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There is no independent standardized self-management approach available for chronic obstructive pulmonary disease (COPD).,The aim of this project was to develop and test a novel self-management manual for individuals with COPD.,Participants with a confirmed diagnosis of COPD were recruited from primary care.,A novel self-management manual was developed with health care professionals and patients.,Five focus groups were conducted with individuals with COPD (N = 24) during development to confirm and enhance the content of the prototype manual.,The Self-management Programme of Activity, Coping and Education for Chronic Obstructive Pulmonary Disease (SPACE for COPD) manual was developed as the focus of a comprehensive self-management approach facilitated by health care professionals.,Preference for delivery was initial face-to-face consultation with telephone follow-up.,The SPACE for COPD manual was piloted with 37 participants in primary care.,Outcome measures included the Self-Report Chronic Respiratory Questionnaire, Incremental Shuttle Walk Test, and Endurance Shuttle Walking Test (ESWT); measurements were taken at baseline and 6 weeks.,The pilot study observed statistically significant improvements for the dyspnea domain of the Self-Report Chronic Respiratory Questionnaire and ESWT.,Dyspnea showed a mean change of 0.67 (95% confidence interval 0.23-1.11, P = 0.005).,ESWT score increased by 302.25 seconds (95% confidence interval 161.47-443.03, P < 0.001).,This article describes the development and delivery of a novel self-management approach for COPD.,The program, incorporating the SPACE for COPD manual, appears to provoke important changes in exercise capacity and breathlessness for individuals with COPD managed in primary care. | People with chronic obstructive pulmonary disease (COPD) continue to experience dyspnea with activities of daily living (ADL) despite optimal medical management.,Information and communication technologies may facilitate collaborative symptom management and could potentially increase the reach of such interventions to those who are unable to attend face-to-face pulmonary rehabilitation or self-management programs.,The purpose of this randomized study was to test the efficacy of two 6-month dyspnea self-management programs, Internet-based (eDSMP) and face-to-face (fDSMP), on dyspnea with ADL in people living with COPD.,We randomly assigned 50 participants with moderate to severe COPD who were current Internet users to either the eDSMP (n = 26) or fDSMP (n = 24) group.,The content of the two programs was similar, focusing on education, skills training, and ongoing support for dyspnea self-management, including independent exercise.,The only difference was the mode (Internet/personal digital assistant [PDA] or face-to-face) in which the education sessions, reinforcement contacts, and peer interactions took place.,Participants returned to one of two academic clinical sites for evaluation at 3 and 6 months.,The primary outcome of dyspnea with ADL was measured with the Chronic Respiratory Questionnaire.,Secondary outcomes of exercise behavior, exercise performance, COPD exacerbations, and mediators, such as self-efficacy and social support, were also measured.,A satisfaction survey was administered and a semistructured exit interview was conducted at the final visit.,The study was stopped early due to multiple technical challenges with the eDSMP, but follow-up was completed on all enrolled participants.,Data were available for 39 participants who completed the study (female: 44%; age: 69.5 ± 8.5 years; percent predicted forced expiratory volume in 1 s: 49.6 ± 17.0%).,The fDSMP and eDSMP showed similar clinically meaningful changes in dyspnea with ADL from baseline to 3 months (fDSMP: + 3.3 points; eDSMP: + 3.5 points) and sustained these improvements at 6 months (fDSMP: + 4.0 points; eDSMP: + 2.5 points; time effects P < .001; group by time P = .51).,Self-reported endurance exercise time (P = .001), physical functioning (P = .04), and self-efficacy for managing dyspnea (P = .02) also showed positive improvements over time in both groups with no significant differences with respect to program modality.,Participants who completed the study reported favorable satisfaction with the programs.,Although there were numerous technical challenges with the eDSMP, both dyspnea self-management programs were effective in reducing dyspnea with ADL in the short term.,Our findings will need to be confirmed in a larger randomized trial with more mature Web and personal digital assistant tools, use of a control group, and longer follow-up.,clinicaltrials.gov NCT00102401, http://www.webcitation.org/5X8CX4gLC | 1 |
We explore potential dysregulation of macrophage phenotypes in COPD pathogenesis through integrated study of human small airway tissue, bronchoalveolar lavage (BAL) and an experimental murine model of COPD.,We evaluated human airway tissue and BAL from healthy controls, normal lung function smokers (NLFS), and COPD subjects.,Both small airways and BAL cells were immunohistochemically stained with anti-CD68 for total macrophages and with anti-CD163 for M2, and anti-iNOS for M1 macrophages.,Multiplex ELISA measured BAL cytokines.,Comparable cigarette smoke-induced experimental COPD mouse model was assessed for relevant mRNA profiles.,We found an increase in pro-inflammatory M1s in the small airways of NLFS and COPD compared to controls with a reciprocal decrease in M2 macrophages, which remained unchanged among pathological groups.,However, luminal macrophages showed a dominant M2 phenotype in both NLFS and COPD subjects.,BAL cytokine skewed towards an M2 profile with increase in CCL22, IL-4, IL-13, and IL-10 in both NLFS and COPDs.,The mouse-model of COPD showed similar increase in mRNA for M2 markers.,Our finding suggests abnormal macrophage switching in both mucosal and luminal areas of COPD patients, that strongly associated with cytokine balance.,There may be potential for beneficial therapeutic cytokine manipulation of macrophage phenotypes in COPD. | Chronic obstructive pulmonary disease (COPD) is characterized by inflammation and remodeling of the lungs.,This results in alterations in extracellular matrix (ECM) and structural changes leading to airflow obstruction.,We studied the expression of tenascin-C (Tn-C) and alpha smooth muscle actin (α-SMA), which act as a marker of myofibroblasts, in large airways from COPD patients.,Our aim was to elucidate whether this expression correlated with smoking or with disease development.,Bronchoscopy was performed on 20 COPD patients (mean age 56 years; range 39-61; FEV1/FVC < 70% and FEV1 median 53% (range 33-69) of predicted).,Age and smoking matched smokers (S) without COPD (n = 13) and age matched non-smokers (NS) (n = 14) served as controls.,Bronchial mucosal biopsies were analyzed by immunohistochemistry.,The distribution of Tn-C expression was assessed and graded in three levels, and the number of spindle shaped cells staining positive for α-SMA were counted.,Biopsies from COPD patients had more (P < 0.001) Tn-C expression than the two control groups.,A significantly (P < 0.05) increased number of spindle shaped cells expressing α-SMA was observed in COPD patients compared with the controls.,Smokers and nonsmokers did not differ in this respect.,The expression of Tn-C correlated positively (P < 0.001) to the number of α-SMA positive cells.,We demonstrate increased expression of Tn-C and α-SMA positive cells in the large airways in COPD.,This was not associated to smoking per se, but to the presence of airway obstruction.,Our findings add new information regarding remodeling characteristics and highlight the large airways as a potential site for airways obstruction in COPD. | 1 |
Advanced chronic obstructive pulmonary disease (COPD) often leads to hospitalisation and invasive aspergillosis (IA) is a serious complication.,Aspergillus sensitisation may worsen symptoms in COPD.,We identified published papers between January 2000 and May 2019 with > 50 subjects and GOLD criteria for grade II, III or IV (FEV1/FVC < 70% and FEV1 < 80%) using standardised criteria in multiple countries, to re-estimate the prevalence of COPD.,Hospitalised COPD patients develop IA in 1.3-3.9%, based on positive cultures of Aspergillus spp. and radiological findings.,Given limited data on per-patient annual hospitalisation rates, we assumed a conservative 10.5% estimate.,Annual IA mortality in COPD was estimated using the literature rates of 43-72%.,A separate literature search assessed the impact of Aspergillus sensitisation on severity of COPD (by FEV1).,We re-estimated the global prevalence of COPD GOLD stages II-IV at 552,300,599 people (7.39% of the population) with 339,206,893 (8.58%) in Asia, 85,278,783 (8.52%) in the Americas, 64,298,051 (5.37%) in Africa, 59,484,329 (7.77%) in Europe and 4,032,543 (10.86%) in Oceania.,An estimated 57,991,563 (10.5%) people with COPD are admitted to hospital annually and of these 753,073 (1.3%) - 2,272,322 (3.9%) develop IA and 540,451-977,082 deaths are predicted annually.,Aspergillus sensitisation prevalence in COPD was 13.6% (7.0-18.3%) and not related to lower predicted FEV1% (P > 0.05).,The prevalence of COPD is much higher than previously estimated.,Overall COPD mortality may be higher than estimated and IA probably contributes to many deaths.,Improved rapid diagnosis of IA using culture and non-culture based techniques is required in COPD hospital admissions to reduce mortality. | Despite the availability of guideline recommendations, diagnostic confusion between COPD and asthma appears common, and often it is very difficult to decide whether the obstruction is caused by asthma or COPD in a patient with airway obstruction.,However, there are well-defined features that help in differentiating asthma from COPD in the presence of fixed airflow obstruction.,Nonetheless, the presentations of asthma and COPD can converge and mimic each other, making it difficult to give these patients a diagnosis of either condition.,The association of asthma and COPD in the same patient has been designated mixed asthma-COPD phenotype or overlap syndrome.,However, since the absence of a clear definition and the inclusion of patients with different characteristics under this umbrella term, it may not facilitate treatment decisions, especially in the absence of clinical trials addressing this heterogeneous population.,We are realizing that neither asthma nor COPD are single diseases, but rather syndromes consisting of several endotypes and phenotypes, consequently comprising a spectrum of diseases that must be recognized and adequately treated with targeted therapy.,Therefore, we must treat patients by personalizing therapy on the basis of those treatable traits present in each subject. | 1 |
Evidence regarding the efficacy of nutritional supplementation to enhance exercise training responses in COPD patients with low muscle mass is limited.,The objective was to study if nutritional supplementation targeting muscle derangements enhances outcome of exercise training in COPD patients with low muscle mass.,Eighty‐one COPD patients with low muscle mass, admitted to out‐patient pulmonary rehabilitation, randomly received oral nutritional supplementation, enriched with leucine, vitamin D, and omega‐3 fatty acids (NUTRITION) or PLACEBO as adjunct to 4 months supervised high intensity exercise training.,The study population (51% males, aged 43-80) showed moderate airflow limitation, low diffusion capacity, normal protein intake, low plasma vitamin D, and docosahexaenoic acid.,Intention‐to‐treat analysis revealed significant differences after 4 months favouring NUTRITION for body mass (mean difference ± SEM) (+1.5 ± 0.6 kg, P = 0.01), plasma vitamin D (+24%, P = 0.004), eicosapentaenoic acid (+91%,P < 0.001), docosahexaenoic acid (+31%, P < 0.001), and steps/day (+24%, P = 0.048).,After 4 months, both groups improved skeletal muscle mass (+0.4 ± 0.1 kg, P < 0.001), quadriceps muscle strength (+12.3 ± 2.3 Nm,P < 0.001), and cycle endurance time (+191.4 ± 34.3 s, P < 0.001).,Inspiratory muscle strength only improved in NUTRITION (+0.5 ± 0.1 kPa, P = 0.001) and steps/day declined in PLACEBO (−18%,P = 0.005).,High intensity exercise training is effective in improving lower limb muscle strength and exercise performance in COPD patients with low muscle mass and moderate airflow obstruction.,Specific nutritional supplementation had additional effects on nutritional status, inspiratory muscle strength, and physical activity compared with placebo. | COPD is accompanied by limited physical activity, worse quality of life, and increased prevalence of depression.,A possible link between COPD and depression may be irisin, a myokine, expression of which in the skeletal muscle and brain positively correlates with physical activity.,Irisin enhances the synthesis of brain-derived neurotrophic factor (BDNF), a neurotrophin involved in reward-related processes.,Thus, we hypothesized that mood disturbances accompanying COPD are reflected by the changes in the irisin-BDNF axis.,Case history, routine laboratory parameters, serum irisin and BDNF levels, pulmonary function, and disease-specific quality of life, measured by St George’s Respiratory Questionnaire (SGRQ), were determined in a cohort of COPD patients (n=74).,Simple and then multiple linear regression were used to evaluate the data.,We found that mood disturbances are associated with lower serum irisin levels (SGRQ’s Impacts score and reciprocal of irisin showed a strong positive association; β: 419.97; 95% confidence interval [CI]: 204.31, 635.63; P<0.001).,This association was even stronger among patients in the lower 50% of BDNF levels (β: 434.11; 95% CI: 166.17, 702.05; P=0.002), while it became weaker for patients in the higher 50% of BDNF concentrations (β: 373.49; 95% CI: −74.91, 821.88; P=0.1).,These results suggest that irisin exerts beneficial effect on mood in COPD patients, possibly by inducing the expression of BDNF in brain areas associated with reward-related processes involved in by depression.,Future interventional studies targeting the irisin-BDNF axis (eg, endurance training) are needed to further support this notion. | 1 |
Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome that predominantly affects male smokers or ex-smokers and it has a mortality rate of 55% and a median survival of 5 years.,Pulmonary hypertension (PH) is a frequently fatal complication of CPFE.,Despite this dismal prognosis, no curative therapies exist for patients with CPFE outside of lung transplantation and no therapies are recommended to treat PH.,This highlights the need to develop novel treatment approaches for CPFE.,Studies from our group have demonstrated that both adenosine and its receptor ADORA2B are elevated in chronic lung diseases.,Activation of ADORA2B leads to elevated levels of hyaluronan synthases (HAS) and increased hyaluronan, a glycosaminoglycan that contributes to chronic lung injury.,We hypothesize that ADORA2B and hyaluronan contribute to CPFE.,Using isolated CPFE lung tissue, we characterized expression levels of ADORA2B and HAS.,Next, using a unique mouse model of experimental lung injury that replicates features of CPFE, namely airspace enlargement, PH and fibrotic deposition, we investigated whether 4MU, a HAS inhibitor, was able to inhibit features of CPFE.,Increased protein levels of ADORA2B and HAS3 were detected in CPFE and in our experimental model of CPFE.,Treatment with 4MU was able to attenuate PH and fibrosis but not airspace enlargement.,This was accompanied by a reduction of HAS3-positive macrophages.,We have generated pre-clinical data demonstrating the capacity of 4MU, an FDA-approved drug, to attenuate features of CPFE in an experimental model of chronic lung injury.,This article has an associated First Person interview with the first author of the paper.,Summary: Fibrotic deposition and PH are inhibited by the FDA-approved drug hymecromone, suggesting hyaluronan synthesis inhibition as a potential therapy for CPFE and highlighting a novel mechanism through HAS3-positive macrophages. | Clinical evaluation to differentiate the characteristic features of pulmonary fibrosis and emphysema is often difficult in patients with combined pulmonary fibrosis and emphysema (CPFE), but diagnosis of pulmonary fibrosis is important for evaluating treatment options and the risk of acute exacerbation of interstitial pneumonia of such patients.,As far as we know, it is the first report describing a correlation among clinical, radiological, and whole-lung pathological features in an autopsy cases of CPFE patients.,Experts retrospectively reviewed the clinical charts and examined chest computed tomography (CT) images and pathological findings of an autopsy series of 22 CPFE patients, and compared these with findings from 8 idiopathic pulmonary fibrosis (IPF) patients and 17 emphysema-alone patients.,All patients had a history of heavy smoking.,Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC%) was significantly lower in the emphysema-alone group than the CPFE and IPF-alone groups.,The percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) was significantly lower in the CPFE group than the IPF- and emphysema-alone groups.,Usual interstitial pneumonia (UIP) pattern was observed radiologically in 15 (68.2%) CPFE and 8 (100%) IPF-alone patients and was pathologically observed in all patients from both groups.,Pathologically thick-cystic lesions involving one or more acini with dense wall fibrosis and occasional fibroblastic foci surrounded by honeycombing and normal alveoli were confirmed by post-mortem observation as thick-walled cystic lesions (TWCLs).,Emphysematous destruction and enlargement of membranous and respiratory bronchioles with fibrosis were observed in the TWCLs.,The cystic lesions were always larger than the cysts of honeycombing.,The prevalence of both radiological and pathological TWCLs was 72.7% among CPFE patients, but no such lesions were observed in patients with IPF or emphysema alone (p = 0.001).,The extent of emphysema in CPFE patients with TWCLs was greater than that in patients without such lesions.,Honeycombing with emphysema was also observed in 11 CPFE patients.,TWCLs were only observed in the CPFE patients.,They were classified as lesions with coexistent fibrosing interstitial pneumonia and emphysema, and should be considered an important pathological and radiological feature of CPFE. | 1 |
Several clinical studies suggest common underlying pathogenetic mechanisms of COPD and depressive/anxiety disorders.,We aim to evaluate psychopathological and physical effects of aerobic exercise, proposed in the context of pulmonary rehabilitation, in a sample of COPD patients, through the correlation of some psychopathological variables and physical/pneumological parameters.,Fifty-two consecutive subjects were enrolled.,At baseline, the sample was divided into two subgroups consisting of 38 depression-positive and 14 depression-negative subjects according to the Hamilton Depression Rating Scale (HAM-D).,After the rehabilitation treatment, we compared psychometric and physical examinations between the two groups.,The differences after the rehabilitation program in all assessed parameters demonstrated a significant improvement in psychiatric and pneumological conditions.,The reduction of BMI was significantly correlated with fat mass but only in the depression-positive patients.,Our results suggest that pulmonary rehabilitation improves depressive and anxiety symptoms in COPD.,This improvement is significantly related to the reduction of fat mass and BMI only in depressed COPD patients, in whom these parameters were related at baseline.,These findings suggest that depressed COPD patients could benefit from a rehabilitation program in the context of a multidisciplinary approach. | The aim was to compare the diagnosis of COPD among smokers according to different international guidelines and to compare the outcome when using slow (SVC) and forced vital capacity (FVC).,In order to find current smokers a questionnaire was sent to persons who had been on sick leave for more than two weeks.,Those who smoked more than 8 cigarettes per day were invited to perform a spirometry.,Totally 3,887 spirometries were performed.,In this sample 10.2% fulfilled the NICE COPD-criteria, 14.0% the GOLD COPD-criteria and 21.7% the ERS COPD criteria.,The diagnosis according to NICE and GOLD guidelines is based on FVC and in the ERS guidelines the best value of either SVC or FVC is used.,Thus, substantially more subjects with COPD were found when the best of either SVC or FVC was used.,Forced VC tended to be higher than SVC when lung function was normal and in those with mild obstruction prior to bronchodilatation whereas SVC exceeded FVC after bronchodilatation in those who had severe bronchial obstruction.,The diagnosis of COPD is highly depending on which guidelines are used for defining the disease.,If FVC and not the best of SVC and FVC is used when defining COPD the diagnosis will be missed in a substantial number of patients. | 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. | Chronic obstructive pulmonary disease (COPD) has been consistently associated with increased risk of lung cancer.,However, previous studies have had limited ability to determine whether the association is due to smoking.,The Environment And Genetics in Lung cancer Etiology (EAGLE) population-based case-control study recruited 2100 cases and 2120 controls, of whom 1934 cases and 2108 controls reported about diagnosis of chronic bronchitis, emphysema, COPD (chronic bronchitis and/or emphysema), or asthma more than 1 year before enrollment.,We estimated odds ratios (OR) and 95% confidence intervals (CI) using logistic regression.,After adjustment for smoking, other previous lung diseases, and study design variables, lung cancer risk was elevated among individuals with a history of chronic bronchitis (OR = 2.0, 95% CI = 1.5-2.5), emphysema (OR = 1.9, 95% CI = 1.4-2.8), or COPD (OR = 2.5, 95% CI = 2.0-3.1).,Among current smokers, association between chronic bronchitis and lung cancer was strongest among lighter smokers.,Asthma was associated with a decreased risk of lung cancer in males (OR = 0.48, 95% CI = 0.30-0.78).,These results suggest that the associations of personal history of chronic bronchitis, emphysema, and COPD with increased risk of lung cancer are not entirely due to smoking.,Inflammatory processes may both contribute to COPD and be important for lung carcinogenesis. | 1 |
Although COPD exacerbations are known to occur more frequently in winter, there is little information on hospitalizations and cause-specific mortality.,This study aimed to examine seasonal variations in mortality and exacerbations in patients with COPD during the TIOtropium Safety and Performance In Respimat® (TIOSPIR®) trial.,TIOSPIR was a large-scale, multicenter trial, which assessed the safety and efficacy of tiotropium delivered via HandiHaler® (18 μg once daily) or Respimat® Soft Mist™ (2.5 or 5 μg once daily) inhaler in patients with COPD.,Patients were aged ≥40 years, with a smoking history ≥10 pack-years, and post-bronchodilator forced expiratory volume in 1 second ≤70% and forced expiratory volume in 1 second/forced vital capacity ≤0.70.,COPD exacerbations and deaths were monitored throughout the trial.,The data were pooled to examine seasonal patterns.,Southern hemisphere data were shifted by 6 months to align with northern hemisphere seasons.,TIOSPIR was conducted in 43 northern (n=15,968) and 7 southern (n=1,148) hemisphere (n=1,148) countries.,The median duration of treatment was 835 days, with a mean follow-up of 2.3 years.,Among 19,494 exacerbations, there were clear seasonal differences (winter, 6,646 [34.1%]; spring, 4,515 [23.2%]; summer, 3,198 [16.4%]; autumn, 5,135 [26.3%]).,Exacerbations peaked in early winter (December in the northern hemisphere and June in the southern hemisphere), respiratory hospitalizations in midwinter, and respiratory deaths in early spring.,Although winter poses a 2-fold hazard for COPD exacerbations vs summer, respiratory deaths peak in early spring.,These data suggest that seasonal intensification of preventive treatments may impact COPD morbidity and mortality.,NCT01126437. | Excluding the tropics, exacerbations of chronic obstructive pulmonary disease (COPD) are more frequent in winter.,However, studies that directly relate hospitalizations for exacerbation of COPD to ambient temperature are lacking.,The aim of this study was to assess the influence of temperature on the number of hospitalizations for COPD.,This was a population-based study in a metropolitan area.,All hospital discharges for acute exacerbation of COPD during 2009 in Barcelona and its metropolitan area were analyzed.,The relationship between the number of hospitalizations for COPD and the mean, minimum, and maximum temperatures alongside comorbidity, humidity, influenza rate, and environmental pollution were studied.,A total of 9,804 hospitalization discharges coded with COPD exacerbation as a primary diagnosis were included; 75.4% of cases were male with a mean age of 74.9±10.5 years and an average length of stay of 6.5±6.1 days.,The highest number of admissions (3,644 [37.2%]) occurred during winter, followed by autumn with 2,367 (24.1%), spring with 2,347 (23.9%), and summer with 1,446 (14.7%; P<0.001).,The maximum, minimum, and mean temperatures were associated similarly with the number of hospitalizations.,On average, we found that for each degree Celsius decrease in mean weekly temperature, hospital admissions increased by 5.04% (r2=0.591; P<0.001).,After adjustment for humidity, comorbidity, air pollution, and influenza-like illness, only mean temperatures retained statistical significance, with a mean increase of 4.7% in weekly admissions for each degree Celsius of temperature (r2=0.599, P<0.001).,Mean temperatures are closely and independently related to the number of hospitalizations for COPD. | 1 |
It has recently been proposed that the concept of clinical control in COPD may be useful for deciding treatment in COPD, but the original control criteria (OCC) were considered too restrictive.,Define and subsequently validate “modified” control criteria (MCC) of COPD.,Prospective observational study in COPD patients with a 1-year follow-up.,Control was defined as the presence of low clinical impact and clinical stability.,To evaluate clinical impact, the following clinical parameters were assessed: the degree of dyspnea, use of rescue medication, physical activity, and sputum color.,Stability was assessed by clinical changes and exacerbations in the last 3 months.,The COPD assessment test score and their changes were also evaluated as alternative control criteria.,To define the MCC, adjustment for disease severity using BODEx index (MCC-B) or FEV1 (MCC-F) was evaluated, and the best cutoff point was established.,Time to first combined event (emergency visit, hospitalization, or death) was analyzed to evaluate the predictive capacity of risk of the OCC, MCC-B, and MCC-F.,We included 265 patients, 224 (83.9%) men, with a mean age (±SD) of 68±9 years and FEV1 of 58%±17%.,The proportion of controlled patients was higher using clinical MCC-B or MCC-F (61.5% and 59.6%) than OCC (27.5%).,Similar percentages were found using COPD assessment test scores.,The time to the first combined event was significantly greater in controlled patients using MCC criteria (P<0.001, all cases).,The predictive capacity of risk was similar in MCC-B (c-statistic [C]=0.639) and MCC-F (C=0.637) and higher than OCC (C=0.589).,The new MCC identified a higher number of controlled COPD patients.,These patients have a better quality of life and lower risk of poor outcomes.,The concept of control and the new MCC could be a useful tool to optimize therapy. | Patient-reported outcome (PRO) measures that quantify disease impact have become important measures of outcome in COPD research and treatment.,The objective of this literature review was to comprehensively evaluate psychometric properties of available PRO instruments and the ability of each of them to characterize pharmaceutical treatment effects from published clinical trial evidence.,Identified in this study were several PRO measures, both those that have been used extensively in COPD clinical trials (St George’s Respiratory Questionnaire and Chronic Respiratory Questionnaire) and new instruments whose full value is still to be determined.,This suggests a great need for more information about the patient experience of treatment benefit, but this also may pose challenges to researchers, clinicians, and other important stakeholders (eg, regulatory agencies, pharmaceutical companies) who develop new treatment entities and payers (including but not limited to health technology assessment agencies such as the National Institute for Health and Care Excellence and the Canadian Agency for Drugs and Technologies in Health).,The purpose of this review is to enable researchers and clinicians to gain a broad overview of PRO measures in COPD by summarizing the value and purpose of these measures and by providing sufficient detail for interested audiences to determine which instrument may be the most suitable for evaluating a particular research purpose. | 1 |
Reducing rescue medication use is a guideline-defined goal of asthma treatment, however, little is known about the validity of rescue medicine use as a marker of symptoms in chronic obstructive pulmonary disease (COPD).,To improve patient outcomes, greater insight is needed into the relationship between rescue medication use and alternative COPD outcomes.,A systematic search of electronic databases (Embase®, MEDLINE® and Cochrane CENTRAL) was conducted from database start to 26 May, 2015.,Studies of bronchodilator therapy with a duration of ≥24 weeks were included if they reported either mean change from baseline (CFB) in rescue medication use in puffs/day or % rescue-free days (%RFD), and at least one other COPD endpoint.,Correlation and meta-regression analyses were undertaken to test the association between rescue medication use and other COPD outcomes using weighted means (weights proportional to the sample size of the treatment group) and unweighted means (equal weight for each treatment group).,Each association was assessed at 6 months and study end.,Forty-six studies involving 46,531 patients provided mean data from 145 treatment groups for evaluation.,Changes in both measures of rescue medication use were correlated with changes in trough forced expiratory volume in one second ([FEV1]; Pearson correlation coefficients |r| ≥ 0.63; p < 0.0001) and with St George’s Respiratory Questionnaire (SGRQ) score (|r| ≥ 0.70; p < 0.0001) at study end.,Change in rescue medication use in puffs/day during the study correlated with annualized rates of moderate/severe exacerbations at 6 months and study end (both r = 0.66; p ≤ 0.0028).,CFB in puffs/day was not well correlated with Transition Dyspnoea Index (TDI), but %RFD did correlate with TDI score at 6 months and study end (both r = 0.69; p < 0.0001).,The values for CFB in puffs/day corresponding to the proposed minimal clinically important differences for trough FEV1 and SGRQ score were -1.3 and -0.6 puffs/day, respectively.,A -1.0 puffs/day CFB in rescue use corresponded to a change of 0.26 events/patient-year in moderate/severe exacerbations.,This analysis provides clear evidence of associations at a patient group level between rescue medication use and other clinically important COPD outcomes.,The online version of this article (doi:10.1186/s12931-017-0566-1) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is characterized by a persistent blockage of airflow, prompting episodes of shortness of breath, commonly leading to hospitalization.,Hospitalization may lead to a decline in physical activity following discharge.,Physical activity has been shown to improve symptoms of COPD and reduce readmissions, and to decrease morbidity and mortality.,This study aims to explore, from the perspectives of people with COPD, the barriers to and enablers of participation in physical activity following hospitalization for COPD.,This study had a qualitative descriptive design and included semistructured interviews with 28 adult COPD patients who had been admitted to hospital with a primary diagnosis of exacerbation of COPD.,A plethora of barriers to but fewer enablers of participation in physical activity and pulmonary rehabilitation were identified for this cohort of people.,The main barriers identified were health-related (comorbidities, COPD symptoms, and physical injury or illness) environment-related (weather, transport, and finance), and self-related.,The main enabling factors reported were access to health professionals and equipment, social support, routine and extracurricular activities, personal goals and motivation, and the effect of physical activity and “feeling better”.,This research provides a snapshot of the barriers to and enablers of physical activity and pulmonary rehabilitation in people with COPD.,It is evident that there are significant barriers which hinder the ability of people with COPD to undertake and continue participation in physical activity and pulmonary rehabilitation.,While there are some enablers that may counter these barriers, it is clear that health professionals dealing with people suffering from COPD need to actively recognize and address barriers to physical activity and pulmonary rehabilitation.,Hospital admission may create an opportunity for implementation of interventions promoting physical activity (such as referral to pulmonary rehabilitation), which may assist in reducing hospital readmission, as well as decreasing morbidity and mortality. | 1 |
Self-management support for chronic obstructive pulmonary disease (COPD) patients is recommended by UK national guidelines, but extent of implementation is unknown.,We aimed to describe self-management behaviour and support among COPD patients and explore behaviour associated with having a self-management plan.,We undertook cross-sectional analysis of self-reported data from diagnosed COPD patients in the Birmingham COPD Cohort study.,Questionnaire items relevant to self-management behaviour, knowledge of COPD, receipt of self-management plans and advice from healthcare professionals were examined.,Multiple regression models were used to identify behaviour associated with having a self-management plan.,One-thousand seventy-eight participants (676 males, 62.7%, mean age 69.8 (standard deviation 9.0) years) were included.,The majority reported taking medications as instructed (940, 94.0%) and receiving annual influenza vaccinations (962, 89.2%).,Only 400 (40.4%) participants had self-management plans, 538 (49.9%) reported never having received advice on diet/exercise and 110 (42.7%) current smokers had been offered practical help to stop smoking in the previous year.,General knowledge about COPD was moderate (mean total Bristol COPD Knowledge Questionnaire score: 31.5 (standard deviation 10.7); max score 65), corresponding to 48.5% of questions answered correctly.,Having a self-management plan was positively associated with self-reported adherence to medication (odds ratio 3.10, 95% confidence interval 1.43 to 6.72), attendance at a training course (odds ratio 2.72, 95% confidence interval 1.81 to 4.12), attendance at a support group (odds ratio 6.28, 95% confidence interval 2.96 to 13.35) and better disease knowledge (mean difference 4.87, 95% confidence interval 3.16 to 6.58).,Primary care healthcare professionals should ensure more widespread implementation of individualised self-management plans for all patients and improve the lifestyle advice provided.,Health professionals should ensure all patients with chronic lung disease receive individualized self-management plans and lifestyle advice.,UK national guidelines state that patients with chronic obstructive pulmonary disease (COPD) should receive personalized self-management plans and comprehensive support to help them manage their disease.,Ainee Khan and colleagues at the University of Birmingham analyzed patient questionnaire data gathered during the Birmingham COPD Cohort study to explore self-management behavior, receipt of self-management plans and advice, and patient knowledge of COPD.,Of 1,078 participants, only 400 had self-management plans, and less than half reported receiving lifestyle advice or support.,Those with plans were more likely to adhere to medication, had greater knowledge about COPD and were more likely to attend support groups and training courses.,The authors recommend carefully-planned, wider implementation of COPD self-management plans and associated support. | Clinical guidelines for management of patients with chronic obstructive pulmonary disease (COPD) include recommendations based on high levels of evidence, but gaps exist in their implementation.,The aim of this study was to examine the perspectives of medical practitioners regarding implementation of six high-evidence recommendations for the management of people with COPD.,Semi-structured interviews were conducted with medical practitioners involved with care of COPD patients in hospital and general practice.,Interviews sought medical practitioners’ experience regarding implementation of smoking cessation, influenza vaccination, pulmonary rehabilitation, guideline-based medications, long-term oxygen therapy for hypoxemia and plan and advice for future exacerbations.,Interviews were audiotaped, transcribed verbatim and analyzed using content analysis.,Nine hospital-based medical practitioners and seven general practitioners participated.,Four major categories were identified which impacted on implementation of the target recommendations in the care of patients with COPD: (1) role clarity of the medical practitioner; (2) persuasive communication with the patient; (3) complexity of behavioral change required; (4) awareness and support available at multiple levels.,For some recommendations, strength in all four categories provided significant enablers supporting implementation.,However, with regard to pulmonary rehabilitation and plans and advice for future exacerbations, all identified categories that presented barriers to implementation.,This study of medical practitioner perspectives has indicated areas where significant barriers to the implementation of key evidence-based recommendations in COPD management persist.,Developing strategies to target the identified categories provides an opportunity to achieve greater implementation of those high-evidence recommendations in the care of people with COPD. | 1 |
Obesity is increasingly associated with COPD, but little is known about the prevalence of ectopic fat accumulation in COPD and whether this can possibly be associated with poor clinical outcomes and comorbidities.,The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) substudy tested the hypothesis that COPD is associated with increased ectopic fat accumulation and that this would be associated with COPD-related outcomes and comorbidities.,Computed tomography (CT) images of the thorax obtained in ECLIPSE were used to quantify ectopic fat accumulation at L2-L3 (eg, cross-sectional area [CSA] of visceral adipose tissue [VAT] and muscle tissue [MT] attenuation, a reflection of muscle fat infiltration) and CSA of MT.,A dose-response relationship between CSA of VAT, MT attenuation and CSA of MT and COPD-related outcomes (6-minute walking distance [6MWD], exacerbation rate, quality of life, and forced expiratory volume in 1 second [FEV1] decline) was addressed with the Cochran-Armitage trend test.,Regression models were used to investigate possible relationships between CT body composition indices and comorbidities.,From the entire ECLIPSE cohort, we identified 585 subjects with valid CT images at L2-L3 to assess body composition.,CSA of VAT was increased (P<0.0001) and MT attenuation was reduced (indicating more muscle fat accumulation) in patients with COPD (P<0.002).,Progressively increasing CSA of VAT was not associated with adverse clinical outcomes.,The probability of exhibiting low 6MWD and accelerated FEV1 decline increased with progressively decreasing MT attenuation and CSA of MT.,In COPD, the probability of having diabetes (P=0.024) and gastroesophageal reflux (P=0.0048) at baseline increased in parallel with VAT accumulation, while the predicted MT attenuation increased the probability of cardiovascular comorbidities (P=0.042).,Body composition parameters did not correlate with coronary artery scores or with survival.,Ectopic fat accumulation is increased in COPD, and this was associated with relevant clinical outcomes and comorbidities. | Previous studies have suggested links between chronic obstructive pulmonary disease (COPD), cardiovascular disease, and abdominal obesity.,Although abdominal visceral fat is thought to be associated with cardiovascular risk factors, the degree of visceral fat accumulation in patients with COPD has not been directly studied.,The aim of this study was to investigate the abdominal visceral fat accumulation and the association between visceral fat and the severity and changes in emphysema in COPD patients.,We performed clinical and laboratory tests, including pulmonary function, dyspnea score, and the six-minute walking test in COPD patients (n = 101) and control, which included subjects with a smoking history but without airflow obstruction (n = 62).,We used computed tomography to evaluate the abdominal visceral fat area (VFA), subcutaneous fat area (SFA), and the extent of emphysema.,The COPD group had a larger VFA than the control group.,The prevalence of non-obese subjects with an increased VFA was greater in the Global Initiative for Chronic Obstructive Lung Disease Stages III and IV than in the other stages of COPD.,The extent of emphysema was inversely correlated with waist circumference and SFA.,However, VFA did not decrease with the severity of emphysema.,VFA was positively correlated with the degree of dyspnea.,COPD patients have excessive visceral fat, which is retained in patients with more advanced stages of COPD or severe emphysema despite the absence of obesity. | 1 |
Oxidative stress contributes to chronic obstructive pulmonary disease (COPD) exacerbations and antioxidants can decrease exacerbation rates, although we lack data about the effect of such drugs on exacerbation duration.,The RESTORE (Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD) study was a prospective randomised, double-blind, placebo-controlled study, enrolling patients aged 40-80 years with Global Initiative for Chronic Obstructive Lung Disease stage II/III.,Patients received erdosteine 300 mg twice daily or placebo added to usual COPD therapy for 12 months.,The primary outcome was the number of acute exacerbations during the study.,In the pre-specified intention-to-treat population of 445 patients (74% male; mean age 64.8 years, forced expiratory volume in 1 s 51.8% predicted) erdosteine reduced the exacerbation rate by 19.4% (0.91 versus.,1.13 exacerbations·patient−1·year−1 for erdosteine and placebo, respectively; p=0.01), due to an effect on mild events; the reduction in the rate of mild exacerbations was 57.1% (0.23 versus 0.54 exacerbations·patient−1·year−1 for erdosteine and placebo, respectively; p=0.002).,No significant difference was observed in the rate of moderate and severe exacerbations (0.68 versus 0.59 exacerbations·patient−1·year−1 for erdosteine and placebo, respectively; p=0.054) despite a trend in favour of the comparison group.,Erdosteine decreased the exacerbation duration irrespective of event severity by 24.6% (9.55 versus 12.63 days for erdosteine and placebo, respectively; p=0.023).,Erdosteine significantly improved subject and physician subjective severity scores (p=0.022 and p=0.048, respectively), and reduced the use of reliever medication (p<0.001), but did not affect the St George's Respiratory Questionnaire score or the time to first exacerbation.,In patients with COPD, erdosteine can reduce both the rate and duration of exacerbations.,The percentage of patients with adverse events was similar in both the placebo and erdosteine treatment groups.,RESTORE study: erdosteine reduces both rate and duration of COPD exacerbations with a placebo-like safety profilehttp://ow.ly/BbGI30dRdEt | Chronic obstructive pulmonary disease (COPD) imposes a substantial burden on individuals with the disease, which can include a range of symptoms (breathlessness, cough, sputum production, wheeze, chest tightness) of varying severities.,We present an overview of the biomedical literature describing reported relationships between COPD symptoms and disease burden in terms of quality of life, health status, daily activities, physical activity, sleep, comorbid anxiety, and depression, as well as risk of exacerbations and disease prognosis.,In addition, the substantial variability of COPD symptoms encountered (morning, daytime, and nighttime) is addressed and their implications for disease burden considered.,The findings from this narrative review, which mainly focuses on real-world and observational studies, demonstrate the impact of COPD symptoms on the burden of disease and that improved recognition and understanding of their impact is central to alleviating this burden. | 1 |
Increased interferon gamma (IFNγ) release occurs in Chronic Obstructive Pulmonary Disease (COPD) lungs.,IFNγ supports optimal viral clearance, but if dysregulated could increase lung tissue destruction.,The present study investigates which mediators most closely correlate with IFNγ in sputum in stable and exacerbating disease, and seeks to shed light on the spatial requirements for innate production of IFNγ, as reported in mouse lymph nodes, to observe whether such microenvironmental cellular organisation is relevant to IFNγ production in COPD lung.,We show tertiary follicle formation in severe disease alters the dominant mechanistic drivers of IFNγ production, because cells producing interleukin-18, a key regulator of IFNγ, are highly associated with such structures.,Interleukin-1 family cytokines correlated with IFNγ in COPD sputum.,We observed that the primary source of IL-18 in COPD lungs was myeloid cells within lymphoid aggregates and IL-18 was increased in severe disease.,IL-18 released from infected epithelium or from activated myeloid cells, was more dominant in driving IFNγ when IL-18-producing and responder cells were in close proximity.,Unlike tight regulation to control infection spread in lymphoid organs, this local interface between IL-18-expressing and responder cell is increasingly supported in lung as disease progresses, increasing its potential to increase tissue damage via IFNγ.,The online version of this article (doi:10.1186/s12931-017-0641-7) contains supplementary material, which is available to authorized users. | Understanding the genetic basis of airflow obstruction and smoking behaviour is key to determining the pathophysiology of chronic obstructive pulmonary disease (COPD).,We used UK Biobank data to study the genetic causes of smoking behaviour and lung health.,We sampled individuals of European ancestry from UK Biobank, from the middle and extremes of the forced expiratory volume in 1 s (FEV1) distribution among heavy smokers (mean 35 pack-years) and never smokers.,We developed a custom array for UK Biobank to provide optimum genome-wide coverage of common and low-frequency variants, dense coverage of genomic regions already implicated in lung health and disease, and to assay rare coding variants relevant to the UK population.,We investigated whether there were shared genetic causes between different phenotypes defined by extremes of FEV1.,We also looked for novel variants associated with extremes of FEV1 and smoking behaviour and assessed regions of the genome that had already shown evidence for a role in lung health and disease.,We set genome-wide significance at p<5 × 10−8.,UK Biobank participants were recruited from March 15, 2006, to July 7, 2010.,Sample selection for the UK BiLEVE study started on Nov 22, 2012, and was completed on Dec 20, 2012.,We selected 50 008 unique samples: 10 002 individuals with low FEV1, 10 000 with average FEV1, and 5002 with high FEV1 from each of the heavy smoker and never smoker groups.,We noted a substantial sharing of genetic causes of low FEV1 between heavy smokers and never smokers (p=2·29 × 10−16) and between individuals with and without doctor-diagnosed asthma (p=6·06 × 10−11).,We discovered six novel genome-wide significant signals of association with extremes of FEV1, including signals at four novel loci (KANSL1, TSEN54, TET2, and RBM19/TBX5) and independent signals at two previously reported loci (NPNT and HLA-DQB1/HLA-DQA2).,These variants also showed association with COPD, including in individuals with no history of smoking.,The number of copies of a 150 kb region containing the 5′ end of KANSL1, a gene that is important for epigenetic gene regulation, was associated with extremes of FEV1.,We also discovered five new genome-wide significant signals for smoking behaviour, including a variant in NCAM1 (chromosome 11) and a variant on chromosome 2 (between TEX41 and PABPC1P2) that has a trans effect on expression of NCAM1 in brain tissue.,By sampling from the extremes of the lung function distribution in UK Biobank, we identified novel genetic causes of lung function and smoking behaviour.,These results provide new insight into the specific mechanisms underlying airflow obstruction, COPD, and tobacco addiction, and show substantial shared genetic architecture underlying airflow obstruction across individuals, irrespective of smoking behaviour and other airway disease.,Medical Research Council. | 1 |
The DYNAGITO study was a Phase IIIb, randomized, double-blind, multicenter, active-controlled, parallel-group, 52-week study designed to determine the efficacy and safety of tiotropium and olodaterol combination therapy (TIO+OLO 5/5 μg) versus tiotropium monotherapy (TIO 5 μg) for reducing moderate-to-severe exacerbations of COPD.,This is a prespecified analysis of the DYNAGITO data in Japanese patients.,Enrolled patients had a diagnosis of COPD with at least one moderate-to-severe exacerbation in the previous 12 months.,Of the total 7,880 treated patients in the DYNAGITO study, 461 (TIO+OLO 5/5 μg: n=226, TIO 5 μg: n=235) were Japanese.,The primary endpoint was the annualized rate of moderate-to-severe COPD exacerbations.,The key secondary endpoint was the time to first moderate-to-severe COPD exacerbation, and other secondary endpoints included the annualized rate of exacerbations leading to hospitalization, time to first COPD exacerbation leading to hospitalization, and all-cause mortality.,Safety data were analyzed descriptively.,Combination therapy with TIO+OLO resulted in a 29% lower rate of moderate-to-severe COPD exacerbations relative to TIO monotherapy (rate ratio 0.71; 99% CI: 0.46, 1.10; p=0.0434).,The risk of a first moderate-to-severe COPD exacerbation was 19% lower with TIO+OLO combination therapy than with TIO monotherapy (HR 0.81; 99% CI: 0.57, 1.17; p=0.1379), although this difference was not statistically significant.,The annualized rate of COPD exacerbations requiring hospitalization was 14% lower in the TIO+OLO arm than in the TIO arm (rate ratio 0.86; 95% CI: 0.52, 1.42; p=0.5654).,The adverse event incidence was balanced between treatment arms.,In a prespecified subgroup analysis of Japanese patients in the DYNAGITO study, combination therapy with TIO+OLO was more effective than TIO in reducing exacerbations.,Both treatments were well tolerated. | This retrospective cohort study compared the risks of exacerbations and COPD-related healthcare costs between patients with chronic obstructive pulmonary disease (COPD) initiating tiotropium (TIO) alone and patients initiating triple therapy with fluticasone-salmeterol combination (FSC) added to TIO.,Managed-care enrollees who had an index event of ≥ 1 pharmacy claim for TIO during the study period (January 1, 2003-April 30, 2008) and met other eligibility criteria were categorized into one of two cohorts depending on their medication use.,Patients in the TIO+FSC cohort had combination therapy with TIO and FSC, defined as having an FSC claim on the same date as the TIO claim.,Patients in the TIO cohort had no such FSC use.,The risks of COPD exacerbations and healthcare costs were compared between cohorts during 1 year of follow-up.,The sample comprised 3333 patients (n = 852 TIO+FSC cohort, n = 2481 TIO cohort).,Triple therapy with FSC added to TIO compared with TIO monotherapy was associated with significant reductions in the adjusted risks of moderate exacerbation (hazard ratio 0.772; 95% confidence interval [CI] 0.641, 0.930) and any exacerbation (hazard ratio 0.763; 95% CI 0.646, 0.949) and a nonsignificant reduction in COPD-related adjusted monthly medical costs.,Triple therapy with FSC added to TIO compared with TIO monotherapy was associated with significant reductions in the adjusted risks of moderate exacerbation and any exacerbation over a follow-up period of up to 1 year.,These improvements were gained with triple therapy at roughly equal cost of that of TIO alone. | 1 |
In patients with chronic obstructive pulmonary disease (COPD), exercise capacity is reduced, resulting over time in physical inactivity and worsened health status.,It is unknown whether ventilatory constraints occur during activities of daily life (ADL) in early stages of COPD.,The aim of this study was to assess respiratory mechanics during ADL and to study its consequences on dyspnoea, physical activity and health status in early-stage COPD compared with healthy controls.,In this cross-sectional study, 39 early-stage COPD patients (mean FEV1 88±s.d. 12% predicted) and 20 controls performed 3 ADL: climbing stairs, vacuum cleaning and displacing groceries in a cupboard.,Respiratory mechanics were measured during ADL.,Physical activity was measured with accelerometry.,Health status was assessed by the Nijmegen Clinical Screening Instrument.,Compared with controls, COPD patients had greater ventilatory inefficiency and higher ventilatory requirements during ADL (P<0.05).,Dyspnoea scores were increased in COPD compared with controls (P<0.001).,During ADL, >50% of the patients developed dynamic hyperinflation in contrast to 10-35% of the controls.,Higher dyspnoea was scored by patients with dynamic hyperinflation.,Physical activity was low but comparable between both groups.,From the patients, 55-84% experienced mild-to-severe problems in health status compared with 5-25% of the controls.,Significant ventilatory constraints already occur in early-stage COPD patients during common ADL and result in increased dyspnoea.,Physical activity level is not yet reduced, but many patients already experience limitations in health status.,These findings reinforce the importance of early diagnosis of COPD and assessment of more than just spirometry. | Information about daily physical activity levels (PAL) in subjects with undiagnosed chronic obstructive pulmonary disease (COPD) is scarce.,This study aims to assess PA and to investigate the associations between PA and clinical characteristics in subjects with newly diagnosed COPD.,Fifty-nine subjects with a new spirometry-based diagnosis of mild (n=38) and moderate (n=21) COPD (63±6 years, 68% male) were matched with 65 smoking controls (62±7 years, 75% male).,PA (daily steps, time spent in moderate-to-vigorous intense physical activities (MVPA) and PAL) was measured by accelerometry.,Dyspnoea, complete pulmonary function tests, peripheral muscle strength and exercise capacity served as clinical characteristics.,PA was significantly lower in COPD versus smoking controls (7986±2648 vs 9765±3078 steps, 64 (27-120) vs 110 (55-164) min of MVPA, 1.49±0.21 vs 1.62±0.24 PAL respectively, all p<0.05).,Subjects with COPD with either mild symptoms of dyspnoea (mMRC 1), those with lower diffusion capacity (TL,co), low 6 min walking distance (6MWD) or low maximal oxygen uptake (VO2 peak) had significantly lower PA.,Multiple regression analysis identified 6 MWD and TL,co as independent predictors of PA in COPD.,The reduction in PA starts early in the disease, even when subjects are not yet diagnosed with COPD.,Inactivity is more pronounced in subjects with mild symptoms of dyspnoea, lower levels of diffusion capacity and exercise capacity. | 1 |
Cough and sputum are highly prevalent in patients with chronic obstructive pulmonary disease (COPD).,Pulmonary rehabilitation (PR) has shown to be effective in managing these symptoms.,However, the interpretation of the magnitude of PR effects is hindered by the lack of minimal clinically important differences (MCIDs).,This study established MCIDs for the Leicester cough questionnaire (LCQ) and the cough and sputum assessment questionnaire (CASA-Q), in patients with COPD after PR.,An observational prospective study was conducted in patients with COPD who participated in a 12-weeks community-based PR program.,Anchor- (mean change, receiver operating characteristic curves and linear regression analysis) and distribution-based methods [0.5*standard deviation; standard error of measurement (SEM); 1.96*SEM; minimal detectable change and effect size] were used to compute the MCIDs.,The anchors used were: i) patients and physiotherapists global rating of change scale, ii) COPD assessment test, iii) St.,George’s respiratory questionnaire and iv) occurrence of an exacerbation during PR.,Pooled MCIDs were computed using the arithmetic weighted mean (2/3 for anchor- and 1/3 for distribution-based methods).,Forty-nine patients with COPD (81.6% male, 69.8±7.4years, FEV150.4±19.4%predicted) were used in the analysis.,The pooled MCIDs were 1.3 for LCQ and for CASA-Q domains were: 10.6 - cough symptoms; 10.1 - cough impact; 9.5 - sputum symptoms and 7.8 - sputum impact.,The MCIDs found in this study are potential estimates to interpret PR effects on cough and sputum, and may contribute to guide interventions. | Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | 1 |
The pathogenesis of chronic obstructive pulmonary disease (COPD) involves aberrant responses to cellular stress caused by chronic cigarette smoke (CS) exposure.,However, not all smokers develop COPD and the critical mechanisms that regulate cellular stress responses to increase COPD susceptibility are not understood.,Because microRNAs are well-known regulators of cellular stress responses, we evaluated microRNA expression arrays performed on distal parenchymal lung tissue samples from 172 subjects with and without COPD.,We identified miR-24-3p as the microRNA that best correlated with radiographic emphysema and validated this finding in multiple cohorts.,In a CS exposure mouse model, inhibition of miR-24-3p increased susceptibility to apoptosis, including alveolar type II epithelial cell apoptosis, and emphysema severity.,In lung epithelial cells, miR-24-3p suppressed apoptosis through the BH3-only protein BIM and suppressed homology-directed DNA repair and the DNA repair protein BRCA1.,Finally, we found BIM and BRCA1 were increased in COPD lung tissue, and BIM and BRCA1 expression inversely correlated with miR-24-3p.,We concluded that miR-24-3p, a regulator of the cellular response to DNA damage, is decreased in COPD, and decreased miR-24-3p increases susceptibility to emphysema through increased BIM and apoptosis.,miR-24-3p, a regulator of the DNA damage response, is reduced in chronic obstructive pulmonary disease lung tissue and inhibits susceptibility to epithelial apoptosis and emphysema. | Cigarette smoke is the main risk factor of pulmonary emphysema development, which is characterized by alveolar wall destruction.,Mitochondria are important for alveolar type II (ATII) cell metabolism due to ATP generation.,We isolated ATII cells from control non-smoker and smoker organ donors, and after lung transplant of patients with emphysema to determine mitochondrial function, dynamics and mitochondrial (mt) DNA damage.,We found high mitochondrial superoxide generation and mtDNA damage in ATII cells in emphysema.,This correlated with decreased mtDNA amount.,We also detected high TOP1-cc and low TDP1 levels in mitochondria in ATII cells in emphysema.,This contributed to the decreased resolution of TOP1-cc leading to accumulation of mtDNA damage and mitochondrial dysfunction.,Moreover, we used lung tissue obtained from areas with mild and severe emphysema from the same patients.,We found a correlation between the impaired fusion and fission as indicated by low MFN1, OPA1, FIS1, and p-DRP1 levels and this disease severity.,We detected lower TDP1 expression in severe compared to mild emphysema.,We found high DNA damage and impairment of DNA damage repair in mitochondria in ATII cells isolated from emphysema patients, which contribute to abnormal mitochondrial dynamics.,Our findings provide molecular mechanisms of mitochondrial dysfunction in this disease.,This work was supported by National Institutes of Health (NIH) grant R01 HL118171 (B.K.) and the Catalyst Award from the American Lung Association (K.B.). | 1 |
Tobacco-related lung diseases, including chronic obstructive pulmonary disease (COPD), are major causes of lung-related disability and death worldwide.,Acute exacerbation of COPD (AE-COPD) is commonly associated with upper and lower respiratory tract viral infections and can result in respiratory failure in those with advanced lung disease.,We sought to determine the mechanism underlying COPD exacerbation and host response to pathogen-derived factors.,Over a 24-month period, we assessed the viral causes for upper and lower respiratory tract infections in patients with COPD (n = 155) and control subjects (n = 103).,We collected nasal and bronchoalveolar lavage fluid and peripheral blood under baseline and exacerbated conditions.,We determined the effect of human rhinovirus (HRV) proteinases on T-cell activation in human subjects and mice.,HRVs are isolated from nasal and lung fluid from subjects with AE-COPD.,Bronchoalveolar lavage fluid and CD4 T cells from patients with COPD exhibited a TH1 and TH2 cell cytokine phenotype during acute infection.,HRV-encoded proteinase 2A activated monocyte-derived dendritic cells in vitro and induced strong TH1 and TH2 immune responses from CD4 T cells.,Intranasal administration of recombinant rhinovirus proteinase 2A in mice resulted in an increase in airway hyperreactivity, lung inflammation, and IL-4 and IFN-γ production from CD4 T cells.,Our findings suggest that patients with severe COPD show TH1- and TH2-biased responses during AE-COPD.,HRV-encoded proteinase 2A, like other microbial proteinases, could provide a TH1- and TH2-biasing adjuvant factor during upper and lower respiratory tract infection in patients with severe COPD.,Alteration of the immune response to secreted viral proteinases might contribute to worsening of dyspnea and respiratory failure in patients with COPD. | Moraxella catarrhalis causes approximately 10% of exacerbations in chronic obstructive pulmonary disease (COPD) and also colonizes the lower airway in stable patients.,Little is known about the effects of colonization by M. catarrhalis on airway inflammation and protease-antiprotease balance, and how these changes compare to those seen during exacerbations.,Since COPD is a progressive inflammatory disease, elucidating the effects of bacterial colonization and exacerbation on airway inflammation is relevant to understanding disease progression in COPD.,Our aims were (1) Analyze changes in airway inflammation in colonization and exacerbation of COPD due to M. catarrhalis; (2) Explore protease-antiprotease balance in colonization and exacerbation due to M. catarrhalis.,Our hypothesis were (1) Acquisition of a new strain of M. catarrhalis in COPD increases airway inflammation from baseline and alters the protease-antiprotease balance towards a more proteolytic environment; (2) These changes are greater during exacerbations associated with M. catarrhalis as compared to colonization.,Thirty-nine consecutive COPD patients with 76 acquisitions of a new strain of M. catarrhalis over a 6-year period were identified in a prospective study.,Seventy-six pre-acquisition sputum supernatant samples, obtained just before acquisition of M catarrhalis, and 76 acquisition samples (34 were associated with exacerbation, 42 with colonization) were analyzed for IL-8, TNF-α, Neutrophil Elastase (NE) and Secretory leukocyte protease inhibitor (SLPI).,Changes were compared in paired samples from each patient.,IL-8, TNF-α and NE were significantly elevated after acquisition of M. catarrhalis, compared to pre-acquisition samples (p =< 0.001 for all three).,These changes were present in colonization (p = 0.015 for IL-8; p =< 0.001 for TNF-α and NE) as well as in exacerbation (p =< 0.001 for all three), compared to pre-acquisition levels.,SLPI was significantly lower after acquisition (p =< 0.001), in colonization (p =< 0.001) as well as in exacerbation (p = 0.004), compared to pre-acquisition levels.,SLPI levels correlated negatively with NE levels (R2 = 0.07; p = 0.001).,Acquisition of M. catarrhalis in COPD causes increased airway inflammation and worsening protease-antiprotease imbalance during exacerbations and also in colonization, even in the absence of increased symptoms.,These effects could contribute to progression of airway disease in COPD. | 1 |
As only some smokers develop COPD with emphysema, we explored the molecular pathogenesis of early-stage COPD with emphysema using gene expression profiling of human lung tissues.,First, 110 subjects who had smoked more than ten pack-years were classified into three groups: COPD with emphysema, COPD without emphysema, and healthy smokers.,COPD and emphysema were confirmed by post-bronchodilator forced expiratory volume in 1 second/forced vital capacity <0.7 and by chest computed tomography.,Lung tissues obtained surgically from the 110 subjects were processed and used for RNA-Seq analysis.,Among the 110 subjects, 29 had COPD with emphysema, 21 had COPD without emphysema, and 60 were healthy smokers; their mean post-bronchodilator forced expiratory volume in 1 second values were 78%, 80%, and 94%, respectively.,Using RNA-Seq, we evaluated 16,676 genes expressed in lung tissues.,Among them, 1,226 genes in the COPD with emphysema group and 434 genes in the COPD without emphysema group were differentially expressed genes compared to the expression in healthy smokers.,In the COPD with emphysema group, ACER2 and LMAN2L were markedly increased and decreased, respectively.,In the COPD without emphysema group, the CHRM3 gene, previously reported to be associated with COPD, and HDAC10 were markedly increased and decreased, respectively.,Our study identified differences in gene expression in subjects with COPD according to emphysema status using RNA-Seq transcriptome analysis.,These findings may have mechanistic implications in COPD. | Recently, several genes and genetic loci associated with both asthma and chronic obstructive pulmonary disease (COPD) have been described as common susceptibility factors for the two diseases.,In complex diseases such as asthma and COPD, a large number of molecular and cellular components may interact through complex networks involving gene-gene and gene-environment interactions.,We sought to understand the functional and regulatory pathways that play central roles in the pathobiology of asthma and COPD and to understand the overlap between these pathways.,We searched the PubMed database up to September 2012 to identify genes found to be associated with asthma, COPD, tuberculosis, or essential hypertension in at least two independent reports of candidate-gene associations or in genome-wide studies.,To learn how the identified genes interact with each other and other cellular proteins, we conducted pathway-based analysis using Ingenuity Pathway Analysis software.,We identified 108 genes and 58 genes that were significantly associated with asthma and COPD in at least two independent studies, respectively.,These susceptibility genes were grouped into networks based on functional annotation: 12 (for asthma) and eleven (for COPD) networks were identified.,Analysis of the networks for overlap between the two diseases revealed that the networks form a single complex network with 229 overlapping molecules.,These overlapping molecules are significantly involved in canonical pathways including the “aryl hydrocarbon receptor signaling,” “role of cytokines in mediating communication between immune cells,” “glucocorticoid receptor signaling,” and “IL-12 signaling and production in macrophages” pathways.,The Jaccard similarity index for the comparison between asthma and COPD was 0.81 for the network-level comparison, and the odds ratio was 3.62 (P < 0.0001) for the asthma/COPD pair in comparison with the tuberculosis/ essential hypertension pair.,In conclusion, although the identification of asthma and COPD networks is still far from complete, these networks may be used as frameworks for integrating other genome-scale information including expression profiling and phenotypic analysis.,Network overlap between asthma and COPD may indicate significant overlap between the pathobiology of these two diseases, which are thought to be genetically related. | 1 |
The relationship of functional parameters such as lung mechanics, chest kinematics, metabolism and peripheral and respiratory muscle function with the level of exercise tolerance remains a controversial subject.,While it has been previously shown that pulmonary rehabilitation is capable of improving exercise tolerance in patients afflicted by COPD, as expressed by values of 6-minute walking test (6MWT), the degree of contribution to this change by each of the aforementioned parameters remains unclear.,To investigate the correlation between changes in exercise capacity and other functional markers following pulmonary rehabilitation in COPD and to determine which parameters are more closely related to improvements of exercise tolerance.,Three hundred and twenty-seven patients with COPD (with average, 95% CI for forced expiratory volume in the first second [FEV1]: 45% [25%-83%] predicted, age: 64 [48-80] years, and BMI: 27 [13.5-40.4] kg/m2) participated in this study.,Thirty percent of the patients had pulmonary hypertension as comorbidity.,Patients underwent a pulmonary rehabilitation program with 20-30 minutes sessions two to three times per day for 4 weeks.,The program was composed of chest wall-stretching, controlled breathing exercises, and a personalized training schedule for cycling and treadmill use.,Measurements of 6MWT, lung function, chest wall expansion, grip strength, maximal inspiratory pressure, and breath holding time were taken.,The Body mass index, airflow Obstruction, Dyspnea and Exercise capacity (BODE-index), body mass index [BMI], FEV1, 6MWT, modified Medical Research Dyspnea Scale score, and an alternative scale score (for BMI, FEV1, 6MWT, and COPD Assessment Test) were calculated.,Rehabilitation resulted in a generalized improvement in 6MWT among patients (average: 360 [95% CI: 178-543 m] vs average: 420 [95% CI: 238-601 m], p<0.05).,Improvements in exercise tolerance were found to be most closely associated with changes in composite BODE-index (R2=−0.6), Alternative Scale (R2=−0.56), dyspnea score (modified Medical Research Dyspnea Scale R2=−0.54), and health status (COPD Assessment Test R2=−0.4, p<0.05).,In addition, improvements in exercise tolerance were found to moderately correlate with improvements in inspiratory vital capacity (IVC, R2=0.34, p<0.05).,Post-rehabilitation changes in IVC displayed a connection with grip strength (R2=0.6) and chest expansion (R2=0.48).,Enhancements in exercise tolerance had correlation with changes in IVC, BODE-index, and the new Alternative Scale.,However, comprehensive assessment needs to include considerations of chest kinematics and peripheral and respiratory muscle function as well. | 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. | 1 |
The long-acting muscarinic antagonist (LAMA) umeclidinium (UMEC) and the combination of UMEC with the long-acting β2-agonist (LABA) vilanterol (UMEC/VI) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD) in the US and EU.,They are not indicated for the treatment of asthma.,In this 52-week, double-blind, placebo-controlled, parallel-group safety study (GSK study DB2113359; NCT01316887), patients were randomized 2:2:1 to UMEC/VI 125/25 mcg, UMEC 125 mcg, or placebo.,Study endpoints included adverse events (AEs), clinical chemistry and hematology parameters, vital signs, 12-lead, and 24-hour Holter electrocardiograms.,COPD exacerbations and rescue medication use were assessed as safety parameters; lung function was also evaluated.,The incidence of on-treatment AEs, serious AEs (SAEs), and drug-related AEs was similar between treatment groups (AEs: 52-58%; SAEs: 6-7%; drug-related AEs: 12-13%).,Headache was the most common AE in each treatment group (8-11%).,AEs associated with the LAMA and LABA pharmacologic classes occurred at a low incidence across treatment groups.,No clinically meaningful effects on vital signs or laboratory assessments were reported for active treatments versus placebo.,The incidences of atrial arrhythmias with UMEC/VI 125/25 mcg were similar to placebo; for UMEC 125 mcg, the incidences of ectopic supraventricular beats, sustained supraventricular tachycardia, and ectopic supraventricular rhythm were ≥2% greater than placebo.,With active treatments, COPD exacerbations were fewer (13-15% of patients reporting ≥1 exacerbation) and on average less rescue medication was required (1.6-2.2 puffs/day) versus placebo (24% reporting ≥1 exacerbation, 2.6 puffs/day).,Both active treatments improved lung function versus placebo.,UMEC/VI 125/25 mcg and UMEC 125 mcg were well tolerated over 12 months in patients with COPD. | Indacaterol is a novel, once-daily (od), inhaled, long-acting ß2-agonist bronchodilator for maintenance treatment of airflow limitation in patients with COPD.,The aim of this study was to evaluate the efficacy of indacaterol on dyspnea, using available randomized placebo-controlled trials.,A systematic search was made of MEDLINE, EMBASE, the Cochrane trials databases, and a manual search of journals.,Randomized placebo-controlled trials of 12 weeks or more comparing indacaterol with placebo were reviewed, and eligible studies were included in a meta-analysis.,The odds ratio (OR) for likelihood of achieving TDI score ≥ 1 after 12 weeks of treatment was used as an outcome measure to compare indacaterol to placebo.,Six trials were included in the analysis.,Relative to placebo, the overall ORs for response were: indacaterol 75 μg od 1.784 (95% CI 1.282 to 2.482); indacaterol 150 μg od 2.149 (95% CI 1.746 to 2.645); and indacaterol 300 μg od 2.458 (95% CI 2.010 to 3.006).,Overall OR for response in TDI tended to increase with higher indacaterol doses.,Patients receiving indacaterol had clinically significant improvements in symptoms of dyspnea compared to placebo.,Incremental benefits in TDI were observed with increasing doses.,Indacaterol may provide patients and physicians with a useful treatment option in symptomatic patients with dyspnea. | 1 |
To describe and compare demographic and clinical profile of patients newly initiated on aclidinium (ACL) or tiotropium (TIO) and identify factors associated with newly initiated ACL in real-life clinical practice during 2013 in Catalonia.,We performed a population-based, retrospective, observational study with data obtained from the Information System for Research Development in Primary Care, a population database that contains information of 5.8 million inhabitants (more than 80% of the Catalan population).,Patients over 40 years old, with a recorded diagnosis of COPD and newly initiated treatment with either ACL or TIO during the study period (January to December 2013), were selected.,A descriptive analysis of demographic and clinical characteristics was performed, and treatment adherence was also assessed for both cohorts.,A total of 8,863 individuals were identified, 4,293 initiated with ACL and 4,570 with TIO.,They had a mean age of 69.4 years (standard deviation: 11.3), a median COPD duration of 3 years (interquartile range: 0-8), and 71% were males.,Patients treated with ACL were older, with more respiratory comorbidities, a longer time since COPD diagnosis, worse forced expiratory volume in 1 second (% predicted), and with a higher rate of exacerbations during the previous year compared with TIO.,It was found that 41.3% of patients with ACL and 62.3% of patients with TIO had no previous COPD treatment.,Inhaled corticosteroid and long-acting β2-agonist were the most frequent concomitant medications (32.9% and 32.6%, respectively).,Approximately 75% of patients were persistent with ACL or TIO at 3 months from the beginning of treatment, and more than 50% of patients remained persistent at 9 months.,Patients initiated with ACL had more severe COPD and were taking more concomitant respiratory medications than patients initiated with TIO.,ACL was more frequently initiated as part of triple therapy, while TIO was more frequently initiated as monotherapy. | The long-acting muscarinic antagonists umeclidinium (UMEC) and tiotropium (TIO) are approved once-daily maintenance therapies for COPD.,This study investigated the efficacy and safety of UMEC versus TIO in COPD.,This was a 12-week, multicenter, randomized, blinded, double-dummy, parallel-group, non-inferiority study.,Patients were randomized 1:1 to UMEC 62.5 μg plus placebo or TIO 18 μg plus placebo.,The primary end point was trough forced expiratory volume in 1 second (FEV1) at day 85 (non-inferiority margin −50 mL; per-protocol [PP] population).,Other end points included weighted mean FEV1 over 0-24 and 12-24 hours post-dose.,Patient-reported outcomes comprised Transition Dyspnea Index score, St George’s Respiratory Questionnaire total score, and COPD Assessment Test score.,Adverse events were also assessed.,In total, 1,017 patients were randomized to treatment.,In the PP population, 489 and 487 patients received UMEC and TIO, respectively.,In the PP population, change from baseline in trough FEV1 was greater with UMEC versus TIO at day 85, meeting non-inferiority and superiority margins (difference: 59 mL; 95% confidence interval [CI]: 29-88; P<0.001).,Similar results were observed in the intent-to-treat analysis of trough FEV1 at day 85 (53 mL, 95% CI: 25-81; P<0.001).,Improvements in weighted mean FEV1 over 0-24 hours post-dose at day 84 were similar with UMEC and TIO but significantly greater with UMEC versus TIO over 12-24 hours post-dose (70 mL; P=0.015).,Clinically meaningful improvements in Transition Dyspnea Index and St George’s Respiratory Questionnaire were observed with both treatments at all time points.,No differences were observed between UMEC and TIO in patient-reported outcomes.,Overall incidences of adverse events were similar for UMEC and TIO.,UMEC 62.5 μg demonstrated superior efficacy to TIO 18 μg on the primary end point of trough FEV1 at day 85.,Safety profiles were similar for both treatments. | 1 |
Statins by their anti-inflammatory and endothelial stabilizing effect can be beneficial in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH).,The present study was done to evaluate the effect of rosuvastatin on pulmonary functions and quality of life (QOL) in patients with concomitant COPD and PH.,It was a prospective, randomized, double-blind, placebo-controlled, study conducted in patients with COPD and PH.,A total of sixty patients were assigned to receive either rosuvastatin 10 mg or placebo once a day in addition to their conventional treatment for 12 weeks.,Routine blood investigations, pulmonary functions, echocardiogram, exercise capacity, and QOL using a questionnaire were assessed at the baseline and after 12 weeks.,In patients of rosuvastatin group, there was a statistically significant increase in peak expiratory flow rate (PEFR) (P = 0.04) but no significant change in other pulmonary functions: Forced vital capacity (FVC), forced expiratory volume at 1 s (FVC, FEV1, FEV1/FVC), and echocardiogram parameters.,There was a significant increase in 6-min walk test (6-min walk distance) (P = 0.03) at the end of 12 weeks.,On comparing with placebo, rosuvastatin showed a significant reduction (P = 0.045) in COPD exacerbations while adverse effects did not differ.,Statins have a favorable effect on patients with COPD and PH regarding the improvement in PEFR, COPD exacerbations, and exercise capacity.,Such effects can be beneficial in these patients and more so in patients with concomitant coronary artery disease or hyperlipidemia where long-term benefits of statins have been established. | Chronic obstructive pulmonary disease (COPD) patients present a high prevalence of cardiovascular disease.,This excess of comorbidity could be related to a common pathogenic mechanism, but it could also be explained by the existence of common risk factors.,The objective of this study was to determine whether COPD patients present greater cardiovascular comorbidity than control subjects and whether COPD can be considered a risk factor per se.,1200 COPD patients and 300 control subjects were recruited for this multicenter, cross-sectional, case-control study.,Compared with the control group, the COPD group showed a significantly higher prevalence of ischemic heart disease (12.5% versus 4.7%; P < 0.0001), cerebrovascular disease (10% versus 2%; P < 0.0001), and peripheral vascular disease (16.4% versus 4.1%; P < 0.001).,In the univariate risk analysis, COPD, hypertension, diabetes, obesity, and dyslipidemia were risk factors for ischemic heart disease.,In the multivariate analysis adjusted for the remaining factors, COPD was still an independent risk factor (odds ratio: 2.23; 95% confidence interval: 1.18-4.24; P = 0.014).,COPD patients show a high prevalence of cardiovascular disease, higher than expected given their age and the coexistence of classic cardiovascular risk factors. | 1 |
Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease.,The aim of this systematic review was to quantify the disease burden of COPD in China and to determine the risk factors of the disease.,The number of studies included in the review was 47 with an average quality assessment score of 7.70 out of 10.,Reported COPD prevalence varied between 1.20% and 8.87% in different provinces/cities across China.,The prevalence rate of COPD was higher among men (7.76%) than women (4.07%).,The disease was more prevalent in rural areas (7.62%) than in urban areas (6.09%).,The diagnostic rate of COPD patients in China varied from 23.61% to 30.00%.,The percentage of COPD patients receiving outpatient treatment was around 50%, while the admission rate ranged between 8.78% and 35.60%.,Tobacco exposure and biomass fuel/solid fuel usage were documented as two important risk factors of COPD.,COPD ranked among the top three leading causes of death in China.,The direct medical cost of COPD ranged from 72 to 3,565 USD per capita per year, accounting for 33.33% to 118.09% of local average annual income.,The most commonly used scales for the assessment of quality of life (QoL) included Saint George Respiratory Questionnaire, Airways Questionnaire 20, SF-36, and their revised versions.,The status of QoL was worse among COPD patients than in non-COPD patients, and COPD patients were at higher risks of depression.,The COPD burden in China was high in terms of economic burden and QoL.,In view of the high smoking rate and considerable concerns related to air pollution and smog in China, countermeasures need to be taken to improve disease prevention and management to reduce disease burdens raised by COPD. | 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 |
The novel long-acting β 2-agonist olodaterol demonstrated an acceptable safety profile in short-term phase II clinical studies.,This analysis of four randomized, double-blind, placebo-controlled, parallel-group, phase III studies (1222.11, NCT00782210; 1222.12, NCT00782509; 1222.13, NCT00793624; 1222.14, NCT00796653) evaluated the long-term safety of olodaterol once daily (QD) in a large cohort of patients with moderate to very severe (Global initiative for chronic Obstructive Lung Disease 2-4) chronic obstructive pulmonary disease (COPD).,The studies compared olodaterol (5 or 10 μg) QD via Respimat®, formoterol 12 μg twice daily (BID) via Aerolizer® (1222.13 and 1222.14), and placebo for 48 weeks.,Patients continued receiving background maintenance therapy, with ∼60% receiving concomitant cardiovascular therapy and 25% having a history of concomitant cardiac disease.,Pre-specified analyses of pooled data assessed the adverse events (AEs) and serious AEs in the whole population, and in subgroups with cardiac disease, along with in-depth electrocardiogram and Holter monitoring.,In total, 3104 patients were included in the safety analysis: 876 received olodaterol 5 μg, 883 received olodaterol 10 μg, 885 received placebos, and 460 received formoterol 12 μg BID.,Overall incidence of on-treatment AEs (71.2%), serious AEs (16.1%), and deaths (1.7%) were balanced across treatment groups.,Respiratory and cardiovascular AEs, including major adverse cardiac events, were reported at similar frequencies in placebo and active treatment groups.,The safety profiles of both olodaterol 5 μg (marketed and registered dose) and 10 μg QD delivered via Respimat® are comparable to placebo and formoterol BID in this population, with no safety signals identified. | 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 |
The association between exposure to ambient particles with a median aerodynamic diameter less than 10/2.5 µm (particulate matter, PM10/2.5) and COPD remains unclear.,Our study objective was to examine the association between ambient PM10/2.5 concentrations and lung functions in adults.,A cross-sectional study was conducted in southern China.,Seven clusters were randomly selected from four cities across Guangdong province.,Residents aged ≥20 years in the participating clusters were randomly recruited; all eligible participants were examined with a standardised questionnaire and spirometry.,COPD was defined as a post-bronchodilator FEV1/FVC less than 70%.,Atmosphere PM sampling was conducted across the clusters along with our survey.,Of the subjects initially recruited, 84.4% (n=5993) were included for analysis.,COPD prevalence and atmosphere PM concentration varied significantly among the seven clusters.,COPD prevalence was significantly associated with elevated PM concentration levels: adjusted OR 2.416 (95% CI 1.417 to 4.118) for >35 and ≤75 µg/m3 and 2.530 (1.280 to 5.001) for >75 µg/m3 compared with the level of ≤35 µg/m3 for PM2.5; adjusted OR 2.442 (95% CI 1.449 to 4.117) for >50 and ≤150 µg/m3 compared with the level of ≤50 µg/m3 for PM1.,A 10 µg/m3 increase in PM2.5 concentrations was associated with a 26 mL (95% CI −43 to −9) decrease in FEV1, a 28 mL (−49 to −8) decrease in FVC and a 0.09% decrease (−0.170 to −0.010) in FEV1/FVC ratio.,The associations of COPD with PM10 were consistent with PM2.5 but slightly weaker.,Exposure to higher PM concentrations was strongly associated with increased COPD prevalence and declined respiratory function.,ChiCTR-OO-14004264; Post-results. | Due to the rapid urbanization of the world population, a better understanding of the detrimental effects of exposure to urban air pollution on chronic lung disease is necessary.,Strong epidemiological evidence suggests that exposure to particulate matter (PM) air pollution causes exacerbations of pre-existing lung conditions, such as, chronic obstructive pulmonary disease (COPD) resulting in increased morbidity and mortality.,However, little is known whether a chronic, low-grade exposure to ambient PM can cause the development and progression of COPD.,The deposition of PM in the respiratory tract depends predominantly on the size of the particles, with larger particles deposited in the upper and larger airways and smaller particles penetrating deep into the alveolar spaces.,Ineffective clearance of this PM from the airways could cause particle retention in lung tissues, resulting in a chronic, low-grade inflammatory response that may be pathogenetically important in both the exacerbation, as well as, the progression of lung disease.,This review focuses on the adverse effects of exposure to ambient PM air pollution on the exacerbation, progression, and development of COPD. | 1 |
Viral infection is a common trigger for acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,The aim of this study is to investigate the expression of cytokines in AECOPD.,Patients with AECOPD requiring hospitalization were recruited.,Meanwhile healthy volunteers of similar age that accepted routine check-ups and showed no clinical symptoms of inflammatory diseases were also recruited.,Induced sputum and serum were collected.,Induced sputum of participants was processed and tested for thirteen viruses and bacteria.,Forty cytokines were assayed in serum using the Quantibody Human Inflammation Array 3 (Ray Biotech, Inc.).,The most common virus detected in virus positive AECOPD (VP) was influenza A (16%).,No virus was found in controls.,Circulating levels of IL-6, TNF-α, and MCP-1 were elevated in VP and coinfection subjects (p < 0.05), while the levels of 37 other cytokines showed no difference, compared with virus negative groups and controls (p > 0.05).,Additionally, VP patients were less likely to have received influenza vaccination.,VP patients had a systemic inflammation response involving IL-6, TNF-α, and MCP-1 which may be due to virus-induced activation of macrophages.,There are important opportunities for further investigating AECOPD mechanisms and for the development of better strategies in the management and prevention of virus-related AECOPD. | 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. | 1 |
Sputum eosinophilia occurs in approximately one-third of stable chronic obstructive pulmonary disease (COPD) patients and can predict exacerbation risk and response to corticosteroid treatments.,Sputum induction, however, requires expertise, may not always be successful, and does not provide point-of-care results.,Easily applicable diagnostic markers that can predict sputum eosinophilia in stable COPD patients have the potential to progress COPD management.,This study investigated the correlation and predictive relationship between peripheral blood and sputum eosinophils.,It also examined the repeatability of blood eosinophil counts.,Stable COPD patients (n=141) were classified as eosinophilic or noneosinophilic based on their sputum cell counts (≥3%), and a cross-sectional analysis was conducted comparing their demographics, clinical characteristics, and blood cell counts.,Receiver operating characteristic curve analysis was used to assess the predictive ability of blood eosinophils for sputum eosinophilia.,Intraclass correlation coefficient was used to examine the repeatability of blood eosinophil counts.,Blood eosinophil counts were significantly higher in patients with sputum eosinophilia (n=45) compared to those without (0.3×109/L vs 0.15×109/L; P<0.0001).,Blood eosinophils correlated with both the percentage (ρ=0.535; P<0.0001) and number of sputum eosinophils (ρ=0.473; P<0.0001).,Absolute blood eosinophil count was predictive of sputum eosinophilia (area under the curve =0.76, 95% confidence interval [CI] =0.67-0.84; P<0.0001).,At a threshold of ≥0.3×109/L (specificity =76%, sensitivity =60%, and positive likelihood ratio =2.5), peripheral blood eosinophil counts enabled identification of the presence or absence of sputum eosinophilia in 71% of the cases.,A threshold of ≥0.4×109/L had similar classifying ability but better specificity (91.7%) and higher positive likelihood ratio (3.7).,In contrast, ≥0.2×109/L offered a better sensitivity (91.1%) for ruling out sputum eosinophilia.,There was a good agreement between two measurements of blood eosinophil count over a median of 28 days (intraclass correlation coefficient =0.8; 95% CI =0.66-0.88; P<0.0001).,Peripheral blood eosinophil counts can help identify the presence or absence of sputum eosinophilia in stable COPD patients with a reasonable degree of accuracy. | Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY | 1 |
Long-acting muscarinic receptor antagonists (LAMAs) are the cornerstone for the treatment of chronic obstructive pulmonary disease (COPD); furthermore, tiotropium is approved as add-on therapy in severe asthmatic patients.,Accumulating evidence suggests that LAMAs may modulate airway contractility and airway hyperresponsiveness not only by blocking muscarinic acetylcholine receptors (mAchRs) expressed on airway smooth muscle but also via anti-inflammatory mechanisms by blocking mAchRs expressed on inflammatory cells, submucosal glands, and epithelial cells.,The aim of this systematic review, performed according to the PRISMA-P guidelines, was to provide a synthesis of the literature on the anti-inflammatory impact of muscarinic receptor antagonists in the airways.,Most of the current evidence originates from studies on tiotropium, that demonstrated a reduction in synthesis and release of cytokines and chemokines, as well as the number of total and differential inflammatory cells, induced by different pro-inflammatory stimuli.,Conversely, few data are currently available for aclidinium and glycopyrronium, whereas no studies on the potential anti-inflammatory effect of umeclidinium have been reported.,Overall, a large body of evidence supports the beneficial impact of tiotropium against airway inflammation.,Further well-designed randomized controlled trials are needed to better elucidate the anti-inflammatory mechanisms leading to the protective effect of LAMAs against exacerbations via identifying suitable biomarkers. | Chronic obstructive pulmonary disease (COPD) is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow.,The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it, such as glucocorticoids and bronchodilators, have significant therapeutic effects; however, they also cause side effects, including infection and immunosuppression.,Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs.,Among these new drugs, we focussed on thioredoxin (Trx).,Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance, blocking the NF-κB and MAPK signalling pathways, suppressing the activation and migration of inflammatory cells and the production of cytokines, inhibiting the synthesis and the activation of adhesion factors and growth factors, and controlling the cAMP-PKA and PI3K/Akt signalling pathways.,The mechanism by which Trx affects COPD is different from glucocorticoid-based mechanisms which regulate the inflammatory reaction in association with suppressing immune responses.,In addition, Trx also improves the insensitivity of COPD to steroids by inhibiting the production and internalisation of macrophage migration inhibitory factor (MIF).,Taken together, these findings suggest that Trx may be the ideal drug for treating COPD. | 1 |
This retrospective, observational study of a routine clinical practice reports the feasibility and efficiency of home-based pulmonary rehabilitation (PR), including transcutaneous neuromuscular electrical stimulation (NMES) or usual endurance physical exercise (UEPE), on exercise tolerance, anxiety/depression, and health-related quality of life (HRQoL) in patients with COPD.,Seventy-one patients with COPD participated in home-based PR with NMES (Group NMES [GNMES]), while 117 patients participated in home-based PR with the UEPEs (Group UEPE [GUEPE]).,NMES was applied for 30 minutes twice a day, every day.,The endurance exercises in GUEPE began with a minimum 10-minute session at least 5 days a week, with the goal being 30-45 minutes per session.,Three upper and lower limb muscle strengthening exercises lasting 10-15 minutes were also proposed to both the groups for daily practice.,Moreover, PR in both the groups included a weekly 90-minute session based on an educational needs assessment.,The sessions comprised endurance physical exercise for GUEPE, NMES for GNMES, resumption of physical daily living activities, therapeutic patient education, and psychosocial support to facilitate health behavior changes.,Before and after PR, functional mobility and physical exercise capacity, anxiety, depression, and HRQoL were evaluated at home.,The study revealed that NMES significantly improved functional mobility (−18.8% in GNMES and −20.6% in GUEPE), exercise capacity (+20.8% in GNMES and +21.8% in GUEPE), depression (−15.8% in GNMES and −30.1% in GUEPE), and overall HRQoL (−7.0% in GNMES and −18.5% in GUEPE) in the patients with COPD, regardless of the group (GNMES or GUEPE) or severity of airflow obstruction.,Moreover, no significant difference was observed between the groups with respect to these data (P>0.05).,Home-based PR including self-monitored NMES seems feasible and effective for severely disabled COPD patients with severe exercise intolerance. | There is a need for a validated short instrument that can be used in routine practice to quantify potential short-term change in Health-Related Quality of Life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD).,Our aim is to determine the validity and reliability of the VQ11 questionnaire dedicated to the routine assessment of HRQoL.,181 COPD patients (40-85 yrs, I to IV GOLD stages) completed the VQ11, and several tests.,One week later, 49 of these patients completed the VQ11 again.,Confirmatory factor analysis supported the two-level hierarchical structure of the VQ11 with 11 items covering three components and HRQoL at a higher level.,The VQ11 showed good internal consistency and good reproducibility (r = 0.88).,Concurrent validity showed significant correlations between VQ11 total scores and St George’s Respiratory Questionnaire-C (r = 0.70), Short Form-36 (r = -0.66 for the physical component and -0.63 for the mental component).,We obtained significant correlations with MRC Dyspnea Grades (r = 0.59), the Hospital Anxiety and Depression Scale total score (r = 0.62), and the BODE index (r = 0.53).,The VQ11 has good measurement properties and provides a valid and reliable measure of COPD-specific HRQoL.,It is ready for use in routine practice.,The study was approved by the University of Montpellier 1 Ethics Committee and the Regional Ethics Committee (authorization number: A00332-53). | 1 |
Evidence and guidelines are becoming increasingly clear about imbalance between the risks and benefits of inhaled corticosteroids (ICSs) in patients with COPD.,While selected patients may benefit from ICS-containing regimens, ICSs are often inappropriately prescribed with - according to Belgian market research data - up to 70% of patients in current practice receiving ICSs, usually as a fixed combination with a long-acting β2-adrenoreceptor agonist.,Studies and recommendations support withdrawal of ICSs in a large group of patients with COPD.,However, historical habits appear difficult to change even in the light of recent scientific evidence.,We have built a collaborative educational platform with chest physicians and primary care physicians to increase awareness and provide guidance and support in this matter. | This study aimed to assess the adherence rate of pharmacological treatment to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline published in 2011 and the prevalence of comorbidities among patients with COPD in Hong Kong (HK).,Patients were recruited from five tertiary respiratory centers and followed up for 12 months.,Data on baseline physiological, spirometric parameters, use of COPD medications and coexisting comorbidities were collected.,The relationship between guideline adherence rate and subsequent COPD exacerbations was assessed.,Altogether, 450 patients were recruited.,The mean age was 73.7±8.5 years, and 92.2% of them were males.,Approximately 95% of them were ever-smokers, and the mean post-bronchodilator (BD) forced expiratory volume in 1 second was 50.8%±21.7% predicted.,The mean COPD Assessment Test and modified Medical Research Council Dyspnea Scale were 13.2±8.1 and 2.1±1.0, respectively.,In all, five (1.1%), 164 (36.4%), eight (1.8%) and 273 (60.7%) patients belonged to COPD groups A, B, C and D, respectively.,The guideline adherence rate for pharmacological treatment ranged from 47.7% to 58.1% in the three clinic visits over 12 months, with overprescription of inhaled corticosteroids (ICS) and underutilization of long-acting BDs in group B COPD patients.,Guideline nonadherence was not associated with increased risk of exacerbation after adjustment of confounding variables.,However, this study was not powered to assess a difference in exacerbations.,In all, 80.9% of patients had at least one comorbidity.,A suboptimal adherence to GOLD guideline 2011, with overprescription of ICS, was identified.,The commonly found comorbidities also aligned with the trend observed in other observational cohorts. | 1 |
Existing data on COPD prevalence are limited or totally lacking in many regions of Europe.,The geographic information system inverse distance weighted (IDW) interpolation technique has proved to be an effective tool in spatial distribution estimation of epidemiological variables, when real data are few and widely separated.,Therefore, in order to represent cartographically the prevalence of COPD in Europe, an IDW interpolation mapping was performed.,The point prevalence data provided by 62 studies from 19 countries (21 from 5 Northern European countries, 11 from 3 Western European countries, 14 from 5 Central European countries, and 16 from 6 Southern European countries) were identified using validated spirometric criteria.,Despite the lack of data in many areas (including all regions of the eastern part of the continent), the IDW mapping predicted the COPD prevalence in the whole territory, even in extensive areas lacking real data.,Although the quality of the data obtained from some studies may have some limitations related to different confounding factors, this methodology may be a suitable tool for obtaining epidemiological estimates that can enable us to better address this major public health problem. | 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 |
Chronic obstructive pulmonary disease (COPD) can greatly impact the quality of life by limiting patients’ activities.,However, data on impact of symptomatic burden on the health care resource utilization (HCRU) and employment in COPD are lacking.,We examined the association between COPD Assessment Test (CAT) score and direct/indirect costs associated with HCRU and work productivity.,Data from >2,100 patients with COPD consulting for routine care were derived from respiratory disease-specific programs in Europe, the USA and China.,Questionnaires, including CAT and Work Productivity and Activity Impairment (WPAI), were used to collect the past and current disease status data and HCRU characteristics from physicians (general practitioners/specialists) and patients.,A regression approach was used to quantify the association of CAT with HCRU and WPAI variables.,CAT score was modeled as a continuous independent variable (range: 0-40).,Ninety percent of patients with COPD had a CAT score ≥10.,Short-acting therapy and maintenance bronchodilator monotherapy, respectively, were currently prescribed to patients with CAT scores of 10-19 (5.8% and 27.6%), 20-29 (5.1% and 13.1%) and 30-40 (2.8% and 6.6%).,Prescribing of maintenance bronchodilator dual therapy was low across the CAT score groups (0-9, 7.8%; 10-19, 6.4%; 20-29, 5.9%; 30-40, 4.4%), whereas maintenance triple combination therapy was prescribed more commonly in patients with higher CAT scores (0-9, 16.1%; 10-19, 23.2%; 20-29, 25.9%; 30-40, 35.5%).,Increasing CAT scores were significantly associated with a higher frequency of primary care physician visits (P<0.001), pulmonologist visits (P=0.007), exacerbations requiring hospitalization (P<0.001) and WPAI scores (P<0.001).,Most patients with COPD presented with high symptom levels, despite being treated for COPD.,Increasing symptom burden was associated with increasing HCRU and had a detrimental impact on work productivity. | Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease associated with various systemic comorbidities including osteoporosis.,Osteoporosis and its related fractures are common and have significant impacts on quality of life and even respiratory function in patients with COPD.,COPD-associated osteoporosis is however extremely undertreated.,Recent studies have suggested that both decreased bone mineral density (BMD) and impaired bone quality contribute to bone fragility, causing fractures in COPD patients.,Various clinical risk factors of osteoporosis in COPD patients, including older age, emaciation, physical inactivity, and vitamin D deficiency, have also been described.,It is critically important for pulmonologists to be aware of the high prevalence of osteoporosis in COPD patients and evaluate them for such fracture risks.,Routine screening for osteoporosis will enable physicians to diagnose COPD patients with comorbid osteoporosis at an early stage and give them appropriate treatment to prevent fracture, which may lead to improved quality of life as well as better long-term prognosis. | 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. | Sleep quality is often poor in patients with chronic obstructive pulmonary disease (COPD).,A cross-sectional European survey investigated the prevalence of night-time symptoms in COPD to evaluate the level of disconnect between physician and patient perceptions of the presence of night-time symptoms, and to compare the characteristics of patients with and without night-time symptoms.,A total of 251 primary care physicians and 251 respiratory specialists completed record forms on 2,807 patients with COPD.,The forms captured information on patient demographics, lung function, COPD severity, and symptoms.,Patients completed questionnaires on the time of day when their COPD symptoms bothered them, and the impact of COPD on their ability to get up in the morning and on sleep.,Data were compared between groups (those with and without night-time symptoms) using t-tests or Wilcoxon signed rank tests.,The kappa statistic was used to assess the level of disconnect between physician and patient perceptions of the impact of night-time symptoms.,Most patients (78%) reported night-time disturbance.,Patients with night-time symptoms experienced more daytime breathlessness (mean modified Medical Research Council dyspnea scale score 2.4 versus 1.1) and exacerbations in the previous 12 months (mean 1.7 versus 0.4), and received more maintenance therapy (mean of 2.8 versus 2.3 products) than those without.,Concordance between the frequency of physician-reported (67.9% of patients) and patient-reported (68.5% of patients) night-time symptoms was good.,Physicians significantly underestimated the impact of COPD on the patient’s ability to get up in the morning and on sleep (fair-moderate agreement).,Physician-reported night-time symptoms were present for 41.2% of patients who could be categorized by Global initiative for chronic Obstructive Lung Disease (GOLD) group (n=937), increasing from 20.9% of those in the low-risk group to 77.4% of those in the high-riskgroup.,Patients with COPD experience night-time symptoms regardless of GOLD group, that impact on their ability to get up in the morning and on their sleep quality. | 1 |
The purpose of this study was to quantitatively assess the effects of water-based Liuzijue exercise on patients with COPD and compare it with land-based Liuzijue exercise.,Participants were randomly allocated to one of three groups: the water-based Liuzijue exercise group (WG), the land-based Liuzijue exercise group (LG), and the control group (CG).,CG participants accepted no exercise intervention, while training groups performed Liuzijue exercise according to Health Qigong Liuzijue (People’s Republic of China) in different environments for 60-min sessions twice a week for 3 months.,Of the 50 patients enrolled, 45 (90%) completed the 3-month intervention.,The CG showed decreased expiratory muscle strength, extensor and flexor endurance ratio (ER) of the elbow joints and flexor peak torque (PT), total work (TW), and ER of the knee joints (p<0.05).,Both training groups showed improved respiratory muscle strength, which differed from the CG (p<0.001).,In addition, extensor and flexor TW of the elbow joints in the training groups were increased (p<0.01), and the WG differed from the CG in extensor TW and ER and flexor TW (p<0.01), while the LG differed from the CG in flexor TW and extensor ER (p<0.05).,PT, PT/body weight (BW), and TW in the knee joint extensor in the training groups were increased as well (PT and PT/BW: p<0.05, TW: p<0.01), and the WG differed from the CG in terms of knee joints outcomes, while the LG differed from the CG in flexor TW only (p<0.05).,Water-based Liuzijue exercise has beneficial effects on COPD patients’ respiratory muscle strength and peripheral skeletal muscle function, and additional benefits may exist in endurance of upper limbs and strength and endurance of lower limbs when compared with land-based Liuzijue exercise. | Objectives.,To evaluate the sustaining effects of Tai Chi Qigong (TCQ) in improving the psychosocial health in chronic obstructive pulmonary disease (COPD) patients in the sixth month.,Background.,COPD affects both physical and emotional aspects of life.,Measures to minimize patients' suffering need to be implemented.,Methods.,206 COPD patients were randomly assigned into three groups: TCQ group, exercise group, and control group.,The TCQ group completed a three-month TCQ program, the exercise group practiced breathing and walking exercise, and the control group received usual care.,Results.,Significant group-by-time interactions in quality of life (QOL) using St.,George's respiratory questionnaire (P = 0.002) and the perceived social support from friends using multidimensional scale of perceived social support (P = 0.04) were noted.,Improvements were observed in the TCQ group only.,Conclusions.,TCQ has sustaining effects in improving psychosocial health; it is also a useful and appropriate exercise for COPD patients. | 1 |
Purpose: Clinically important deterioration (CID) in chronic obstructive pulmonary disease (COPD) is a novel composite endpoint that assesses disease stability.,The association between short-term CID and future economic and quality of life (QoL) outcomes has not been previously assessed.,This analysis considers 3-year data from the TOwards a Revolution in COPD Health (TORCH) study, to examine this question.,Patients and methods: This post hoc analysis of TORCH (NCT00268216) compared costs and utilities at 3 years among patients without CID (CID-) and with CID (CID+) at 24 weeks.,A positive CID status was defined as either: a deterioration in forced expiratory volume in 1 second (FEV1) of ≥100 mL from baseline; or a ≥4-unit increase from baseline in St George’s Respiratory Questionnaire (SGRQ) total score; or the incidence of a moderate/severe exacerbation.,Patients from all treatment arms were included.,Utility change was based on the EQ-5D utility index.,Costs were based on healthcare resource utilization from 24 weeks to end of follow-up combined with unit costs for the UK (2016 GBP), and reported as per patient per year (PPPY).,Adjusted estimates were generated controlling for baseline characteristics, treatment assignment, and number of CID criteria met.,Results: Overall, 3,769 patients completed the study and were included in the analysis (stable CID- patients, n=1,832; unstable CID+ patients, n=1,937).,At the end of follow-up, CID- patients had higher mean (95% confidence interval [CI]) utility scores than CID+ patients (0.752 [0.738, 0.765] vs 0.697 [0.685, 0.71]; difference +0.054; P<0.001), and lower costs PPPY (£538 vs £916; difference: £378 [95% CI: £244, £521]; P<0.001).,The cost differential was primarily driven by the difference in general hospital ward days (P=0.003).,Conclusion: This study demonstrated that achieving early stability in COPD by preventing short-term CID is associated with better preservation of future QoL alongside reduced healthcare service costs. | Assessing clinically important measures of disease progression is essential for evaluating therapeutic effects on disease stability in chronic obstructive pulmonary disease (COPD).,This analysis assessed whether providing additional bronchodilation with the long-acting muscarinic antagonist umeclidinium (UMEC) to patients treated with inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) therapy would improve disease stability compared with ICS/LABA therapy alone.,This integrated post hoc analysis of four 12-week, randomized, double-blind trials (NCT01772134, NCT01772147, NCT01957163, NCT02119286) compared UMEC 62.5 µg with placebo added to open-label ICS/LABA in symptomatic patients with COPD (modified Medical Research Council dyspnea scale score ≥ 2).,A clinically important deterioration (CID) was defined as: a decrease from baseline of ≥ 100 mL in trough forced expiratory volume in 1 s (FEV1), an increase from baseline of ≥ 4 units in St George’s Respiratory Questionnaire (SGRQ) total score, or a moderate/severe exacerbation.,Risk of a first CID was evaluated in the intent-to-treat (ITT) population and in patients stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) classification, exacerbation history and type of ICS/LABA therapy.,Adverse events (AEs) were also assessed.,Overall, 1637 patients included in the ITT population received UMEC + ICS/LABA (n = 819) or placebo + ICS/LABA (n = 818).,Additional bronchodilation with UMEC reduced the risk of a first CID by 45-58% in the ITT population and all subgroups analyzed compared with placebo (all p < 0.001).,Improvements were observed in reducing FEV1 (69% risk reduction; p < 0.001) and exacerbation (47% risk reduction; p = 0.004) events in the ITT population.,No significant reduction in risk of a SGRQ CID was observed.,AE incidence was similar between treatment groups.,Symptomatic patients with COPD receiving ICS/LABA experience frequent deteriorations.,Additional bronchodilation with UMEC significantly reduced the risk of CID and provided greater short-term stability versus continued ICS/LABA therapy in these patients.,GlaxoSmithKline (study number: 202067).,Plain language summary available for this article.,The online version of this article (10.1007/s12325-018-0771-4) contains supplementary material, which is available to authorized users. | 1 |
Depression is a common comorbidity among patients with Chronic Obstructive Pulmonary Disease (COPD) and has a significant impact on the course of the disease.,The aim of this study is to determine association between COPD Assessment Test (CAT) and major depression among clinically stable out-patient COPD subjects with mild hypoxemia.,Case-control study.,Cases were 30 patients with major depression and controls were 30 patients without depression.,Major depression was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders criteria by a psychiatric evaluation.,All possible predictive variables were included in a multivariate logistic regression model to assess the association between major depression and each independent variable, while controlling for the sleep parameters.,CAT score >20 was associated with major depression (OR 7.88; 95% CI 1.96 - 31.7; p = 0.004).,CAT score >20 was associated with major depression, suggesting CAT as a predictor variable of major depression among COPD patients with mild hypoxemia, and indicating that an additional specific evaluation for the presence of major depression should be done. | This study was conducted to investigate the association between the chronic obstructive pulmonary disease (COPD) assessment test (CAT) and depression in COPD patients.,The Korean versions of the CAT and patient health questionnaire-9 (PHQ-9) were used to assess COPD symptoms and depressive disorder, respectively.,In total, 803 patients with COPD were enrolled from 32 hospitals and the prevalence of depression was 23.8%.,The CAT score correlated well with the PHQ-9 score (r=0.631; P<0.001) and was significantly associated with the presence of depression (β±standard error, 0.452±0.020; P<0.001).,There was a tendency toward increasing severity of depression in patients with higher CAT scores.,By assessment groups based on the 2011 Global Initiative for Chronic Obstructive Lung Disease guidelines, the prevalence of depression was affected more by current symptoms than by airway limitation.,The area under the receiver operating characteristic curve for the CAT was 0.849 for predicting depression, and CAT scores ≥21 had the highest accuracy rate (80.6%).,Among the eight CAT items, energy score showed the best correlation and highest power of discrimination.,CAT scores are significantly associated with the presence of depression and have good performance for predicting depression in COPD patients. | 1 |
Beta-blockers are associated with reduced mortality in patients with cardiovascular disease but are often under prescribed in those with concomitant COPD, due to concerns regarding respiratory side-effects.,We investigated the effects of beta-blockers on outcomes in patients with COPD and explored within-class differences between different agents.,We searched the Cochrane Central Register of Controlled Trials, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Medline for observational studies and randomized controlled trials (RCTs) investigating the effects of beta-blocker exposure versus no exposure or placebo, in patients with COPD, with and without cardiovascular indications.,A meta-analysis was performed to assess the association of beta-blocker therapy with acute exacerbations of COPD (AECOPD), and a network meta-analysis was conducted to investigate the effects of individual beta-blockers on FEV1.,Mortality, all-cause hospitalization, and quality of life outcomes were narratively synthesized.,We included 23 observational studies and 14 RCTs.,In pooled observational data, beta-blocker therapy was associated with an overall reduced risk of AECOPD versus no therapy (HR 0.77, 95%CI 0.70 to 0.85).,Among individual beta-blockers, only propranolol was associated with a relative reduction in FEV1 versus placebo, among 199 patients evaluated in RCTs.,Narrative syntheses on mortality, all-cause hospitalization and quality of life outcomes indicated a high degree of heterogeneity in study design and patient characteristics but suggested no detrimental effects of beta-blocker therapy on these outcomes.,The class effect of beta-blockers remains generally positive in patients with COPD.,Reduced rates of AECOPD, mortality, and improved quality of life were identified in observational studies, while propranolol was the only agent associated with a deterioration of lung function in RCTs. | Observational studies indicate that beta-blockers are associated with a reduced risk of exacerbation and mortality in patients with chronic obstructive pulmonary disease (COPD) even without overt cardiovascular disease, but data from randomized controlled trials (RCT) are lacking.,The aim of this RCT is to investigate whether beta-blocker therapy in patients with COPD without diagnosed cardiovascular disease is associated with a decreased 1-year risk of the composite endpoint of death, exacerbations, or cardiovascular events.,The Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) study is an open-label, multicentre, prospective RCT.,A total of 1700 patients with COPD will be randomly assigned to either standard COPD care and metoprolol at a target dose of 100 mg per day or to standard COPD care only.,The primary endpoint is a composite of death, COPD exacerbations, and cardiovascular events.,Major exclusion criteria are ischemic heart disease, left-sided heart failure, cerebrovascular disease, critical limb ischemia, and atrial fibrillation/flutter.,Study visits are an inclusion visit, a metoprolol titration visit at 1 month, follow-up by telephone at 6 months, and a final study visit after 1 year.,Outcome data are obtained from medical history and record review during study visits, as well as from national registries.,BRONCHIOLE is a pragmatic randomized trial addressing the potential of beta-blockers in patients with COPD.,The trial is expected to provide relevant clinical data on the efficacy of this treatment on patient-related outcomes in patients with COPD.,ClinicalTrials.gov, ID: NCT03566667.,Registered on 25 June 2018. | 1 |
Increasing evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD.,Recent data provide evidence for a role in the NLRP3 inflammasome in the airway inflammation observed in COPD.,Cigarette smoke activates innate immune cells by triggering pattern recognition receptors (PRRs) to release “danger signal”.,These signals act as ligands to Toll-like receptors (TLRs), triggering the production of cytokines and inducing innate inflammation.,In smokers who develop COPD there appears to be a specific pattern of inflammation in the airways and parenchyma as a result of both innate and adaptive immune responses, with the predominance of CD8+ and CD4+ cells, and in the more severe disease, with the presence of lymphoid follicles containing B lymphocytes and T cells.,Furthermore, viral and bacterial infections interfere with the chronic inflammation seen in stable COPD and exacerbations via pathogen-associated molecular patterns (PAMPs).,Finally, autoimmunity is another novel aspect that may play a critical role in the pathogenesis of COPD.,This review is un update of the currently discussed roles of inflammatory and immune responses in the pathogenesis of COPD. | Macrophages have been implicated in the pathogenesis of COPD.,M1 and M2 macrophages constitute subpopulations displaying pro- and anti-inflammatory properties.,We hypothesized that smoking cessation affects macrophage heterogeneity in the lung of patients with COPD.,Our aim was to study macrophage heterogeneity using the M2-marker CD163 and selected pro- and anti-inflammatory mediators in bronchoalveolar lavage (BAL) fluid and induced sputum from current smokers and ex-smokers with COPD.,114 COPD patients (72 current smokers; 42 ex-smokers, median smoking cessation 3.5 years) were studied cross-sectionally and underwent sputum induction (M/F 99/15, age 62 ± 8 [mean ± SD] years, 42 (31-55) [median (range)] packyears, post-bronchodilator FEV1 63 ± 9% predicted, no steroids past 6 months).,BAL was collected from 71 patients.,CD163+ macrophages were quantified in BAL and sputum cytospins.,Pro- and anti-inflammatory mediators were measured in BAL and sputum supernatants.,Ex-smokers with COPD had a higher percentage, but lower number of CD163+ macrophages in BAL than current smokers (83.5% and 68.0%, p = 0.04; 5.6 and 20.1 ×104/ml, p = 0.001 respectively).,The percentage CD163+ M2 macrophages was higher in BAL compared to sputum (74.0% and 30.3%, p < 0.001).,BAL M-CSF levels were higher in smokers than ex-smokers (571 pg/ml and 150 pg/ml, p = 0.001) and correlated with the number of CD163+ BAL macrophages (Rs = 0.38, p = 0.003).,No significant differences were found between smokers and ex-smokers in the levels of pro-inflammatory (IL-6 and IL-8), and anti-inflammatory (elafin, and Secretory Leukocyte Protease Inhibitor [SLPI]) mediators in BAL and sputum.,Our data suggest that smoking cessation partially changes the macrophage polarization in vivo in the periphery of the lung towards an anti-inflammatory phenotype, which is not accompanied by a decrease in inflammatory parameters. | 1 |
In models of COPD, environmental stressors induce innate immune responses, inflammasome activation and inflammation.,However, the interaction between these responses and their role in driving pulmonary inflammation in stable COPD is unknown.,To investigate the activation of innate immunity and inflammasome pathways in the bronchial mucosa and bronchoalveolar lavage (BAL) of patients with stable COPD of different severity and control healthy smokers and non-smokers.,Innate immune mediators (interleukin (IL)-6, IL-7, IL-10, IL-27, IL-37, thymic stromal lymphopoietin (TSLP), interferon γ and their receptors, STAT1 and pSTAT1) and inflammasome components (NLRP3, NALP7, caspase 1, IL-1β and its receptors, IL-18, IL-33, ST2) were measured in the bronchial mucosa using immunohistochemistry.,IL-6, soluble IL-6R, sgp130, IL-7, IL-27, HMGB1, IL-33, IL-37 and soluble ST2 were measured in BAL using ELISA.,In bronchial biopsies IL-27+ and pSTAT1+ cells are increased in patients with severe COPD compared with control healthy smokers.,IL-7+ cells are increased in patients with COPD and control smokers compared with control non-smokers.,In severe stable COPD IL-7R+, IL-27R+ and TSLPR+ cells are increased in comparison with both control groups.,The NALP3 inflammasome is not activated in patients with stable COPD compared with control subjects.,The inflammasome inhibitory molecules NALP7 and IL-37 are increased in patients with COPD compared with control smokers.,IL-6 levels are increased in BAL from patients with stable COPD compared with control smokers with normal lung function whereas IL-1β and IL-18 were similar across all groups.,Increased expression of IL-27, IL-37 and NALP7 in the bronchial mucosa may be involved in progression of stable COPD. | Asthma and chronic obstructive pulmonary disease (COPD) display features of overlap in airway physiology and airway inflammation.,Whether inflammatory phenotypes in airway disease describe similar mediator expression is unknown.,To explore the relationship of airway inflammation and cytokine and chemokine expression in asthma and COPD.,Subjects with asthma and COPD (n = 54 and n = 49) were studied.,Clinical characteristics and sputum were collected at entry into the study.,A 2-step sputum processing method was performed for supernatant and cytospin preparation.,Meso Scale Discovery and Luminex platforms were used to measure cytokines, chemokines and matrix metalloproteinase levels.,Analytes sensitive to dithiothreitol (DTT) that had increased recovery in the 2-step sputum process were IL-1β, 4, 5, 10, 13, IFN-γ, TNFRI, GM-CSF, CCL2, 3, 4, 5, 13 and 17.,There was a differential expression in IL-8, TNFRI and TNFRII between asthma and COPD [mean fold difference (95% CI): IL-8, 2.6 (1.3-5.4), p = 0.01; TNFRI, 2.1 (1.3-5.4), p = 0.03; TNFRII, 2.6 (1.2-5.6), p = 0.02].,In neutrophilic and eosinophilic airway inflammation, TNFα, TNFRI, TNFRII, IL-6, IL-8 and IL-5 could differentiate between these phenotypes.,However, these phenotypes were unrelated to the diagnosis of asthma or COPD.,Recovery of sputum mediators sensitive to DTT can be improved using the described sputum processing technique.,Within airway inflammatory sub-phenotypes there is a differential pattern of mediator expression that is independent of disease.,Whether these inflammatory phenotypes in asthma and COPD confer distinct pathogeneses, therapeutic responses and clinical phenotypes needs to be further evaluated. | 1 |
The functional work capacity of chronic obstructive pulmonary disease (COPD) patients is usually assessed with walk tests such as the 6-minute walk test (6MWT) or the shuttle test.,Because these exercise modalities require a controlled environment which limits their use by pulmonologists and severely restricts their use among general practitioners, different modalities of a short (1 minute or less) sit-to-stand test were recently proposed.,In this study, we evaluated a new modality of a semipaced 3-minute chair rise test (3CRT) in 40 patients with COPD, and compared the reproducibility of physiological responses and symptoms during the 3CRT and their interchangeability with the 6MWT.,The results demonstrate that physiological variables, heart rate, pulse oxygen saturation, work done, and symptoms (Borg dyspnea and fatigue scores), during the 3CRT were highly reproducible, and that the physiological responses and symptoms obtained during the 3CRT and the 6MWT were interchangeable for most patients.,Moreover, these preliminary data suggest that patients able to perform more than 50 rises during 3 minutes had no significant disability.,The simplicity and ease of execution of the 3CRT will facilitate the assessment of exercise symptoms and disability in COPD patients during routine consultations with pulmonologists and general practitioners, and will thus contribute to the improved management of COPD patients. | Chronic obstructive pulmonary disease (COPD) is characterized by irreversible, progressive obstruction of lung airflow.,Dyspnea (shortness of breath [SOB]) is the COPD symptom which most negatively impacts patients’ daily activities.,To assess how SOB affects daily activities, 37 items were drafted through focus group discussions and cognitive interviews with COPD patients to develop a patient-reported outcome instrument: the Shortness of Breath with Daily Activities questionnaire (SOBDA).,Psychometric analysis was conducted to reduce the number of items and evaluate the measurement properties of the final SOBDA.,Prospective, observational study of 334 COPD patients, recruited from 24 pulmonology and internal medicine clinics in the United States.,The 37-item SOBDA was administered to patients each evening for 28 days using an electronic diary.,Patients answered every item and rated their level of SOB experienced that day during specific activities.,Item selection was conducted by examining item characteristics, dimensionality, and Rasch model analysis results.,The decision to delete an item was based on psychometric evidence, content validity, and expert clinical input.,The final SOBDA instrument was evaluated for internal consistency, reproducibility, convergent validity, known-groups validity, and responsiveness.,Twenty-four items from the 37-item pool were removed following the item selection process: nine items were removed due to high item-to-item correlations; five due to floor effects; three due to infrequent activity; one due to gender bias; two due to low factor loadings; three due to unordered response options; and one due to expert’s discretion.,Internal consistency and reproducibility of the final SOBDA were demonstrated by Cronbach Alpha = 0.87, and intra-class correlation coefficient = 0.91.,Convergent validity was demonstrated by high correlation with the CRQ-SAS (0.60) and SGRQ-C (0.61).,Known groups validity was demonstrated by significant difference between ratings of the mMRC and clinical global rating of severity.,Evaluation of the ability to detect change was not performed owing to too few responders at the end of the study.,Through the empirical item reduction process, 13 items were selected from the 37-item pool generated during qualitative development.,The final 13-item SOBDA is a reliable and valid instrument for use in clinical trials. | 1 |
Monitoring pathological mechano-acoustic signals emanating from the lungs is critical for timely and cost-effective healthcare delivery.,Adventitious lung sounds including crackles, wheezes, rhonchi, bronchial breath sounds, stridor or pleural rub and abnormal breathing patterns function as essential clinical biomarkers for the early identification, accurate diagnosis and monitoring of pulmonary disorders.,Here, we present a wearable sensor module comprising of a hermetically encapsulated, high precision accelerometer contact microphone (ACM) which enables both episodic and longitudinal assessment of lung sounds, breathing patterns and respiratory rates using a single integrated sensor.,This enhanced ACM sensor leverages a nano-gap transduction mechanism to achieve high sensitivity to weak high frequency vibrations occurring on the surface of the skin due to underlying lung pathologies.,The performance of the ACM sensor was compared to recordings from a state-of-art digital stethoscope, and the efficacy of the developed system is demonstrated by conducting an exploratory research study aimed at recording pathological mechano-acoustic signals from hospitalized patients with a chronic obstructive pulmonary disease (COPD) exacerbation, pneumonia, and acute decompensated heart failure.,This unobtrusive wearable system can enable both episodic and longitudinal evaluation of lung sounds that allow for the early detection and/or ongoing monitoring of pulmonary disease. | The gait abnormalities were linked to the balance deficits in the previous studies.,However, the deviations in the gait parameters in COPD are currently not known.,The study aims to compare gait parameters, static and dynamic balance, and risk of falls in COPD with those in non-COPD individuals.,Fourty-two patients with COPD aged 45 years and gender-matched control subjects were included in the study.,Gait parameters were assessed by Win-Track gait analyzer, the static balance was assessed by posturography, and the dynamic balance was assessed by the time up and go test.,The fear of falls was assessed by Falls Efficacy Scale.,COPD individuals had decreased static and dynamic balance as assessed by posturography (p < 0.05) and TUG (p < 0.01), respectively.,A significant difference in swing duration (p=0.004) and also increased risk of falls (p < 0.01) was observed in COPD patients as compared to non-COPD individuals.,COPD individuals have increased swing duration, reduced static and dynamic balance, and increased fear of falls as compared to non-COPD individuals. | 1 |
Chronic obstructive pulmonary disease (COPD) is a serious, yet preventable and treatable, disease.,The success of its treatment relies largely on the proper implementation of recommendations, such as the recently released Global Strategy for Diagnosis, Management, and Prevention of COPD (GOLD 2011, of late December 2011).,The primary objective of this study was to examine the extent to which GOLD 2011 is being used correctly among Czech respiratory specialists, in particular with regard to the correct classification of patients.,The secondary objective was to explore what effect an erroneous classification has on inadequate use of inhaled corticosteroids (ICS).,In order to achieve these goals, a multi-center, cross-sectional study was conducted, consisting of a general questionnaire and patient-specific forms.,A subjective classification into the GOLD 2011 categories was examined, and then compared with the objectively computed one.,Based on 1,355 patient forms, a discrepancy between the subjective and objective classifications was found in 32.8% of cases.,The most common reason for incorrect classification was an error in the assessment of symptoms, which resulted in underestimation in 23.9% of cases, and overestimation in 8.9% of the patients' records examined.,The specialists seeing more than 120 patients per month were most likely to misclassify their condition, and were found to have done so in 36.7% of all patients seen.,While examining the subjectively driven ICS prescription, it was found that 19.5% of patients received ICS not according to guideline recommendations, while in 12.2% of cases the ICS were omitted, contrary to guideline recommendations.,Furthermore, with consideration to the objectively-computed classification, it was discovered that 15.4% of patients received ICS unnecessarily, whereas in 15.8% of cases, ICS were erroneously omitted.,It was therefore concluded that Czech specialists tend either to under-prescribe or overuse inhaled corticosteroids. | Inhaled corticosteroids (ICS) reduce COPD exacerbation frequency and slow decline in health related quality of life but have little effect on lung function, do not reduce mortality, and increase the risk of pneumonia.,We systematically reviewed trials in which ICS have been withdrawn from patients with COPD, with the aim of determining the effect of withdrawal, understanding the differing results between trials, and making recommendations for improving methodology in future trials where medication is withdrawn.,Trials were identified by two independent reviewers using MEDLINE, EMBASE and CINAHL, citations of identified studies were checked, and experts contacted to identify further studies.,Data extraction was completed independently by two reviewers.,The methodological quality of each trial was determined by assessing possible sources of systematic bias as recommended by the Cochrane collaboration.,We included four trials; the quality of three was adequate.,In all trials, outcomes were generally worse for patients who had had ICS withdrawn, but differences between outcomes for these patients and patients who continued with medication were mostly small and not statistically significant.,Due to data paucity we performed only one meta-analysis; this indicated that patients who had had medication withdrawn were 1.11 (95% CI 0.84 to 1.46) times more likely to have an exacerbation in the following year, but the definition of exacerbations was not consistent between the three trials, and the impact of withdrawal was smaller in recent trials which were also trials conducted under conditions that reflected routine practice.,There is no evidence from this review that withdrawing ICS in routine practice results in important deterioration in patient outcomes.,Furthermore, the extent of increase in exacerbations depends on the way exacerbations are defined and managed and may depend on the use of other medication.,In trials where medication is withdrawn, investigators should report other medication use, definitions of exacerbations and management of patients clearly.,Intention to treat analyses should be used and interpreted appropriately. | 1 |
Despite the availability of treatment guidelines and inhaled medications for asthma and chronic obstructive pulmonary disease (COPD), much remains to be done to lessen the burden of these respiratory diseases for patients.,The challenge of selecting effective and efficacious drugs for patients is a key focus area for healthcare professionals.,Here we discuss the concept of “drivers of effectiveness”- features of a medicine which may increase or decrease its effectiveness in the presence of real-world factors - and highlight the importance of considering these drivers in the early stages of drug development, and exploring their impact in carefully designed pragmatic trials.,Using the Salford Lung Studies (SLS) in asthma and COPD as an illustrative example, we discuss various features of the inhaled corticosteroid/long-acting β2-agonist combination, fluticasone furoate/vilanterol (FF/VI), as potential drivers of effectiveness that may have contributed to the improved patient outcomes observed with initiation of FF/VI versus continuation of usual care in the UK primary care setting. | To assess the treatment progression during the 24 months following a formal diagnosis of chronic obstructive pulmonary disease (COPD) in the UK primary care setting.,A retrospective cohort of newly diagnosed COPD patients was identified in the Clinical Practice Research Datalink (CPRD) from 1/1/2008 until 31/12/2009.,Maintenance therapy prescribed within the first 3 months of diagnosis and in the subsequent 3-month intervals for 24 months were analyzed.,Treatment classes included long-acting β2-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), inhaled corticosteroids (ICSs), and respective combinations.,At each 3-month interval, discontinuation, switching, addition, and stepping down patterns were analyzed cumulatively for the first 12 months and over the 24-month of follow-up.,A total of 3199 patients with at least one prescription of a maintenance therapy at baseline and during 4th-6th month interval were included in the analysis.,At diagnosis (0-3 months), the most frequently prescribed maintenance therapy was LABA+ICS (43%), followed by LAMA (24%) and LABA+LAMA+ICS (23%).,Nearly half the patients (LABA-50%, LAMA-43%) starting on a monobronchodilator had additions to their treatment in 24 months.,Compared to other medications, patients starting on a LAMA were most likely to escalate to triple therapy in 24 months.,Nearly one-fourth of the patients prescribed triple therapy at baseline stepped down to LABA+ICS (25%) or LAMA (31%) within 24 months.,Disease progression is evident over the 24 months after COPD diagnosis, as more patients were prescribed additional maintenance therapy in the 24-month period compared to baseline.,The changes in therapy suggest that it is difficult to achieve a consistently improved COPD disease state. | 1 |
Exercise tolerance is an important endpoint in chronic obstructive pulmonary disease (COPD) clinical trials.,Little is known about the comparative measurement properties of constant work rate cycle ergometry (CWRCE) and the endurance shuttle walking test (ESWT).,The objective of this sub-analysis of the TORRACTO® study was to directly compare the endurance measurement properties of CWRCE and ESWT in patients with COPD in a multicentre, multinational setting.,We predicted that both tests would be similarly reliable, but that the ESWT would be more responsive to bronchodilation than CWRCE.,This analysis included 151 patients who performed CWRCE and ESWT at baseline and week 6 after receiving once-daily placebo, tiotropium/olodaterol (T/O) 2.5/5 μg or T/O 5/5 μg.,Reproducibility was assessed by comparing their respective performance at baseline and week 6 in the placebo group.,Responsiveness to bronchodilation was assessed by comparing endurance time at week 6 with T/O with baseline values and placebo.,The locus of symptom limitation and end-exercise Borg scales for breathing and leg discomfort for both tests were also analysed.,The intraclass correlation coefficients for CWRCE and ESWT were 0.56 [95% confidence interval (CI) 0.37-0.71] and 0.75 (95% CI 0.63-0.84).,More patients were limited by breathing discomfort during the ESWT than during CWRCE, whereas more patients were limited by leg discomfort or breathing/leg discomfort during CWRCE than the ESWT (p <0.0001).,Both tests were responsive to bronchodilator treatment: there was a 19% increase in endurance time from baseline at week 6 (p = 0.0006) assessed with CWRCE, and a 20% increase in endurance time assessed with ESWT (p = 0.0013).,Both exercise tests performed well in a multicentre clinical trial.,Although the locus of symptom limitation differed between the two tests, both were reliable and responsive to bronchodilation.,For future clinical trials, the choice of test should depend on the study requirements.,NCT01525615.,The reviews of this paper are available via the supplemental material section. | The distance of 6-minute walk test (D6MWT) has been widely used in the assessment of functional status in patients with COPD, while very little attention has been paid to the role of steps of 6-minute walk test (S6MWT).,The purpose of this study was to investigate the relationship between S6MWT and other physiologic parameters of COPD.,Seventy patients with stable COPD were enrolled consecutively in this cross-sectional study.,Pulmonary function tests, including spirometry, impulse oscillometry (IOS) and the single-breath diffusing capacity of the lungs for carbon monoxide (DLCO), were carried out at rest.,Quality of life was assessed by health-related quality of life (HRQoL) questionnaires, including modified Medical Research Council dyspnea scale (mMRC), St George’s Respiratory Questionnaire, Chronic Obstructive Pulmonary Disease Assessment Test (CAT) and Clinical Chronic Obstructive Pulmonary Questionnaire.,Both steps and distance were measured in the following 6-minute walk test (6MWT).,Both S6MWT and D6MWT showed significant correlation with spirometry, IOS, DLCO parameters and HRQoL questionnaires score.,Both pre- and post-6MWT inspiratory capacity showed significant correlation with S6MWT (ρ=0.338, P=0.004; ρ=0.359, P=0.002, respectively), whereas did not correlate with D6MWT (ρ=0.145, P=0.230; ρ=0.160, P=0.189, respectively).,In stepwise multiple regression analysis, mMRC grade, age and CAT score remained as significant predictors in the final model for D6MWT (adjusted R2=0.445, P<0.01).,DLCO and CAT score remained as significant predictors in the final model for S6MWT (adjusted R2=0.417, P<0.01).,S6MWT is efficient in the evaluation of functional status and quality of life in COPD and has significant correlation with various parameters indicating disease severity.,Additionally, S6MWT might be better in predicting lung hyperinflation in COPD compared with D6MWT. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by a decline of lung function and symptoms such as chronic bronchitis and emphysema leading from lung tissue destruction.,Increased activity of matrix metalloproteinases (MMPs) and an imbalance between MMPs and their tissue inhibitors (TIMPs) are considered as factors influencing the pathogenesis of COPD.,We investigated the role of genetic polymorphism and expression level of MMP-9 and concentration of its complexes with TIMPs in the development of COPD among Polish patients.,We analyzed SNP in the promoter region of MMP-9 gene (rs3918242) using PCR-RFLP method among 335 COPD patients and 309 healthy individuals.,Additionally, 60 COPD patients and 61 controls were tested for copy number variants (CNV) of MMP-9 (by quantitative real-time PCR) and serum levels of MMP-9 and its complexes with TIMP1 and TIMP2 (using ELISA).,All subjects were analyzed for lung function using spirometry (FEV1% and FEV1/FVC parameters).,We observed that allele and genotype frequencies of the SNP rs3918242, as well as the number of gene copies, were similar in COPD patient and controls groups.,Serum levels of MMP-9 and MMP-9/TIMP1 complex were significantly higher in COPD patients in comparison to controls groups, although independently of analyzed gene polymorphisms.,Additionally, the significant inverse relationships between parameters of lung function (FEV1% and FEV1/FVC) and proteins level were found in ridge regression models, especially we found that FEV1% decreased when MMP-9 level increased in controls and patients with COPD group.,In conclusion, we found that COPD patients were predisposed to produce more MMP-9 and MMP-9/TIMP1 complex than healthy individuals.,This phenomenon is probably associated with the disease-related lung environment but not with genetic features of the MMP-9. | Chronic obstructive pulmonary disease (COPD) is characterized by the progression of irreversible airflow limitation and is a leading cause of morbidity and mortality worldwide.,Although several crucial mechanisms of COPD pathogenesis have been studied, the precise mechanism remains unknown.,Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are released from almost all cell types and are recognized as novel cell-cell communication tools.,They have been shown to carry and transfer a wide variety of molecules, such as microRNAs, messenger RNAs, and proteins, which are involved in physiological functions and the pathology of various diseases.,Recently, EVs have attracted considerable attention in pulmonary research.,In this review, we summarize the recent findings of EV-mediated COPD pathogenesis.,We also discuss the potential clinical usefulness of EVs as biomarkers and therapeutic agents for the treatment of COPD. | 1 |
Acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with a significant mortality, health and economic burden.,Their diagnosis, assessment and management remain suboptimal and unchanged for decades.,Recent clinical and translational studies revealed that the significant heterogeneity in mechanisms and outcomes of exacerbations could be resolved by grouping them etiologically.,This is anticipated to lead to a better understanding of the biological processes that underlie each type of exacerbation and to allow the introduction of precision medicine interventions that could improve outcomes.,This review summarises novel data on the diagnosis, phenotyping, targeted treatment and prevention of COPD exacerbations. | Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD.,To characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes.,We surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene.,We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes.,The stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies.,Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated.,We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events and bronchiectasis.,Subtypes of COPD have distinct bacterial compositions and stabilities over time.,Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future.,This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient.,Results, NCT01360398. | 1 |
We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.,Three studies of ≥1-year duration met the inclusion criteria.,Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%).,At baseline, 57-75% of patients had ≥2% blood eosinophils.,Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.,For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001).,No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively).,In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo).,No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.,Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. | To assess the treatment progression during the 24 months following a formal diagnosis of chronic obstructive pulmonary disease (COPD) in the UK primary care setting.,A retrospective cohort of newly diagnosed COPD patients was identified in the Clinical Practice Research Datalink (CPRD) from 1/1/2008 until 31/12/2009.,Maintenance therapy prescribed within the first 3 months of diagnosis and in the subsequent 3-month intervals for 24 months were analyzed.,Treatment classes included long-acting β2-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), inhaled corticosteroids (ICSs), and respective combinations.,At each 3-month interval, discontinuation, switching, addition, and stepping down patterns were analyzed cumulatively for the first 12 months and over the 24-month of follow-up.,A total of 3199 patients with at least one prescription of a maintenance therapy at baseline and during 4th-6th month interval were included in the analysis.,At diagnosis (0-3 months), the most frequently prescribed maintenance therapy was LABA+ICS (43%), followed by LAMA (24%) and LABA+LAMA+ICS (23%).,Nearly half the patients (LABA-50%, LAMA-43%) starting on a monobronchodilator had additions to their treatment in 24 months.,Compared to other medications, patients starting on a LAMA were most likely to escalate to triple therapy in 24 months.,Nearly one-fourth of the patients prescribed triple therapy at baseline stepped down to LABA+ICS (25%) or LAMA (31%) within 24 months.,Disease progression is evident over the 24 months after COPD diagnosis, as more patients were prescribed additional maintenance therapy in the 24-month period compared to baseline.,The changes in therapy suggest that it is difficult to achieve a consistently improved COPD disease state. | 1 |
Background: Combination therapy with a long-acting bronchodilator and an inhaled corticosteroid (ICS) is recommended in patients with chronic obstructive pulmonary disease (COPD) who have frequent exacerbations.,The efficacy and tolerability of the combination of budesonide/formoterol have been demonstrated in patients with COPD when administered via the dry powder inhaler (DPI) in a 1-year study and when administered via the hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) in a 6-month study.,Objective: This study assessed the long-term efficacy and tolerability of budesonide/formoterol HFA pMDI in patients with moderate to very severe COPD.,Methods: This was a 12-month, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled, multicentre study (NCT00206167) of 1964 patients aged ≥40 years with moderate to very severe COPD conducted from 2005 to 2007 at 237 sites in the US, Europe and Mexico.,After 2 weeks of treatment based on previous therapy (ICSs, short-acting bronchodilators allowed), patients received one of the following treatments twice daily: budesonide/formoterol pMDI 160/4.5 μg × two inhalations (320/9 μg); budesonide/formoterol pMDI 80/4.5 μg × two inhalations (160/9 μg); formoterol DPI 4.5 μg × two inhalations (9 μg); or placebo.,Main outcome measures: The co-primary efficacy variables were pre-dose forced expiratory volume in 1 second (FEV1) and 1-hour post-dose FEV1.,Results: Budesonide/formoterol 320/9 μg demonstrated greater improvements in pre-dose FEV1 versus formoterol (p = 0.008), and both budesonide/formoterol doses demonstrated greater improvements in 1-hour post-dose FEV1 versus placebo (p < 0.001).,The rate of COPD exacerbations was lower in both budesonide/formoterol groups compared with formoterol and placebo (p ≤ 0.004).,Both budesonide/formoterol doses were more effective than placebo (p ≤ 0.006) for controlling dyspnoea and improving health status (St George’s Respiratory Questionnaire).,All treatments were generally well tolerated.,The incidence of pneumonia was not different for active (3.4-4.0%) and placebo (5.0%) groups.,Conclusions: Budesonide/formoterol pMDI (320/9 μg and 160/9 μg) improved pulmonary function and reduced symptoms and exacerbations over 1 year in patients with moderate to very severe COPD.,Only budesonide/formoterol pMDI 320/9 μg demonstrated greater efficacy for both co-primary variables compared with formoterol DPI 9 μg.,Both budesonide/formoterol pMDI dosages were well tolerated relative to formoterol and placebo.,Supplementary material is available for this article at 10.2165/00003495-200969050-00004 and is accessible for authorized users. | Little is known about factors that determine health status decline in clinical trials of COPD.,To examine health status changes over 3 years in the TORCH study of salmeterol+fluticasone propionate (SFC) vs. salmeterol alone, fluticasone propionate alone or placebo.,St George's Respiratory Questionnaire (SGRQ) was administered at baseline then every 6 months.,Data from 4951 patients in 28 countries were available.,SFC produced significant improvements over placebo in all three SGRQ domains during the study: (Symptoms -3.6 [95% CI -4.8, -2.4], Activity -2.8 [95% CI -3.9, -1.6], Impacts -3.2 [95% CI -4.3, -2.1]) but the pattern of change over time differed between domains.,SGRQ deteriorated faster in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III & IV relative to GOLD stage II (p < 0.001).,There was no difference in the relationship between deterioration in SGRQ Total score and forced expiratory volume in one second (FEV1) decline (as % predicted) in men and women.,Significantly faster deterioration in Total score relative to FEV1 % predicted was seen in older patients (≥ 65 years) and there was an age-related change in Total score that was independent of change in FEV1.,The relationship between deterioration in FEV1 and SGRQ did not differ in different world regions, but patients in Asia-Pacific showed a large improvement in score that was unrelated to FEV1 change.,In addition to treatment effects, health status changes in clinical trials may be influenced by demographic and disease-related factors.,Deterioration in health status appears to be fastest in older persons and those with severe airflow limitation.,ClinicalTrials.gov: NCT00268216 | 1 |
The major marker utilized to monitor COPD patients is forced expiratory volume in one second (FEV1).,However, asingle measurement of FEV1 cannot reliably predict subsequent decline.,Recent studies indicate that T lymphocytes and eosinophils are important determinants of disease stability in COPD.,We therefore measured cytokine levels in the lung lavage fluid and plasma of COPD patients in order to determine if the levels of T cell or eosinophil related cytokines were predictive of the future course of the disease.,Baseline lung lavage and plasma samples were collected from COPD subjects with moderately severe airway obstruction and emphysematous changes on chest CT.,The study participants were former smokers who had not had a disease exacerbation within the past six months or used steroids within the past two months.,Those subjects who demonstrated stable disease over the following six months (ΔFEV1 % predicted = 4.7 ± 7.2; N = 34) were retrospectively compared with study participants who experienced a rapid decline in lung function (ΔFEV1 % predicted = -16.0 ± 6.0; N = 16) during the same time period and with normal controls (N = 11).,Plasma and lung lavage cytokines were measured from clinical samples using the Luminex multiplex kit which enabled the simultaneous measurement of several T cell and eosinophil related cytokines.,Stable COPD participants had significantly higher plasma IL-2 levels compared to participants with rapidly progressive COPD (p = 0.04).,In contrast, plasma eotaxin-1 levels were significantly lower in stable COPD subjects compared to normal controls (p < 0.03).,In addition, lung lavage eotaxin-1 levels were significantly higher in rapidly progressive COPD participants compared to both normal controls (p < 0.02) and stable COPD participants (p < 0.05).,These findings indicate that IL-2 and eotaxin-1 levels may be important markers of disease stability in advanced emphysema patients.,Prospective studies will need to confirm whether measuring IL-2 or eotaxin-1 can identify patients at risk for rapid disease progression. | COPD is underdiagnosed and its early assessment is problematic.,It has been suggested that symptomatic smokers with normal FEV1/FVC (Stage 0 COPD, GOLD criteria) can develop COPD in the future.,Potential early biomarkers in COPD include the matrix metallo-proteinases (MMPs).,It is not yet known, whether alterations in MMP expression are associated with smoking alone or with the risk of developing COPD.,In this cross-sectional study MMP-8, MMP-9 and MMP-12 were determined from induced sputum and plasma by ELISA, immunocytochemistry, zymography, and/or Western blot in non-smokers (n = 32), smokers with symptoms (Stage 0, GOLD criteria) (n = 23) or without symptoms (n = 23).,Only MMP-8 differentiated Stage 0 COPD from non-symptomatic smokers (p = 0.02).,MMP-9 levels were significantly elevated in the induced sputum of non-symptomatic smokers and Stage 0 COPD (p = 0.01, p < 0.001) compared to non-smokers, but did not differ between the two subgroups of smokers.,MMP-12 was higher only at Stage 0 compared to non-smokers (p = 0.04).,MMP-8, MMP-9 and MMP-12 immunoreactivity was localized in macrophages and neutrophils, especially in smokers.,MMP-8 levels correlated significantly with the small airway flow parameters (MEF50, MEF25) (p = 0.005 and p = 0.0004) and markers of neutrophil activation (myeloperoxidase, lactoferrin).,In conclusion MMP-8 may differentiate Stage 0 from healthy smokers. | 1 |
NVA237 (glycopyrronium bromide) is a once-daily long-acting muscarinic antagonist (LAMA) in development for chronic obstructive pulmonary disease (COPD).,The GLycopyrronium bromide in COPD airWays clinical Study 2 (GLOW2) evaluated the efficacy and safety of NVA237 in moderate-to-severe COPD over 52 weeks.,Patients were randomised 2:1:1 to NVA237 50 μg, placebo or open-label tiotropium 18 μg for 52 weeks.,Primary end-point was trough forced expiratory volume in 1 s (FEV1) at 12 weeks.,1,066 patients were randomised, 810 completed the study.,At week 12, trough FEV1 increased significantly by 97 mL with NVA237 (95% CI 64.6-130.2; p<0.001) and 83 mL with tiotropium (95% CI 45.6-121.4; p<0.001).,Compared with placebo, NVA237 produced significant improvements in dyspnoea (Transition Dyspnoea Index at week 26; p=0.002) and health status (St George's Respiratory Questionnaire at week 52; p<0.001).,NVA237 significantly reduced the risk of moderate-to-severe COPD exacerbations by 34% (p=0.001) and the use of rescue medication (p=0.039), versus placebo.,NVA237-placebo and tiotropium-placebo differences were comparable for all outcomes.,Safety profiles were similar across groups.,NVA237 50 μg provided significant improvements in lung function, dyspnoea, health status, exacerbations and rescue medication use, versus placebo, and was comparable to tiotropium.,NVA237 can potentially be an alternative choice of LAMA for COPD patients. | Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations.,This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).,We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers.,In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.,COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function.,Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage.,The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study.,The distribution of these variables within each GOLD stage was wide.,Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation.,The amount of emphysema increased with GOLD severity.,The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage.,Some gender differences were also identified.,The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease. | 1 |
The association between exposure to ambient particles with a median aerodynamic diameter less than 10/2.5 µm (particulate matter, PM10/2.5) and COPD remains unclear.,Our study objective was to examine the association between ambient PM10/2.5 concentrations and lung functions in adults.,A cross-sectional study was conducted in southern China.,Seven clusters were randomly selected from four cities across Guangdong province.,Residents aged ≥20 years in the participating clusters were randomly recruited; all eligible participants were examined with a standardised questionnaire and spirometry.,COPD was defined as a post-bronchodilator FEV1/FVC less than 70%.,Atmosphere PM sampling was conducted across the clusters along with our survey.,Of the subjects initially recruited, 84.4% (n=5993) were included for analysis.,COPD prevalence and atmosphere PM concentration varied significantly among the seven clusters.,COPD prevalence was significantly associated with elevated PM concentration levels: adjusted OR 2.416 (95% CI 1.417 to 4.118) for >35 and ≤75 µg/m3 and 2.530 (1.280 to 5.001) for >75 µg/m3 compared with the level of ≤35 µg/m3 for PM2.5; adjusted OR 2.442 (95% CI 1.449 to 4.117) for >50 and ≤150 µg/m3 compared with the level of ≤50 µg/m3 for PM1.,A 10 µg/m3 increase in PM2.5 concentrations was associated with a 26 mL (95% CI −43 to −9) decrease in FEV1, a 28 mL (−49 to −8) decrease in FVC and a 0.09% decrease (−0.170 to −0.010) in FEV1/FVC ratio.,The associations of COPD with PM10 were consistent with PM2.5 but slightly weaker.,Exposure to higher PM concentrations was strongly associated with increased COPD prevalence and declined respiratory function.,ChiCTR-OO-14004264; Post-results. | Due to the rapid urbanization of the world population, a better understanding of the detrimental effects of exposure to urban air pollution on chronic lung disease is necessary.,Strong epidemiological evidence suggests that exposure to particulate matter (PM) air pollution causes exacerbations of pre-existing lung conditions, such as, chronic obstructive pulmonary disease (COPD) resulting in increased morbidity and mortality.,However, little is known whether a chronic, low-grade exposure to ambient PM can cause the development and progression of COPD.,The deposition of PM in the respiratory tract depends predominantly on the size of the particles, with larger particles deposited in the upper and larger airways and smaller particles penetrating deep into the alveolar spaces.,Ineffective clearance of this PM from the airways could cause particle retention in lung tissues, resulting in a chronic, low-grade inflammatory response that may be pathogenetically important in both the exacerbation, as well as, the progression of lung disease.,This review focuses on the adverse effects of exposure to ambient PM air pollution on the exacerbation, progression, and development of COPD. | 1 |
The ADAM33 gene is associated with the pathophysiology of Chronic Obstructive Pulmonary Disease (COPD) and atherosclerosis.,In this study we investigated all-cause, COPD and cardiovascular mortality, in relation to single nucleotide polymorphisms (SNPs) in ADAM33 (Q_1, S_1, S_2, T_1 and T_2) that were genotyped in 1,390 subjects from the Vlagtwedde/Vlaardingen cohort.,Participants were examined at entry in 1989/1990 and followed up till evaluation of the vital status on December 31st, 2008.,Using Cox proportional hazards regression we estimated the risk of the SNPs in relation to mortality, adjusting for gender, age, FEV1, height, place of residence and packyears of smoking.,Additionally, we performed stratified analyses according to gender and smoking habits.,After 18 years, 284 (20.4%) subjects had died (107 due to cardiovascular disease and 20 due to COPD).,Individuals homozygous for the minor allele of SNP T_2 had an increased risk of all-cause and cardiovascular mortality compared to wild types: hazard ratio 3.6 (95% confidence interval 2.0 to 6.7) and 3.4 (1.2 to 9.5) respectively.,Individuals homozygous for the minor allele of S_1, S_2, T_2 or Q_1 had a significantly increased risk of COPD mortality.,In stratified analyses the risk of all-cause mortality associated with SNP T_2 did not change: females 3.5 (1.5 to 8.3), males 3.1 (1.2 to 7.6), never smokers 3.8 (0.9 to 16.3), ever smokers 3.6 (1.8 to 7.2).,This study shows for the first time that ADAM33 is a pleiotropic gene that is associated with all-cause, COPD and cardiovascular mortality, independent of potential confounders. | 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 |
This systematic review and meta-analysis aimed to provide current evidence regarding the effectiveness of telemonitoring for preventing COPD exacerbations, focusing on severe exacerbations requiring hospitalisation or emergency room (ER) visits.,We systematically searched for randomised controlled trials using nine databases from August to September 2020 following the Cochrane Collaboration Guidelines.,Of 2159 records identified, 22 studies involving 2906 participants met the inclusion criteria.,The participants in 55% and 59% of studies had severe airflow limitations and severe exacerbation histories in the preceding year, respectively.,The most commonly telemonitored data were oxygen saturation (91%) and symptoms (73%).,A meta-analysis showed that telemonitoring did not reduce the number of admissions (12 studies) but decreased the number of ER visits due to severe exacerbations [7 studies combined, standardised mean difference (SMD) = −0.14; 95% confidence interval (CI): −0.28, −0.01].,Most studies reported no benefit in mortality, quality of life, or cost-effectiveness.,All eight studies that surveyed participant satisfaction reported high satisfaction levels.,Our review suggested that adding telemonitoring to usual care reduced unnecessary ER visits but was unlikely to prevent hospitalisations due to COPD exacerbations and that telemonitoring was well-accepted by patients with COPD and could be easily integrated into their existing care. | Chronic obstructive pulmonary disease (COPD) is a major health problem and an economic burden globally.,There is growing interest in how electronic health (eHealth) can be used to provide efficient health care.,Telemonitoring, where the patient’s health-related data is transmitted to a health care provider, can be used to detect early signs of exacerbations.,A successful implementation of telemonitoring systems into clinical practice requires in-depth knowledge of the users’ preferences.,The aim of this study was to explore perceptions of the use of a home telemonitoring system among patients with COPD.,Semistructured individual interviews were carried out with 8 women and 5 men who were participants in a project aimed at developing and evaluating a telemonitoring system.,The web-based telemonitoring system measured pulmonary function, subjective symptoms, and oxygen saturation.,Participants were interviewed after having used the system for 2-4 months.,Interview transcripts were analyzed with qualitative content analysis.,The analysis resulted in the theme A transition toward increased control and security and four categories: using with (in)security, affecting technical concern or confidence, providing easy access to health care, and increasing control over the disease.,The participants reported various perceptions of using the telemonitoring system.,They expressed initial feelings of insecurity, both in terms of operating the system and in terms of their disease.,However, the practical management of the telemonitoring system became easier with time; the participants gradually gained confidence and improved their self-management.,New technology was perceived as an important complement to existing health care, but the importance of maintaining a human contact in real life or through the telemonitoring system was emphasized.,This study captured a transition among the participants from being insecure and experiencing technical concerns to acquiring technical confidence and improving disease management.,Telemonitoring can be a valuable complement to health care, leading to increased self-knowledge, a sense of security, and improved self-management.,Suggestions to improve the further development and implementation of telemonitoring systems include better patient education and the involvement of end users in the technical development process.,Additional research is needed, particularly in the design of user-friendly systems, as well as in developing tools to predict which patients are most likely to find the equipment useful, as this may result in increased empowerment, improved quality of life, reduced costs, and a contribution to equity in health. | 1 |
Readmissions are common following acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and are partially responsible for increased morbidity and mortality in COPD.,Numerous factors have been shown to predict readmission of patients previously admitted to hospital for AECOPD; however, factors related to readmission in patients who are triaged in emergency departments (EDs) and sent directly home are poorly understood.,We postulate that patients seen in the ED for AECOPD and directly sent home have a high readmission rate, and we suspect that inadequate management and follow-up contribute to this high readmission rate.,We conducted a 1-year retrospective study of all patients seen in the ED for AECOPD at an inner-city tertiary care hospital; 30- and 90-day readmission rates for COPD and all-cause admissions to the ED and hospital were determined.,Patients discharged directly home from the ED were compared with those admitted to hospital for management.,Patient, treatment, and system variables that could potentially impact readmission were documented.,Multivariate Poisson regression models were used to determine which factors predicted readmissions.,The readmission rates in the ED group (n=240) were significantly higher than that in the hospitalized group (n=271): 1) the 90-day ED readmissions (1.29 vs 0.51, p<0.0001) and 30-day ED readmissions (0.54 vs 0.20, p<0.0001) (ED vs hospitalized groups) were significantly higher in the ED group; 2) the time to first readmission was significantly shorter in the ED group than in the hospitalized group (24.1±22 vs 31.8±27.8 days; p<0.05).,Cardiovascular comorbidities (p<0.00001), substance abuse disorder (p<0.001), and mental illness (p<0.001) were the strongest predictors of readmission in the ED group.,Age (p<0.01), forced expiratory volume in 1 second (p<0.001), and cardiovascular comorbidities (p<0.05) were the best predictors for both 30- and 90-day COPD readmission rates in the ED group.,Only 50% of the ED group patients received bronchodilators, oral steroids, and antibiotics inclusively, and only 68% were referred for community follow-up.,The need for oral steroids to treat AECOPD predicted future 90-day COPD readmissions in the ED group (p<0.003).,Patients discharged directly home from EDs have a significantly higher risk of readmission to EDs than those who are hospitalized.,One possible reason for this is that COPD management is variable in EDs with <50% receiving appropriate therapy. | Chronic obstructive pulmonary disease (COPD) is a chronic, irreversible disease and a leading cause of worldwide morbidity and mortality.,In Canada, COPD is the fourth leading cause of death.,This systematic review was undertaken to update healthcare professionals and decision makers regarding the recent clinical, humanistic and economic burden evidence in Canada.,A systematic literature search was conducted in PubMed, EMBASE, and Cochrane databases to identify original research published January 2000 through December 2012 on the burden of COPD in Canada.,Each search was conducted using controlled vocabulary and key words, with “COPD” as the main search concept and limited to Canadian studies, written in English and involving human subjects.,Selected studies included randomized controlled trials, observational studies and systematic reviews/meta-analyses that reported healthcare resource utilization, quality of life and/or healthcare costs.,Of the 972 articles identified through the literature searches, 70 studies were included in this review.,These studies were determined to have an overall good quality based on the quality assessment.,COPD patients were found to average 0-4 annual emergency department visits, 0.3-1.5 annual hospital visits, and 0.7-5 annual physician visits.,Self-care management was found to lessen the overall risk of emergency department (ED) visits, hospitalization and unscheduled physician visits.,Additionally, integrated care decreased the mean number of hospitalizations and telephone support reduced the number of annual physician visits.,Overall, 60-68 % of COPD patients were found to be inactive and 60-72 % reported activity restriction.,Pain was found to negatively correlate with physical activity while breathing difficulties resulted in an inability to leave home and reduced the ability to handle activities of daily living.,Evidence indicated that treating COPD improved patients’ overall quality of life.,The average total cost per patient ranged between CAN $2444-4391 from a patient perspective to CAN $3910-6693 from a societal perspective.,Furthermore, evidence indicated that COPD exacerbations lead to higher costs.,The clinical, humanistic and economic burden of COPD in Canada is substantial.,Use of self-care management programs, telephone support, and integrated care may reduce the overall burden to Canadian patients and society. | 1 |
The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear.,The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA).,This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 µg, once-daily tiotropium (TIO) 18 µg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 µg twice daily.,The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks.,An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone.,773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial.,At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) −7 mL (SE 17.4) with a lower limit for non-inferiority of −60 mL.,There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001).,At 12 weeks, GLY+SAL/FP produced significant improvement in St George's Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff −2.154, p=0.02).,GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff −0.72 puffs/day, p<0.001).,Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively.,GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP.,Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP.,NCT01513460. | The choice between lower limit of normal or fixed value of forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC) < 0.70 as the criterion for confirming airway obstruction is an open issue.,In this study, we compared the criteria of lower limit of normal and fixed FEV1/FVC for diagnosis of airway obstruction, with a focus on healthy elderly people.,We selected 367 healthy nonsmoking subjects aged 65-93 years from 1971 participants in the population-based SARA (Salute Respiratoria nell’Anziano, Italian for “Respiratory Health in the Elderly”) study, analyzed their spirometric data, and tested the relationship between spirometric indices and anthropometric variables.,The lower limit of normal for FEV1/FVC was calculated as the fifth percentile of the normal distribution for selected subjects.,While FEV1 and FVC decreased significantly with aging, the relationship between FEV1/FVC and age was not statistically significant in men or women.,The lower limit of normal for FEV1/FVC was 0.65 in men and 0.67 in women.,Fifty-five participants (15%) had FEV1/FVC < 0.70 and would have been inappropriately classified as obstructed according to the Global Initiative for Obstructive Lung Disease, American Thoracic Society/European Respiratory Society, and Canadian guidelines on chronic obstructive pulmonary disease.,By applying different FEV1/FVC thresholds for the different age groups, as previously proposed in the literature, (0.70 for <70 years, 0.65 for 70-80 years, and 0.60 for >80 years) the percentage of patients classified as obstructed decreased to 6%.,No subjects older than 80 years had an FEV1/FVC < 0.60.,The present results confirm the inadequacy of FEV1/FVC < 0.70 as a diagnostic criterion for airway obstruction after the age of 65 years.,FEV1/FVC < 0.65 and <0.67 (for men and women, respectively) could identify subjects with airway obstruction in such a population.,Further reduction of the threshold after 80 years is not justified. | 1 |
Few studies have evaluated the contribution of multiple virus and bacterial infections in acute exacerbation of chronic obstructive pulmonary disease.,This study estimated the burden of multiple viral and bacterial respiratory infections in moderate to very severe chronic obstructive pulmonary disease patients that were prospectively followed‐up during a 12‐month pilot study.,Clinical data were collected monthly and sputum was collected at the time of each acute exacerbation event.,Classical culture techniques for bacteria and multiplex polymerase chain reaction (PCR) and microarray detection assays were performed to identify viral and atypical bacterial pathogens in the sputum.,Overall, 51 patients were included and 45 acute exacerbation events were investigated clinically and microbiologically.,Among the 45 acute exacerbation events, 44% had evidence of viral infection involving human rhinovirus (HRV) and metapneumovirus (hMPV) in 20% and 18%, respectively.,Intracellular bacteria were not found in sputum by PCR.,Common bacterial pathogens were identified in 42% of acute exacerbation patients, most frequently Branhamella catarrhalis, Streptococcus pneumoniae and Haemophilus influenzae.,Viral or virus and bacteria co‐infections were detected in 27% of acute exacerbation events (n = 12) with HRV and hMPV involved in 92% of cases.,Patients with co‐infections did not present greater clinical severity scores at exacerbation and more recurrence of acute exacerbation events at 3 and 6 months than those with single infections (P > 0.4).,These results suggest that HRV and hMPV may be contributors or cofactors of AECOPD.,These findings indicate that viral or virus and bacterial co‐infections do not impact significantly on the clinical severity of acute exacerbation of chronic obstructive pulmonary disease and recurrence at 3 and 6 months.,J.,Med.,Virol.,85:866-873, 2013.,© 2013 Wiley Periodicals, Inc. | Chronic Obstructive Pulmonary Disease is the third leading cause of death in the US, and is associated with periodic exacerbations, which account for the largest proportion of health care utilization, and lead to significant morbidity, mortality, and worsening lung function.,A subset of patients with COPD have frequent exacerbations, occurring 2 or more times per year.,Despite many interventions to reduce COPD exacerbations, there is a significant lack of knowledge in regards to their mechanisms and predisposing factors.,We describe here an important observation that defines antibody deficiency as a potential risk factor for frequent COPD exacerbations.,We report a case series of patients who have frequent COPD exacerbations, and who were found to have an underlying primary antibody deficiency syndrome.,We also report on the outcome of COPD exacerbations following treatment in a subset with of these patients with antibody deficiency.,We identified patients with COPD who had 2 or more moderate to severe exacerbations per year; immune evaluation including serum immunoglobulin levels and pneumococcal IgG titers was performed.,Patients diagnosed with an antibody deficiency syndrome were treated with either immunoglobulin replacement therapy or prophylactic antibiotics, and their COPD exacerbations were monitored over time.,A total of 42 patients were identified who had 2 or more moderate to severe COPD exacerbations per year.,Twenty-nine patients had an underlying antibody deficiency syndrome: common variable immunodeficiency (8), specific antibody deficiency (20), and selective IgA deficiency (1).,Twenty-two patients had a follow-up for at least 1 year after treatment of their antibody deficiency, which resulted in a significant reduction of COPD exacerbations, courses of oral corticosteroid use and cumulative annual dose of oral corticosteroid use, rescue antibiotic use, and hospitalizations for COPD exacerbations.,This case series identifies antibody deficiency as a potentially treatable risk factor for frequent COPD exacerbations; testing for antibody deficiency should be considered in difficult to manage frequently exacerbating COPD patients.,Further prospective studies are warranted to further test this hypothesis. | 1 |
Chronic obstructive pulmonary disease (COPD) is a widespread disease.,It produces some night symptoms such as nighttime cough and dyspnea.,Then subjective and objective changes in sleep pattern are expected.,Present study was conducted to determine frequency of sleepiness and quality of sleep in patients with COPD.,Present case-control study has been performed on 120 patients with diagnosis of COPD who had been referred to pulmonary disease clinic in a University teaching hospital.,One hundred twenty age- and sex- matched healthy individuals were recruited in the study and served as control.,Spirometry (PFT) was performed for all patients.,Patients were categorized under 3 groups in relation to their PFT as follow: mild COPD (FEV1/FVC<70% and FEV1≥80%), moderate COPD (FEV1/FVC<70% and 50%≤FEV1<80%), and severe COPD (FEV1/FVC<70% and FEV1<50%).,Pittsburgh Sleep Quality questionnaire (PSQI) and Epworth Sleepiness Scale (ESS) were used to estimate quality of sleep and daytime sleepiness in the patients and control group.,The collected data were analyzed using version 16 SPSS software.,Student’s T- test, Chi- square and multiple logistic regressions were used as appropriated.,120 patients with COPD (79 males and 41 females) and 120 normal individuals responded to the questionnaires.,Mean scores of quality of sleep were 8.03±3.66 and 4.2±2.8 in COPD patients and control group respectively.,32.1% of the patients had good sleep quality (PSQI score less than 5) and 67.9% had poor sleep quality.,Daytime sleepiness (ESS≥ 10) was present in 34.8% of the patients and 15% of control people.,Multiple logistic regressions showed that the patients reported significantly worse sleep quality and more daytime sleepiness than control group [OR=2.9; 95% CI (1.6-3.7) & OR=3.5; 95% CI (2.5-4.3) respectively].,Results of present study confirmed that COPD is associated with daytime sleepiness and poor quality of sleep, possibly attributable to nighttime respiratory difficulties and concomitant sleep apnea.,Assessment of the patients for symptoms of sleep apnea, daytime sleepiness should be a part of regular follow up visits of patients with COPD. | Patients with respiratory disease experience disturbed sleep, but there is no widely accepted measure of sleep impairment due to respiratory disease.,We developed and evaluated the psychometric performance of a patient-reported measure to assess the impact on sleep due to respiratory disease, the COPD and Asthma Sleep Impact Scale (CASIS).,Identification of the items forming the CASIS was guided by patient interviews and focus groups.,An observational study involving patients from the US and UK was then conducted to assess the psychometric characteristics of the measure.,Qualitative data from 162 patients were used to develop the CASIS (n = 78 COPD; n = 84 asthma).,The observational study included 311 patients with COPD and 324 patients with asthma.,The final seven items used in the CASIS were identified based on factor and item response theory analyses.,Internal consistency was 0.90 (COPD) and 0.92 (asthma), and test-retest reliability was 0.84 (both groups).,In the COPD sample, CASIS scores were significantly correlated with the Saint George's Respiratory Questionnaire scores (all p < 0.0001) and differed significantly by patient-reported disease severity, exacerbation status, and overall health status (all p ≤ 0.005).,In the asthma sample, CASIS scores were significantly correlated with the Asthma Quality of Life Questionnaire scores (all p < 0.0001) and differed significantly by clinician and patient-reported disease severity, exacerbation status, and overall health status (all p ≤ 0.0005).,The CASIS shows good internal consistency, test-retest reliability, and construct validity and may be useful in helping to understand the impact that COPD and asthma have on sleep outcomes. | 1 |
Existing studies primarily explored chronic obstructive pulmonary disease (COPD) in smokers, whereas the clinical characteristics and the disease course of passive or nonsmokers have been rarely described.,In the present study, patients hospitalized and diagnosed as acute exacerbation of COPD (AECOPD) were recruited and followed up until being discharged.,Clinical and laboratory indicators were ascertained and delved into.,A total of 100 patients were covered, namely, 52 active smokers, 34 passive smokers, and 14 nonsmokers.,As revealed from the results here, passive or nonsmokers developed less severe dyspnea (patients with modified Medical Research Council scale (mMRC) <2, 0.0% vs.,8.8% vs.,14.3%, p < 0.05, active, passive, and nonsmokers, respectively), higher oxygenation index (206.4 ± 45.5 vs.,241.2 ± 51.1 vs.,242.4 ± 41.8 mmHg, p < 0.01), as well as lower arterial partial pressure of carbon dioxide (70.8 ± 12.7 vs.,58.85 ± 9.9 vs.,56.6 ± 6.5 mmHg, p < 0.001).,Despite lower treatment intensity over these patients, amelioration of dyspnea, mitigation of cough, and elevation of oxygenation index were comparable to those of active smokers.,However, in terms of patients exhibiting mMRC ≥2 and type 2 respiratory failure, amelioration of dyspnea was more common in nonsmokers as compared with passive smokers (46.4% vs.,83.3%, p < 0.05, passive and nonsmokers, respectively).,In terms of patients exhibiting Global Initiative for COPD severity <3, mMRC ≥2, and type 2 respiratory failure, active smokers achieved the least mitigation of cough symptom (8.7% vs.,35.0% vs.,44.4%, p < 0.05).,Similar results could be achieved after the effects of confounders were excluded, with the most prominent amelioration of dyspnea (odds ratio (OR) 3.8, 95% confidence interval (CI) 1.1-13.6, p < 0.05, as compared with active smokers) and cough (OR 3.3, 95% CI 1.0-10.7, p < 0.05) in nonsmokers, and relatively better amelioration of hypoxemia in passive smokers (oxygenation index change, 39.0 ± 34.6 vs.,51.5 ± 32.4 vs.,45.3 ± 25.4 mmHg, p < 0.05).,In brief, passive or nonsmokers with AECOPD were subjected to less severe disease, and nonsmokers, especially patients with more severe disease, might achieve the optimal enhancement of clinical presentation after treatment. | COPD often coexists with chronic conditions that may influence disease prognosis.,We investigated associations between chronic (co)morbidities and exacerbations in primary care COPD patients.,Retrospective cohort study based on 2012-2013 electronic health records from 179 Dutch general practices.,Comorbidities from patients with physician-diagnosed COPD were categorized according to International Classification of Primary Care (ICPC) codes.,Chi-squared tests, uni- and multivariable logistic, and Cox regression analyses were used to study associations with exacerbations, defined as oral corticosteroid prescriptions.,Fourteen thousand six hundred three patients with COPD could be studied (mean age 67 (SD 12) years, 53% male) for two years.,At baseline 12,826 (88%) suffered from ≥1 comorbidities, 3263 (22%) from ≥5.,The most prevalent comorbidities were hypertension (35%), coronary heart disease (19%), and osteoarthritis (18%).,Several comorbidities showed statistically significant associations with frequent (i.e., ≥2/year) exacerbations: heart failure (odds ratio [OR], 95% confidence interval: 1.72; 1.38-2.14), blindness & low vision (OR 1.46; 1.21-1.75), pulmonary cancer (OR 1.85; 1.28-2.67), depression 1.48; 1.14-1.91), prostate disorders (OR 1.50; 1.13-1.98), asthma (OR 1.36; 1.11-1.70), osteoporosis (OR 1.41; 1.11-1.80), diabetes (OR 0.80; 0.66-0.97), dyspepsia (OR 1.25; 1.03-1.50), and peripheral vascular disease (OR 1.20; 1.00-1.45).,From all comorbidity categories, having another chronic respiratory disease beside COPD showed the highest risk for developing a new exacerbation (Cox hazard ratio 1.26; 1.17-1.36).,Chronic comorbidities are highly prevalent in primary care COPD patients.,Several chronic comorbidities were associated with having frequent exacerbations and increased exacerbation risk. | 1 |
The economic burden of chronic obstructive pulmonary disease (COPD) exacerbations is significant, but the impact of other sources on the overall cost of COPD management is largely unknown.,We aimed to estimate overall costs for patients experiencing none, one, or two or more exacerbations per year in the UK.,A retrospective cohort of prevalent COPD patients was identified in the Clinical Practice Research Datalink UK database.,Patients with information recorded for at least 12 months before and after cohort entry date were included (first prevalent COPD diagnosis confirmed by spirometry on/after April 1, 2009).,Patients were categorized as having none, one, or two or more moderate-to-severe COPD exacerbations in the 12 months after cohort entry and further classified by the Global initiative for chronic Obstructive Lung Disease (GOLD) category of airflow obstruction and the Medical Research Council dyspnea scale.,Study outcomes included counts of general practitioner interactions, moderate-severe COPD exacerbations, and non-COPD hospitalizations.,Estimated resource use costs were calculated using National Health Service reference costs for 2010-2011.,The cohort comprised 58,589 patients (mean age 69.5 years, mean dyspnea grade 2.5, females 46.6%, current smokers 33.1%).,The average total annual per patient cost of COPD management, excluding medications, was £2,108 for all patients and £1,523, £2,405, and £3,396 for patients experiencing no, one, or two or more moderate-to-severe exacerbations, respectively.,General practitioner interactions contributed most to these annual costs, accounting for £1,062 (69.7%), £1,313 (54.6%), and £1,592 (46.9%) in patients with no, one, or two or more moderate-to-severe exacerbations, respectively.,Disease management strategies focused on reducing costs in primary care may help reduce total COPD costs significantly. | Exacerbations of chronic obstructive pulmonary disease (COPD) lead to significant increases in resource utilization and cost to the health care system.,COPD patients with chronic bronchitis and a history of exacerbations pose an additional burden to the system.,This study examined health care utilization and cost among these patients.,For this retrospective analysis, data were extracted from a large national health plan with a predominantly Medicare population.,This study involved patients who were aged 40-89 years, had been enrolled continuously for 24 months or more, had at least two separate insurance claims for COPD with chronic bronchitis (International Classification of Diseases, Ninth Revision, Clinical Modification code 491.xx), and had pharmacy claims for COPD maintenance medications between January 1, 2007, and March 31, 2009.,Two years of data were examined for each patient; the index date was defined as the first occurrence of COPD.,Baseline characteristics were obtained from the first year of data, with health outcomes tracked in the second year.,Severe exacerbation was defined by COPD-related hospitalization or death; moderate exacerbation was defined by oral or parenteral corticosteroid use.,Adjusted numbers of exacerbations and COPD-related costs per patient were estimated controlling for demographic and clinical characteristics.,The final study sample involved 8554 patients; mean age was 70.1 ± 8.6 years and 49.8% of the overall population had exacerbation, 13.9% had a severe exacerbation only, 29.1% had a moderate exacerbation only, and 6.8% had both a severe and moderate exacerbation.,COPD-related mean annual costs were $4069 (all figures given in US dollars) for the overall population and $6381 for patients with two or more exacerbations.,All-cause health care costs were $18,976 for the overall population and $23,901 for patients with history of two or more exacerbations.,Severity of exacerbations, presence of cardiovascular disease, diabetes, and long-term oxygen use were associated with higher adjusted costs.,The results indicate that despite treatment with maintenance medications, COPD patients continue to have exacerbations resulting in higher costs.,New medications and disease management interventions are warranted to reduce the severity and frequency of exacerbations and the related cost impact of the disease. | 1 |
Preserved Ratio Impaired Spirometry (PRISm), defined as a reduced FEV1 in the setting of a preserved FEV1/FVC ratio, is highly prevalent and is associated with increased respiratory symptoms, systemic inflammation, and mortality.,Studies investigating quantitative chest tomographic features, genetic associations, and subtypes in PRISm subjects have not been reported.,Data from current and former smokers enrolled in COPDGene (n = 10,192), an observational, cross-sectional study which recruited subjects aged 45-80 with ≥10 pack years of smoking, were analyzed.,To identify epidemiological and radiographic predictors of PRISm, we performed univariate and multivariate analyses comparing PRISm subjects both to control subjects with normal spirometry and to subjects with COPD.,To investigate common genetic predictors of PRISm, we performed a genome-wide association study (GWAS).,To explore potential subgroups within PRISm, we performed unsupervised k-means clustering.,The prevalence of PRISm in COPDGene is 12.3%.,Increased dyspnea, reduced 6-minute walk distance, increased percent emphysema and decreased total lung capacity, as well as increased segmental bronchial wall area percentage were significant predictors (p-value <0.05) of PRISm status when compared to control subjects in multivariate models.,Although no common genetic variants were identified on GWAS testing, a significant association with Klinefelter’s syndrome (47XXY) was observed (p-value < 0.001).,Subgroups identified through k-means clustering include a putative “COPD-subtype”, “Restrictive-subtype”, and a highly symptomatic “Metabolic-subtype”.,PRISm subjects are clinically and genetically heterogeneous.,Future investigations into the pathophysiological mechanisms behind and potential treatment options for subgroups within PRISm are warranted.,Clinicaltrials.gov Identifier: NCT000608764.,The online version of this article (doi:10.1186/s12931-014-0089-y) contains supplementary material, which is available to authorized users. | Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/FVC).,Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV1 and FEV1/FVC across 19 studies (total N = 50,047).,We identified three novel loci not previously associated with pulmonary function.,SNPs in or near DNER (smallest P JMA = 5.00×10−11), HLA-DQB1 and HLA-DQA2 (smallest P JMA = 4.35×10−9), and KCNJ2 and SOX9 (smallest P JMA = 1.28×10−8) were associated with FEV1/FVC or FEV1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction.,The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated.,We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue.,DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers.,Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects. | 1 |
MicroRNAs (MiRNA) are small non-coding RNAs that regulate gene expression.,The aim of this study was to identify miRNAs differentially expressed between mild and moderately emphysematous lung, as well as their functional target mRNAs.,Resected lung from patients with COPD undergoing lung cancer surgery was profiled using miRNA (Agilent Human miRNA profiler G4470 V1.01) and mRNA (OperonV2.0) microarrays.,Cells of lung origin (BEAS-2B and HFL1) were profiled using mRNA microarrays (Illumina HumanHT-12 V3) after in vitro manipulation.,COPD patients had mean (SD) age 68 (6) years, FEV1 72 (17)% predicted and gas transfer (KCO) 70 (10)% predicted.,Five miRNAs (miR-34c, miR-34b, miR-149, miR-133a and miR-133b) were significantly down-regulated in lung from patients with moderate compared to mild emphysema as defined by gas transfer (p < 0.01).,In vitro upregulation of miR-34c in respiratory cells led to down-regulation of predicted target mRNAs, including SERPINE1, MAP4K4, ZNF3, ALDOA and HNF4A.,The fold change in ex-vivo expression of all five predicted target genes inversely correlated with that of miR-34c in emphysematous lung, but this relationship was strongest for SERPINE1 (p = 0.05).,Differences in miRNA expression are associated with emphysema severity in COPD patients.,MiR-34c modulates expression of its putative target gene, SERPINE1, in vitro in respiratory cell lines and ex vivo in emphysematous lung tissue. | Abnormal apoptotic events in chronic obstructive pulmonary disease (COPD) subvert cellular homeostasis and may play a primary role in its pathogenesis.,However, studies in human subjects are limited.,p53 and bcl2 protein expression was measured by western blot on lung tissue specimens from 43 subjects (23 COPD smokers and 20 non-COPD smokers), using beta-actin as internal control.,Additionally, p53 and bcl2 expression patterns were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded lung tissue sections from the same individuals.,Western blot analysis showed statistically significant increased p53 protein levels in COPD smokers in comparison with non-COPD smokers (p = 0.038), while bcl2 protein levels were not statistically different between the two groups.,Lung immunohistochemistry showed increased ratio of positive p53-stained type II pneumocytes/total type II pneumocytes in COPD smokers compared to non-COPD smokers (p = 0.01), whereas the p53 staining ratio in alveolar macrophages and in lymphocyte-like cells did not differ statistically between the two groups.,On the other hand, bcl2 expression did not differ between the two groups in all three cell types.,The increased expression of pro-apoptotic p53 in type II pneumocytes of COPD patients not counterbalanced by the anti-apoptotic bcl2 could reflect increased apoptosis in the alveolar epithelium of COPD patients.,Our results confirm previous experiments and support the hypothesis of a disturbance in the balance between the pro- and anti-apoptotic mediators in COPD. | 1 |
Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden.,Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance.,The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic.,Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested.,Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects.,Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease.,Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76.,Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association.,We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage.,These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10.,In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD. | Chronic obstructive pulmonary disease (COPD), a major cause of death and morbidity worldwide, is characterized by expiratory airflow limitation that is not fully reversible, deregulated chronic inflammation, and emphysematous destruction of the lungs.,Despite the fact that COPD is a steadily growing global healthcare problem, the conventional therapies remain palliative, and regenerative approaches for disease management are not available yet.,We aim to provide an overview of key reviews, experimental, and clinical studies addressing lung emphysema development and repair mechanisms published in the past decade.,Novel aspects discussed herein include integral revision of the literature focused on lung microflora changes in COPD, autoimmune component of the disease, and environmental risk factors other than cigarette smoke.,The time span of studies on COPD, including emphysema, chronic bronchitis, and asthmatic bronchitis, covers almost 200 years, and several crucial mechanisms of COPD pathogenesis are described and studied.,However, we still lack the holistic understanding of COPD development and the exact picture of the time-course and interplay of the events during stable, exacerbated, corticosteroid-treated COPD states, and transitions in-between.,Several generally recognized mechanisms will be discussed shortly herein, ie, unregulated inflammation, proteolysis/antiproteolysis imbalance, and destroyed repair mechanisms, while novel topics such as deviated microbiota, air pollutants-related damage, and autoimmune process within the lung tissue will be discussed more extensively.,Considerable influx of new data from the clinic, in vivo and in vitro studies stimulate to search for novel concise explanation and holistic understanding of COPD nowadays. | 1 |
Chronic obstructive pulmonary disease (COPD) is a multifactorial chronic respiratory disease, characterized by an obstructive pattern.,Understanding the genetic predisposition of COPD is essential to develop personalized treatment regimens.,MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that modulate the expression levels of specific proteins based on sequence complementarity with their target mRNA molecules.,Emerging evidences demonstrated the potential use of miRNAs as a disease biomarker.,This pilot study aimed to investigate the association of the MIR-196a2 rs11614913 (C/T) polymorphism with COPD susceptibility, the clinical outcome and bronchodilator response to short-acting β2-agonist.,Genotyping of rs11614913 polymorphism was determined in 108 COPD male patients and 116 unrelated controls using real-time polymerase chain reaction technology.,In silico target prediction and network core analysis were performed.,COPD patients did not show significant differences in the genotype distribution (p = 0.415) and allele frequencies (p = 0.306) of the studied miRNA when compared with controls.,There were also no associations with GOLD stage, dyspnea grade, disease exacerbations, COPD assessment test for estimating impact on health status score, or the frequency of intensive care unit admission.,However, COPD patients with CC genotype corresponded to the smallest bronchodilator response after Salbutamol inhalation, the heterozygotes (CT) had an intermediate response, while those with the TT genotype showed the highest response (p < 0.001).,In conclusion MIR-196a2 rs11614913 polymorphism is associated with the bronchodilator response of COPD in our sample of the Egyptian population, generating hypothesis of the potential use of MIR-196a2 variant as a pharmacogenetic marker for COPD. | Chronic obstructive pulmonary disease (COPD) is a major public health problem with increasing prevalence worldwide.,The primary aim of this study was to identify genes and gene ontologies associated with COPD severity.,Gene expression profiling was performed on total RNA extracted from lung tissue of 18 former smokers with COPD.,Class comparison analysis on mild (n = 9, FEV1 80-110% predicted) and moderate (n = 9, FEV1 50-60% predicted) COPD patients identified 46 differentially expressed genes (p<0.01), of which 14 genes were technically confirmed by quantitative real-time-PCR.,Biological replication in an independent test set of 58 lung samples confirmed the altered expression of ten genes with increasing COPD severity, with eight of these genes (NNMT, THBS1, HLA-DPB1, IGHD, ETS2, ELF1, PTGDS and CYRBD1) being differentially expressed by greater than 1.8 fold between mild and moderate COPD, identifying these as candidate determinants of COPD severity.,These genes belonged to ontologies potentially implicated in COPD including angiogenesis, cell migration, proliferation and apoptosis.,Our secondary aim was to identify gene ontologies common to airway obstruction, indicated by impaired FEV1 and KCO.,Using gene ontology enrichment analysis we have identified relevant biological and molecular processes including regulation of cell-matrix adhesion, leukocyte activation, cell and substrate adhesion, cell adhesion, angiogenesis, cell activation that are enriched among genes involved in airflow obstruction.,Exploring the functional significance of these genes and their gene ontologies will provide clues to molecular changes involved in severity of COPD, which could be developed as targets for therapy or biomarkers for early diagnosis. | 1 |
Corticosteroids (CS) have limited efficacy in the treatment of chronic obstructive pulmonary disease (COPD). p38 mitogen-activated protein kinase (MAPK) activation is increased in lung macrophages of COPD.,We investigated whether p38 MAPK inhibition can modulate CS insensitivity of peripheral blood mononuclear cells (PBMCs) from patients with COPD.,PBMCs from patients with COPD (n=8) or healthy smokers (n=8) were exposed to lipopolysaccharide (LPS) with a selective p38 MAPK inhibitor (GW856553; 10−10-10−6 M), with dexamethasone (10−10-10−6 M), or with both.,Phosphorylated glucocorticoid receptor (GR) was measured by Western blot.,Baseline (P<0.01) and LPS-induced (P<0.05) CXCL8 release was greater in PBMCs from COPD compared to healthy smokers.,Inhibition of LPS-induced CXCL8 release by dexamethasone (10−6 M) was reduced, and baseline and LPS-induced p38 MAPK activation increased in PBMCs of COPD.,GW856553 (10−9 and 10−10 M) synergistically increased the inhibitory effect of dexamethasone (10−8 and 10−6 M) on LPS-induced CXCL8 release in COPD.,Similar results were obtained for IL-6 release.,GW856553 inhibited dexamethasone- and LPS-activated phosphorylation of serine 211 on GR.,CS insensitivity in COPD PBMCs is reversed by inhibition of p38 MAPK activity, partly by preventing phosphorylation of GR at serine 211.,p38 MAPK inhibition may be beneficial in COPD by restoring CS sensitivity. | Macrolides reduce exacerbations in patients with COPD.,Their effects on health status has not been assessed as primary outcome and is less clear.,This study assessed the effects of prophylactic azithromycin on cough-specific health status in COPD-patients with chronic productive cough.,In this randomised controlled trial 84 patients met the eligibility criteria: age of ≥40 years, COPD GOLD stage ≥2 and chronic productive cough.,The intervention-group (n = 42) received azithromycin 250 mg 3 times a week and the control-group (n = 42) received a placebo.,Primary outcome was cough-specific health status at 12 weeks, measured with the Leicester Cough Questionnaire (LCQ).,Secondary outcomes included generic and COPD-specific health status and exacerbations.,Changes in adverse events and microbiology were monitored.,Mean age of participants was 68 ± 10 years and mean FEV1 was 1.36 ± 0.47 L.,The improvement in LCQ total score at 12 weeks was significantly greater with azithromycin (difference 1.3 ± 0.5, 95% CI 0.3;2.3, p = 0.01) and met the minimal clinically important difference.,Similar results were found for the domain scores, and COPD-specific and generic health status questionnaires.,Other secondary endpoints were non-significant.,No imbalances in adverse events were found.,Prophylactic azithromycin improved cough-specific health status in COPD-patients with chronic productive cough to a clinically relevant degree.,ClinicalTrials.gov NCT01071161 | 1 |
Acute exacerbations are the leading causes of hospitalization and mortality in patients with COPD.,Prognostic tools for patients with chronic COPD exist, but there are scarce data regarding acute exacerbations.,We aimed to identify the prognostic factors of death and readmission after exacerbation of COPD.,This was a retrospective study conducted in the Department of Internal Medicine of Geneva University Hospitals.,All patients admitted to the hospital with a diagnosis of exacerbation of COPD between 2008 and 2011 were included.,The studied variables included comorbidities, Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity classification, and biological and clinical parameters.,The main outcome was death or readmission during a 5-year follow-up.,The secondary outcome was death.,Survival analysis was performed (log-rank and Cox).,We identified a total of 359 patients (195 men and 164 women, average age 72 years).,During 5-year follow-up, 242 patients died or were hospitalized for the exacerbation of COPD.,In multivariate analysis, age (hazard ratio [HR] 1.03, 95% CI 1.02-1.05; P<0.0001), severity of airflow obstruction (forced expiratory volume in 1 s <30%; HR 4.65, 95% CI 1.42-15.1; P=0.01), diabetes (HR 1.47, 95% CI 1.003-2.16; P=0.048), cancer (HR 2.79, 95% CI 1.68-4.64; P<0.0001), creatinine (HR 1.003, 95% CI 1.0004-1.006; P=0.02), and respiratory rate (HR 1.03, 95% CI 1.003-1.05; P=0.028) on admission were significantly associated with the primary outcome.,Age, cancer, and procalcitonin were significantly associated with the secondary outcome.,COPD remains of ominous prognosis, especially after exacerbation requiring hospitalization.,Baseline pulmonary function remains the strongest predictor of mortality and new admission.,Demographic factors, such as age and comorbidities and notably diabetes and cancer, are closely associated with the outcome of the patient.,Respiratory rate at admission appears to be the most prognostic clinical parameter.,A prospective validation is, however, still required to enable the identification of patients at higher risk of death or readmission. | Limited information is available about predictors of short-term outcomes in patients with exacerbation of chronic obstructive pulmonary disease (eCOPD) attending an emergency department (ED).,Such information could help stratify these patients and guide medical decision-making.,The aim of this study was to develop a clinical prediction rule for short-term mortality during hospital admission or within a week after the index ED visit.,This was a prospective cohort study of patients with eCOPD attending the EDs of 16 participating hospitals.,Recruitment started in June 2008 and ended in September 2010.,Information on possible predictor variables was recorded during the time the patient was evaluated in the ED, at the time a decision was made to admit the patient to the hospital or discharge home, and during follow-up.,Main short-term outcomes were death during hospital admission or within 1 week of discharge to home from the ED, as well as at death within 1 month of the index ED visit.,Multivariate logistic regression models were developed in a derivation sample and validated in a validation sample.,The score was compared with other published prediction rules for patients with stable COPD.,In total, 2,487 patients were included in the study.,Predictors of death during hospital admission, or within 1 week of discharge to home from the ED were patient age, baseline dyspnea, previous need for long-term home oxygen therapy or non-invasive mechanical ventilation, altered mental status, and use of inspiratory accessory muscles or paradoxical breathing upon ED arrival (area under the curve (AUC) = 0.85).,Addition of arterial blood gas parameters (oxygen and carbon dioxide partial pressures (PO2 and PCO2)) and pH) did not improve the model.,The same variables were predictors of death at 1 month (AUC = 0.85).,Compared with other commonly used tools for predicting the severity of COPD in stable patients, our rule was significantly better.,Five clinical predictors easily available in the ED, and also in the primary care setting, can be used to create a simple and easily obtained score that allows clinicians to stratify patients with eCOPD upon ED arrival and guide the medical decision-making process. | 1 |
No observational studies have evaluated the “real-world” effectiveness of dual bronchodilation comprising a long-acting β2-agonist plus a long-acting muscarinic antagonist vs that of triple therapy (long-acting β2-agonist plus long-acting muscarinic antagonist plus inhaled corticosteroid) in COPD.,DACCORD is a non-interventional, observational clinical study that recruited patients following COPD maintenance therapy initiation or change in maintenance therapy between or within therapeutic class.,Given the non-interventional nature of the study, the decision to initiate or change medication had to be made by the patients’ physicians prior to inclusion in DACCORD.,We used a matched-pairs analysis to compare disease progression in two patient groups: those receiving dual bronchodilation vs those receiving triple therapy (each group n=1,046).,In two subgroups of patients matched according to a broad range of demographic and disease characteristics, over 1 year, fewer patients receiving dual bronchodilation exacerbated than those receiving triple therapy (15.5% vs 26.6%; P<0.001), with a greater improvement from baseline in COPD Assessment Test total score at 1 year (mean±SD −2.9±5.8 vs −1.4±5.5;P<0.001).,When analyzed according to prior therapy, the highest rate of exacerbations was in patients on triple therapy prior to the study who remained on triple therapy.,Those changing from mono-bronchodilator to dual bronchodilation had the greatest COPD Assessment Test total score improvement.,In this “real-life” cohort of patients with COPD, most of whom had not exacerbated in the 6 months prior to entry, triple therapy did not seem to improve outcomes compared with dual bronchodilation in terms of either exacerbations or health status.,Our analyses clearly demonstrate the potential impact of prior medication on study results, something that should be taken into account when interpreting the results even of controlled clinical trials. | The aim of this study was to measure HrQoL during acute exacerbations of COPD using generic and disease-specific instruments, and to assess completeness, proportion with best or worst health state, sensitivity to change and discriminative ability for each instrument.,EQ-5D, SF-12 and SGRQ were obtained from COPD patients with GOLD stage III and IV hospitalized for an acute exacerbation both at admission and discharge.,To assess the instruments' properties, utility values were calculated for EQ-5D and SF-12, and a total score was derived from the SGRQ.,Mean utilities ranged from 0.54 (SF-12, stage IV) to 0.62 (EQ-5D, stage III) at admission, and from 0.58 (SF-12, stage IV) to 0.84 (EQ-5D, stage III) at discharge.,Completeness was best for EQ-5D and SGRQ, while no utility value for the SF-12 could be calculated for more than 30%.,For SGRQ subscales, the minimal score occurred in up to 11% at admission, while full health was observed for the EQ-5D at discharge in 13%.,Sensitivity to change was generally good, whereas discrimination between COPD stages was low for the EQ-5D.,Acute exacerbations seriously impair health status and quality of life.,The EQ-5D is generally suitable to measure HrQoL in exacerbations of severe COPD, although the high proportion of patients reporting full health at discharge poses a problem.,The main issue with the SF-12 is the high proportion of missing values in a self-assessed setting.,Properties of the SGRQ were satisfactory.,However, since no utility values can be derived from this disease-specific instrument, it is not suitable for cost-utility analyses in health-economic evaluations. | 1 |
Supplemental Digital Content is available in the text,This study compares the prevalence rates of comorbidities between chronic obstructive pulmonary disease (COPD) and non-COPD control patients reported in literature.,Literature was searched in several electronic databases.,After the selection of studies by following précised eligibility criteria, meta-analyses of odds ratios (ORs) were carried out with subgroup and sensitivity analyses under random effects model.,Eleven studies (47,695,183 COPD and 47,924,876 non-COPD control patients’ data) were used for meta-analysis.,Average age of COPD patients was 66.66 ± 8.72 years of whom 55.4 ± 11.9% were males.,The prevalence of cardiovascular comorbidities [OR 1.90, 95% confidence interval (95% CI) 1.59-2.28; P < .00001], cerebrovascular comorbidities (OR 1.84, 95% CI 1.47-2.31; P < .00001), hypertension (OR 1.45, 95% CI 1.31-1.61; P < .00001), diabetes mellitus (OR 1.22, 95% CI 1.07-1.38; P = .003), neurological and psychiatric disorders (OR 1.78, 95% CI 1.48-2.14; P < .00001), gut and renal disorders (OR 1.96, 95% CI 1.43-2.68; P < .00001), musculoskeletal disorders (OR 1.51, 95% CI 1.27-1.78; P < .00001), non-COPD respiratory comorbidities (OR 2.81, 95% CI 2.52-3.14; P < .00001), and cancer (OR 1.67, 95% CI 1.25-2.23; P = .0005) were significantly higher in COPD patients than in non-COPD controls.,COPD is associated with significantly higher comorbidities than in other diseases that should be taken into consideration in COPD control strategies. | A high prevalence of bronchiectasis was found by chest computed tomography (CT) in patients with moderate-severe chronic obstructive pulmonary disease (COPD), and it was shown to be associated with more severe symptoms, higher frequency of exacerbations and mortality.,The risk factors for bronchiectasis in COPD are not yet clarified.,High-resolution computed tomography (HRCT) of chest was performed in patients with moderate-severe COPD, and the presence and the extent of bronchiectasis were evaluated by two radiologists.,Demographic data, respiratory symptoms, lung function, previous pulmonary tuberculosis, serum inflammatory markers, serum total immunoglobulin E (T-IgE), and sputum culture of Pseudomonas aeruginosa were compared between those with and without bronchiectasis.,Multivariate logistic regression analysis was used to determine the independent factors associated with bronchiectasis.,We enrolled 190 patients with stable COPD, of which 87 (87/190, 45.8%) had bronchiectasis on HRCT.,Compared with those without bronchiectasis, COPD patients with bronchiectasis were more likely to be males (P = 0.021), had a lower body mass index (BMI) (P = 0.019), a higher prevalence of previous tuberculosis (P = 0.005), longer history of dyspnea (P < 0.001), more severe dyspnea (P = 0.041), higher frequency of acute exacerbation (P = 0.002), higher serum concentrations of C-reactive protein (CRP) (P = 0.017), fibrinogen (P = 0.016), and T-IgE [P = 0.004; for log10(T-IgE), P <0.001].,COPD patients with bronchiectasis also showed poorer lung function (for FEV1/FVC, P = 0.013; for FEV1%predicted, P = 0.012; for global initiative for chronic obstructive lung disease (GOLD) grades, P = 0.035), and a higher positive rate of sputum P aeruginosa (P = 0.020).,Logistic regression analysis demonstrated that male gender (P = 0.021), previous tuberculosis (P = 0.021), and increased level of serum T-IgE [for log10(T-IgE), P < 0.001] were risk factors for coexistent bronchiectasis.,More notably, the level of serum T-IgE [log10(T-IgE)] was positively correlated with the extent of bronchiectasis in COPD patients (r = 0.208, P = 0.05).,Higher serum T-IgE, male gender, and previous tuberculosis are independent risk factors for coexistent bronchiectasis in COPD.,The association of T-IgE with the extent of bronchiectasis also suggests that further investigations are needed to explore the potential role of IgE in the pathogenesis of bronchiectasis in COPD. | 1 |
The prevalence of physical frailty and its clinical characteristics in advanced chronic obstructive pulmonary disease (COPD) is unknown, as well as the usefulness of functional capacity tests to screen for physical frailty.,The aim of the study was to evaluate the proportion and clinical portrait of COPD patients with chronic respiratory failure exhibiting physical frailty at the time of referral to home-based pulmonary rehabilitation.,We also evaluate the usefulness of the short physical performance battery (SPPB) and timed-up and go (TUG) as potential screening tools for physical frailty.,Finally, we evaluated the specific contribution of gait speed to the frailty Fried total score.,This was a prospective observational study in which physical frailty was defined using Fried criteria (body mass loss, exhaustion, low physical activity, slower walking and weakness).,Clinical portrait was documented from daily physical activity, exercise tolerance, functional capacity, anxiety and depressive symptoms, health-related quality of life, and fatigue scores.,The ability of the SPPB and TUG to predict physical frailty was investigated using receiver operating characteristic curves.,Contribution of each Fried criteria was evaluated with a principal component analysis (PCA).,Amongst the 44 included participants (FEV1, 33 ± 13% of predicted), 19 were physically frail.,Frail individuals had lower daily steps number, exercise tolerance and functional capacity, and higher fatigue, anxiety, and depressive symptom scores (p<0.05) compared to non-frail individuals.,SPPB and TUG did not have an acceptable detection accuracy for screening physical frailty.,PCA indicated that gait speed was the main contributor to the Fried total score of physical frailty.,Physical frailty affects a large proportion of COPD patients with chronic respiratory failure starting a home-based intervention and was associated with worse clinical status.,Although the present results need to be confirmed by adequately powered studies, gait speed seems to have the potential to become a simple screening tool for physical frailty in this population. | 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. | 1 |
Little is known about the impact of exacerbations on COPD progression or whether inhaled corticosteroid (ICS) use and blood eosinophil count (BEC) affect progression.,We aimed to assess this in a prospective observational study.,The study population included patients with mild to moderate COPD, aged ≥35 years, with a smoking history, who were followed up for ≥3 years from first to last spirometry recording using two large UK electronic medical record databases: Clinical Practice Research Datalink (CPRD) and Optimum Patient Care Research Database (OPCRD).,Multilevel mixed-effects linear regression models were used to determine the relationship between annual exacerbation rate following initiation of therapy (ICS vs non-ICS) and FEV1 decline.,Effect modification by blood eosinophils was studied through interaction terms.,Of 12178 patients included (mean age 66 years; 48% female), 8981 (74%) received ICS.,In patients with BEC ≥350 cells/µL not on ICS, each exacerbation was associated with subsequent acceleration of FEV1 decline of 19.4 mL/year (95% CI 12.0 to 26.7, p<0.0001).,This excess decline was reduced by 15.1 mL/year (6.6 to 23.6) to 4.3 mL/year (1.9 to 6.7, p<0.0001) in those with BEC ≥350 cells/µL treated with ICS.,Exacerbations are associated with a more rapid loss of lung function among COPD patients with elevated blood eosinophils, defined as ≥350 cells/µL, not treated with ICS.,More aggressive prevention of exacerbations using ICS in such patients may prevent excess loss of lung function. | Previous studies have shown that opportunities to diagnose chronic obstructive pulmonary disease (COPD) early are often missed in primary care.,This retrospective study aimed to utilize secondary data from the United Kingdom (UK) healthcare system to understand the impact of early versus late diagnosis of COPD.,Newly diagnosed COPD patients were identified in the UK Clinical Practice Research Database from 2011 to 2014.,Patients whose 5-year medical data before diagnosis revealed ≥3 counts of eight indicators of early COPD were deemed as late-diagnosed, whereas others were deemed as early-diagnosed.,We assessed patients’ characteristics; time-to-first, risk, and rates of exacerbation; and healthcare resource utilization (COPD-related clinic visits, Accident and Emergency visits, and hospitalizations) in late- versus early-diagnosed patients.,Of 10,158 patients included in the study, 6783 (67%) were identified as late-diagnosed and 3375 (33%) as early-diagnosed.,The median time-to-first exacerbation was shorter in late-diagnosed (14.5 months) versus early-diagnosed (29.0 months) patients, with a significant risk of exacerbation (hazard ratio 1.46 [95% confidence interval: 1.38-1.55]).,Additionally, the exacerbation rate (per 100 person-years) over 3 years was higher in late (108.9) versus early (57.2) diagnosed patients.,Late-diagnosed patients had a significantly higher rate of COPD hospitalizations (per 1000 patient years) compared with early-diagnosed patients during 2 and 3 years of follow-ups (P = 0.0165 and P < 0.0001, respectively).,Results showed that a significant percentage of COPD patients in UK primary care are diagnosed late.,A late COPD diagnosis is associated with a shorter time-to-first exacerbation and a higher rate and risk of exacerbations compared with early diagnosis.,Additionally, late diagnosis of COPD is associated with a higher rate of COPD-related hospitalizations compared with early diagnosis. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with increased postoperative complications.,Recently, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classified COPD patients into four groups based on spirometry results and the severity of symptoms.,The objective of this study was to evaluate the impact of GOLD groups on postoperative complications.,We reviewed the medical records of COPD patients who underwent preoperative spirometry between April and August 2013 at a tertiary hospital in Korea.,We divided the patients into GOLD groups according to the results of spirometry and self-administered questionnaires that assessed the symptom severity and exacerbation history.,GOLD groups, demographic characteristics, and operative conditions were analyzed.,Among a total of 405 COPD patients, 70 (17.3%) patients experienced various postoperative complications, including infection, wound, or pulmonary complications.,Thoracic surgery, upper abdominal surgery, general anesthesia, large estimated blood loss during surgery, and longer anesthesia time were significant risk factors for postoperative complications.,Patients in high-risk group (GOLD groups C or D) had an increased risk of postoperative complications compared to those in low-risk group (GOLD groups A or B).,COPD patients in GOLD groups representing a high exacerbation risk have an increased risk of postoperative complications compared to those with low risk. | 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. | 1 |
Classification of COPD is usually based on the severity of airflow, which may not sensitively differentiate subpopulations.,Using a multiscale imaging-based cluster analysis (MICA), we aim to identify subpopulations for current smokers with COPD.,Among the SPIROMICS subjects, we analyzed computed tomography images at total lung capacity (TLC) and residual volume (RV) of 284 current smokers.,Functional variables were derived from registration of TLC and RV images, e.g. functional small airways disease (fSAD%).,Structural variables were assessed at TLC images, e.g. emphysema and airway wall thickness and diameter.,We employed an unsupervised method for clustering.,Four clusters were identified.,Cluster 1 had relatively normal airway structures; Cluster 2 had an increase of fSAD% and wall thickness; Cluster 3 exhibited a further increase of fSAD% but a decrease of wall thickness and airway diameter; Cluster 4 had a significant increase of fSAD% and emphysema.,Clinically, Cluster 1 showed normal FEV1/FVC and low exacerbations.,Cluster 4 showed relatively low FEV1/FVC and high exacerbations.,While Cluster 2 and Cluster 3 showed similar exacerbations, Cluster 2 had the highest BMI among all clusters.,Association of imaging-based clusters with existing clinical metrics suggests the sensitivity of MICA in differentiating subpopulations.,The online version of this article (10.1186/s12931-018-0888-7) contains supplementary material, which is available to authorized users. | Parametric response mapping (PRM) of paired CT lung images has been shown to improve the phenotyping of COPD by allowing for the visualization and quantification of non-emphysematous air trapping component, referred to as functional small airways disease (fSAD).,Although promising, large variability in the standard method for analyzing PRMfSAD has been observed.,We postulate that representing the 3D PRMfSAD data as a single scalar quantity (relative volume of PRMfSAD) oversimplifies the original 3D data, limiting its potential to detect the subtle progression of COPD as well as varying subtypes.,In this study, we propose a new approach to analyze PRM.,Based on topological techniques, we generate 3D maps of local topological features from 3D PRMfSAD classification maps.,We found that the surface area of fSAD (SfSAD) was the most robust and significant independent indicator of clinically meaningful measures of COPD.,We also confirmed by micro-CT of human lung specimens that structural differences are associated with unique SfSAD patterns, and demonstrated longitudinal feature alterations occurred with worsening pulmonary function independent of an increase in disease extent.,These findings suggest that our technique captures additional COPD characteristics, which may provide important opportunities for improved diagnosis of COPD patients. | 1 |
Numerous studies have investigated the association between eosinophilia and clinical outcome of patients with chronic obstructive pulmonary disease (COPD) but the evidence is conflicting.,We conducted a pooled analysis of outcome measures comparing eosinophilic and non-eosinophilic COPD patients.,We searched articles indexed in four databases using Medical Subject Heading or Title and Abstract words including COAD, COPD, eosinophil, eosinophilia, eosinopenia from inception to December 2016.,Observational studies and randomized controlled trials with parallel groups comparing COPD patients with and without eosinophilia were included.,Comparing to the non-eosinophilic group, those with eosinophilic COPD had a similar risk for exacerbation in 12 months [Odds ratio = 1.07, 95% confidence interval (CI) 0.86-1.32, P = 0.55] and in-hospital mortality [OR = 0.52, 95% CI 0.25-1.07].,Eosinophilia was associated with reduced length of hospital stay (P = 0.04).,Subsequent to therapeutic interventions, eosinophilic outpatients performed better in pulmonary function tests [Mean Difference = 1.64, 95% CI 0.05-3.23, P < 0.001].,Inclusion of hospitalized patients nullified the effect.,Improvement of quality of life was observed in eosinophilic subjects [Standardized Mean Difference = 1.83, 95% CI 0.02-3.64, P = 0.05], independent of hospitalization status.,In conclusion, blood eosinophilia may be predictive of favorable response to steroidal and bronchodilator therapies in patients with stable COPD. | Long-term exposure to tobacco smoke causes local inflammation in the airways that involves not only innate immune cells, including NK cells, but also adaptive immune cells such as cytotoxic (CD8+) and helper (CD4+) T-cells.,We have previously demonstrated that long-term tobacco smoking increases extracellular concentration of the CD4+-recruiting cytokine interleukin (IL)-16 locally in the airways.,Here, we hypothesized that tobacco smoking alters IL-16 biology at the systemic level and that this effect involves oxygen free radicals (OFR).,We quantified extracellular IL-16 protein (ELISA) and intracellular IL-16 in NK cells, T-cells, B-cells, and monocytes (flow cytometry) in blood samples from long-term tobacco smokers with and without chronic obstructive pulmonary disease (COPD) and in never-smokers.,NK cells from healthy blood donors were stimulated with water-soluble tobacco smoke components (cigarette smoke extract) with or without an OFR scavenger (glutathione) in vitro and followed by quantification of IL-16 protein.,The extracellular concentrations of IL-16 protein in blood did not display any substantial differences between groups.,Notably, intracellular IL-16 protein was detected in all types of blood leukocytes.,All long-term smokers displayed a decrease in this IL-16 among NK cells, irrespective of COPD status.,Further, both NK and CD4+ T-cell concentrations displayed a negative correlation with pack-years.,Moreover, cigarette smoke extract caused release of IL-16 protein from NK cells in vitro, and this was not affected by glutathione, in contrast to the decrease in intracellular IL-16, which was prevented by this drug.,Long-term exposure to tobacco smoke does not markedly alter extracellular concentrations of IL-16 protein in blood.,However, it does decrease the intracellular IL-16 concentrations in blood NK cells, the latter effect involving OFR.,Thus, long-term tobacco smoking exerts an impact at the systemic level that involves NK cells; innate immune cells that are critical for host defense against viruses and tumors - conditions that are overrepresented among smokers. | 1 |
Familial clustering of chronic obstructive pulmonary disease (COPD) is well established, but the familial risk of COPD has not been determined among adoptees.,The aim was to determine whether the familial transmission of COPD is related to disease in biological and/or adoptive parents.,Historic cohort study.,80 214 (50% females).,The Swedish Multi-Generation Register was used to follow all Swedish-born adoptees born in 1932-2004 (n=80 214) between 1 January 1964 and 31 December 2010 for COPD (n=1978).,The risk of COPD was estimated in adoptees with at least one biological parent with COPD but no adoptive parent with COPD (n=162) compared with adoptees without a biological or adoptive parent with COPD.,The risk of COPD was also determined in adoptees with at least one adoptive parent but no biological parent with COPD (n=110), and in adoptees with both affected biological and adoptive parents (n=162).,COPD in adoptees.,Adoptees with COPD in at least one biological parent but no adoptive parent were more likely to have COPD than adoptees without a biological or adoptive parent with COPD (standardised incidence ratio, SIR=1.98 (95% CI 1.69 to 2.31)).,The familial SIR for adoptees with both a biological parent and an adoptive parent with COPD was 1.68 (95% CI 1.39 to 2.00).,Adoptees with at least one adoptive parent with COPD but no biological parent with COPD were not at an increased risk of COPD (SIR=1.12 (95% CI 0.92 to 1.35)).,The findings of the study show that the familial transmission of COPD is associated with COPD in biological but not adoptive parents, suggesting that genetic or early life factors are important in the familial transmission of COPD. | Rtp801, a stress - related protein triggered by adverse environmental conditions, inhibits mTOR and enhances oxidative stress - dependent cell death.,We postulated that Rtp801 acts as potential amplifying switch in the development of cigarette smoke - induced lung injury, leading to emphysema.,Rtp801 was overexpressed in human emphysematous lungs and in lungs of mice exposed to cigarette smoke.,The upregulation of Rtp801 expression by cigarette smoke in the lung relied on oxidative stress - dependent activation of the CCAAT response element.,Rtp801 was necessary and sufficient for NF - κ B activation in cultured cells and, when forcefully expressed in mouse lungs, it promoted NF - kB activation, alveolar inflammation, oxidative stress, and apoptosis of alveolar septal cells.,On the other hand, Rtp801 − / − mice were markedly protected against acute cigarette smoke - induced lung injury, partly via increased mTOR signaling, and, when exposed chronically, against emphysema.,Our data support the notion that Rtp801 may represent an important molecular sensor and mediator of lung injury to cigarette smoke. | 1 |
The association of inhaled corticosteroids (ICS) and pneumonia in patients with chronic obstructive pulmonary disease (COPD) is still controversial.,From the National Health Insurance Database of Taiwan, COPD cases with history of acute exacerbation (AE) were identified (COPD cohort).,Time-dependent Cox regression analysis was applied to investigate the risk factors for pneumonia with COPD severity controlled by surrogate variables.,Among the COPD cohort, those who continuously used ICS for more than 360 days without interruption were selected (ICS cohort).,The incidence rate of pneumonia during ICS use was compared with those before ICS use and after ICS discontinuation by using pair t test.,A total of 6034 and 842 cases were identified as the COPD and ICS cohorts, respectively.,In the COPD cohort, recent ICS use was independently associated with pneumonia (hazard ratio: 1.06 [1.02-1.11] for per 80 mg of budesonide).,Other independent risk factors included age, male, diabetes mellitus, malignancy, low income, baseline pneumonia event, and recent use of oral corticosteroids and aminophylline.,In the ICS cohort, while AE rate gradually decreased, the incidence rate of pneumonia significantly increased after ICS use (from 0.10 to 0.21 event/person-year, P = 0.001).,This study demonstrates the association between ICS use and pneumonia in patients with COPD and history of AE.,ICS should be judiciously used in indicated COPD patients. | Effects of pulmonary diseases [asthma, chronic obstructive pulmonary disease (COPD), and lung tuberculosis (TB)] on subsequent lung cancer development have been reported.,However, whether patients with coexisting pulmonary diseases are at greater risk of developing various histologic types of lung cancer remains elusive.,Patients newly diagnosed with lung cancer between 2004 and 2008 were identified from National Health Insurance Research Database (Taiwan).,The histologic types of lung cancer were further confirmed using Taiwan Cancer Registry Database.,Cox proportional hazard regression was used to calculate the hazard ratio (HR) of coexisting asthma, COPD and/or TB to estimate lung cancer risk by histologic type.,During the study period, 32,759 cases of lung cancer were identified from 15,219,024 residents age 20 years and older, who were free from the disease before 2003.,Coexisting pulmonary diseases showed stronger association with lung cancer than specific lung disorders.,Specifically, among men, the HRs for squamous cell carcinoma (SqCC) were 3.98 (95% CI, 3.22-4.93), 2.68 (95% CI, 2.45-2.93), and 2.57 (95% CI, 2.10-3.13) for individuals with asthma+COPD+TB, asthma+COPD, and COPD+TB, respectively.,Among women, the HRs for SqCC were 3.64 (95% CI, 1.88-7.05), 3.35 (95% CI, 1.59-7.07), and 2.21 (95% CI, 1.66-2.94) for individuals with TB, COPD+TB, and asthma+COPD, respectively.,Adenocarcinoma HRs for men and women were 2.00 (95% CI, 1.54-2.60) and 2.82 (95% CI, 1.97-4.04) for individuals with asthma+COPD+TB, 2.28 (95% CI, 1.91-2.73) and 2.16 (95% CI, 1.57-2.95) for COPD+TB, and 1.76 (95% CI, 1.04-2.97) and 2.04 (95% CI, 1.02-4.09) for individuals with asthma+TB.,Specifically, small cell carcinoma (SmCC) HRs among men were 3.65 (95% CI, 1.97-6.80), 2.20 (95% CI, 1.45-3.36), and 2.14 (95% CI, 1.86-2.47) for those with asthma+TB, asthma+COPD+TB, and asthma+ COPD, respectively.,Among women, the HRs of SmCC were 8.97 (95% CI, 3.31-24.28), 3.94 (95% CI, 1.25-12.35) and 3.33 (95% CI, 2.23-4.97) for those with asthma+COPD+TB, COPD+TB, and asthma+COPD, respectively.,Patients with coexistence of pulmonary diseases were more susceptible to lung cancer.,Affected persons deserve greater attention while undergoing cancer screening. | 1 |
COPD may lead to cognitive impairment or even dementia.,However, the current conclusions are inconsistent with little evidence from prospective, large-sample studies.,This study was designed to explore the association of COPD with mild cognitive impairment (MCI) and dementia risk based on a cohort study.,All participants were from the Chinese Longitudinal Health Longevity Survey (CLHLS) 2011/2012 waves.,The follow-up survey was conducted in 2014 and the incidence of MCI and dementia were recorded.,During the 3-year follow-up period, 712 new cases of MCI and 83 new cases of dementia were diagnosed.,The incidence of MCI and dementia were higher in those with COPD than those without COPD at baseline.,Cox analysis showed that the HRs of COPD for MCI and dementia incidence were 1.486 (95% CI: 1.207-1.855) and 1.896 (95% CI: 1.079-3.330), respectively after adjusting for related covariates.,For different baseline smoking status, those who were current smokers had the highest HRs of COPD for MCI and dementia.,Baseline COPD was independently associated with increased risk of MCI and dementia incidence among Chinese elderly, and the association was more pronounced among those who were current smokers. | COPD is an important comorbidity of lung cancer, but the impact of COPD on the outcomes of lung cancer remains uncertain.,Because both COPD and lung cancer are heterogeneous diseases, we evaluated the link between COPD phenotypes and the prognosis of different histological subtypes of lung cancer.,In this retrospective study, subjects with a newly and pathologically confirmed diagnosis of lung cancer were enrolled from patients preparing for lung cancer surgery.,All participants underwent pulmonary function test (PFT).,The diagnosis of COPD was based on GOLD criteria.,Lung cancer subtypes and COPD phenotypes were categorized by WHO classification of lung tumors and computer quantitative analysis of PFT.,The HRs were estimated by Cox regression analysis.,Among 2,222 lung cancer patients, 32.6% coexisted with COPD.,After adjustment for age, sex, body mass index (BMI), smoking status, and therapy method, COPD was significantly associated with the decreased overall survival (OS) of lung cancer (HR 1.28, 95% CI 1.05-1.57).,With the increased severity of COPD, the OS of lung cancer was gradually worsened (HR 1.23, 95% CI 1.08-1.39).,But surgical treatment and high BMI were independent prognostic protective factors (HR 0.46, 95% CI 0.37-0.56; HR 0.96, 95% CI 0.94-0.99).,Moreover, in terms of disease heterogeneity, emphysema-predominant phenotype of COPD was an independent prognostic risk factor for squamous carcinoma (HR 2.53, 95% CI 1.49-4.30).,No significant relationship between COPD phenotype and lung cancer prognosis was observed among adenocarcinoma, small cell lung cancer, large cell lung cancer, and other subtype patients.,These findings suggest that COPD, especially emphysema-predominant phenotype, is an independent prognostic risk factor for squamous carcinoma only. | 1 |
As of 11 July, 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic has infected over 12.7 million people around the world and caused more than 560,000 deaths [1].,Given the devastating impact that COVID-19 can have on the lung, it is natural to fear for patients with underlying COPD.,Estimating their excess risk for contracting COVID-19 and, in particular, its more severe respiratory manifestations has been a challenging exercise in this pandemic for various reasons.,First, the reporting on cases has concentrated on hospitalised and intensive care unit (ICU) patients, rather than on mild, outpatient cases.,This is in part also due to the variability in testing strategies across the world, where some nations with stricter testing requirements and scarce testing resources have focused on testing only those requiring hospitalisation.,COPD patients have increased risk of severe pneumonia and poor outcomes when they develop COVID-19.,This may be related to poor underlying lung reserves or increased expression of ACE-2 receptor in small airways.https://bit.ly/37dSB8l | Angiotensin-converting enzyme 2 (ACE2) has been identified as the cell entry receptor used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1, 2].,Importantly, smokers and patients with COPD are at an increased risk of severe complications and a higher mortality upon SARS-CoV-2 infection [3].,We hypothesised that ACE2 expression is increased in lungs of smokers and patients with COPD, which may at least partially explain their higher risk of a more severe course of coronavirus disease 2019 (COVID-19).,Therefore, we aimed to investigate the expression of ACE2 on both mRNA and protein level in a large number of lung tissue specimens of well-phenotyped subjects, including never-smokers, current smokers without airflow limitation, and patients with COPD.,This study demonstrates increased protein levels of ACE2 in alveolar and bronchial epithelium of smokers and subjects with COPD, which might facilitate host cell entry of SARS-CoV-2https://bit.ly/2ZazOrd | 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. | The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented.,However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease.,TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV1, 43% current smokers).,To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV1 to segment patients into three groups: moderate COPD (GOLD stage II and above: ≥ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937).,Compared with placebo, SFC improved post-bronchodilator FEV1: 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4, 29) in GOLD stage IV.,SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage.,Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV.,The rates of adverse events were similar across treatment arms and increased with disease severity.,Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages.,In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV1 across GOLD stages.,Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease.,The effects were similar to those reported for the study as a whole.,Thus, SFC is an effective treatment option for patients with GOLD stage II COPD.,Clinicaltrial.gov registration NCT00268216; Study number: SCO30003 | 1 |
Macrolides reduce exacerbations in patients with COPD.,Their effects on health status has not been assessed as primary outcome and is less clear.,This study assessed the effects of prophylactic azithromycin on cough-specific health status in COPD-patients with chronic productive cough.,In this randomised controlled trial 84 patients met the eligibility criteria: age of ≥40 years, COPD GOLD stage ≥2 and chronic productive cough.,The intervention-group (n = 42) received azithromycin 250 mg 3 times a week and the control-group (n = 42) received a placebo.,Primary outcome was cough-specific health status at 12 weeks, measured with the Leicester Cough Questionnaire (LCQ).,Secondary outcomes included generic and COPD-specific health status and exacerbations.,Changes in adverse events and microbiology were monitored.,Mean age of participants was 68 ± 10 years and mean FEV1 was 1.36 ± 0.47 L.,The improvement in LCQ total score at 12 weeks was significantly greater with azithromycin (difference 1.3 ± 0.5, 95% CI 0.3;2.3, p = 0.01) and met the minimal clinically important difference.,Similar results were found for the domain scores, and COPD-specific and generic health status questionnaires.,Other secondary endpoints were non-significant.,No imbalances in adverse events were found.,Prophylactic azithromycin improved cough-specific health status in COPD-patients with chronic productive cough to a clinically relevant degree.,ClinicalTrials.gov NCT01071161 | Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation.,Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear.,Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7).,Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro.,In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy.,CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression.,Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression.,Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion.,Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis.,Egr-1 −/− mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema.,We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo.,The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury. | 1 |
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide.,Low-grade systemic inflammation is considered a hallmark of COPD that potentially links COPD to increased rate of systemic manifestations of the disease.,Obesity with/without the metabolic syndrome and cachexia represent two poles of metabolic abnormalities that may relate to systemic inflammation.,On one hand systemic inflammatory syndrome likely reflects inflammation in the lungs, i.e. results from lung-to plasma spillover of inflammatory mediators.,On the other hand, obesity-related hypoxia results in local inflammatory response within adipose tissue per se, and may contribute to elevations in circulatory mediators by spillover from the adipose tissue to the systemic compartment.,The extent to which systemic hypoxia contributes to the adipose tissue inflammation remains unknown.,We assume that in patients with COPD and concurrent obesity at least three factors play a role in the systemic inflammatory syndrome: the severity of pulmonary impairment, the degree of obesity-related adipose tissue hypoxia, and the severity of systemic hypoxia due to reduced pulmonary functions.,The present review summarizes the epidemiological and clinical evidence linking COPD to obesity, the role of adipose tissue as an endocrine organ, and the role of hypoxia in adipose tissue inflammation. | One hundred million deaths were caused by tobacco in the 20th century, and it is estimated that there will be up to one billion deaths attributed to tobacco use in the 21st century.,Chronic obstructive pulmonary disease (COPD) is rapidly becoming a global public health crisis with smoking being recognized as its most important causative factor.,The most effective available treatment for COPD is smoking cessation.,There is mounting evidence that the rate of progression of COPD can be reduced when patients at risk of developing the disease stop smoking, while lifelong smokers have a 50% probability of developing COPD during their lifetime.,More significantly, there is also evidence that the risk of developing COPD falls by about half with smoking cessation.,Several pharmacological interventions now exist to aid smokers in cessation; these include nicotine replacement therapy, bupropion, and varenicline.,All pharmacotherapies for smoking cessation are more efficacious than placebo, with odds ratios of about 2.,Pharmacologic therapy should be combined with nonpharmacologic (behavioral) therapy.,Unfortunately, despite the documented efficacy of these agents, the absolute number of patients who are abstinent from smoking at 12 months of follow-up is low. | 1 |
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. | Transforming growth factor-beta1 (TGF-β1) is a multipotential cytokine with angiogenic activity.,There are only limited data about its role in airway remodeling in COPD.,We have previously shown that the reticular basement membrane (Rbm) is hypervascular in the airways of current smokers either with or without chronic obstructive pulmonary disease (COPD).,This study evaluated TGF-β1 immunostaining in the Rbm and its relationship to vascularity in smokers with or without COPD.,Bronchial biopsies from 15 smokers with normal lung function, 19 current and 14 ex-smokers with COPD were immunostained for TGF-β1 antibody and compared to 17 healthy controls.,The percentage area of tissue and also number and area of vessels staining positively for TGF-β1 were measured and compared between groups.,Some bronchial biopsies from current smoking COPD subjects were also stained for phosphorylated (active) Smad2/3.,Epithelial TGF- β1 staining was not different between COPD current smokers and normal controls.,TGF-β1 stained vessels in the Rbm were increased in smokers with normal lung function, current smoking COPD and ex-smokers with COPD compared to controls [median (range) for number of vessels/mm Rbm 2.5 (0.0-12.7), 3.4 (0.0-8.1) and 1.0 (0.0-6.3) vs.,0.0 (0.0-7.0), p<0.05].,Percentage of vessels stained was also increased in these clinical groups.,Preliminary data suggest that in current smoking COPD subjects endothelial cells and cells in the Rbm stain positively for phosphorylated Smad2/3 suggesting TGF-β1 is functionally active in this situation.,Vessel-associated TGF-β1 activity is increased in the bronchial Rbm in smokers and especially those with COPD. | 1 |
The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) a pandemic [1].,COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,COVID-19 displays symptoms ranging from mild to severe (pneumonia) that can lead to death in some individuals [2-4].,As of 18 April 2020, there have been 2 280 945 cases of COVID-19 worldwide and 156 354 deaths [5].,SARS-CoV-2 uses the angiotensin-converting enzyme II (ACE-2) as the cellular entry receptor [6].,While the virus can infect individuals of any age, to date, most of the severe cases have been described in those >55 years of age and with significant comorbidities, such as COPD [7].,Here, we determined whether patients with COPD have increased expression of ACE-2 in bronchial epithelial cells in the lower respiratory tract.,Smokers and those with COPD have increased airway expression of ACE-2, which is the entry receptor for the COVID-19 virus.,This may explain the increased risk of severe COVID-19 in these subpopulations and highlight the importance of smoking cessation.https://bit.ly/3bC29es | Chronic obstructive pulmonary disease (COPD) causes significant morbidity and mortality worldwide.,Estimation of incidence, prevalence and disease burden through routine insurance data is challenging because of under-diagnosis and under-treatment, particularly for early stage disease in health care systems where outpatient International Classification of Diseases (ICD) diagnoses are not collected.,This poses the question of which criteria are commonly applied to identify COPD patients in claims datasets in the absence of ICD diagnoses, and which information can be used as a substitute.,The aim of this systematic review is to summarize previously reported methodological approaches for the identification of COPD patients through routine data and to compile potential criteria for the identification of COPD patients if ICD codes are not available.,A systematic literature review was performed in Medline via PubMed and Google Scholar from January 2000 through October 2018, followed by a manual review of the included studies by at least two independent raters.,Study characteristics and all identifying criteria used in the studies were systematically extracted from the publications, categorized, and compiled in evidence tables.,In total, the systematic search yielded 151 publications.,After title and abstract screening, 38 publications were included into the systematic assessment.,In these studies, the most frequently used (22/38) criteria set to identify COPD patients included ICD codes, hospitalization, and ambulatory visits.,Only four out of 38 studies used methods other than ICD coding.,In a significant proportion of studies, the age range of the target population (33/38) and hospitalization (30/38) were provided.,Ambulatory data were included in 24, physician claims in 22, and pharmaceutical data in 18 studies.,Only five studies used spirometry, two used surgery and one used oxygen therapy.,A variety of different criteria is used for the identification of COPD from routine data.,The most promising criteria set in data environments where ambulatory diagnosis codes are lacking is the consideration of additional illness-related information with special attention to pharmacotherapy data.,Further health services research should focus on the application of more systematic internal and/or external validation approaches. | 1 |
Inhaled corticosteroids (ICSs) are indicated for the prevention of exacerbations in COPD; however, a significant proportion of patients at low risk of exacerbations are treated with ICSs.,We conducted a systematic review including a diversity of types of study designs and safety outcomes with the objective of describing the risk of adverse effects associated with the long-term use of ICSs in patients with COPD.,A total of 90 references corresponding to 83 studies were included, including 26 randomised clinical trials (RCTs), 33 cohort studies, and 24 nested case-control (NCC) studies.,Analysis of 19 RCTs showed that exposure to ICSs for ≥1 year increased the risk of pneumonia by 41% (risk ratio 1.41, 95% CI 1.23-1.61).,Additionally, cohort and NCC studies showed an association between ICSs and risk of tuberculosis and mycobacterial disease.,There was a strong association between ICS use and local disorders such as oral candidiasis and dysphonia.,The association between ICSs and the risk of diabetes and fractures was less clear and appeared significant only at high doses of ICSs.,Since most patients with COPD are elderly and with frequent comorbidities, an adequate risk-benefit balance is crucial for the indication of ICSs.,Long-term use of inhaled corticosteroids in COPD is associated with a significantly increased risk of side-effects, especially oral candidiasis, dysphonia, pneumonia, mycobacterial disease, diabetes and fractureshttps://bit.ly/3t0AGfO | Computed tomography scan images have been used to identify different radiological COPD phenotypes based on the presence and severity of emphysema, bronchial wall thickening, and bronchiectasis.,Bronchiectasis is defined as an abnormal dilation of the bronchi, usually as a result of chronic airway inflammation and/or infection.,The prevalence of bronchiectasis in patients with COPD is high, especially in advanced stages.,The identification of bronchiectasis in COPD has been defined as a different clinical COPD phenotype with greater symptomatic severity, more frequent chronic bronchial infection and exacerbations, and poor prognosis.,A causal association has not yet been proven, but it is biologically plausible that COPD, and particularly the infective and exacerbator COPD phenotypes, could be the cause of bronchiectasis without any other known etiology, beyond any mere association or comorbidity.,The study of the relationship between COPD and bronchiectasis could have important clinical implications, since both diseases have different and complementary therapeutic approaches.,Longitudinal studies are needed to investigate the development of bronchiectasis in COPD, and clinical trials with treatments aimed at reducing bacterial loads should be conducted to investigate their impact on the reduction of exacerbations and improvements in the long-term evolution of the disease. | 1 |
Myeloid-derived suppressor cells (MDSCs) are present in the human lung microenvironment, and they may be involved in the local inflammatory process in chronic obstructive pulmonary disease (COPD).,Chronic inflammation in COPD may induce immunogenic cell death of structural airway cells, causing the release of damage-associated molecular patterns (DAMPs).,DAMPs may activate the innate and adaptive immune system.,The relationship between MDSCs and DAMPs in COPD is poorly described in the available literature.,Objectives.,(1) Assessment of MDSC percentage and DAMP concentration in bronchoalveolar lavage fluid (BALF) and peripheral blood.,(2) Analysis of the relationship between MDSC percentage and chosen DAMPs.,Patients and Methods.,30 COPD patients were included.,Using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry, MDSCs were assessed in BALF and peripheral blood.,The concentration of DAMPs was estimated using sandwich ELISA.,Using the Bradford method, the total protein concentrations were evaluated.,Results.,The percentage of MDSCs among MC in BALF correlated well with the concentration of defensin and heat shock protein 27.,Assessing the percentage of MDSCs among all leukocytes in BALF, we revealed a significant correlation with the concentration of defensin, hyaluronic acid, and surfactant protein A.,No dependencies occurred between DAMPs and MDSCs in peripheral blood.,Conclusion.,MDSCs and DAMPs occur in the COPD patient lung microenvironment.,Significant correlations between them found in BALF may indicate their influence on the local inflammatory process in COPD.,These relationships allow better understanding of the inflammatory process in COPD. | Chronic obstructive pulmonary disease (COPD) is associated with increased lung cancer risk.,We evaluated the association of statin use with lung cancer risk in COPD patients and identified which statins possess the highest chemopreventive potential.,After adjustment for age, sex, CCI, diabetes, hypertension, dyslipidemia, urbanization level, and monthly income according to propensity scores, lung cancer risk in the statin users was lower than that in the statin nonusers (adjusted hazard ratio [aHR] = 0.37).,Of the individual statins, lovastatin and fluvastatin did not reduce lung cancer risk significantly.,By contrast, lung cancer risk in patients using rosuvastatin, simvastatin, atorvastatin, and pravastatin was significantly lower than that in statin nonusers (aHRs = 0.41, 0.44, 0.52, and 0.58, respectively).,Statins dose-dependently reduced lung cancer risk in all subgroups and the main model with additional covariates (nonstatin drug use).,The study cohort comprised all patients diagnosed with COPD at health care facilities in Taiwan (n = 116,017) between January 1, 2001 and December 31, 2012.,Our final study cohort comprised 43,802 COPD patients: 10,086 used statins, whereas 33,716 did not.,Patients were followed up to assess lung cancer risk or protective factors.,In addition, we also considered demographic characteristics, namely age, sex, comorbidities (diabetes, hypertension, dyslipidemia, and Charlson comorbidity index [CCI]), urbanization level, monthly income, and nonstatin drug use.,The index date of statin use was the COPD confirmation date.,To examine the dose-response relationship, we categorized statin use into four groups in each cohort: < 28, 28-90, 91-365, and > 365 cumulative defined daily doses (cDDDs).,Patients receiving < 28 cDDDs were defined as nonstatin users.,Statins dose-dependently exert a significant chemopreventive effect against lung cancer in COPD patients.,Rosuvastatin, simvastatin, and atorvastatin exhibited the highest chemopreventive potential. | 1 |
The well-recognized individual heterogeneity within COPD patients has led to a growing interest in greater personalization in the approach of these patients.,Thus, the treatable traits strategy has been proposed as a further step towards precision medicine in the management of chronic airway disease, both in stable phase and acute exacerbations.,The aim of this paper is to perform a critical review on the treatable traits strategy and propose a guide to approach COPD patients in the light of this new concept.,An innovative stepwise approach is proposed - a multidisciplinary model based on two distinct phases, with the potential to be implemented in both primary care and hospital settings.,The first phase is the initial and focused assessment of a selected subset of treatable traits, which should be addressed in all COPD patients in both settings (primary care and hospital).,As some patients may present with advanced disease at diagnosis or may progress despite this initial treatment requiring a more specialized assessment, they should progress to a second phase, in which a broader approach is recommended.,Beyond stable COPD, we explore how the treatable traits strategy may be applied to reduce the risk of future exacerbations and improve the management of COPD exacerbations.,Since many treatable traits have already been related to exacerbation risk, the strategy proposed here represents an opportunity to be proactive.,Although it still lacks prospective validation, we believe this is the way forward for the future of the COPD approach. | Fixed dose combination (FDC) dual bronchodilators that co-administer a long acting β2-adrenoceptor agonist (LABA) and a long acting muscarinic antagonist (LAMA) are a new class of inhaled treatment for chronic obstructive pulmonary disease (COPD).,This review focuses on the clinical evidence for the benefit of LABA/LAMA FDCs compared with monocomponent treatments, and also compared with active comparators that are widely used for the treatment of COPD, namely tiotropium and salmeterol-fluticasone.,Novel FDC dual bronchodilators include QVA149 and umeclidinium/vilanterol (UMEC/VI).,Long term clinical trials show that QVA149 and UMEC/VI are superior to monocomponent therapy in terms of trough forced expiratory volume in 1 s (FEV1), although the FEV1 improvement was limited to approximately 80-90% of the added monocomponent values.,This suggests that the effect of combining a LABA and a LAMA is not fully additive.,LABA/LAMA FDC were associated with the largest mean changes in symptoms and health status that were above the minimal clinically important difference, in contrast to the monocomponents.,Furthermore, these LABA/LAMA FDCs demonstrated superiority over the active comparators tiotropium and salmeterol-fluticasone in terms of trough FEV1 and patient-reported outcomes.,LABA/LAMA FDCs offer a simplified means of maximizing bronchodilation for COPD patients, with the improvements in lung function being mirrored by benefits in terms of symptoms and exacerbations.,The use of LABA/LAMA FDCs in clinical practice is set to grow and further studies are needed to define their optimal place in treatment guidelines. | 1 |
According to the current clinical practice guidelines for chronic obstructive pulmonary disease (COPD), the addition of inhaled corticosteroids (ICS) to long-acting β2 agonist therapy is recommended in patients with moderate-to-severe disease and an increased risk of exacerbations.,However, ICS are largely overprescribed in clinical practice, and most patients are unlikely to benefit from long-term ICS therapy.,Evidence from recent randomized-controlled trials supports the hypothesis that ICS can be safely and effectively discontinued in patients with stable COPD and in whom ICS therapy may not be indicated, without detrimental effects on lung function, health status, or risk of exacerbations.,This article summarizes the evidence supporting the discontinuation of ICS therapy, and proposes an algorithm for the implementation of ICS withdrawal in patients with COPD in clinical practice.,Given the increased risk of potentially serious adverse effects and complications with ICS therapy (including pneumonia), the use of ICS should be limited to the minority of patients in whom the treatment effects outweigh the risks. | The benefit harm profile of inhaled corticosteroids, and their effect on patient oriented outcomes and comorbid pneumonia, osteoporosis and cardiovascular disease in patients with chronic obstructive pulmonary disease remain uncertain.,An overview of the evidence on the risks and benefits of inhaled corticosteroids (fluticasone and budesonide) in chronic obstructive pulmonary disease from recent randomized controlled trials and systematic reviews.,Observational studies on adverse effects were also evaluated.,Evidence from recent meta-analysis suggests a modest benefit from inhaled corticosteroid long-acting beta-agonist combination inhalers on the frequency of exacerbations, (rate ratio [RR], 0.82; 95% confidence interval [CI]: 0.78 to 0.88), in improvements in quality of life measures, and forced expiratory volume in one second when compared to long-acting beta-agonists alone.,On the outcome of pneumonia, our updated meta-analysis of trials (n = 24 trials; RR, 1.56; 95% CI: 1.40-1.74, P < 0.0001) and observational studies (n = 4 studies; RR, 1.44; 95% CI: 1.20-1.75, P = 0.0001) shows a significant increase in the risk of pneumonia with the inhaled corticosteroids currently available (fluticasone and budesonide).,Evidence for any intraclass differences in the risk of pneumonia between currently available formulations is inconclusive due to the absence of head to head trials.,Inhaled corticosteroids have no cardiovascular effects.,Among patients with chronic obstructive pulmonary disease, clinicians should carefully balance these long-term risks of inhaled corticosteroid against their symptomatic benefits. | 1 |
Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY | The evolution of knowledge concerning COPD and its components - emphysema, chronic bronchitis, and asthmatic bronchitis - covers 200 years.,The stethoscope and spirometer became important early tools in diagnosis and assessment.,Spirometry remains the most effective means of identification and assessment of the course of COPD and responses to therapy, and is grossly underused for this purpose.,Knowledge of the pathogenesis, course and prognosis, and new approaches to therapy have dramatically improved our understanding of this important clinical entity.,Smoking cessation improves the early course of disease.,Long-term oxygen improves the length and quality of life in selected patients with hypoxemia.,Surgery benefits a select few.,Today, COPD is a steadily growing global healthcare problem, with increasing morbidity and mortality.,Early identification and prevention, and treatment of emerging stages of disease through smoking cessation and a growing number of bronchoactive drugs promises to change the outcome. | 1 |
NVA237 (glycopyrronium bromide) is a once-daily long-acting muscarinic antagonist (LAMA) in development for chronic obstructive pulmonary disease (COPD).,The GLycopyrronium bromide in COPD airWays clinical Study 2 (GLOW2) evaluated the efficacy and safety of NVA237 in moderate-to-severe COPD over 52 weeks.,Patients were randomised 2:1:1 to NVA237 50 μg, placebo or open-label tiotropium 18 μg for 52 weeks.,Primary end-point was trough forced expiratory volume in 1 s (FEV1) at 12 weeks.,1,066 patients were randomised, 810 completed the study.,At week 12, trough FEV1 increased significantly by 97 mL with NVA237 (95% CI 64.6-130.2; p<0.001) and 83 mL with tiotropium (95% CI 45.6-121.4; p<0.001).,Compared with placebo, NVA237 produced significant improvements in dyspnoea (Transition Dyspnoea Index at week 26; p=0.002) and health status (St George's Respiratory Questionnaire at week 52; p<0.001).,NVA237 significantly reduced the risk of moderate-to-severe COPD exacerbations by 34% (p=0.001) and the use of rescue medication (p=0.039), versus placebo.,NVA237-placebo and tiotropium-placebo differences were comparable for all outcomes.,Safety profiles were similar across groups.,NVA237 50 μg provided significant improvements in lung function, dyspnoea, health status, exacerbations and rescue medication use, versus placebo, and was comparable to tiotropium.,NVA237 can potentially be an alternative choice of LAMA for COPD patients. | Chronic obstructive pulmonary disease (COPD) and asthma may overlap and converge in older people (overlap syndrome).,It was hypothesized that patients with overlap syndrome may have different clinical characteristics such as sputum eosinophilia, and better responsiveness to treatment with inhaled corticosteroid (ICS).,Sixty-three patients with stable COPD (forced expiratory volume in 1 second [FEV1] ≤80%) underwent pulmonary function tests, including reversibility of airflow limitation, arterial blood gas analysis, analysis of inflammatory cells in induced sputum, and chest high-resolution computed tomography.,The inclusion criteria for COPD patients with asthmatic symptoms included having asthmatic symptoms such as episodic breathlessness, wheezing, cough, and chest tightness worsening at night or in the early morning (COPD with asthma group).,The clinical features of COPD patients with asthmatic symptoms were compared with those of COPD patients without asthmatic symptoms (COPD without asthma group).,The increases in FEV1 in response to treatment with ICS were significantly higher in the COPD with asthma group.,The peripheral eosinophil counts and sputum eosinophil counts were significantly higher.,The prevalence of patients with bronchial wall thickening on chest high-resolution computed tomography was significantly higher.,A significant correlation was observed between the increases in FEV1 in response to treatment with ICS and sputum eosinophil counts, and between the increases in FEV1 in response to treatment with ICS and the grade of bronchial wall thickening.,Receiver operating characteristic curve analysis revealed 82.4% sensitivity and 84.8% specificity of sputum eosinophil count for detecting COPD with asthma, using 2.5% as the cutoff value.,COPD patients with asthmatic symptoms had some clinical features.,ICS should be considered earlier as a potential treatment in such patients.,High sputum eosinophil counts and bronchial wall thickening on chest high-resolution computed tomography might therefore be a good predictor of response to ICS. | 1 |
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. | 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 |
Chronic obstructive pulmonary disease (COPD) symptoms in the morning, including dyspnea and sputum production, affect patients’ quality of life and limit their ability to carry out even simple morning activities.,It is now emerging that these symptoms are associated with increased risk of exacerbations and work absenteeism, suggesting that they have a more profound impact on patients than previously thought.,The development of validated patient-reported outcome (PRO) questionnaires to capture patients’ experience of COPD symptoms in the morning is, therefore, vital for establishing effective and comprehensive management strategies.,Although it is well established that long-acting bronchodilators are effective in improving COPD symptoms, the limited available data on their impact on morning symptoms and activities have been obtained with non-validated PRO questionnaires.,In this review, we discuss the impact of COPD symptoms in the morning and available tools used to evaluate them, and highlight specific gaps that need to be addressed to develop standardized instruments able to meet regulatory requirement.,We also present available evidence on the effect of pharmacological therapies on morning symptoms. | Chronic obstructive pulmonary disease (COPD) patients may suffer from poor sleep and health-related quality of life.,We hypothesized that disturbed sleep in COPD is correlated with quality of life.,In 180 patients with COPD (forced expired volume in 1 second [FEV1] 47.6 ± 15.2% predicted, 77.8% male, aged 65.9 ± 11.7 years), we administered general (Health Utilities Index 3) and disease-specific (St George’s Respiratory) questionnaires and an index of disturbed sleep (Pittsburgh Sleep Quality Index).,Overall scores indicated poor general (Health Utilities Index 3: 0.52 ± 0.38), disease- specific (St George’s: 57.0 ± 21.3) quality of life and poor sleep quality (Pittsburgh 11.0 ± 5.4).,Sleep time correlated with the number of respiratory and anxiety symptoms reported at night.,Seventy-seven percent of the patients had Pittsburg scores >5, and the median Pittsburgh score was 12.,On multivariate regression, the Pittsburgh Sleep Quality Index was an independent predictor of both the Health Utilities Index 3 and the St George’s scores, accounting for 3% and 5%, respectively, of the scores.,Only approximately 25% of the patients demonstrated excessive sleepiness (Epworth Sleepiness Scale >9).,Most patients with COPD suffer disturbed sleep.,Sleep quality was correlated with general and disease-specific quality of life.,Only a minority of COPD patients complain of being sleepy. | 1 |
Smoking prevalence is frequently estimated on the basis of self-reported smoking status.,That can lead to an underestimation of smoking rates.,The aim of this study was to evaluate the difference between self-reported smoking status and that determined through the use of objective measures of smoking at a pulmonary outpatient clinic.,This was a cross-sectional study involving 144 individuals: 51 asthma patients, 53 COPD patients, 20 current smokers, and 20 never-smokers.,Smoking status was determined on the basis of self-reports obtained in interviews, as well as through tests of exhaled carbon monoxide (eCO) and urinary cotinine.,All of the asthma patients and COPD patients declared they were not current smokers.,In the COPD and asthma patients, the median urinary cotinine concentration was 167 ng/mL (range, 2-5,348 ng/mL) and 47 ng/mL (range, 5-2,735 ng/mL), respectively (p < 0.0001), whereas the median eCO level was 8 ppm (range, 0-31 ppm) and 5 ppm (range, 2-45 ppm), respectively (p < 0.05).,In 40 (38%) of the patients with asthma or COPD (n = 104), there was disagreement between the self-reported smoking status and that determined on the basis of the urinary cotinine concentration, a concentration > 200 ng/mL being considered indicative of current smoking.,In 48 (46%) of those 104 patients, the self-reported non-smoking status was refuted by an eCO level > 6 ppm, which is also considered indicative of current smoking.,In 30 (29%) of the patients with asthma or COPD, the urinary cotinine concentration and the eCO level both belied the patient claims of not being current smokers.,Our findings suggest that high proportions of smoking pulmonary patients with lung disease falsely declare themselves to be nonsmokers.,The accurate classification of smoking status is pivotal to the treatment of lung diseases.,Objective measures of smoking could be helpful in improving clinical management and counseling. | To determine the underdiagnosis rate in new COPD cases at the end of a nine-year follow-up period-in the study designated "Projeto Latino-Americano de Investigação em Obstrução Pulmonar" (PLATINO, Latin-American Pulmonary Obstruction Investigation Project)-and compare that with the underdiagnosis rate during the initial phase of the study, as well as to identify the clinical features exhibited by the subjects who were not diagnosed until the end of the follow-up phase.,The study population comprised the 1,000 residents of the city of São Paulo, Brazil, who took part in the PLATINO study.,Of those, 613 participated in the follow-up phase, during which the subjects were assessed with the same instruments and equipment employed in the initial phase of the study.,We used the chi-square test or the independent sample t-test to analyze the underdiagnosis rate and to identify the characteristics of the subjects who were not diagnosed until the end of the follow-up phase.,The underdiagnosis rate for new COPD cases at the end of the nine-year follow-up period was 70.0%.,The underdiagnosis rate during the follow-up phase was 17.5% lower than that reported for the initial phase of the study.,The subjects who were not diagnosed until the end of the follow-up phase presented with fewer respiratory symptoms, better pulmonary function, and less severe disease than did those previously diagnosed with COPD.,The underdiagnosis rate for new COPD cases was lower in the follow-up phase of the study than in the initial phase.,The subjects who were not diagnosed until the end of the follow-up phase of the PLATINO study presented with the same clinical profile as did those who were not diagnosed in the initial phase.,These findings underscore the need for spirometry in order to confirm the diagnosis of COPD and provide early intervention.,Determinar a taxa de subdiagnóstico em novos casos de DPOC em uma amostra de pacientes após nove anos de seguimento do estudo "Projeto Latino-Americano de Investigação em Obstrução Pulmonar" (PLATINO) e compará-la à taxa de subdiagnóstico obtida na fase inicial do estudo, assim como identificar as características clínicas dos indivíduos subdiagnosticados na fase de seguimento.,A população desse estudo foi composta por 1.000 residentes na cidade de São Paulo que fizeram parte do estudo PLATINO.,Desses, 613 indivíduos participaram da fase de seguimento.,Os indivíduos foram avaliados utilizando-se os mesmos instrumentos e equipamentos na fase inicial do estudo.,O teste do qui-quadrado ou o teste t para amostras independentes foi utilizado para analisar a taxa de subdiagnóstico e identificar as características dos indivíduos subdiagnosticados durante a fase de seguimento.,A taxa de subdiagnóstico para novos casos da DPOC após nove anos de acompanhamento foi de 70,0%.,A taxa de subdiagnóstico na fase de seguimento foi 17,5% menor que a da fase inicial do estudo.,Os indivíduos subdiagnosticados na fase de seguimento apresentavam poucos sintomas respiratórios, função pulmonar mais preservada e menor gravidade da doença do que aqueles previamente diagnosticados com DPOC.,A taxa de subdiagnóstico na fase de seguimento foi menor que a da fase inicial do estudo.,Os indivíduos subdiagnosticados na fase de seguimento do estudo PLATINO apresentavam o mesmo perfil clínico daqueles subdiagnosticados na fase inicial.,Esses achados reforçam a necessidade da utilização da espirometria para o diagnóstico de DPOC e possibilitar a intervenção precoce. | 1 |
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. | Although respiratory symptoms are characteristic features of COPD, there is no standardised method for quantifying their severity in stable disease.,To evaluate the EXACT-Respiratory Symptom (E-RS) measure, a daily diary comprising 11 of the 14 items in the Exacerbations of Chronic Pulmonary Disease Tool (EXACT).,Qualitative: patient focus group and interviews to address content validity.,Quantitative: secondary data analyses to test reliability and validity.,Qualitative: n=84; mean (SD) age 65 (10) years, FEV1 1.2(0.4) L; 44% male.,Subject descriptions of their respiratory symptoms were consistent with E-RS content and structure.,Quantitative: n=188; mean (SD) age 66 (10) years, FEV1 1.2(0.5) L; 50% male.,Factor analysis (FA) showed 3 subscales: RS-Breathlessness, RS-Cough & Sputum, and RS-Chest Symptoms; second-order FA supported a general factor and total score.,Reliability (total and subscales): 0.88, 0.86, 0.73, 0.81; 2-day test-retest ICC: 0.90, 0.86, 0.87, 0.82, respectively.,Validity: Total scores correlated significantly (p < 0.0001) with SGRQ Total (r=0.75), Symptoms (r=0.66), Activity (r=0.57), Impact (r=0.70) scores; subscale correlations were also significant (r=0.26, p < 0.05 (RS-Chest Symptoms with Activity) to r=0.69, p < 0.0001 (RS-Cough & Sputum with Symptoms).,RS-Breathlessness correlated with rescue medication use (r=0.32, p < 0.0001), clinician-reported mMRC (r=0.33, p < 0.0001), and FEV1% predicted (r=-0.17, p < 0.05).,E-RS scores differentiated groups based on chronic bronchitis diagnosis (p < 0.01-0.001), smoking status (p < 0.05-0.001), and rescue medication use (p < 0.05-0.0001).,Results suggest the RS-Total is a reliable and valid instrument for evaluating respiratory symptom severity in stable COPD.,Further study of sensitivity to change is warranted. | 1 |
The GOLD report provides a framework for classifying COPD in a way that reflects its clinical impact and allows treatment recommendations.,The GOLD 2017 proposes a new classification whereby patients are grouped as A-D according to their symptoms and history of exacerbations.,However, the clinical characteristics and outcomes in these patients are not well documented.,In this prospective observational study, we analyzed data from the Ishinomaki COPD Network Registry.,All patients with stable COPD were classified into the four groups defined by GOLD 2017.,The patient demographics, clinical characteristics, number of exacerbations, and mortality rate during 1 year of follow-up were compared between the groups.,Four hundred and one patients with stable COPD were identified.,There were 240 patients (59.9%) in group A, 122 (30.4%) in group B, 16 (4.0%) in group C, and 23 (5.7%) in group D.,Patients in groups B, C, and D had ORs of 2.95, 3.92, and 5.45, respectively, for risk of exacerbation relative to group A.,Groups C and D experienced exacerbations more frequently, including exacerbations leading to hospital admission, than groups A and B (both P<0.001) during the 1-year follow-up period.,Patients with a high risk of exacerbation (groups C and D) had a lower body mass index, showed more symptoms, used more respiratory medications, and had more severe airflow limitation than patients at low risk of exacerbation (groups A and B).,Mortality was not different between the high-risk and low-risk groups.,The results of our study provide evidence that the GOLD 2017 classification identifies patients with COPD at risk of exacerbations, including those requiring hospitalization, but has a poor ability to predict mortality. | COPD is a heterogeneous disease, and the available prognostic indexes are therefore limited.,This study aimed to identify the factors associated with acute exacerbation leading to hospitalization.,This was a retrospective study of consecutive patients with COPD (meeting the Global Initiative for Chronic Obstructive Lung Disease [GOLD] diagnostic criteria) hospitalized at the Ninth Hospital of Xi’an Affiliated Hospital of Xi’an Jiaotong University between October 2014 and September 2016.,During follow-up after first hospitalization, the patients who had been rehospitalized within 1 year for acute exacerbation were grouped into the frequent exacerbation (FE) group, while the others were grouped into the infrequent exacerbation (IE) group.,The baseline demographic, clinical, laboratory, pulmonary function, and imaging data were compared between the two groups.,Compared with the IE group, the FE group had lower forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) (P=0.005), FEV1%pred (P=0.002), maximal mid-expiratory flow (MMEF25-75%pred) (P=0.003), and ratio of carbon monoxide diffusion capacity to alveolar ventilation (DLCO/VA) (P=0.03) and higher resonant frequency (Fres; P=0.04).,According to generations of bronchi, the percentage of the wall area (%WA) of lobes was found to be higher in the FE group.,Emphysema index (EI), mean emphysema density (MED)whole and MEDleft lung in the FE group were significantly worse than in the IE group (P<0.05).,Using logistic regression, exacerbation hospitalizations in the past year (odds ratio [OR] 14.4, 95% CI 6.1-34.0, P<0.001) and EI >10% (OR 2.9, 95% CI 1.2-7.1, P=0.02) were independently associated with frequent acute exacerbation of COPD (AECOPD) hospitalization.,Exacerbation hospitalizations in the past year and imaging features of emphysema (EI) were independently associated with FE hospitalization. | 1 |
COPD is characterized by an ongoing inflammatory process of the airways that leads to obstruction or limitation of airflow.,It is mainly associated with exposure to cigarette smoke.,In addition, it is considered, at present, a serious public health problem, ranking fourth in mortality worldwide.,Many cells participate in the pathophysiology of COPD, the most important are neutrophils, macrophages and CD4+ and CD8+ T cells.,Neutrophil migration to the inflammation area could be mediated largely by cytokines related to CD4+ Th17 lymphocytes, because it has been shown that IL-17A, IL-17F and IL-22 act as inducers for CXCL8, CXCL1, CXCL5, G-CSF, and GM-CSF secretion by epithelial cells of the airways.,The aims of these molecules are differentiation, proliferation and recruitment of neutrophils.,Furthermore, it is believed that CD4+ lymphocytes Th17 may be involved in protection against pathogens for which Th1 and Th2 are not prepared to fight.,In COPD exacerbations, there is an increased cellularity in the lung region and respiratory tract.,Therefore, the increase in the number of neutrophils and macrophages in the airways and the increase in proinflammatory cytokines are directly related to the severity of exacerbations and that is the importance of the functions of Th17 profile in this entity. | As chronic obstructive pulmonary disease (COPD) is a heterogeneous disease it is unlikely that all patients will benefit equally from a given therapy.,Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, has been shown to improve lung function in moderate and severe COPD but its effect on exacerbations in unselected populations was inconclusive.,This led to the question of whether a responsive subset existed that could be investigated further.,The datasets of two previous replicate, randomized, double-blind, placebo-controlled, parallel-group studies (oral roflumilast 500 μg or placebo once daily for 52 weeks) that were inconclusive regarding exacerbations were combined in a post-hoc, pooled analysis to determine whether roflumilast reduced exacerbations in a more precisely defined patient subset.,The pooled analysis included 2686 randomized patients.,Roflumilast significantly decreased exacerbations by 14.3% compared with placebo (p = 0.026).,Features associated with this reduction were: presence of chronic bronchitis with or without emphysema (26.2% decrease, p = 0.001), presence of cough (20.9% decrease, p = 0.006), presence of sputum (17.8% decrease, p = 0.03), and concurrent use of inhaled corticosteroids (ICS; 18.8% decrease, p = 0.014).,The incidence of adverse events was similar with roflumilast and placebo (81.5% vs 80.1%), but more patients in the roflumilast group had events assessed as likely or definitely related to the study drug (21.5% vs 8.3%).,This post-hoc, pooled analysis showed that roflumilast reduced exacerbation frequency in a subset of COPD patients whose characteristics included chronic bronchitis with/without concurrent ICS.,These observations aided the design of subsequent phase 3 studies that prospectively confirmed the reduction in exacerbations with roflumilast treatment.,ClinicalTrials.gov identifiers: NCT00076089 and NCT00430729. | 1 |
Recent advances in multidetector computed tomography (MDCT) facilitate acquiring important clinical information for managing patients with COPD.,MDCT can detect the loss of lung tissue associated with emphysema as a low-attenuation area (LAA) and the thickness of airways as the wall area percentage (WA%).,The percentage of small pulmonary vessels <5 mm2 (% cross-sectional area [CSA] <5) has been recently recognized as a parameter for expressing pulmonary perfusion.,We aimed to analyze the longitudinal changes in structural abnormalities using these CT parameters and analyze the effect of exacerbation and smoking cessation on structural changes in COPD patients.,We performed pulmonary function tests (PFTs), an MDCT, and a COPD assessment test (CAT) in 58 patients with COPD at the time of their enrollment at the hospital and 2 years later.,We analyzed the change in clinical parameters including CT indices and examined the effect of exacerbations and smoking cessation on the structural changes.,The CAT score and forced expiratory volume in 1 second (FEV1) did not significantly change during the follow-up period.,The parameters of emphysematous changes significantly increased.,On the other hand, the WA% at the distal airways significantly decreased or tended to decrease, and the %CSA <5 slightly but significantly increased over the same period, especially in ex-smokers.,The parameters of emphysematous change were greater in patients with exacerbations and continued to progress even after smoking cessation.,In contrast, the WA% and %CSA <5 did not change in proportion to emphysema progression.,The WA% at the distal bronchi and the %CSA <5 did not change in parallel with parameters of LAA over the same period.,We propose that airway disease and vascular remodeling may be reversible to some extent by smoking cessation and appropriate treatment.,Optimal management may have a greater effect on pulmonary vascularity and airway disease than parenchymal deconstruction in the early stage of COPD. | Chronic obstructive pulmonary disease (COPD) is increasingly being recognized as a highly heterogeneous disorder, composed of varying pathobiology.,Accurate detection of COPD subtypes by image biomarkers are urgently needed to enable individualized treatment thus improving patient outcome.,We adapted the Parametric Response Map (PRM), a voxel-wise image analysis technique, for assessing COPD phenotype.,We analyzed whole lung CT scans of 194 COPD individuals acquired at inspiration and expiration from the COPDGene Study.,PRM identified the extent of functional small airways disease (fSAD) and emphysema as well as provided CT-based evidence that supports the concept that fSAD precedes emphysema with increasing COPD severity.,PRM is a versatile imaging biomarker capable of diagnosing disease extent and phenotype, while providing detailed spatial information of disease distribution and location.,PRMs ability to differentiate between specific COPD phenotypes will allow for more accurate diagnosis of individual patients complementing standard clinical techniques. | 1 |
Evidence suggests that there is an association between chronic obstructive pulmonary disease (COPD) and coronary heart disease (CHD).,An important etiological link between COPD and CHD may be an underlying systemic inflammatory process.,Given that COPD patients are at greater risk of cardiovascular mortality, understanding the burden of CHD on COPD patients could permit future risk attenuation.,Longitudinal cohort analyses of the Third National Health and Nutrition Examination Survey from 1988-1994 were performed. 3,681 individuals ≥40 years of age with good quality spirometry data were included.,Participants were divided into 5 groups: 1) no COPD, no CHD; 2) COPD without inflammation, no CHD; 3) COPD with inflammation, no CHD; 4) CHD only, and 5) CHD + COPD.,A novel “inflammatory” COPD designation included those with COPD and clinical evidence of inflammation (i.e., CRP ≥95.24 nmol/L).,The risk for CHD mortality was significant only for the CHD group (HR 5.56, 95% CI 3.24-9.55) and the COPD + CHD group (HR 5.02, 95% CI 2.83-8.90).,Similarly, the risk for cardiovascular disease (CVD) mortality was significant only for the CHD group (HR 4.25, 95% CI 2.70-6.69) and the CHD + COPD group (HR 4.12, 95% CI 2.60-6.54) after adjusting for nonmodifiable CHD risk factors (age, gender, race/ethnicity, family history of CHD).,After adjusting for modifiable CHD risk factors (diabetes, BMI, physical activity, systolic blood pressure, cholesterol, and smoking), hazard ratios of the two groups remained similar but attenuated.,For total mortality, the risk was significant for the four groups: the non-inflammatory COPD group; the COPD with inflammation group, the CHD group, and the COPD + CHD group.,Our study did not confirm that inflammatory COPD may be a CHD risk equivalent.,However, due to the small size of the “inflammatory” COPD group, further prospective replication and validation is needed.,Moreover, given that COPD results from inflammation, the systemic inflammation associated with COPD may have worsened comorbid conditions and may have lead to the increased total mortality found in the COPD with inflammation and COPD + CHD groups which requires further investigation. | The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999-2000.,Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples.,Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments.,Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis.,The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale.,Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey.,COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%-9%.,In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%-14%) than among women (range 5%-11%).,A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries.,Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment.,This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey.,A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey. | 1 |
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. | Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. | 1 |
Exacerbations are important outcomes in COPD both from a clinical and an economic perspective.,Most studies investigating predictors of exacerbations were performed in COPD patients participating in pharmacological clinical trials who usually have moderate to severe airflow obstruction.,This study was aimed to investigate whether predictors of COPD exacerbations depend on the COPD population studied.,A network of COPD health economic modelers used data from five COPD data sources - two population-based studies (COPDGene® and The Obstructive Lung Disease in Norrbotten), one primary care study (RECODE), and two studies in secondary care (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoint and UPLIFT) - to estimate and validate several prediction models for total and severe exacerbations (= hospitalization).,The models differed in terms of predictors (depending on availability) and type of model.,FEV1% predicted and previous exacerbations were significant predictors of total exacerbations in all five data sources.,Disease-specific quality of life and gender were predictors in four out of four and three out of five data sources, respectively.,Age was significant only in the two studies including secondary care patients.,Other significant predictors of total exacerbations available in one database were: presence of cough and wheeze, pack-years, 6-min walking distance, inhaled corticosteroid use, and oxygen saturation.,Predictors of severe exacerbations were in general the same as for total exacerbations, but in addition low body mass index, cardiovascular disease, and emphysema were significant predictors of hospitalization for an exacerbation in secondary care patients.,FEV1% predicted, previous exacerbations, and disease-specific quality of life were predictors of exacerbations in patients regardless of their COPD severity, while age, low body mass index, cardiovascular disease, and emphysema seem to be predictors in secondary care patients only. | Hospitalisation due to acute exacerbations of COPD (AECOPD) is common, and subsequent mortality high.,The DECAF score was derived for accurate prediction of mortality and risk stratification to inform patient care.,We aimed to validate the DECAF score, internally and externally, and to compare its performance to other predictive tools.,The study took place in the two hospitals within the derivation study (internal validation) and in four additional hospitals (external validation) between January 2012 and May 2014.,Consecutive admissions were identified by screening admissions and searching coding records.,Admission clinical data, including DECAF indices, and mortality were recorded.,The prognostic value of DECAF and other scores were assessed by the area under the receiver operator characteristic (AUROC) curve.,In the internal and external validation cohorts, 880 and 845 patients were recruited.,Mean age was 73.1 (SD 10.3) years, 54.3% were female, and mean (SD) FEV1 45.5 (18.3) per cent predicted.,Overall mortality was 7.7%.,The DECAF AUROC curve for inhospital mortality was 0.83 (95% CI 0.78 to 0.87) in the internal cohort and 0.82 (95% CI 0.77 to 0.87) in the external cohort, and was superior to other prognostic scores for inhospital or 30-day mortality.,DECAF is a robust predictor of mortality, using indices routinely available on admission.,Its generalisability is supported by consistent strong performance; it can identify low-risk patients (DECAF 0-1) potentially suitable for Hospital at Home or early supported discharge services, and high-risk patients (DECAF 3-6) for escalation planning or appropriate early palliation.,UKCRN ID 14214. | 1 |
COPD is a significant cause of morbidity and mortality.,In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation.,Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy.,In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention.,In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13.,The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions.,We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD. | CD56+ natural killer (NK) and CD56+ T cells, from sputum or bronchoalveolar lavage of subjects with chronic obstructive pulmonary disease (COPD) are more cytotoxic to highly susceptible NK targets than those from control subjects.,Whether the same is true in lung parenchyma, and if NK activity actually contributes to emphysema progression are unknown.,To address these questions, we performed two types of experiments on lung tissue from clinically-indicated resections (n = 60).,First, we used flow cytometry on fresh single-cell suspension to measure expression of cell-surface molecules (CD56, CD16, CD8, NKG2D and NKp44) on lung lymphocytes and of the 6D4 epitope common to MICA and MICB on lung epithelial (CD326+) cells.,Second, we sequentially isolated CD56+, CD8+ and CD4+ lung lymphocytes, co-cultured each with autologous lung target cells, then determined apoptosis of individual target cells using Annexin-V and 7-AAD staining.,Lung NK cells (CD56+ CD3−) and CD56+ T cells (CD56+ CD3+) were present in a range of frequencies that did not differ significantly between smokers without COPD and subjects with COPD.,Lung NK cells had a predominantly “cytotoxic” CD56+ CD16+ phenotype; their co-expression of CD8 was common, but the percentage expressing CD8 fell as FEV1 % predicted decreased.,Greater expression by autologous lung epithelial cells of the NKG2D ligands, MICA/MICB, but not expression by lung CD56+ cells of the activating receptor NKG2D, correlated inversely with FEV1 % predicted.,Lung CD56+ lymphocytes, but not CD4+ or CD8+ conventional lung T cells, rapidly killed autologous lung cells without additional stimulation.,Such natural cytotoxicity was increased in subjects with severe COPD and was unexplained in multiple regression analysis by age or cancer as indication for surgery.,These data show that as spirometry worsens in COPD, CD56+ lung lymphocytes exhibit spontaneous cytotoxicity of autologous structural lung cells, supporting their potential role in emphysema progression.,ClinicalTrials.gov NCT00281229 | 1 |
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