a stringlengths 138 8.15k | b stringlengths 138 8.15k | label int64 1 1 |
|---|---|---|
Lung cancer and chronic obstructive pulmonary disease (COPD) are two major lung diseases.,Epidermal growth factor receptor (EGFR) mutations, v‐Ki‐ras2 Kirsten rat sarcoma (KRAS) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements represent driver mutations that are frequently assessed on initial evaluation of non-small-cell lung cancer (NSCLC).,The present study focused on the expression of driver mutations in NSCLC patients presenting with COPD and further evaluated the association between NSCLC and COPD.,Data from 501 consecutive patients with histologically proven recurrent or metastatic NSCLC were analyzed retrospectively.,The patients underwent spirometry and genotyping of EGFR, ALK, and KRAS in tissue samples.,Patient characteristics and expression of driver mutations were compared between the COPD and non-COPD groups.,Among 350 patients with spirometric results, 106 (30.3%) were diagnosed with COPD, 108 (30.9%) had EGFR mutations, 31 (8.9%) had KRAS mutations, and 34 (9.7%) showed ALK rearrangements.,COPD was independently associated with lower prevalences of EGFR mutations (95% confidence interval [CI], 0.254-0.931, p = 0.029) and ALK rearrangements (95% CI, 0.065-0.600, p = 0.004).,The proportions of EGFR mutations and ALK rearrangements decreased as the severity of airflow obstruction increased (p = 0.001).,In never smokers, the prevalence of EGFR mutations was significantly lower in the COPD group than in the non-COPD group (12.7% vs.,49.0%, p = 0.002).,COPD-related NSCLC patients exhibited low prevalences of EGFR mutations and ALK rearrangements compared with the non-COPD group.,Further studies are required regarding the molecular mechanisms underlying lung cancer associated with COPD. | While it is relatively well known that the prognosis of patients with lung cancer (LC) treated with surgery is worse in the presence of chronic obstructive pulmonary disease (COPD), it is unknown if this assessment can be extrapolated to patients with advanced disease treated with chemotherapy and/or tyrosine kinase inhibitors.,The aim of our study is to analyze the clinical characteristics and survival rates in patients with LC and COPD, and to compare these to the patients without airflow obstruction.,From 471 evaluable patients, 324 (69%) were not treated with surgery due to disseminated disease (stages 3B and 4).,Of them, 47.7% also had COPD.,All patients were treated at the moment of diagnosis according to National Comprehensive Cancer Network guidelines with platinum-based chemotherapy or tyrosine kinase inhibitors.,Kaplan-Meier curves showed no significant differences in overall survival between COPD and non-COPD patients (log-rank P=0.65).,In the multivariate Cox proportional hazard model adjusting for the most relevant variables, the adjusted hazard ratio (HRadj) was statistically significant for performance status (HRadj =1.33, 95% confidence interval [CI]: 1.11-1.59; P=0.002) and clinical stage (HRadj =0.67, 95% CI: 0.50-0.89; P=0.006), but not for COPD status (HRadj =1.20, 95% CI: 0.83-1.50; P=0.46).,Our conclusion is that at present, when using standard care in advanced LC (stages 3B and 4), COPD does not have a significant deleterious impact on overall survival. | 1 |
Low concentrations of hemoglobin have previously been demonstrated in many patients with COPD.,There is evidence of anemia as a prognostic factor in acute exacerbations, but the detailed relationship between concentrations of hemoglobin and mortality is not known.,A register-based cohort of patients admitted for the first time to Danish hospitals for acute exacerbations of COPD from 2007 through 2012 was established.,Age, sex, comorbidities, medication, renal function, and concentrations of hemoglobin were retrieved.,Sex-specific survival analyses were fitted for different rounded concentrations of hemoglobin.,The cohort encompassed 6,969 patients.,Hemoglobin below 130 g/L was present in 39% of males and below 120 g/L in 24% of females.,The in-hospital mortality rates for patients with hemoglobin below or above these limits were 11.6% and 5.4%, respectively.,After discharge, compared to hemoglobin 130 g/L, the hazard ratio (HR) for males with hemoglobin 120 g/L was 1.45 (95% confidence interval [CI] 1.22-1.73), adjusted HR 1.37 (95% CI 1.15-1.64).,Compared to hemoglobin 120 g/L, the HR for females with hemoglobin 110 g/L was 1.4 (95% CI 1.17-1.68), adjusted HR 1.28 (95% CI 1.06-1.53).,In conclusion, low concentrations of hemoglobin are frequent in COPD patients with acute exacerbations, and predict long-term mortality. | To date, clinico-physiologic indices have not been compared with quantitative CT imaging indices in determining the risk of chronic obstructive pulmonary disease (COPD) exacerbation.,We therefore compared clinico-physiologic and CT imaging indices as risk factors for COPD exacerbation in patients with COPD.,We retrospectively analyzed 260 COPD patients from pulmonary clinics at 11 hospitals in Korea from June 2005 to November 2009 and followed-up for at least one year.,At the time of enrollment, none of these patients had COPD exacerbations for at least 2 months.,All underwent clinico-physiologic and radiological evaluation for risk factors of COPD exacerbation.,After 1 yr, 106 of the 260 patients had at least one exacerbation of COPD.,Multiple logistic regression analysis showed that old age, high Charlson Index, and low FEV1 were significant in a clinico-physiologic model, with C-statistics of 0.69, and that increased age and emphysema index were significant in a radiologic model, with C-statistics of 0.64.,The difference between the two models was statistically significant (P = 0.04 by bootstrap analysis).,Combinations of clinico-physiologic risk factors may be better than those of imaging risk factors in predicting COPD exacerbation. | 1 |
Despite the availability of national and international guidelines, evidence suggests that chronic obstructive pulmonary disease (COPD) treatment is not always prescribed according to recommendations.,This study evaluated the current management of patients with COPD using a large UK primary-care database.,This analysis used electronic patient records and patient-completed questionnaires from the Optimum Patient Care Research Database.,Data on current management were analyzed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and presence or absence of a concomitant asthma diagnosis, in patients with a COPD diagnosis at ≥35 years of age and with spirometry results supportive of the COPD diagnosis.,A total of 24,957 patients were analyzed, of whom 13,557 (54.3%) had moderate airflow limitation (GOLD Stage 2 COPD).,The proportion of patients not receiving pharmacologic treatment for COPD was 17.0% in the total COPD population and 17.7% in the GOLD Stage 2 subset.,Approximately 50% of patients in both cohorts were receiving inhaled corticosteroids (ICS), either in combination with a long-acting β2-agonist (LABA; 26.7% for both cohorts) or a LABA and a long-acting muscarinic antagonist (LAMA; 23.2% and 19.9%, respectively).,ICS + LABA and ICS + LABA + LAMA were the most frequently used treatments in GOLD Groups A and B.,Of patients without concomitant asthma, 53.7% of the total COPD population and 50.2% of the GOLD Stage 2 subset were receiving ICS.,Of patients with GOLD Stage 2 COPD and no exacerbations in the previous year, 49% were prescribed ICS.,A high proportion of GOLD Stage 2 COPD patients were symptomatic on their current management (36.6% with modified Medical Research Council score ≥2; 76.4% with COPD Assessment Test score ≥10).,COPD is not treated according to GOLD and National Institute for Health and Care Excellence recommendations in the UK primary-care setting.,Some patients receive no treatment despite experiencing symptoms.,Among those on treatment, most receive ICS irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history.,Many patients on treatment continue to have symptoms. | Current guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend the regular use of inhaled bronchodilator therapy in order to relieve symptoms and prevent exacerbations.,A variety of inhaler devices are currently available to COPD patients, and the choice of device is an important consideration because it can influence patients’ adherence to treatment, and thus potentially affect the long-term outcome.,The Respimat® Soft Mist™ Inhaler (SMI) generates a slow-moving aerosol with a high fine particle fraction, resulting in deposition of a higher proportion of the dose in the lungs than pressurized metered-dose inhalers (pMDIs) or some dry powder inhalers (DPIs).,We review clinical studies of inhaler satisfaction and preference comparing Respimat® SMI against other inhalers in COPD patients.,Using objective and validated patient satisfaction instruments, Respimat® SMI was consistently shown to be well accepted by COPD patients, largely due to its inhalation and handling characteristics.,In comparative studies with pMDIs, the patient total satisfaction score with Respimat® SMI was statistically and clinically significantly higher than with the pMDI.,In comparative studies with DPIs, the total satisfaction score was statistically significantly higher than for the Turbuhaler® DPI, but only the performance domain of satisfaction was clinically significantly higher for Respimat® SMI.,Whether the observed higher levels of patient satisfaction reported with Respimat® SMI might be expected to result in improved adherence to therapy and thus provide benefits consistent with those recently shown to be associated with sustained bronchodilator treatment in patients with COPD remains to be proven. | 1 |
A new phenotype with overlapping characteristics between asthma and chronic obstructive pulmonary disease (COPD) called asthma-COPD overlap syndrome (ACOS) is emerging among inflammation diseases.,To date, there is no agreement on specific criteria to define this syndrome, and the current guidelines are insufficient to classify the analogy and differences between overlap and COPD or asthma phenotypes.,It would be necessary to identify new biomarkers able to identify these diseases clearly.,Thus, the aim of this study was to identify a serum and supernatant of sputum microRNA (miRNA) expression profile of miRNA-145 and miRNA-338 in patients with asthma (n=13), COPD (n=31), and ACOS (n=8) and controls (n=7).,The expression was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR).,For statistical analysis, the ANOVA test, Kruskal-Wallis test, Mann-Whitney U-test, and Spearman’s rank correlation were used.,The main finding of this work is that the expression of miRNA-338 is higher in the supernatant of different obstructive diseases than in peripheral blood, while miRNA-145 is higher only in the supernatant of asthma patients.,The expression of both selected miRNAs is higher in the supernatant of asthma and COPD patients than in controls.,Differences in sputum miRNA expression profile were observed between patients with ACOS and asthma or COPD, which underline the potential role of miRNA as a biomarker that is able to discriminate patients with ACOS, asthma, and COPD. | In recent years, the so-called asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) has received much attention, not least because elderly individuals may present characteristics suggesting a diagnosis of both asthma and COPD.,At present, ACOS is described clinically as persistent airflow limitation combined with features of both asthma and COPD.,The aim of this paper is, therefore, to review the currently available literature focusing on symptoms and clinical characteristics of patients regarded as having ACOS.,Based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, a systematic literature review was performed.,A total of 11 studies met the inclusion criteria for the present review.,All studies dealing with dyspnea (self-reported or assessed by the Medical Research Council dyspnea scale) reported more dyspnea among patients classified as having ACOS compared to the COPD and asthma groups.,In line with this, ACOS patients have more concomitant wheezing and seem to have more cough and sputum production.,Compared to COPD-only patients, the ACOS patients were found to have lower FEV1% predicted and FEV1/FVC ratio in spite of lower mean life-time tobacco exposure.,Furthermore, studies have revealed that ACOS patients seem to have not only more frequent but also more severe exacerbations.,Comorbidity, not least diabetes, has also been reported in a few studies, with a higher prevalence among ACOS patients.,However, it should be acknowledged that only a limited number of studies have addressed the various comorbidities in patients with ACOS.,The available studies indicate that ACOS patients may have more symptoms and a higher exacerbation rate than patients with asthma and COPD only, and by that, probably a higher overall respiratory-related morbidity.,Similar to patients with COPD, ACOS patients seem to have a high occurrence of comorbidity, including diabetes.,Further research into the ACOS, not least from well-defined prospective studies, is clearly needed. | 1 |
Dendritic cells (DCs) control immunity and play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD).,However, the expression of function-associated surface molecules on circulating DCs in COPD is unknown.,Four-colour flow cytometry was used to compare blood DC surface molecules of 54 patients with COPD (median age: 59 years; median FEV1: 38% predicted, median CAT score: 24) with two age-matched control groups with normal lung function: 21 current smokers and 21 never-smokers.,Concentrations of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) and the mDC/pDC ratio did not differ between the groups.,The increased expression of BDCA-1, BDCA-3, CD86 and CCR5 on mDCs in patients with COPD did not significantly differ from smokers with normal lung function.,In contrast, COPD was specifically characterised by a decreased expression of the anti-inflammatory co-stimulatory molecule PD-L1 on pDCs and an increased expression of the pro-inflammatory co-stimulatory molecule OX40 ligand (OX40L) on mDCs.,These changes were not confined to patients with elevated systemic inflammation markers (leukocytes, c-reactive protein, interleukin-6, fibrinogen).,The ratio of OX40L to PD-L1 expression (OX40L/PD-L1 ratio), a quantitative measure of imbalanced DC co-stimulation, correlated with the severity of pulmonary emphysema in patients with COPD.,An imbalance of DC co-stimulation might contribute to the pathogenesis of COPD.,The online version of this article (doi:10.1186/s12931-015-0174-x) contains supplementary material, which is available to authorized users. | There is mounting evidence that perforin and granzymes are important mediators in the lung destruction seen in COPD.,We investigated the characteristics of the three main perforin and granzyme containing peripheral cells, namely CD8+ T lymphocytes, natural killer (NK; CD56+CD3-) cells and NKT-like (CD56+CD3+) cells.,Peripheral blood mononuclear cells (PBMCs) were isolated and cell numbers and intracellular granzyme B and perforin were analysed by flow cytometry.,Immunomagnetically selected CD8+ T lymphocytes, NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells were used in an LDH release assay to determine cytotoxicity and cytotoxic mechanisms were investigated by blocking perforin and granzyme B with relevant antibodies.,The proportion of peripheral blood NKT-like (CD56+CD3+) cells in smokers with COPD (COPD subjects) was significantly lower (0.6%) than in healthy smokers (smokers) (2.8%, p < 0.001) and non-smoking healthy participants (HNS) (3.3%, p < 0.001).,NK (CD56+CD3-) cells from COPD subjects were significantly less cytotoxic than in smokers (16.8% vs 51.9% specific lysis, p < 0.001) as were NKT-like (CD56+CD3+) cells (16.7% vs 52.4% specific lysis, p < 0.001).,Both cell types had lower proportions expressing both perforin and granzyme B.,Blocking the action of perforin and granzyme B reduced the cytotoxic activity of NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells from smokers and HNS.,In this study, we show that the relative numbers of peripheral blood NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells in COPD subjects are reduced and that their cytotoxic effector function is defective. | 1 |
Cellular senescence has been associated with the structural and functional decline observed during physiological lung aging and in chronic obstructive pulmonary disease (COPD).,Airway epithelial cells are the first line of defense in the lungs and are important to COPD pathogenesis.,However, the mechanisms underlying airway epithelial cell senescence, and particularly the role of telomere dysfunction in this process, are poorly understood.,We aimed to investigate telomere dysfunction in airway epithelial cells from patients with COPD, in the aging murine lung and following cigarette smoke exposure.,We evaluated colocalization of γ-histone protein 2A.X and telomeres and telomere length in small airway epithelial cells from patients with COPD, during murine lung aging, and following cigarette smoke exposure in vivo and in vitro.,We found that telomere-associated DNA damage foci increase in small airway epithelial cells from patients with COPD, without significant telomere shortening detected.,With age, telomere-associated foci increase in small airway epithelial cells of the murine lung, which is accelerated by cigarette smoke exposure.,Moreover, telomere-associated foci predict age-dependent emphysema, and late-generation Terc null mice, which harbor dysfunctional telomeres, show early-onset emphysema.,We found that cigarette smoke accelerates telomere dysfunction via reactive oxygen species in vitro and may be associated with ataxia telangiectasia mutated-dependent secretion of inflammatory cytokines interleukin-6 and -8.,We propose that telomeres are highly sensitive to cigarette smoke-induced damage, and telomere dysfunction may underlie decline of lung function observed during aging and in COPD. | The aim of the present study was to characterize and quantify the numbers and expression levels of cells markers associated with dendritic cell (DC) maturation in small airways in current smokers and non-smokers with or without chronic obstructive pulmonary disease (COPD).,Lung tissues from the following 32 patients were obtained during resection for lung cancer: Eight smokers with COPD, eight non-smokers with COPD, eight current smokers without COPD and eight non-smokers without COPD, serving as a control.,The tissue sections were immunostained for cluster of differentiation (CD)83+ and CD1a+ to delineate mature and immature DCs, and chemokine receptor type 7 (CCR7+) to detect DC migratory ability.,Myeloid DCs were collected from the lung tissues, and subsequently the CD83+ and CCR7+ expression levels in the lung myeloid DCs were detected using flow cytometry.,The expression levels of CD83+, CD1a+ and CCR7+ mRNA in total lung RNA were evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR).,Evident chronic bronchitis and emphysema pathological changes were observed in the lung tissues of patients with COPD.,The results revealed that the numbers of CD83+ and CCR7+ DCs were reduced but the numbers of CD1a+ DCs were significantly increased in the COPD group as compared with the control group (P<0.05, respectively).,Using RT-qPCR, the expression levels of CCR7+ and CD83+ mRNA were found to be reduced in the smokers with COPD as compared with the non-smokers without COPD group (P<0.05, respectively).,Excessive local adaptive immune responses are key elements in the pathogenesis of COPD.,Cigarette smoke may stimulate immune responses by impairing the homing of airway DCs to the lymph nodes and reduce the migratory potential of DCs.,The present study revealed that COPD is associated with reduced numbers of mature CD83+ DCs and lower CCR7+ expression levels in small airways. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is defined as a disease characterized by persistent, progressive airflow limitation.,Recent studies have underlined that COPD is correlated to many systemic manifestations, probably due to an underlying pattern of systemic inflammation.,In COPD fractional exhaled Nitric Oxide (FeNO) levels are related to smoking habits and disease severity, showing a positive relationship with respiratory functional parameters.,Moreover FeNO is increased in patients with COPD exacerbation, compared with stable ones.,In alpha-1 antitrypsin deficiency, a possible cause of COPD, FeNO levels may be monitored to early detect a disease progression.,FeNO measurements may be useful in clinical setting to identify the level of airway inflammation, per se and in relation to comorbidities, such as pulmonary arterial hypertension and cardiovascular diseases, either in basal conditions or during treatment.,Finally, some systemic inflammatory diseases, such as psoriasis, have been associated with higher FeNO levels and potentially with an increased risk of developing COPD.,In these systemic inflammatory diseases, FeNO monitoring may be a useful biomarker for early diagnosis of COPD development. | 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 |
Chronic obstructive pulmonary disease (COPD) is characterized by chronic pulmonary and systematic inflammation.,An abnormal adaptive immune response leads to an imbalance between pro- and anti-inflammatory processes.,T-helper (Th), T-cytotoxic (Tc) and T-regulatory (Treg) cells may play important roles in immune and inflammatory responses.,This study was conducted to clarify the changes and imbalance of cytokines and T lymphocyte subsets in patients with COPD, especially during acute exacerbations (AECOPD).,Twenty-three patients with stable COPD (SCOPD) and 21 patients with AECOPD were enrolled in the present study.,In addition, 20 age-, sex- and weight-matched non-smoking healthy volunteers were included as controls.,The serum levels of selected cytokines (TGF-β, IL-10, TNF-α, IL-17 and IL-9) were measured by enzyme-linked immunosorbent assay (ELISA) kits.,Furthermore, the T lymphocyte subsets collected from peripheral blood samples were evaluated by flow cytometry after staining with anti-CD3-APC, anti-CD4-PerCP, anti-CD8- PerCP, anti-CD25-FITC and anti-FoxP3-PE monoclonal antibodies.,Importantly, to remove the confounding effects of inflammatory factors, the authors introduced a concept of “inflammation adjustment” and corrected each measured value using representative inflammatory markers, such as TNF-α and IL-17.,Unlike the other cytokines, serum TGF-β levels were considerably higher in patients with AECOPD relative to the control group regardless of adjustment.,There were no significant differences in the percentages of either CD4+ or CD8+ T cells among the three groups.,Although Tregs were relatively upregulated during acute exacerbations, their capacities of generation and differentiation were far from sufficient.,Finally, the authors noted that the ratios of Treg/IL-17 were similar among groups.,These observations suggest that in patients with COPD, especially during acute exacerbations, both pro-inflammatory and anti-inflammatory reactions are strengthened, with the pro-inflammatory reactions dominating.,Although the Treg/IL-17 ratios were normal, the regulatory T cells were still insufficient to suppress the accompanying increases in inflammation.,All of these changes suggest a complicated mechanism of pro- and anti-inflammatory imbalance which needs to be further investigated. | Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome characterized by varying degrees of airflow limitation and diffusion impairment.,There is increasing evidence to suggest that COPD is also characterized by systemic inflammation.,The primary goal of this study was to identify soluble proteins in plasma that associate with the severity of airflow limitation in a COPD cohort with stable disease.,A secondary goal was to assess whether unique markers associate with diffusion impairment, based on diffusion capacity of carbon monoxide (DLCO), independent of the forced expiratory volume in 1 second (FEV1).,A cross sectional study of 73 COPD subjects was performed in order to examine the association of 25 different plasma proteins with the severity of lung function impairment, as defined by the baseline measurements of the % predicted FEV1 and the % predicted DLCO.,Plasma protein concentrations were assayed using multiplexed immunobead-based cytokine profiling.,Associations between lung function and protein concentrations were adjusted for age, gender, pack years smoking history, current smoking, inhaled corticosteroid use, systemic corticosteroid use and statin use.,Plasma concentrations of CCL2/monocyte chemoattractant protein-1 (CCL2/MCP-1), CCL4/macrophage inflammatory protein-1β (CCL4/MIP -1β), CCL11/eotaxin, and interleukin-13 (IL-13) were inversely associated with the % FEV1.,Plasma concentrations of soluble Fas were associated with the % DLCO, whereas CXCL9/monokine induced by interferon-γ (CXCL9/Mig), granulocyte- colony stimulating factor (G-CSF) and IL-13 showed inverse relationships with the % DLCO.,Systemic inflammation in a COPD cohort is characterized by cytokines implicated in inflammatory cell recruitment and airway remodeling.,Plasma concentrations of IL-13 and chemoattractants for monocytes, T lymphocytes, and eosinophils show associations with increasing severity of disease.,Soluble Fas, G-CSF and CXCL9/Mig may be unique markers that associate with disease characterized by disproportionate abnormalities in DLCO independent of the FEV1. | 1 |
Data regarding osteoporosis in COPD patients in Taiwan remain limited.,The primary end point of this study was to evaluate the prevalence and risk factors of osteoporosis in COPD patients in Taiwan.,The secondary end point was to examine the association between osteoporosis and health-related quality of life (HRQL) in COPD patients.,This prospective cross-sectional study enrolled 125 COPD patients (mean age 73.6 years, forced expiratory volume in 1 second [FEV1] 1.19±0.43 L) who had bone mineral-density measurements performed consecutively.,Demographic data, lung function, and HRQL including modified Medical Research Council dyspnea scale, St George’s Respiratory Questionnaire, oxygen-cost diagram, Center for Epidemiologic Studies - depression scale, and COPD Assessment Test scores were recorded.,A total of 50 (40%) participants were diagnosed as having osteoporosis.,In a multivariate logistic regression model including age, smoking amount (pack-year), body mass index (BMI), and FEV1, only BMI (odds ratio 0.824, 95% confidence interval 0.73-0.93; P=0.002) and FEV1 (odds ratio 0.360, 95% confidence interval 0.13-0.98; P=0.046) were negatively associated with an increased risk of osteoporosis in COPD patients.,In addition, COPD patients with osteoporosis had significantly higher modified Medical Research Council dyspnea scale scores (1.7±0.8 vs 1.4±0.8, P=0.046), St George’s Respiratory Questionnaire scores (36.6 vs 28.0, P=0.01), and COPD Assessment Test scores (14.7±8 vs 11.5±7, P=0.019), and lower oxygen-cost diagram score (4.8±1.8 vs 5.4±1.6, P=0.045) than patients without osteoporosis.,The prevalence of osteoporosis in COPD patients was high at a community hospital in Taiwan.,BMI and FEV1 were the independent risk factors for osteoporosis in COPD.,In addition, COPD patients with osteoporosis had worse HRQL than those without osteoporosis. | To characterize the distribution of BMI in a population-based sample of COPD patients and to evaluate the impact of obesity on their health status, exercise tolerance, systemic inflammation and comorbidity.,A population-based sample of 3,797 subjects aged 40-80 years from the EPI-SCAN study was selected.,Subjects were categorized according their body mass index (BMI) as underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2) or obese (BMI≥30.0 kg/m2).,Subjects were evaluated with post-bronchodilator spirometry and 6-minute walk tests.,Smoking habits, respiratory symptoms, generic and specific quality of life, daily physical activities, comorbidities and systemic inflammatory biomarkers were recorded.,The prevalence of obesity or being overweight was higher in the 382 COPD patients than in the subjects without airflow limitation (29.4%, 95%CI 24.8-33.9% vs.,24.3, 95%CI 22.9-25.8; and 44.7%, 95%CI 39.7-49.6% vs.,43.0%, 95%CI 41.3-44.6, respectively; p = 0.020).,In the COPD subgroup, obese subjects presented more dyspnea and less chronic cough, chronic bronchitis or chronic phlegm than normal-weight patients, as well as a worse health status.,Moreover, reduced exercise tolerance and higher plasmatic C-reactive protein levels were found in the obese patients, who also presented a greater prevalence of cardiovascular disease (adjusted odds ratio 4.796, 95%CI 1.806-12.736, p = 0.002).,In a population-based sample, obesity is more prevalent in COPD patients than in subjects without airflow limitation.,Furthermore, obesity affects the clinical manifestations, quality of life and exercise tolerance of COPD patients, and it may contribute to a phenotype characterized by increased systemic inflammation and greater frequency of cardiovascular comorbidity. | 1 |
Acute hypercapnic respiratory failure (AHRF) treated with non-invasive ventilation in the ICU is frequently caused by chronic obstructive pulmonary disease (COPD) exacerbations and obesity-hypoventilation syndrome, the latter being most often associated with obstructive sleep apnea.,Overlap syndrome (a combination of COPD and obstructive sleep apnea) may represent a major burden in this population, and specific diagnostic pathways are needed to improve its detection early after ICU discharge.,To evaluate whether pulmonary function tests can identify a high probability of obstructive sleep apnea in AHRF survivors and outperform common screening questionnaires to identify the disorder.,Fifty-three patients surviving AHRF (31 males; median age 67 years (interquartile range: 62-74) participated in the study.,Anthropometric data were recorded and body plethysmography was performed 15 days after ICU discharge.,A sleep study was performed 3 months after ICU discharge.,The apnea-hypopnea index was negatively associated with static hyperinflation as measured by the residual volume to total lung capacity ratio in the % of predicted (coefficient = -0.64; standard error 0.17; 95% CI -0.97 to -0.31; p<0.001).,A similar association was observed in COPD patients only: coefficient = -0.65; standard error 0.19; 95% CI -1.03 to -0.26; p = 0.002.,Multivariate analysis with penalized maximum likelihood confirmed that the residual volume to total lung capacity ratio was the main contributor for apnea-hypopnea index variance in addition to classic predictors.,Screening questionnaires to select patients at risk for sleep-disordered breathing did not perform well.,In AHRF survivors, static hyperinflation is negatively associated with the apnea-hypopnea index in both COPD and non-COPD patients.,Measuring static hyperinflation in addition to classic predictors may help to increase the recognition of obstructive sleep apnea as common screening tools are of limited value in this specific population. | Noninvasive positive-pressure ventilation (NPPV) might be superior to conventional mechanical ventilation (CMV) in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPDs).,Inefficient clearance of respiratory secretions provokes NPPV failure in patients with hypercapnic encephalopathy (HE).,This study compared CMV and NPPV combined with a noninvasive strategy for clearing secretions in HE and AECOPD patients.,The present study is a prospective cohort study of AECOPD and HE patients enrolled between October 2013 and August 2015 in a critical care unit of a major university teaching hospital in China.,A total of 74 patients received NPPV and 90 patients received CMV.,Inclusion criteria included the following: physician-diagnosed AECOPD, spontaneous airway clearance of excessive secretions, arterial blood gas analysis requiring intensive care, moderate-to-severe dyspnea, and a Kelly-Matthay scale score of 3 to 5.,Exclusion criteria included the following: preexisting psychiatric/neurological disorders unrelated to HE, upper gastrointestinal bleeding, upper airway obstruction, acute coronary syndromes, preadmission tracheostomy or endotracheal intubation, and urgent endotracheal intubation for cardiovascular, psychomotor agitation, or severe hemodynamic conditions.,Intensive care unit participants were managed by NPPV.,Participants received standard treatment consisting of controlled oxygen therapy during NPPV-free periods; antibiotics, intravenous doxofylline, corticosteroids (e.g., salbutamol and ambroxol), and subcutaneous low-molecular-weight heparin; and therapy for comorbidities if necessary.,Nasogastric tubes were inserted only in participants who developed gastric distension.,No pharmacological sedation was administered.,The primary and secondary outcome measures included comparative complication rates, durations of ventilation and hospitalization, number of invasive devices/patient, and in-hospital and 1-year mortality rates.,Arterial blood gases and sensorium levels improved significantly within 2 hours in the NPPV group with lower hospital mortality, fewer complications and invasive devices/patient, and superior weaning off mechanical ventilation.,Mechanical ventilation duration, hospital stay, or 1-year mortality was similar between groups.,NPPV combined with a noninvasive strategy to clear secretions during the first 2 hours may offer advantages over CMV in treating AECOPD patients complicated by HE. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with increased risk of severe COVID-19, but the mechanisms are unclear.,Besides, patients with severe COVID-19 have been reported to have increased levels of several immune mediators.,Ninety-two proteins were quantified in 315 plasma samples from 118 asthmatics, 99 COPD patients and 98 healthy controls (age 40-90 years), who were recruited in Colombia before the COVID-19 pandemic.,Protein levels were compared between each disease group and healthy controls.,Significant proteins were compared to the gene signatures of SARS-CoV-2 infection reported in the “COVID-19 Drug and Gene Set Library” and with experimentally tested protein biomarkers of severe COVID-19.,Forty-one plasma proteins showed differences between patients and controls.,Asthmatic patients have increased levels in IL-6 while COPD patients have a broader systemic inflammatory dysregulation driven by HGF, OPG, and several chemokines (CXCL9, CXCL10, CXCL11, CX3CL1, CXCL1, MCP-3, MCP-4, CCL3, CCL4 and CCL11).,These proteins are involved in chemokine signaling pathways related with response to viral infections and some, were found up-regulated upon SARS-CoV-2 experimental infection of Calu-3 cells as reported in the COVID-19 Related Gene Sets database.,An increase of HPG, CXCL9, CXCL10, IL-6, MCP-3, TNF and EN-RAGE has also been experimentally detected in patients with severe COVID-19.,COPD patients have altered levels of plasma proteins that have been reported increased in patients with severe COVID-19.,Our study suggests that COPD patients have a systemic dysregulation in chemokine networks (including HGF and CXCL9) that could make them more susceptible to severe COVID-19.,Also, that IL-6 levels are increased in some asthmatic patients (especially in females) and this may influence their response to COVID-19.,The findings in this study depict a novel panel of inflammatory plasma proteins in COPD patients that may potentially associate with increased susceptibility to severe COVID-19 and might be useful as a biomarker signature after future experimental validation. | Alveolar apoptosis is increased in the emphysematous lung.,However, mechanisms involved are not fully understood.,Recently, we demonstrated that levels of TRAIL receptor 1 and 2, levels of p53, and Bax/Bcl-xL ratio were elevated in the lung of subjects with emphysema, despite smoking cessation.,Thus, we postulate that due to chronic pulmonary oxidative stress, the emphysematous lung would be abnormally sensitive to TRAIL-mediated apoptosis.,A549 cells were exposed to rTRAIL, cigarette smoke extract, and/or H2O2 prior to caspase-3 activity measurement and annexin V staining assessment.,In addition, freshly resected lung samples were obtained from non-emphysematous and emphysematous subjects and exposed ex vivo to rTRAIL for up to 18 hours.,Lung samples were harvested and levels of active caspase-3 and caspase-8 were measured from tissue lysates.,Both cigarette smoke extract and H2O2 were able to sensitize A549 cells to TRAIL-mediated apoptosis.,Moreover, following exposure to rTRAIL, caspase-3 and -8 were activated in lung explants from emphysematous subjects while being decreased in lung explants from non-emphysematous subjects.,Alveolar sensitivity to TRAIL-mediated apoptosis is strongly increased in the emphysematous lung due to the presence of oxidative stress.,This might be a new mechanism leading to increased alveolar apoptosis and persistent alveolar destruction following smoking cessation. | 1 |
Cardiovascular (CVS) comorbidities are common in COPD and contribute significantly to morbidity and mortality, especially following acute exacerbations of COPD (AECOPD).,Beta-blockers (BBs) are safe and effective in COPD patients, with demonstrated survival benefit following myocardial infarction.,We sought to determine if BBs are under-prescribed in patients hospitalized with AECOPD.,We also sought to determine inpatient rates of CVS and cerebrovascular complications, and their impact on patient outcomes.,Retrospective hospital data was collected over a 12-month period.,The medical records of all patients >40 years of age coded with a diagnosis of AECOPD were analyzed.,Prevalent use and incident initiation of BBs were assessed.,Comorbidities including indications and contraindications for BB use were analyzed.,Of the 366 eligible patients, 156 patients (42.6%) had at least one indication for BB use - of these patients, only 53 (34.0%) were on BB therapy and 61 (39.1%) were not on BB therapy but had no listed contraindication.,Prevalent use of BBs at the time of admission in all 366 patients was 19.7%, compared with 45.6%, 39.6% and 45.9% use of anti-platelets, statins and angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers, respectively.,CVS and cerebrovascular complications were common in this population (57 patients, 16%) and were associated with longer length of stay (p<0.01) and greater inpatient mortality (p=0.02).,BBs are under-prescribed in COPD patients despite clear indication(s) for their use.,Further work is required to explore barriers to BB prescribing in COPD patients. | 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 |
1) To estimate the annual cost of patients with stable chronic obstructive pulmonary disease (COPD) followed in primary care in Spain; 2) To analyze the possible cost predictor variables.,A multicenter, epidemiological, observational, descriptive study.,Sociodemographic data, severity of disease, associated comorbidity, treatment followed by patients, quality of life (SF-12 questionnaire), health care resource utilization in the previous 12 months and duration of working disability due to COPD were collected.,A total of 10,711 patients (75.6% men; 24.4% women) with a mean age of 67.1 ± 9.66 years were evaluated.,The mean forced expiratory volume in one second (FEV1) value was 57.4 ± 13.4%.,The total cost per patient per year was €1,922.60 ± 2,306.44.,The largest component of this cost was hospitalization (€788.72 ± 1,766.65), followed by cost of drugs (€492.87 ± 412.15) and visits to emergency rooms (€134.32 ± 195.44).,Linear regression analysis found associated heart disease, FEV1, physical component of quality of life, number of medical visits (primary care physician, pneumologist and emergency room), hospital admissions (frequency and duration of stay) and duration of working disability to be significant predictors of the total annual cost.,The total annual cost of a COPD patient followed in primary care in Spain was considered high in this study.,The presence of associated heart disease, severity of airflow obstruction, physical component of quality of life, health care resource utilization and duration of work disability were found to be predictor of cost. | 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 |
Club cell protein (CC16) is expressed primarily by club cells possesses anti-inflammatory properties and is located in the bronchiolar epithelium.,Previous studies have demonstrated that CC16 deficiency is associated with the progression of chronic obstructive pulmonary disease (COPD).,In the present study, the therapeutic effects of recombinant rat CC16 protein in mice with COPD were examined and the underlying mechanisms investigated.,A total of 30 adult male C57/BL6 mice were randomly divided into three groups (10 mice/group).,A mouse COPD model was generated by exposing 20 mice to cigarette smoke (CS) for 24 weeks.,A total of 10 mice were treated intranasally with rCC16 (2.5 µg/g body weight) and control mice were exposed to normal room air.,Results indicated that rCC16 treatment ameliorated pathological damage in the lungs and reduced the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8, which were induced by CS exposure.,After rCC16 administration, endogenous CC16 was upregulated and the body weight of COPD mice was increased, whereas the opposite was observed in CS-exposed mice.,Additionally, rCC16 treatment inhibited the DNA binding of NF-κB/p65 in lung tissues and reduced nuclear translocation of NF-κB/p65 in BALF and epithelial cells.,Moreover, rCC16 treatment lead to a decrease in the total number of BALF cells, including macrophages, which was elevated in COPD mice.,In conclusion, the present results demonstrate that rCC16 has therapeutic effects on COPD by downregulating pro-inflammatory factors via the NF-κB pathway. | We conducted this study to identify the influences and synergistic effects of smoking status and polymorphisms in hedgehog interacting protein (HHIP) on chronic obstructive pulmonary disease (COPD) and lung function decline.,A cohort containing 306 COPD patients and 743 healthy subjects was recruited from 25,000 subjects.,All selected subjects had chronic cough for over 2 years or a smoking history above 20 pack-years.,After 8 years, all subjects were divided into 2 cohorts according to whether they had quit smoking or not.,A follow-up of all patients was completed after another period of 10 years.,Three variants in HHIP were genotyped to investigate the impacts of gene susceptibility on the development of COPD and lung function decline.,During the follow-up tests, forced expiratory volume in 1 s (FEV1) ratios decreased more significantly in COPD patients than in healthy subjects.,For variant rs7654947, FEV1 decreased more significantly in CC and CT subjects than in TT subjects.,FEV1 in COPD patients with a CC genotype from smoking cohorts reduced markedly when compared to ex-smoking cohorts (case, 30.75% vs.,35.5%; total, 28% vs.,32%).,Our results showed that smoking and HHIP variant rs7654947 were associated with COPD development and lung function decline.,Moreover, we found that cigarette smoking and gene susceptibility have cooperative effects on COPD risk and lung function decline. | 1 |
COPD is a frequent but underdiagnosed disease whose diagnosis relies on the spirometric demonstration of bronchial obstruction.,Spirometry use by general practitioners could represent the first line in COPD diagnosis.,Because duration of spirometry is retarding its development in primary care, we decided to measure the time it requires in the primary-care context in France.,Ten volunteer general practitioners were trained during two 3-hour theoretical and practical continuing education sessions.,Then, from October 2013 to May 2014, they included patients without any known respiratory disease but at risk of developing COPD (age: ≥40 years, smoker: ≥20 pack-years).,The duration of spirometry and its quality were evaluated according to the following acceptability criteria: 1) expiration ≥6 seconds or reaching a plateau; 2) good start with an early peak flow, curve peaked on top and not flat; 3) no artifacts; and 4) reproducibility criteria, ie, forced expiratory volume in 1 second and forced vital capacity differences between the two best spirometry curves ≤0.15 L.,Quality of the spirograms was defined as optimal when all the criteria were met and acceptable when all the criteria were satisfied except the reproducibility criterion, otherwise, it was unacceptable.,For the 152 patients included, the 142 assessable spirometries lasted for 15.2±5.9 minutes.,Acceptability criteria 1-3, respectively, were satisfied for 90.1%, 89.4%, and 91.5% of patients and reproducibility criterion 4 for 56.3%.,Quality was considered optimal for 58.5% of the curves and acceptable for 30.2%.,The duration of spirometry renders it poorly compatible with the current primary-care practice in France other than for dedicated consultations.,Moreover, the quality of spirometry needs to be improved. | 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. | 1 |
Two new protocols have been developed for bicycle exercise testing in chronic obstructive pulmonary disease (COPD) with an individualized cardiopulmonary exercise test (ICPET) and subsequent customized endurance test (CET), which generate less interindividual spread in endurance time compared with the standard endurance test.,Main objectives of this study were to improve the prediction algorithm for WMAX for the ICPET and validate the CET by examining treatment effects on exercise performance of indacaterol/glycopyrronium (IND/GLY) compared with placebo.,COPD patients, with forced expiratory volume in 1 s (FEV1) 40-80% predicted, were recruited.,Pooled baseline data from two previous studies (n = 38) were used for the development of an improved WMAX prediction algorithm.,Additional COPD patients (n = 14) were recruited and performed the ICPET, using the new prediction formula at visit 1.,Prior to the CET at visits 2 and 3, they were randomized to a single dose of IND/GLY (110/50 µg) or placebo.,The improved multiple regression algorithm for WMAX includes diffusing capacity for carbon monoxide (DLCO), FEV1, sex, age and height and correlated to measured WMAX (R2 = 0.89 and slope = 0.89).,Treatment with IND/GLY showed improvement in endurance time versus placebo, mean 113 s [95% confidence interval (CI): 6-220], p = 0.037, with more prominent effect in patients with FEV1 < 70% predicted.,The two new protocols for ICPET (including the new improved algorithm) and CET were retested with consistent results.,In addition, the CET showed a significant and clinically relevant prolongation of endurance time for IND/GLY versus placebo in a small number of patients. | The study investigates which physical performance or muscle function/mass tests significantly correlate with objectively measured physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) and could potentially serve to identify physically inactive COPD patients in routine clinical practice.,A cross-sectional, observational study was conducted in outpatients with moderate to very severe COPD.,PA was measured during one week with the StepWatch Activity Monitor®, an ankle-worn accelerometer, and expressed in steps per day.,Physical fitness and peripheral muscle function/mass were evaluated by the 4-meter gait speed (4MGS) test, the 6-minute walk distance (6MWD), the 30-second chair stand test (30sCST), the timed up and go test (TUGT), handgrip strength, arm muscle area, calf circumference, the fat-free mass index (FFMI), and ultrasound measurement of the quadriceps muscle.,Spearman’s rank correlation analysis and ROC analysis were performed.,The study population (N=111, 69% men, mean age 68 years) walked a mean of 8059 steps/day.,The daily step count strongly correlated with the 6MWD (rho=0.684, p<0.001) and moderately with the 4MGS (rho=0.464, p<0.001), the TUGT (rho= −0.463, p<0.001), and the 30sCST (rho=0.402, p<0.001).,The correlation with the FFMI was weak (rho=0.210, p=0.027), while the other parameters did not significantly correlate with the daily step count.,The 6MWD had the best discriminative power to identify patients with very low PA defined as <5000 steps/day (AUC=0.802 [95% CI: 0.720-0.884], p<0.001), followed by the TUGT, the 4MGS, and the 30sCST.,The 6MWD, the 4MGS, the TUGT, and the 30sCST are easy to perform in any clinical setting and may be used by clinicians in the screening of physically inactive COPD patients. | 1 |
The goals of COPD therapy are to prevent and control symptoms, reduce the frequency and severity of exacerbations, and improve exercise tolerance.,The triple combination therapy of inhaled corticosteroids (ICSs), long-acting beta2 agonists (LABAs), and long-acting muscarinic antagonists (LAMAs) has become an option for maintenance treatment of COPD and as a “step-up” therapy from single or double combination treatments.,There is evidence that triple combination ICS/LABA/LAMA with different inhalers improves lung function, symptoms, and health status and reduces exacerbations.,A new triple fixed-dose combination of extrafine beclomethasone dipropionate (100 µg/puff)/formoterol fumarate (6 µg/puff)/glycopyrronium bromide (12.5 µg/puff) has been developed as a hydrofluoroalkane pressurized metered dose inhaler.,Two large pivotal studies showed that this extrafine fixed ICS/LABA/LAMA triple combination is superior to fixed ICS/LABA combined therapy and also superior to the LAMA tiotropium in terms of lung function and exacerbation prevention in COPD patients at risk of exacerbation.,This review considers the new information provided by these clinical trials of extrafine triple therapy and the implications for the clinical management of COPD patients. | An extrafine formulation of the long-acting muscarinic antagonist glycopyrronium bromide (GB) is in development for chronic obstructive pulmonary disease (COPD), in combination with beclometasone dipropionate and formoterol fumarate - a “fixed triple”.,This two-part study was randomized, double blind, placebo controlled in patients with moderate-to-severe COPD: Part 1: single-dose escalation, GB 12.5, 25, 50, 100 or 200 μg versus placebo; Part 2: repeat-dose (7-day), four-period crossover, GB 12.5, 25 or 50 μg twice daily (BID) versus placebo, with an open-label extension in which all patients received tiotropium 18 μg once daily.,On the morning of Day 8 in all five periods, patients also received formoterol 12 μg.,In study Part 1, 27 patients were recruited.,All GB doses significantly increased from baseline forced expiratory volume in 1 second (FEV1) area under the curve (AUC0-12h) and peak FEV1, with a trend toward greater efficacy with higher GB dose.,All adverse events were mild-moderate in severity, with a lower incidence with GB than placebo and no evidence of a dose-response relationship.,In study Part 2, of 38 patients recruited, 34 completed the study.,Adjusted mean differences from placebo in 12 h trough FEV1 on Day 7 (primary) were 115, 142 and 136 mL for GB 12.5, 25 and 50 μg BID, respectively (all P<0.001).,GB 25 and 50 μg BID were superior (P<0.05) to GB 12.5 μg BID for pre-dose morning FEV1 on Day 8.,For this endpoint, GB 25 and 50 μg BID were also superior to tiotropium.,Compared with Day 7, addition of formoterol significantly increased Day 8 FEV1 peak and AUC0-12h with all GB doses and placebo (all P<0.001).,All adverse events were mild-moderate in severity and there was no indication of a dose-related relationship.,This study provides initial evidence on bronchodilation, safety and pharmacokinetics of extrafine GB BID.,Overall, the results suggest that GB 25 μg BID is the optimal dose in patients with COPD. | 1 |
Chronic respiratory diseases (CRD) are common among patients with coronavirus disease 2019 (COVID-19).,We sought to determine the association between CRD (including disease overlap) and the clinical outcomes of COVID-19.,Data of diagnoses, comorbidities, medications, laboratory results, and clinical outcomes were extracted from the national COVID-19 reporting system.,CRD was diagnosed based on International Classification of Diseases-10 codes.,The primary endpoint was the composite outcome of needing invasive ventilation, admission to intensive care unit, or death within 30 days after hospitalization.,The secondary endpoint was death within 30 days after hospitalization.,We included 39,420 laboratory-confirmed patients from the electronic medical records as of May 6, 2020.,Any CRD and CRD overlap was present in 2.8% and 0.2% of patients, respectively.,Chronic obstructive pulmonary disease (COPD) was most common (56.6%), followed by bronchiectasis (27.9%) and asthma (21.7%).,COPD-bronchiectasis overlap was the most common combination (50.7%), followed by COPD-asthma (36.2%) and asthma-bronchiectasis overlap (15.9%).,After adjustment for age, sex, and other systemic comorbidities, patients with COPD (odds ratio [OR]: 1.71, 95% confidence interval [CI]: 1.44-2.03) and asthma (OR: 1.45, 95% CI: 1.05-1.98), but not bronchiectasis, were more likely to reach to the composite endpoint compared with those without at day 30 after hospitalization.,Patients with CRD were not associated with a greater likelihood of dying from COVID-19 compared with those without.,Patients with CRD overlap did not have a greater risk of reaching the composite endpoint compared with those without.,CRD was associated with the risk of reaching the composite endpoint, but not death, of COVID-19. | •We analysed data from 1054 hospitalised adults tested for SARS-CoV-2.,•COVID-19 patients less frequently were smokers or had COPD vs negative patients.,•Over a fifth of COVID-19 patients were healthcare workers vs <6% negative patients.,•About a third of COVID-19 patients reported anosmia vs <10% negative patients.,•COVID-19 patients had longer hospitalisation and invasive ventilation duration.,We analysed data from 1054 hospitalised adults tested for SARS-CoV-2.,COVID-19 patients less frequently were smokers or had COPD vs negative patients.,Over a fifth of COVID-19 patients were healthcare workers vs <6% negative patients.,About a third of COVID-19 patients reported anosmia vs <10% negative patients.,COVID-19 patients had longer hospitalisation and invasive ventilation duration.,Most reports describing the characteristics of patients hospitalised with COVID-19 lack a comparator group.,We compared clinical characteristics, symptoms, and outcomes of adults presenting to hospital during the pandemic first wave, who tested positive and negative for SARS-CoV-2.,Detailed patient data was obtained from a large, controlled, non-randomised trial of molecular point-of-care testing versus laboratory RT-PCR for SARS-CoV-2 in adults presenting to a large UK hospital with suspected COVID-19.,1054 patients were included: 352 (33.4%) tested positive and 702 (66.6%) negative.,13.4% (47/352) COVID-19-positive patients had COPD versus 18.7% (131/702) of COVID-19-negative patients (difference=5.3% [95%CI −9.7% to −0.5%], p = 0.0297).,5.7% (20/352) of COVID-19-positive patients were smokers versus 16.5% (116/702) of negative patients (difference=−10.8% [−14.4% to −7.0%], p = 0.0001).,70.5% (248/352) of COVID-19-positive patients were White-British versus 85.5% (600/702) of negative patients (difference=−15.0% [−20.5% to −9.7%], p<0.0001).,20.9% (39/187) of COVID-19-positive patients were healthcare workers versus 5.2% (15/287) of negative patients (p<0.0001).,Anosmia was reported in 33.1% (47/142) versus 8.8% (19/216) of COVID-19-positive and negative patients respectively (p<0.0001).,Non-SARS-CoV-2 respiratory viruses or atypical bacteria were detected in 2.5% (5/197) of COVID-19 patients versus 7.9% (24/302) of COVID-19-negative patients (p = 0.0109).,Hospitalisation duration and 30-day-mortality were higher in COVID-19 patients and invasive ventilation was more frequent (11.1% vs 2.8%, p<0.0001), and longer (14.5 vs 4.7 days, p = 0.0015).,There were substantial differences between patients with and without COVID-19 in terms of ethnicity, healthcare worker-status, comorbidities, symptoms, and outcomes.,These data can inform healthcare planning for the next phase of the pandemic. | 1 |
Little is known about the microbiota shift induced by exacerbation in chronic obstructive pulmonary disease (COPD) patients.,The sputa microbiota of COPD patients was evaluated when clinically stable and during acute exacerbations of the disease.,Sputa microbiota was analyzed using 16S ribosomal RNA gene pyrosequencing and quantitative polymerase chain reaction-based pathogen detection.,Nine COPD patients were enrolled.,Pyrosequencing of 16S rRNA genes identified 2,267 unique bacterial operational taxonomic units.,Principal microbiota shifts during exacerbation were in either Proteobacteria, Firmicutes or Bacteroidetes.,Streptococcus and Moraxella levels were detected during exacerbation in severe (Global Initiative for Chronic Obstructive Lung Disease 3) COPD patients.,Most of the clinically-important genera found in the sputum with the pyrosequencing of 16S rRNA gene correlated with specific quantitative polymerase chain reactions for bacteria while respiratory viruses were nearly absent.,Sputum microbiotas of exacerbated COPD patients are complex.,This pilot study shows a clear shift in the microbiota of patients during exacerbation.,The nature of this shift varies from patient to patient in such a way that the treatment should be patient-specific.,Further studies are needed to establish the impact of microbial exacerbations on the pulmonary microbiota. | Although culture-independent techniques have shown that the lungs are not sterile, little is known about the lung microbiome in chronic obstructive pulmonary disease (COPD).,We used pyrosequencing of 16S amplicons to analyze the lung microbiome in two ways: first, using bronchoalveolar lavage (BAL) to sample the distal bronchi and air-spaces; and second, by examining multiple discrete tissue sites in the lungs of six subjects removed at the time of transplantation.,We performed BAL on three never-smokers (NS) with normal spirometry, seven smokers with normal spirometry (“heathy smokers”, HS), and four subjects with COPD (CS).,Bacterial 16 s sequences were found in all subjects, without significant quantitative differences between groups.,Both taxonomy-based and taxonomy-independent approaches disclosed heterogeneity in the bacterial communities between HS subjects that was similar to that seen in healthy NS and two mild COPD patients.,The moderate and severe COPD patients had very limited community diversity, which was also noted in 28% of the healthy subjects.,Both approaches revealed extensive membership overlap between the bacterial communities of the three study groups.,No genera were common within a group but unique across groups.,Our data suggests the existence of a core pulmonary bacterial microbiome that includes Pseudomonas, Streptococcus, Prevotella, Fusobacterium, Haemophilus, Veillonella, and Porphyromonas.,Most strikingly, there were significant micro-anatomic differences in bacterial communities within the same lung of subjects with advanced COPD.,These studies are further demonstration of the pulmonary microbiome and highlight global and micro-anatomic changes in these bacterial communities in severe COPD patients. | 1 |
The superiority of tiotropium/olodaterol is demonstrated in improvement of lung function, dyspnea, lung hyperinflation, and quality of life compared with either monotherapy in patients with chronic obstructive pulmonary disease (COPD).,Japanese Respiratory Society Guidelines for COPD management include improvement of exercise tolerance and daily physical activity as the treatment goals; however, there is limited evidence in Japanese patients with COPD.,A protocol is developed for the VESUTO® study that investigates the efficacy of tiotropium/olodaterol fixed-dose combination (FDC) compared with tiotropium alone on inspiratory capacity (IC, volume from functional residual capacity to total lung capacity), exercise capacity, and daily physical activity in Japanese patients with COPD.,A total of 180 Japanese patients with COPD, aged ≥40 years will be enrolled into the double-blind, multicenter, active-controlled, crossover study (NCT02629965) and will be randomized to receive either tiotropium/olodaterol FDC or tiotropium for 6 weeks each [two puffs via RESPIMAT® (Boehringer Ingelheim, Ingelheim, Germany) inhaler in the morning].,The primary endpoint is IC at rest measured at 60 min post-dose after 6 weeks treatment.,The secondary endpoints include the 6-min walk distance (6MWD) at 90 min post-dose and physical activity measured by the activity monitor in the last 2 weeks of the 6-week treatment periods.,Lung function tests will also be assessed after 6 weeks treatment.,A mixed-effects model repeated measures approach will be used for the primary and secondary endpoints.,The VESUTO® study is the first randomized interventional study to investigate exercise capacity (6MWD) and physical activity measured by a 3-axis accelerometer in Japanese patients with COPD.,The study could provide additional evidence of long-acting muscarinic antagonist (LAMA) + long-acting β2-agonist (LABA) combination therapy on patients’ physical activities as well as lung function.,ClinicalTrials.gov: NCT02629965 (registered on December 1, 2015).,The VESUTO study was funded by Nippon Boehringer Ingelheim Co., Ltd., Tokyo, Japan.,The online version of this article (doi:10.1007/s12325-017-0554-3) contains supplementary material, which is available to authorized users. | Physical activity limitation is common in chronic obstructive pulmonary disease (COPD), and is associated with worse health status, and increased hospitalisation and mortality.,Long-acting bronchodilators, either alone or in combination, have been shown to improve exercise intolerance.,However, none of these studies were designed with physical activity as primary outcome.,This study assessed the effect of indacaterol/glycopyrronium fixed dose combination (IND/GLY) 110/50 μg once daily (OD) versus placebo on lung hyperinflation (inspiratory capacity [IC]) and physical activity in patients with moderate-to-severe COPD.,In this multicentre, randomised, double-blind, placebo-controlled crossover study, patients received IND/GLY or placebo OD in two 21-day treatment periods (14-day washout between periods).,Eligible patients were ≥40 years of age, current or ex-smokers (smoking history ≥10 pack-years), with post-salbutamol forced expiratory volume in 1 s (FEV1) 40-80 % predicted, and FEV1:forced vital capacity <0.70.,The co-primary endpoints were peak IC after 21 days and average daily activity-related energy expenditure.,Key secondary endpoints were average number of steps per day and the duration of at least moderate activity per day.,Peak IC and FEV1 on Day 1, and trough IC and FEV1 after 21 days were other secondary endpoints.,A total of 194 patients were randomised (65.5 % male, mean age 62.8 years, mean FEV1 61.6 % predicted), with 183 (94.3 %) completing the study.,Compared with placebo, IND/GLY significantly increased peak IC after 21 days (difference 202 mL, p < 0.0001), activity-related energy expenditure (difference 36.7 kcal/day, p = 0.040), and the average number of steps per day (difference 358, p = 0.029), with a trend towards an improvement in the duration of at least moderate activity (difference 4.4 min, p = 0.264).,IND/GLY was associated with statistically significant improvements versus placebo in peak IC and FEV1 on Day 1, and trough IC and FEV1 after 21 days.,The incidence of treatment-emergent adverse events was 22.8 % with IND/GLY and 22.9 % with placebo.,In this study, compared with placebo, IND/GLY reduced hyperinflation, and, despite no patient education or lifestyle advice, improved daily physical activity levels.,This suggests that IND/GLY has the potential to impact two of the main clinical concerns in the care of patients with COPD.,ClinicalTrials.gov number: NCT01996319.,The online version of this article (doi:10.1186/s12890-016-0256-7) contains supplementary material, which is available to authorized users. | 1 |
To validate a Portuguese-language version of the COPD assessment test (CAT) for use in Brazil and to assess the reproducibility of this version.,This was multicenter study involving patients with stable COPD at two teaching hospitals in the city of Fortaleza, Brazil.,Two independent observers (twice in one day) administered the Portuguese-language version of the CAT to 50 patients with COPD.,One of those observers again administered the scale to the same patients one week later.,At baseline, the patients were submitted to pulmonary function testing and the six-minute walk test (6MWT), as well as completing the previously validated Portuguese-language versions of the Saint George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (MMRC) dyspnea scale, and hospital anxiety and depression scale (HADS).,Inter-rater and intra-rater reliability was excellent (intraclass correlation coefficient [ICC] = 0.96; 95% CI: 0.93-0.97; p < 0.001; and ICC = 0.98; 95% CI: 0.96-0.98; p < 0.001, respectively).,Bland Altman plots showed good test-retest reliability.,The CAT total score correlated significantly with spirometry results, 6MWT distance, SGRQ scores, MMRC dyspnea scale scores, and HADS-depression scores.,The Portuguese-language version of the CAT is a valid, reproducible, and reliable instrument for evaluating patients with COPD in Brazil.,Realizar a validação e verificar a reprodutibilidade da versão em português do Brasil do COPD Assessment Test (CAT).,Estudo multicêntrico, no qual foram selecionados pacientes com DPOC estável em dois hospitais de ensino na cidade de Fortaleza, CE.,A versão do CAT foi aplicada duas vezes a 50 pacientes com DPOC por dois observadores independentes no mesmo dia.,Após uma semana, esse mesmo questionário foi aplicado novamente aos mesmos pacientes por um dos observadores.,No primeiro dia, os pacientes foram submetidos à prova de função pulmonar e ao teste de caminhada de seis minutos (TC6) e responderam as versões validadas de qualidade de vida relacionada à saúde (QVRS).,(SGRQ), escala de dispneia Modified Medical Research Council (MMRC) e hospital anxiety and depression scale (HADS).,As reprodutibilidades interobservador e intraobservador foram excelentes (coeficiente de correlação intraclasse [CCI] = 0,96; IC95%: 0,93-0,97; p < 0,001; e CCI = 0,98; IC95%: 0,96-0,98; p < 0,001, respectivamente).,As disposições gráficas de Bland Altman demonstraram boa confiabilidade teste-reteste.,Houve correlações significativas do escore total do CAT com os resultados de espirometria, TC6, SGRQ, escala de dispneia MMRC e HADS-depressão.,A versão brasileira do CAT é um instrumento válido, reprodutível e confiável para a avaliação dos pacientes com DPOC na população brasileira. | Exercise tests are important to characterise chronic obstructive pulmonary disease patients and predict their prognosis, but are often not available outside of rehabilitation or research settings.,Our aim was to assess the predictive performance of the sit-to-stand and handgrip strength tests.,The prospective cohort study in Dutch and Swiss primary care settings included a broad spectrum of patients (n=409) with Global Initiative for Chronic Obstructive Lung Disease stages II to IV.,To assess the association of the tests with outcomes, we used Cox proportional hazards (mortality), negative binomial (centrally adjudicated exacerbations) and mixed linear regression models (longitudinal health-related quality of life) while adjusting for age, sex and severity of disease.,The sit-to-stand test was strongly (adjusted hazard ratio per five more repetitions of 0.58, 95% CI 0.40-0.85; p=0.004) and the handgrip strength test moderately strongly (0.84, 95% CI 0.72-1.00; p=0.04) associated with mortality.,Both tests were also significantly associated with health-related quality of life but not with exacerbations.,The sit-to-stand test alone was a stronger predictor of 2-year mortality (area under curve 0.78) than body mass index (0.52), forced expiratory volume in 1 s (0.61), dyspnoea (0.63) and handgrip strength (0.62).,The sit-to-stand test may close an important gap in the evaluation of exercise capacity and prognosis of chronic obstructive pulmonary disease patients across practice settings.,The 1-min sit-to-stand test predicts mortality in COPD patients and can easily be implemented across practice settingshttp://ow.ly/mxrPx | 1 |
Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation. | The COPD Assessment Test (CAT™) is a new short health status measure for routine use.,New questionnaires require reference points so that users can understand the scores; descriptive scenarios are one way of doing this.,A novel method of creating scenarios is described.,A Bland and Altman plot showed a consistent relationship between CAT scores and scores obtained with the St George's Respiratory Questionnaire for COPD (SGRQ-C) permitting a direct mapping process between CAT and SGRQ items.,The severity associated with each CAT item was calculated using a probabilistic model and expressed in logits (log odds of a patient of given severity affirming that item 50% of the time).,Severity estimates for SGRQ-C items in logits were also available, allowing direct comparisons with CAT items.,CAT scores were categorised into Low, Medium, High and Very High Impact.,SGRQ items of corresponding severity were used to create scenarios associated with each category.,Each CAT category was associated with a scenario comprising 12 to 16 SGRQ-C items.,A severity 'ladder' associating CAT scores with exemplar health status effects was also created.,Items associated with 'Low' and 'Medium' Impact appeared to be subjectively quite severe in terms of their effect on daily life.,These scenarios provide users of the CAT with a good sense of the health impact associated with different scores.,More generally they provide a surprising insight into the severity of the effects of COPD, even in patients with apparently mild-moderate health status impact. | 1 |
Substantial evidence suggests that there is genetic susceptibility to chronic obstructive pulmonary disease (COPD).,To identify common genetic risk variants, we performed a genome-wide association study in 2940 cases and 1380 smoking controls with normal lung function.,We demonstrate a novel susceptibility locus at 4q22.1 in FAM13A (rs7671167, OR=0.76, P=8.6×10−8) and provide evidence of replication in one case-control and two family-based cohorts (for all studies, combined P=1.2×10−11). | Chronic obstructive pulmonary disease (COPD) is influenced by both environmental and genetic factors.,ADAM33 (a disintegrin and metalloproteinase 33) has been one of the most exciting candidate genes for asthma since its first association with the disease in Caucasian populations.,Recently, ADAM33 was shown to be associated with excessive decline of lung function and COPD.,The aim of this study was to evaluate the potential relationship between polymorphisms of ADAM33 and COPD in a Han population in northeastern China.,A total of 312 COPD patients and a control group of 319 healthy volunteers were recruited for this study.,Eight polymorphic loci (V4, T+1, T2, T1, S2, S1, Q-1, and F+1) of ADAM33 were selected for genotyping.,Genotypes were determined by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.,Statistically significant differences in the distributions of the T2G, T1G, S2C, and Q-1G alleles between patients and controls were observed (P < 0.001, odds ratio (OR) = 2.81, 95% confidence interval (CI) = 2.19-3.61; P < 0.001, OR = 2.60, 95% CI = 2.06-3.30; P = 0.03, OR = 1.31, 95% CI = 1.02-1.69; and P < 0.001, OR = 1.93, 95% CI = 1.50-2.50, respectively).,Haplotype analysis showed that the frequencies of the CGGGGAGC, CGGGGAGT, CGGGCAGC, and CGGGGGGC haplotypes were significantly higher in the case group than in the control group (P = 0.0002, 0.0001, 0.0005, and 0.0074, respectively).,In contrast, the haplotype CGAAGAGC was more common in the control group than in the case group (P < 0.0001).,These preliminary results suggest an association between ADAM33 polymorphisms and COPD in a Chinese Han population. | 1 |
A decrease in bone mineral density (BMD) is a systemic consequence of chronic obstructive pulmonary disease (COPD).,Past reports have rarely examined any correlation between sarcopenia and BMD.,We investigated the relationship cross-sectionally between the presence of sarcopenia and BMD reduction in COPD patients.,COPD patients aged 50 or older with qualifying spirometry and dual-energy X-ray absorptiometry data were from participants in the Korean National Health and Nutrition Examination Surveys IV and V (2008-2011).,There were 286 (33.3%) subjects in the sarcopenia group and 572 (66.7%) in the non-sarcopenia group.,The sarcopenia group had lower T-scores than the non-sarcopenia group (femur: -0.73±0.88 vs. -0.18±0.97, p < 0.001; femur neck: -1.44±0.98 vs. -0.99±1.06, p < 0.001; lumbar: -1.38±1.36 vs. -0.84±1.38, p < 0.001).,The prevalences of osteopenia and osteoporosis were 60.8% and 22.0%, respectively, in the sarcopenia group and 45.6% and 13.3% in the non-sarcopenia group (both p < 0.001).,After adjusting for multiple variables, the presence of sarcopenia associated with increased the risk of osteopenia, osteoporosis, and a low BMD (OR = 3.227, 95% CI = 2.125-4.899, p < 0.001, OR = 6.952, 95% CI = 3.418-14.139, p < 0.001, and OR = 3.495, 95% CI = 2.315-5.278, p < 0.001, respectively).,In a subgroup analysis, similar OR changes were confirmed in the high-body-weight group (n = 493) (OR = 2.248, 95% CI = 1.084-4.665, p = 0.030, OR = 4.621, 95% CI = 1.167-18.291, p = 0.029, and OR = 2.376, 95% CI = 1.158-4.877, p = 0.018, respectively).,The presence of sarcopenia was associated with increased the risk for decreased BMD in COPD. | To evaluate the prevalence of sarcopenia in COPD patients, as well as to determine whether sarcopenia correlates with the severity and prognosis of COPD.,A cross-sectional study with COPD patients followed at the pulmonary outpatient clinic of our institution.,The patients underwent dual-energy X-ray absorptiometry.,The diagnosis of sarcopenia was made on the basis of the skeletal muscle index, defined as appendicular lean mass/height2 only for low-weight subjects and adjusted for fat mass in normal/overweight subjects.,Disease severity (COPD stage) was evaluated with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.,The degree of obstruction and prognosis were determined by the Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE) index.,We recruited 91 patients (50 females), with a mean age of 67.4 ± 8.7 years and a mean BMI of 25.8 ± 6.1 kg/m2.,Sarcopenia was observed in 36 (39.6%) of the patients, with no differences related to gender, age, or smoking status.,Sarcopenia was not associated with the GOLD stage or with FEV1 (used as an indicator of the degree of obstruction).,The BMI, percentage of body fat, and total lean mass were lower in the patients with sarcopenia than in those without (p < 0.001).,Sarcopenia was more prevalent among the patients in BODE quartile 3 or 4 than among those in BODE quartile 1 or 2 (p = 0.009).,The multivariate analysis showed that the BODE quartile was significantly associated with sarcopenia, regardless of age, gender, smoking status, and GOLD stage.,In COPD patients, sarcopenia appears to be associated with unfavorable changes in body composition and with a poor prognosis.,Avaliar a prevalência de sarcopenia em pacientes com DPOC e determinar se sarcopenia está correlacionada com a gravidade e o prognóstico de DPOC.,Estudo retrospectivo em pacientes com DPOC atendidos no ambulatório de pneumologia de nossa instituição.,Os pacientes realizaram absorciometria de dupla energia por raios X.,O diagnóstico de sarcopenia foi baseado no índice de massa muscular esquelética, definido como massa magra apendicular/altura2 somente para indivíduos com baixo peso, sendo ajustado pela massa gorda para aqueles com peso normal/sobrepeso.,A gravidade da doença (estádio da DPOC) foi avaliada com os critérios da Global Initiative for Chronic Obstructive Lung Disease (GOLD).,O grau de obstrução e o prognóstico foram determinados pelo índice Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE).,Foram incluídos 91 pacientes (50 mulheres), com média de idade de 67,4 ± 8,7 anos e média de IMC de 25,8 ± 6,1 kg/m2.,Sarcopenia foi diagnosticada em 36 (39,6%) dos pacientes, sem diferenças relacionadas a sexo, idade ou status tabágico.,Não houve associação de sarcopenia com estádios GOLD ou VEF1 (utilizado como indicador do grau de obstrução).,O IMC, a porcentagem de gordura corporal e a massa magra total foram menores nos pacientes com sarcopenia do que naqueles sem a doença (p < 0,001).,A prevalência de sarcopenia foi maior nos pacientes com BODE nos quartis 3 ou 4 que naqueles com BODE nos quartis 1 ou 2 (p = 0,009).,A análise multivariada mostrou que os quartis do BODE estavam significativamente associados à sarcopenia, independentemente de idade, gênero, status tabágico e estádio GOLD.,Em pacientes com DPOC, sarcopenia parece estar associada a alterações desfavoráveis na composição corporal e pior prognóstico. | 1 |
Telemonitoring (TM) of patients with COPD has gained much interest, but studies have produced conflicting results.,We aimed to investigate the effect of TM with the option of video consultations on quality of life (QoL) in patients with severe COPD.,COPD patients at high risk of exacerbations were eligible for the 6-month study and a total of 281 patients were equally randomized to either TM (n=141) or usual care (n=140).,TM comprised recording of symptoms, oxygen saturation, spirometry, and video consultations.,Algorithms generated alerts if readings breached thresholds.,Both groups filled in a health-related QoL questionnaire (15D©) and the COPD Assessment Test (CAT) at baseline and at 6 months.,Within-group differences were analyzed by paired t-test.,Most of the enrolled patients had severe COPD (86% with Global Initiative for Chronic Obstructive Lung Disease stage 3 or 4 and 45% with admission for COPD within the last year, respectively).,No difference in drop-out rate and mortality was found between the groups, and likewise there was no difference in 15D or CAT at baseline.,At 6 months, a significant improvement of 0.016 in 15D score (p=0.03; minimal clinically important difference 0.015) was observed in the TM group (compared to baseline), while there was no improvement in the control group −0.003 (p=0.68).,After stratifying 15D score at baseline to <0.75 or ≥0.75, respectively, there was a significant difference in the <0.75 TM group of 0.037 (p=0.001), which is a substantial improvement.,No statistically significant changes were found in CAT score.,Compared to the nonintervention group, TM as an add-on to usual care over a 6-month period improved QoL, as assessed by the 15D questionnaire, in patients with severe COPD, whereas no difference between groups was observed in CAT score. | Tele monitoring (TM) of patients with chronic obstructive pulmonary disease (COPD) has gained much interest, but studies have produced conflicting results.,Our aim was to investigate the effect of TM with the option of video consultations on exacerbations and hospital admissions in patients with severe COPD.,Patients with severe COPD at high risk of exacerbations were eligible for the study.,Of 560 eligible patients identified, 279 (50%) declined to participate.,The remaining patients were equally randomized to either TM (n=141) or usual care (n=140) for the 6-month study period.,TM comprised recording of symptoms, saturation, spirometry, and weekly video consultations.,Algorithms generated alerts if readings breached thresholds.,Both groups received standard care.,The primary outcome was number of hospital admissions for exacerbation of COPD during the study period.,Most of the enrolled patients had severe COPD (forced expiratory volume in 1 second <50%pred in 86% and ≥hospital admission for COPD in the year prior to enrollment in 45%, respectively, of the patients).,No difference in drop-out rate and mortality was found between the groups.,With regard to the primary outcome, no significant difference was found in hospital admissions for COPD between the groups (P=0.74), and likewise, no difference was found in time to first admission or all-cause hospital admissions.,Compared with the control group, TM group patients had more moderate exacerbations (ie, treated with antibiotics/corticosteroid, but not requiring hospital admission; P<0.001), whereas the control group had more visits to outpatient clinics (P<0.001).,Our study of patients with severe COPD showed that TM including video consultations as add-on to standard care did not reduce hospital admissions for exacerbated COPD, but TM may be an alternative to visits at respiratory outpatient clinics.,Further studies are needed to establish the optimal role of TM in the management of severe COPD. | 1 |
The economic burden of COPD has not been well studied in China.,This study investigated the total costs caused by COPD and the influencing factors for the high economic burden in urban areas of China.,A cross-sectional study was carried out among 678 COPD patients in four cities in China in 2011.,The average annual direct medical costs (DMCs), direct nonmedical costs (DNMCs), and indirect costs (ICs) on COPD were measured by median and mean (± standard deviation).,Logistic regression model was used to explore factors related to high total costs on COPD.,The median annual DMCs, DNMCs, and ICs per COPD patient were RMB 5565 Yuan (US$ 862), 0 Yuan (US$ 0), and 0 Yuan (US$ 0), respectively, and the mean annual DMCs, DNMCs, and ICs per COPD patient were RMB 11968 (±22422) Yuan [US$ 1853 (±3472)], 539 (±2092) Yuan [US$ 83 (±324)], and 2087 (±8110) Yuan [US$ 323 (±1256)], respectively.,The annual DMCs, DNMCs, and ICs for diagnosed COPD patients were RMB 195.70 billion Yuan (US$ 30.30 billion), 8.78 billion Yuan (US$ 1.36 billion), and 34.10 billion Yuan (US$ 5.28 billion), respectively, in China.,Hospitalization accounted for 56.7% of the total costs.,High economic burden was significantly related to age, acute exacerbations, and disease severity in COPD patients.,COPD posed a heavy economic burden in China.,Measures to delay the disease progression and to reduce the risks of acute exacerbation and hospitalization will help substantially lower the costs for COPD care. | Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide.,Few studies have focused on the quality of life (QoL) associated medical costs for COPD in China.,A cross-sectional survey of 678 COPD patients was conducted in four major cities (Beijing, Shanghai, Guangzhou and Chengdu), China, in 2011.,Data on socio-demographic information, health conditions and medical costs were collected through a face-to-face interview combined with medical record searching.,The EuroQol (EQ-5D) health questionnaire was applied to assess the QoL of COPD patients.,Among 678 patients with COPD, nearly 40% had difficulties in mobility, usual activities and pain/discomfort, one third had various degrees of anxiety/depression, and one fifth had difficulties in self-care.,The COPD patients had a median utility score of 0.768 and a median visual analog scale score of 70.,The degree of difficulties in any dimensions significantly increased, and utility and health scores decreased with severity of the disease.,Age, gender and disease severity were significantly associated with the quality of life after taking other covariates into consideration.,Poorer QoL was a significant indicator of higher direct medical costs for COPD patients.,Impaired quality of life was significantly linked to increased medical costs for COPD patients and could be an important measure for policy- and decision-making in COPD care. | 1 |
Chronic obstructive pulmonary disease (COPD) is a common disease that leads to huge economic and social burden.,Efficient and effective management of stable COPD is essential to improve quality of life and reduce medical expenditure.,The Internet of Things (IoT), a recent breakthrough in communication technology, seems promising in improving health care delivery, but its potential strengths in COPD management remain poorly understood.,We have developed a mobile phone-based IoT (mIoT) platform and initiated a randomized, multicenter, controlled trial entitled the ‘MIOTIC study’ to investigate the influence of mIoT among stable COPD patients.,In the MIOTIC study, at least 600 patients with stable GOLD group C or D COPD and with a history of at least two moderate-to-severe exacerbations within the previous year will be randomly allocated to the control group, which receives routine follow-up, or the intervention group, which receives mIoT management.,Endpoints of the study include (1) frequency and severity of acute exacerbation; (2) symptomatic evaluation; (3) pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) measurement; (4) exercise capacity; and (5) direct medical cost per year.,Results from this study should provide direct evidence for the suitability of mIoT in stable COPD patient management. | Although medical treatment of COPD has advanced, nonadherence to medication regimens poses a significant barrier to optimal management.,Underuse, overuse, and improper use continue to be the most common causes of poor adherence to therapy.,An average of 40%-60% of patients with COPD adheres to the prescribed regimen and only 1 out of 10 patients with a metered dose inhaler performs all essential steps correctly.,Adherence to therapy is multifactorial and involves both the patient and the primary care provider.,The effect of patient instruction on inhaler adherence and rescue medication utilization in patients with COPD does not seem to parallel the good results reported in patients with asthma.,While use of a combined inhaler may facilitate adherence to medications and improve efficacy, pharmacoeconomic factors may influence patient’s selection of both the device and the regimen.,Patient’s health beliefs, experiences, and behaviors play a significant role in adherence to pharmacological therapy.,This manuscript reviews important aspects associated with medication adherence in patients with COPD and identifies some predictors of poor adherence. | 1 |
Regular physical activity (PA) is recommended for persons with chronic obstructive pulmonary disease (COPD).,Interventions that promote PA and sustain long-term adherence to PA are needed.,We examined the effects of an Internet-mediated, pedometer-based walking intervention, called Taking Healthy Steps, at 12 months.,Veterans with COPD (N=239) were randomized in a 2:1 ratio to the intervention or wait-list control.,During the first 4 months, participants in the intervention group were instructed to wear the pedometer every day, upload daily step counts at least once a week, and were provided access to a website with four key components: individualized goal setting, iterative feedback, educational and motivational content, and an online community forum.,The subsequent 8-month maintenance phase was the same except that participants no longer received new educational content.,Participants randomized to the wait-list control group were instructed to wear the pedometer, but they did not receive step-count goals or instructions to increase PA.,The primary outcome was health-related quality of life (HRQL) assessed by the St George’s Respiratory Questionnaire Total Score (SGRQ-TS); the secondary outcome was daily step count.,Linear mixed-effect models assessed the effect of intervention over time.,One participant was excluded from the analysis because he was an outlier.,Within the intervention group, we assessed pedometer adherence and website engagement by examining percent of days with valid step-count data, number of log-ins to the website each month, use of the online community forum, and responses to a structured survey.,Participants were 93.7% male (223/238) with a mean age of 67 (SD 9) years.,At 12 months, there were no significant between-group differences in SGRQ-TS or daily step count.,Between-group difference in daily step count was maximal and statistically significant at month 4 (P<.001), but approached zero in months 8-12.,Within the intervention group, mean 76.7% (SD 29.5) of 366 days had valid step-count data, which decreased over the months of study (P<.001).,Mean number of log-ins to the website each month also significantly decreased over the months of study (P<.001).,The online community forum was used at least once during the study by 83.8% (129/154) of participants.,Responses to questions assessing participants’ goal commitment and intervention engagement were not significantly different at 12 months compared to 4 months.,An Internet-mediated, pedometer-based PA intervention, although efficacious at 4 months, does not maintain improvements in HRQL and daily step counts at 12 months.,Waning pedometer adherence and website engagement by the intervention group were observed.,Future efforts should focus on improving features of PA interventions to promote long-term behavior change and sustain engagement in PA.,Clinicaltrials.gov NCT01102777; https://clinicaltrials.gov/ct2/show/NCT01102777 (Archived by WebCite at http://www.webcitation.org/6iyNP9KUC) | Accessible interventions to train patients with chronic obstructive pulmonary disease (COPD) are needed.,We designed urban trails of different intensities (low, moderate and high) in different types of public spaces (boulevard, beach and park).,We aimed to validate the trails’ design by assessing the physiological response to unsupervised walking trails of: (1) different intensities in COPD patients, and (2) same intensity from different public spaces in healthy adults.,On different days and under standardized conditions, 10 COPD patients walked the three intensity trails designed in a boulevard space, and 10 healthy subjects walked the three intensity trails in three different spaces.,We measured physiological response and energy expenditure using a gas analyzer.,We compared outcomes across trails intensity and/or spaces using mixed-effects linear regression.,In COPD patients, physiological response and energy expenditure increased significantly according to the trails intensity: mean (SD) peak V˙O2 15.9 (3.5), 17.4 (4.7), and 17.7 (4.4) mL/min/kg (p-trend = 0.02), and MET-min 60 (23), 64 (26), 72 (31) (p-trend<0.01) in low, moderate and high intensity trails, respectively.,In healthy subjects there were no differences in physiological response to walking trails of the same intensity across different spaces.,We validated the trails design for the training of COPD patients by showing that the physiological response to and energy expenditure on unsupervised walking these trails increased according to the predefined trails’ intensity and did not change across trails of the same intensity in different public space.,Walkable public spaces allow the design of trails that could be used for the training of COPD patients in the community. | 1 |
We conducted a randomized controlled trial of a digital health system supporting clinical care through monitoring and self-management support in community-based patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,The aim of this study was to determine the efficacy of a fully automated Internet-linked, tablet computer-based system of monitoring and self-management support (EDGE‚ sElf-management anD support proGrammE) in improving quality of life and clinical outcomes.,We compared daily use of EDGE with usual care for 12 months.,The primary outcome was COPD-specific health status measured with the St George’s Respiratory Questionnaire for COPD (SGRQ-C).,A total of 166 patients were randomized (110 EDGE, 56 usual care).,All patients were included in an intention to treat analysis.,The estimated difference in SGRQ-C at 12 months (EDGE−usual care) was −1.7 with a 95% CI of −6.6 to 3.2 (P=.49).,The relative risk of hospital admission for EDGE was 0.83 (0.56-1.24, P=.37) compared with usual care.,Generic health status (EQ-5D, EuroQol 5-Dimension Questionnaire) between the groups differed significantly with better health status for the EDGE group (0.076, 95% CI 0.008-0.14, P=.03).,The median number of visits to general practitioners for EDGE versus usual care were 4 versus 5.5 (P=.06) and to practice nurses were 1.5 versus 2.5 (P=.03), respectively.,The EDGE clinical trial does not provide evidence for an effect on COPD-specific health status in comparison with usual care, despite uptake of the intervention.,However, there appears to be an overall benefit in generic health status; and the effect sizes for improved depression score, reductions in hospital admissions, and general practice visits warrants further evaluation and could make an important contribution to supporting people with COPD.,International Standard Randomized Controlled Trial Number (ISRCTN): 40367841; http://www.isrctn.com/ISRCTN40367841 (Archived by WebCite at http://www.webcitation.org/6pmfIJ9KK) | We aimed to estimate the prevalence, healthcare costs and number of deaths among people with chronic obstructive pulmonary disease (COPD) in England and Scotland 2011-2030.,We adapted the Dutch COPD Model by using English and Scottish demographic, COPD incidence, COPD prevalence, smoking prevalence and mortality data to make projections.,In England, the prevalence of COPD was estimated to be 1.79% (95% uncertainty interval 1.77-1.81) in 2011, increasing to 2.19% (1.85-2.33) by 2030.,In Scotland, prevalence was 2.03% (1.96-2.10) in 2011 increasing to 2.20% (1.98-2.40) in 2030.,These increases were driven by more women developing COPD.,Annual direct healthcare costs of COPD in England were estimated to increase from £1.50 billon (1.18-2.50) in 2011 to £2.32 (1.85-3.08) billion in 2030.,In Scotland, costs increased from £159 million (128-268) in 2011 to £207 (165-274) million in 2030.,The deaths in England were estimated to increase from 99,200 (92,500-128,500) in 2011, to 129,400 (126,400-133,400) by 2030.,In Scotland, in 2011 there were 9,700 (9,000-12,300) deaths and 13,900 (13,400-14,500) deaths in 2030.,The number of people with COPD will increase substantially over the coming years in England and Scotland, particularly in females.,Services need to adapt to this increasing demand. | 1 |
To evaluate differentially expressed long noncoding RNAs (lncRNAs) and the potential role of lncRNA TUG1 in patients with chronic obstructive pulmonary disease (COPD).,Total RNA was extracted from both COPD and non-COPD lung tissues, and microarray analysis was performed with 25,628 lncRNA probes and 20,106 mRNA probes.,In addition, five up-regulated and five down-regulated lncRNAs were selected for identification using quantitative real-time polymerase chain reaction.,COPD cell model was established by transforming growth factor β (TGF-β) treatment.,Cell Counting Kit-8 assay was used to detect BEAS-2B and HFL1 cell proliferation after TUG-siRNA transfection with TGF-β treatment.,In addition, the expression levels of α-SMA and fibronectin proteins were determined using Western blot in BEAS-2B and HFL1 cells after TUG-siRNA transfection with TGF-β treatment.,There were 8,376 (32.7%) differentially expressed lncRNAs and 5,094 (25.3%) differentially expressed mRNAs in COPD lung tissues compared with non-COPD lung tissues.,Five of the analyzed lncRNAs (BC038205, BC130595, TUG1, MEG3, and LOC646329) were markedly increased, while five lncRNAs (LOC729178, PLAC2, LOC339529, LINC00229, and SNHG5) were significantly decreased in COPD lung tissues compared with non-COPD lung tissues (n=20) (***P<0.001).,Knockdown of lncRNA TUG1 promotes BEAS-2B and HFL1 cell proliferation after TGF-β treatment through inhibiting the expression levels of α-SMA and fibronectin.,Abundant, differentially expressed lncRNAs and mRNAs were identified by microarray analysis and these might play a partial or key role in the diagnosis of patients with COPD.,LncRNA TUG1 may become a very important class of biomarker and may act as a potential diagnostic and therapeutic target for patients with COPD. | Heightened inflammation, including expression of COX-2, is associated with COPD pathogenesis.,RelB is an NF-κB family member that attenuates COX-2 in response to cigarette smoke by a mechanism that may involve the miRNA miR-146a.,There is no information on the expression of RelB in COPD or if RelB prevents COX-2 expression through miR-146a.,RelB, Cox-2 and miR-146a levels were evaluated in lung fibroblasts and blood samples derived from non-smokers (Normal) and smokers (At Risk) with and without COPD by qRT-PCR.,RelB and COX-2 protein levels were evaluated by western blot.,Human lung fibroblasts from Normal subjects and smokers with and without COPD, along with RelB knock-down (siRNA) in Normal cells, were exposed to cigarette smoke extract (CSE) in vitro and COX-2 mRNA/protein and miR-146a levels assessed.,Basal expression of RelB mRNA and protein were significantly lower in lung cells derived from smokers with and without COPD, the latter of which expressed more Cox-2 mRNA and protein in response to CSE.,Knock-down of RelB in Normal fibroblasts increased Cox-2 mRNA and protein induction by CSE.,Basal miR-146a levels were not different between the three groups, and only Normal fibroblasts increased miR-146a expression in response to smoke.,There was a positive correlation between systemic RelB and Cox-2 mRNA levels and circulating miR-146a levels were higher only in GOLD stage I subjects.,Our data indicate that RelB attenuates COX-2 expression in lung structural cells, such that loss of pulmonary RelB may be an important determinant in the aberrant, heightened inflammation associated with COPD pathogenesis. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) contribute significantly to disease progression.,However, the effect on tissue structure and turnover is not well described.,There is an urgent clinical need for biomarkers of disease activity associated with disease progression.,Extracellular matrix (ECM) turnover reflects activity in tissues and consequently assessment of ECM turnover may serve as biomarkers of disease activity.,We hypothesized that the turnover of lung ECM proteins were altered during exacerbations of COPD.,69 patients with COPD hospitalised for an exacerbation were recruited at admission and returned for a 4 weeks follow-up.,Competitive ELISAs measuring circulating protein fragments in serum or plasma assessed the formation and degradation of collagen types III (Pro-C3 and C3M, respectively), IV (P4NP 7S and C4M, respectively), and VI (Pro-C6 and C6M, respectively), and degradation of elastin (ELM7 and EL-NE) and versican (VCANM).,Circulating levels of C3M, C4M, C6M, ELM7, and EL-NE were elevated during an exacerbation of COPD as compared to follow-up (all P <0.0001), while VCANM levels were decreased (P <0.0001).,Pro-C6 levels were decreased and P4NP 7S levels were elevated during exacerbation (P <0.0001).,Pro-C3 levels were unchanged.,At time of exacerbation, degradation/formation ratios were increased for collagen types III and VI and decreased for collagen type IV.,Exacerbations of COPD resulted in elevated levels of circulating fragments of structural proteins, which may serve as markers of disease activity.,This suggests that patients with COPD have accelerated ECM turnover during exacerbations which may be related to disease progression. | The ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) is a measure used to diagnose airflow obstruction and is highly heritable.,We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs) associated with the FEV1/FVC ratio, analyzed as a percent of the predicted value.,Identified SNPs were examined in an independent set of 835 Family Heart Study participants enriched for airflow obstruction.,Four SNPs in tight linkage disequilibrium on chromosome 4q31 were associated with the percent predicted FEV1/FVC ratio with p-values of genome-wide significance in the Framingham sample (best p-value = 3.6e-09).,One of the four chromosome 4q31 SNPs (rs13147758; p-value 2.3e-08 in Framingham) was genotyped in the Family Heart Study and produced evidence of association with the same phenotype, percent predicted FEV1/FVC (p-value = 2.0e-04).,The effect estimates for association in the Framingham and Family Heart studies were in the same direction, with the minor allele (G) associated with higher FEV1/FVC ratio levels.,Results from the Family Heart Study demonstrated that the association extended to FEV1 and dichotomous airflow obstruction phenotypes, particularly among smokers.,The SNP rs13147758 was associated with the percent predicted FEV1/FVC ratio in independent samples from the Framingham and Family Heart Studies producing a combined p-value of 8.3e-11, and this region of chromosome 4 around 145.68 megabases was associated with COPD in three additional populations reported in the accompanying manuscript.,The associated SNPs do not lie within a gene transcript but are near the hedgehog-interacting protein (HHIP) gene and several expressed sequence tags cloned from fetal lung.,Though it is unclear what gene or regulatory effect explains the association, the region warrants further investigation. | 1 |
Nasal gene expression profiling is a promising method to characterize COPD non-invasively.,We aimed to identify a nasal gene expression profile to distinguish COPD patients from healthy controls.,We investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile observed in bronchial epithelium.,Genome wide gene expression analysis was performed on nasal epithelial brushes of 31 severe COPD patients and 22 controls, all current smokers, using Affymetrix Human Gene 1.0 ST Arrays.,We repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of mild-to-moderate COPD patients and controls.,In nasal epithelium, 135 genes were significantly differentially expressed between severe COPD patients and controls, 21 being up- and 114 downregulated in COPD (false discovery rate < 0.01).,Gene Set Enrichment Analysis (GSEA) showed significant concordant enrichment of COPD-associated nasal and bronchial gene expression in both independent cohorts (FDRGSEA < 0.001).,We identified a nasal gene expression profile that differentiates severe COPD patients from controls.,Of interest, part of the nasal gene expression changes in COPD mimics differentially expressed genes in the bronchus.,These findings indicate that nasal gene expression profiling is potentially useful as a non-invasive biomarker in COPD.,ClinicalTrials.gov registration number NCT01351792 (registration date May 10, 2011), ClinicalTrials.gov registration number NCT00848406 (registration date February 19, 2009), ClinicalTrials.gov registration number NCT00807469 (registration date December 11, 2008).,The online version of this article (10.1186/s12931-017-0696-5) contains supplementary material, which is available to authorized users. | Recently, it was shown that chronic tobacco smoking evokes specific cellular and molecular changes in white blood cells by an excess of G protein-coupled receptor 15 (GPR15)-expressing T cells as well as a hypomethylation at DNA CpG site cg05575921 in granulocytes.,In the present study, we aimed to clarify the general usefulness of these two biomarkers as putative signs of non-cancerous change in homeostasis of the lungs.,In a clinical cohort consisting of 42 patients with chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD) and pneumonia and a control cohort of 123 volunteers, the content of GPR15-expressing blood cells as well as the degree of methylation at cg05575921 were analysed by flow-cytometry and pyrosequencing, respectively.,Smoking behaviour was estimated by questionnaire and cotinine level in plasma.,Never-smoking patients could be distinguished from former and current smokers by both the proportion of GPR15-expressing T cells as well as cg05575921 methylation in granulocytes, with 100% and 97% specificity and 100% sensitivity, respectively.,However, both parameters were not affected by lung diseases.,The degrees of both parameters were not changed neither in non-smoking nor smoking patients, compared to appropriate control cohorts of volunteers.,The degree of GPR15-expressing cells among T cells as well as the methylation at cg05575921 in granulocytes in blood are both rather signs of tobacco-smoking induced systemic inflammation because they don’t indicate specifically non-cancerous pathological changes in the lungs. | 1 |
Expiratory flow limitation (EFL) is seen in some patients presenting with a COPD exacerbation; however, it is unclear how EFL relates to the clinical features of the exacerbation.,We hypothesized that EFL when present contributes to symptoms and duration of recovery during a COPD exacerbation.,Our aim was to compare changes in EFL with symptoms in subjects with and without flow-limited breathing admitted for a COPD exacerbation.,A total of 29 subjects with COPD were recruited within 48 hours of admission to West China Hospital for an acute exacerbation.,Daily measurements of post-bronchodilator spirometry, resistance, and reactance using the forced oscillation technique and symptom (Borg) scores until discharge were made.,Flow-limited breathing was defined as the difference between inspiratory and expiratory respiratory system reactance (EFL index) greater than 2.8 cmH2O·s·L−1.,The physiological predictors of symptoms during recovery were determined by mixed-effect analysis.,Nine subjects (31%) had flow-limited breathing on admission despite similar spirometry compared to subjects without flow-limited breathing.,Spirometry and resistance measures did not change between enrolment and discharge.,EFL index values improved in subjects with flow-limited breathing on admission, with resolution in four patients.,In subjects with flow-limited breathing on admission, symptoms were related to inspiratory resistance and EFL index values.,In subjects without flow-limited breathing, symptoms related to forced expiratory volume in 1 second/forced vital capacity.,In the whole cohort, EFL index values at admission was related to duration of stay (Rs=0.4, P=0.03).,The presence of flow-limited breathing as well as abnormal respiratory system mechanics contribute independently to symptoms during COPD exacerbations. | COPD patients have increased numbers of macrophages and neutrophils in the lungs.,Interleukin-6 (IL-6) trans-signaling via its soluble receptor sIL-6R, governs the influx of innate immune cells to inflammatory foci through regulation of the chemokine CCL3.,We hypothesized that there would be enhanced levels of IL-6, sIL-6R and CCL3 in COPD sputum.,59 COPD patients, 15 HNS and 15 S underwent sputum induction and processing with phosphate buffered saline to obtain supernatants for IL-6, sIL-6R and CCL3 analysis.,Cytoslides were produced for differential cell counting and immunocytochemistry (COPD; n = 3) to determine cell type surface expression of the CCL3 receptors CCR5 and CCR1.,COPD patients expressed higher levels (p < 0.05) of sIL-6R and CCL3 compared to controls (sIL-6R medians pg/ml: COPD 166.4 vs S 101.1 vs HNS 96.4; CCL3 medians pg/ml: COPD 117.9 vs S 0 vs HNS 2.7).,COPD sIL-6R levels were significantly correlated with sputum neutrophil (r = 0.5, p < 0.0001) and macrophage (r = 0.3, p = 0.01) counts.,Immunocytochemical analysis revealed that CCR5 and CCR1 were exclusively expressed on airway macrophages.,Enhanced airway generation of sIL-6R may promote IL-6 trans-signaling in COPD.,Associated upregulation of CCL3 may facilitate the recruitment of macrophages into the airways by ligation of CCR1 and CCR5.,The online version of this article (doi:10.1186/s12931-014-0103-4) contains supplementary material, which is available to authorized users. | 1 |
Inhibition of phosphoinositide 3-kinase δ (PI3Kδ) exerts corrective effects on the dysregulated migration characteristics of neutrophils isolated from patients with chronic obstructive pulmonary disease (COPD).,To develop novel, induced sputum endpoints to demonstrate changes in neutrophil phenotype in the lung by administering nemiralisib, a potent and selective inhaled PI3Kδ inhibitor, to patients with stable COPD or patients with acute exacerbation (AE) of COPD.,In two randomized, double-blind, placebo-controlled clinical trials patients with A) stable COPD (N=28, randomized 3:1) or B) AECOPD (N=44, randomized 1:1) received treatment with inhaled nemiralisib (1mg).,Endpoints included induced sputum at various time points before and during treatment for the measurement of transcriptomics (primary endpoint), inflammatory mediators, functional respiratory imaging (FRI), and spirometry.,In stable COPD patients, the use of nemiralisib was associated with alterations in sputum neutrophil transcriptomics suggestive of an improvement in migration phenotype; however, the same nemiralisib-evoked effects were not observed in AECOPD.,Inhibition of sputum inflammatory mediators was also observed in stable but not AECOPD patients.,In contrast, a placebo-corrected improvement in forced expiratory volume in 1 sec of 136 mL (95% Credible Intervals −46, 315mL) with a probability that the true treatment ratio was >0% (Pr(θ>0)) of 93% was observed in AECOPD.,However, FRI endpoints remained unchanged.,We provide evidence for nemiralisib-evoked changes in neutrophil migration phenotype in stable COPD but not AECOPD, despite improving lung function in the latter group.,We conclude that induced sputum can be used for measuring evidence of alteration of neutrophil phenotype in stable patients, and our study provides a data set of the sputum transcriptomic changes during recovery from AECOPD. | COPD, characterized by long-term poorly irreversible airway limitation and persistent respiratory symptoms, has resulted in enormous challenges to human health worldwide, with increasing rates of prevalence, death, and disability.,Although its origin was thought to be in the interactions of genetic with environmental factors, the effects of environmental factors on the disease during different life stages remain little known.,Without clear mechanisms and radical cure for it, early screening and prevention of COPD seem to be important.,In this review, we will discuss the etiologic origins for poor lung function and COPD caused by specific adverse effects during corresponding life stages, as well as try to find new insights and potential prevention strategies for this disease. | 1 |
Most guidelines recommend pulmonary rehabilitation (PR) for patients with chronic obstructive pulmonary disease (COPD) and modified Medical Research Council dyspnea scale (mMRC) levels ≥2, but the effectiveness of PR in patients with less advanced disease is not well established.,Our aim was to investigate the effects of PR in patients with COPD and mMRC ≤1.,The methodology was developed as a part of evidence-based guideline development and is in accordance with the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group.,We identified randomized controlled trials (RCTs) through a systematic, multidatabase literature search and selected RCTs comparing the effects of PR with usual care in patients with COPD and mMRC ≤1.,Predefined critical outcomes were health-related quality of life (HRQoL), adverse effects and mortality, while walking distance, maximal exercise capacity, muscle strength, and dropouts were important outcomes.,Two authors independently extracted data, assessed trial eligibility and risk of bias, and graded the evidence.,Meta-analyses were performed when deemed feasible.,Four RCTs (489 participants) were included.,On the basis of moderate-quality evidence, we found a clinically and statistically significant improvement in short-term HRQoL of 4.2 units (95% confidence interval [CI]: [−4.51 to −3.89]) on St George’s Respiratory Questionnaire, but not at the longest follow-up.,We also found a statistically significant improvement of 25.71 m (95% CI: [15.76-35.65]) in the 6-minute walk test with PR; however, this improvement was not considered clinically relevant.,No difference was found for mortality, and insufficient data prohibited meta-analysis for muscle strength and maximal exercise capacity.,No adverse effects were reported.,We found a moderate quality of evidence suggesting a small, significant improvement in short-term HRQoL and a clinically nonsignificant improvement in walking distance following PR in patients with COPD and mild symptoms.,This resulted in a weak recommendation of routine PR in these patients using the GRADE approach. | 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 |
Statins have, due to their anti-inflammatory properties, been suggested to potentially improve chronic obstructive pulmonary disease (COPD) outcomes.,We aimed to investigate the effect of statins on time to first exacerbation and all-cause mortality in high-risk COPD outpatients.,All outpatients with COPD seen at the Department of Respiratory Medicine, Copenhagen University Hospital Amager and Hvidovre, Denmark in 2016 were identified and followed for 3.5 years in this retrospective, registry-based cohort study of time to first acute exacerbation of COPD (AECOPD) or death.,AECOPD was defined as a rescue course of oral corticosteroid and/or hospital admission.,The association was estimated using time-varying crude and multivariable Cox proportional hazard regression.,The cohort comprised 950 COPD outpatients, mean (SD) age 71 (11) years, and FEV1 44% predicted (IQR 33%; 57%).,The annual exacerbation rate was 0.88 (1.68) and 211 patients (22%) had a history of hospital admission for AECOPD in the 12 months prior to index date.,Three hundred and ninety-three patients (41.4%) were defined as statin users, with 131 (33.3%) having filled the first prescription for statin after index date.,Statin use was not associated with reduced risk of AECOPD.,When stratifying for moderate and severe exacerbations in a sub-analysis in the same model, statin use did not have an increased HR for exacerbation of either severity (HR = 1.02 (95% CI 0.85to 1.24; p = 0.811) and HR = 1.07 (95% CI 0.89 to 1.29; p = 0.492) respectively).,Statin use was not associated with all-cause mortality (HR 1.05 (95% CI, 0.75 to 1.47, p = 0.777)).,We did not find any association between statin use and risk of AECOPD or all-cause mortality.,The result adds to the evidence that an aggressive approach with statin treatment upfront is not beneficial in COPD, unless prescribed according to current guidelines for cardiovascular diseases. | To clarify how low BMI and weight loss were associated with risk of chronic obstructive pulmonary disease (COPD) mortality, in a large prospective cohort of the general population across Japan, the Japan Collaborative Cohort Study, conducted between 1988 and 2009.,A total of 45,837 male residents were observed for a median period of 19.1 years.,Self-administered questionnaires, collecting information on BMI, weight loss since the age of 20, lifestyles, history of diseases, as well as records of COPD mortality, were analysed at 2019.,During follow-up, 268 participants died from COPD.,The multivariate-adjusted hazard ratio (95% confidence interval) of COPD mortality associated with a 1-SD increment of body mass index (BMI) was 0.48 (0.41-0.57), while for weight change from age of 20 (+ 2.0 kg) it was 0.63 (0.59-0.68).,These associations were persistently observed after stratifications with smoking status, excluding those having airway symptoms in the baseline survey, and excluding early COPD deaths within 5, 10 and 15 years.,Our study suggests that BMI and weight change since the age of 20 could be markers for COPD prognosis, indicated by risk of COPD mortality. | 1 |
Patients with COPD have frequent exacerbations.,The role of respiratory viral infection is just emerging.,We wished to determine prospectively the incidence of viral infection in exacerbated and stable COPD patients as well as smokers who do not have airways obstruction.,Stable and exacerbated COPD patients were recruited along with a group of patients who had smoked but who did not have any airways obstruction.,Spirometry was performed and sputum specimens were tested for a range of 12 different respiratory viruses using PCR.,One hundred and thirty-six patients with exacerbations of COPD, 68 stable COPD patients and 16 non-obstructed smokers were recruited.,A respiratory virus was detected in 37% of exacerbations, 12% of stable COPD patients and 12% of non-obstructed smokers, p < 0.0005.,Rhinovirus was most frequently detected.,The symptom of fever was associated with virus detection, p < 0.05.,Infection with more than one virus was only found in the exacerbated COPD patients.,Respiratory viral infection is associated with exacerbations of COPD.,Rhinovirus was the most common infecting agent identified and in two cases human metapneumovirus was also detected.,Dual infections were only seen amongst those patients admitted to hospital with acute exacerbations of COPD.,Viruses were more commonly detected in those with more severe airways disease. | COPD exacerbations are associated with neutrophilic airway inflammation.,Adhesion molecules on the surface of neutrophils may play a key role in their movement from blood to the airways.,We analysed adhesion molecule expression on blood and sputum neutrophils from COPD subjects and non-obstructed smokers during experimental rhinovirus infections.,Blood and sputum were collected from 9 COPD subjects and 10 smoking and age-matched control subjects at baseline, and neutrophil expression of the adhesion molecules and activation markers measured using flow cytometry.,The markers examined were CD62L and CD162 (mediating initial steps of neutrophil rolling and capture), CD11a and CD11b (required for firm neutrophil adhesion), CD31 and CD54 (involved in neutrophil transmigration through the endothelial monolayer) and CD63 and CD66b (neutrophil activation markers).,Subjects were then experimentally infected with rhinovirus-16 and repeat samples collected for neutrophil analysis at post-infection time points.,At baseline there were no differences in adhesion molecule expression between the COPD and non-COPD subjects.,Expression of CD11a, CD31, CD62L and CD162 was reduced on sputum neutrophils compared to blood neutrophils.,Following rhinovirus infection expression of CD11a expression on blood neutrophils was significantly reduced in both subject groups.,CD11b, CD62L and CD162 expression was significantly reduced only in the COPD subjects.,Blood neutrophil CD11b expression correlated inversely with inflammatory markers and symptom scores in COPD subjects.,Following rhinovirus infection neutrophils with higher surface expression of adhesion molecules are likely preferentially recruited to the lungs.,CD11b may be a key molecule involved in neutrophil trafficking in COPD exacerbations. | 1 |
The combination of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) is associated with substantial morbidity and mortality.,We hypothesized that predictors of OSA among patients with COPD may be distinct from OSA in the general population.,Therefore, we investigated associations between traditional OSA risk factors (e.g. age), and sleep questionnaires [e.g.,Epworth Sleepiness Scale] in 44 patients with advanced COPD.,As a second aim we proposed a pilot, simplified screening test for OSA in patients with COPD.,In a prospective, observational study of patients enrolled in the UCSD Pulmonary Rehabilitation Program we collected baseline characteristics, cardiovascular events (e.g. atrial fibrillation), and sleep questionnaires [e.g.,Pittsburgh Sleep Quality Index (PSQI)].,For the pilot questionnaire, a BMI ≥25 kg/m2 and the presence of cardiovascular disease were used to construct the pilot screening test.,Male: 59%; OSA 66%.,FEV1 (mean ± SD) = 41.0±18.2% pred., FEV1/FVC = 41.5±12.7%].,Male gender, older age, and large neck circumference were not associated with OSA.,Also, Epworth Sleepiness Scale and the STOP-Bang questionnaire were not associated with OSA in univariate logistic regression.,In contrast, BMI ≥25 kg/m2 (OR = 3.94, p = 0.04) and diagnosis of cardiovascular disease (OR = 5.06, p = 0.03) were significantly associated with OSA [area under curve (AUC) = 0.74].,The pilot COPD-OSA test (OR = 5.28, p = 0.05) and STOP-Bang questionnaire (OR = 5.13, p = 0.03) were both associated with OSA in Receiver Operating Characteristics (ROC) analysis.,The COPD-OSA test had the best AUC (0.74), sensitivity (92%), and specificity (83%).,A ten-fold cross-validation validated our results.,We found that traditional OSA predictors (e.g. gender, Epworth score) did not perform well in patients with more advanced COPD.,Our pilot test may be an easy to implement instrument to screen for OSA.,However, a larger validation study is necessary before further clinical implementation is warranted. | Background: The objective of the present analysis is to describe the outcomes of high-intensity non-invasive positive pressure ventilation (NPPV) aimed at maximally decreasing PaCO2 as an alternative to conventional NPPV with lower ventilator settings in stable hypercapnic COPD patients.,Methods: Physiological parameters, exacerbation rates and long-term survival were assessed in 73 COPD patients (mean FEV1 30±12 %predicted) who were established on high-intensity NPPV due to chronic hypercapnic respiratory failure between March 1997 and May 2006.,Results: Controlled NPPV with breathing frequencies of 21±3 breath/min and mean inspiratory/expiratory positive airway pressures of 28±5/5±1 cmH2O led to significant improvements in blood gases, lung function and hematocrit after two months.,Only sixteen patients (22%) required hospitalisation due to exacerbation during the first year, with anaemia increasing the risk for exacerbation.,Two- and five-year survival rates of all patients were 82% and 58%, respectively.,The five year survival rate was 32% and 83% in patients with low (≤39%) and high (≥55%) hematocrit, respectively.,Conclusion: High-intensity NPPV improves blood gases, lung function and hematocrit, and is also associated with low exacerbation rates and a favourable long-term outcome.,The current report strongly emphasises the need for randomised controlled trials evaluating the role of high-intensity NPPV in stable hypercapnic COPD patients. | 1 |
Chronic obstructive pulmonary disease (COPD) is a common airway disease characterized by an exaggerated pulmonary inflammatory response.,Long noncoding MIR155 host gene (lncRNA MIR155HG) has been identified to be related to the macrophage polarization in COPD.,However, the detailed function of MIR155HG in cigarette smoke (CS)-mediated COPD remains largely unknown.,The expression level of MIR155HG was elevated while miR-218-5p was decreased in lung tissues of smokers without or with COPD, especially in smokers with COPD, and cigarette smoke extract (CSE)-treated human pulmonary microvascular endothelial cell (HPMECs) in a dose- and time-dependent manner.,Then, functional experiments showed that MIR155HG deletion could reverse CSE exposure-induced apoptosis and inflammation in HPMECs.,MiR-218-5p was confirmed to be a target of MIR155HG and rescue assay showed miR-218-5p inhibitor attenuated the inhibitory action of MIR155HG knockdown on CSE-induced HPMECs.,Subsequently, miR-218-5p was found to target bromodomain containing 4 (BRD4) directly, and miR-218-5p overexpression overturned CSE-induced injury of HPMECs via regulating BRD4.,Additionally, co-expression analysis indicated MIR155HG indirectly regulated BRD4 expression in HPMECs via miR-218-5p.,Thus, we concluded that MIR155HG contributed to the apoptosis and inflammation of HPMECs in smoke-related COPD by regulating miR-128-5p/BRD4 axis, providing a novel insight on the pathogenesis of COPD and a therapeutic strategy on COPD treatments. | The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | 1 |
Reduced physical capacity (PC) and physical activity (PA) are common in COPD patients and associated with poor outcome.,However, they represent different aspects of physical functioning and interventions do not affect them in the same manner.,To address this, a new PC-PA quadrant concept was recently generated to identify clinical characteristics of sub-groups of physical functioning.,The objective of this study was to I) proof the new concept and to verify their differentiating clinical characteristics, II) evaluate the consistency of the concept over time, III) assess whether patients changed their quadrant affiliation over time, IV) and to test if changes in quadrant affiliations are associated with changes in clinical characteristics.,In a longitudinal, prospective, non-interventional cohort with mild to very severe COPD patients, PC and PA as well as respiratory variables, COPD-specific health status, comorbidities, survival, and exacerbations were yearly assessed.,Data from 283 patients were analysed at baseline.,Mean (min/max) follow-up time was 2.4 (0.5/6.8) years.,The PC-PA quadrants could be characterized as follows: I) “can’t do, don’t do”: most severe and symptomatic, several comorbidities II) “can do, don’t do”: severe but less symptomatic, several comorbidities III) “can’t do, do do”: few patients, severe and symptomatic, less comorbidities IV) “can do, do do”: mildest and less symptomatic, less comorbidities, lowest exacerbation frequency.,Of the 172 patients with at least one follow-up, 58% patients never changed their quadrant affiliation, while 17% declined either PC, PA or both, 11% improved their PC, PA or both, and 14% showed improvement and decline in PC, PA or both during study period.,None of the clinical characteristics or their annual changes showed consistent significant and relevant differences between all individual sub-groups.,Our findings suggest that there are no clinical characteristics allowing to distinguish between the PC-PA quadrants and the concept seems not able to illustrate disease process.,However, the already low PA but preserved PC in the “can do, don’t do” quadrant raises the question if regularly assessment of PA in clinical practice would be more sensitive to detect progressive deterioration of COPD compared to the commonly used PC.,www.ClinicalTrials.gov, NCT01527773. | The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed.,Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD.,We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012.,Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence.,86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both.,Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence.,Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low.,As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence.,Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence.,Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment. | 1 |
The aim of this study was to determine if an interactive web-based pulmonary rehabilitation (PR) programme is a feasible alternative to conventional PR.,Randomised controlled feasibility trial.,Participants with a diagnosis of chronic obstructive pulmonary disease were recruited from PR assessments, primary care and community rehabilitation programmes.,Patients randomised to conventional rehabilitation started the programme according to the standard care at their referred site on the next available date.,103 patients were recruited to the study and randomised: 52 to conventional rehabilitation (mean (±SD) age 66 (±8) years, Medical Research Council (MRC) 3 (IQR2-4)); 51 to the web arm (mean (±SD) age 66 (±10) years, MRC 3 (IQR2-4)).,Participants had to be willing to participate in either arm of the trial, have internet access and be web literate.,Patients randomised to the web-based programme worked through the website, exercising and recording their progress as well as reading educational material.,Conventional PR consisted of twice weekly, 2 hourly sessions (an hour for exercise training and an hour for education).,Recruitment rates, eligibility, patient preference and dropout and completion rates for both programmes were collected.,Standard outcomes for a PR assessment including measures of exercise capacity and quality of life questionnaires were also evaluated.,A statistically significant improvement (p≤0.01) was observed within each group in the endurance shuttle walk test (WEB: mean change 189±211.1; PR classes: mean change 184.5±247.4 s) and Chronic Respiratory disease Questionnaire-Dyspnoea (CRQ-D; WEB: mean change 0.7±1.2; PR classes: mean change 0.8±1.0).,However, there were no significant differences between the groups in any outcome.,Dropout rates were higher in the web-based programme (57% vs 23%).,An interactive web-based PR programme is feasible and acceptable when compared with conventional PR.,Future trials maybe around choice-based PR programmes for select patients enabling stratification of patient care.,ISRCTN03142263; Results. | Pulmonary rehabilitation is known to improve function and quality of life for people with chronic obstructive pulmonary disease (COPD).,However, little research has been conducted on the influence of culture on experiences of pulmonary rehabilitation.,This study examined factors influencing uptake of pulmonary rehabilitation by Māori with COPD in New Zealand.,Grounded theory nested within kaupapa Māori methodology.,Transcripts were analyzed from interviews and focus groups with 15 Māori and ten New Zealand non-Māori invited to attend pulmonary rehabilitation for COPD.,Māori participants had either attended a mainstream hospital-based program, a community-based program designed “by Māori, for Māori”, or had experienced both.,Several factors influencing uptake of pulmonary rehabilitation were common to all participants regardless of ethnicity: 1) participants’ past experiences (eg, of exercise; of health care systems), 2) attitudes and expectations, 3) access issues (eg, time, transport, and conflicting responsibilities), and 4) initial program experiences.,These factors were moderated by the involvement of family and peers, interactions with health professionals, the way information on programs was presented, and by new illness events.,For Māori, however, several additional factors were also identified relating to cultural experiences of pulmonary rehabilitation.,In particular, Māori participants placed high value on whakawhanaungatanga: the making of culturally meaningful connections with others.,Culturally appropriate communication and relationship building was deemed so important by some Māori participants that when it was absent, they felt strongly discouraged to attend pulmonary rehabilitation.,Only the more holistic services offered a program in which they felt culturally safe and to which they were willing to return for ongoing rehabilitation.,Lack of attention to cultural factors in the delivery of pulmonary rehabilitation may be a barrier to its uptake by indigenous, minority ethnic groups, such as New Zealand Māori.,Indigenous-led or culturally responsive health care interventions for COPD may provide a solution to this issue. | 1 |
It is known that the contribution of risk alleles to chronic obstructive pulmonary disease (COPD) may vary between populations.,Further, previous studies involving various ethnic groups have revealed associations between COPD and genetic polymorphisms in families with sequence similarity 13, member A (FAM13A), micro-RNA 2054 (MIR2054), SET domain containing protein 7 (SETD7), ring finger protein 150 (RNF150), hedgehog interacting protein (HHIP), and vascular endothelial growth factor A (VEGFA).,Our objective was to explore the association between these gene polymorphism and COPD in members of Chinese Li minority population.,The Chinese Li population case-control study was conducted to assess genetic associations with COPD risk.,Seven single nucleotide polymorphisms (SNPs) located on chromosome 4, including FAM13A, MIR2054, SETD7, RNF150, and HHIP, and nine SNPs in the VEGFA gene were genotyped among 234 cases and 240 controls using Sequenom Mass-ARRAY® platform.,Linkage disequilibrium (LD) analysis was performed using Haploview software and the associations of the SNP frequencies with COPD were analyzed using chi-square (χ2) tests, genetic models analysis, and haplotype analysis.,By χ2 we found the minor allele “G” of rs17050782 was with increased COPD risk in allele model.,In genetic models, we found the minor allele of rs7671167 (P=0.028 by dominant model) and rs17050782 (P=0.008 by recessive model) was associated with the increased risk of COPD disease.,Likewise, an increased risk of developing COPD was associated with the “GGCGC” haplotype of VEGFA (odds ratio =1.48, 95% confidence interval =1.02-2.12, P=0.037).,Our results were the first time to reveal that SNPs from FAM13A (rs7671167), SETD7 (rs17050782), and a haplotype of VEGFA (“GGCGC”) are potential susceptibility loci associated with increased COPD risk in Chinese Li minority population. | In utero and/or childhood environmental tobacco smoke exposure is well known to adversely affect lung function and to depreciate child's health in many ways.,Fewer studies have assessed the long-term effects on COPD development and disease severity in later adulthood.,COPD patients were interviewed using a structured questionnaire regarding their personal as well as the smoking habits of their parents.,Data were compared with the disease history, e.g.,COPD exacerbation rate, and their lung function data.,Between 2003 and 2004 COPD patients were recruited a) in a private practice specialized in pulmonary medicine (n = 133) and b) in a hospital (n = 158). 75% of their fathers and only 15.4 of all mothers smoked regularly.,COPD patients from smoking mothers had lower FEV1 predicted than those raised in household without maternal smoking exposure: 39.4 ± 9.5% vs.,51.9 ± 6.0% (P = 0.037).,Fathers had no effect on FEV1 regardless if they are smokers or non-smokers.,Rate of severe exacerbations requiring hospitalization remained unaffected by parental second hand smoke exposure.,Maternal smoking negatively affects lung function of their offspring even in late adulthood when they develop COPD.,It even aggravates the cumulative effect of active cigarette consumption.,Clinical course of the COPD remained unaffected. | 1 |
In pulmonary function testing by spirometry, bronchodilator responsiveness (BDR) evaluates the degree of volume and airflow improvement in response to an inhaled short-acting bronchodilator (BD).,The traditional, binary categorization (present vs absent BDR) has multiple pitfalls and limitations.,To overcome these limitations, a novel classification that defines five categories (negative, minimal, mild, moderate and marked BDR), and based on % and absolute changes in forced expiratory volume in 1 s (FEV1), has been recently developed and validated in patients with chronic obstructive pulmonary disease, and against multiple objective and subjective measurements.,In this study, working on several large spirometry cohorts from two different institutions (n=31 598 tests), we redefined the novel BDR categories based on delta post-BD-pre-BD FEV1 % predicted values.,Our newly proposed BDR partition is based on several distinct intervals for delta post-BD-pre-BD % predicted FEV1 using Global Lung Initiative predictive equations.,In testing, training and validation cohorts, the model performed well in all BDR categories.,In a validation set that included only normal baseline spirometries, the partition model had a higher rate of misclassification, possibly due to unrestricted BD use prior to baseline testing.,A partition that uses delta % predicted FEV1 with the following intervals ≤0%, 0%-2%, 2%-4%, 4%-8% and >8% may be a valid and easy-to-use tool for assessing BDR in spirometry.,We confirmed in our cohorts that these thresholds are characterized by low variance and that they are generally gender-independent and race-independent.,Future validation in other cohorts and in other populations is needed. | It is unknown whether aggressive medication strategies should be used for early COPD with or without lung hyperinflation.,We aimed to explore the characteristics and bronchodilator responsiveness of early COPD patients (stages I and II) with/without lung hyperinflation.,Four hundred and six patients with COPD who performed both lung volume and bronchodilation tests were retrospectively analyzed.,Residual volume to total lung capacity >120% of predicted values indicated lung hyperinflation.,The characteristics and bronchodilator responsiveness were compared between the patients with and without lung hyperinflation across all stages of COPD.,The percentages of patients with lung hyperinflation were 72.7% in the entire cohort, 19.4% in stage I, 68.5% in stage II, 95.3% in stage III, and 100.0% in stage IV.,The patients with lung hyperinflation exhibited poorer lung function but better bronchodilator responsiveness of both forced expiratory volume in 1 second and forced vital capacity than those without lung hyperinflation during early COPD (t=2.21-5.70, P=0.000-0.029), especially in stage I, while age, body mass index, smoking status, smoking history, and disease duration were similar between the two subgroups in the same stages.,From stages I to IV of subgroups with lung hyperinflation, stage I patients had the best bronchodilator responsiveness.,Use of bronchodilator responsiveness of forced vital capacity to detect the presence of lung hyperinflation in COPD patients showed relatively high sensitivities (69.5%-75.3%) and specificities (70.3%-75.7%).,We demonstrated the novel finding that early COPD patients with lung hyperinflation are associated with poorer lung function but better bronchodilator responsiveness and established a simple method for detecting lung hyperinflation. | 1 |
Cardiovascular diseases (CVDs) are arguably the most important comorbidities in chronic obstructive pulmonary disease (COPD).,CVDs are common in people with COPD, and their presence is associated with increased risk for hospitalization, longer length of stay and all-cause and CVD-related mortality.,The economic burden associated with CVD in this population is considerable and the cumulative cost of treating comorbidities may even exceed that of treating COPD itself.,Our understanding of the biological mechanisms that link COPD and various forms of CVD has improved significantly over the past decade.,But despite broad acceptance of the prognostic significance of CVDs in COPD, there remains widespread under-recognition and undertreatment of comorbid CVD in this population.,The reasons for this are unclear; however institutional barriers and a lack of evidence-based guidelines for the management of CVD in people with COPD may be contributory factors.,In this review, we summarize current knowledge relating to the prevalence and incidence of CVD in people with COPD and the mechanisms that underlie their coexistence.,We discuss the implications for clinical practice and highlight opportunities for improved prevention and treatment of CVD in people with COPD.,While we advocate more active assessment for signs of cardiovascular conditions across all age groups and all stages of COPD severity, we suggest targeting those aged under 65 years.,Evidence indicates that the increased risks for CVD are particularly pronounced in COPD patients in mid-to-late-middle-age and thus it is in this age group that the benefits of early intervention may prove to be the most effective. | Chronic obstructive pulmonary disease (COPD) is a progressive, chronic respiratory disease with a significant socioeconomic burden.,Exacerbations, the sudden and sustained worsening of symptoms, can lead to hospitalization and reduce quality of life.,Major limitations of previous telemonitoring interventions for COPD include low compliance, lack of consensus on what constitutes an exacerbation, limited numbers of patients, and short monitoring periods.,We developed a telemonitoring system based on a digital health platform that was used to collect data from the 1-year EDGE (Self Management and Support Programme) COPD clinical trial aiming at daily monitoring in a heterogeneous group of patients with moderate to severe COPD.,The objectives of the study were as follows: first, to develop a systematic and reproducible approach to exacerbation identification and to track the progression of patient condition during remote monitoring; and second, to develop a robust algorithm able to predict COPD exacerbation, based on vital signs acquired from a pulse oximeter.,We used data from 110 patients, with a combined monitoring period of more than 35,000 days.,We propose a finite-state machine-based approach for modeling COPD exacerbation to gain a deeper insight into COPD patient condition during home monitoring to take account of the time course of symptoms.,A robust algorithm based on short-period trend analysis and logistic regression using vital signs derived from a pulse oximeter is also developed to predict exacerbations.,On the basis of 27,260 sessions recorded during the clinical trial (average usage of 5.3 times per week for 12 months), there were 361 exacerbation events.,There was considerable variation in the length of exacerbation events, with a mean length of 8.8 days.,The mean value of oxygen saturation was lower, and both the pulse rate and respiratory rate were higher before an impending exacerbation episode, compared with stable periods.,On the basis of the classifier developed in this work, prediction of COPD exacerbation episodes with 60%-80% sensitivity will result in 68%-36% specificity.,All 3 vital signs acquired from a pulse oximeter (pulse rate, oxygen saturation, and respiratory rate) are predictive of COPD exacerbation events, with oxygen saturation being the most predictive, followed by respiratory rate and pulse rate.,Combination of these vital signs with a robust algorithm based on machine learning leads to further improvement in positive predictive accuracy.,International Standard Randomized Controlled Trial Number (ISRCTN): 40367841; http://www.isrctn.com/ISRCTN40367841 (Archived by WebCite at http://www.webcitation.org/6olpMWNpc) | 1 |
To integrate evidence from randomised controlled trials (RCTs) and observational studies on the efficacy of inhaled treatments for chronic obstructive pulmonary disease using network meta-analyses.,Systematic searches MEDLINE and Embase based on predetermined criteria.,Network meta-analyses of RCTs investigated efficacy on exacerbations (long-term: ≥20 weeks of treatment; short-term: <20 weeks), lung function (≥12 weeks), health-related quality of life, mortality and adverse events.,Qualitative comparisons of efficacies between RCTs and observational studies.,212 RCTs and 19 observational studies were included.,Compared with combined long-acting beta-adrenoceptor agonists and long-acting muscarinic antagonists (LABA+LAMA), triple therapy (LABA+LAMA+inhaled corticosteroid) was significantly more effective at reducing exacerbations (long-term 0.85 (95% CI: 0.78 to 0.94; short-term 0.67 (95% CI: 0.49 to 0.92)) and mortality (0.72 (95% CI: 0.59 to 0.89)) but was also associated with increased pneumonia (1.35 (95% CI: 1.10 to 1.67)).,No differences in lung function (0.02 (95% CI: −0.10 to 0.14)), health-related quality of life (−1.12 (95% CI: −3.83 to 1.59)) or other adverse events (1.02 (95% CI: 0.96 to 1.08)) were found.,Most of the observational evidence trended in the same direction as pooled RCT data.,Further evidence, especially pragmatic trials, are needed to fully understand the characteristics of patient subgroups who may benefit from triple therapy and for those whom the extra risk of adverse events, such as pneumonia, may outweigh any benefits.,CRD42018088013. | Chronic obstructive pulmonary disease (COPD) is a common and deadly disease.,One of the hallmarks of COPD is an accelerated decline in lung function, as measured by spirometry.,Inflammation, oxidative stress and other pathways are hypothesized to be important in this deterioration.,Because progressive airflow obstruction is associated with considerable morbidity and mortality, a major goal of COPD treatment has been to slow or prevent the accelerated decline in lung function.,Until recently, the only known effective intervention was smoking cessation.,However, newly reported large clinical trials have shown that commonly used medications may help slow the rate of lung function decline.,The effect of these medications is modest (and thus required such large, expensive trials) and to be of clinical benefit, therapy would likely need to start early in the course of disease and be prolonged.,Such a treatment strategy aimed at preservation of lung function would need to be balanced against the side effects and costs of prolonged therapy.,A variety of newer classes of medications may help target other pathophysiologically important pathways, and could be used in the future to prevent lung function decline in COPD. | 1 |
Pulmonary rehabilitation (PR) is a guideline-recommended multifaceted intervention that improves the physical and psychological well-being of people with chronic respiratory diseases (CRDs), though most of the evidence derives from trials in high-resource settings.,In low- and middle-income countries, PR services are under-provided.,We aimed to review the effectiveness, components and mode of delivery of PR in low-resource settings.,Following Cochrane methodology, we systematically searched (1990 to October 2018; pre-publication update March 2020) MEDLINE, EMBASE, CABI, AMED, PUBMED, and CENTRAL for controlled clinical trials of adults with CRD (including but not restricted to chronic obstructive pulmonary disease) comparing PR with usual care in low-resource settings.,After duplicate selection, we extracted data on exercise tolerance, health-related quality of life (HRQoL), breathlessness, included components, and mode of delivery.,We used Cochrane risk of bias (RoB) to assess study quality and synthesised data narratively.,From 8912 hits, we included 13 studies: 11 were at high RoB; 2 at moderate RoB.,PR improved functional exercise capacity in 10 studies, HRQoL in 12, and breathlessness in 9 studies.,One of the two studies at moderate RoB showed no benefit.,All programmes included exercise training; most provided education, chest physiotherapy, and breathing exercises.,Low cost services, adapted to the setting, used limited equipment and typically combined outpatient/centre delivery with a home/community-based service.,Multicomponent PR programmes can be delivered in low-resource settings, employing a range of modes of delivery.,There is a need for a high-quality trial to confirm the positive findings of these high/moderate RoB studies. | COPD is associated with significant economic burden.,The objective of this study was to explore the direct and indirect costs associated with COPD and identify the key cost drivers of disease management in Greece.,A Delphi panel of Greek pulmonologists was conducted, which aimed at eliciting local COPD treatment patterns and resource use.,Resource use was translated into costs using official health insurance tariffs and Diagnosis-Related Groups (DRGs).,In addition, absenteeism and caregiver’s costs were recorded in order to quantify indirect COPD costs.,The total costs of managing COPD per patient per year were estimated at €4,730, with direct (medical and nonmedical) and indirect costs accounting for 62.5% and 37.5%, respectively.,COPD exacerbations were responsible for 32% of total costs (€1,512).,Key exacerbation-related cost drivers were hospitalization (€830) and intensive care unit (ICU) admission costs (€454), jointly accounting for 85% of total exacerbation costs.,Annual maintenance phase costs were estimated at €835, with pharmaceutical treatment accounting for 77% (€639.9).,Patient time costs were estimated at €146 per year.,The average number of sick days per year was estimated at 16.9, resulting in productivity losses of €968.,Caregiver’s costs were estimated at €806 per year.,The management of COPD in Greece is associated with intensive resource use and significant economic burden.,Exacerbations and productivity losses are the key cost drivers.,Cost containment policies should focus on prioritizing treatments that increase patient compliance as these can lead to reduction of exacerbations, longer maintenance phases, and thus lower costs. | 1 |
Features of the deaths caused by COPD (chronic obstructive pulmonary disease) in cancer patients remained a controversial issue.,This study aimed to characterize the demographic characteristics and mortality rates of the deaths from COPD in patients with cancer.,In total, 7,846,370 cancer patients aged 40 years or older in the United States were identified from the Surveillance, Epidemiology, and End Results database (1975-2016).,Mortality rates and SMRs (standardized mortality ratios) adjusted by age, race, sex, and calendar year were calculated to investigate the risk of COPD deaths in cancer survivors and to compare it with the general population.,A total of 119,228 COPD deaths in patients with cancer were recorded, with a mortality rate of 261.5/100,000 person-years, nearly two-fold that of the general population (SMR, 2.17; 95% CI [confidence interval], 2.16-2.18).,The proportion of cancer survivors dying from COPD increased from 0.9% in 1975 to 3.4% in 2016.,Patients with lung cancer had a higher overall risk (SMR, 9.23; 95% CI, 9.12-9.35) than those with extrapulmonary malignancies.,Among all extrapulmonary sites, laryngeal (SMR, 5.54; 95% CI, 5.34-5.75) and esophageal cancers (SMR, 4.33; 95% CI, 4.04-4.63) had the highest SMR.,The risk of death from COPD increased with follow-up time. | Airway remodelling is the major pathological feature of chronic obstructive pulmonary disease (COPD), and leads to poorly reversible airway obstruction.,Current pharmacological interventions are ineffective in controlling airway remodelling.,In the present study, we investigated the potential role of artesunate in preventing and treating airway remodelling and the underlying molecular mechanisms in vitro and in vivo.,A COPD rat model was established by cigarette smoke (CS) exposure.,After 12 weeks of artesunate treatment, pathological changes in the lung tissues of COPD rats were examined by ELISA and histochemical and immunohistochemical staining.,A lung functional experiment was also carried out to elucidate the effects of artesunate.,Human bronchial smooth muscle (HBSM) cells were used to clarify the underlying molecular mechanisms.,Artesunate treatment inhibited CS-induced airway inflammation and oxidative stress in a dose-dependent manner and significantly reduced airway remodelling by inhibiting α-smooth muscle actin (α-SMA) and cyclin D1 expression.,PPAR-γ was upregulated and TGF-β1/Smad2/3 signalling was inactivated by artesunate treatment in vivo and in vitro.,Furthermore, PPAR-γ knockdown by siRNA transfection abolished artesunate-mediated inhibition of HBSM cell proliferation by activiting the TGF-β1/Smad2/3 signalling pathway and downregulating the expression of α-SMA and cyclin D1 in HBSM cells.,These findings suggest that artesunate could be used to treat airway remodelling by regulating PPAR-γ/TGF-β1/Smad signalling in the context of COPD.,The online version contains supplementary material available at 10.1186/s12931-021-01687-y. | 1 |
Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV1.,There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline in FEV1.,A cohort of 148 COPD patients (100 men) was monitored daily for a median of 2.91 years (interquartile range [IQR], 2.1 to 4.8).,At recruitment, median age was 68.5 years (IQR, 62.5 to 73.6) and FEV1 as percentage of predicted (FEV1%Pred) was 38.5% (IQR, 27.7 to 50.3).,During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR, 1.48 to 3.96) and FEV1 declined by 40.2 mL/yr or as FEV1%Pred by 1.5%/yr.,Concerning inflammatory markers, sputum interleukin (IL)-6 rose by 9 pg/mL/yr, sputum neutrophil count rose by 1.64 × 106 cells per gram sputum per year, an plasma fibrinogen rose by 0.10 g/L/yr (all p < 0.05).,Patients with frequent exacerbations (≥ 2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063 g/L/yr (p = 0.046, n = 130) and 29.5 pg/mL/yr (p < 0.001, n = 98), respectively, compared to patients with infrequent exacerbations (< 2.52/yr).,Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV1%Pred decline of 0.42%/yr (p = 0.018).,Similarly, a high neutrophil count or fibrinogen were associated with a faster FEV1%Pred decline of 0.97%/yr (p = 0.001) and 0.40%/yr (p = 0.014), respectively.,In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function. | This cohort study of patients with chronic obstructive pulmonary disease (COPD) was performed to evaluate the status of inhaled corticosteroid (ICS) prescriptions following the 2017 revision of the Global Initiative for Chronic Obstructive Lung Disease guidelines.,A total of 1144 patients from the Korean Obstructive Lung Disease and Korea Chronic Obstructive Pulmonary Disorders Subgroup Study cohorts, with final follow-up visits completed between 2017 and 2018, were analyzed.,Features indicative of ICS usage were as follows: a history of asthma, blood eosinophils of ≥300 cells/μl, or ≥ 2 exacerbations in the year prior to enrollment.,Among baseline ICS users, we compared annual total and severe exacerbation rates, based on ICS continuation or withdrawal.,ICS-containing regimens were prescribed to 46.3% of the enrolled of patients in 2014; this decreased to 38.8% in 2017, and long-acting dual bronchodilators were used instead.,Among ICS users in 2017, 47.5% did not exhibit features indicative of ICS usage; 478 used ICS at baseline, and ICS was withdrawn in 77 (16.1%) during the study period.,The proportion of patients with asthma and the baseline annual exacerbation rate were greater in the ICS withdrawal groinup than in the ICS continued group (56.6% vs. 41%, p = 0.01; 0.79 vs.,0.53, p < 0.001).,Annual exacerbation rates during the follow-up period were similar between the ICS-withdrawal and ICS -continued groups (0.48 vs.,0.47, p = 0.84); however, former exhibited a significantly higher rate of severe exacerbation (0.22 vs.,0.12, p = 0.03).,Prescriptions of ICS to treat COPD decreased with increased use of long-acting dual bronchodilators.,ICS withdrawal might impact severe exacerbation; the potential risks and benefits of withdrawing ICS should therefore be considered based on patients’ characteristics. | 1 |
Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. | Apoptosis plays a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD), and this process can be regulated by mitochondrial transcription factor A (mtTFA).,Epigenetics is involved in the regulation and modification of the genes involved in lung cancer and COPD.,In this study, we determined the expression of mtTFA and its methylation levels in the COPD patients with lung cancer.,Twenty-one squamous cell lung cancer patients, 11 with COPD and 10 without COPD, undergoing pneumonectomy were enrolled.,The apoptotic index (AI) of pulmonary vascular endothelial cells was analyzed by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay.,The expression of mtTFA mRNA and protein was measured using PCR, immunohistochemistry and Western-blot.,Methylation of the mtTFA promoter was detected using bisulfite sequencing PCR.,Compared to the non-COPD group, the AI was higher, and expression of mtTFA mRNA and protein was lower in the COPD group (P<0.001).,Expression of the mtTFA protein was positively correlated with FEV1/Pre (r = 0.892, P<0.001), and negatively correlated with AI (r = −0.749, P<0.001) and smoke index (r = −0.763, P<0.001).,Percentage of mtTFA promoter methylation in the COPD patients was significantly higher compared to the non-COPD patients (P<0.05).,These results suggest that the expression of mtTFA mRNA and protein is down-regulated in the lung tissue from the COPD patients with squamous cell lung cancer, and the level of mtTFA protein is related to apoptosis of pulmonary vascular endothelial cells.,Aberrant mtTFA methylation may also play an important role in the pathogenesis of COPD. | 1 |
Purpose: COPD patients often do not report acute exacerbations to healthcare providers - unreported exacerbations.,It is not known whether variances in symptoms, airway obstruction, aetiology and inflammatory responses account for differences in reporting of COPD exacerbations.,The aims of the study were to compare symptoms, lung function changes, aetiology and inflammatory markers between exacerbations that were reported to healthcare providers or treated, with those that were unreported and untreated.,Patients and methods: We recruited a cohort of COPD patients and collected clinical data and blood and airway samples when stable and during acute exacerbations.,Virological and bacterial analyses were carried out and inflammatory markers measured.,Results: We found no differences in symptoms, lung function, incidence of infection and inflammatory markers between reported and unreported exacerbations.,Subjects who reported all exacerbations had higher BODE scores, lower FEV1 and more exacerbations compared with those who did not.,Conclusion: The failure to report exacerbations is not related to the severity, aetiology or inflammatory profile of the exacerbation.,Patients with less severe COPD and less frequent exacerbations are less likely to report exacerbations.,The decision to report an exacerbation is not an objective marker of exacerbation severity and therefore studies that do not count unreported exacerbations will underestimate the frequency of clinically significant exacerbations.,A better understanding of the factors that determine non-reporting of exacerbations is required to improve exacerbation reporting.,Trial registration: ClinicalTrials.gov Identifier: NCT01376830.,Registered June 17, 2011 | Telehealth is an approach to disease management, which may hold the potential of improving some of the features associated with COPD, including positive impact on disease progression, and thus possibly limiting further reduction in quality of life (QoL).,Our objective was, therefore, to summarize studies addressing the impact of telehealth on QoL in patients with COPD.,Systematic review.,A series of systematic searches were carried out using the following databases: PubMed, EMBASE, Cochrane Controlled Trials Register, and ClinicalTrials.gov (last updated November 2015).,A predefined search algorithm was utilized with the intention to capture all results related to COPD, QoL, and telehealth published since year 2000.,Primary outcome was QoL, assessed by validated measures.,Out of the 18 studies fulfilling the criteria for inclusion in this review, three studies found statistically significant improvements in QoL for patients allocated to telemedical interventions.,However, all of the other included studies found no statistically significant differences between control and telemedical intervention groups in terms of QoL.,Telehealth does not make a strong case for itself when exclusively looking at QoL as an outcome, since statistically significant improvements relative to control groups have been observed only in few of the available studies.,Nonetheless, this does not only rule out the possibility that telehealth is superior to standard care with regard to other outcomes but also seems to call for more research, not least in large-scale controlled trials. | 1 |
Fat-free mass (FFM) depletion has been shown to be a better predictor of mortality than BMI in chronic obstructive pulmonary disease (COPD) patients.,The specific aim of the current study was to assess the nutritional status of stable COPD patients in relation to fat free mass index profiles.,We investigated 65 male moderate-to-severe stable COPD patients.,A self-reported questionnaire was applied about general characteristics and smoking history.,Nutritional intake was assessed by using a 54-item quantitative food frequency questionnaire.,Weight, height, mid-upper arm circumference (MUAC), waist circumference (WC), handgrip strength and body composition measurements were taken by a trained dietitian.,The data were analyzed with SPSS 15.0 software.,The mean age of the patients was 62.1 ± 8.9 years.,Among all of the patients 13.8% was underweight (BMI < 21 kg/m2) and 18.5% had a low fat-free mass index (FFMI < 16 kg/m2).,The percentages of the patients who did not meet the daily recommended intakes (RNI) were highest for magnesium (93.8%) and calcium (92.3%).,Mean daily consumptions of milk-yogurt, red meat and fruits were significantly low in the low FFMI group compared to normal FFMI group (for all; p < 0.05).,Patients with normal FFMI had significantly higher weight, height, WC, MUAC, handgrip strength, fat and fat-free mass than the patients with low FFMI (for all; p < 0.05).,Dieticians should be aware of COPD patients with low FFMI in order to evaluate the nutritional intake and therefore plan nutritional strategies to improve prognosis of the disease. | Being overweight or obese is associated with a higher rate of survival in patients with advanced chronic obstructive pulmonary disease (COPD).,This paradoxical relationship indicates that the influence of nutritional status on functional parameters should be further investigated.,To investigate the impact of nutritional status on body composition, exercise capacity and respiratory muscle strength in severe chronic obstructive pulmonary disease patients.,Thirty-two patients (nine women) were divided into three groups according to their body mass indices (BMI): overweight/obese (25 ≤ BMI ≤ 34.9 kg/m2, n=8), normal weight (18.5 ≤ BMI ≤ 24.9 kg/m2, n=17) and underweight (BMI <18.5 kg/m2, n=7).,Spirometry, bioelectrical impedance, a six-minute walking distance test and maximal inspiratory and expiratory pressures were assessed.,Airway obstruction was similar among the groups (p=0.30); however, overweight/obese patients had a higher fat-free mass (FFM) index [FFMI=FFM/body weight2 (mean±SEM: 17±0.3 vs.,15±0.3 vs.,14±0.5 m/kg2, p<0.01)], exercise capacity (90±8 vs. 79±6 vs. 57±8 m, p=0.02) and maximal inspiratory pressure (63±7 vs. 57±5 vs. 35±8 % predicted, p=0.03) in comparison to normal weight and underweight patients, respectively.,In addition, on backward multiple regression analysis, FFMI was the unique independent predictor of exercise capacity (partial r=0.52, p<0.01).,Severe chronic obstructive pulmonary disease (COPD) patients who were overweight or obese had a greater FFM, exercise capacity and inspiratory muscle strength than patients with the same degree of airflow obstruction who were of normal weight or underweight, and higher FFM was independently associated with higher exercise capacity.,These characteristics of overweight or obese patients might counteract the drawbacks of excess weight and lead to an improved prognosis in COPD. | 1 |
Concerns have been raised that treatment of COPD with inhaled corticosteroids may increase pneumonia risk.,Responding to a request from the European Medicines Agency Pharmacovigilance Risk Assessment Committee, a pooled analysis of interventional studies compared pneumonia risk with inhaled budesonide-containing versus non-budesonide-containing treatments and the impact of other clinically relevant factors.,AstraZeneca-sponsored, parallel-group, double-blind, randomized controlled trials meeting the following criteria were included: >8 weeks’ duration; ≥60 patients with COPD; inhaled budesonide treatment arm (budesonide/formoterol or budesonide); and non-budesonide-containing comparator arm (formoterol or placebo).,Primary and secondary outcomes were time to first pneumonia treatment-emergent serious adverse event (TESAE) and treatment-emergent adverse event (TEAEs), respectively, analyzed using Cox regression models stratified by study.,Eleven studies were identified; 10,570 out of 10,574 randomized patients receiving ≥1 dose of study treatment were included for safety analysis (budesonide-containing, n=5,750; non-budesonide-containing, n=4,820).,Maximum exposure to treatment was 48 months.,The overall pooled hazard ratio (HR), comparing budesonide versus non-budesonide-containing treatments, was 1.15 for pneumonia TESAEs (95% confidence interval [CI]: 0.83, 1.57) and 1.13 for pneumonia TEAEs (95% CI: 0.94, 1.36).,The annual incidence of pneumonia TESAEs was 1.9% and 1.5% for budesonide-containing and non-budesonide-containing treatments, respectively.,Comparing budesonide/formoterol with non-budesonide-containing treatment, the HRs for pneumonia TESAEs and TEAEs were 1.00 (95% CI: 0.69, 1.44) and 1.21 (95% CI: 0.93, 1.57), respectively.,For budesonide versus placebo, HRs were 1.57 for pneumonia TESAEs (95% CI: 0.90, 2.74) and 1.07 for pneumonia TEAEs (95% CI: 0.83, 1.38).,This pooled analysis found no statistically significant increase in overall risk for pneumonia TESAEs or TEAEs with budesonide-containing versus non-budesonide-containing treatments.,However, a small increase in risk with budesonide-containing treatment cannot be ruled out; there is considerable heterogeneity in study designs and patient characteristics, particularly in the early budesonide studies, and each study contributes <40 pneumonia TESAEs. | Non-invasive phenotyping of chronic respiratory diseases would be highly beneficial in the personalised medicine of the future.,Volatile organic compounds can be measured in the exhaled breath and may be produced or altered by disease processes.,We investigated whether distinct patterns of these compounds were present in chronic obstructive pulmonary disease (COPD) and clinically relevant disease phenotypes.,Breath samples from 39 COPD subjects and 32 healthy controls were collected and analysed using gas chromatography time-of-flight mass spectrometry.,Subjects with COPD also underwent sputum induction.,Discriminatory compounds were identified by univariate logistic regression followed by multivariate analysis: 1. principal component analysis; 2. multivariate logistic regression; 3. receiver operating characteristic (ROC) analysis.,Comparing COPD versus healthy controls, principal component analysis clustered the 20 best-discriminating compounds into four components explaining 71% of the variance.,Multivariate logistic regression constructed an optimised model using two components with an accuracy of 69%.,The model had 85% sensitivity, 50% specificity and ROC area under the curve of 0.74.,Analysis of COPD subgroups showed the method could classify COPD subjects with far greater accuracy.,Models were constructed which classified subjects with ≥2% sputum eosinophilia with ROC area under the curve of 0.94 and those having frequent exacerbations 0.95.,Potential biomarkers correlated to clinical variables were identified in each subgroup.,The exhaled breath volatile organic compound profile discriminated between COPD and healthy controls and identified clinically relevant COPD subgroups.,If these findings are validated in prospective cohorts, they may have diagnostic and management value in this disease. | 1 |
Frequent exacerbators are a specific phenotype of chronic obstructive pulmonary disease (COPD), whose clinical characteristics and prognostic biomarkers during severe acute exacerbation (AECOPD) have not yet been fully elucidated.,The aim of this study was to investigate the clinical features of severe AECOPD in frequent exacerbators and explore the predictive value of the neutrophil-to-lymphocyte ratio (NLR) for outcome in this phenotype during severe exacerbation.,A total of 604 patients with severe AECOPD were retrospectively included in the study.,Subjects were defined as frequent exacerbators if they experienced two or more exacerbations in the past year.,Clinical characteristics and worse outcome (ICU admission, or invasive ventilation, or in-hospital mortality) during severe AECOPD were compared between frequent exacerbators and non-frequent ones.,Furthermore, the relationship between NLR and worse outcome in frequent exacerbators was analyzed using logistic regression and receiver operating characteristic (ROC).,Among 604 patients with severe AECOPD, 282 (46.69%) were frequent exacerbators and 322 (53.31%) were non-frequent exacerbators.,Compared with the non-frequent ones, frequent exacerbators presented higher levels of NLR (5.93 [IQR, 3.40-9.28] vs 4.41 [IQR, 2.74-6.80]; p<0.001), and more worse outcome incidence (58 [20.57%] vs 38 [11.80%]; p=0.003).,Moreover, among the frequent exacerbators, NLR levels in the patients with worse outcome were much higher than in those without worse outcome (11.09 [IQR, 7.74-16.49] vs 5.28 [IQR, 2.93-7.93]; p<0.001).,Increased NLR was significantly associated with a higher risk of worse outcome in frequent exacerbators (OR, 1.43; 95% CI, 1.28-1.64; p<0.001).,Furthermore, ROC analysis revealed that a cut-off value of 10.23, NLR could predict worse outcome of severe AECOPD in frequent exacerbators (sensitivity 62.1%, specificity 92.0%, AUC 0.833).,Frequent exacerbators exhibited an increased level of NLR and a higher proportion of worse outcome during severe AECOPD.,NLR is expected to be a promising predictive biomarker for the prognosis of severe AECOPD in frequent exacerbators. | The major characteristic of COPD is systemic inflammation.,The parameters such as neutrophil-to-lymphocyte ratio (NLR) and eosinophil-to-basophil ratio (EBR) in routine blood test (RBT) are considered to be the underlying biomarkers of inflammation.,We hypothesized that the prognosis of patients with COPD can be predicted with RBT.,Patients with COPD in stable stage were enrolled.,The RBT, pulmonary function testing (PFT), BODE index, C-reactive protein (CRP), procalcitonin, and erythrocyte sedimentation rate (ESR) were performed at enrollment and every follow-up once in every 3 months during the 24-month follow-up period.,Meanwhile, exacerbation count and mortality incidence were recorded.,The correlation between the prognostic biomarkers and the prognosis of patients was analyzed.,The NLR and EBR in RBT have a significant correlation with the severity of patients with COPD.,The NLR is an independent predictor for mortality and the EBR is an independent predictor for exacerbation.,As an inexpensive, accessible, and convenient assay, RBT may be used as a practical means in the prediction of prognosis of patients with COPD in future clinical settings. | 1 |
The molecular and clinical features of a complex disease can be influenced by other diseases affecting the same individual.,Understanding disease-disease interactions is therefore crucial for revealing shared molecular mechanisms among diseases and designing effective treatments.,Here we introduce Flow Centrality (FC), a network-based approach to identify the genes mediating the interaction between two diseases in a protein-protein interaction network.,We focus on asthma and COPD, two chronic respiratory diseases that have been long hypothesized to share common genetic determinants and mechanisms.,We show that FC highlights potential mediator genes between the two diseases, and observe similar outcomes when applying FC to 66 additional pairs of related diseases.,Further, we perform in vitro perturbation experiments on a widely replicated asthma gene, GSDMB, showing that FC identifies candidate mediators of the interactions between GSDMB and COPD-associated genes.,Our results indicate that FC predicts promising gene candidates for further study of disease-disease interactions.,Complex diseases often share genetic determinants and symptoms, but the mechanistic basis of disease interactions remains elusive.,Here, the authors propose a network topological measure to identify proteins linking complex diseases in the interactome, and identify mediators between COPD and asthma. | Since the discovery of alpha-1 antitrypsin in the early 1960s, several new genes have been suggested to play a role in chronic obstructive pulmonary disease (COPD) pathogenesis.,Yet, in spite of those advances, much about the genetic basis of COPD still remains to be discovered.,Unbiased approaches, such as genome-wide association (GWA) studies, are critical to identify genes and pathways and to verify suggested genetic variants.,Indeed, most of our current understanding about COPD candidate genes originates from GWA studies.,Experiments in form of cross-study replications and advanced meta-analyses have propelled the field towards unravelling details about COPD's pathogenesis.,Here, we review the discovery of genetic variants in association with COPD phenotypes by discussing the available approaches and current findings.,Limitations of current studies are considered and future directions provided. | 1 |
Individuals with COPD may present reduced peripheral muscle strength, leading to impaired mobility.,Comprehensive pulmonary rehabilitation (PR) should include strength training, in particular to lower limbs.,Furthermore, simple tools for the assessment of peripheral muscle performance are required.,To assess the peripheral muscle performance of COPD patients by the sit-to-stand test (STST), as compared to the one-repetition maximum (1-RM), considered as the gold standard for assessing muscle strength in non-laboratory situations, and to evaluate the responsiveness of STST to a PR program.,Sixty moderate-to-severe COPD inpatients were randomly included into either the specific strength training group or into the usual PR program group.,Patients were assessed on a 30-second STST and 1-minute STST, 1-RM, and 6-minute walking test (6MWT), before and after PR.,Bland-Altman plots were used to evaluate the agreement between 1-RM and STST.,The two groups were not different at baseline.,In all patients, 1-RM was significantly related to the 30-second STST (r=0.48, P<0.001) and to 1-minute STST (r=0.36, P=0.005).,The 30-second STST was better tolerated in terms of the perceived fatigue (P=0.002) and less time consuming (P<0.001) test.,In the specific strength training group significant improvements were observed in the 30-second STST (P<0.001), 1-minute STST (P=0.005), 1-RM (P<0.001), and in the 6MWT (P=0.001).,In the usual PR program group, significant improvement was observed in the 30-second STST (P=0.042) and in the 6MWT (P=0.001).,Our study shows that in stable moderate-to-severe inpatients with COPD, STST is a valid and reliable tool to assess peripheral muscle performance of lower limbs, and is sensitive to a specific PR program. | Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability internationally.,Alveolar hypoxia and consequent hypoxemia increase in prevalence as disease severity increases.,Ventilation/perfusion mismatch resulting from progressive airflow limitation and emphysema is the key driver of this hypoxia, which may be exacerbated by sleep and exercise.,Uncorrected chronic hypoxemia is associated with the development of adverse sequelae of COPD, including pulmonary hypertension, secondary polycythemia, systemic inflammation, and skeletal muscle dysfunction.,A combination of these factors leads to diminished quality of life, reduced exercise tolerance, increased risk of cardiovascular morbidity, and greater risk of death.,Concomitant sleep-disordered breathing may place a small but significant subset of COPD patients at increased risk of these complications.,Long-term oxygen therapy has been shown to improve pulmonary hemodynamics, reduce erythrocytosis, and improve survival in selected patients with severe hypoxemic respiratory failure.,However, the optimal treatment for patients with exertional oxyhemoglobin desaturation, isolated nocturnal hypoxemia, or mild-to-moderate resting daytime hypoxemia remains uncertain. | 1 |
Chronic bronchitis (CB) has been related to poor outcomes in Chronic Obstructive Pulmonary Disease (COPD).,From a clinical standpoint, we have shown that subjects with CB in a group with moderate to severe airflow obstruction were younger, more likely to be current smokers, male, Caucasian, had worse health related quality of life, more dyspnea, and increased exacerbation history compared to those without CB.,We sought to further refine our clinical characterization of chronic bronchitics in a larger cohort and analyze the CT correlates of CB in COPD subjects.,We hypothesized that COPD patients with CB would have thicker airways and a greater history of smoking, acute bronchitis, allergic rhinitis, and occupational exposures compared to those without CB.,We divided 2703 GOLD 1-4 subjects in the Genetic Epidemiology of COPD (COPDGene®) Study into two groups based on symptoms: chronic bronchitis (CB+, n = 663, 24.5%) and no chronic bronchitis (CB-, n = 2040, 75.5%).,Subjects underwent extensive clinical characterization, and quantitative CT analysis to calculate mean wall area percent (WA%) of 6 segmental airways was performed using VIDA PW2 (http://www.vidadiagnostics.com).,Square roots of the wall areas of bronchi with internal perimeters 10 mm and 15 mm (Pi10 and Pi15, respectively), % emphysema, %gas trapping, were calculated using 3D Slicer (http://www.slicer.org).,There were no differences in % emphysema (11.4 ± 12.0 vs.,12.0 ± 12.6%, p = 0.347) or % gas trapping (35.3 ± 21.2 vs.,36.3 ± 20.6%, p = 0.272) between groups.,Mean segmental WA% (63.0 ± 3.2 vs.,62.0 ± 3.1%, p < 0.0001), Pi10 (3.72 ± 0.15 vs.,3.69 ± 0.14 mm, p < 0.0001), and Pi15 (5.24 ± 0.22 vs.,5.17 ± 0.20, p < 0.0001) were greater in the CB + group.,Greater percentages of gastroesophageal reflux, allergic rhinitis, histories of asthma and acute bronchitis, exposures to dusts and occupational exposures, and current smokers were seen in the CB + group.,In multivariate binomial logistic regression, male gender, Caucasian race, a lower FEV1%, allergic rhinitis, history of acute bronchitis, current smoking, and increased airway wall thickness increased odds for having CB.,Histories of asthma, allergic rhinitis, acute bronchitis, current smoking, a lower FEV1%, Caucasian race, male gender, and increased airway wall thickness are associated with CB.,These data provide clinical and radiologic correlations to the clinical phenotype of CB. | The receptor for advanced glycation end products (RAGE) is a multiligand signal transduction receptor that can initiate and perpetuate inflammation.,Its soluble isoform (sRAGE) acts as a decoy receptor for RAGE ligands, and is thought to afford protection against inflammation.,With the present study, we aimed at determining whether circulating sRAGE is correlated with emphysema and chronic cor pulmonale in chronic obstructive pulmonary disease (COPD).,In 200 COPD patients and 201 age- and sex-matched controls, we measured lung function by spirometry, and sRAGE by ELISA method.,We also measured the plasma levels of two RAGE ligands, N-epsilon-carboxymethyl lysine and S100A12, by ELISA method.,In the COPD patients, we assessed the prevalence and severity of emphysema by computed tomography (CT), and the prevalence of chronic cor pulmonale by echocardiography.,Multiple quantile regression was used to assess the effects of emphysema, chronic cor pulmonale, smoking history, and comorbid conditions on the three quartiles of sRAGE.,sRAGE was significantly lower (p = 0.007) in COPD patients (median 652 pg/mL, interquartile range 484 to 1076 pg/mL) than in controls (median 869 pg/mL, interquartile range 601 to 1240 pg/mL), and was correlated with the severity of emphysema (p < 0.001), the lower the level of sRAGE the greater the degree of emphysema on CT.,The relationship remained statistically significant after adjusting for smoking history and comorbid conditions.,In addition, sRAGE was significantly lower in COPD patients with chronic cor pulmonale than in those without (p = 0.002).,Such difference remained statistically significant after adjusting for smoking history, comorbidities, and emphysema severity.,There was no significant difference in the plasma levels of the two RAGE ligands between cases and controls.,sRAGE is significantly lower in patients with COPD than in age- and sex-matched individuals without airflow obstruction.,Emphysema and chronic cor pulmonale are independent predictors of reduced sRAGE in COPD. | 1 |
Inhaled corticosteroids (ICS) are associated with an increased risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD).,Other factors such as severity of airflow limitation and concurrent asthma may further raise the possibility of developing pneumonia.,This study assessed the risk of pneumonia associated with ICS in patients with COPD.,Electronic Medical Record data linked to National Health Registries were collected from COPD patients and matched reference controls in 52 Swedish primary care centers (2000-2014).,Levels of ICS treatment (high, low, no ICS) and associated comorbidities were assessed.,Patients were categorized by airflow limitation severity.,A total of 6623 patients with COPD and 48,566 controls were analyzed.,Patients with COPD had a more than 4-fold increase in pneumonia versus reference controls (hazard ratio [HR] 4.76, 95% confidence interval [CI]: 4.48-5.06).,ICS use increased the risk of pneumonia by 20-30% in patients with COPD with forced expiratory volume in 1 s ≥ 50% versus patients not using ICS.,Asthma was an independent risk factor for pneumonia in the COPD population.,Multivariate analysis identified independent predictors of pneumonia in the overall population.,The highest risk of pneumonia was associated with high dose ICS (HR 1.41, 95% CI: 1.23-1.62).,Patients with COPD have a greater risk of pneumonia versus reference controls; ICS use and concurrent asthma increased the risk of pneumonia further. | The diagnosis of COPD is dependent upon clinical judgment and confirmation of the presence of airflow obstruction using spirometry.,Spirometry is now routinely available; however, spirometry incorrectly performed or interpreted can lead to misdiagnosis.,We aimed to determine whether spirometry undertaken in primary care for patients suspected to have COPD was of sufficient quality and whether their spirometry was correctly interpreted.,Two chest physicians re-read all spirometric readings for both quality of the procedure and interpretation, received as a part of COPD validation studies using data from the Clinical Practice Research Datalink (CPRD).,We then used logistic regression to investigate predictors of correct interpretation.,Spirometry traces were obtained for 306 patients, of which 221 (72.2%) were conducted in primary care.,Of those conducted in primary care, 98.6% (n=218) of spirometry traces were of adequate quality.,Of those traces that were of adequate quality and conducted in primary care, and in whom a general practitioner (GP) diagnosis of COPD had been made, 72.5% (n=218) were consistent with obstruction.,Historical records for asthma diagnosis significantly decreased odds of correct interpretation.,The quality of the spirometry procedure undertaken in primary care is high.,However, this was not reflected in the quality of interpretation, suggesting an unmet training in primary care.,The quality of the spirometry procedure as demonstrated by spirometric tracings provides a re-assurance for the use of spirometric values available in the electronic health care record databases for research purposes. | 1 |
Severe exacerbations of COPD, ie, those leading to hospitalization, have profound clinical implications for patients and significant economic consequences for society.,The prevalence and burden of severe COPD exacerbations remain high, despite recognition of the importance of exacerbation prevention and the availability of new treatment options.,Severe COPD exacerbations are associated with high mortality, have negative impact on quality of life, are linked to cardiovascular complications, and are a significant burden on the health-care system.,This review identified risk factors that contribute to the development of severe exacerbations, treatment options (bronchodilators, antibiotics, corticosteroids [CSs], oxygen therapy, and ventilator support) to manage severe exacerbations, and strategies to prevent readmission to hospital.,Risk factors that are amenable to change have been highlighted.,A number of bronchodilators have demonstrated successful reduction in risk of severe exacerbations, including long-acting muscarinic antagonist or long-acting β2-agonist mono- or combination therapies, in addition to vaccination, mucolytic and antibiotic therapy, and nonpharmacological interventions, such as pulmonary rehabilitation.,Recognition of the importance of severe exacerbations is an essential step in improving outcomes for patients with COPD.,Evidence-based approaches to prevent and manage severe exacerbations should be implemented as part of targeted strategies for disease management. | The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | 1 |
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. | In the 2014 Global initiative for chronic Obstructive Lung Disease guidelines, bronchiectasis was for the first time defined as a comorbidity of chronic obstructive pulmonary disease (COPD), and this change has been retained in the 2015 update, which emphasizes the influence of bronchiectasis in the natural history of COPD.,The present meta-analysis was aimed at summarizing the impact of bronchiectasis on patients with COPD.,Databases including Embase, PubMed, and the Cochrane Central Register of Controlled Trials were searched comprehensively to identify all relevant human clinical studies published until August 2014.,Bronchiectasis was confirmed either by computed tomography or high-resolution computed tomography.,One or more clinicopathological or demographical characteristics, including age, sex, smoking history, daily sputum production, exacerbations, inflammatory biomarkers, lung function, and colonization by potentially pathogenic microorganisms (PPMs), were compared between COPD patients with and without bronchiectasis.,Six observational studies with 881 patients were included in the meta-analysis.,The mean prevalence of bronchiectasis in patients with COPD was 54.3%, ranging from 25.6% to 69%.,Coexistence of bronchiectasis and COPD occurred more often in male patients with longer smoking history.,Patients with COPD and comorbid bronchiectasis had greater daily sputum production, more frequent exacerbation, poorer lung function, higher level of inflammatory biomarkers, more chronic colonization by PPMs, and higher rate of Pseudomonas aeruginosa isolation.,In spite of the heterogeneity between included studies and detectable publication bias, this meta-analysis demonstrated the impact of bronchiectasis in patients with COPD in all directions, indicating that coexistence of bronchiectasis should be considered a pathological phenotype of COPD, which may have a predictive value. | 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. | Chronic obstructive pulmonary disease (COPD) is a preventable and treatable lung disease characterized by airflow limitation that is not fully reversible.,In a significant proportion of patients with COPD, reduced lung elastic recoil combined with expiratory flow limitation leads to lung hyperinflation during the course of the disease.,Development of hyperinflation during the course of COPD is insidious.,Dynamic hyperinflation is highly prevalent in the advanced stages of COPD, and new evidence suggests that it also occurs in many patients with mild disease, independently of the presence of resting hyperinflation.,Hyperinflation is clinically relevant for patients with COPD mainly because it contributes to dyspnea, exercise intolerance, skeletal muscle limitations, morbidity, and reduced physical activity levels associated with the disease.,Various pharmacological and nonpharmacological interventions have been shown to reduce hyperinflation and delay the onset of ventilatory limitation in patients with COPD.,The aim of this review is to address the more recent literature regarding the pathogenesis, assessment, and management of both static and dynamic lung hyperinflation in patients with COPD.,We also address the influence of biological sex and obesity and new developments in our understanding of hyperinflation in patients with mild COPD and its evolution during progression of the disease. | 1 |
Supplemental Digital Content is available in the text.,Cardiovascular disease is a common comorbidity and cause of mortality in chronic obstructive pulmonary disease.,A better understanding of mechanisms of cardiovascular risk in chronic obstructive pulmonary disease patients is needed to improve clinical outcomes.,We hypothesized that such patients have increased arterial stiffness, wave reflections, and subclinical atherosclerosis compared with controls and that these findings would be independent of smoking status and other confounding factors.,A total of 458 patients with a diagnosis of chronic obstructive pulmonary disease and 1657 controls (43% were current or ex-smokers) with no airflow limitation were matched for age, sex, and body mass index.,All individuals underwent assessments of carotid-femoral (aortic) pulse wave velocity, augmentation index, and carotid intima-media thickness.,The mean age of the cohort was 67±8 years and 58% were men.,Patients with chronic obstructive pulmonary disease had increased aortic pulse wave velocity (9.95±2.54 versus 9.27±2.41 m/s; P<0.001), augmentation index (28±10% versus 25±10%; P<0.001), and carotid intima-media thickness (0.83±0.19 versus 0.74±0.14 mm; P<0.001) compared with controls.,Chronic obstructive pulmonary disease was associated with increased levels of each vascular biomarker independently of physiological confounders, smoking, and other cardiovascular risk factors.,In this large case-controlled study, chronic obstructive pulmonary disease was associated with increased arterial stiffness, wave reflections, and subclinical atherosclerosis, independently of traditional cardiovascular risk factors.,These findings suggest that the cardiovascular burden observed in this condition may be mediated through these mechanisms and supports the concept that chronic obstructive pulmonary disease is an independent risk factor for cardiovascular disease. | 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 |
Chronic obstructive pulmonary disease (COPD) is associated with local and systemic inflammation.,The knowledge of interaction and co-variation of the inflammatory responses in different compartments is meagre.,Healthy controls (n = 23), smokers with (n = 28) and without (n = 29) COPD performed spirometry and dental examinations.,Saliva, induced sputum, bronchoalveolar lavage (BAL) fluid and serum were collected.,Inflammatory markers were assessed in all compartments using ELISA, flow cytometry and RT-PCR.,Negative correlations between lung function and saliva IL-8 and matrix metalloproteinase-9 (MMP-9) were found in smokers with COPD.,IL-8 and MMP-9 in saliva correlated positively with periodontal disease as assessed by gingival bleeding in non-smokers.,Tumor necrosis factor-α (TNF-α) in saliva, serum and TNF-α mRNA expression on macrophages in BAL-fluid were lower in smokers than in non-smokers.,There were positive correlations between soluble TNF-α receptor 1 (sTNFR1) and soluble TNF-α receptor 2 (sTNFR2) in sputum, BAL-fluid and serum in all groups.,Sputum interleukin-8 (IL-8) or interleukin-6 (IL-6) was positively correlated with sTNFR1 or sTNFR2 in non-smokers and with sTNFR2 in COPD.,Saliva which is convenient to collect and analyse, may be suitable for biomarker assessment of disease activity in COPD.,An attenuated TNF-α expression was demonstrated by both protein and mRNA analyses in different compartments suggesting that TNF-α response is altered in moderate and severe COPD.,Shedding of TNFR1 or TNFR2 is similarly regulated irrespective of airflow limitation. | Genetic factors play a role in the development and severity of chronic obstructive pulmonary disease (COPD).,The pathogenesis of COPD is a multifactorial process including an inflammatory cell profile.,Recent studies revealed that single nucleotide polymorphisms (SNPs) within ADAM33 increased the susceptibility to COPD through changing the airway inflammatory process and lung function.,In this paper, we investigated associations of four polymorphisms (T1, T2, S2 and Q-1) of ADAM33 as well as their haplotypes with pulmonary function and airway inflammatory process in an East Asian population of patients with COPD.,We found that T1, T2 and Q-1 were significantly associated with the changes of pulmonary function and components of cells in sputum of COPD, and T1 and Q-1 were significantly associated with cytokines and mediators of inflammation in airway of COPD in recessive models. 10 haplotypes were significantly associated with transfer factor of the lung for carbon monoxide in the disease state, 4 haplotypes were significantly associated with forced expiratory volume in one second, and other haplotypes were associated with airway inflammation.,We confirmed for the first time that ADAM33 was involved in the pathogenesis of COPD by affecting airway inflammation and immune response in an East Asian population.,Our results made the genetic background of COPD, a common and disabling disease, more apparent, which would supply genetic support for the study of the mechanism, classification and treatment for this disease.,The online version of this article (doi:10.1186/1471-2466-14-173) contains supplementary material, which is available to authorized users. | 1 |
Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020.,No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers.,We systematically searched electronic databases from inception to March 24, 2020.,Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.,Study quality was assessed using a modified version of the Newcastle-Ottawa Scale.,We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI).,In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed.,A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients.,All studies were included in the meta-analysis.,The crude case fatality rate of COVID-19 was 7.4%.,The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively.,COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)].,This was associated with higher mortality (60%).,Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications.,The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers.,Current smokers also had a higher mortality rate of 38.5%.,Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD.,Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate.,Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers. | Chronic obstructive pulmonary disease (COPD) is the leading cause of death worldwide, and poses a substantial economic and social burden.,Telemonitoring has been proposed as a solution to this growing problem, but its impact on patient outcome is equivocal.,This randomized controlled trial aimed to investigate effectiveness of telemonitoring in improving COPD patient outcome.,In total, 106 subjects were randomly assigned to the telemonitoring (n = 53) or usual care (n = 53) group.,During the two months following discharge, telemonitoring group patients had to report their symptoms daily using an electronic diary.,The primary outcome measure was time to first re-admission for COPD exacerbation within six months of discharge.,During the follow-up period, time to first re-admission for COPD exacerbation was significantly increased in the telemonitoring group than in the usual care group (p = 0.026).,Telemonitoring was also associated with a reduced number of all-cause re-admissions (0.23 vs.,0.68/patient; p = 0.002) and emergency room visits (0.36 vs.,0.91/patient; p = 0.006).,In conclusion, telemonitoring intervention was associated with improved outcomes among COPD patients admitted for exacerbation in a country characterized by a small territory and high accessibility to medical services.,The findings are encouraging and add further support to implementation of telemonitoring as part of COPD care. | 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 | COPD is a leading cause of morbidity and mortality worldwide.,Patients suffer from refractory breathlessness, unrecognized anxiety and depression, and decreased quality of life.,Palliative care improves symptom management, patient reported health-related quality of life, cost savings, and mortality though the majority of patients with COPD die without access to palliative care.,There are many barriers to providing palliative care to patients with COPD including the difficulty in prognosticating a patient’s course causing referrals to occur late in a patient’s disease.,Additionally, physicians avoid conversations about advance care planning due to unique communication barriers present with patients with COPD.,Lastly, many health systems are not set up to provide trained palliative care physicians to patients with chronic disease including COPD.,This review analyzes the above challenges, the available data regarding palliative care applied to the COPD population, and proposes an alternative approach to address the unmet needs of patients with COPD with proactive primary palliative care. | 1 |
Among patients with chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM) is a common comorbidity and is probably associated with increased systemic inflammation and worse prognosis.,Metformin, with its pleiotropic anti-inflammatory and antioxidant actions, may offer theoretical benefits in COPD patients with DM.,Thus, this study aimed to investigate the effects of DM and metformin use on mortality in the clinical trajectory of COPD.,This was a retrospective cohort study comprising patients with spirometry-confirmed COPD and an age of ≥40 years from 2008 to 2014.,The primary outcome of interest was all-cause mortality.,We evaluated the effects of DM on mortality through the clinical course of COPD and we also assessed the impact of metformin use on survival of the COPD population.,Among 4231 COPD patients, 556 (13%) had DM, and these patients had 1.62 times higher hazards of 2-year mortality than those without DM (95% confidence interval [CI], 1.15-2.28) after adjusting for age, gender, COPD stage, comorbidities and prior COPD hospitalization.,Over a 2-year period, metformin users had a significantly lower risk of death (hazard ratio, 0.46; 95% CI, 0.23-0.92) compared with non-metformin users in patients with coexistent COPD and DM.,Moreover, metformin users had similar survival to COPD patients without DM.,This study shows that DM is associated with an increased risk of death in COPD patients and metformin use seems to mitigate the hazard.,Our findings suggest a potential role of metformin in the management of DM in COPD.,The online version of this article (10.1186/s12931-019-1035-9) contains supplementary material, which is available to authorized users. | Severe exacerbations of COPD are commonly associated with hyperglycaemia, which predicts adverse outcomes.,Metformin is a well-established anti-hyperglycaemic agent in diabetes mellitus, possibly augmented with anti-inflammatory effects, but its effects in COPD are unknown.,We investigated accelerated metformin therapy in severe COPD exacerbations, primarily to confirm or refute an anti-hyperglycaemic effect, and secondarily to explore its effects on inflammation and clinical outcome.,This was a multicentre, randomised, double-blind, placebo-controlled trial testing accelerated metformin therapy in non-diabetic patients, aged ≥35 years, hospitalised for COPD exacerbations.,Participants were assigned in a 2:1 ratio to 1 month of metformin therapy, escalated rapidly to 2 g/day, or matched placebo.,The primary end point was mean in-hospital blood glucose concentration.,Secondary end points included the concentrations of fructosamine and C reactive protein (CRP), and scores on the COPD Assessment Test and Exacerbations of Chronic Pulmonary Disease Tool.,52 participants (mean (±SD) age 67±9 years) were randomised (34 to metformin, 18 to placebo).,All were included in the primary end point analysis.,The mean blood glucose concentrations in the metformin and placebo groups were 7.1±0.9 and 8.0±3.3 mmol/L, respectively (difference −0.9 mmol/L, 95% CI −2.1 to +0.3; p=0.273).,No significant between-group differences were observed on any of the secondary end points.,Adverse reactions, particularly gastrointestinal effects, were more common in metformin-treated participants.,Metformin did not ameliorate elevations in blood glucose concentration among non-diabetic patients admitted to hospital for COPD exacerbations, and had no detectable effect on CRP or clinical outcomes.,ISRCTN66148745 and NCT01247870. | 1 |
Lymphotoxin β-receptor (LTβR)-signalling orchestrates lymphoid neogenesis and subsequent tertiary lymphoid structures (TLS)1,2, associated with severe chronic inflammatory diseases spanning multiple organ systems3-6.,How LTβR-signalling drives chronic tissue damage particularly in the lung, which mechanism(s) regulate this process, and whether LTβR-blockade might be of therapeutic value has remained unclear.,Here we demonstrate increased expression of LTβR-ligands on adaptive and innate immune-cells, enhanced non-canonical NF-κB signalling and enriched LTβR-target gene expression in epithelial cells of lungs from patients with smoking-associated chronic obstructive pulmonary disease (COPD) and mice exposed to chronic cigarette smoke.,Therapeutic inhibition of LTβR-signalling in young and aged mice disrupted smoking-related inducible bronchus-associated lymphoid tissue (iBALT), induced lung tissue regeneration, and reverted airway-fibrosis and systemic muscle wasting.,Mechanistically, LTβR-signalling blockade dampened epithelial non-canonical NF-κB activation, reduced TGFβ-signalling in airways, induced regeneration by preventing epithelial cell-death and by activating Wnt/β-catenin-signalling in alveolar epithelial progenitor cells.,These findings highlight that LTβR-signalling inhibition represents a viable therapeutic option combining anti-TLS, anti-apoptotic with tissue regenerative strategies. | Chronic Obstructive Pulmonary Disease (COPD) is a common lung disease characterized by breathing difficulty as a consequence of narrowed airways.,Previous studies have shown that COPD is correlated with neutrophil infiltration into the airways through chemotactic migration.,However, whether neutrophil chemotaxis can be used to characterize and diagnose COPD is not well established.,In the present study, we developed a microfluidic platform for evaluating neutrophil chemotaxis to sputum samples from COPD patients.,Our results show increased neutrophil chemotaxis to COPD sputum compared to control sputum from healthy individuals.,The level of COPD sputum induced neutrophil chemotaxis was correlated with the patient’s spirometry data.,The cell morphology of neutrophils in a COPD sputum gradient is similar to the morphology displayed by neutrophils exposed to an IL-8 gradient, but not a fMLP gradient.,In competing gradients of COPD sputum and fMLP, neutrophils chemotaxis and cell morphology are dominated by fMLP. | 1 |
In epidemiological studies, items about physician-diagnosed COPD are often used.,There is a lack of validation and standardization of these items.,In a general population-based study, 1,050 subjects completed a questionnaire and performed spirometry, including forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) after inhalation of 400 µg of salbutamol.,COPD was defined as the ratio of FEV1/FVC <0.7 after bronchodilation.,Physician-diagnosed COPD was defined as an affirmative answer to the single item: “Have you ever had COPD diagnosed by a physician?”, physician-diagnosed COPD/emphysema as an affirmative answer to any of the two single items; “Have you ever had COPD diagnosed by a physician?”,or “Have you ever been told by a physician that you have emphysema?”, physician-diagnosed chronic bronchitis as an affirmative answer to; “Have you ever been told by a physician that you have chronic bronchitis?”,and physician-diagnosed COPD, emphysema or chronic bronchitis was defined as an affirmative answer to either of the three items above.,For the single item about physician-diagnosed COPD, the sensitivity was around 0.11 and the specificity was almost 0.99 in relation to COPD.,The sensitivity of the combined items about COPD/emphysema in detecting COPD was 0.11 and the specificity was high, 0.985.,When the items about physician-diagnosed COPD, emphysema or chronic bronchitis were merged as one entity, the sensitivity went up (0.13) and the specificity went down (0.95).,Items about physician-diagnosed COPD have low sensitivity but a very high specificity, indicating that these items will minimize the proportion of false positives.,The low sensitivity will underestimate the total burden of COPD in the general population.,Items about physician-diagnosed COPD may be used in studies of risk factors for COPD, but are not recommended in prevalence studies. | Spirometric diagnosis of chronic obstructive pulmonary disease (COPD) is based on the ratio of forced expiratory volume in 1 second (FEV1)/vital capacity (VC), either as a fixed value <0.7 or below the lower limit of normal (LLN).,Forced vital capacity (FVC) is a proxy for VC.,The first aim was to compare the use of FVC and VC, assessed as the highest value of FVC or slow vital capacity (SVC), when assessing the FEV1/VC ratio in a general population setting.,The second aim was to evaluate the characteristics of subjects with COPD who obtained a higher SVC than FVC.,Subjects (n=1,050) aged 50-64 years were investigated with FEV1, FVC, and SVC after bronchodilation.,Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPDFVC was defined as FEV1/FVC <0.7, GOLDCOPDVC as FEV1/VC <0.7 using the maximum value of FVC or SVC, LLNCOPDFVC as FEV1/FVC below the LLN, and LLNCOPDVC as FEV1/VC below the LLN using the maximum value of FVC or SVC.,Prevalence of GOLDCOPDFVC was 10.0% (95% confidence interval [CI] 8.2-12.0) and the prevalence of LLNCOPDFVC was 9.5% (95% CI 7.8-11.4).,When estimates were based on VC, the prevalence became higher; 16.4% (95% CI 14.3-18.9) and 15.6% (95% CI 13.5-17.9) for GOLDCOPDVC and LLNCOPDVC, respectively.,The group of additional subjects classified as having COPD based on VC, had lower FEV1, more wheeze and higher residual volume compared to subjects without any COPD.,The prevalence of COPD was significantly higher when the ratio FEV1/VC was calculated using the highest value of SVC or FVC compared with using FVC only.,Subjects classified as having COPD when using the VC concept were more obstructive and with indications of air trapping.,Hence, the use of only FVC when assessing airflow limitation may result in a considerable under diagnosis of subjects with mild COPD. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) have increased risk of cardiovascular events.,This study evaluated the association between high-sensitivity cardiac troponin I concentration and cardiovascular events in patients with COPD and heightened cardiovascular risk.,In a double-blind randomized controlled trial, 16,485 patients with COPD and cardiovascular disease or risk factors were randomized to once daily inhaled placebo, fluticasone furoate (100 μg), vilanterol (25 μg), or their combination.,Plasma high-sensitivity cardiac troponin I concentrations were measured in a subgroup of 1,599 patients.,Outcomes were on-treatment cardiovascular events and COPD exacerbations over a median of 18 months, and cardiovascular death over a median of 27 months.,Baseline plasma cardiac troponin I concentrations were above the limit of detection (1.2 ng/l) in 1,542 (96%) patients.,Concentrations were unaffected by inhaled therapies at 3 months (p > 0.05).,Compared with the lowest quintile (cardiac troponin <2.3 ng/l), patients in the highest quintile (≥7.7 ng/l) were at greater risk of cardiovascular events (hazard ratio [HR] 3.7; 95% confidence interval [CI]: 1.3 to 10.1; p = 0.012) and cardiovascular death (HR: 20.1; 95% CI: 2.4 to 165.2; p = 0.005) after adjustment for risk factors.,By contrast, there were no differences in exacerbations between quintiles (HR: 1.1; 95% CI: 0.8 to 1.5; p = 0.548).,In patients with COPD and heightened cardiovascular risk, plasma cardiac troponin I concentrations are a specific and major indicator of future cardiovascular events and cardiovascular death.,Inhaled therapies did not affect cardiac troponin I concentrations consistent with their neutral effect on mortality and cardiovascular outcomes.,(Study to Evaluate the Effect of Fluticasone Furoate/Vilanterol on Survival in Subjects With Chronic Obstructive Pulmonary Disease [SUMMIT]; NCT01313676) | It is well known that increased airflow limitation as measured by spirometry is associated with the risk of exacerbation in patients with COPD.,The forced oscillation technique (FOT) is a noninvasive method used to assess respiratory impedance (resistance and reactance) with minimal patient cooperation required.,The clinical utility of the FOT in assessing the risk of exacerbations of COPD is yet to be determined.,We examined the relationship between respiratory impedance as measured by FOT and exacerbations in patients with COPD.,Among 310 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stages I-IV) who presented at the outpatient clinic of the Showa University Hospital from September 2014 through January 2015, 119 were collected and assigned into 2 groups according to their history of exacerbation: exacerbators and nonexacerbators.,Respiratory resistance components and respiratory reactance components, as measured by FOT, were compared between the two groups.,Exacerbators were significantly older and had a higher white blood cell count than nonexacerbators.,Resistance at 20 Hz, reactance at 5 Hz (X5), resonant frequency (Fres), and area of low reactance (ALX) differed significantly between the two groups.,In addition, among patients with stage II COPD, there were significant differences in X5, Fres, and ALX between the two groups despite no significant differences in respiratory function as assessed by spirometry.,Finally, receiver operating characteristic curve analysis revealed that the reactance components rather than the resistance components were associated with the risk of exacerbation.,There were significant differences in respiratory impedance between exacerbators and nonexacerbators in patients with moderate COPD.,FOT is a promising tool for assessing future exacerbations in patients with COPD. | 1 |
Objective To systematically review the risk of mortality associated with long term use of tiotropium delivered using a mist inhaler for symptomatic improvement in chronic obstructive pulmonary disease.,Data sources Medline, Embase, the pharmaceutical company clinical trials register, the US Food and Drug Administration website, and ClinicalTrials.gov for randomised controlled trials from inception to July 2010.,Study selection Trials were selected for inclusion if they were parallel group randomised controlled trials of tiotropium solution using a mist inhaler (Respimat Soft Mist Inhaler, Boehringer Ingelheim) versus placebo for chronic obstructive pulmonary disease; the treatment duration was more than 30 days, and they reported data on mortality.,Relative risks of all cause mortality were estimated using a fixed effect meta-analysis, and heterogeneity was assessed with the I2 statistic.,Results Five randomised controlled trials were eligible for inclusion.,Tiotropium mist inhaler was associated with a significantly increased risk of mortality (90/3686 v 47/2836; relative risk 1.52, 95% confidence interval, 1.06 to 2.16; P=0.02; I2=0%).,Both 10 µg (2.15, 1.03 to 4.51; P=0.04; I2=9%) and 5 µg (1.46, 1.01 to 2.10; P=0.04; I2=0%) doses of tiotropium mist inhaler were associated with an increased risk of mortality.,The overall estimates were not substantially changed by sensitivity analysis of the fixed effect analysis of the five trials combined using the random effects model (1.45, 1.02 to 2.07; P=0.04), limiting the analysis to three trials of one year’s duration each (1.50, 1.05 to 2.15), or the inclusion of additional data on tiotropium mist inhaler from another investigational drug programme (1.42, 1.01 to 2.00).,The number needed to treat for a year with the 5 µg dose to see one additional death was estimated to be 124 (95% confidence interval 52 to 5682) based on the average control event rate from the long term trials.,Conclusions This meta-analysis explains safety concerns by regulatory agencies and indicates a 52% increased risk of mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease. | Two 1-year studies evaluated the long-term efficacy and safety of tiotropium 5 or 10 μg versus placebo, inhaled via the Respimat® Soft Mist™ Inhaler (SMI).,The two studies were combined and had 4 co-primary endpoints (trough FEV1 response, Mahler Transition Dyspnea Index [TDI] and St George’s Respiratory Questionnaire scores all at week 48, and COPD exacerbations per patient-year).,A total of 1990 patients with COPD participated (mean FEV1: 1.09 L).,The mean trough FEV1 response of tiotropium 5 or 10 μg relative to placebo was 127 or 150 mL, respectively (both P < 0.0001).,The COPD exacerbation rate was significantly lower with tiotropium 5 μg (RR = 0.78; P = 0.002) and tiotropium 10 μg (RR = 0.73; P = 0.0008); the health-related quality of life and Mahler TDI co-primary endpoints were significantly improved with both doses (both P < 0.0001).,Adverse events were generally balanced except anticholinergic class effects, which were more frequent with active treatment.,Fatal events occurred in 2.4% (5 μg), 2.7% (10 μg), and 1.6% (placebo) of patients; these differences were not significant.,Tiotropium Respimat® SMI 5 μg demonstrated sustained improvements in patients with COPD relative to placebo and similar to the 10 μg dose but with a lower frequency of anticholinergic adverse events. | 1 |
Long non-coding RNAs (lncRNAs) have critical regulatory roles in protein-coding gene expression.,Aberrant expression profiles of lncRNAs have been observed in various human diseases.,In this study, we investigated transcriptome profiles in lung tissues of chronic cigarette smoke (CS)-induced COPD mouse model.,We found that 109 lncRNAs and 260 mRNAs were significantly differential expressed in lungs of chronic CS-induced COPD mouse model compared with control animals.,GO and KEGG analyses indicated that differentially expressed lncRNAs associated protein-coding genes were mainly involved in protein processing of endoplasmic reticulum pathway, and taurine and hypotaurine metabolism pathway.,The combination of high throughput data analysis and the results of qRT-PCR validation in lungs of chronic CS-induced COPD mouse model, 16HBE cells with CSE treatment and PBMC from patients with COPD revealed that NR_102714 and its associated protein-coding gene UCHL1 might be involved in the development of COPD both in mouse and human.,In conclusion, our study demonstrated that aberrant expression profiles of lncRNAs and mRNAs existed in lungs of chronic CS-induced COPD mouse model.,From animal models perspective, these results might provide further clues to investigate biological functions of lncRNAs and their potential target protein-coding genes in the pathogenesis of COPD. | Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants.,We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD.,Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD.,By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung.,IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD.,Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC.,Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD.,Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD. | 1 |
Lipid metabolism plays an important role in many lung functions.,Disorders of lipid metabolism are part of the pathogenesis of chronic obstructive pulmonary disease (COPD).,Lipids are involved in numerous cross-linkages with inflammation.,Recent studies strongly support the involvement of fatty acids as participants in inflammation.,They are involved in the initiation and resolution of inflammation, including acting as a substrate for the formation of lipid mediators of inflammation resolution.,Specialized pro-inflammatory mediators (SPMs) belonging to the classes of lipoxins, resolvins, maresins, and protectins, which are formed enzymatically from unsaturated fatty acids, are now described.,Disorders of their production and function are part of the pathogenesis of COPD.,SPMs are currently the subject of active research in order to find new drugs.,Short-chain fatty acids are another important participant in metabolic and immune processes, and their role in the pathogenesis of COPD is of great clinical interest. | Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema.,Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses.,To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire.,In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations.,We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD.,In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD. | 1 |
Lung-function decline is one of the possible mechanisms leading to Chronic Obstructive Pulmonary Disease (COPD).,We analyzed data obtained from two population-based surveys of adults (n = 2026) conducted in the same individuals 5-9 years (y) after their baseline examination in three Latin-American cities.,Post BronchoDilator (postBD) FEV1 decline in mL/y, as %predicted/y (%P/y) and % of baseline/y (%B/y) was calculated and the influence of age, gender, BMI, baseline lung function, BD response, exacerbations rate evaluated using multivariate models.,Expressed in ml/y, the mean annual postBD FEV1 decline was 27 mL (0.22%P, 1.32%B) in patients with baseline COPD and 36 (0.14%P, 1.36%B) in those without.,Faster decline (in mL/y) was associated with higher baseline lung function, with significant response to bronchodilators, older age and smoking at baseline, also in women with chronic cough and phlegm, or ≥2 respiratory exacerbations in the previous year, and in men with asthma.,Lung function decline in a population-based cohort did not differ in obstructed and non-obstructed individuals, it was proportional to baseline FEV1, and was higher in smokers, elderly, and women with respiratory symptoms. | There is growing evidence about sex-related phenotypes of COPD.,However, the sex differences in COPD mainly result from smokers.,This study evaluated the sex differences in nonsmoking patients with COPD, focusing on structural changes in the lungs in airway diseases and emphysema.,Ninety-seven nonsmoking patients, defined as having <1 pack-year of lifetime cigarette smoking, diagnosed with COPD were selected from a Korean COPD cohort.,Emphysema extent and mean wall area percentage (WA%) on computed tomography were compared between the male and female groups.,The 97 patients with COPD included 62 females and 35 males.,Emphysema index was significantly lower (3.5±4.2 vs 6.2±5.7, P<0.01) and mean WA% on computed tomography was significantly higher (71.8%±5% vs 69.4%±5%, P<0.01) in females than in males, after adjusting for age, body mass index, history of biomass exposure, and postbronchodilator forced expiratory volume in 1 second (% of predicted).,WA% was higher and emphysema extent was lower in nonsmoking females with COPD than in nonsmoking males with COPD.,These findings suggest that males may be predisposed to an emphysema phenotype and females may be predisposed to an airway phenotype of COPD. | 1 |
Medications for respiratory disorders including asthma and chronic obstructive pulmonary disease (COPD) are typically delivered to the lung by means of a handheld inhaler.,Patient preference for and ability to use the inhaler may influence their adherence to maintenance therapy, and adherence may affect treatment outcomes.,In this study, patient experience of using a dry powder inhaler (DPI), the ELLIPTA™ DPI, in clinical trials of a new maintenance therapy for asthma and COPD was investigated.,The ELLIPTA DPI has been designed to contain two separate blister strips from which inhalation powder can be delivered, and to be simple to use with a large, easy-to-read dose counter.,Semi-structured, in-depth, qualitative interviews were carried out 2-4 weeks after patients had completed one of six phase IIIa clinical trials using the ELLIPTA DPI.,Interview participants were asked about their satisfaction with various attributes of the inhaler and their preference for the ELLIPTA DPI relative to currently-prescribed inhalers, and responses were explored using an inductive content analysis approach.,Participants also rated the performance of the inhaler on several criteria, using a subjective 1-10 scale.,Participants with asthma (n = 33) and COPD (n = 42) reported high levels of satisfaction with the ELLIPTA DPI.,It was frequently described as straightforward to operate and easy to use by interview participants.,Ergonomic design, mouthpiece fit, and dose counter visibility and ease of interpretation emerged as frequently cited drivers of preference for the ELLIPTA DPI compared with their current prescribed inhaler.,Of participants with asthma, 71% preferred the ELLIPTA DPI to DISKUS™ and 60% to metered dose inhalers.,Of participants with COPD, 86% preferred the ELLIPTA DPI to DISKUS, 95% to HandiHaler™, and 85% to metered dose inhalers.,Overall average performance scores were >9 (out of 10) in participants with asthma and COPD.,The ELLIPTA DPI was associated with high patient satisfaction and was preferred to other inhalers by interview participants with asthma and COPD.,The development of an inhaler that is regarded as easy and intuitive to use may have positive implications for adherence to therapy in asthma and COPD.,Asthma: NCT01165138, NCT01431950.,COPD: NCT01053988, NCT01054885, NCT01009463, NCT01017952. | At present there is no cure for chronic obstructive pulmonary disease (COPD).,However, some nonpharmacologic treatments, such as rehabilitation and lung volume reduction surgery, as well as pharmacologic intervention, can relieve some of the patient’s symptoms and improve quality of life, while also reducing the rate of exacerbations and hospitalizations.,There needs to be a paradigm shift away from the unjustified nihilistic approach to COPD towards considering it a preventable and treatable disease.,After patients quit smoking and start to lead healthier lifestyles, long-acting bronchodilators, such as long-acting beta-adrenergic agents (LABA) and long-acting antimuscarinic agents (LAMA), are recommended as the cornerstone of treatment for COPD, either as monotherapy or in combination.,COPD is characterized by a reduced maximum expiratory flow and slow forced emptying of the lungs, which progress over time and are not completely reversible.,In this condition, gas gets trapped in the lungs and pulmonary hyperinflation occurs.,LABA and LAMA improve airway patency and deflate the lungs.,Indacaterol is the first once-daily LABA approved for treatment of COPD, and is administered by inhalation through the Breezhaler® device.,The speed of bronchodilation is similar to that with salbutamol (ie, about five minutes) and longer (ie, 24 hours) than that with traditional LABA, with the same 12-hour effect as salmeterol and formoterol, both of which require twice-daily administration.,This is why indacaterol has been called the “ultra-LABA”.,On the one hand, the fast onset of action provides immediate relief of symptoms, and on the other, its constant 24-hour bronchodilation provides “pharmacologic stenting” which facilitates lung emptying, thereby decreasing trapped gas and pulmonary hyperinflation.,Once-daily administration of a fast and long-acting bronchodilator can improve patient adherence with therapy, which is known to be a major problem for many medical treatments.,Dose-finding trials have shown that 75 μg is the minimum dose needed to achieve clinically important improvement.,However, indacaterol 150 μg and 300 μg achieve an even greater improvement in lung function and patient-oriented outcomes.,Further, these two doses of indacaterol significantly reduce pulmonary hyperinflation, thereby improving exercise tolerance and ability to perform day-to-day activities.,It is more effective on lung volumes at the 300 μg dose than formoterol, and better than salmeterol and tiotropium at the 150 μg dose, at least in the acute setting.,It is noteworthy that few studies document these results in patients with COPD and moderate airflow obstruction.,These are exactly the kind of patients our research should be concentrating on, in view of the accelerated decay in forced expiratory volume in one second at this stage of the disease.,Finally, all the relevant studies show that indacaterol is consistently well tolerated by patients with COPD at every stage, and that it has a high safety profile. | 1 |
The COPD assessment test (CAT) consists of eight nonspecific scores of quality of life.,The aim of this study was to compare the health-related quality of life and severity of airflow limitation in patients with asthma, COPD, and asthma-COPD overlap syndrome (ACOS) using the CAT.,We examined CAT and lung functions in 138 patients with asthma, 99 patients with COPD, 51 patients with ACOS, and 44 patients with chronic cough as a control.,The CAT score was recorded in all subjects, and the asthma control test was also administered to patients with asthma and ACOS.,The CAT scores were compared, and the relationships between the scores and lung function parameters were analyzed.,The total CAT scores and scores for cough, phlegm, and dyspnea were higher in patients with ACOS than in patients with asthma and COPD.,The total CAT scores were correlated with the percent predicted forced expiratory volume in 1 second only in patients with COPD.,The total CAT scores and dyspnea scores adjusted by the percent predicted forced expiratory volume in 1 second were higher in patients with ACOS than in patients with COPD and asthma.,The CAT scores and asthma control test scores were more closely correlated in patients with ACOS than in patients with asthma.,Patients with ACOS have higher disease impacts and dyspnea sensation unproportional to the severity of airflow limitation. | The association between vitamin D and clinical parameters in obstructive lung diseases (OLDs), including COPD and bronchial asthma, was previously investigated.,As asthma-COPD overlap syndrome (ACOS) is a new clinical entity, the prevalence of vitamin D levels in ACOS is unknown.,Our aim was to assess the levels of circulating vitamin D (25-hydroxyvitamin D [25(OH)D]) in different OLDs, including ACOS patients, and its correlation with clinical parameters.,A total of 106 men and women (control, n=21; asthma, n=44; COPD, n=21; and ACOS, n=20) were involved in the study.,All patients underwent detailed clinical examinations; disease control and severity was assessed by disease-specific questionnaires (COPD assessment test, asthma control test, and modified Medical Research Council); furthermore, 25(OH)D levels were measured in all patients.,The 25(OH)D level was significantly lower in ACOS and COPD groups compared to asthma group (16.86±1.79 ng/mL and 14.27±1.88 ng/mL vs 25.66±1.91 ng/mL).,A positive correlation was found between 25(OH)D level and forced expiratory volume in 1 second (r=0.4433; P<0.0001), forced vital capacity (FVC) (r=0.3741; P=0.0004), forced expiratory flow between 25% and 75% of FVC (r=0.4179; P<0.0001), and peak expiratory flow (r=0.4846; P<0.0001) in OLD patient groups.,Asthma control test total scores and the 25(OH)D level showed a positive correlation in the ACOS (r=0.4761; P=0.0339) but not in the asthma group.,Higher COPD assessment test total scores correlated with decreased 25(OH)D in ACOS (r=−0.4446; P=0.0495); however, this was not observed in the COPD group.,Vitamin D deficiency is present in ACOS patients and circulating 25(OH)D level may affect disease control and severity. | 1 |
More than one third of individuals with chronic obstructive pulmonary disease (COPD) experience comorbid symptoms of depression and anxiety.,This review aims to provide an overview of the burden of depression and anxiety in those with COPD and to outline the contemporary advances and challenges in the management of depression and anxiety in COPD.,Symptoms of depression and anxiety in COPD lead to worse health outcomes, including impaired health-related quality of life and increased mortality risk.,Depression and anxiety also increase health care utilization rates and costs.,Although the quality of the data varies considerably, the cumulative evidence shows that complex interventions consisting of pulmonary rehabilitation interventions with or without psychological components improve symptoms of depression and anxiety in COPD.,Cognitive behavioral therapy is also an effective intervention for managing depression in COPD, but treatment effects are small.,Cognitive behavioral therapy could potentially lead to greater benefits in depression and anxiety in people with COPD if embedded in multidisciplinary collaborative care frameworks, but this hypothesis has not yet been empirically assessed.,Mindfulness-based treatments are an alternative option for the management of depression and anxiety in people with long-term conditions, but their efficacy is unproven in COPD.,Beyond pulmonary rehabilitation, the evidence about optimal approaches for managing depression and anxiety in COPD remains unclear and largely speculative.,Future research to evaluate the effectiveness of novel and integrated care approaches for the management of depression and anxiety in COPD is warranted. | There is a wide variability in measurement methodology of physical activity.,This study investigated the effect of different analysis techniques on the statistical power of physical activity outcomes after pulmonary rehabilitation.,Physical activity was measured with an activity monitor armband in 57 patients with COPD (mean ± SD age, 66 ± 7 years; FEV1, 46 ± 17% predicted) before and after 3 months of pulmonary rehabilitation.,The choice of the outcome (daily number of steps [STEPS], time spent in at least moderate physical activity [TMA], mean metabolic equivalents of task level [METS], and activity time [ACT]), impact of weekends, number of days of assessment, postprocessing techniques, and influence of duration of daylight time (DT) on the sample size to achieve a power of 0.8 were investigated.,The STEPS and ACT (1.6-2.3 metabolic equivalents of task) were the most sensitive outcomes.,Excluding weekends decreased the sample size for STEPS (83 vs 56), TMA (160 vs 148), and METS (251 vs 207).,Using 4 weekdays (STEPS and TMA) or 5 weekdays (METS) rendered the lowest sample size.,Excluding days with < 8 h wearing time reduced the sample size for STEPS (56 vs 51).,Differences in DT were an important confounder.,Changes in physical activity following pulmonary rehabilitation are best measured for 4 weekdays, including only days with at least 8 h of wearing time (during waking hours) and considering the difference in DT as a covariate in the analysis.,ClinicalTrials.gov; No.: NCT00948623; URL: www.clinicaltrials.gov | 1 |
COPD is characterized by chronic bronchitis, chronic airway obstruction, and emphysema, leading to a progressive and irreversible decline in lung function.,Inflammation is central for the development of COPD.,Chronic inflammation in COPD mainly involves the infiltration of neutrophils, macrophages, lymphocytes, and other inflammatory cells into the small airways.,The contribution of resident airway structural cells to the inflammatory process is also important in COPD.,Airway remodeling consists of detrimental changes in structural tissues and cells including airway wall thickening, epithelial metaplasia, goblet cell hypertrophy, and smooth muscle hyperplasia.,Persistent airway inflammation might contribute to airway remodeling and small airway obstruction.,However, the underlying mechanisms remain unclear.,In this review, we will provide an overview of recent insights into the role of major immunoinflammatory cells in COPD airway remodeling. | Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | 1 |
In most countries, nearly 6% of the adults are suffering from chronic obstructive pulmonary disease (COPD), which puts a huge economic burden on the society.,Moreover, COPD has been considered as an independent risk factor for pulmonary embolism (PE).,In this review, we summarized the existing evidence that demonstrates the associations between COPD exacerbation and PE from various aspects, including epidemiology, pathophysiological changes, risk factors, clinical features, management, and prognosis.,We searched the terms “chronic obstructive pulmonary disease,” “pulmonary embolism,” “exacerbations,” and “thromboembolic” in PubMed database and collected the results up to April 2018.,The language was limited to English.,We thoroughly examined the titles and abstracts of all studies that met our search strategy.,The data from prospective studies, meta-analyses, retrospective studies, and recent reviews were selected for preparing this review.,The prevalence of PE in patients with COPD exacerbation varied a lot among different studies, mainly due to the variations in race, sample size, study design, research setting, and enrollment criteria.,Overall, whites and African Americans showed significantly higher prevalence of PE than Asian people, and the hospitalized patients showed higher prevalence of PE compared to those who were evaluated in emergency department.,PE is easily overlooked in patients with COPD exacerbation due to the similar clinical symptoms.,However, several factors have been identified to contribute to the increased risk of PE during COPD exacerbation.,Obesity and lower limb asymmetry were described as independent predictors for PE.,Moreover, due to the high risk of PE, thromboprophylaxis has been used as an important treatment for hospitalized patients with COPD exacerbation.,According to the previous studies, COPD patients with PE experienced an increased risk of death and prolonged length of hospital stay.,Therefore, the thromboembolic risk in patients with acute exacerbation of COPD, especially in the hospitalized patients, should carefully be evaluated. | Patients with chronic obstructive pulmonary disease (COPD) have a modified clinical presentation of venous thromboembolism (VTE) but also a worse prognosis than non-COPD patients with VTE.,As it may induce therapeutic modifications, we evaluated the influence of the initial VTE presentation on the 3-month outcomes in COPD patients.,COPD patients included in the on-going world-wide RIETE Registry were studied.,The rate of pulmonary embolism (PE), major bleeding and death during the first 3 months in COPD patients were compared according to their initial clinical presentation (acute PE or deep vein thrombosis (DVT)).,Of the 4036 COPD patients included, 2452 (61%; 95% CI: 59.2-62.3) initially presented with PE.,PE as the first VTE recurrence occurred in 116 patients, major bleeding in 101 patients and mortality in 443 patients (Fatal PE: first cause of death).,Multivariate analysis confirmed that presenting with PE was associated with higher risk of VTE recurrence as PE (OR, 2.04; 95% CI: 1.11-3.72) and higher risk of fatal PE (OR, 7.77; 95% CI: 2.92-15.7).,COPD patients presenting with PE have an increased risk for PE recurrences and fatal PE compared with those presenting with DVT alone.,More efficient therapy is needed in this subtype of patients. | 1 |
Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are linked to several mitochondrial alterations.,Cigarette smoke (CS) alters the structure and function of mitochondria.,OPA1 is the main inner mitochondrial GTPase responsible for the fusion events.,OPA1 undergoes proteolytic cleavage from long to short forms during acute stress and mitophagy.,However, the exact role of OPA1 isoforms and related proteins during CS-induced mitophagy and COPD is not clear.,Lung tissues from non-smokers, smokers, COPD and IPF were used to determine the relative expression of OPA1 and related proteins.,Additionally, we used mouse lungs from chronic (6 months) CS exposure to evaluate the status of OPA1.,Primary lung fibroblasts from normal and COPD patients and naked mole rat (NMR) lung fibroblasts, human fetal lung fibroblast (HFL1), mouse embryonic fibroblast from wild type (WT), OPA1−/−, MFN1 and MFN2−/− were used to determine the effect of CS on OPA1 isoforms.,Various mitochondrial fusion promoters/activators (BGP-15, leflunomide, M1) and fission inhibitor (DRP1) were used to determine their effect on OPA1 status and cigarette smoke extract (CSE)-induced lung epithelial (BEAS2B) cell damage, respectively.,Seahorse flux analyzer was used to determine the effect of these compounds in BEAS2B cells with and without CSE exposure.,Short OPA1 isoforms were predominantly detected and significantly increased in COPD subjects.,Acute CSE treatment in various cell lines except NMR was found to increase the conversion of long to short OPA1 isoforms.,CSE treatment significantly increased mitochondrial stress-related protein SLP2 in all the cells used.,OPA1 interacting partners like prohibitins (PHB1 and 2) were also altered depending on the CS exposure.,Finally, BGP-15 and leflunomide treatment were able to preserve the long OPA1 isoform in cells treated with CSE.,The long OPA1 isoform along with SLP2 and prohibitins play a crucial role in CS-induced lung damage, causing mitophagy/mitochondrial dysfunction in COPD, which may be used as a novel therapeutic target in COPD.,Image 1,•Smoking is the main causative factor for Chronic Obstructive Pulmonary Disease (COPD) which is associated with mitochondrial dysfunction and altered mitophagy.,•Various strategies and models ranging from human samples, mouse models and naked mole rat fibroblasts were used to determine the behavior of the OPA1 forms by cigarette smoke and in COPD.,•Cigarette smoke exposure and in patients with COPD the lung cellular levels of S-OPA1 are significantly increased, along with SLP-2 levels with altered prohibitins.,•Compounds like BGP-15 and leflunomide promoted/maintained the L-OPA1 levels.,•Long OPA1 isoforms along with SLP2 and prohibitins play a crucial role in tobacco smoke-induced lung damage during mitophagy/mitochondrial dysfunction in COPD, which can be a therapeutic target in COPD.,Smoking is the main causative factor for Chronic Obstructive Pulmonary Disease (COPD) which is associated with mitochondrial dysfunction and altered mitophagy.,Various strategies and models ranging from human samples, mouse models and naked mole rat fibroblasts were used to determine the behavior of the OPA1 forms by cigarette smoke and in COPD.,Cigarette smoke exposure and in patients with COPD the lung cellular levels of S-OPA1 are significantly increased, along with SLP-2 levels with altered prohibitins.,Compounds like BGP-15 and leflunomide promoted/maintained the L-OPA1 levels.,Long OPA1 isoforms along with SLP2 and prohibitins play a crucial role in tobacco smoke-induced lung damage during mitophagy/mitochondrial dysfunction in COPD, which can be a therapeutic target in COPD. | The Notch signaling pathway plays critical role for determining cell fate by controlling proliferation, differentiation, and apoptosis.,In the current study, we investigated the roles of the Notch signaling pathway in cigarette smoke (CS)-induced endothelial apoptosis in chronic obstructive pulmonary disease (COPD).,We obtained surgical specimens from 10 patients with COPD and 10 control participants.,Notch1, 2, and 4 express in endothelial cells, whereas Notch3 mainly localizes in smooth muscle cells.,Compared with control groups, we found that the expression of Notch1, 3, and 4 decreased, as well as their target genes Hes1 and Hes2, while the expression of Notch2 and extracellular signal-regulated kinase (ERK)1/2 increased in COPD patients compared with controls, as well as in human pulmonary microvascular endothelial cells (HPMECs) when exposed to CS extract (CSE).,Overexpression of Notch1 with N1ICD in HPMECs markedly alleviated the cell apoptosis induced by CSE.,The ERK signaling pathway was significantly activated by CSE, which correlated with CSE-induced apoptosis.,However, this activation can be abolished by N1ICD overexpression.,Furthermore, treatment of PD98059 (ERK inhibitor) significantly alleviated CSE-induced apoptosis, as well as reduced the methylation of mitochondrial transcription factor A (mtTFA) promoter, which was correlated with CS-induced endothelial apoptosis.,These results suggest that CS alters Notch signaling in pulmonary endothelial cells.,Notch1 protects against CS-induced endothelial apoptosis in COPD through inhibiting the ERK pathway, while the ERK pathway further regulates the methylation of mtTFA promotor. | 1 |
Background: Glycopyrrolate administered by a novel, investigational eFlow® Closed System (CS) nebulizer (eFlow CS) is being evaluated for the maintenance treatment of chronic obstructive pulmonary disease (COPD).,The eFlow CS is a hand-held, vibrating membrane nebulizer optimized to deliver 1 mL of glycopyrrolate solution into the lung in <3 minutes.,Clinical studies have shown improvements in lung function of subjects treated with nebulized glycopyrrolate.,Methods: The aerosol performance of the eFlow CS nebulizer was characterized by delivered dose, aerodynamic droplet size distribution and nebulization time.,Simulated use nebulizer performance over 60 days was assessed by volume median diameter (VMD), nebulized amount, and nebulization time.,Nebulization outputs were assayed to ensure adequate delivery of glycopyrrolate with an acceptable impurity profile.,Aerosol condensates were analyzed for glycopyrrolate concentration and impurities by ultra-high-performance liquid chromatography and compared with non-nebulized samples.,Results: The mean mass median aerodynamic diameter, geometric standard deviation, and fine particle fraction were 3.7 μm, 1.7, and 72%, respectively, and independent of formulation strength (25 and 50 μg/mL).,Delivered dose was 88% of the nominal dose for both formulation strengths.,The mean delivered dose, assessed by breathing simulation, was 56.8% for 25 μg/mL and 62.6% for 50 μg/mL.,Nebulization times were 1-2.5 minutes with no apparent increasing trend with use over a 60-day period.,The nebulized amount showed no significant changes, whereas the VMD showed a slight, but not pharmaceutically relevant, increase (0.1-0.2 μm) after 60-day simulated use.,Glycopyrrolate concentration and impurity levels of nebulized samples were statistically similar to those of non-nebulized samples.,Conclusion: The eFlow CS generates glycopyrrolate aerosols with high delivered dose, short treatment time, and small droplet size with narrow size distribution suitable for central and peripheral airway deposition.,The unit dose vial mitigates medication misuse and ensures dose uniformity.,Results support the use of glycopyrrolate/eFlow CS for the treatment of COPD. | Long-acting bronchodilators are central in the pharmacological management of patients with chronic obstructive pulmonary disease (COPD).,The aim of this systematic review is to provide an overview of the studies evaluating the safety and clinical efficacy of inhaled glycopyrronium bromide, a novel long-acting muscarinic antagonist, in patients with COPD.,This study was performed as a systematic literature review.,Inhaled glycopyrronium bromide seems to be a safe and well tolerated long-acting muscarinic antagonist with a fast onset of action.,In patients suffering from moderate to severe COPD, glycopyrronium bromide has clinically important effects on level of forced expiratory volume in one second, use of relief medication, percentage of days with no use of rescue medication, daytime dyspnea scores, and probably also on health status.,Furthermore, in this group of patients, glycopyrronium bromide has beneficial effects on dynamic hyperinflation and exercise tolerance.,Glycopyrronium bromide has been shown to reduce the rate of exacerbations in patients with moderate to severe COPD, but long-term controlled trials with exacerbation rate as the primary outcome variable have not been published yet.,Once-daily inhaled glycopyrronium bromide has characteristics important for use in COPD, including a fast onset of action, sustained 24-hour bronchodilatation, and improvement in exercise tolerance, and therefore appears to have the potential for a significant role in the future management of COPD. | 1 |
The safety, lung function efficacy, and symptomatic benefits of combined tiotropium and olodaterol in patients with COPD were established in the 1-year TONADO® studies (NCT01431274; NCT01431287).,As tiotropium is predominantly excreted by the kidneys, the long-term safety profile of tiotropium/olodaterol was investigated in patients with renal impairment in a prespecified safety analysis of the TONADO studies.,These were 2 replicate, randomized, double-blind, parallel-group, 52-week Phase III studies that assessed tiotropium/olodaterol compared with tiotropium or olodaterol alone (all via Respimat®) in patients with moderate-to-very severe COPD.,In this analysis, renal impairment was defined as mild (creatinine clearance [CLcr] 60-89 mL/min), moderate (CLcr 30-59 mL/min) or severe (CLcr 15-29 mL/min).,Adverse events (AEs) were pooled from both studies.,Of 3,041 patients included in this analysis, 1,333 (43.8%) had mild, 404 (13.3%) had moderate, and 5 (0.2%) had severe renal impairment; these were distributed equally between treatment groups.,Almost one-quarter of all treated patients (23.4%) had a history of cardiac disorder, 45.6% had hypertension, and 13.3% had glucose metabolism disorders, including diabetes.,AEs with olodaterol, tiotropium, and tiotropium/olodaterol occurred in 75.1%, 70.8%, and 72.0% of patients with no renal impairment, 75.7%, 74.0%, and 73.3% with mild renal impairment, and 84.3%, 79.5%, and 79.7% with moderate renal impairment, respectively.,There was no notable effect of renal impairment on the proportion of patients with an AE, and no differences were observed between tiotropium/olodaterol versus the monocomponents.,There was no difference in the incidence of major adverse cardiac events, renal and urinary tract AEs, or potential anticholinergic effects with increasing severity of renal impairment.,Over half the patients enrolled in the TONADO studies had renal impairment, and there was a high level of pre-existing cardiovascular comorbidity.,The safety and tolerability of tiotropium/olodaterol is comparable to the monocomponents, irrespective of the level of renal impairment. | The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with lung fibroblast senescence, a process characterized by an irreversible proliferation arrest associated with secretion of inflammatory mediators.,ROS production, known to induce senescence, is increased in COPD fibroblasts and mitochondria dysfunction participates in this process.,Among the battery of cellular responses against oxidative stress damage, heme oxygenase (HO)‐1 plays a critical role in defending the lung against oxidative stress and inflammation.,Therefore, we investigated whether pharmacological induction of HO‐1 by chronic hemin treatment attenuates senescence and improves dysfunctional mitochondria in COPD fibroblasts.,Fibroblasts from smoker controls (S‐C) and COPD patients were isolated from lung biopsies.,Fibroblasts were long‐term cultured in the presence or absence of hemin, and/or ZnPP or QC‐15 (HO‐1 inhibitors).,Lung fibroblasts from smokers and COPD patients displayed in long‐term culture a senescent phenotype, characterized by a reduced replicative capacity, an increased senescence and inflammatory profile.,These parameters were significantly higher in senescent COPD fibroblasts which also exhibited decreased mitochondrial activity (respiration, glycolysis, and ATP levels) which led to an increased production of ROS, and mitochondria biogenesis and impaired mitophagy process.,Exposure to hemin increased the gene and protein expression level of HO‐1 in fibroblasts and diminished ROS levels, senescence, the inflammatory profile and simultaneously rescued mitochondria dysfunction by restoring mitophagy in COPD cells.,The effects of hemin were abolished by a cotreatment with ZnPP or QC‐15.,We conclude that HO‐1 attenuates senescence in COPD fibroblasts by protecting, at least in part, against mitochondria dysfunction and restoring mitophagy. | Cigarette smoke (CS)-induced mitochondrial damage with increased reactive oxygen species (ROS) production has been implicated in COPD pathogenesis by accelerating senescence.,Mitophagy may play a pivotal role for removal of CS-induced damaged mitochondria, and the PINK1 (PTEN-induced putative kinase 1)-PARK2 pathway has been proposed as a crucial mechanism for mitophagic degradation.,Therefore, we sought to investigate to determine if PINK1-PARK2-mediated mitophagy is involved in the regulation of CS extract (CSE)-induced cell senescence and in COPD pathogenesis.,Mitochondrial damage, ROS production, and cell senescence were evaluated in primary human bronchial epithelial cells (HBEC).,Mitophagy was assessed in BEAS-2B cells stably expressing EGFP-LC3B, using confocal microscopy to measure colocalization between TOMM20-stained mitochondria and EGFP-LC3B dots as a representation of autophagosome formation.,To elucidate the involvement of PINK1 and PARK2 in mitophagy, knockdown and overexpression experiments were performed.,PINK1 and PARK2 protein levels in lungs from patients were evaluated by means of lung homogenate and immunohistochemistry.,We demonstrated that CSE-induced mitochondrial damage was accompanied by increased ROS production and HBEC senescence.,CSE-induced mitophagy was inhibited by PINK1 and PARK2 knockdown, resulting in enhanced mitochondrial ROS production and cellular senescence in HBEC.,Evaluation of protein levels demonstrated decreased PARK2 in COPD lungs compared with non-COPD lungs.,These results suggest that PINK1-PARK2 pathway-mediated mitophagy plays a key regulatory role in CSE-induced mitochondrial ROS production and cellular senescence in HBEC.,Reduced PARK2 expression levels in COPD lung suggest that insufficient mitophagy is a part of the pathogenic sequence of COPD. | 1 |
Asthma and chronic obstructive pulmonary disease are inflammatory lung disorders responsible for significant morbidity and mortality worldwide.,While the importance of allergic responses in asthma is well known, respiratory viral and bacterial infections and pollutants especially cigarette smoke are important factors in the pathogenesis of both diseases.,Corticosteroid treatment remains the first preference of treatment in either disease, however these therapies are not always completely effective, and are associated with side effects and steroid resistance.,Due to such limitations, development of new treatments represents a major goal for both the pharmaceutical industry and academic researchers.,There are now excellent reasons to promote NF-κB signalling intermediates and Rel family proteins as potential therapeutic targets for both asthma and chronic obstructive pulmonary disease.,This notion is supported by the fact that much of the underlying inflammation of both diseases independent of stimuli, is mediated at least in part, by NF-κB mediated signalling events in several cell types.,Also, a range of inhibitors of NF-κB signalling intermediates are now available, including DNA oligonucleotides and DNA-peptide molecules that act as NF-κB decoy sequences, small molecule inhibitors such as IKK-β inhibitors, and proteasome inhibitors affecting NF-κB signalling, that have either shown promise in animal models or have begun clinical trials in other disorders.,This review will focus on the role of NF-κB in both diseases, will discuss its suitability as a target, and will highlight recent key studies that support the potential of NF-κB as a therapeutic target in these two important inflammatory lung diseases. | BMP and activin membrane-bound inhibitor (BAMBI) is postulated to inhibit or modulate transforming growth factor β (TGF-β) signaling.,Furthermore, strong upregulation of BAMBI expression following in vitro infection of chronic obstructive pulmonary disease (COPD) lung tissue has been demonstrated.,In this study, we investigated whether TGF-β/BAMBI pathway is associated with COPD.,Blood samples were obtained from 27 healthy controls (HC), 24 healthy smokers (HS) and 29 COPD patients.,Elevated Th17/Treg ratios, and increased levels of BAMBI protein and mRNA (in plasma and CD4+ T cells respectively), were observed in COPD compared with HC and HS.,BAMBI expression was first observed on human CD4+ T cells, with a typical membrane-bound pattern.,The enhanced plasma BAMBI levels in COPD positively correlated with the increased plasma TGF-β1 levels and Th17/Treg ratio.,Together, an impaired TGF-β/BAMBI pathway may promote the inflammation leading to Th17/Treg imbalance, which is a new mechanism in smokers who develop COPD. | 1 |
Dual bronchodilator maintenance therapy may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) versus long-acting muscarinic antagonist (LAMA) monotherapy.,The efficacy and safety of US-approved LAMA/long-acting beta-agonist (LABA) combinations versus tiotropium (TIO), a LAMA, were assessed.,This systematic review and meta-analysis (GSK: 206938), conducted in MEDLINE, MEDLINE In-process, and EMBASE following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, identified randomized clinical trials (>8 weeks) in moderate-to-severe COPD (per Global Initiative for Chronic Obstructive Lung Disease guidelines), receiving LAMA/LABA or TIO.,Endpoints: difference in change from baseline in lung function (forced expiratory volume in 1 s [FEV1]; trough, peak, area under the curve 0-3 h post-dose (AUC0-3), St George’s Respiratory Questionnaire (SGRQ) responder rate (≥4-unit improvement), SGRQ total score, and rescue medication use at 12 and 24 weeks.,Safety was also assessed.,From 5683 citations, the meta-analysis included eight clinical trials.,LAMA/LABA significantly improved FEV1 trough (Week 12: 63.0 mL, 95% confidence intervals [CI]: 39.2, 86.8; Week 24: 66.1 mL, 95% CI: 40.0, 92.3), peak (Week 12: 91.5 mL, 95% CI: 70.5, 112.4; Week 24: 92.4 mL, 95% CI: 72.9, 111.9), AUC0-3 (Week 12: 126.8 mL, 95% CI: 108.1, 145.4), SGRQ responder rate at Week 12 (risk ratio: 1.19; 95% CI: 1.09, 1.28), mean SGRQ total score (Week 12: −1.87, 95% CI: −2.72, −1.02; Week 24: −1.05, 95% CI: −2.02, −0.09), and rescue medication use (Week 24: −0.47 puffs/day, 95% CI: −0.64, −0.30) versus TIO (all p ≤ 0.03).,The SGRQ responder rate at 24 weeks and adverse events were not significantly different between treatments.,US-approved LAMA/LABA therapies improved lung function, SGR,Q and rescue medication use versus TIO, without compromising safety.,Dual maintenance therapies combining two types of long-acting bronchodilator appear to be effective and safe for treating moderate-to-severe chronic obstructive pulmonary disease (COPD).,Given that patients with COPD often have poor quality of life and, in the US, incur substantial healthcare costs, it is vital to provide optimal symptom management to improve lung function and limit exacerbations over time.,Beth Hahn at GSK, North Carolina, and co-workers carried out a literature review and meta-analysis of 8 clinical trials, which indicates that combined long-acting muscarinic antagonist (LAMA)/long-acting beta-agonist (LABA) treatments-currently prescribed in the US-are an effective and safe way of tackling COPD symptoms.,The team compared patients using LAMA/LABA for 12 weeks with those on single LAMA (tiotropium) treatment and found LAMA/LABA significantly improved lung function and reduced exacerbation risk. | Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms that significantly impair health-related quality of life.,Despite this, COPD treatment and its management are mainly based on lung function assessments.,There is increasing evidence that conventional lung function measures alone do not correlate well with COPD symptoms and their associated impact on patients’ everyday lives.,Instead, symptoms should be assessed routinely, preferably by using patient-centered questionnaires that provide a more accurate guide to the actual burden of COPD.,Numerous questionnaires have been developed in an attempt to find a simple and reliable tool to use in everyday clinical practice.,In this paper, we review three such patient-reported questionnaires recommended by the latest Global Initiative for Chronic Obstructive Lung Disease guidelines, ie, the modified Medical Research Council questionnaire, the clinical COPD questionnaire, and the COPD Assessment Test, as well as other symptom-specific questionnaires that are currently being developed. | 1 |
Despite optimal pharmacological therapy and pulmonary rehabilitation, patients with COPD continue to be breathless.,There is a need to develop additional strategies to alleviate symptoms.,Learning to sing requires control of breathing and posture and might have benefits that translate into daily life.,To test this hypothesis we performed a randomised controlled trial, comparing a six week course of twice weekly singing classes to usual care, in 28 COPD patients.,The experience of singing was assessed in a qualitative fashion, through interviews with a psychologist.,In addition, we surveyed patients with chronic respiratory conditions who participated in a series of open singing workshops.,In the RCT, the physical component score of the SF36 improved in the singers (n = 15) compared to the controls (n = 13); +7.5(14.6) vs. -3.8(8.4) p = 0.02.,Singers also had a significant fall in HAD anxiety score; -1.1(2.7) vs.,+0.8(1.7) p = 0.03.,Singing did not improve single breath counting, breath hold time or shuttle walk distance.,In the qualitative element, 8 patients from the singing group were interviewed.,Positive effects on physical sensation, general well-being, community/social support and achievement/efficacy emerged as common themes. 150 participants in open workshops completed a questionnaire. 96% rated the workshops as "very enjoyable" and 98% thought the workshop had taught them something about breathing in a different way. 81% of attendees felt a "marked physical difference" after the workshop.,Singing classes can improve quality of life measures and anxiety and are viewed as a very positive experience by patients with respiratory disease; no adverse consequences of participation were observed.,Current Controlled Trials - ISRCTN17544114. | Depression is common in COPD patients.,Around 40% are affected by severe depressive symptoms or clinical depression.,It is not easy to diagnose depression in COPD patients because of overlapping symptoms between COPD and depression.,However, the six-item Hamilton Depression Subscale appears to be a useful screening tool.,Quality of life is strongly impaired in COPD patients and patients’ quality of life emerges to be more correlated with the presence of depressive symptoms than with the severity of COPD.,Nortriptyline and imipramine are effective in the treatment of depression, but little is known about the usefulness of newer antidepressants.,In patients with milder depression, pulmonary rehabilitation as well as cognitive-behavioral therapy are effective.,Little is known about the long-term outcome in COPD patients with co-morbid depression.,Preliminary data suggest that co-morbid depression may be an independent protector for mortality. | 1 |
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and the traditional variables extracted from computed tomography (CT) images may not be sufficient to describe all the topological features of lung tissues in COPD patients.,We employed an unsupervised three-dimensional (3D) convolutional autoencoder (CAE)-feature constructor (FC) deep learning network to learn from CT data and derive tissue pattern-clusters jointly.,We then applied exploratory factor analysis (EFA) to discover the unobserved latent traits (factors) among pattern-clusters.,CT images at total lung capacity (TLC) and residual volume (RV) of 541 former smokers and 59 healthy non-smokers from the cohort of the SubPopulations and Intermediate Outcome Measures in the COPD Study (SPIROMICS) were analyzed.,TLC and RV images were registered to calculate the Jacobian (determinant) values for all the voxels in TLC images.,3D Regions of interest (ROIs) with two data channels of CT intensity and Jacobian value were randomly extracted from training images and were fed to the 3D CAE-FC model. 80 pattern-clusters and 7 factors were identified.,Factor scores computed for individual subjects were able to predict spirometry-measured pulmonary functions.,Two factors which correlated with various emphysema subtypes, parametric response mapping (PRM) metrics, airway variants, and airway tree to lung volume ratio were discriminants of patients across all severity stages.,Our findings suggest the potential of developing factor-based surrogate markers for new COPD phenotypes. | Classification of COPD is usually based on the severity of airflow, which may not sensitively differentiate subpopulations.,Using a multiscale imaging-based cluster analysis (MICA), we aim to identify subpopulations for current smokers with COPD.,Among the SPIROMICS subjects, we analyzed computed tomography images at total lung capacity (TLC) and residual volume (RV) of 284 current smokers.,Functional variables were derived from registration of TLC and RV images, e.g. functional small airways disease (fSAD%).,Structural variables were assessed at TLC images, e.g. emphysema and airway wall thickness and diameter.,We employed an unsupervised method for clustering.,Four clusters were identified.,Cluster 1 had relatively normal airway structures; Cluster 2 had an increase of fSAD% and wall thickness; Cluster 3 exhibited a further increase of fSAD% but a decrease of wall thickness and airway diameter; Cluster 4 had a significant increase of fSAD% and emphysema.,Clinically, Cluster 1 showed normal FEV1/FVC and low exacerbations.,Cluster 4 showed relatively low FEV1/FVC and high exacerbations.,While Cluster 2 and Cluster 3 showed similar exacerbations, Cluster 2 had the highest BMI among all clusters.,Association of imaging-based clusters with existing clinical metrics suggests the sensitivity of MICA in differentiating subpopulations.,The online version of this article (10.1186/s12931-018-0888-7) contains supplementary material, which is available to authorized users. | 1 |
Pulmonary rehabilitation (PR), delivered as a supervised multidisciplinary program including exercise training, is one of the cornerstones in the chronic obstructive pulmonary disease (COPD) management.,We performed a systematic review and meta-analysis to assess the effect on mortality of a supervised early PR program, initiated during or within 4 weeks after hospitalization with an acute exacerbation of COPD compared with usual post-exacerbation care or no PR program.,Secondary outcomes were days in hospital, COPD related readmissions, health-related quality of life (HRQoL), exercise capacity (walking distance), activities of daily living (ADL), fall risk and drop-out rate.,We identified randomized trials through a systematic search using MEDLINE, EMBASE and Cocharne Library and other sources through October 2017.,Risk of bias was assessed regarding randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases using the Cochrane Risk of Bias tool.,We included 13 randomized trials (801 participants).,Our meta-analyses showed a clinically relevant reduction in mortality after early PR (4 trials, 319 patients; RR = 0.58 (95% CI: [0.35 to 0.98])) and at the longest follow-up (3 trials, 127 patients; RR = 0.55 (95% CI: [0.12 to 2.57])).,Early PR reduced number of days in hospital by 4.27 days (1 trial, 180 patients; 95% CI: [− 6.85 to − 1.69]) and hospital readmissions (6 trials, 319 patients; RR = 0.47 (95% CI: [0.29 to 0.75])).,Moreover, early PR improved HRQoL and walking distance, and did not affect drop-out rate.,Several of the trials had unclear risk of bias in regard to the randomization and blinding, for some outcome there was also a lack of power.,Moderate quality of evidence showed reductions in mortality, number of days in hospital and number of readmissions after early PR in patients hospitalized with a COPD exacerbation.,Long-term effects on mortality were not statistically significant, but improvements in HRQoL and exercise capacity appeared to be maintained for at least 12 months.,Therefore, we recommend early supervised PR to patients with COPD-related exacerbations.,PR should be initiated during hospital admission or within 4 weeks after hospital discharge.,The online version of this article (10.1186/s12890-018-0718-1) contains supplementary material, which is available to authorized users. | Reduced physical activity (PA) in patients with COPD is associated with a poor prognosis.,Increasing PA is a key therapeutic target, but thus far few strategies have been found effective in this patient group.,To investigate the effectiveness of a 12-week semiautomated telecoaching intervention on PA in patients with COPD in a multicentre European randomised controlled trial.,343 patients from six centres, encompassing a wide spectrum of disease severity, were randomly allocated to either a usual care group (UCG) or a telecoaching intervention group (IG) between June and December 2014.,This 12-week intervention included an exercise booklet and a step counter providing feedback both directly and via a dedicated smartphone application.,The latter provided an individualised daily activity goal (steps) revised weekly and text messages as well as allowing occasional telephone contacts with investigators.,PA was measured using accelerometry during 1 week preceding randomisation and during week 12.,Secondary outcomes included exercise capacity and health status.,Analyses were based on modified intention to treat.,Both groups were comparable at baseline in terms of factors influencing PA.,At 12 weeks, the intervention yielded a between-group difference of mean, 95% CI (lower limit - upper limit; ll-ul) +1469, 95% CI (971 to 1965) steps/day and +10.4, 95% CI (6.1 to 14.7) min/day moderate PA; favouring the IG (all p≤0.001).,The change in 6-min walk distance was significantly different (13.4, 95% CI (3.40 to 23.5) m, p<0.01), favouring the IG.,In IG patients, an improvement could be observed in the functional state domain of the clinical COPD questionnaire (p=0.03) compared with UCG.,Other health status outcomes did not differ.,The amount and intensity of PA can be significantly increased in patients with COPD using a 12-week semiautomated telecoaching intervention including a step counter and an application installed on a smartphone.,NCT02158065. | 1 |
Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV1.,There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline in FEV1.,A cohort of 148 COPD patients (100 men) was monitored daily for a median of 2.91 years (interquartile range [IQR], 2.1 to 4.8).,At recruitment, median age was 68.5 years (IQR, 62.5 to 73.6) and FEV1 as percentage of predicted (FEV1%Pred) was 38.5% (IQR, 27.7 to 50.3).,During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR, 1.48 to 3.96) and FEV1 declined by 40.2 mL/yr or as FEV1%Pred by 1.5%/yr.,Concerning inflammatory markers, sputum interleukin (IL)-6 rose by 9 pg/mL/yr, sputum neutrophil count rose by 1.64 × 106 cells per gram sputum per year, an plasma fibrinogen rose by 0.10 g/L/yr (all p < 0.05).,Patients with frequent exacerbations (≥ 2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063 g/L/yr (p = 0.046, n = 130) and 29.5 pg/mL/yr (p < 0.001, n = 98), respectively, compared to patients with infrequent exacerbations (< 2.52/yr).,Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV1%Pred decline of 0.42%/yr (p = 0.018).,Similarly, a high neutrophil count or fibrinogen were associated with a faster FEV1%Pred decline of 0.97%/yr (p = 0.001) and 0.40%/yr (p = 0.014), respectively.,In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function. | Airway inflammation in COPD can be measured using biomarkers such as induced sputum and FeNO.,This study set out to explore the heterogeneity of COPD using biomarkers of airway and systemic inflammation and pulmonary function by principal components analysis (PCA).,In 127 COPD patients (mean FEV1 61%), pulmonary function, FeNO, plasma CRP and TNF-α, sputum differential cell counts and sputum IL8 (pg/ml) were measured.,Principal components analysis as well as multivariate analysis was performed.,PCA identified four main components (% variance): (1) sputum neutrophil cell count and supernatant IL8 and plasma TNF-α (20.2%), (2) Sputum eosinophils % and FeNO (18.2%), (3) Bronchodilator reversibility, FEV1 and IC (15.1%) and (4) CRP (11.4%).,These results were confirmed by linear regression multivariate analyses which showed strong associations between the variables within components 1 and 2.,COPD is a multi dimensional disease.,Unrelated components of disease were identified, including neutrophilic airway inflammation which was associated with systemic inflammation, and sputum eosinophils which were related to increased FeNO.,We confirm dissociation between airway inflammation and lung function in this cohort of patients. | 1 |
Chronic obstructive pulmonary disease (COPD) exacerbations can negatively impact disease severity, progression, mortality and lead to hospitalizations.,We aimed to develop a model that predicts a patient’s risk of hospitalization due to severe exacerbations (defined as COPD-related hospitalizations) of COPD, using Swedish patient level data.,Patient level data for 7823 Swedish patients with COPD was collected from electronic medical records (EMRs) and national registries covering healthcare contacts, diagnoses, prescriptions, lab tests, hospitalizations and socioeconomic factors between 2000 and 2013.,Models were created using machine-learning methods to predict risk of imminent exacerbation causing patient hospitalization due to COPD within the next 10 days.,Exacerbations occurring within this period were considered as one event.,Model performance was assessed using the Area under the Precision-Recall Curve (AUPRC).,To compare performance with previous similar studies, the Area Under Receiver Operating Curve (AUROC) was also reported.,The model with the highest mean cross validation AUPRC was selected as the final model and was in a final step trained on the entire training dataset.,The most important factors for predicting severe exacerbations were exacerbations in the previous six months and in whole history, number of COPD-related healthcare contacts and comorbidity burden.,Validation on test data yielded an AUROC of 0.86 and AUPRC of 0.08, which was high in comparison to previously published attempts to predict COPD exacerbation.,Our work suggests that clinically available information on patient history collected via automated retrieval from EMRs and national registries or directly during patient consultation can form the basis for future clinical tools to predict risk of severe COPD exacerbations. | This study aimed to generate real-world evidence to assess the burden of comorbidities in COPD patients, to effectively manage these patients and optimize the associated healthcare resource allocation.,ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients using electronic medical record data collected between 2000 and 2014.,These patients were studied for prevalence of various comorbidities and for association of these comorbidities with exacerbations, mortality, and healthcare costs compared with an age-, sex-, and comorbidities-matched non-COPD reference population.,A total of 17,479 patients with COPD were compared with 84,514 non-COPD reference population.,A significantly higher prevalence of various comorbidities was observed in COPD patients 2 years post-diagnosis vs. reference population, with the highest percentage increase observed for cardiovascular diseases (81.8% vs.,30.7%).,Among the selected comorbidities, lung cancer was relatively more prevalent in COPD patients vs. reference population (relative risk, RR = 5.97, p < 0.0001).,Ischemic heart disease, hypertension, depression, anxiety, sleep disorders, osteoporosis, osteoarthritis, and asthma caused increased mortality rates in COPD patients.,Comorbidities that were observed to be significantly associated with increased number of severe exacerbations in COPD patients included heart failure, ischemic heart disease, depression/anxiety, sleep disorders, osteoporosis, lung cancer, and stroke.,The cumulative healthcare costs associated with comorbidities over 2 years after the index date were observed to be significantly higher in COPD patients (€27,692) vs. reference population (€5141) (p < 0.0001).,The data support the need for patient-centered treatment strategies and targeted healthcare resource allocation to reduce the humanistic and economic burden associated with COPD comorbidities.,Co-existing conditions should be taken into consideration when treating patients with chronic lung disease to ensure coherent and cost-effective disease management.,In a large-scale study of the Swedish population, Björn Ställberg at Uppsala University and co-workers analyzed electronic medical records spanning fourteen years for 17,479 patients with chronic obstructive pulmonary disease (COPD) and compared their health status with 84,514 age-, sex- and comorbidity-matched non-COPD members of the population.,Patients with COPD were significantly more likely to suffer from co-morbidities two years after initial diagnosis than their non-COPD counterparts, with cardiovascular diseases being the most common comorbidities.,Lung cancer, hypertension, depression and sleep disorders were among other comorbidities more prevalent in the COPD population.,These data support the need for fully integrated, targeted healthcare to reduce mortality and the economic burden associated with COPD. | 1 |
Viral respiratory infections may precipitate acute exacerbations of COPD (AECOPD).,However, little is known about viral etiology related to AECOPD in Asia.,We aimed to study the viral etiology of AECOPD in Hong Kong.,Patients admitted to an acute hospital in Hong Kong with AECOPD were recruited prospectively from May 1, 2004, to April 30, 2005.,Nasopharyngeal aspirate was collected and assessed by polymerase chain reaction (PCR) and viral culture.,Spirometry was performed in the stable phase at 2 to 3 months after hospital discharge.,There were 262 episodes of AECOPD among 196 patients (mean age, 75.7 ± 7.7 years [± SD]; 160 men).,Mean FEV1 was 39.6 ± 18.9% of predicted normal, and FEV1/FVC ratio was 58.0 ± 15.2%.,Fifty-eight episodes (22.1%) yielded positive viral PCR results.,The viruses identified were influenza A (7.3%), coronavirus OC43 (4.6%), rhinovirus (3.1%), influenza B (2.7%), and respiratory syncytial virus (2.3%).,The diagnostic yield of viral identification by PCR was 2.7 times higher than that based on conventional viral culture.,The rates of identifying a positive viral etiology by PCR were similar among the subjects with FEV1 ≥ 50%, ≥ 30 to 50%, and < 30% of predicted normal.,Viral infection appeared to have no effect on subsequent readmissions or mortality rate over a study period of 1 year,Influenza A and two less-attended viruses, coronavirus OC43 and rhinovirus, were the common etiologic agents in patients hospitalized with AECOPD in Hong Kong.,These should be considered in developing diagnostic and intervening strategies pertaining to AECOPD. | Respiratory viruses frequently are recovered in the upper-respiratory tract during acute exacerbations of COPD (AECOPD), but their role as contributing pathogens remains unclear.,The usefulness of procalcitonin and C-reactive protein as indicators of the presence or absence of viral infection in this setting also needs to be evaluated.,The study was of a prospective cohort of patients with COPD admitted to the ED for AECOPD.,Reverse transcriptase-polymerase chain reaction (RT-PCR) for 14 respiratory viruses was performed on nasopharyngeal swabs collected at admission and after recovery in stable condition.,Eighty-six patients (mean age, 72 years; male, 64%) were included.,During AECOPD, upper-respiratory viral infections were detected in 44 (51%) patients: picornavirus in 22, metapneumovirus in seven, coronavirus in eight, influenza A/B in two, parainfluenza in two, and respiratory syncytial virus in three.,A dual infection was present in three patients.,After recovery, viruses were detected in only eight (11%) of 71 patients (P < .001 compared with AECOPD phase).,In five of these patients, no virus had been identified during the initial exacerbation, thus suggesting a new viral infection acquired during follow-up.,During AECOPD, procalcitonin and C-reactive protein levels did not differ significantly between patients with or without a proven viral infection.,Prevalence of upper-respiratory viral infection, as detected from nasopharyngeal swab by RT-PCR, is high in AECOPD and low after clinical recovery, suggesting that AECOPD frequently are triggered by viral infections initiated in the upper-respiratory tract.,In our study, serum procalcitonin and C-reactive protein did not discriminate virus-associated exacerbations from others.,clinicaltrials.gov; Identifier: NCT00448604. | 1 |
To illuminate patients’ lived experiences of going through the process of being diagnosed with chronic obstructive pulmonary disease (COPD).,A phenomenological-hermeneutic analysis was applied in the interpretation of interviews with eight persons diagnosed with mild or moderate COPD.,One main theme ‘living in negotiation’, and three themes ‘living with a body out of step with the diagnosis’, ‘dealing with the past’, and ‘being challenged by the future’ reflected the process participants were living through in their quest for acceptance and a new balance in life.,Participants found that the diagnostic processes were confusing, and that the diagnosis itself was ‘a slap in the face’.,Unclear messages gave rise to fluctuating between an understanding of the condition as ‘not too severe’, insecurity, and fear.,Shame and guilt related to the diagnosis had origins in the past, and in combination with the idea of ‘chronic’ the COPD diagnosis interfered with the present moment and gave rise to uncertainty for the future.,The understanding of the present is related to negotiations not only with the past, but also with the future.,Thus temporal aspects of the diagnosis are of great significance for the process of finding acceptance.,Regardless of disease severity, the diagnosis seems to be a breakdown of life, which puts life itself at stake.,Medical professionals should be aware that the way the diagnosis is disclosed and communicated has considerable significance for how individuals understand and deal with their illness.,The diagnosis should be communicated face-to-face, clearly and with empathy, and followed by information about COPD.,Physicians should allow time and listen to the patients’ stories, and thus develop a shared understanding of the temporal aspect of the illness and patients’ needs and concerns.,Thus, good communication is essential in determining whether the patient remains in negotiation, or enters a process toward acceptance and new understanding. | 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 |
Exacerbations explain much of the cost of COPD.,Higher blood eosinophil cell counts at admission for acute exacerbation of COPD increase the risk of subsequent exacerbations and hospitalizations.,However, there is no literature on the economic burden of patients with this inflammatory profile.,The objective of this study is to assess the cost of health-care service utilization according to different counts of blood eosinophils.,The observational retrospective cohort included all first hospitalizations for COPD exacerbation between April 2006 and March 2013.,The eosinophilic group was defined by blood eosinophil counts on admission ≥200 cells/µL and/or ≥2% of the total white blood cell count.,Study outcomes were: total costs (2016 Canadian dollars) (index hospitalization and 1-year follow-up), total index hospitalization costs, total 1-year costs (all-cause readmissions, ambulatory and emergency service use), and 1-year COPD-related costs (only cost for COPD after initial discharge).,Sensitivity analyses were conducted to evaluate the impact of different eosinophil cut-offs on outcomes.,In total, 479 patients were included, 173 in the eosinophilic group (92 in the higher cut-off).,The average total cost was $18,263 ($6,706 for the index hospitalization), without significant difference between groups (P=0.3).,The average 1-year COPD-related cost was higher in the eosinophilic group ($3,667 vs $2,472, P=0.006), with an adjusted mean difference of $1,416.,Analysis of data using the higher cut-off of ≥400 cells or ≥3% was associated with a slightly larger difference in 1-year COPD-related costs between groups ($4,060 vs $2,629, P=0.003), with an adjusted mean difference of $1,640.,A higher blood eosinophil cell count at admission for a first hospitalization is associated with an increase in total 1-year COPD-related costs. | 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 |
Frailty is an important clinical syndrome that is consistently associated with adverse outcomes in older people.,The relevance of frailty to chronic respiratory disease and its management is unknown.,To determine the prevalence of frailty among patients with stable COPD and examine whether frailty affects completion and outcomes of pulmonary rehabilitation.,816 outpatients with COPD (mean (SD) age 70 (10) years, FEV1% predicted 48.9 (21.0)) were recruited between November 2011 and January 2015.,Frailty was assessed using the Fried criteria (weight loss, exhaustion, low physical activity, slowness and weakness) before and after pulmonary rehabilitation.,Predictors of programme non-completion were identified using multivariate logistic regression, and outcomes were compared using analysis of covariance, adjusting for age and sex.,209/816 patients (25.6%, 95% CI 22.7 to 28.7) were frail.,Prevalence of frailty increased with age, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, Medical Research Council (MRC) score and age-adjusted comorbidity burden (all p≤0.01).,Patients who were frail had double the odds of programme non-completion (adjusted OR 2.20, 95% CI 1.39 to 3.46, p=0.001), often due to exacerbation and/or hospital admission.,However, rehabilitation outcomes favoured frail completers, with consistently better responses in MRC score, exercise performance, physical activity level and health status (all p<0.001).,After rehabilitation, 71/115 (61.3%) previously frail patients no longer met case criteria for frailty.,Frailty affects one in four patients with COPD referred for pulmonary rehabilitation and is an independent predictor of programme non-completion.,However, patients who are frail respond favourably to rehabilitation and their frailty can be reversed in the short term. | COPD is one of the most debilitating diseases.,Frailty syndrome and advanced age may decrease the acceptance of illness, quality of life, and worsen health conditions in these patients, as well as lead to an increase in health care expenses.,The aim of the study was to assess how the level of frailty affects the acceptance of illness in elderly patients with COPD.,We also aimed to evaluate the associations between sociodemographic and clinical factors and the level of acceptance of illness, anxiety, and frailty in this group of patients.,The study included 102 COPD patients with a mean age of 63.2 (standard deviation =6.5) years and grades I (3%), II (37%), III (52%), and IV (8%) by Global Initiative for Chronic Obstructive Lung Disease.,The Polish versions of the Acceptance of Illness Scale and Tilburg frailty indicator were used.,Frailty syndrome was found in 77 (75.5%) patients, with an average score of 7.42 (standard deviation =2.24).,Coexisting diseases such as hypertension (46.07%), coronary artery disease (32.35%), heart failure (28.43%), diabetes (18.63%), and heart arrhythmia (9.8%) were found among the subjects.,The overall level of acceptance of illness was 20.6 (standard deviation =7.62).,A lower level of acceptance of illness was associated with a higher level of frailty, especially in the physical and social domain.,Elderly patients with severe COPD are more prone to frailty and decreased acceptance of their disease in comparison to patients with other chronic diseases.,Assessment and management of frailty in the care of older COPD patients are likely to improve risk stratification significantly and help personalize management, leading to better patient outcomes. | 1 |
Skeletal muscle dysfunction in patients with chronic obstructive pulmonary disease (COPD) is not fully reversed by exercise training.,Antioxidants are critical for muscle homeostasis and adaptation to training.,However, COPD patients experience antioxidant deficits that worsen after training and might impact their muscle response to training.,Nutritional antioxidant supplementation in combination with pulmonary rehabilitation (PR) would further improve muscle function, oxidative stress, and PR outcomes in COPD patients.,Sixty-four COPD patients admitted to inpatient PR were randomized to receive 28 days of oral antioxidant supplementation targeting the previously observed deficits (PR antioxidant group; α-tocopherol: 30 mg/day, ascorbate: 180 mg/day, zinc gluconate: 15 mg/day, selenomethionine: 50 μg/day) or placebo (PR placebo group).,PR consisted of 24 sessions of moderate-intensity exercise training.,Changes in muscle endurance (primary outcome), oxidative stress, and PR outcomes were assessed.,Eighty-one percent of the patients (FEV1 = 58.9 ± 20.0%pred) showed at least one nutritional antioxidant deficit.,Training improved muscle endurance in the PR placebo group (+37.4 ± 45.1%, p < 0.001), without additional increase in the PR antioxidant group (-6.6 ± 11.3%; p = 0.56).,Nevertheless, supplementation increased the α-tocopherol/γ-tocopherol ratio and selenium (+58 ± 20%, p < 0.001, and +16 ± 5%, p < 0.01, respectively), muscle strength (+11 ± 3%, p < 0.001), and serum total proteins (+7 ± 2%, p < 0.001), and it tended to increase the type I fiber proportion (+32 ± 17%, p = 0.07).,The prevalence of muscle weakness decreased in the PR antioxidant group only, from 30.0 to 10.7% (p < 0.05).,While the primary outcome was not significantly improved, COPD patients demonstrate significant improvements of secondary outcomes (muscle strength and other training-refractory outcomes), suggesting a potential “add-on” effect of the nutritional antioxidant supplementation (vitamins C and E, zinc, and selenium) during PR.,This trial is registered with NCT01942889. | This study aimed to evaluate the effects of vitamin D intake on COPD exacerbation and FEV1 in the patients with severe and very severe COPD.,This double blind placebo control randomized clinical trial study was done in the Ashayer university hospital in Khorramabad in 2012.,Eighty eight patients with severe and very severe COPD were randomly selected from those who recoursed to the internal medicine clinic of Ashayer hospital.,They were randomly allocated to case and placebo group.,The patients received routine treatment for COPD.,Along with the routine treatment, placebo group received 100,000 IU of oral vitamin D per month, for 6 months.,Data was analyzed using SPSS computer software, paired t-test, independent t-test, non parametric t-test and Pearson correlation coefficients.,In each group, there were 44 patients.,After the intervention, there were significant differences in FEV1 and the number of COPD exacerbation between the case and control group patients.,Also, after the study, in the case group, FEV1 was increased and the number of COPD exacerbation was decreased significantly.,Vitamin D intake decreased COPD exacerbation and improved FEV1 in the patients with severe and very severe COPD.,It is suggested that baseline serum vitamin D levels will recorded in similar studies and the effect of vitamin D intake will evaluated regarding the baseline serum vitamin D levels. | 1 |
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by multiple subtypes and variable disease progression.,Blood biomarkers have been variably associated with subtype, severity, and disease progression.,Just as combined clinical variables are more highly predictive of outcomes than individual clinical variables, we hypothesized that multiple biomarkers may be more informative than individual biomarkers to predict subtypes, disease severity, disease progression, and mortality.,Fibrinogen, C-Reactive Protein (CRP), surfactant protein D (SP-D), soluble Receptor for Advanced Glycation Endproducts (sRAGE), and Club Cell Secretory Protein (CC16) were measured in the plasma of 1465 subjects from the COPDGene cohort and 2746 subjects from the ECLIPSE cohort.,Regression analysis was performed to determine whether these biomarkers, individually or in combination, were predictive of subtypes, disease severity, disease progression, or mortality, after adjustment for clinical covariates.,In COPDGene, the best combinations of biomarkers were: CC16, sRAGE, fibrinogen, CRP, and SP-D for airflow limitation (p < 10−4), SP-D, CRP, sRAGE and fibrinogen for emphysema (p < 10−3), CC16, fibrinogen, and sRAGE for decline in FEV1 (p < 0.05) and progression of emphysema (p < 10−3), and all five biomarkers together for mortality (p < 0.05).,All associations except mortality were validated in ECLIPSE.,The combination of SP-D, CRP, and fibrinogen was the best model for mortality in ECLIPSE (p < 0.05), and this combination was also significant in COPDGene.,This comprehensive analysis of two large cohorts revealed that combinations of biomarkers improve predictive value compared with clinical variables and individual biomarkers for relevant cross-sectional and longitudinal COPD outcomes.,The online version of this article (doi:10.1186/s12931-017-0597-7) contains supplementary material, which is available to authorized users. | Chronic Obstructive Pulmonary Disease (COPD) is characterised by reduced lung function and is the third leading cause of death globally.,Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97.,A genetic risk score was associated with COPD susceptibility (odds ratios per standard deviation of the risk score (~6 alleles) (95% confidence interval) 1.24 (1.20-1.27), P=5.05x10-49) and we observed a 3.7 fold difference in COPD risk between highest and lowest genetic risk score deciles in UK Biobank.,The 97 signals show enrichment in development, elastic fibres and epigenetic regulation pathways.,We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications. | 1 |
COPD is a complex, heterogeneous condition.,Even in the early clinical stages, COPD carries a significant burden, with breathlessness frequently leading to a reduction in exercise capacity and changes that correlate with long-term patient outcomes and mortality.,Implementation of an effective management strategy is required to reduce symptoms, preserve lung function, quality of life, and exercise capacity, and prevent exacerbations.,However, current clinical practice frequently differs from published guidelines on the management of COPD.,This review focuses on the current scientific evidence and expert opinion on the management of moderate COPD: the symptoms arising from moderate airflow obstruction and the burden these symptoms impose, how physical activity can improve disease outcomes, the benefits of dual bronchodilation in COPD, and the limited evidence for the benefits of inhaled corticosteroids in this disease.,We emphasize the importance of maximizing bronchodilation in COPD with inhaled dual-bronchodilator treatment, enhancing patient-related outcomes, and enabling the withdrawal of inhaled corticosteroids in COPD in well-defined patient groups. | 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 |
Abstract: Chronic obstructive pulmonary disease (COPD) is a major public health problem and its prevalence and mortality are increasing throughout the world, including the Asia-Pacific region.,To arrest these worldwide trends, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Expert Panel's global strategy for the diagnosis, management, and prevention of COPD was published in 2001.,Based on recently published clinical trials, the GOLD statement was updated in 2003.,The Asia-Pacific COPD Roundtable Group, a taskforce of expert respirologists from the Asia-Pacific region, has recently formulated a consensus statement on implementation of the GOLD strategy for COPD in the Asia-Pacific region.,The key issues identified by the COPD Roundtable Group for comment are: (i) where there is no access to spirometry, diagnosis of COPD could be suspected on the basis of history, symptoms and physical signs; (ii) inhaled bronchodilators are the preferred regular treatment for COPD in the region, but oral bronchodilators may be considered if the cost of inhaled bronchodilators is a barrier to treatment; (iii) the use of an Metered Dose Inhaler with spacer in place of a nebulizer is recommended in the treatment of acute airflow obstruction in patients with COPD; (iv) influenza vaccination is recommended for all patients with COPD in communities where there is a high likelihood of Severe Acute Respitory Syndrome; and (v) simplified pulmonary rehabilitation programmes should be established in areas where comprehensive programmes are unavailable.,Physical exercise training and education on smoking cessation should be core elements of any rehabilitation program.,In summary, the COPD Roundtable Group supports implementation of the GOLD strategy for the diagnosis, management and prevention of COPD in the Asia-Pacific region, subject to the additions and modifications to the guidelines suggested above. | 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 |
To assess clinical characteristics and device satisfaction of patients with chronic obstructive pulmonary disease (COPD) treated with glycopyrrolate/eFlow® Closed System (CS) nebulizer (further referred to as eFlow) under real-world conditions.,Patients with COPD currently using eFlow were identified by the study sponsor.,Consenting patients who met study inclusion criteria completed a cross-sectional survey that included a device satisfaction questionnaire.,Means, medians, and standard deviations were calculated.,Sixty-six patients met inclusion criteria and completed the survey.,Participants’ mean ± standard deviation age was 64.9 ± 11.9 years and the majority were white (86.4%) and female (59.1%).,Almost two-thirds were former smokers.,Thirty-nine (59.1%) reported their COPD to be severe/very severe and 38 (57.6%) reported a COPD exacerbation resulting in a hospitalization, ER visit, or medication modification over the past 12 months.,Among 55 participants who had previously used another type of nebulizer, 44 (80%) were overall “much more”/“somewhat more” satisfied with the eFlow compared with their previous nebulizer(s).,Regardless of prior nebulizer use, 60 (90.9%) participants were “satisfied”/“very satisfied” overall with the eFlow.,Assembly and disassembly, operation, and cleaning were perceived as being “easy”/“very easy” by at least 65% of participants.,Among all participants, 57 (86.4%) were “confident”/“very confident” of glycopyrrolate administration.,On a Likert scale of 1 (“I don’t like it”) to 7 (“I like it a lot”), mean scores were at least 5.9 for portability, ease of cleaning, size, weight, short administration time, and relative silence of the device.,Over 80% of participants said they “probably”/"definitely" would continue to use eFlow.,Based on this real-world study, the majority of patients were highly satisfied with, and confident in, using eFlow. | Rescue medication use is common in chronic obstructive pulmonary disease (COPD) patients and tends to increase with symptoms and disease severity.,An analysis of baseline rescue medication use was conducted to inform on patient phenotypes and subsequent effects on lung function, symptoms, and safety following 12 weeks of nebulized glycopyrrolate (GLY) 25 µg twice daily or placebo in patients with moderate-to-very-severe COPD.,Pooled data from the 12-week, placebo-controlled GOLDEN 3 and 4 studies (n=781) were used to assign patients into quarters based on baseline rescue medication use (ie, average puffs-per-day) during the run-in period.,Placebo-adjusted trough forced expiratory volume in 1 second (FEV1), St.,George’s Respiratory Questionnaire (SGRQ) total score and EXAcerbations of COPD Tool-Respiratory Symptoms (EXACT-RS) total score data were reported; safety was evaluated by reviewing the incidence of adverse events (AEs) and serious AEs (SAEs).,Baseline rescue medication use was a proxy for disease severity, evidenced by decreased lung function, increased health status scores, symptom scores and use of background long-acting β2-agonists and inhaled corticosteroids across quarters and treatment groups.,Treatment with GLY led to greater improvements from baseline in trough FEV1, SGRQ and EXACT-RS scores compared with placebo in all rescue medication use quarters.,Additionally, the SGRQ and EXACT-RS exhibited greater improvement with increased baseline rescue medication use with GLY treatment.,In the Q4 patients, SGRQ (≥4-unit reduction) or EXACT-RS (≥2-unit reduction) responders were significantly greater with GLY compared with placebo.,AE and SAE incidences were similar across quartiles.,These results suggest that baseline rescue medication use assessments may be useful in the management of COPD.,Treatment with nebulized GLY improved lung function and symptom scores, regardless of baseline rescue medication use.,These results support the use of nebulized GLY for the treatment of COPD, independent of baseline rescue medication use. | 1 |
Public health is a priority for the Chinese Government.,Evidence-based decision making for health at the province level in China, which is home to a fifth of the global population, is of paramount importance.,This analysis uses data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to help inform decision making and monitor progress on health at the province level.,We used the methods in GBD 2017 to analyse health patterns in the 34 province-level administrative units in China from 1990 to 2017.,We estimated all-cause and cause-specific mortality, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), summary exposure values (SEVs), and attributable risk.,We compared the observed results with expected values estimated based on the Socio-demographic Index (SDI).,Stroke and ischaemic heart disease were the leading causes of death and DALYs at the national level in China in 2017.,Age-standardised DALYs per 100 000 population decreased by 33·1% (95% uncertainty interval [UI] 29·8 to 37·4) for stroke and increased by 4·6% (-3·3 to 10·7) for ischaemic heart disease from 1990 to 2017.,Age-standardised stroke, ischaemic heart disease, lung cancer, chronic obstructive pulmonary disease, and liver cancer were the five leading causes of YLLs in 2017.,Musculoskeletal disorders, mental health disorders, and sense organ diseases were the three leading causes of YLDs in 2017, and high systolic blood pressure, smoking, high-sodium diet, and ambient particulate matter pollution were among the leading four risk factors contributing to deaths and DALYs.,All provinces had higher than expected DALYs per 100 000 population for liver cancer, with the observed to expected ratio ranging from 2·04 to 6·88.,The all-cause age-standardised DALYs per 100 000 population were lower than expected in all provinces in 2017, and among the top 20 level 3 causes were lower than expected for ischaemic heart disease, Alzheimer's disease, headache disorder, and low back pain.,The largest percentage change at the national level in age-standardised SEVs among the top ten leading risk factors was in high body-mass index (185%, 95% UI 113·1 to 247·7]), followed by ambient particulate matter pollution (88·5%, 66·4 to 116·4).,China has made substantial progress in reducing the burden of many diseases and disabilities.,Strategies targeting chronic diseases, particularly in the elderly, should be prioritised in the expanding Chinese health-care system.,China National Key Research and Development Program and Bill & Melinda Gates Foundation. | Traditional Chinese medicine (TCM) has been used to treat chronic obstructive pulmonary disease (COPD) for many years.,This study aimed to evaluate the efficacy and safety of the comprehensive therapy based on the three common TCM patterns in stable COPD patients.,A four-center, open-label randomized controlled method was conducted.,A total of 352 patients were divided into the trial group (n = 176, treated with conventional Western medicine and Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules, and Yi-Qi Zi-Shen granules based on the TCM patterns respectively) and the control group (n = 176, treated with conventional Western medicine).,The frequency and duration of acute exacerbation, lung function, clinical symptoms, 6-minute walking distance (6MWD), dyspnea scale and quality of life were observed during a 6-month treatment period and at a further 12-month follow-up.,A total of 306 patients completed the study fully.,The full analysis set (FAS) population was 350 and the per-protocol analysis set (PPS) population was 306.,After the 6-month treatment and 12-month follow-up, there were significant differences between the trial and control group in the following: frequency of acute exacerbation (FAS: P = 0.000; PPS: P = 0.000); duration of acute exacerbation (FAS: P = 0.000; PPS: P = 0.001); FEV1 (FAS: P = 0.007; PPS: P = 0.008); symptoms (FAS: P = 0.001; PPS: P = 0.001); 6MWD (FAS: P = 0.045; PPS: P = 0.042); dyspnea scale (FAS: P = 0.002; PPS: P = 0.004); and physical domain (FAS: P = 0.000; PPS: P = 0.000), psychological domain (FAS: P = 0.008; PPS: P = 0.011), social domain (FAS: P = 0.001; PPS: P = 0.000) and environment domain (FAS: P = 0.015; PPS: P = 0.009) of the WHOQOL-BREF questionnaire.,There were no differences between the trial and control group in FVC, FEV1% and adverse events.,Based on the TCM patterns, Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules and Yi-Qi Zi-Shen granules have beneficial effects on measured outcomes in stable COPD patients over the 6-month treatment and 12-month follow-up, with no relevant between-group differences in adverse events.,This trial was registered at Chinese Clinical Trial Register Center, ChiCTR-TRC-11001406. | 1 |
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. | Most interventions aimed at reducing hospitalizations and emergency department (ED) visits in patients with chronic obstructive pulmonary disease (COPD) have employed resource-intense programs in high-risk individuals.,Although COPD is a progressive disease, little is known about the effectiveness of proactive interventions aimed at preventing hospitalizations and ED visits in the much larger population of low-risk (no known COPD-related hospitalizations or ED visits in the prior year) patients, some of whom will eventually become high-risk.,We tested the effect of a simple educational and self-efficacy intervention (n = 2243) versus usual care (n = 2182) on COPD/breathing-related ED visits and hospitalizations in a randomized study of low-risk patients at three Veterans Affairs (VA) medical centers in the upper Midwest.,Administrative data was used to track VA admissions and ED visits.,A patient survey was used to determine health-related events outside the VA.,Rates of COPD-related VA hospitalizations in the education and usual care group were not significantly different (3.4 versus 3.6 admissions per 100 person-years, respectively; 95% CI of difference −1.3 to 1.0, P = 0.77).,The much higher patient-reported rates of non-VA hospitalizations for breathing-related problems were lower in the education group (14.0 versus 19.0 per 100 person-years; 95% CI −8.6 to −1.4, P = 0.006).,Rates of COPD-related VA ED visits were not significantly different (6.8 versus 5.3; 95% CI −0.1 to 3.0, P = 0.07), nor were non-VA ED visits (32.4 versus 36.5; 95% CI −9.3 to 1.1, P = 0.12).,All-cause VA admission and ED rates did not differ.,Mortality rates (6.9 versus 8.3 per 100 person-years, respectively; 95% CI −3.0 to 0.4, P = 0.13) did not differ.,An educational intervention that is practical for large numbers of low-risk patients with COPD may reduce the rate of breathing-related hospitalizations.,Further research that more closely tracks hospitalizations to non-VA facilities is needed to confirm this finding. | 1 |
Cachectic patients with chronic obstructive pulmonary disease (COPD) may benefit from nutritional support.,This double‐blind, randomized, controlled trial evaluated the safety and efficacy of targeted medical nutrition (TMN) vs. an isocaloric comparator in pre‐cachectic and cachectic patients with COPD.,Patients aged ≥50 years with moderate‐to‐severe COPD and involuntary weight loss or low body mass index (16-18 kg/m2) were randomized 1:1 to receive TMN (~230 kcal; 2 g omega‐3 fatty acids; 10 μg 25‐hydroxy‐vitamin D3) or isocaloric comparator twice daily for 12 weeks (ClinicalTrials.gov Identifier: NCT02442908).,Primary safety endpoints comprised adverse events and changes in vital signs, laboratory parameters, and concomitant medications.,Secondary efficacy endpoints included changes in weight, body composition, exercise tolerance, metabolic biomarkers, and systemic inflammation.,Forty‐five patients were randomized to receive TMN (n = 22; mean 69.2 years) or isocaloric comparator (n = 23; mean 69.7 years).,TMN was well tolerated.,Adverse events were similar in number and type in both groups.,Compliance to both products was good (TMN, 79%; comparator, 77%).,Both groups gained weight, but the TMN group gained comparatively more fat mass (P = 0.0013).,Reductions in systolic blood pressure (P = 0.0418) and secondary endpoints of triglycerides (P = 0.0217) and exercise‐induced fatigue (P = 0.0223) and dyspnoea (P = 0.0382), and increases in high‐density lipoprotein cholesterol (P = 0.0254), were observed in the TMN vs. the comparator group by week 12.,Targeted medical nutrition containing high‐dose omega‐3 fatty acids, vitamin D, and high‐quality protein is well tolerated with a good safety profile and has positive effects on blood pressure and blood lipids and on exercise‐induced fatigue and dyspnoea.,Therefore, this TMN could be clinically beneficial in the nutritional and metabolic support of pre‐cachectic and cachectic patients with COPD. | A decrease in bone mineral density (BMD) is a systemic consequence of chronic obstructive pulmonary disease (COPD).,Past reports have rarely examined any correlation between sarcopenia and BMD.,We investigated the relationship cross-sectionally between the presence of sarcopenia and BMD reduction in COPD patients.,COPD patients aged 50 or older with qualifying spirometry and dual-energy X-ray absorptiometry data were from participants in the Korean National Health and Nutrition Examination Surveys IV and V (2008-2011).,There were 286 (33.3%) subjects in the sarcopenia group and 572 (66.7%) in the non-sarcopenia group.,The sarcopenia group had lower T-scores than the non-sarcopenia group (femur: -0.73±0.88 vs. -0.18±0.97, p < 0.001; femur neck: -1.44±0.98 vs. -0.99±1.06, p < 0.001; lumbar: -1.38±1.36 vs. -0.84±1.38, p < 0.001).,The prevalences of osteopenia and osteoporosis were 60.8% and 22.0%, respectively, in the sarcopenia group and 45.6% and 13.3% in the non-sarcopenia group (both p < 0.001).,After adjusting for multiple variables, the presence of sarcopenia associated with increased the risk of osteopenia, osteoporosis, and a low BMD (OR = 3.227, 95% CI = 2.125-4.899, p < 0.001, OR = 6.952, 95% CI = 3.418-14.139, p < 0.001, and OR = 3.495, 95% CI = 2.315-5.278, p < 0.001, respectively).,In a subgroup analysis, similar OR changes were confirmed in the high-body-weight group (n = 493) (OR = 2.248, 95% CI = 1.084-4.665, p = 0.030, OR = 4.621, 95% CI = 1.167-18.291, p = 0.029, and OR = 2.376, 95% CI = 1.158-4.877, p = 0.018, respectively).,The presence of sarcopenia was associated with increased the risk for decreased BMD in COPD. | 1 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.