies.,ICS/LABA led to greater improvements in St George’s Respiratory Questionnaire total scores compared to LABA alone in patients in FORWARD with ≥67 eosinophils/µL.,Higher blood eosinophil count in patients with COPD is associated with an increased beneficial effect from ICS in terms of exacerbation reduction.,Further prospective data are required to assess the role of blood eosinophils as a biomarker for therapeutic recommendations. | 1 |
Treatment guidance for chronic obstructive pulmonary disease (COPD) recommends inhaled corticosteroid (ICS)+long-acting muscarinic antagonist+long-acting β2-agonist (LABA) triple therapy for patients who experience recurrent exacerbations, persistent breathlessness, or exercise limitation on dual therapy.,However, information is limited on pathways to triple therapy in the UK.,A retrospective cohort study was conducted using de-identified patient-level data from UK primary care electronic medical records from January 1, 2005 to May 1, 2016.,Data were included from patients who had their first triple therapy regimen (index date) recorded during the study period and a minimum of 12 months’ pre-index data.,Treatment pathways to triple therapy were recorded, and the proportion of patients on triple therapy before their COPD diagnosis was determined.,Adherence to triple therapy was estimated using the proportion of days covered (PDC).,After applying eligibility criteria, 82,300 patients were included, with a mean age at COPD diagnosis of 64.7 years.,The major treatment pathway (27.9%) was the first initiation of ICS+LABA prior to triple therapy.,Following COPD diagnosis, the median time to triple therapy was approximately 3.5 years.,The estimated mean adherence to triple therapy was 81.8% PDC.,Multivariate analysis showed that the following groups were more likely to have received previous therapy prior to triple therapy: females (versus males), patients with asthma (versus those without asthma), severe COPD (versus those with non-severe COPD), or fewer exacerbations (versus those with more exacerbations).,Treatment pathways to triple therapy in the UK are diverse, highlighting the need to better understand factors involved in clinical decision-making. | COPD patients are often prescribed multiple medications for their respiratory disease and comorbidities.,This can lead to complex medication regimens resulting in poor adherence, medication errors, and drug-drug interactions.,The relationship between clinical outcomes and medication burden beyond medication count in COPD is largely unknown.,The aim of this study was to explore the relationships of medication burden in COPD with clinical outcomes, comorbidities, and multidimensional indices.,In a cross-sectional study, COPD patients (n=222) were assessed for demographic information, comorbidities, medication use, and clinical outcomes.,Complexity of medication regimens was quantified using the validated medication regimen complexity index (MRCI).,Participants (58.6% males) had a mean (SD) age of 69.1 (8.3) years with a postbronchodilator forced expiratory volume in 1 second % predicted of 56.5 (20.4) and a median of five comorbidities.,The median (q1, q3) total MRCI score was 24 (18.5, 31).,COPD-specific medication regimens were more complex than those of non-COPD medications (median MRCI: 14.5 versus 9, respectively; P<0.0001).,Complex dosage formulations contributed the most to higher MRCI scores of COPD-specific medications while dosing frequency primarily drove the complexity associated with non-COPD medications.,Participants in Global Initiative for Chronic Obstructive Lung Disease quadrant D had the highest median MRCI score for COPD medications (15.5) compared to those in quadrants A (13.5; P=0.0001) and B (12.5; P<0.0001).,Increased complexity of COPD-specific treatments showed significant but weak correlations with lower lung function and 6-minute walk distance, higher St George’s Respiratory Questionnaire and COPD assessment test scores, and higher number of prior year COPD exacerbations and hospitalizations.,Comorbid cardiovascular, gastrointestinal, or metabolic diseases individually contributed to higher total MRCI scores and/or medication counts for all medications.,Charlson Comorbidity Index and COPD-specific comorbidity test showed the highest degree of correlation with total MRCI score (ρ=0.289 and ρ=0.326; P<0.0001, respectively).,In COPD patients, complex medication regimens are associated with disease severity and specific class of comorbidities. | 1 |
The expression and localization of transforming growth factor-β (TGF-β) pathway proteins in different compartments of the lower airways of patients with stable COPD is unclear.,We aimed to determine TGF-β pathway protein expression in patients with stable COPD.,The expression and localization of TGF-β pathway components was measured in the bronchial mucosa and peripheral lungs of patients with stable COPD (n = 44), control smokers with normal lung function (n = 24), and control nonsmoking subjects (n = 11) using immunohistochemical analysis.,TGF-β1, TGF-β3, and connective tissue growth factor expression were significantly decreased in the bronchiolar epithelium, with TGF-β1 also decreased in alveolar macrophages, in patients with stable COPD compared with control smokers with normal lung function.,TGF-β3 expression was increased in the bronchial lamina propria of both control smokers with normal lung function and smokers with mild/moderate stable COPD compared with control nonsmokers and correlated significantly with pack-years of smoking.,However, TGF-β3+ cells decreased in patients with severe/very severe COPD compared with control smokers.,Latent TGF-β binding protein 1 expression was increased in the bronchial lamina propria in subjects with stable COPD of all severities compared with control smokers with normal lung function.,Bone morphogenetic protein and activin membrane-bound inhibitor expression (BAMBI) in the bronchial mucosa was significantly increased in patients with stable COPD of all severities compared with control subjects.,No other significant differences were observed between groups for all the other molecules studied in the bronchial mucosa and peripheral lung.,Expression of TGF-βs and their regulatory proteins is distinct within different lower airway compartments in stable COPD.,Selective reduction in TGF-β1 and enhanced BAMBI expression may be associated with the increase in autoimmunity in COPD. | Bone-marrow derived mesenchymal stromal cells (MSCs) have potent immunomodulatory and tissue reparative properties, which may be beneficial in the treatment of inflammatory diseases such as COPD.,This study examined the mechanisms by which human MSCs protect against elastase induced emphysema.,Using a novel human relevant pre-clinical model of emphysema the efficacy of human MSC therapy and optimal cell dose were investigated.,Protective effects were examined in the lung through histological examination.,Further in vivo experiments examined the reparative abilities of MSCs after tissue damage was established and the role played by soluble factors secreted by MSCs.,The mechanism of MSC action was determined in using shRNA gene knockdown.,Human MSC therapy and MSC conditioned media exerted significant cytoprotective effects when administered early at the onset of the disease.,These protective effects were due to significant anti-inflammatory, anti-fibrotic and anti-apoptotic mechanisms, mediated in part through MSC production of hepatocyte growth factor (HGF).,When MSC administration was delayed, significant protection of the lung architecture was observed but this was less extensive.,MSC cell therapy was more effective than MSC conditioned medium in this emphysema model. | 1 |
Both the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ) were recommended as comprehensive symptom measures by the Global Initiative for Chronic Obstructive Lung disease.,The main objective of this work was to compare the evaluation of symptom severity with the CAT and the CCQ and find a cutoff value of the CCQ for the Chinese clinical population.,Patients diagnosed with stable COPD in the outpatient department who completed the CAT and CCQ were enrolled from November 2015 to December 2016.,Scores of 0-10, 11-20, 21-30, and 31-40 represent low, medium, high, and very high impact level, respectively, by CAT.,Scores of the CCQ can be considered as acceptable (CCQ<1), acceptable for moderate disease (1≤CCQ<2), instable-severe limited (2≤CCQ<3), and very instable-very severe limited (CCQ≥3).,According to the CAT, only 20.4% of patients belonged to the high (21≤CAT≤30) and very high (31≤CAT≤40) impact levels, which were statistically lower than those of the CCQ, which classified over half of the population (51.1%) into the instable-severe limited (2≤CCQ<3) and very instable-very severe limited (CCQ≥3) categories (P<0.001).,The kappa of agreement for the symptom groups by CAT and CCQ (cutoff point 1.5) was 0.495, but only slight agreement (0.144) was found between the CAT and CCQ with the cutoff point of 1.0.,The CAT and the total CCQ had a strong correlation (rho=0.776, P<0.01).,The CCQ 1.0 and 1.5 corresponded to CAT 4.2 and 9.7, respectively.,The CAT 10.0 was equivalent to 1.53 of the CCQ.,In addition, with higher scores of the CAT and CCQ, subjects displayed more impairment in lung function, higher levels on modified Medical Research Council, and higher exacerbation rates in the last year (P<0.001).,Similarly, patients with more exacerbations presented worse scores on the CAT and total CCQ as well as its 3 domains (P<0.001).,Compared with the CAT, the CCQ was more likely to classify the patients into more severe categories, and 1.5 might be a better cutoff point for the CCQ than 1.0.,Both the CAT and the overall CCQ with its 3 domains were able to discriminate between groups of patients that differ in COPD severity. | COPD is currently the fourth cause of morbidity and mortality in the developed world.,Patients with COPD experience a progressive deterioration and disability, which lead to a worsening in their health-related quality of life (HRQoL).,The aim of this work is to assess the Health-Related Quality of Life (HRQoL) of patients with stable COPD followed in primary care and to identify possible predictors of disease.,It is a multicenter, epidemiological, observational, descriptive study.,Subjects of both sexes, older than 40 years and diagnosed of COPD at least 12 months before starting the study were included.,Sociodemographic data, severity of disease, comorbidity, and use of health resources in the previous 12 months were collected.,All patients were administered a generic quality-of-life questionnaire, the SF-12, that enables to calculate two scores, the physical (PCS-12) and the mental (MCS-12) component summary scores.,10,711 patients were evaluated (75.6% men, 24.4% women), with a mean age of 67.1 years (SD 9.66).,The mean value of FEV1 was 35.9 ± 10.0%.,Mean PCS-12 and MCS-12 scores were 36.0 ± 9.9 and 48.3 ± 10.9, respectively.,Compared to the reference population, patients with COPD had a reduction of PCS-12, even in mild stages of the disease.,The correlation with FEV1 was higher for PCS-12 (r = 0.38) than for MCS-12 (r = 0.12).,Predictors for both HRQoL components were sex, FEV1, use of oxygen therapy, and number of visits to emergency rooms and hospital admissions.,Other independent predictors of PCS-12 were age, body mass index and educational level.,Patients with stable COPD show a reduction of their HRQoL, even in mild stages of the disease.,The factors determining the HRQoL include sex, FEV1, use of oxygen therapy, and number of visits to emergency rooms and hospital admissions. | 1 |
Previous studies have established a higher prevalence of vitamin D deficiency in patients with COPD, but the relationship between vitamin D levels and COPD exacerbations remains controversial.,In addition, the effect of vitamin D levels on imaging characteristics remains mostly unexplored.,Using cross-sectional and longitudinal follow up data from the COPDGene Study, we assessed the association between vitamin D levels on respiratory symptoms, exacerbations, and imaging characteristics.,We hypothesized that vitamin D deficiency will be associated with worse respiratory-related outcomes.,Current and former smokers between ages 45-80 were enrolled the COPDGene Study.,Subjects completed questionnaires, spirometry, six-minute walk test, and chest computed tomography scans.,A subset of subjects had measurement of serum concentration of 25-hydroxyvitamin D (25(OH)D).,Vitamin D deficiency was defined as serum concentration less than 20 ng/mL.,Longitudinal follow up was conducted via a web-based or telephone questionnaire.,Vitamin D levels were measured on 1544 current and former smokers, of which 981 subjects had sufficient vitamin D levels and 563 subjects had vitamin D deficiency.,Subjects with vitamin D deficiency were younger with increased likelihood of being African American, being current smokers, having a lower percent predicted FEV1, and having COPD.,Vitamin D deficiency was associated with worse quality of life, increased dyspnea, decreased exercise tolerance, and increased frequency of severe exacerbations.,Vitamin D deficiency was also associated with increased segmental airway wall thickness on chest CT scans.,Vitamin D deficiency was associated with increased respiratory symptoms, decreased functional status, increased frequency of severe exacerbations, as well as airway wall thickening on chest CT scans.,Further research is needed to determine the potential impact of vitamin D supplementation to improve disease outcomes. | Although vitamin D is well known for its function in calcium homeostasis and bone mineralization, several studies have shown positive effects on muscle strength and physical function.,In addition, vitamin D has been associated with pulmonary function and the incidence of airway infections.,As vitamin D deficiency is highly prevalent in chronic obstructive pulmonary disease (COPD) patients, supplementation might have a beneficial effect in these patients.,To assess the effect of vitamin D supplementation on respiratory muscle strength and physical performance in vitamin D-deficient COPD patients.,Secondary outcomes are pulmonary function, handgrip strength, exacerbation rate, and quality of life.,We performed a randomized, double-blind, placebo-controlled pilot trial.,Participants were randomly allocated to receive 1,200 IU vitamin D3 per day (n=24) or placebo (n=26) during 6 months.,Study visits were conducted at baseline, and at 3 and 6 months after randomization.,During the visits, blood was collected, respiratory muscle strength was measured (maximum inspiratory and expiratory pressure), physical performance and 6-minute walking tests were performed, and handgrip strength and pulmonary function were assessed.,In addition, participants kept a diary card in which they registered respiratory symptoms.,At baseline, the mean (standard deviation [SD]) serum 25-hydroxyvitamin D (25(OH)D) concentration (nmol/L) was 42.3 (15.2) in the vitamin D group and 40.6 (17.0) in the placebo group.,Participants with vitamin D supplementation had a larger increase in serum 25(OH)D compared to the placebo group after 6 months (mean difference (SD): +52.8 (29.8) vs +12.3 (25.1), P<0.001).,Primary outcomes, respiratory muscle strength and physical performance, did not differ between the groups after 6 months.,In addition, no differences were found in the 6-minute walking test results, handgrip strength, pulmonary function, exacerbation rate, or quality of life.,Vitamin D supplementation did not affect (respiratory) muscle strength or physical performance in this pilot trial in vitamin D-deficient COPD patients. | 1 |
COPD is the third-largest killer in the world, and certainly takes a toll on the health care system.,Recurrent COPD exacerbations accelerate lung-function decline, worsen mortality, and consume over US$50 billion in health care spending annually.,This has led to a tide of payment reforms eliciting interest in strategies reducing preventable COPD exacerbations.,In this review, we analyze and discuss the evidence for COPD action plan-based self-management strategies.,Although action plans may provide stabilization of acute symptomatology, there are several limitations.,These include patient-centered attributes, such as comprehension and adherence, and nonadherence of health care providers to established guidelines.,While no single intervention can be expected independently to translate into improved outcomes, structured together within a comprehensive integrated disease-management program, they may provide a robust paradigm. | The Continuing to Confront COPD International Patient Survey estimated the prevalence and burden of COPD across 12 countries.,Using data from this survey we evaluated the economic impact of COPD.,This cross-sectional, population-based survey questioned 4,343 subjects aged 40 years and older, fulfilling a case definition of COPD based on self-reported physician diagnosis or symptomatology.,Direct cost measures were based on exacerbations of COPD (treated and those requiring emergency department visits and/or hospitalisation), contacts with healthcare professionals, and COPD medications.,Indirect costs were calculated from work loss values using the Work Productivity and Activity Impairment scale.,Combined direct and indirect costs estimated the total societal costs per patient.,The annual direct costs of COPD ranged from $504 (South Korea) to $9,981 (USA), with inpatient hospitalisations (5 countries) and home oxygen therapy (3 countries) being the key drivers of direct costs.,The proportion of patients completely prevented from working due to their COPD ranged from 6% (Italy) to 52% (USA and UK) with 8 countries reporting this to be ≥20%.,Total societal costs per patient varied widely from $1,721 (Russia) to $30,826 (USA) but a consistent pattern across countries showed greater costs among those with increased burden of COPD (symptoms, health status and more severe disease) and a greater number of comorbidities.,The economic burden of COPD is considerable across countries, and requires targeted resources to optimise COPD management encompassing the control of symptoms, prevention of exacerbations and effective treatment of comorbidities.,Strategies to allow COPD patients to remain in work are important for addressing the substantial wider societal costs. | 1 |
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease associated with various systemic comorbidities including osteoporosis.,Osteoporosis and its related fractures are common and have significant impacts on quality of life and even respiratory function in patients with COPD.,COPD-associated osteoporosis is however extremely undertreated.,Recent studies have suggested that both decreased bone mineral density (BMD) and impaired bone quality contribute to bone fragility, causing fractures in COPD patients.,Various clinical risk factors of osteoporosis in COPD patients, including older age, emaciation, physical inactivity, and vitamin D deficiency, have also been described.,It is critically important for pulmonologists to be aware of the high prevalence of osteoporosis in COPD patients and evaluate them for such fracture risks.,Routine screening for osteoporosis will enable physicians to diagnose COPD patients with comorbid osteoporosis at an early stage and give them appropriate treatment to prevent fracture, which may lead to improved quality of life as well as better long-term prognosis. | Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Comorbidities are often reported in patients with COPD and may influence the cost of care.,Yet, the extent by which comorbidities affect costs remains to be determined.,To review, quantify and evaluate excess costs of comorbidities in COPD.,Using a systematic review approach, Pubmed and Embase were searched for studies analyzing excess costs of comorbidities in COPD.,Resulting studies were evaluated according to study characteristics, comorbidity measurement and cost indicators.,Mark-up factors were calculated for respective excess costs.,Furthermore, a checklist of quality criteria was applied.,Twelve studies were included.,Nine evaluated comorbidity specific costs; three examined index-based results.,Pneumonia, cardiovascular disease and diabetes were associated with the highest excess costs.,The mark-up factors for respective excess costs ranged between 1.5 and 2.5 in the majority of cases.,On average the factors constituted a doubling of respective costs in the comorbid case.,The main cost driver, among all studies, was inpatient cost.,Indirect costs were not accounted for by the majority of studies.,Study heterogeneity was high.,The reviewed studies clearly show that comorbidities are associated with significant excess costs in COPD.,The inclusion of comorbid costs and effects in future health economic evaluations of preventive or therapeutic COPD interventions seems highly advisable. | 1 |
Increased small airway resistance and decreased lung elasticity contribute to the airflow limitation in chronic obstructive pulmonary disease (COPD).,The lesion that corresponds to loss of lung elasticity is emphysema; the small airway obstruction is due to inflammatory narrowing and obliteration.,Despite their convergence in altered physiology, different mechanisms contribute to these processes.,The relationships between gene expression and these specific phenotypes may be more revealing than comparison with lung function.,We measured the ratio of alveolar surface area to lung volume (SA/V) in lung tissue from 43 smokers.,Two samples from 21 subjects, in which SA/V differed by >49 cm2/mL were profiled to select genes whose expression correlated with SA/V.,Significant genes were tested for replication in the 22 remaining subjects.,The level of expression of 181 transcripts was related to SA/V ( p < 0.05).,When these genes were tested in the 22 remaining subjects as a replication, thirty of the 181 genes remained significantly associated with SA/V (P < 0.05) and the direction of association was the same in 164/181.,Pathway and network analysis revealed enrichment of genes involved in protein ubiquitination, and western blotting showed altered expression of genes involved in protein ubiquitination in obstructed individuals.,This study implicates modified protein ubiquitination and degradation as a potentially important pathway in the pathogenesis of emphysema.,The online version of this article (doi:10.1186/1471-2466-14-187) contains supplementary material, which is available to authorized users. | COPD (chronic obstructive pulmonary disease) is a major incurable global health burden and will become the third largest cause of death in the world by 2020.,It is currently believed that an exaggerated inflammatory response to inhaled irritants, in particular cigarette smoke, causes progressive airflow limitation.,This inflammation, where macrophages, neutrophils and T-cells are prominent, leads to oxidative stress, emphysema, small airways fibrosis and mucus hypersecretion.,The mechanisms and mediators that drive the induction and progression of chronic inflammation, emphysema and altered lung function are poorly understood.,Current treatments have limited efficacy in inhibiting chronic inflammation, do not reverse the pathology of disease and fail to modify the factors that initiate and drive the long-term progression of disease.,Therefore there is a clear need for new therapies that can prevent the induction and progression of COPD.,Animal modelling systems that accurately reflect disease pathophysiology continue to be essential to the development of new therapies.,The present review highlights some of the mouse models used to define the cellular, molecular and pathological consequences of cigarette smoke exposure and whether they can be used to predict the efficacy of new therapeutics for COPD. | 1 |
Genome Wide Association Studies (GWAS) and expression quantitative trait locus (eQTL) analyses have identified genetic associations with a wide range of human phenotypes.,However, many of these variants have weak effects and understanding their combined effect remains a challenge.,One hypothesis is that multiple SNPs interact in complex networks to influence functional processes that ultimately lead to complex phenotypes, including disease states.,Here we present CONDOR, a method that represents both cis- and trans-acting SNPs and the genes with which they are associated as a bipartite graph and then uses the modular structure of that graph to place SNPs into a functional context.,In applying CONDOR to eQTLs in chronic obstructive pulmonary disease (COPD), we found the global network “hub” SNPs were devoid of disease associations through GWAS.,However, the network was organized into 52 communities of SNPs and genes, many of which were enriched for genes in specific functional classes.,We identified local hubs within each community (“core SNPs”) and these were enriched for GWAS SNPs for COPD and many other diseases.,These results speak to our intuition: rather than single SNPs influencing single genes, we see groups of SNPs associated with the expression of families of functionally related genes and that disease SNPs are associated with the perturbation of those functions.,These methods are not limited in their application to COPD and can be used in the analysis of a wide variety of disease processes and other phenotypic traits. | Understanding the genetic basis of airflow obstruction and smoking behaviour is key to determining the pathophysiology of chronic obstructive pulmonary disease (COPD).,We used UK Biobank data to study the genetic causes of smoking behaviour and lung health.,We sampled individuals of European ancestry from UK Biobank, from the middle and extremes of the forced expiratory volume in 1 s (FEV1) distribution among heavy smokers (mean 35 pack-years) and never smokers.,We developed a custom array for UK Biobank to provide optimum genome-wide coverage of common and low-frequency variants, dense coverage of genomic regions already implicated in lung health and disease, and to assay rare coding variants relevant to the UK population.,We investigated whether there were shared genetic causes between different phenotypes defined by extremes of FEV1.,We also looked for novel variants associated with extremes of FEV1 and smoking behaviour and assessed regions of the genome that had already shown evidence for a role in lung health and disease.,We set genome-wide significance at p<5 × 10−8.,UK Biobank participants were recruited from March 15, 2006, to July 7, 2010.,Sample selection for the UK BiLEVE study started on Nov 22, 2012, and was completed on Dec 20, 2012.,We selected 50 008 unique samples: 10 002 individuals with low FEV1, 10 000 with average FEV1, and 5002 with high FEV1 from each of the heavy smoker and never smoker groups.,We noted a substantial sharing of genetic causes of low FEV1 between heavy smokers and never smokers (p=2·29 × 10−16) and between individuals with and without doctor-diagnosed asthma (p=6·06 × 10−11).,We discovered six novel genome-wide significant signals of association with extremes of FEV1, including signals at four novel loci (KANSL1, TSEN54, TET2, and RBM19/TBX5) and independent signals at two previously reported loci (NPNT and HLA-DQB1/HLA-DQA2).,These variants also showed association with COPD, including in individuals with no history of smoking.,The number of copies of a 150 kb region containing the 5′ end of KANSL1, a gene that is important for epigenetic gene regulation, was associated with extremes of FEV1.,We also discovered five new genome-wide significant signals for smoking behaviour, including a variant in NCAM1 (chromosome 11) and a variant on chromosome 2 (between TEX41 and PABPC1P2) that has a trans effect on expression of NCAM1 in brain tissue.,By sampling from the extremes of the lung function distribution in UK Biobank, we identified novel genetic causes of lung function and smoking behaviour.,These results provide new insight into the specific mechanisms underlying airflow obstruction, COPD, and tobacco addiction, and show substantial shared genetic architecture underlying airflow obstruction across individuals, irrespective of smoking behaviour and other airway disease.,Medical Research Council. | 1 |
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide.,The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD.,Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I-II/A-B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography-high resolution mass spectrometry metabolomics platform.,Pathway analyses revealed that several altered metabolites are involved in oxidative stress.,Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10−7).,Sex stratification indicated that the separation was driven by females (p=2.4×10−7) relative to males (p=4.0×10−4).,Significantly altered metabolites were confirmed quantitatively using targeted metabolomics.,Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10−3) relative to males (p=0.10).,The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p<0.0001), but not females (r=0.44; p=0.15), potentially related to observed dysregulation of the miR-29 family in the lung.,These findings highlight the role of oxidative stress in COPD, and suggest that sex-enhanced dysregulation in oxidative stress, and potentially the autotaxin-lysoPA axis, are associated with disease mechanisms and/or prevalence.,Oxidative stress and the autotaxin-lysoPA axis evidence sex-associated metabotypes in the serum of COPD patientshttp://ow.ly/kAeE309MpdI | 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 |
Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD).,It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.,Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts.,The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.,Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.,Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence.,Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma. | Increasing age is associated with poor prognosis in patients with COPD.,This analysis from the replicate Phase III OTEMTO® and TONADO® studies examined the efficacy and safety of tiotropium, a long-acting anticholinergic, combined with olodaterol, a long-acting β2-agonist, compared to monotherapies and placebo in patients with COPD aged 40 years to <65 years, 65 years to <75 years, 75 years to <85 years, and ≥85 years.,In these double-blind, parallel-group, active-controlled, multicenter, randomized studies, patients received tiotropium + olodaterol 2.5/5 μg or 5/5 μg, tiotropium 5 μg or 2.5 μg (TONADO only), olodaterol 5 μg (TONADO only), or placebo (OTEMTO only).,This analysis used the approved doses of tiotropium + olodaterol 5/5 μg, tiotropium 5 μg, and olodaterol 5 μg.,Primary end points at 12 weeks (OTEMTO) or 24 weeks (TONADO) included St George’s Respiratory Questionnaire (SGRQ) total score, forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 3 hours (AUC0-3) response, and trough FEV1 response.,A total of 1,621 patients were randomized (40 years to <65 years, n=749; 65 years to <75 years, n=674; 75 years to <85 years, n=186; ≥85 years, n=12) in OTEMTO and 5,162 patients (40 years to <65 years, n=2,654; 65 years to <75 years, n=1,967; 75 to <85 years, n=528; ≥85 years, n=13) in TONADO.,FEV1 AUC0-3 and trough FEV1 responses improved with tiotropium + olodaterol 5/5 μg at 12 weeks and 24 weeks compared to monotherapies or placebo for all age groups.,SGRQ scores generally improved with tiotropium + olodaterol 5/5 μg after 12 weeks in OTEMTO and improved after 24 weeks in all age groups in TONADO.,In all age groups receiving tiotropium + olodaterol 5/5 μg compared to monotherapies or placebo, transition dyspnea index scores generally improved, while rescue medication usage improved.,No differences were noted in relative responses to treatment or safety when using tiotropium + olodaterol 5/5 μg compared to monotherapies or placebo across all age groups. | 1 |
Since the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups A-D were introduced, the lung function changes according to group have been evaluated rarely.,We investigated the rate of decline in annual lung function in patients categorized according to the 2014 GOLD guidelines.,Patients with COPD included in the Korean Obstructive Lung Disease (KOLD) prospective study, who underwent yearly postbronchodilator spirometry at least three times, were included.,The main outcome was the annual decline in postbronchodilator forced expiratory volume in 1 second (FEV1), which was analyzed by random-slope and random-intercept mixed linear regression.,A total 175 participants were included.,No significant postbronchodilator FEV1 decline was observed between the groups (−34.4±7.9 [group A]; −26.2±9.4 [group B]; −22.7±16.0 [group C]; and −24.0±8.7 mL/year [group D]) (P=0.79).,The group with less symptoms (−32.3±7.2 vs −25.0±6.5 mL/year) (P=0.44) and the low risk group (−31.0±6.1 vs −23.6±7.7 mL/year) (P=0.44) at baseline showed a more rapid decline in the postbronchodilator FEV1, but the trends were not statistically significant.,However, GOLD stages classified by FEV1 were significantly related to the annual lung function decline.,There was no significant difference in lung function decline rates according to the GOLD groups.,Prior classification using postbronchodilator FEV1 predicts decline in lung function better than does the new classification. | Chronic obstructive pulmonary disease (COPD) is an obstructive and progressive airway disease associated with an important reduction in daily physical activity and psychological problems that contribute to the patient’s disability and poor health-related quality of life (HRQoL).,Nowadays, pulmonary rehabilitation (PR) plays an essential role in the management of symptomatic patients with COPD, by breaking the vicious circle of dyspnea-decreased activity-deconditioning-isolation.,Indeed the main benefits of comprehensive PR programs for patients with COPD include a decrease in symptoms (dyspnea and fatigue), improvements in exercise tolerance and HRQoL, reduction of health care utilization (particularly bed-days), as well as an increase in physical activity.,Several randomized studies and meta-analyses greatly established the benefits of PR, which additionally, is recommended in a number of influential guidelines.,This review aimed to highlight the impact of PR on COPD patients, focusing on the clinical usefulness of PR, which provides patients a good support for change. | 1 |
The objective of this study is to assess whether statin use is associated with beneficial effects on COPD outcomes.,We conducted a systematic review and meta-analysis of all available studies describing the association between statin use and COPD mortality, exacerbations and cardiovascular events.,Medline, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched, with no restrictions.,The hazard ratio (HR) with 95% confidence interval (CI) was estimated.,Fifteen studies with a total of 238,459 patients were included.,Nine articles provided data on all-cause mortality (124,543 participants), and they gave a HR of 0.62 (95% CI 0.52 to 0.73).,Three studies provided data on cancer mortality (90,077 participants), HR 0.83 (0.65 to 1.08); four studies on COPD mortality (88,767 participants), HR 0.48 (0.23 to 0.99); and three studies on cardiovascular mortality (90,041 participants), HR 0.93 (0.50 to 1.72).,Six articles provided data on COPD exacerbation with or without hospitalization (129,796 participants), HR 0.64 (0.55 to 0.75).,Additionally, the use of statins was associated with a significant reduction risk of myocardial infarction, but not for stroke.,Our systematic review showed a clear benefit of statins in patients with COPD. | The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known.,We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database.,951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012.,Individuals were selected for ≥1 of 8 algorithms to identify people with COPD.,General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested.,All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard.,The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed.,951 questionnaires were sent and 738 (78%) returned.,After quality control, 696 (73.2%) patients were included in the final analysis.,All four algorithms including a specific COPD diagnostic code performed well.,Using a diagnostic code alone, the PPV was 86.5% (77.5-92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7-94.5%) but reduced case numbers by 10%.,Algorithms without specific diagnostic codes had low PPVs (range 12.2-44.4%).,Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes.,Requiring spirometry or COPD medications only marginally improved accuracy.,The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004. | 1 |
Chronic obstructive pulmonary disease exacerbations (COPDEs) are associated with increased morbidity and mortality.,Cell-free DNA (cfDNA) is a novel biomarker associated with clinical outcomes in several disease states but has not been studied in COPD.,The objectives of this study were to assess cfDNA levels during a COPDE, to evaluate the association of cfDNA with clinical parameters and to explore the prognostic implications of cfDNA levels on long-term survival.,This was an observational study that assessed cfDNA levels in patients admitted to hospital for a COPDE.,Plasma cfDNA levels of COPDE patients were compared to those of matched stable COPD patients and healthy controls.,Multivariable and Cox regression analyses were used to assess the association of cfDNA levels with blood gas parameters and long-term survival.,A total of 62 patients (46 males, forced expiratory volume in 1 second [FEV1] 38%±13%) were included.,The median cfDNA levels on admission for COPDE patients was 1,634 ng/mL (interquartile range [IQR] 1,016-2,319) compared to 781 ng/mL (IQR 523-855) for stable COPD patients, matched for age and disease severity, and 352 ng/mL (IQR 209-636) for healthy controls (P<0.0001, for both comparisons). cfDNA was correlated with partial arterial pressure of carbon dioxide (PaCO2, r=0.35) and pH (r=−0.35), P=0.01 for both comparisons.,In a multivariable analysis, PaCO2 was the only independent predictor of cfDNA.,Using a cfDNA level of 1,924 ng/mL (threshold for abnormal PaCO2), those with high levels had a trend for increased 5-year mortality risk adjusted for age, sex and FEV1% (hazard ratio 1.92, 95% confidence interval 0.93-3.95, P=0.08).,Plasma cfDNA might offer a novel technique to identify COPD patients at increased risk of poor outcomes, but the prognostic utility of this measurement requires further study. | Viruses are a common cause of exacerbations in chronic obstructive pulmonary disease (COPD).,They activate toll-like receptors (TLRs) 3, 7, and 8, leading to a pro-inflammatory response.,We have characterized the responses of TLR3 and TLR7/8 in lung tissue explants from COPD patients and control smokers.,We prepared lung whole tissue explants (WTEs) from patients undergoing surgery for confirmed or suspected lung cancer.,In order to mimic the conditions of viral infection, we used poly(I:C) for TLR3 stimulation and R848 for TLR7/8 stimulation.,These TLR ligands were used alone and in combination.,The effects of tumor necrosis factor α (TNFα) neutralization and dexamethasone on TLR responses were examined.,Inflammatory cytokine release was measured by enzyme-linked immunosorbent assay and gene expression by quantitative real-time polymerase chain reaction.,WTEs from COPD patients released higher levels of pro-inflammatory cytokines compared with WTEs from smokers.,Activation of multiple TLRs led to a greater than additive release of TNFα and CCL5.,TNFα neutralization and dexamethasone treatment decreased cytokine release.,This WTE model shows an enhanced response of COPD compared with controls, suggesting an increased response to viral infection.,There was amplification of innate immune responses with multiple TLR stimulation. | 1 |
Low adherence to Global initiative for chronic Obstructive Lung Disease (GOLD) guideline recommendations has been reported worldwide.,There has been no study on the adherence to GOLD guidelines for COPD treatment in Turkey.,To investigate the rates of adherence to GOLD 2010 guidelines for COPD treatment among pulmonologists.,A multi-center, cross-sectional, observational study was carried out in eleven pulmonary outpatient clinics across Turkey.,Adherence to GOLD was evaluated through hospital records.,Demographic and clinical data were recorded.,Study included 719 patients (mean age: 62.9±9.7 years; males 85.4%) of whom 16 was classified as GOLD Stage I, 238 as II, 346 as III, and 119 as IV, and only 59.5% received appropriate treatment.,Rates of guideline adherence varied across GOLD stages (I, 6.3%; II, 14.7%; III, 84.4%; and IV, 84%).,Causes of inappropriate therapies were overtreatment (Stage I, 100% and Stage II, 91.1%), undertreatment (Stage III, 3.3% and Stage IV, 10.9%) and lack of treatment (Stage II, 3.8%; Stage III, 2.3%; and Stage IV, 5.9%).,The most preferred regimen (43.4%) was long-acting β2-agonist-inhaled corticosteroid-long-acting muscarinic antagonist.,Overall, 614 patients (89%) received treatment containing inhaled corticosteroid.,Pulmonologists in Turkey have low rates of adherence to GOLD guidelines in COPD treatment.,Inappropriateness of therapies was due to overtreatment in early stages and excessive use of inhaled corticosteroid (ICS) in all disease stages. | To estimate the potential cost savings by following the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline recommendations in patients being treated for chronic obstructive pulmonary disease (COPD) with the combination of long-acting β2-agonist (LABA), long-acting muscarinic antagonist (LAMA) or inhaled corticosteroids (ICS).,The Geisinger Health System (GHS) database was utilized to identify subjects between January 1, 2004 to March 12, 2007.,The index date was based on the first prescription of a LAMA plus LABA, LAMA plus LABA/ICS, or LABA plus ICS.,Patients were included in the study if they: had a COPD diagnosis; had data representative of treatment 12 months prior to and 12 months post index date; were 40 years of age or over; had no prior diagnosis for asthma; and had pulmonary function test (PFT) data.,We examined the baseline characteristics of these patients along with their healthcare resource utilization.,Based on PFT data within 30 days of the index date, a subgroup was classified as adhering or non-adhering to GOLD guidelines.,A total of 364 subjects could be classified as adhering or non-adherent to current GOLD guidelines based on their PFT results.,The adherent subgroup received COPD medications consistent with current GOLD guidelines.,Of the LAMA plus LABA cohort, 25 patients adhered and 39 patients were non-adherent to current GOLD guidelines.,In the cohort of LABA plus ICS, 74 patients were adherent and 180 patients non-adherent to current GOLD guidelines.,In the cohort of LAMA plus LABA/ICS, 21 patients were adherent and 25 patients non-adherent to current GOLD guidelines.,GOLD adherence was associated with mean total cost of all services savings of $5,889 for LAMA plus LABA, $3,330 for LABA + ICS, and $10,217 for LAMA plus LABA/ICS cohorts.,Staging of COPD with a PFT and adherence to current GOLD guidelines was associated with lower costs in subjects with moderate to severe COPD.,Appropriate use of LAMA plus LABA, LABA plus ICS, and LAMA plus LABA/ICS has economic as well as clinical benefits for patients and payers. | 1 |
Recently, two “fixed triple” single-inhaler combinations of an inhaled corticosteroid (ICS), a long-acting β2-agonist (LABA), and a long-acting muscarinic antagonist (LAMA) have become available for patients with COPD.,This review presents the clinical evidence that led to the approval of these triple therapies, discusses the role of ICS in patients with COPD, and presents data on the relative efficacy of “fixed triple” (ICS/LAMA/LABA) therapy vs LAMA, ICS/LABA, and LAMA/LABA combinations, and summarizes studies in which ICS/LABAs were combined with LAMAs to form “open triple” combinations.,Of the five main fixed triple studies completed so far, three evaluated the efficacy and safety of an extrafine formulation of beclometasone dipropionate, formoterol fumarate, and glycopyrronium; the other two studies evaluated fluticasone furoate, vilanterol, and umeclidinium.,Overall, compared to LAMA, ICS/LABA, or LAMA/LABA, triple therapy decreased the risk of exacerbations and improved lung function and health status, with a favorable benefit-to-harm ratio.,Furthermore, triple therapy showed a promising signal in terms of improved survival.,The evidence suggests that triple therapy is the most effective treatment in moderate/severe symptomatic patients with COPD at risk of exacerbations, with marginal if any risk of side effects including pneumonia.,Ongoing studies are examining the role of triple therapy in less severe symptomatic patients with COPD and asthma-COPD overlap. | There is controversy regarding the significance of radiological consolidation in the context of COPD exacerbation (eCOPD).,While some studies into eCOPD exclude these cases, consolidation is a common feature of eCOPD admissions in real practice.,This study aims to address the question of whether consolidation in eCOPD is a distinct clinical phenotype with implications for management decisions and outcomes.,The European COPD Audit was carried out in 384 hospitals from 13 European countries between 2010 and 2011 to analyze guideline adherence in eCOPD.,In this analysis, admissions were split according to the presence or not of consolidation on the admission chest radiograph.,Groups were compared in terms of clinical and epidemiological features, existing treatment, clinical care utilized and mortality.,14,111 cases were included comprising 2,714 (19.2%) with consolidation and 11,397 (80.8%) without.,The risk of radiographic consolidation increased with age, female gender, cardiovascular diseases, having had two or more admissions in the previous year, and sputum color change.,Previous treatment with inhaled steroids was not associated.,Patients with radiographic consolidation were significantly more likely to receive antibiotics, oxygen and non-invasive ventilation during the admission and had a lower survival from admission to 90-day follow-up.,Patients admitted for COPD exacerbation who have radiological consolidation have a more severe illness course, are treated more intensively by clinicians and have a poorer prognosis.,We recommend that these patients be considered a distinct subset in COPD exacerbation. | 1 |
Poor treatment adherence in patients with chronic obstructive pulmonary disease (COPD) or asthma is a global public health concern with severe consequences in terms of patient health and societal costs.,A potentially promising tool for addressing poor compliance is eHealth.,This review investigates the effects of eHealth interventions on medication adherence in patients with COPD or asthma.,A systematic literature search was conducted in the databases of Cochrane Library, PsycINFO, PubMed, and Embase for studies with publication dates between January 1, 2000, and October 29, 2020.,We selected randomized controlled trials targeting adult patients with COPD or asthma, which evaluated the effectiveness of an eHealth intervention on medication adherence.,The risk of bias in the included studies was examined using the Cochrane Collaboration’s risk of bias tool.,The results were narratively reviewed.,In total, six studies focusing on COPD and seven focusing on asthma were analyzed.,Interventions were mostly internet-based or telephone-based, and could entail telemonitoring of symptoms and medication adherence, education, counseling, consultations, and self-support modules.,Control groups mostly comprised usual care conditions, whereas a small number of studies used a face-to-face intervention or waiting list as the control condition.,For COPD, the majority of eHealth interventions were investigated as an add-on to usual care (5/6 studies), whereas for asthma the majority of interventions were investigated as a standalone intervention (5/7 studies).,Regarding eHealth interventions targeting medication adherence for COPD, two studies reported nonsignificant effects, one study found a significant effect in comparison to usual care, and three reported mixed results.,Of the seven studies that investigated eHealth interventions targeting medication adherence in asthma, three studies found significant effects, two reported nonsignificant effects, and two reported mixed effects.,The mixed results on the effectiveness of eHealth interventions in improving treatment adherence for asthma and COPD are presumably related to the type, context, and intensity of the interventions, as well as to differences in the operationalization and measurement of adherence outcomes.,Much remains to be learned about the potential of eHealth to optimize treatment adherence in COPD and asthma. | The use of information technology can make pulmonary rehabilitation interventions in people with chronic obstructive pulmonary disease (COPD) more flexible and thereby has the potential to reach a larger proportion of the population.,However, the success of using information technology in pulmonary rehabilitation is dependent on the end-user’s competence in information technology and access to the Internet.,The aim was to describe the access to, and the use, knowledge, and preferences of information technology and technical equipment among people with COPD.,Telephone interviews were conducted using a standardised questionnaire on information technology and technical devises addressing the household, access to and usage of the Internet, contact with authorities, e-commerce, security, the workplace, digital competence, and disabilities.,Questions were also posed regarding participants’ views on a future eHealth tool for COPD, appropriate content, and the potential likelihood for them to use an eHealth tool for exercise training.,In total 137 persons agreed to participate, 17 dropped out resulting in 120 included participants (response rate 88%).,The participants (86 women) were aged 51 to 92 years (mean: 72.5), and all severity grades of COPD according to GOLD A-D were represented.,Over 90% had access to the Internet.,Smartphones were used by 81%, and over 90% used apps.,Participants had high knowledge of how to use the Internet, 91% had used the Internet during the last 3 months, 85% almost every day.,The most common requests for a future eHealth tool for COPD were evidence-based and trustworthy information on COPD, (including medication, exercise training, inhalation and breathing techniques), communication (chat) with others and with health carers.,Access to individually adjusted exercise training, and support, (motivation via prompts, chat rooms, digital information board) was also desired.,The present study showed that people with COPD in Sweden have high access and ability to use the Internet and information technology.,They are frequent users and most of them take part in the digital society, even to a higher extent than the general population.,The results show that the use of an eHealth tool could be a suitable strategy for people with COPD. | 1 |
To investigate the clinical features, diagnosis, and treatment status of elderly patients with chronic obstructive pulmonary disease (COPD) complicated with lung cancer.,This was a retrospective study of 206 patients aged >60 years with COPD and newly diagnosed lung cancer at the Tianjin Chest Hospital Respiratory Centre between September 2008 and September 2013.,Lung function, radiology, and clinical data were retrieved.,Among all patients, 57% (117/206) were hospitalized due to acute COPD aggravation, 47% (96/206) had COPD grade III or IV, 95% (195/206), showed diffusion dysfunction in pulmonary function examination, 90% (185/206) had a history of smoking, and 26% (54/206) were treated with inhaled corticosteroids for COPD treatment.,Ninety-eight patients suffered from squamous carcinoma, 73 from adenocarcinoma, and 35 from small-cell carcinoma.,Clinical staging was I in 36 patients, II in 47 patients, III in 78 patients, and IV in 45 patients.,Initial treatments were surgery in 59 patients, chemotherapy in 30 patients, and no treatment in 117 patients.,Multivariate analysis showed that age (P<0.001), COPD grades (P=0.01), clinical staging (P<0.001), and pulmonary diffusion function (P=0.007) were independent factors associated with patients with COPD being given treatments for lung cancer.,Younger patients with lower COPD grades, earlier lung cancer stage, and better pulmonary diffusion function are more likely to receive treatments. | Patients with COPD might not report mild exacerbation.,The frequency, risk factors, and impact of mild exacerbation on COPD status are unknown.,The present study was performed to compare features between mild exacerbation and moderate or severe exacerbation in Japanese patients with COPD.,An observational COPD cohort was designed at Keio University and affiliated hospitals to prospectively investigate the management of COPD comorbidities.,This study analyzes data only from patients with COPD who had completed annual examinations and questionnaires over a period of 2 years (n=311).,Among 59 patients with mild exacerbations during the first year, 32.2% also experienced only mild exacerbations in the second year.,Among 60 patients with moderate or severe exacerbations during the first year, 40% also had the same severity of exacerbation during the second year.,Findings of the COPD assessment test and the symptom component of the St George’s Respiratory Questionnaire at steady state were worse in patients with mild exacerbations than in those who were exacerbation free during the 2-year study period, although the severity of the ratio of predicted forced expiratory volume in 1 second did not differ between them.,Severe airflow limitation (the ratio of predicted forced expiratory volume in 1 second <50%) and experience of mild exacerbations independently advanced the likelihood of an elevated COPD assessment test score to ≥2 per year.,The severity of COPD exacerbation seemed to be temporally stable over 2 years, and even mild exacerbations adversely impacted the health-related quality of life of patients with COPD. | 1 |
Reduced physical activity (PA) in patients with COPD is associated with a poor prognosis.,Increasing PA is a key therapeutic target, but thus far few strategies have been found effective in this patient group.,To investigate the effectiveness of a 12-week semiautomated telecoaching intervention on PA in patients with COPD in a multicentre European randomised controlled trial.,343 patients from six centres, encompassing a wide spectrum of disease severity, were randomly allocated to either a usual care group (UCG) or a telecoaching intervention group (IG) between June and December 2014.,This 12-week intervention included an exercise booklet and a step counter providing feedback both directly and via a dedicated smartphone application.,The latter provided an individualised daily activity goal (steps) revised weekly and text messages as well as allowing occasional telephone contacts with investigators.,PA was measured using accelerometry during 1 week preceding randomisation and during week 12.,Secondary outcomes included exercise capacity and health status.,Analyses were based on modified intention to treat.,Both groups were comparable at baseline in terms of factors influencing PA.,At 12 weeks, the intervention yielded a between-group difference of mean, 95% CI (lower limit - upper limit; ll-ul) +1469, 95% CI (971 to 1965) steps/day and +10.4, 95% CI (6.1 to 14.7) min/day moderate PA; favouring the IG (all p≤0.001).,The change in 6-min walk distance was significantly different (13.4, 95% CI (3.40 to 23.5) m, p<0.01), favouring the IG.,In IG patients, an improvement could be observed in the functional state domain of the clinical COPD questionnaire (p=0.03) compared with UCG.,Other health status outcomes did not differ.,The amount and intensity of PA can be significantly increased in patients with COPD using a 12-week semiautomated telecoaching intervention including a step counter and an application installed on a smartphone.,NCT02158065. | Pulmonary rehabilitation (PR) provides benefit for patients with chronic obstructive pulmonary disease (COPD) in terms of quality of life (QoL) and exercise capacity; however, the effects diminish over time.,Our aim was to evaluate a maintenance programme for patients who had completed PR.,Primary and secondary care PR programmes in Norfolk.,148 patients with COPD who had completed at least 60% of a standard PR programme were randomised and data are available for 110 patients.,Patients had greater than 20 pack year smoking history and less than 80% predicted forced expiratory volume in 1 s but no other significant disease or recent respiratory tract infection.,Patients were randomised to receive a maintenance programme or standard care.,The maintenance programme consisted of 2 h (1 h individually tailored exercise training and 1 h education programme) every 3 months for 1 year.,The Chronic Respiratory Questionnaire (CRQ) (primary outcome), endurance shuttle walk test (ESWT), EuroQol (EQ5D), hospital anxiety and depression score (HADS), body mass index (BMI), body fat, activity levels (overall score and activity diary) and exacerbations were assessed before and after 12 months.,There was no statistically significant difference between the groups for the change in CRQ dyspnoea score (primary end point) at 12 months which amounted to 0.19 (−0.26 to 0.64) units or other domains of the CRQ.,There was no difference in the ESWT duration (−10.06 (−191.16 to 171.03) seconds), BMI, body fat, EQ5D, MET-minutes, activity rating, HADS, exacerbations or admissions.,A maintenance programme of three monthly 2 h sessions does not improve outcomes in patients with COPD after 12 months.,We do not recommend that our maintenance programme is adopted.,Other methods of sustaining the benefits of PR are required.,NCT00925171. | 1 |
It remains unclear whether severe exacerbation and pneumonia of COPD differs between patients treated with budesonide/formoterol and those treated with fluticasone/salmeterol.,Therefore, we conducted a comparative study of those who used budesonide/formoterol and those treated with fluticasone/salmeterol for COPD.,Subjects in this population-based cohort study comprised patients with COPD who were treated with a fixed combination of budesonide/formoterol or fluticasone/salmeterol.,All patients were recruited from the Taiwan National Health Insurance database.,The outcomes including severe exacerbations, pneumonia, and pneumonia requiring mechanical ventilation (MV) were measured.,During the study period, 11,519 COPD patients receiving fluticasone/salmeterol and 7,437 patients receiving budesonide/formoterol were enrolled in the study.,Pairwise matching (1:1) of fluticasone/salmeterol and budesonide/formoterol populations resulted in to two similar subgroups comprising each 7,295 patients.,Patients receiving fluticasone/salmeterol had higher annual rate and higher risk of severe exacerbation than patients receiving budesonide/formoterol (1.2219/year vs 1.1237/year, adjusted rate ratio, 1.08; 95% CI, 1.07-1.10).,In addition, patients receiving fluticasone/salmeterol had higher incidence rate and higher risk of pneumonia than patients receiving budesonide/formoterol (12.11 per 100 person-years vs 10.65 per 100 person-years, adjusted hazard ratio [aHR], 1.13; 95% CI, 1.08-1.20).,Finally, patients receiving fluticasone/salmeterol had higher incidence rate and higher risk of pneumonia requiring MV than patients receiving budesonide/formoterol (3.94 per 100 person-years vs 3.47 per 100 person-years, aHR, 1.14; 95% CI, 1.05-1.24).,A similar trend was seen before and after propensity score matching analysis, intention-to-treat, and as-treated analysis with and without competing risk.,Based on this retrospective observational study, long-term treatment with fixed combination budesonide/formoterol was associated with fewer severe exacerbations, pneumonia, and pneumonia requiring MV than fluticasone/salmeterol in COPD patients. | Airway absorption and bioavailability of inhaled corticosteroids (ICSs) may be influenced by differences in pharmacokinetic properties such as lipophilicity and patient characteristics such as lung function.,This study aimed to further investigate and clarify the distribution of budesonide and fluticasone in patients with severe chronic obstructive pulmonary disease (COPD) by measuring the systemic availability and sputum concentration of budesonide and fluticasone, administered via combination inhalers with the respective long-acting β2-agonists, formoterol and salmeterol.,This was a randomized, double-blind, double-dummy, two-way crossover, multicenter study.,Following a run-in period, 28 patients with severe COPD (mean age 65 years, mean forced expiratory volume in 1 second [FEV1] 37.5% predicted normal) and 27 healthy subjects (mean age 31 years, FEV1 103.3% predicted normal) received two single-dose treatments of budesonide/formoterol (400/12 μg) and salmeterol/fluticasone (50/500 μg), separated by a 4-14-day washout period.,ICS concentrations were measured over 10 hours post-inhalation in plasma in all subjects, and over 6 hours in spontaneously expectorated sputum in COPD patients.,The primary end point was the area under the curve (AUC) of budesonide and fluticasone plasma concentrations in COPD patients relative to healthy subjects.,Mean plasma AUC values were lower in COPD patients versus healthy subjects for budesonide (3.07 μM·hr versus 6.21 μM·hr) and fluticasone (0.84 μM·hr versus 1.50 μM·hr), and the dose-adjusted AUC (geometric mean) ratios in healthy subjects and patients with severe COPD for plasma budesonide and fluticasone were similar (2.02 versus 1.80; primary end point).,In COPD patients, the Tmax and the mean residence time in the systemic circulation were shorter for budesonide versus fluticasone (15.5 min versus 50.8 min and 4.41 hrs versus 12.78 hrs, respectively) and Cmax was higher (1.08 μM versus 0.09 μM).,The amount of expectorated fluticasone (percentage of estimated lung-deposited dose) in sputum over 6 hours was significantly higher versus budesonide (ratio 5.21; p = 0.006).,Both treatments were well tolerated.,The relative systemic availabilities of budesonide and fluticasone between patients with severe COPD and healthy subjects were similar.,In patients with COPD, a larger fraction of fluticasone was expectorated in the sputum as compared with budesonide.,Trial registration number NCT00379028 | 1 |
Key characteristics of chronic obstructive pulmonary disease (COPD) that significantly affect health-related quality of life (HRQoL) include chest symptoms, dyspnea, cough, sputum production, and exacerbations.,Additional areas of impact are sleep, fatigue, emotional well-being, social functioning, and coping.,Patient-reported outcomes (PROs) are essential to evaluate symptoms, impact of symptoms on activities of daily living, and treatment response.,This review summarizes COPD-specific PRO endpoints from randomized controlled trials of approved and commonly used COPD drugs.,A search conducted in “ClinicalTrials.gov” to identify COPD clinical trials (only completed Phase III and IV) incorporating PRO endpoints yielded a total of 104 clinical trials for inclusion in this analysis.,Both symptom-based and HRQoL-specific PRO measures were reported.,Several COPD-specific PRO measures are available; however, the St.,George’s Respiratory Questionnaire (SGRQ) and the Baseline and Transition Dyspnea Indexes (BDI/TDI) were reported in the majority of the studies.,Results reflected a gap in terms of full coverage of key impacted areas from a patient’s perspective.,Methodological issues identified in this review related to scoring of instruments require careful consideration, as these challenges may limit the complete assessment of drug benefits.,Selection of PRO measures aligned with the expected treatment benefit of a drug in a clinical trial should reflect patients’ perspective holistically. | The response to a bronchodilator is considered as crucial to diagnose COPD and to distinguish COPD from asthma.,COPD is characterized by progressive airflow obstruction that is only partly reversible, whereas asthma is associated with airflow obstruction that is often reversible either spontaneously or with treatment.,In spite of the partly reversible airflow obstruction, patients with COPD may show a significant bronchodilator response both in terms of an increase in forced expiratory volume in 1 second (FEV1) or in forced vital capacity (FVC) after an adequate dose of an inhaled bronchodilator.,Changes in FEV1 or FVC characterize, respectively, flow or volume response after bronchodilator administration.,This overview will deal with the reversibility testing characteristics and its clinical significance in COPD patients. (www.actabiomedica.it) | 1 |
Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century.,The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD.,Our understanding of the key molecular mechanisms which drive the pathological changes are not complete.,In this article we will provide a historical overview of key histopathological studies which have helped shape our understanding of SAD and discuss the hallmark features of airway remodelling, mucous plugging and inflammation.,We focus on the relationship between SAD and emphysema, SAD in the early stages of COPD, and the mechanisms which cause SAD progression, including bacterial colonization and exacerbations.,We discuss the need to specifically target SAD to attenuate the progression of COPD. | To describe a murine model of emphysema induced by a combination of exposure to cigarette smoke (CS) and instillation of porcine pancreatic elastase (PPE).,A total of 38 C57BL/6 mice were randomly divided into four groups: control (one intranasal instillation of 0.9% saline solution); PPE (two intranasal instillations of PPE); CS (CS exposure for 60 days); and CS + PPE (two intranasal instillations of PPE + CS exposure for 60 days).,At the end of the experimental protocol, all animals were anesthetized and tracheostomized for calculation of respiratory mechanics parameters.,Subsequently, all animals were euthanized and their lungs were removed for measurement of the mean linear intercept (Lm) and determination of the numbers of cells that were immunoreactive to macrophage (MAC)-2 antigen, matrix metalloproteinase (MMP)-12, and glycosylated 91-kDa glycoprotein (gp91phox) in the distal lung parenchyma and peribronchial region.,Although there were no differences among the four groups regarding the respiratory mechanics parameters assessed, there was an increase in the Lm in the CS + PPE group.,The numbers of MAC-2-positive cells in the peribronchial region and distal lung parenchyma were higher in the CS + PPE group than in the other groups, as were the numbers of cells that were positive for MMP-12 and gp91phox, although only in the distal lung parenchyma.,Our model of emphysema induced by a combination of PPE instillation and CS exposure results in a significant degree of parenchymal destruction in a shorter time frame than that employed in other models of CS-induced emphysema, reinforcing the importance of protease-antiprotease imbalance and oxidant-antioxidant imbalance in the pathogenesis of emphysema. | 1 |
Supplemental digital content is available in the text.,Chronic obstructive pulmonary disease (COPD) is associated with altered metabolism and body composition that accompany poor outcomes.,We aimed to determine whether metabolic derangements in COPD are associated with skeletal muscle deconditioning and/or physical inactivity, independent of pulmonary obstruction.,We characterized serum metabolites associated with muscle oxidative capacity or physical activity in 44 COPD patients (forced expiratory volume in 1 s [FEV1] = 61% ± 4% predicted) and 63 current and former smokers with normal spirometry (CON) (FEV1 = 93% ± 2% predicted).,Medial gastrocnemius oxidative capacity was assessed at rest from the recovery rate constant (k) of muscle oxygen consumption using near-infrared spectroscopy.,Step counts and physical activity (average vector magnitude units [VMU] per minute) were measured over 5-7 d using triaxial accelerometry.,Untargeted prime and lipid metabolites were measured using liquid chromatography and mass spectrometry.,Muscle k (1.12 ± 0.05 vs 1.68 ± 0.06 min−1, P < 0.0001, d = 1.58) and VMU per minute (170 ± 26 vs 450 ± 50 VMU per minute, P = 0.004, d = 1.04) were lower in severe COPD (FEV1 < 50% predicted, n = 14-16) compared with CON (n = 56-60).,A total of 129 prime metabolites and 470 lipids with known identity were quantified.,Using sex as a covariate, lipidomics revealed 24 differentially expressed lipids (19 sphingomyelins) in COPD, consequent to a diminished sex difference of sphingomyelins in COPD (false discovery rate [FDR] < 0.05, n = 44).,Total, and some individual, fatty acid concentrations were greater in severe COPD than CON (FDR < 0.05, n = 16, d = 0.56-1.02).,After adjusting for FEV1% predicted, we observed that grouped diacylglycerides (ρ = −0.745, FDR = 0.03) and triacylglycerides (ρ = −0.811, FDR = 0.01) were negatively associated with muscle oxidative capacity, but not physical activity, in severe COPD (n = 14).,Strong negative associations relate impaired mitochondrial function to the accumulation of serum aclyglycerides in severe COPD. | 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 |
Triple combination therapy involving long-acting muscarinic antagonists long-acting β2 agonists, and inhaled corticosteroids has recently become an option for maintenance treatment of COPD.,Some add-on clinical trials have reported the benefits of these combinations.,However, the process to step up to triple therapy varies for individual cases.,Keio University and affiliated hospitals conducted an observational COPD cohort study, recruiting patients diagnosed as having COPD by pulmonary physicians and those referred for investigation of possible COPD.,Their prescription history and clinical course were retrospectively analyzed based on the physicians’ medical records and patient questionnaires.,This study was registered with UMIN (UMIN000003470, April 10, 2010).,A total of 95 of the 445 COPD patients (21%) were treated with inhaled corticosteroids/long-acting β2 agonists/long-acting muscarinic antagonists as maintenance therapy, including 12 in COPD Grade I, 31 in Grade II, 38 in Grade III, and 14 in Grade IV, based on the Global Initiative for Chronic Obstructive Lung Disease spirometric grading.,For more than half of the patients on triple therapy, the treatment had been intensified due to unsatisfactory improvement of symptoms, and 32% were treated with triple therapy due to comorbid asthma.,In contrast, there were COPD patients whose therapy was maintained after starting with triple therapy because of their serious conditions or concurrent exacerbation at diagnosis (8%).,Triple therapy was often prescribed in the real-life management of COPD, even in patients whose airflow limitation was not severe.,To better control symptoms was the major reason for choosing triple therapy, regardless of the severity of COPD, in Japan. | To quantify the relationship between severity of chronic obstructive pulmonary disease (COPD) as expressed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and the annual exacerbation frequency in patients with COPD.,We performed a systematic literature review to identify randomized controlled trials and cohort studies reporting the exacerbation frequency in COPD patients receiving usual care or placebo.,Annual frequencies were determined for total exacerbations defined by an increased use of health care (event-based), total exacerbations defined by an increase of symptoms, and severe exacerbations defined by a hospitalization.,The association between the mean forced expiratory volume in one second (FEV1)% predicted of study populations and the exacerbation frequencies was estimated using weighted log linear regression with random effects.,The regression equations were applied to the mean FEV1% predicted for each GOLD stage to estimate the frequency per stage.,Thirty-seven relevant studies were found, with 43 reports of total exacerbation frequency (event-based, n = 19; symptom-based, n = 24) and 14 reports of frequency of severe exacerbations.,Annual event-based exacerbation frequencies per GOLD stage were estimated at 0.82 (95% confidence interval 0.46-1.49) for mild, 1.17 (0.93-1.50) for moderate, 1.61 (1.51-1.74) for severe, and 2.10 (1.51-2.94) for very severe COPD.,Annual symptom-based frequencies were 1.15 (95% confidence interval 0.67-2.07), 1.44 (1.14-1.87), 1.76 (1.70-1.88), and 2.09 (1.57-2.82), respectively.,For severe exacerbations, annual frequencies were 0.11 (95% confidence interval 0.02-0.56), 0.16 (0.07-0.33), 0.22 (0.20-0.23), and 0.28 (0.14-0.63), respectively.,Study duration or type of study (cohort versus trial) did not significantly affect the outcomes.,This study provides an estimate of the exacerbation frequency per GOLD stage, which can be used for health economic and modeling purposes. | 1 |
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