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Objective To test the effectiveness of telemonitoring integrated into existing clinical services such that intervention and control groups have access to the same clinical care.,Design Researcher blind, multicentre, randomised controlled trial.,Setting UK primary care (Lothian, Scotland).,Participants Adults with at least one admission for chronic obstructive pulmonary disease (COPD) in the year before randomisation.,We excluded people who had other significant lung disease, who were unable to provide informed consent or complete the study, or who had other significant social or clinical problems.,Interventions Participants were recruited between 21 May 2009 and 28 March 2011, and centrally randomised to receive telemonitoring or conventional self monitoring.,Using a touch screen, telemonitoring participants recorded a daily questionnaire about symptoms and treatment use, and monitored oxygen saturation using linked instruments.,Algorithms, based on the symptom score, generated alerts if readings were omitted or breached thresholds.,Both groups received similar care from existing clinical services.,Main outcome measures The primary outcome was time to hospital admission due to COPD exacerbation up to one year after randomisation.,Other outcomes included number and duration of admissions, and validated questionnaire assessments of health related quality of life (using St George’s respiratory questionnaire (SGRQ)), anxiety or depression (or both), self efficacy, knowledge, and adherence to treatment.,Analysis was intention to treat.,Results Of 256 patients completing the study, 128 patients were randomised to telemonitoring and 128 to usual care; baseline characteristics of each group were similar.,The number of days to admission did not differ significantly between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.66 to 1.44).,Over one year, the mean number of COPD admissions was similar in both groups (telemonitoring 1.2 admissions per person (standard deviation 1.9) v control 1.1 (1.6); P=0.59).,Mean duration of COPD admissions over one year was also similar between groups (9.5 days per person (standard deviation 19.1) v 8.8 days (15.9); P=0.88).,The intervention had no significant effect on SGRQ scores between groups (68.2 (standard deviation 16.3) v 67.3 (17.3); adjusted mean difference 1.39 (95% confidence interval −1.57 to 4.35)), or on other questionnaire outcomes.,Conclusions In participants with a history of admission for exacerbations of COPD, telemonitoring was not effective in postponing admissions and did not improve quality of life.,The positive effect of telemonitoring seen in previous trials could be due to enhancement of the underpinning clinical service rather than the telemonitoring communication.,Trial registration ISRCTN96634935.,Funding: The trial was funded by an NHS applied research programme grant from the Chief Scientist Office of the Scottish government (ARPG/07/03).,The funder had no role in study design and the collection, analysis, and interpretation of data and the writing of the article and the decision to submit it for publication.,NHS Lothian supported the telemonitoring service and the clinical services. | The ability to objectively differentiate exacerbations of chronic obstructive pulmonary disease (COPD) from day-to-day symptom variations would be an important development in clinical practice and research.,We assessed the ability of domiciliary pulse oximetry to achieve this.,40 patients with moderate-severe COPD collected daily data on changes in symptoms, heart-rate (HR), oxygen saturation (SpO2) and peak-expiratory flow (PEF) over a total of 2705 days. 31 patients had data suitable for baseline analysis, and 13 patients experienced an exacerbation.,Data were expressed as multiples of the standard deviation (SD) observed from each patient when stable.,In stable COPD, the SD for HR, SpO2 and PEF were approximately 5 min-1, 1% and 10l min-1.,There were detectable changes in all three variables just prior to exacerbation onset, greatest 2-3 days following symptom onset.,A composite Oximetry Score (mean magnitude of SpO2 fall and HR rise) distinguished exacerbation onset from symptom variation (area under receiver-operating characteristic curve, AUC = 0.832, 95%CI 0.735-0.929, p = 0.003).,In the presence of symptoms, a change in Score of ≥1 (average of ≥1SD change in both HR and SpO2) was 71% sensitive and 74% specific for exacerbation onset.,We have defined normal variation of pulse oximetry variables in a small sample of patients with COPD.,A composite HR and SpO2 score distinguished exacerbation onset from symptom variation, potentially facilitating prompt therapy and providing validation of such events in clinical trials. | 1 |
Chronic obstructive pulmonary disease (COPD) is prevalent and poses a heavy burden worldwide.,However, patients know little about COPD, and primary health care providers have poor therapy capability in China.,Enjoying Breathing Program aims to establish a new comprehensive COPD patient management system, including early detection, standardized therapy, and follow-up in China.,The goal of the study is to 1) describe the intervention for physicians and patients and 2) to assess the effectiveness of this program.,It is the first nationwide trial involving all levels of health care institutions from primary health care institutions to tertiary hospitals.,It includes a series of structured but individualized intervention for both health care providers and COPD patients.,Primary health care providers from pilot hospitals will take both online and face-to-face courses, including the procedure of COPD patients’ management and prevention, diagnosis and treatment.,Once the patients are diagnosed with COPD, they will undertake standard therapy and self-management education program, perform rehabilitation exercises, and be followed up by primary health care providers every 3 months.,The primary outcome will be exacerbation-related hospital/emergency admission and the change of patients’ awareness and primary health care providers’ knowledge of COPD within 36 months.,Secondary outcome will include the change of pulmonary function test, structured COPD patients’ management, two-way referral, and standardized therapy.,A comprehensive COPD patient management model to promote the standardized therapy will be established; this will improve COPD patients’ awareness and health quality.,This study has been registered at www.ClinicalTrials.gov (registration identifier: NCT04318912). | Pulmonary rehabilitation is a cornerstone of care for COPD but uptake of traditional centre-based programmes is poor.,We assessed whether home-based pulmonary rehabilitation, delivered using minimal resources, had equivalent outcomes to centre-based pulmonary rehabilitation.,A randomised controlled equivalence trial with 12 months follow-up.,Participants with stable COPD were randomly assigned to receive 8 weeks of pulmonary rehabilitation by either the standard outpatient centre-based model, or a new home-based model including one home visit and seven once-weekly telephone calls from a physiotherapist.,The primary outcome was change in 6 min walk distance (6MWD).,We enrolled 166 participants to receive centre-based rehabilitation (n=86) or home-based rehabilitation (n=80).,Intention-to-treat analysis confirmed non-inferiority of home-based rehabilitation for 6MWD at end-rehabilitation and the confidence interval (CI) did not rule out superiority (mean difference favouring home group 18.6 m, 95% CI −3.3 to 40.7).,At 12 months the CI did not exclude inferiority (−5.1 m, −29.2 to 18.9).,Between-group differences for dyspnoea-related quality of life did not rule out superiority of home-based rehabilitation at programme completion (1.6 points, −0.3 to 3.5) and groups were equivalent at 12 months (0.05 points, −2.0 to 2.1).,The per-protocol analysis showed the same pattern of findings.,Neither group maintained postrehabilitation gains at 12 months.,This home-based pulmonary rehabilitation model, delivered with minimal resources, produced short-term clinical outcomes that were equivalent to centre-based pulmonary rehabilitation.,Neither model was effective in maintaining gains at 12 months.,Home-based pulmonary rehabilitation could be considered for people with COPD who cannot access centre-based pulmonary rehabilitation.,NCT01423227, clinicaltrials.gov. | 1 |
A single administration of mesenchymal stromal cells (MSCs) has been shown to reduce lung inflammation in experimental elastase-induced emphysema; however, effects were limited in terms of lung-tissue repair and cardiac function improvement.,We hypothesized that two doses of MSCs could induce further lung and cardiovascular repair by mitigating inflammation and remodeling in a model of emphysema induced by multiple elastase instillations.,We aimed to comparatively investigate the effects of one versus two doses of MSCs, administered 1 week apart, in a murine model of elastase-induced emphysema.,C57BL/6 mice were randomly divided into control (CTRL) and emphysema (E) groups.,Mice in the E group received porcine pancreatic elastase (0.2 IU, 50 μL) intratracheally once weekly for four consecutive weeks; the CTRL animals received sterile saline (50 μL) using the same protocol.,Three hours after the last instillation, the E group was further randomized to receive either saline (SAL) or murine MSCs (105 cells) intratracheally, in one or two doses (1 week apart).,Fourteen days later, mice were euthanized, and all data analyzed.,Both one and two doses of MSCs improved lung mechanics, reducing keratinocyte-derived chemokine and transforming growth factor-β levels in lung homogenates, total cell and macrophage counts in bronchoalveolar lavage fluid (BALF), and collagen fiber content in airways and blood vessels, as well as increasing vascular endothelial growth factor in lung homogenates and elastic fiber content in lung parenchyma.,However, only the two-dose group exhibited reductions in tumor necrosis factor-α in lung tissue, BALF neutrophil and lymphocyte count, thymus weight, and total cellularity, as well as CD8+ cell counts and cervical lymph node CD4+ and CD8+ T cell counts, as well as further increased elastic fiber content in the lung parenchyma and reduced severity of pulmonary arterial hypertension.,Two doses of MSCs enhanced lung repair and improvement in cardiac function, while inducing T cell immunosuppression, mainly of CD8+ cells, in elastase-induced emphysema. | Histone deacetylase 2 (HDAC2) is a class I histone deacetylase family member that plays a critical role in suppressing inflammatory gene expression in the airways, lung parenchyma, and alveolar macrophages in patients with chronic obstructive pulmonary disease (COPD).,However, the expression of HDAC2 in peripheral blood monocytes (PBMCs), nuclear factor kappa B (NF-κB) p65, and serum inflammatory cytokine levels in COPD patients, smokers, and non-smokers remains unclear.,PBMCs were obtained from COPD patients, healthy smokers, and healthy nonsmokers.,The HDAC2 and NF-κB p65 expression were quantified by Western Blot.,HDAC activity was assessed by an HDAC fluorometric immunoprecipitation activity assay kit.,Serum tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) levels were measured by ELISA.,HDAC2 expression and HDAC activity were decreased in PBMCs in COPD patients compared with smokers and non-smokers.,Increased NF-κB p65 expression, serum TNF-α and IL-8 levels were observed in COPD patients compared with nonsmokers.,The FEV1%pred was positively correlated with HDAC2 expression and HDAC activity in COPD patients.,Smokers had decreased HDAC activity, increased NF-κB p65 expression and serum TNF-α compared with nonsmokers.,HDAC2 expression was decreased in PBMCs of COPD patients and was correlated with disease severity.,The reduction of HDAC2 expression not only directly enhances the expression of inflammatory genes, but may account for the activation of NF-κB mediated inflammation.,Decreased HDAC2 may serve as a potential biomarker of COPD and predict the decline of lung function. | 1 |
The aim of this study was to investigate the predicting value of miR-146a/b for acute exacerbation chronic obstructive pulmonary disease (AECOPD) and COPD, and to explore their associations with inflammatory cytokines in AECOPD and stable COPD patients.,One hundred six AECOPD, 122 stable COPD patients, and 110 health volunteers with age and sex matched to total COPD patients (AECOPD and stable COPD) were enrolled.,Blood samples were collected from all participants.,Relative expression of miR-146a/b was determined by real-time polymerase chain reaction.,Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), leukotriene B4 (LTB-4) expression in serum from AECOPD and stable COPD patients were assessed using commercial ELISA kit.,Serum levels of miR-146a and miR-146b were down regulated in AECOPD patients compared with stable COPD patients and HCs. miR-146a and miR-146b are of good values for predicting the risk of AECOPD in HCs with AUC of 0.702 and 0.715.,Additionally, miR-146a and miR-146b could distinguish AECOPD from stable COPD patients with AUC of 0.670 and 0.643.,In AECOPD patients, levels of miR-146a in AECOPD patients were negatively associated with TNF-α, IL-6, IL-8, and LTE-4 expression.,In stable COPD patients, miR-146a expressions were negatively correlated with TNF-α, IL-1β, IL-6, IL-8, and LTE-4 levels.,And, the expressions of miR-146b in AECOPD patients were negatively associated with IL-1β and LTB-4 expression.,While in stable COPD patients, miR-146b expressions were only negatively correlated with TNF-α level.,In conclusion, miR-146a and miR-146b were negatively correlated with inflammatory cytokines, and could be promising biomarkers for predicting the risk of AECOPD in stable COPD patients and healthy individuals. | Chronic obstructive pulmonary disease (COPD) is a common, highly debilitating disease of the airways, primarily caused by smoking.,Chronic inflammation and structural remodelling are key pathological features of this disease, in part caused by the aberrant function of airway smooth muscle (ASM) cells under the regulation of transforming growth factor (TGF)‐β. miRNA are short, noncoding gene transcripts involved in the negative regulation of specific target genes, through their interactions with mRNA.,Previous studies have proposed that mRNA‐145 (miR‐145) may interact with SMAD3, an important downstream signalling molecule of the TGF‐β pathway.,TGF‐β was used to stimulate primary human ASM cells isolated from healthy nonsmokers, healthy smokers and COPD patients.,This resulted in a TGF‐β‐dependent increase in CXCL8 and IL‐6 release, most notably in the cells from COPD patients.,TGF‐β stimulation increased SMAD3 expression, only in cells from COPD patients, with a concurrent increased miR‐145 expression.,Regulation of miR‐145 was found to be negatively controlled by pathways involving the MAP kinases, MEK‐1/2 and p38 MAPK.,Subsequent, overexpression of miR‐145 (using synthetic mimics) in ASM cells from patients with COPD suppressed IL‐6 and CXCL8 release, to levels comparable to the nonsmoker controls.,Therefore, this study suggests that miR‐145 negatively regulates pro‐inflammatory cytokine release from ASM cells in COPD by targeting SMAD3. | 1 |
The BEACON study evaluated the efficacy and safety of QVA149, a once-daily dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist (LABA) indacaterol and long-acting muscarinic antagonist (LAMA) glycopyrronium (NVA237), in development for the treatment of patients with chronic obstructive pulmonary disease (COPD), compared with the free-dose concurrent administration of indacaterol plus glycopyrronium (IND+GLY).,In this multicenter, double-blind, parallel group study, patients with stage II or stage III COPD (Global initiative for chronic Obstructive Lung Disease [GOLD] 2010) were randomized (1:1) to once-daily QVA149 (110 μg indacaterol/50 μg glycopyrronium) or concurrent administration of indacaterol (150 μg) and glycopyrronium (50 μg) via the Breezhaler® device (Novartis AG, Basel, Switzerland) for 4 weeks.,The primary endpoint was to evaluate the noninferiority of QVA149 as compared with concurrent administration of IND+GLY, for trough forced expiratory volume in 1 second (FEV1) after 4 weeks of treatment.,The other assessments included FEV1 area under the curve from 0 to 4 hours (AUC0-4 hours) at day 1 and week 4, symptom scores, rescue medication use, safety, and tolerability over the 4-week study period.,Of 193 patients randomized, 187 (96.9%) completed the study.,Trough FEV1 at week 4 for QVA149 and IND+GLY was 1.46 L ± 0.02 and 1.46 L ± 0.18, respectively.,The FEV1 AUC0-4 hours at day 1 and week 4 were similar between the two treatment groups.,Both treatment groups had a similar reduction in symptom scores and rescue medication use for the 4-week treatment period.,Overall, 25.6% of patients in QVA149 group and 25.2% in the IND+GLY group experienced an adverse event, with the majority being mild-to-moderate in severity.,No deaths were reported during the study or during the 30 days follow-up period.,The BEACON study demonstrated that once-daily QVA149 provides an efficacy and safety profile similar to the concurrent administration of its monocomponents indacaterol and glycopyrronium. | Ipratropium bromide/albuterol Respimat inhaler (CVT-R) was developed as an environmentally friendly alternative to ipratropium bromide/albuterol metered-dose inhaler (CVT-MDI), which uses a chlorofluorocarbon propellant.,The objective of this study was to evaluate patient satisfaction, device usage, and long-term safety of CVT-R compared to CVT-MDI, and to the simultaneous administration of ipratropium bromide hydrofluoroalkane (HFA; I) and albuterol HFA (A) metered-dose inhalers as dual monotherapies (I + A).,This is a 48-week, open-label, randomized, active-controlled, parallel-group study (n = 470) comparing CVT-R to CVT-MDI and to I + A.,Patients were at least 40 years of age, diagnosed with chronic obstructive pulmonary disease (COPD), and current or exsmokers.,Patients were randomized to receive: (1) CVT-R, one inhalation four times daily (QID); or (2) CVT-MDI, two inhalations QID; or (3) I + A two inhalations of each inhaler QID.,Patient Satisfaction and Preference Questionnaire (PASAPQ) performance score (primary endpoint) and adverse events.,PASAPQ performance score was significantly higher (CVT-R versus CVT-MDI, 9.6; and CVT-R versus I + A, 6.2; both P < 0.001) when using CVT-R compared to CVT-MDI or I + A at all visits starting from week 3, while CVT-MDI and I + A treatment groups were similar.,Time to first COPD exacerbation was slightly longer in the CVT-R group compared to the other treatment groups, although it did not reach statistical significance (CVT-R versus CVT-MDI, P = 0.57; CVT-R versus I + A, P = 0.22).,Rates of withdrawal and patient refusal to continue treatment were lower in CVT-R compared with CVT-MDI and I + A groups (CVT-R versus CVT-MDI, P = 0.09; CVT-R versus I + A, P = 0.005).,The percentage of patients reporting adverse events and serious adverse events was similar across all three treatment groups.,CVT-R is an effective, environmentally friendly inhaler that provides patients with a high level of user satisfaction and may positively impact clinical outcomes while having no adverse impacts on patients using the device. | 1 |
The association between asthma-chronic obstructive pulmonary diseases (COPD) overlap syndrome (ACOS) and tuberculosis (TB) has yet to be studied.,The newly diagnosed TB patients (age > 20 y) treated from January 2000 to December 2008 were included (ACOS cohort, n = 10 751; non-ACOS cohort, n = 42 966).,The non-ACOS cohort involved patients with confirmed absence of ACOS.,We calculated incidence rate ratios (IRRs) for TB in the ACOS and non-ACOS cohorts by using poisson regression analysis.,Cox proportional hazards regression models were used to determine the adjusted HR (aHR) for TB in the ACOS cohort compared with the non-ACOS cohort.,The aHR for TB was 2.41 (95% confidence interval [CI], 2.19-2.66) in the ACOS cohort.,The TB risk was significantly higher in the ACOS cohort than in the non-ACOS cohort when stratified by age, sex, comorbidities, and atopy.,Within the ACOS cohort, the aHR was higher among patients receiving SABAs+SAMAs, LABAs+LAMAs, and ICSs (aHR [95% CI]: 3.06 [2.75-3.41], 3.68 [2.93-4.61], and 2.79 [1.25-6.22], respectively; all P < .05).,Furthermore, patients with more than 15 outpatient visits and hospitalizations per year demonstrated the highest aHR (8.09; 95% CI, 6.85-9.56).,ACOS cohort potentially develop incident TB, regardless of the age,sex, comorbidities and atopy; even without receiving the inhalers.This risk is higher, especially in the ACOS cohort have a high frequency of medical services or receiving the inhalers such as SABAs+SAMAs, LABAs+LAMAs and ICSs. | The combination of asthma and chronic obstructive pulmonary disease (COPD), or ACOS is a recently defined syndrome.,The epidemiology of the condition is poorly described and previous research has suggested ACOS is associated with worse outcomes than either condition alone.,We therefore decided to complete a systematic review of the published literature.,This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines.,A structured search was performed in the PubMed, Embase, and Medline databases up to Feb 2015 to identify studies reporting incidence, prevalence, health care utilization, morbidity, or mortality in COPD and asthma.,A total of 19 studies were included in the present study.,The pooled prevalence of overlap among COPD was 27% (95% CI: 0.16-0.38, p<0.0001) and 28% (95% CI: 0.09-0.47, p = 0.0032) in the population and hospital-based studies, respectively.,We found no significant difference between ACOS and COPD in terms of gender, smoking status, lung function and 6mWD.,However, in comparison to subject with only COPD, ACOS subjects were significantly younger, had higher BMI, healthcare utilization, and lower HRQoL.,ACOS is a common condition that exists in a substantial proportion of subjects with COPD.,ACOS represents a distinct clinical phenotype with more frequent exacerbations, hospitalization, worse health-related quality of life, and higher healthcare costs than either disease alone.,There is a critical need to better define the management and treatment of this syndrome. | 1 |
Malnutrition is common in patients with COPD; however, little is known about its impacts on health-related quality of life (QoL) among patients with COPD.,This study aimed to explore the nutritional status and dietary intake among outpatients with COPD in Vietnam and its possible associations with QoL.,A cross-sectional study was carried out in COPD outpatients visiting the COPD management unit at the National Lung Hospital, Hanoi, Vietnam between May 2017 and July 2017.,Consecutive outpatients with a confirmed diagnosis of COPD were recruited with written inform consent.,The nutritional status of participants was assessed using Subjective Global Assessment (SGA), and dietary intake via a 24-hour recall interview.,The St George Respiratory Questionnaire (SGRQ) for COPD was used to investigate the participants’ QoL.,Sociodemographic and clinical data were extracted from hospital records.,Of 168 COPD outpatients involved in the study, three-quarters (74.4%) were diagnosed as malnourished (SGA B/C) and 81.5% reported unintentional weight loss.,Most of the patients did not meet their estimated energy and protein requirements (85.7% and 89.9%, respectively).,Malnutrition was significantly associated with disease severity (P=0.039) and ratio of protein intake to estimated requirement (P=0.005).,QoL was low for all levels of malnutrition or disease severity, with well-nourished participants and those with less disease severity having better QoL (P=0.006 and P<0.001, respectively).,With an extra meal per day, the odds of having malnutrition decreased 5.6 times (P<0.05) and the total SGRQ reduced 3.61 scores (P<0.05) indicating a better QoL.,Malnutrition and weight loss are prevalent among COPD outpatients.,Most of the patients had inadequate dietary intake and low QoL.,Nutrition counselling including increasing the number of meals per day with a focus on energy- and protein-rich foods may help improving nutritional status and QoL of patients with COPD in Vietnam. | Diet and nutrition may be important modifiable risk factors for the development, progression and management of obstructive lung diseases such as asthma and chronic obstructive pulmonary disease (COPD).,This review examines the relationship between dietary patterns, nutrient intake and weight status in obstructive lung diseases, at different life stages, from in-utero influences through childhood and into adulthood.,In vitro and animal studies suggest important roles for various nutrients, some of which are supported by epidemiological studies.,However, few well-designed human intervention trials are available to definitively assess the efficacy of different approaches to nutritional management of respiratory diseases.,Evidence for the impact of higher intakes of fruit and vegetables is amongst the strongest, yet other dietary nutrients and dietary patterns require evidence from human clinical studies before conclusions can be made about their effectiveness. | 1 |
The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) questionnaire is a short patient-completed questionnaire, which is used to assess the health status of patients with stable COPD.,However, whether it is a good tool to evaluate the response to treatment in acute exacerbation of COPD (AECOPD) has been less studied.,The patients were assessed at two visits, at admission and on the seventh day.,Anthropometric variables were collected at admission.,CAT and lung function were measured twice at the above time points.,At the second visit, the health status of the patients were divided into five groups based on a 5-point Likert scale, ranging from 1 to 5, which represents “much better,” “slightly better,” “no change,” “slightly worse,” and “much worse.”,Responders were those who reported “much better” or “slightly better,” and nonresponders were those who claimed “no change,” “worse,” or “much worse.”,In total, 225 patients were recruited.,The average CAT score at admission was 24.82±7.41, which declined to 17.41±7.35 on the seventh day.,There were 81.33% responders, whose improvement in CAT score (9.37±5.24) was much higher than that of the nonresponders (−1.36±4.35).,A moderate correlation was observed between the changes in CAT score and improvement in FEV1, FEV1%, and the length of hospital stay.,There was a strong correlation between the changes in CAT score and health status.,A 3.5-unit improvement in the CAT score, with highest area under the curve, was the cutoff to differentiate responders from nonresponders.,The evolution of CAT scores during exacerbation can provide useful information to assess the health status of patients with AECOPD.,A 3.5-unit improvement in CAT score is the best cutoff to differentiate between patients who have a response or no response to treatment, which offers a convenient and easy way for clinicians to monitor the health status of patients with an AECOPD. | Both the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ) were recommended as comprehensive symptom measures by the Global Initiative for Chronic Obstructive Lung disease.,The main objective of this work was to compare the evaluation of symptom severity with the CAT and the CCQ and find a cutoff value of the CCQ for the Chinese clinical population.,Patients diagnosed with stable COPD in the outpatient department who completed the CAT and CCQ were enrolled from November 2015 to December 2016.,Scores of 0-10, 11-20, 21-30, and 31-40 represent low, medium, high, and very high impact level, respectively, by CAT.,Scores of the CCQ can be considered as acceptable (CCQ<1), acceptable for moderate disease (1≤CCQ<2), instable-severe limited (2≤CCQ<3), and very instable-very severe limited (CCQ≥3).,According to the CAT, only 20.4% of patients belonged to the high (21≤CAT≤30) and very high (31≤CAT≤40) impact levels, which were statistically lower than those of the CCQ, which classified over half of the population (51.1%) into the instable-severe limited (2≤CCQ<3) and very instable-very severe limited (CCQ≥3) categories (P<0.001).,The kappa of agreement for the symptom groups by CAT and CCQ (cutoff point 1.5) was 0.495, but only slight agreement (0.144) was found between the CAT and CCQ with the cutoff point of 1.0.,The CAT and the total CCQ had a strong correlation (rho=0.776, P<0.01).,The CCQ 1.0 and 1.5 corresponded to CAT 4.2 and 9.7, respectively.,The CAT 10.0 was equivalent to 1.53 of the CCQ.,In addition, with higher scores of the CAT and CCQ, subjects displayed more impairment in lung function, higher levels on modified Medical Research Council, and higher exacerbation rates in the last year (P<0.001).,Similarly, patients with more exacerbations presented worse scores on the CAT and total CCQ as well as its 3 domains (P<0.001).,Compared with the CAT, the CCQ was more likely to classify the patients into more severe categories, and 1.5 might be a better cutoff point for the CCQ than 1.0.,Both the CAT and the overall CCQ with its 3 domains were able to discriminate between groups of patients that differ in COPD severity. | 1 |
We aimed to evaluate correlations between computed tomography (CT) parameters and pulmonary function test (PFT) parameters according to disease severity in patients with chronic obstructive pulmonary disease (COPD), and to determine whether CT parameters can be used to predict PFT indices.,A total of 370 patients with COPD were grouped based on disease severity according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-IV criteria.,Emphysema index (EI), air-trapping index, and airway parameters such as the square root of wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10) were measured using automatic segmentation software.,Clinical characteristics including PFT results and quantitative CT parameters according to GOLD criteria were compared using ANOVA.,The correlations between CT parameters and PFT indices, including the ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) and FEV1, were assessed.,To evaluate whether CT parameters can be used to predict PFT indices, multiple linear regression analyses were performed for all patients, Group 1 (GOLD I and II), and Group 2 (GOLD III and IV).,Pulmonary function deteriorated with increase in disease severity according to the GOLD criteria (p < 0.001).,Parenchymal attenuation parameters were significantly worse in patients with higher GOLD stages (p < 0.001), and Pi10 was highest for patients with GOLD III (4.41 ± 0.94 mm).,Airway parameters were nonlinearly correlated with PFT results, and Pi10 demonstrated mild correlation with FEV1/FVC in patients with GOLD II and III (r = 0.16, p = 0.06 and r = 0.21, p = 0.04, respectively).,Parenchymal attenuation parameters, airway parameters, EI, and Pi10 were identified as predictors of FEV1/FVC for the entire study sample and for Group 1 (R2 = 0.38 and 0.22, respectively; p < 0.001).,However, only parenchymal attenuation parameter, EI, was identified as a predictor of FEV1/FVC for Group 2 (R2 = 0.37, p < 0.001).,Similar results were obtained for FEV1.,Airway and parenchymal attenuation parameters are independent predictors of pulmonary function in patients with mild COPD, whereas parenchymal attenuation parameters are dominant independent predictors of pulmonary function in patients with severe COPD. | Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century.,The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD.,Our understanding of the key molecular mechanisms which drive the pathological changes are not complete.,In this article we will provide a historical overview of key histopathological studies which have helped shape our understanding of SAD and discuss the hallmark features of airway remodelling, mucous plugging and inflammation.,We focus on the relationship between SAD and emphysema, SAD in the early stages of COPD, and the mechanisms which cause SAD progression, including bacterial colonization and exacerbations.,We discuss the need to specifically target SAD to attenuate the progression of COPD. | 1 |
Asthma and chronic obstructive pulmonary disease (COPD) are obstructive airway disorders which differ in their underlying causes and phenotypes but overlap in patterns of pharmacological treatments.,In both asthma and COPD, oxidative stress contributes to airway inflammation by inducing inflammatory gene expression.,The redox-sensitive transcription factor, nuclear factor (NF)-kappaB (NF-κB), is an important participant in a broad spectrum of inflammatory networks that regulate cytokine activity in airway pathology.,The anti-inflammatory actions of glucocorticoids (GCs), a mainstay treatment for asthma, involve inhibition of NF-κB induced gene transcription.,Ligand bound GC receptors (GRs) bind NF-κB to suppress the transcription of NF-κB responsive genes (i.e., transrepression).,However, in severe asthma and COPD, the transrepression of NF-κB by GCs is negated as a consequence of post-translational changes to GR and histones involved in chromatin remodeling.,Therapeutics which target NF-κB activation, including inhibitors of IκB kinases (IKKs) are potential treatments for asthma and COPD.,Furthermore, reversing GR/histone acetylation shows promise as a strategy to treat steroid refractory airway disease by augmenting NF-κB transrepression.,This review examines NF-κB signaling in airway inflammation and its potential as target for treatment of asthma and COPD. | Noninvasive imaging of macrophages activity has raised increasing interest for diagnosis of chronic obstructive respiratory diseases (COPD), which make them attractive vehicles to deliver contrast agents for diagnostic or drugs for therapeutic purposes.,This study was designed to monitor and evaluate the migration of differently polarized M1 and M2 iron labeled macrophage subsets to the lung of a LPS-induced COPD animal model and to assess their polarization state once they have reached the inflammatory sites in the lung after intravenous injection.,Ex vivo polarized bone marrow derived M1 or M2 macrophages were first efficiently and safely labeled with amine-modified PEGylated dextran-coated SPIO nanoparticles and without altering their polarization profile.,Their biodistribution in abdominal organs and their homing to the site of inflammation in the lung was tracked for the first time using a free-breathing non-invasive MR imaging protocol on a 4.7T magnet after their intravenous administration.,This imaging protocol was optimized to allow both detection of iron labeled macrophages and visualization of inflammation in the lung.,M1 and M2 macrophages were successfully detected in the lung starting from 2 hours post injection with no variation in their migration profile.,Quantification of cytokines release, analysis of surface membrane expression using flow cytometry and immunohistochemistry investigations confirmed the successful recruitment of injected iron labeled macrophages in the lung of COPD mice and revealed that even with a continuum switch in the polarization profile of M1 and M2 macrophages during the time course of inflammation a balanced number of macrophage subsets predominate. | 1 |
Persistent exposure to cigarette smoke or biomass fuels induces oxidative stress and apoptosis in bronchial epithelium, which is one of the most important pathogenic mechanisms of chronic obstructive pulmonary disease (COPD).,Fine particulate matter (PM2.5) is an aggravating risk factor of COPD exacerbation.,Animal evidence showed PM2.5accelerated lung inflammation and oxidative stress in COPD mice, but the mechanism is still not clear.,Recently, we found that miR-194-3p is a novel biomarker of both COPD and PM2.5 exposure, and miR-194 family has been reported to be involved in cell proliferation and apoptosis.,Thus, we propose a hypothesis: PM2.5 can accelerate apoptotic response of airway epithelial cells in COPD and miR-194 is a potential involved regulator.,Human bronchial epithelial cells (HBEpiCs) were treated with normal media, cigarette smoke solution (CSS) and PM2.5-CSS for 24 h. miR-194-3p mimics, inhibitors and scrambled controls were non-transfected or pre-transfected into HBEpiCs for 48 h.,MircroRNAs and mRNA expression were quantified by qRT-PCR.,Protein expression was analyzed by western blotting.,Caspase activities, mitochondrial membrane potential and TUNEL-positive cells were detected to analyze apoptosis.,Bioinformatics and luciferase analysis were used to identify the predicted binding site of miR-194-3p and potential targets.,In our study, we found that PM2.5 significantly aggravated apoptosis in cigarette-inflamed HBEpiCs. miR-194-3p was dramatically downregulated in PM2.5-CSS-treated HBEpiCs.,Bioinformatics and luciferase experiments reported that death-associated protein kinase 1 (DAPK1), regulating caspase 3 activities in apoptosis, was directly targeted by miR-194-3p.,Inhibition of miR-194-3p increased DAPK1 expression and apoptosis in normal HBEpiCs.,Importantly, overexpression of miR-194-3p suppressed apoptosis in PM2.5-CSS HBEpiCs.,These results suggested that miR-194-3p was a protective regulator involved in apoptosis pathway and a potential therapeutic target for treatment of bronchial epithelial injury aggravation induced by PM2.5. | Pneumoconiosis may play an important role in the development of chronic obstructive pulmonary disease (COPD), and the complication of COPD may impose a heavy burden of illness.,The study was conducted in Hunan Province in China from December 1, 2015, to December 1, 2016.,Consecutive underground male pneumoconiosis patients employed for at least 1 year were recruited from the Hunan Occupational Disease Prevention Institute.,Patient information, respiratory symptoms and clinical data were collected using a structured questionnaire.,The diagnosis of COPD were assessed using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.,Logistic regression analyses were conducted to examine the clinical and demographic risk factors of COPD among pneumoconiosis patients.,The prevalence of COPD in our sample of pneumoconiosis patients was 18.65% (119/638).,In pneumoconiosis patients with and without smoking history, the prevalence of COPD was 19.32 and 16.77%.,Compared with non-COPD patients, those with COPD are older in age, have longer exposure time, have lower body mass index (BMI), have a higher smoking index and have worse pulmonary function (all p < 0.05).,For the five respiratory symptoms (cough, sputum, wheeze, dyspnea, and chest tightness), only the presence of wheeze and the severity scores for wheeze or dyspnea showed significant differences between the COPD and non-COPD groups (p < 0.01).,Multivariate logistic regression analysis revealed that advanced pneumoconiosis category, older age and the presence of wheeze symptoms were significant risk factors for the development of COPD among pneumoconiosis patients.,Pneumoconiosis patients are at a high risk of COPD, and pneumoconiosis patients with COPD may suffer more severe respiratory symptoms, such as wheeze and dyspnea, than patients without COPD.,Advanced pneumoconiosis category, older age and the presence of wheeze symptoms are associated with an increased risk of COPD in pneumoconiosis.,We proposed that a routine assessment of lung function is necessary for timely and adequate clinical management. | 1 |
Chronic obstructive pulmonary disease (COPD) is a disease characterised by persistent airflow limitation that is not fully reversible and is currently the fourth leading cause of death globally.,It is now well established that cardiovascular-related comorbidities contribute to morbidity and mortality in COPD, with approximately 50% of deaths in COPD patients attributed to a cardiovascular event (e.g. myocardial infarction).,Cardiovascular disease (CVD) and COPD share various risk factors including hypertension, sedentarism, smoking and poor diet but the underlying mechanisms have not been fully established.,However, there is emerging and compelling experimental and clinical evidence to show that increased oxidative stress causes pulmonary inflammation and that the spill over of pro-inflammatory mediators from the lungs into the systemic circulation drives a persistent systemic inflammatory response that alters blood vessel structure, through vascular remodelling and arterial stiffness resulting in atherosclerosis.,In addition, regulation of endothelial-derived vasoactive substances (e.g. nitric oxide (NO)), which control blood vessel tone are altered by oxidative damage of vascular endothelial cells, thus promoting vascular dysfunction, a key driver of CVD.,In this review, the detrimental role of oxidative stress in COPD and comorbid CVD are discussed and we propose that targeting oxidant-dependent mechanisms represents a novel strategy in the treatment of COPD-associated CVD. | COPD is mainly caused by tobacco smoking and is associated with a high frequency of coronary artery disease.,There is growing recognition that the inflammation in COPD is not only confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs, including blood vessels. α1-antitrypsin-low-density lipoprotein (AT-LDL) complex is an oxidatively modified LDL that accelerates atherosclerosis.,Curcumin, one of the best-investigated natural products, is a powerful antioxidant.,However, the effects of curcumin on AT-LDL remain unknown.,We hypothesized that Theracurmin®, a highly absorptive curcumin with improved bioavailability using a drug delivery system, ameliorates the inflammatory status in subjects with mild COPD.,This is a randomized, double-blind, parallel-group study.,Subjects with stages I-II COPD according to the Japanese Respiratory Society criteria were randomly assigned to receive 90 mg Theracurmin® or placebo twice a day for 24 weeks, and changes in inflammatory parameters were evaluated.,There were no differences between the Theracurmin® and placebo groups in terms of age, male/female ratio, or body mass index in 39 evaluable subjects.,The percent changes in blood pressure and hemoglobin A1c and LDL-cholesterol, triglyceride, or high-density lipoprotein-cholesterol levels after treatment were similar for the two groups.,However, the percent change in the AT-LDL level was significantly (P=0.020) lower in the Theracurmin® group compared with the placebo group.,Theracurmin® reduced levels of atherosclerotic AT-LDL, which may lead to the prevention of future cardiovascular events in mild COPD subjects. | 1 |
Baarsma et al. report increased expression and posttranslational modification of the noncanonical ligand WNT-5A in COPD.,Fibroblast-derived WNT-5A inhibits canonical WNT-β-catenin-driven alveolar epithelial cell-mediated wound healing and transdifferentiation, and thus contributes to impaired lung regeneration and COPD pathogenesis.,Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide.,One main pathological feature of COPD is the loss of functional alveolar tissue without adequate repair (emphysema), yet the underlying mechanisms are poorly defined.,Reduced WNT-β-catenin signaling is linked to impaired lung repair in COPD; however, the factors responsible for attenuating this pathway remain to be elucidated.,Here, we identify a canonical to noncanonical WNT signaling shift contributing to COPD pathogenesis.,We demonstrate enhanced expression of noncanonical WNT-5A in two experimental models of COPD and increased posttranslationally modified WNT-5A in human COPD tissue specimens.,WNT-5A was increased in primary lung fibroblasts from COPD patients and induced by COPD-related stimuli, such as TGF-β, cigarette smoke (CS), and cellular senescence.,Functionally, mature WNT-5A attenuated canonical WNT-driven alveolar epithelial cell wound healing and transdifferentiation in vitro.,Lung-specific WNT-5A overexpression exacerbated airspace enlargement in elastase-induced emphysema in vivo.,Accordingly, inhibition of WNT-5A in vivo attenuated lung tissue destruction, improved lung function, and restored expression of β-catenin-driven target genes and alveolar epithelial cell markers in the elastase, as well as in CS-induced models of COPD.,We thus identify a novel essential mechanism involved in impaired mesenchymal-epithelial cross talk in COPD pathogenesis, which is amenable to therapy. | The length of time for cigarette smoke (CS) exposure to cause emphysema in mice is drastically reduced when CS exposure is combined with viral infection.,However, the extent of inflammatory responses and lung pathologies of mice exposed to CS and infected with influenza A virus (IAV), respiratory syncytial virus (RSV), or treated with the viral derivative dsRNA (polyinosine-polycytidylic acid [poly (I:C)] have not been compared.,Mice were exposed to CS or filtered air for 4 weeks and received a single dose of vehicle, AV, or RSV infection and extent of inflammation and emphysema was evaluated 14 d later.,In another set of experiments, mice were instilled with poly (I:C) twice a week during the third and fourth weeks of CS exposure and immediately analyzed for extent of inflammation and lung pathologies.,In CS-exposed mice, inflammation was characterized mainly by macrophages, lymphocytes, and neutrophils after IAV infection, mainly by lymphocytes, and neutrophils after RSV infection, and mainly by lymphocytes and neutrophils after poly (I:C) instillations.,Despite increased inflammation, extent of emphysema by poly (I:C) was very mild; but was robust and similar for both IAV and RSV infections with enhanced MMP-12 mRNA expression and TUNEL positivity.,Both IAV and RSV infections increased the levels of IL-17, IL-1β, IL-12b, IL-18, IL-23a, Ccl-2, Ccl-7 mRNAs in the lungs of CS-exposed mice with IAV causing more increases than RSV.,CS-induced inflammatory responses and extent of emphysematous changes differ depending on the type of viral infection.,These animal models may be useful to study the mechanisms by which different viruses exacerbate CS-induced inflammation and emphysema. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity, places substantial time and cost burden on the health care system, and is now the third leading cause of death in the US.,Many interventions are available to appropriately manage patients with COPD; however, fully implementing these strategies to help improve outcomes may be difficult.,Collaboration between an interprofessional team of health care professionals (which includes physicians, nurses, respiratory therapists, physical therapists, dietitians, pharmacists, and many others) and COPD patients and caregivers is necessary to optimally manage these patients and to truly impact outcomes in this devastating disease.,Prescribing evidence-based non-pharmacological and pharmacological therapies is an important start, but a true team-based approach is critical to successfully implement comprehensive care in patients with COPD.,The goal of this review is to employ a case-based approach to provide practical information regarding the roles of the interprofessional team in implementing strategies to optimally manage COPD patients. | We sought to assess continuity of care for elderly patients in Korea and to examine any association between continuity of care and health outcomes (hospitalization, emergency department visits, health care costs).,This was a retrospective cohort study using the Korea National Health Insurance Claims Database.,Elderly people, 65-84 yr of age, who were first diagnosed with diabetes mellitus (n=268,220), hypertension (n=858,927), asthma (n=129,550), or chronic obstructive pulmonary disease (COPD, n=131,512) in 2002 were followed up for four years, until 2006.,The mean of the Continuity of Care Index was 0.735 for hypertension, 0.709 for diabetes mellitus, 0.700 for COPD, and 0.663 for asthma.,As continuity of care increased, in all four diseases, the risks of hospitalization and emergency department visits decreased, as did health care costs.,In the Korean health care system, elderly patients with greater continuity of care with health care providers had lower risks of hospital and emergency department use and lower health care costs.,In conclusion, policy makers need to develop and try actively the program to improve the continuity of care in elderly patients with chronic diseases. | 1 |
Atherosclerosis prevalence is increased in chronic obstructive pulmonary disease (COPD) patients, independent of other risk factors.,The etiology of the excess vascular disease in COPD is unknown, although it is presumably related to an underlying (if cryptic) systemic immune response.,Autoantibodies with specificity for glucose-regulated protein 78 (GRP78), a multifunctional component of the unfolded protein response, are common in COPD patients and linked to comorbidities of this lung disease.,We hypothesized anti-GRP78 autoreactivity might also be a risk factor for atherosclerosis in COPD patients.,Carotid intima-medial thickness (cIMT) was measured in 144 current and former smokers by ultrasound.,Concentrations of circulating IgG autoantibodies against full-length GRP78, determined by ELISA, were greater among subjects with abnormally increased cIMT (p <, 0.01).,Plasma levels of autoantibodies against a singular GRP78 peptide segment, amino acids 246-260 (anti-GRP78aa 246-260), were even more highly correlated with cIMT, especially among males with greater than or equal to moderate COPD (rs = 0.62, p = 0.001).,Anti-GRP78aa 246-260 concentrations were independent of CRP, IL-6, and TNF-α levels.,GRP78 autoantigen expression was upregulated among human aortic endothelial cells (HAECs) stressed by incubation with tunicamycin (an unfolded protein response inducer) or exposure to culture media flow disturbances.,Autoantibodies against GRP78aa 246-260, isolated from patient plasma by immunoprecipitation, induced HAEC production of proatherosclerotic mediators, including IL-8.,In conclusion, anti-GRP78 autoantibodies are highly associated with carotid atherosclerosis in COPD patients and exert atherogenic effects on HAECs.,These data implicate Ag-specific autoimmunity in the pathogenesis of atherosclerosis among COPD patients and raise possibilities that directed autoantibody reduction might ameliorate vascular disease in this high-risk population. | 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 |
Chronic obstructive pulmonary disease (COPD) is set to become the third most frequent cause of death and also the third largest cause of global morbidity by 2020.,In China, where the population is aging rapidly, COPD has become one of the leading causes of disability and a large economic burden.,An epidemiological assessment of the COPD in China is required, with a focus on the number of cases living with disease, main determinants of the disease and time trends.,We systematically searched large Chinese bibliographic databases and English databases to identify spirometry-based epidemiological studies of the prevalence of COPD in China diagnosed according to GOLD criteria.,We estimated age- and gender-specific prevalence of COPD using a multilevel mixed-effect logistic regression.,We also presented the time trends of COPD between 1990 and 2010 by age, gender and setting (urban vs rural).,In 1990, the prevalence of COPD ranged from 0.49% (95% CI = 0.29-0.85) in <20 years group to 20.95% (95% CI = 14.04-27.04) in> = 80 years group, and the crude prevalence for China was 2.70% (95% CI = 1.86-3.51).,In 2010, the prevalence in <20 years was 0.55% (95% CI = 0.37-1.04) and in> = 80 years was 22.89% (95% CI = 18.13-28.96), with the crude prevalence for China of 3.84% (95% CI = 3.30-4.77).,The COPD prevalence in males was about two-fold higher than in females, and it increased with increasing age.,Between 1990-2010, the total number of Chinese people living with COPD increased by 66.73%, from 30.90 million (95% CI = 21.28-40.02) in 1990 to 51.52 million (95% CI = 44.26-63.93) in 2010.,This increase was most striking in middle age, and greater in females than in males from 30 years up to 64 years.,Our estimates, which used an independent approach to acquiring data and development of analytical methods, and were based on a more complete data set, are remarkably similar to those produced recently by the GBD 2013 collaboration, differing by only about 5% in the estimated number of COPD cases in 1990 and by 1% in 2010.,COPD is a highly prevalent disease in China and its importance is growing steadily.,The number of people living with COPD has increased substantially between 1990 and 2010.,COPD is more frequent in males and in rural areas.,Optimised primary and secondary prevention and treatment is urgently needed to counter this growing trend.,Improved epidemiological studies will be required to assist development of more effective strategies of prevention and treatment of COPD in China in the next decade and beyond. | Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | 1 |
As lung function declines rapidly in the early stages of chronic obstructive pulmonary disease (COPD), the effects of bronchodilators in patients with moderate disease and those who have not previously received maintenance therapy are of interest.,OTEMTO® 1 and 2 were two replicate, 12-week, Phase III studies investigating the benefit of tiotropium + olodaterol on lung function and quality of life in patients with moderate to severe disease.,Post hoc analyses were performed to assess the benefits for patients according to disease severity and treatment history.,Four subgroup analyses were performed: Global initiative for chronic Obstructive Lung Disease (GOLD) 2/3, GOLD A/B/C/D, treatment naive/not treatment naive and receiving inhaled corticosteroids (ICS) at baseline/not receiving ICS at baseline.,Primary end points were change in forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h response, change in trough FEV1 and St George’s Respiratory Questionnaire (SGRQ) total score.,Transition Dyspnoea Index (TDI) focal score was a secondary end point, and SGRQ and TDI responder analyses were further end points; all were assessed at 12 weeks.,In all subgroups, patients receiving tiotropium + olodaterol responded better overall than those receiving tiotropium monotherapy.,Improvements with tiotropium + olodaterol over placebo or tiotropium monotherapy were noted across GOLD 2/3 and GOLD A/B/C/D; however, improvements in SGRQ total score were most evident in the GOLD B subgroup.,Moreover, lung-function outcomes were generally greater in those patients who had been receiving previous long-acting bronchodilator and/or ICS maintenance treatment.,These data suggest that tiotropium + olodaterol should be considered as a treatment option in patients with moderate COPD who are initiating maintenance therapy, as well as those with more severe disease.,ClinicalTrials.gov: NCT01964352 and NCT02006732.,The online version of this article (doi:10.1186/s12931-016-0387-7) contains supplementary material, which is available to authorized users. | The objective of this study was to estimate the relative efficacy and safety of fixed-dose combination aclidinium/formoterol 400/12 μg twice daily compared to tiotropium 18 μg once daily in adult patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).,A systematic literature review performed in March 2014, using a predefined search strategy in MEDLINE, EMBASE and Cochrane Library, identified 17 randomized placebo-controlled trials, (tiotropium n = 15; aclidinium/formoterol n = 2).,Outcomes of interest were: bronchodilation (peak and trough forced expiratory volume in 1 s (FEV1)), COPD symptoms [Transition Dyspnea Index (TDI) focal score and % of responders (>1 unit improvement)] and Health Related Quality of Life (HRQoL) [St.,George’s Respiratory Questionnaire (SGRQ) total score and % responders (>4 unit improvement)], % of patients with ≥1 exacerbations, adverse events (AE), serious adverse events (SAE), hospitalization and mortality, all at 24 weeks.,In the absence of head-to-head trials between aclidinium/formoterol and tiotropium, a Bayesian indirect treatment comparison (ITC) was used with placebo as common control.,Regarding bronchodilation, aclidinium/formoterol was found to be more efficacious than tiotropium at peak FEV1, with mean difference in change from baseline (DCFB) 143 mL [95% credible interval (CrI): 112, 174] and at trough FEV1 [DCFB 26 mL (95% CrI −2, 55)].,Aclidinium/formoterol is expected to be more efficacious than tiotropium in improving dyspnea symptoms measured by TDI [DCFB 0.54 points (95% CrI 0.09, 0.99); odds ratio (OR) of responders 1.51 (95% CrI 1.11, 2.06)].,SGRQ results are comparable for aclidinium/formoterol versus tiotropium [DCFB −0.52 (95% CrI −2.21, 1.17); OR of responders 1.16 (95% CrI 0.47, 2.87)].,The ITC results suggest similar safety profiles regarding AEs, SAEs and hospitalization.,Based on the ITC, aclidinium/formoterol is expected to be more efficacious than tiotropium in terms of lung function and symptom control while providing comparable HRQoL results and safety profile.,AstraZeneca.,The online version of this article (doi:10.1007/s12325-016-0299-4) contains supplementary material, which is available to authorized users. | 1 |
The molecular and clinical features of a complex disease can be influenced by other diseases affecting the same individual.,Understanding disease-disease interactions is therefore crucial for revealing shared molecular mechanisms among diseases and designing effective treatments.,Here we introduce Flow Centrality (FC), a network-based approach to identify the genes mediating the interaction between two diseases in a protein-protein interaction network.,We focus on asthma and COPD, two chronic respiratory diseases that have been long hypothesized to share common genetic determinants and mechanisms.,We show that FC highlights potential mediator genes between the two diseases, and observe similar outcomes when applying FC to 66 additional pairs of related diseases.,Further, we perform in vitro perturbation experiments on a widely replicated asthma gene, GSDMB, showing that FC identifies candidate mediators of the interactions between GSDMB and COPD-associated genes.,Our results indicate that FC predicts promising gene candidates for further study of disease-disease interactions.,Complex diseases often share genetic determinants and symptoms, but the mechanistic basis of disease interactions remains elusive.,Here, the authors propose a network topological measure to identify proteins linking complex diseases in the interactome, and identify mediators between COPD and asthma. | Exacerbations of chronic obstructive pulmonary disease (COPD), characterized by acute deterioration in symptoms, may be due to bacterial or viral infections, environmental exposures, or unknown factors.,Exacerbation frequency may be a stable trait in COPD patients, which could imply genetic susceptibility.,Observing the genes, networks, and pathways that are up- and down-regulated in COPD patients with differing susceptibility to exacerbations will help to elucidate the molecular signature and pathogenesis of COPD exacerbations.,Gene expression array and plasma biomarker data were obtained using whole-blood samples from subjects enrolled in the Treatment of Emphysema With a Gamma-Selective Retinoid Agonist (TESRA) study.,Linear regression, weighted gene co-expression network analysis (WGCNA), and pathway analysis were used to identify signatures and network sub-modules associated with the number of exacerbations within the previous year; other COPD-related phenotypes were also investigated.,Individual genes were not found to be significantly associated with the number of exacerbations.,However using network methods, a statistically significant gene module was identified, along with other modules showing moderate association.,A diverse signature was observed across these modules using pathway analysis, marked by differences in B cell and NK cell activity, as well as cellular markers of viral infection.,Within two modules, gene set enrichment analysis recapitulated the molecular signatures of two gene expression experiments; one involving sputum from asthma exacerbations and another involving viral lung infections.,The plasma biomarker myeloperoxidase (MPO) was associated with the number of recent exacerbations.,A distinct signature of COPD exacerbations may be observed in peripheral blood months following the acute illness.,While not predictive in this cross-sectional analysis, these results will be useful in uncovering the molecular pathogenesis of COPD exacerbations.,The online version of this article (doi:10.1186/s12920-014-0072-y) contains supplementary material, which is available to authorized users. | 1 |
Here, we characterize a subset of ILC3s that express Neuropilin1 (NRP1) and are present in lymphoid tissues, but not in the peripheral blood or skin.,NRP1+ group 3 innate lymphoid cells (ILC3s) display in vitro lymphoid tissue inducer (LTi) activity.,In agreement with this, NRP1+ ILC3s are mainly located in proximity to high endothelial venules (HEVs) and express cell surface molecules involved in lymphocyte migration in secondary lymphoid tissues via HEVs.,NRP1 was also expressed on mouse fetal LTi cells, indicating that NRP1 is a conserved marker for LTi cells.,Human NRP1+ ILC3s are primed cells because they express CD45RO and produce higher amounts of cytokines than NRP1− cells, which express CD45RA.,The NRP1 ligand vascular endothelial growth factor A (VEGF-A) served as a chemotactic factor for NRP1+ ILC3s.,NRP1+ ILC3s are present in lung tissues from smokers and patients with chronic obstructive pulmonary disease, suggesting a role in angiogenesis and/or the initiation of ectopic pulmonary lymphoid aggregates.,•NRP1+ ILC3s are present in lymphoid tissues, but not in the peripheral blood or skin•NRP1+ ILC3s express CD45RO and produce higher amounts of cytokines than NRP1− ILC3s•NRP1 is a marker for human ILC3s with LTi phenotype and in vitro LTi activity•NRP1+ ILC3s are present in lung tissues from smokers and COPD patients,NRP1+ ILC3s are present in lymphoid tissues, but not in the peripheral blood or skin,NRP1+ ILC3s express CD45RO and produce higher amounts of cytokines than NRP1− ILC3s,NRP1 is a marker for human ILC3s with LTi phenotype and in vitro LTi activity,NRP1+ ILC3s are present in lung tissues from smokers and COPD patients,Shikhagaie et al. find that NRP1 expressing human ILC3s are LTi-like cells, which are present in fetal tissues and adult lymphoid tissues, but not in peripheral blood or skin.,NRP1+ ILC3s cells are primed and migrate in response to VEGF-A.,In addition, their presence in the lungs of smokers and COPD patients provides insight into the formation of ectopic lymphoid aggregates. | Chronic Obstructive Pulmonary Disease (COPD) is a progressive airway disease characterised by neutrophilic airway inflammation or bronchitis.,Neutrophilic bronchitis is associated with both bacterial colonisation and lung function decline and is common in exacerbations of COPD.,Despite current available therapies to control inflammation, neutrophilic bronchitis remains common.,This study tested the hypothesis that azithromycin treatment, as an add-on to standard medication, would significantly reduce airway neutrophil and neutrophils chemokine (CXCL8) levels, as well as bacterial load.,We conducted a randomised, double-blind, placebo-controlled study in COPD participants with stable neutrophilic bronchitis.,Eligible participants (n = 30) were randomised to azithromycin 250 mg daily or placebo for 12 weeks in addition to their standard respiratory medications.,Sputum was induced at screening, randomisation and monthly for a 12 week treatment period and processed for differential cell counts, CXCL8 and neutrophil elastase assessment.,Quantitative bacteriology was assessed in sputum samples at randomisation and the end of treatment visit.,Severe exacerbations where symptoms increased requiring unscheduled treatment were recorded during the 12 week treatment period and for 14 weeks following treatment.,A sub-group of participants underwent chest computed tomography scans (n = 15).,Nine participants with neutrophilic bronchitis had a potentially pathogenic bacteria isolated and the median total bacterial load of all participants was 5.22×107 cfu/mL.,Azithromycin treatment resulted in a non-significant reduction in sputum neutrophil proportion, CXCL8 levels and bacterial load.,The mean severe exacerbation rate was 0.33 per person per 26 weeks in the azithromycin group compared to 0.93 exacerbations per person in the placebo group (incidence rate ratio (95%CI): 0.37 (0.11,1.21), p = 0.062).,For participants who underwent chest CT scans, no alterations were observed.,In stable COPD with neutrophilic bronchitis, add-on azithromycin therapy showed a trend to reduced severe exacerbations sputum neutrophils, CXCL8 levels and bacterial load.,Future studies with a larger sample size are warranted.,Australian New Zealand Clinical Trials Registry ACTRN12609000259246 | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is a common disease with significant health and economic consequences.,This study assesses the burden of COPD in the general population, and the influence of exacerbations (E-COPD) on disease progression and costs.,This is a secondary data analysis of healthcare administrative databases of the region of Lombardy, in northern Italy.,The study included ≥ 40 year-old patients hospitalized for a severe E-COPD (index event) during 2006.,Patients were classified in relation to the number and type of E-COPD experienced in a three-year pre-index period.,Subjects were followed up until December 31st, 2009, collecting data on healthcare resource use and vital status.,15857 patients were enrolled -9911 males, mean age: 76 years (SD 10).,Over a mean follow-up time of 2.4 years (1.36), 81% of patients had at least one E-COPD with an annual rate of 3.2 exacerbations per person-year and an all-cause mortality of 47%.,A history of exacerbation influenced the occurrence of new E-COPD and mortality after discharge for an E-COPD.,On average, the healthcare system spent 6725€ per year per person (95%CI 6590-6863).,Occurrence and type of exacerbations drove the direct healthcare cost.,Less than one quarter of patients presented claims for pulmonary function tests.,COPD imposes a substantial burden on healthcare systems, mainly attributable to the type and occurrence of E-COPD, or in other words, to the exacerbator phenotypes.,A more tailored approach to the management of COPD patients is required. | A combination of inhaled corticosteroid and long-acting beta2 agonist (ICS/LABA) is used frequently to treat chronic obstructive pulmonary disease (COPD) patients.,The aim of the study was to determine whether prescribing ICS/LABA to COPD patients in primary care in 2009/10 was within the GOLD guidelines and whether and to what degree patient characteristics were associated with prescription of these drugs by GPs.,This was a cross-sectional study in seven Norwegian GP practices.,Patients registered with a diagnosis of asthma or COPD in the previous five years were included.,Among the 376 patients included in the analysis, 149 patients had COPD, defined as a post-bronchodilator FEV1/FVC <0.7 and 55.6% of these patients were treated with ICS/LABA.,The rate of prescribing was significantly higher in the COPD patients also diagnosed with asthma than in those with COPD as the only diagnosis, 66.7%, and 39.0%, respectively (P = 0.001).,The prescribing rate in the latter subgroup would have been 18.6% if the 2007 GOLD guidelines had been followed.,One or more exacerbations in the previous year was the strongest predictor of ICS/LABA prescribing in the COPD patients who were not registered with a concomitant diagnosis of asthma (OR 3.2, 95% CI 1.0-10.0) but this association was limited to the patients with severe disease (FEV1% predicted <50) (OR 13.5, 95% CI 1.8-101.1).,Cardiovascular disease was associated with decreased ICS/LABA prescribing (OR 0.4, 95% CI 0.2-0.8) in the COPD group.,A Kappa coefficient of 0.32 was found between the actual prescribing rate and that recommended in the 2007 GOLD guidelines.,Overprescribing of ICS/LABA for the COPD patients was shown.,Previous exacerbation was a strong predictor of ICS/LABA prescribing only in patients with severe COPD.,Because of the low emphasis on previous exacerbation when prescribing for COPD patients with mild to moderate disease, the actual prescribing rate agreed more closely with the GOLD guidelines from 2007 than with those published in 2011.,Cardiovascular disease was associated with decreased prescribing, indicating that GPs adjust the treatment in cases with multimorbidity. | 1 |
The Global Initiative defines COPD for chronic obstructive lung disease as an entirely preventable and treatable disease characterized by sputum production, bacterial colonisation, neutrophilic bronchial airway inflammation and poor health status.,The World Health Organization (WHO) estimates that COPD will become the fourth-most common cause of death worldwide, just behind ischemic heart disease, cerebrovascular disease and HIV/AIDS, by 2030.,The aim of this study was to determine the main structure feature of sputum potentially pathogenic microorganisms in subjects with COPD during the clinical stable state.,We employed a molecular genetics-based investigation of the bacteria community, including DNA isolation, PCR amplification and DGGE profiling.,PCR-denaturing gradient gel electrophoresis (DGGE) with universal primers targeting the V3 region of the 16S rRNA gene was employed to characterize the overall COPD patient sputum microbiota composition, and some excised gel bands were cloned for sequencing.,Real-time PCR was further utilized to quantitatively analyze the subpopulation of microbiota using group-specific primers targeting Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa.,The DGGE profiles of two groups displayed significant differences between COPD and healthy groups (P < 0.05).,Real-time PCR revealed significant increases of Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa (P < 0.05) in the COPD group compared with the healthy group.,This study revealed strong relationship between alterations of sputum microbiota and COPD.,By determining the content of several types of bacteria, we can provide evidence to aid in the diagnosis and treatment of COPD. | Many epidemiological studies have found a positive association between periodontal disease (PD) and risk of chronic obstructive pulmonary disease (COPD), but this association is varied and even contradictory among studies.,We performed a meta-analysis to ascertain the relationship between PD and COPD.,PubMed and Embase database were searched up to January 10, 2012, for relevant observational studies on the association between PD and risk of COPD.,Data from the studies selected were extracted and analyzed independently by two authors.,The meta-analysis was performed using the Comprehensive Meta-Analysis software.,Fourteen observational studies (one nested case-control, eight case-control, and five cross-sectional) involving 3,988 COPD patients were yielded.,Based on random-effects meta-analysis, a significant association between PD and COPD was identified (odds ratio = 2.08, 95% confidence interval = 1.48-2.91; P<0.001), with sensitivity analysis showing that the result was robust.,Subgroups analyses according to study design, ethnicity, assessment of PD/COPD, and adjusted/unadjusted odds ratios also revealed a significant association.,Publication bias was detected.,Based on current evidence, PD is a significant and independent risk factor of COPD.,However, whether a causal relationships exists remains unclear.,Morever, we suggest performing randomized controlled trails to explore whether periodontal interventions are beneficial in regulating COPD pathogenesis and progression. | 1 |
Antibiotic overuse in respiratory illness is common and is associated with drug resistance and hospital-acquired infection.,Biomarkers that can identify bacterial infections may reduce antibiotic prescription.,We aimed to compare the usefulness of the biomarkers procalcitonin and C-reactive protein (CRP) in patients with pneumonia or exacerbations of asthma or COPD.,Patients with a diagnosis of community-acquired pneumonia or exacerbation of asthma or COPD were recruited during the winter months of 2006 to 2008.,Demographics, clinical data, and blood samples were collected.,Procalcitonin and CRP concentrations were measured from available sera.,Sixty-two patients with pneumonia, 96 with asthma, and 161 with COPD were studied.,Serum procalcitonin and CRP concentrations were strongly correlated (Spearman rank correlation coefficient [rs] = 0.56, P < .001).,Patients with pneumonia had increased procalcitonin and CRP levels (median [interquartile range] 1.27 ng/mL [2.36], 191 mg/L [159]) compared with those with asthma (0.03 ng/mL [0.04], 9 mg/L [21]) and COPD (0.05 ng/mL [0.06], 16 mg/L [34]).,The area under the receiver operating characteristic curve (95% CI) for distinguishing between patients with pneumonia (antibiotics required) and exacerbations of asthma (antibiotics not required), for procalcitonin and CRP was 0.93 (0.88-0.98) and 0.96 (0.93-1.00).,A CRP value > 48 mg/L had a sensitivity of 91% (95% CI, 80%-97%) and specificity of 93% (95% CI, 86%-98%) for identifying patients with pneumonia.,Procalcitonin and CRP levels can both independently distinguish pneumonia from exacerbations of asthma.,CRP levels could be used to guide antibiotic therapy and reduce antibiotic overuse in hospitalized patients with acute respiratory illness. | The identification of biological markers in order to assess different aspects of COPD is an area of growing interest.,The objective of this study was to investigate whether levels of procalcitonin (PCT), C-reactive protein (CRP), and neopterin in COPD patients could be useful in identifying the etiological origin of the exacerbation and assessing its prognosis.,We included 318 consecutive COPD patients: 46 in a stable phase, 217 undergoing an exacerbation, and 55 with pneumonia.,A serum sample was collected from each patient at the time of being included in the study.,A second sample was also collected 1 month later from 23 patients in the exacerbation group.,We compared the characteristics, biomarker levels, microbiological findings, and prognosis in each patient group.,PCT and CRP were measured using an immunofluorescence assay.,Neopterin levels were measured using a competitive immunoassay.,PCT and CRP showed significant differences among the three patient groups, being higher in patients with pneumonia, followed by patients with exacerbation (P < 0.0001).,For the 23 patients with paired samples, PCT and CRP levels decreased 1 month after the exacerbation episode, while neopterin increased.,Neopterin showed significantly lower levels in exacerbations with isolation of pathogenic bacteria, but no differences were found for PCT and CRP.,No significant differences were found when comparing biomarker levels according to the Gram result: PCT (P = 0.191), CRP (P = 0.080), and neopterin (P = 0.109).,However, median values of PCT and CRP were high for Streptococcus pneumoniae, Staphylococcus aureus, and enterobacteria.,All biomarkers were higher in patients who died within 1 month after the sample collection than in patients who died later on.,According to our results, biomarker levels vary depending on the clinical status.,However, the identification of the etiology of infectious exacerbation by means of circulating biomarkers is encouraging, but its main disadvantage is the absence of a microbiological gold standard, to definitively demonstrate their value.,High biomarker levels during an exacerbation episode correlate with the short-term prognosis, and therefore their measurement can be useful for COPD management. | 1 |
Although it is well accepted that air pollution exposure exacerbates preexisting airway disease, it has not been firmly established that long-term pollution exposure increases the risk of new-onset asthma or chronic obstruction pulmonary disease (COPD).,This Workshop brought together experts on mechanistic, epidemiological, and clinical aspects of airway disease to review current knowledge regarding whether air pollution is a causal factor in the development of asthma and/or COPD.,Speakers presented recent evidence in their respective areas of expertise related to air pollution and new airway disease incidence, followed by interactive discussions.,A writing committee summarized their collective findings.,The Epidemiology Group found that long-term exposure to air pollution, especially metrics of traffic-related air pollution such as nitrogen dioxide and black carbon, is associated with onset of childhood asthma.,However, the evidence for a causal role in adult-onset asthma or COPD remains insufficient.,The Mechanistic Group concluded that air pollution exposure can cause airway remodeling, which can lead to asthma or COPD, as well as asthma-like phenotypes that worsen with long-term exposure to air pollution, especially fine particulate matter and ozone.,The Clinical Group concluded that air pollution is a plausible contributor to the onset of both asthma and COPD.,Available evidence indicates that long-term exposure to air pollution is a cause of childhood asthma, but the evidence for a similar determination for adult asthma or COPD remains insufficient.,Further research is needed to elucidate the exact biological mechanism underlying incident childhood asthma, and the specific air pollutant that causes it. | Biomass smoke is the leading cause of COPD in developing countries such as Turkey.,In rural areas of Turkey, females are more exposed to biomass smoke because of traditional lifestyles.,The aim of this study was to determine the adverse effects of biomass smoke on pulmonary functions and define the relationship between duration in years and an index (cumulative exposure index) with altered pulmonary function test results.,A total of 115 females who lived in the village of Kağizman (a borough of Kars located in the eastern part of Turkey) and were exposed to biomass smoke were included in the study.,The control group was generated with 73 individuals living in the same area who were never exposed to biomass smoke.,Twenty-seven (23.8%) females in the study group and four (5.5%) in the control group had small airway disease (P=0.038).,Twenty-two (19.1%) females in the study group and ten (13.7%) in the control group had obstruction (P=0.223).,Twenty (17.3%) females in the study group who were exposed to biomass smoke had restriction compared with ten (13%) in the control group (P=0.189).,The duration needed for the existence of small airway disease was 16 years, for obstructive airway disease was 17 years, and for restrictive airway disease was 17 years.,The intensity of biomass smoke was defined in terms of cumulative exposure index; it was calculated by multiplying hours per day, weeks per month, and total years of smoke exposure and dividing the result by three.,Exposure to biomass smoke is a serious public health problem, especially in rural areas of developing countries, because of its negative effects on pulmonary functions.,As the duration and the intensity of exposure increase, the probability of having altered pulmonary function test results is higher. | 1 |
Factors associated with reduced daily physical activity (DPA) in patients with COPD are still controversial.,Physical inactivity in COPD increases risk of cardiovascular disease, frequent exacerbations, reduced health status, and increased symptoms.,We hypothesised that reduced DPA in patients with COPD is independent of traditional risk factors including age and spirometry.,In this cross-sectional study, DPA (over 7 days) was assessed on 88 community stable patients with COPD and 40 controls free from cardiorespiratory disease.,Spirometry, body composition, number of exacerbations, handgrip strength (HGS), modified Medical Research Council (mMRC), arterial stiffness, 6-min walking distance (6MWD) and BODE index were also determined.,Frequent exacerbation was defined as ≥2 and non-frequent exacerbation < 2.,Patients with COPD had reduced DPA and exercise capacity compared with controls similar in age, BMI and gender, p < 0.001.,Frequent exacerbators had less DPA than infrequent exacerbators and both less than controls, p < 0.001.,Patients with higher BODE index were less active than those with lower index.,Time spent on moderate activity was related to cardiovascular risk factors including arterial stiffness.,The DPA in patients was independent of age, gender, spirometry, body composition and HGS, p > 0.05.,The level of breathlessness was superior to lung function in predicting the level of DPA.,The level of DPA in COPD was independent of traditional risk factors.,Breathlessness score is a better predictor of the DPA than lung function and handgrip strength. | Recent reports indicate that over the next decade rates of chronic obstructive pulmonary disease (COPD) in women will exceed those in men in the western world, though in most jurisdictions, women continue to smoke less compared with men.,Whether female adult smokers are biologically more susceptible to COPD is unknown.,This study reviewed the available evidence to determine whether female adult smokers have a faster decline in forced expiratory volume in one second (FEV1) compared with male adult smokers and whether age modifies the relationship between cigarette smoke and lung function decline.,A systematic review and a meta-analysis was performed of population-based cohort studies that had a follow-up period of at least 3 years, measured FEV1 on at least two different time points, and presented FEV1 data stratified by gender and smoking status in adults.,Of the 646 potentially relevant articles, 11 studies met these criteria and were included in the analyses (N = 55 709 participants).,There was heterogeneity in gender-related results across the studies.,However, on average current smokers had a faster annual decline rate in FEV1% predicted compared with never and former smokers.,Female current smokers had with increasing age a significantly faster annual decline in FEV1% predicted than male current smokers (linear regression analysis, R2 = 0.56; p = 0.008).,Age did not materially affect the rate of decline in FEV1% predicted in male and female former and never smokers (p = 0.775 and p = 0.326, respectively).,As female smokers age, they appear to experience an accelerated decline in FEV1% predicted compared with male smokers.,Future research powered specifically on gender-related changes in lung function is needed to confirm these early findings. | 1 |
Health-related quality of life (HRQoL) should be seen as a tool that provides an overall view of the general clinical condition of a COPD patient.,The aims of this study were to identify variables associated with HRQoL and whether they continue to have an influence in the medium term, during follow-up.,Overall, 543 patients with COPD were included in this prospective observational longitudinal study.,At all four visits during a 5-year follow-up, the patients completed the Saint George’s Respiratory Questionnaire (SGRQ), pulmonary function tests, the 6-min walk test (6MWT), and a physical activity (PA) questionnaire, among others measurements.,Data on hospitalization for COPD exacerbations and comorbidities were retrieved from the personal electronic clinical record of each patient at every visit.,The best fit to the data of the cohort was obtained with a beta-binomial distribution.,The following variables were related over time to SGRQ components: age, inhaled medication, smoking habit, forced expiratory volume in one second, handgrip strength, 6MWT distance, body mass index, residual volume, diffusing capacity of the lung for carbon monoxide, PA (depending on level, 13 to 35% better HRQoL, in activity and impacts components), and hospitalizations (5 to 45% poorer HRQoL, depending on the component).,Among COPD patients, HRQoL was associated with the same variables throughout the study period (5-year follow-up), and the variables with the strongest influence were PA and hospitalizations. | To investigate the association of the GOLD ABCD groups classification with costs and health-related quality of life (HR-QoL) and to compare this with the GOLD 1234 grades classification that was primarily based on lung function only.,In a cross-sectional study, we selected patients diagnosed with chronic obstructive pulmonary disease (COPD) from electronic medical records of general practices.,Multi-level analysis was used with costs (medication, primary care, healthcare, societal), disease-specific and generic HR-QoL as independent variables.,Either the new or the old GOLD stages were included in the analysis together with several covariates (age, gender, living situation, co-morbidity, self-efficacy, smoking, education, employment).,611 patients from 28 general practices were categorised as GOLD-A (n=333), GOLD-B (n=110), GOLD-C (n=80) and GOLD-D (n=88).,Patients in the GOLD-B and GOLD-D groups had the highest prevalence of co-morbidities and the lowest level of physical activity, self-efficacy, and employment.,The models with GOLD ABCD groups were more strongly related to and explained more variance in costs and in disease-specific and generic HR-QoL than the models with GOLD 1234 grades.,The mean Clinical COPD Questionnaire score worsened significantly, with scores 1.04 (GOLD-B), 0.4 (GOLD-C) and 1.21 (GOLD-D) worse than for patients in GOLD-A.,Healthcare costs per patient were significantly higher in GOLD-B (72%), GOLD-C (74%) and GOLD-D (131%) patients than in GOLD-A patients.,The GOLD ABCD groups classification is more closely associated with costs and HR-QoL than the GOLD 1234 grades classification.,Furthermore, patients with GOLD-C had a better HR-QoL than those with GOLD-B but the costs of the two groups did not differ. | 1 |
Purpose: Seasons and weather conditions might influence participation in physical activity and contribute to differences between countries.,This study aimed at investigating whether there were differences in physical activity levels between Norwegian, Danish and Australian people with chronic obstructive pulmonary disease (COPD), and establishing if any variations in physical activity were attributable to seasons.,Patients and methods: A cross-sectional study where study subjects were people with COPD who participated in two separate clinical trials: the iTrain study (Norway, Denmark, and Australia) and the HomeBase study (Australia).,Physical activity was objectively assessed with an activity monitor; variables were total energy expenditure, number of daily steps, awake sedentary time, light, and moderate-to-vigorous intensity physical activity.,Differences in physical activity between countries and seasons were compared, with adjustment for disease severity.,Results: In total, 168 participants were included from Norway (N=38), Denmark (N=36) and Australia (N=94).,After controlling for disease severity, time spent in awake sedentary time was greater in Danish participants compared to the other countries (median 784 minutes/day [660-952] vs 775 minutes/day [626-877] for Norwegians vs 703 minutes/day [613-802] for Australians, P=0.013), whilst time spent in moderate to vigorous physical activity was lower (median 21 minutes/day [4-73] vs 30 minutes/day [7-93] for Norwegians vs 48 minutes/day [19-98] for Australians, P=0.024).,Participants walked more during summer (median 3502 [1253-5407] steps/day) than in spring (median 2698 [1613-5207] steps/day), winter (median 2373 [1145-4206] steps/day) and autumn (median 1603 [738-4040] steps/day), regardless of geography.,The median difference between summer and other seasons exceeded the minimal clinically important difference of 600 steps/day.,However, the differences were not statistically significant (P=0.101).,Conclusion: After controlling for disease severity, Danish participants spent more time in an awake sedentary state and less time in moderate to vigorous physical activity than their counterparts in Norway and Australia.,People with COPD increased their physical activity in summer compared to other seasons.,Weather conditions and seasonal variations may influence outcomes in clinical trials and health registries measuring physical activity over time, irrespective of the interventions delivered, and should be taken into account when interpreting results. | Reduced physical activity is an important feature of Chronic Obstructive Pulmonary Disease (COPD).,Various activity monitors are available but their validity is poorly established.,The aim was to evaluate the validity of six monitors in patients with COPD.,We hypothesized triaxial monitors to be more valid compared to uniaxial monitors.,Thirty-nine patients (age 68±7years, FEV1 54±18%predicted) performed a one-hour standardized activity protocol.,Patients wore 6 monitors (Kenz Lifecorder (Kenz), Actiwatch, RT3, Actigraph GT3X (Actigraph), Dynaport MiniMod (MiniMod), and SenseWear Armband (SenseWear)) as well as a portable metabolic system (Oxycon Mobile).,Validity was evaluated by correlation analysis between indirect calorimetry (VO2) and the monitor outputs: Metabolic Equivalent of Task [METs] (SenseWear, MiniMod), activity counts (Actiwatch), vector magnitude units (Actigraph, RT3) and arbitrary units (Kenz) over the whole protocol and slow versus fast walking.,Minute-by-minute correlations were highest for the MiniMod (r = 0.82), Actigraph (r = 0.79), SenseWear (r = 0.73) and RT3 (r = 0.73).,Over the whole protocol, the mean correlations were best for the SenseWear (r = 0.76), Kenz (r = 0.52), Actigraph (r = 0.49) and MiniMod (r = 0.45).,The MiniMod (r = 0.94) and Actigraph (r = 0.88) performed better in detecting different walking speeds.,The Dynaport MiniMod, Actigraph GT3X and SenseWear Armband (all triaxial monitors) are the most valid monitors during standardized physical activities.,The Dynaport MiniMod and Actigraph GT3X discriminate best between different walking speeds. | 1 |
Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity and mortality in the United States.,Exacerbations- acute worsening of COPD symptoms-can be mild to severe in nature.,Increased healthcare resource use is common among patients with frequent exacerbations, and exacerbations are a major cause of the high 30-day hospital readmission rates associated with COPD.,This review provides a concise overview of the literature regarding the impact of COPD exacerbations on both the patient and the healthcare system, the recommendations for pharmacologic management of COPD, and the strategies employed to improve patient care and reduce hospitalizations and readmissions.,COPD exacerbations significantly impact patients’ health-related quality of life and disease progression; healthcare costs associated with severe exacerbation-related hospitalization range from $7,000 to $39,200.,Timely and appropriate maintenance pharmacotherapy, particularly dual bronchodilators for maximizing bronchodilation, can significantly reduce exacerbations in patients with COPD.,Additionally, multidisciplinary disease-management programs include pulmonary rehabilitation, follow-up appointments, aftercare, inhaler training, and patient education that can reduce hospitalizations and readmissions for patients with COPD.,Maximizing bronchodilation by the appropriate use of maintenance therapy, together with multidisciplinary disease-management and patient education programs, offers opportunities to reduce exacerbations, hospitalizations, and readmissions for patients with COPD. | Asthma and chronic obstructive pulmonary disease (COPD) cause significant morbidity and mortality worldwide, primarily through exacerbations.,Exacerbations are often treated with antibiotics but their optimal course duration is uncertain.,Reducing antibiotic duration may influence antimicrobial resistance but risks treatment failure.,The objective of this article is to review published literature to investigate whether shorter antibiotic therapy duration affects clinical outcomes in the treatment of asthma and COPD exacerbations.,We systematically searched electronic databases (MEDLINE, EMBASE, CINAHL, World Health Organisation International Clinical Trial Registry Platform, the Cochrane library, and ISRCTN) with no language, location, or time restrictions.,We retrieved observational and controlled trials comparing different durations of the same oral antibiotic therapy in the treatment of acute exacerbations of asthma or COPD in adults.,We found no applicable studies for asthma exacerbations.,We included 10 randomized, placebo-controlled trials for COPD patients, all from high-income countries.,The commonest studied antibiotic class was fluoroquinolones.,Antibiotic courses shorter than 6 days were associated with significantly fewer overall adverse events (risk ratio (RR): 0.84, 95% confidence interval (CI): 0.75-0.93, p = 0.001) when compared with those of 7 or more days.,There was no statistically significant difference for clinical success or bacteriological eradication in sputum (RR: 1.00, 95% CI: 0.88-1.13 and RR: 1.06, 95% CI: 0.79-1.44, respectively).,Shorter durations of antibiotics for COPD exacerbations do not seem to confer a higher risk of treatment failure but are associated with fewer adverse events.,This is in keeping with previous studies in community acquired pneumonia, but studies were heterogeneous and differed from usual clinical practice.,Further observational and prospective work is needed to explore the significance of antibiotic duration in the treatment of asthma and COPD exacerbations. | 1 |
Accessible interventions to train patients with chronic obstructive pulmonary disease (COPD) are needed.,We designed urban trails of different intensities (low, moderate and high) in different types of public spaces (boulevard, beach and park).,We aimed to validate the trails’ design by assessing the physiological response to unsupervised walking trails of: (1) different intensities in COPD patients, and (2) same intensity from different public spaces in healthy adults.,On different days and under standardized conditions, 10 COPD patients walked the three intensity trails designed in a boulevard space, and 10 healthy subjects walked the three intensity trails in three different spaces.,We measured physiological response and energy expenditure using a gas analyzer.,We compared outcomes across trails intensity and/or spaces using mixed-effects linear regression.,In COPD patients, physiological response and energy expenditure increased significantly according to the trails intensity: mean (SD) peak V˙O2 15.9 (3.5), 17.4 (4.7), and 17.7 (4.4) mL/min/kg (p-trend = 0.02), and MET-min 60 (23), 64 (26), 72 (31) (p-trend<0.01) in low, moderate and high intensity trails, respectively.,In healthy subjects there were no differences in physiological response to walking trails of the same intensity across different spaces.,We validated the trails design for the training of COPD patients by showing that the physiological response to and energy expenditure on unsupervised walking these trails increased according to the predefined trails’ intensity and did not change across trails of the same intensity in different public space.,Walkable public spaces allow the design of trails that could be used for the training of COPD patients in the community. | Reduced physical activity is an important feature of Chronic Obstructive Pulmonary Disease (COPD).,Various activity monitors are available but their validity is poorly established.,The aim was to evaluate the validity of six monitors in patients with COPD.,We hypothesized triaxial monitors to be more valid compared to uniaxial monitors.,Thirty-nine patients (age 68±7years, FEV1 54±18%predicted) performed a one-hour standardized activity protocol.,Patients wore 6 monitors (Kenz Lifecorder (Kenz), Actiwatch, RT3, Actigraph GT3X (Actigraph), Dynaport MiniMod (MiniMod), and SenseWear Armband (SenseWear)) as well as a portable metabolic system (Oxycon Mobile).,Validity was evaluated by correlation analysis between indirect calorimetry (VO2) and the monitor outputs: Metabolic Equivalent of Task [METs] (SenseWear, MiniMod), activity counts (Actiwatch), vector magnitude units (Actigraph, RT3) and arbitrary units (Kenz) over the whole protocol and slow versus fast walking.,Minute-by-minute correlations were highest for the MiniMod (r = 0.82), Actigraph (r = 0.79), SenseWear (r = 0.73) and RT3 (r = 0.73).,Over the whole protocol, the mean correlations were best for the SenseWear (r = 0.76), Kenz (r = 0.52), Actigraph (r = 0.49) and MiniMod (r = 0.45).,The MiniMod (r = 0.94) and Actigraph (r = 0.88) performed better in detecting different walking speeds.,The Dynaport MiniMod, Actigraph GT3X and SenseWear Armband (all triaxial monitors) are the most valid monitors during standardized physical activities.,The Dynaport MiniMod and Actigraph GT3X discriminate best between different walking speeds. | 1 |
Lung-function decline is one of the possible mechanisms leading to Chronic Obstructive Pulmonary Disease (COPD).,We analyzed data obtained from two population-based surveys of adults (n = 2026) conducted in the same individuals 5-9 years (y) after their baseline examination in three Latin-American cities.,Post BronchoDilator (postBD) FEV1 decline in mL/y, as %predicted/y (%P/y) and % of baseline/y (%B/y) was calculated and the influence of age, gender, BMI, baseline lung function, BD response, exacerbations rate evaluated using multivariate models.,Expressed in ml/y, the mean annual postBD FEV1 decline was 27 mL (0.22%P, 1.32%B) in patients with baseline COPD and 36 (0.14%P, 1.36%B) in those without.,Faster decline (in mL/y) was associated with higher baseline lung function, with significant response to bronchodilators, older age and smoking at baseline, also in women with chronic cough and phlegm, or ≥2 respiratory exacerbations in the previous year, and in men with asthma.,Lung function decline in a population-based cohort did not differ in obstructed and non-obstructed individuals, it was proportional to baseline FEV1, and was higher in smokers, elderly, and women with respiratory symptoms. | The landmark study of Fletcher and Peto on the natural history of tobacco smoke-related chronic airflow obstruction suggested that decline in the forced expiratory volume in the first second (FEV1) in chronic obstructive pulmonary disease (COPD) is slow at the beginning, becoming faster with more advanced disease.,The present authors reviewed spirometric data of COPD patients included in the placebo arms of recent clinical trials to assess the lung function decline of each stage, defined according to the severity of airflow obstruction as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,In large COPD populations the mean rate of FEV1 decline in GOLD stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year, respectively, and lower than 35 mL/year in GOLD stage IV.,Few data on FEV1 decline are available for GOLD stage I.,Hence, the loss of lung function, assessed as expiratory airflow reduction, seems more accelerated and therefore more relevant in the initial phases of COPD.,To have an impact on the natural history of COPD, it is logical to look at the effects of treatment in the earlier stages. | 1 |
To evaluate risk factors associated with exacerbation frequency in primary care.,Information on exacerbations of chronic obstructive pulmonary disease (COPD) has mainly been generated by secondary care-based clinical cohorts.,Retrospective observational cohort study.,Electronic medical records database (England and Wales).,58 589 patients with COPD aged ≥40 years with COPD diagnosis recorded between 1 April 2009 and 30 September 2012, and with at least 365 days of follow-up before and after the COPD diagnosis, were identified in the Clinical Practice Research Datalink.,Mean age: 69 years; 47% female; mean forced expiratory volume in 1s 60% predicted.,Data on moderate or severe exacerbation episodes defined by diagnosis and/or medication codes 12 months following cohort entry were retrieved, together with demographic and clinical characteristics.,Associations between patient characteristics and odds of having none versus one, none versus frequent (≥2) and one versus frequent exacerbations over 12 months follow-up were evaluated using multivariate logistic regression models.,During follow-up, 23% of patients had evidence of frequent moderate-to-severe COPD exacerbations (24% one; 53% none).,Independent predictors of increased odds of having exacerbations during the follow-up, either frequent episodes or one episode, included prior exacerbations, increasing dyspnoea score, increasing grade of airflow limitation, females and prior or current history of several comorbidities (eg, asthma, depression, anxiety, heart failure and cancer).,Primary care-managed patients with COPD at the highest risk of exacerbations can be identified by exploring medical history for the presence of prior exacerbations, greater COPD disease severity and co-occurrence of other medical conditions. | Exacerbations of chronic obstructive pulmonary disease (COPD) are sporadic, acute worsening of symptoms.,Identifying predictors of exacerbation frequency may facilitate medical interventions that reduce exacerbation frequency and severity.,The objective of this study was to determine predictors of exacerbation frequency and mortality.,A total of 227 COPD patients were enrolled in a prospective clinical study between January 2000 and December 2011.,Reported exacerbations were recorded for the year preceding enrollment and annually thereafter, and patients were grouped by median annual exacerbation frequency into those experiencing infrequent exacerbations (less than one exacerbation annually) and frequent exacerbations (one or more exacerbation annually).,Patients experiencing frequent exacerbations were further divided into those experiencing moderately frequent exacerbations (fewer than two exacerbations per year) and severely frequent exacerbations (two or more exacerbations per year).,The rate of clinical relapse and survival was recorded over a 10-year period.,The mean of follow-up time was 5.15 years per patient.,For patients experiencing infrequent, moderately frequent, and severely frequent exacerbations, median exacerbations in the year preceding enrollment were 0.0, 0.5, 1.0, respectively, and more frequent exacerbations correlated with lower baseline forced expiratory volume in one second (FEV1) (0.81 L, 0.75 L, and 0.66 L, respectively), higher comorbidity (70.7%, 75.0%, and 89.4%, respectively), and greater NPPV use during hospitalization (16.4%, 35.9% and 51.1%, respectively).,FEV1 declined and mortality increased with increasing exacerbation frequency.,Exacerbation frequency can be used to generate discreet patient subpopulations, supporting the hypothesis that multiple COPD phenotypes exist and can be used in patient risk stratification. | 1 |
To evaluate the impact of lung function, measured as forced expiratory volume in 1 second (FEV1) % predicted, on health care resource utilization and costs among patients with COPD in a real-world US managed-care population.,This observational retrospective cohort study utilized administrative claim data augmented with medical record data.,The study population consisted of patients with one or more medical claims for pre- and postbronchodilator spirometry during the intake period (July 1, 2012 to June 30, 2013).,The index date was the date of the earliest medical claim for pre- and postbronchodilator spirometry.,Spirometry results were abstracted from patients’ medical records.,Patients were divided into two groups (low FEV1% predicted [,50%] and high FEV1% predicted [≥50%]) based on the 2014 Global Initiative for Chronic Obstructive Lung Disease report.,Health care resource utilization and costs were based on the prevalence and number of discrete encounters during the 12-month postindex follow-up period.,Costs were adjusted to 2014 US dollars.,A total of 754 patients were included (n=297 low FEV1% predicted group, n=457 high FEV1% predicted group).,COPD exacerbations were more prevalent in the low FEV1% predicted group compared with the high group during the 12-month pre- (52.5% vs 39.6%) and postindex periods (49.8% vs 36.8%).,Mean (standard deviation) follow-up all-cause and COPD-related costs were $27,380 ($38,199) and $15,873 ($29,609) for patients in the low FEV1% predicted group, and $22,075 ($28,108) and $10,174 ($18,521) for patients in the high group.,In the multivariable analyses, patients in the low FEV1% predicted group were more likely to have COPD exacerbations and tended to have higher COPD-related costs when compared with patients in the high group.,Real-world data demonstrate that patients with COPD who have low FEV1% predicted levels use more COPD medications, have more COPD exacerbations, and incur higher COPD-related health care costs than those with high FEV1% predicted levels. | In this narrative review, we put self-management in the context of a 50-year history of research about how patients with COPD respond to their illness.,We review a definition of self-management, and emphasize that self-management should be combined with disease management and the chronic care model in order to be effective.,Reviewing the empirical status of self-management in COPD, we conclude that self-management is part and parcel of modern, patient-oriented biopsychosocial care.,In pulmonary rehabilitation programs, self-management is instrumental in improving patients’ functional status and quality of life.,We conclude by emphasizing how studying the way persons with COPD make sense of their illness helps in refining self-management, and thereby patient-reported outcomes in COPD. | 1 |
The objective of this study was to compare the cost-effectiveness of the fixed-dose combination (FDC) of tiotropium + olodaterol Respimat® FDC with tiotropium alone for patients with chronic obstructive pulmonary disease (COPD) in the Italian health care setting using a newly developed patient-level Markov model that reflects the current understanding of the disease.,While previously published models have largely been based around a cohort approach using a Markov structure and GOLD stage stratification, an individual-level Markov approach was selected for the new model.,Using patient-level data from the twin TOnado trials assessing Tiotropium + olodaterol Respimat® FDC versus tiotropium, outcomes were modelled based on the trough forced expiratory volume (tFEV1) of over 1000 patients in each treatment arm, tracked individually at trial visits through the 52-week trial period, and after the trial period it was assumed to decline at a constant rate based on disease stage.,Exacerbation risk was estimated based on a random-effects logistic regression analysis of exacerbations in UPLIFT.,Mortality by age and disease stage was estimated from an analysis of TIOSPIR trial data.,Cost of bronchodilators and other medications, routine management, and costs of treatment for moderate and severe exacerbations for the Italian setting were included.,A cost-effectiveness analysis was conducted over a 15-year time horizon from the perspective of the Italian National Health Service.,Aggregating total costs and quality-adjusted life years (QALYs) for each treatment cohort over 15 years and comparing tiotropium + olodaterol Respimat® FDC with tiotropium alone, resulted in mean incremental costs per patient of €1167 and an incremental cost-effectiveness ratio (ICER) of €7518 per additional QALY with tiotropium + olodaterol Respimat® FDC.,The lung function outcomes observed for tiotropium + olodaterol Respimat® FDC in TOnado drove the results in terms of slightly higher mean life-years (12.24 versus 12.07) exacerbation-free months (11.36 versus 11.32) per patient and slightly fewer moderate and severe exacerbations per patient-year (0.411 versus 0.415; 0.21 versus 0.24) versus tiotropium.,Probabilistic sensitivity analyses showed tiotropium + olodaterol Respimat® FDC to be the more cost-effective treatment in 95.2% and 98.4% of 500 simulations at thresholds of €20,000 and €30,000 per QALY respectively.,Tiotropium + olodaterol Respimat® FDC is a cost-effective bronchodilator in the maintenance treatment of COPD for the Italian health care system. | 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 interventions for chronic obstructive pulmonary disease (COPD) can improve quality of life, reduce hospital admissions, and improve symptoms.,However, many factors impede engagement for patients and practitioners.,Qualitative research, with its focus on subjective experience, can provide invaluable insights into such factors.,Therefore, a systematic review and synthesis of qualitative evidence on COPD self-management from the perspective of patients, carers, and practitioners was conducted.,Following a systematic search and screening, 31 studies were appraised and data extracted for analysis.,This review found that patients can adapt to COPD; however, learning to self-manage is often a protracted process.,Emotional needs are considerable; frustration, depression, and anxiety are common.,In addition, patients can face an assortment of losses and limitations on their lifestyle and social interaction.,Over time, COPD can consume their existence, reducing motivation.,Support from family can prove vital, yet tinged with ambivalence and burden.,Practitioners may not have sufficient time, resources, or appropriate skills or confidence to provide effective self-management support, particularly in regard to patients’ psychosocial needs.,This can compound patients’ capability to engage in self-management.,For COPD self-management to be effective, patients’ psychosocial needs must be prioritised alongside medication and exacerbation management.,In addition, patients’ personal beliefs regarding COPD and its management should be reviewed periodically to avoid problematic behaviours and enhance positive adaptions to the disease.,Patients with COPD are not a homogenous group and no one intervention will prove effective for all.,Finally, practitioners require greater education, training, and support to successfully assist patients. | Exacerbations of chronic obstructive pulmonary disease (COPD) are the third largest cause of emergency hospital admissions in the UK.,This systematic literature review explored the relationship between the hospitalization rates and the COPD comorbidities, anxiety, and depression.,The Centre for Research Dissemination’s framework for systematic reviews was followed using search terms relating to COPD, anxiety, depression, and hospital admission.,Papers identified were assessed for relevance and quality, using a suitable Critical Appraisal Skills Programme tool and Mixed Methods Assessment Tool.,Twenty quantitative studies indicated that anxiety and depression led to a statistically significant increase in the likelihood of COPD patients being hospitalized.,These comorbidities also led to an increased length of stay and a greater risk of mortality postdischarge.,Other significant factors included lower Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise scores, female gender, lower socioeconomic status, poorer patient perceived quality of life, increased severity of lung function, and less improvement in dyspnea from admission to discharge.,It was also highlighted that only 27%-33% of those with depression were being treated for it.,Four qualitative studies revealed that patients saw anxiety and depression as a major factor that affected their ability to cope with and self-manage their condition.,Findings from the systematic review have highlighted a need for better recognition and treatment of anxiety and depression amongst individuals with COPD.,Ongoing research will develop and test strategies for promoting better management and self-management as a means of reducing hospital admissions. | 1 |
We previously reported a Phase 1/2 randomized placebo-controlled trial of systemic administration of bone marrow-derived allogeneic MSCs (remestemcel-L) in COPD.,While safety profile was good, no functional efficacy was observed.,However, in view of growing recognition of effects of inflammatory environments on MSC actions we conducted a post-hoc analysis with stratification by baseline levels of a circulating inflammatory marker, C-reactive protein (CRP) to determine the effects of MSC administration in COPD patients with varying circulating CRP levels.,Time course of lung function, exercise performance, patient reported responses, and exacerbation frequency following four monthly infusions of remestemcel-L vs. placebo were re-assessed in subgroups based on baseline circulating CRP levels.,In COPD patients with baseline CRP ≥ 4 mg/L, compared to COPD patients receiving placebo (N = 17), those treated with remestemcel-L (N = 12), demonstrated significant improvements from baseline in forced expiratory volume in one second, forced vital capacity, and six minute walk distance at 120 days with treatment differences evident as early as 10 days after the first infusion.,Significant although smaller benefits were also detected in those with CRP levels ≥ 2 or ≥ 3 mg/L.,These improvements persisted variably over the 2-year observational period.,No significant benefits were observed in patient reported responses or number of COPD exacerbations between treatment groups.,In an inflammatory environment, defined by elevated circulating CRP, remestemcel-L administration yielded at least transient meaningful pulmonary and functional improvements.,These findings warrant further investigation of potential MSC-based therapies in COPD and other inflammatory pulmonary diseases.,Trial registration: Clinicaltrials.gov NCT00683722. | Interleukin-1 receptor 1 (IL-1R1) inhibition is a potential strategy for treating patients with chronic obstructive pulmonary disease (COPD).,MEDI8968, a fully human monoclonal antibody, binds selectively to IL-1R1, inhibiting activation by IL-1α and IL-1β.,We studied the efficacy and safety/tolerability of MEDI8968 in adults with symptomatic, moderate-to-very severe COPD.,This was a phase II, randomised, double-blind, placebo-controlled, multicentre, parallel-group study.,Subjects aged 45-75 years and receiving standard maintenance therapy with ≥2 exacerbations in the past year were randomised 1:1 to receive placebo or MEDI8968 300 mg (600 mg intravenous loading dose) subcutaneously every 4 weeks, for 52 weeks.,The primary endpoint was the moderate/severe acute exacerbations of COPD (AECOPD) rate (week 56 post-randomisation).,Secondary endpoints were severe AECOPD rate and St George’s Respiratory Questionnaire-COPD (SGRQ-C) score (week 56 post-randomisation).,Of subjects randomised to placebo (n = 164) and MEDI8968 (n = 160), 79.3% and 75.0%, respectively, completed the study.,There were neither statistically significant differences between treatment groups in moderate/severe AECOPD rate ([90% confidence interval]: 0.78 [0.63, 0.96], placebo; 0.71 [0.57, 0.90], MEDI8968), nor in severe AECOPD rate or SGRQ-C scores.,Post-hoc analysis of subject subgroups (by baseline neutrophil count or tertiles of circulating neutrophil counts) did not alter the study outcome.,The incidence of treatment-emergent adverse events (TEAEs) with placebo and MEDI8968 treatment was similar.,The most common TEAE was worsening of COPD.,In this phase II study, MEDI8968 did not produce statistically significant improvements in AECOPD rate, lung function or quality of life.,ClinicalTrials.gov, NCT01448850, date of registration: 06 October 2011.,The online version of this article (doi:10.1186/s12931-017-0633-7) contains supplementary material, which is available to authorized users. | 1 |
Background: Posttranscriptional gene regulation (PTGR) contributes to inflammation through alterations in messenger RNA (mRNA) turnover and translation rates.,RNA-binding proteins (RBPs) coordinate these processes but their role in lung inflammatory diseases is ill-defined.,We evaluated the expression of a curated list of mRNA-binding RBPs (mRBPs) in selected Gene Expression Omnibus (GEO) transcriptomic databases of airway epithelium isolated from chronic obstructive pulmonary disease (COPD), severe asthma (SA) and matched control subjects, hypothesizing that global changes in mRBPs expression could be used to infer their pathogenetic roles and identify novel disease-related regulatory networks.,Methods: A published list of 692 mRBPs [Nat Rev Genet 2014] was searched in GEO datasets originated from bronchial brushings of stable COPD patients (C), smokers (S), non-smokers (NS) controls with normal lung function (n = 6/12/12) (GEO ID: GSE5058) and of (SA) and healthy control (HC) (n = 6/12) (GSE63142).,Fluorescence intensity data were extracted and normalized on the medians for fold change (FC) comparisons.,FCs were set at ≥ |1.5| with a false discovery rate (FDR) of ≤ 0.05.,Pearson correlation maps and heatmaps were generated using tMEV tools v4_9_0.45.,DNA sequence motifs were searched using PScan-ChIP.,Gene Ontology (GO) was performed with Ingenuity Pathway Analysis (IPA) tool.,Results: Significant mRBP expression changes were detected for S/NS, COPD/NS and COPD/S (n = 41, 391, 382, respectively).,Of those, 32% of genes changed by FC ≥ |1.5| in S/NS but more than 60% in COPD/NS and COPD/S (n = 13, 267, 257, respectively).,Genes were predominantly downregulated in COPD/NS (n = 194, 73%) and COPD/S (n = 202, 79%), less so in S/NS (n = 4, 31%).,Unsupervised cluster analysis identified in 4 out of 12 S the same mRBP pattern seen in C, postulating subclinical COPD.,Significant DNA motifs enrichment for transcriptional regulation was found for downregulated RBPs.,Correlation analysis identified five clusters of co-expressed mRBPs.,GO analysis revealed significant enrichments in canonical pathways both specific and shared among comparisons.,Unexpectedly, no significant mRBPs modulation was found in SA compared to controls.,Conclusions: Airway epithelial mRBPs profiling reveals a COPD-specific global downregulation of RBPs shared by a subset of control smokers, the potential of functional cooperation by coexpressed RBPs and significant impact on relevant pathogenetic pathways in COPD.,Elucidation of PTGR in COPD could identify disease biomarkers or pathways for therapeutic targeting. | 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 |
Diseases of accelerated aging often occur together (multimorbidity), and their prevalence is increasing, with high societal and health care costs.,Chronic obstructive pulmonary disease (COPD) is one such condition, in which one half of patients exhibit ≥4 age-related diseases.,Diseases of accelerated aging share common molecular pathways, which lead to the detrimental accumulation of senescent cells.,These senescent cells no longer divide but release multiple inflammatory proteins, known as the senescence-associated secretory phenotype, which may perpetuate and speed disease.,Here, we show that inhibiting miR-570-3p, which is increased in COPD cells, reverses cellular senescence by restoring the antiaging molecule sirtuin-1.,MiR-570-3p is induced by oxidative stress in airway epithelial cells through p38 MAP kinase-c-Jun signaling and drives senescence by inhibiting sirtuin-1.,Inhibition of elevated miR-570-3p in COPD small airway epithelial cells, using an antagomir, restores sirtuin-1 and suppresses markers of cellular senescence (p16INK4a, p21Waf1, and p27Kip1), thereby restoring cellular growth by allowing progression through the cell cycle.,MiR-570-3p inhibition also suppresses the senescence-associated secretory phenotype (matrix metalloproteinases-2/9, C-X-C motif chemokine ligand 8, IL-1β, and IL-6).,Collectively, these data suggest that inhibiting miR-570-3p rejuvenates cells via restoration of sirtuin-1, reducing many of the abnormalities associated with cellular senescence.-Baker, J.,R., Vuppusetty, C., Colley, T., Hassibi, S., Fenwick, P.,S., Donnelly, L.,E., Ito, K., Barnes, P.,J.,MicroRNA-570 is a novel regulator of cellular senescence and inflammaging. | Chronic obstructive pulmonary disease (COPD) is a serious global health problem characterized by chronic airway inflammation, progressive airflow limitation and destruction of lung parenchyma.,Remodeling of the bronchial airways in COPD includes changes in both the bronchial epithelium and the subepithelial extracellular matrix (ECM).,To explore the impact of an aberrant ECM on epithelial cell phenotype in COPD we developed a new ex vivo model, in which normal human bronchial epithelial (NHBE) cells repopulate and differentiate on decellularized human bronchial scaffolds derived from COPD patients and healthy individuals.,By using transcriptomics, we show that bronchial ECM from COPD patients induces differential gene expression in primary NHBE cells when compared to normal bronchial ECM.,The gene expression profile indicated altered activity of upstream mediators associated with COPD pathophysiology, including hepatocyte growth factor, transforming growth factor beta 1 and platelet-derived growth factor B, which suggests that COPD-related changes in the bronchial ECM contribute to the defective regenerative ability in the airways of COPD patients. | 1 |
Health effects of electronic cigarette (EC) use in patients with chronic obstructive pulmonary disease (COPD) are largely unexplored.,We present findings from a long-term prospective assessment of respiratory parameters in a cohort of COPD patients who ceased or substantially reduced conventional cigarette use with ECs.,We prospectively re-evaluated COPD exacerbations, spirometric indices, subjective assessments (using the COPD Assessment Tool [CAT] scores), physical activity (measured by the 6-minute walk distance [6MWD]), and conventional cigarette use in EC users with COPD who were retrospectively assessed previously.,Baseline measurements prior to switching to EC use were compared to follow-up visits at 12, 24, and 36 months.,Age- and sex-matched regularly smoking COPD patients who were not using ECs were included as reference (control) group.,Complete data were available from 44 patients.,Compared to baseline in the EC-user group, there was a marked decline in the use of conventional cigarettes.,Although there was no change in lung function, significant improvements in COPD exacerbation rates, CAT scores, and 6MWD were observed consistently in the EC user group over the 3-year period (p<0.01).,Similar findings were noted in COPD EC users who also smoked conventional cigarettes (“dual users”).,The present study suggests that EC use may ameliorate objective and subjective COPD outcomes and that the benefits gained may persist long-term.,EC use may reverse some of the harm resulting from tobacco smoking in COPD patients. | Comorbidities are common in COPD, but quantifying their burden is difficult.,Currently there is a COPD-specific comorbidity index to predict mortality and another to predict general quality of life.,We sought to develop and validate a COPD-specific comorbidity score that reflects comorbidity burden on patient-centered outcomes.,Using the COPDGene study (GOLD II-IV COPD), we developed comorbidity scores to describe patient-centered outcomes employing three techniques: 1) simple count, 2) weighted score, and 3) weighted score based upon statistical selection procedure.,We tested associations, area under the Curve (AUC) and calibration statistics to validate scores internally with outcomes of respiratory disease-specific quality of life (St.,George's Respiratory Questionnaire, SGRQ), six minute walk distance (6MWD), modified Medical Research Council (mMRC) dyspnea score and exacerbation risk, ultimately choosing one score for external validation in SPIROMICS.,Associations between comorbidities and all outcomes were comparable across the three scores.,All scores added predictive ability to models including age, gender, race, current smoking status, pack-years smoked and FEV1 (p<0.001 for all comparisons).,Area under the curve (AUC) was similar between all three scores across outcomes: SGRQ (range 0·7624-0·7676), MMRC (0·7590-0·7644), 6MWD (0·7531-0·7560) and exacerbation risk (0·6831-0·6919).,Because of similar performance, the comorbidity count was used for external validation.,In the SPIROMICS cohort, the comorbidity count performed well to predict SGRQ (AUC 0·7891), MMRC (AUC 0·7611), 6MWD (AUC 0·7086), and exacerbation risk (AUC 0·7341).,Quantifying comorbidity provides a more thorough understanding of the risk for patient-centered outcomes in COPD.,A comorbidity count performs well to quantify comorbidity in a diverse population with COPD. | 1 |
To validate a Portuguese-language version of the COPD assessment test (CAT) for use in Brazil and to assess the reproducibility of this version.,This was multicenter study involving patients with stable COPD at two teaching hospitals in the city of Fortaleza, Brazil.,Two independent observers (twice in one day) administered the Portuguese-language version of the CAT to 50 patients with COPD.,One of those observers again administered the scale to the same patients one week later.,At baseline, the patients were submitted to pulmonary function testing and the six-minute walk test (6MWT), as well as completing the previously validated Portuguese-language versions of the Saint George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (MMRC) dyspnea scale, and hospital anxiety and depression scale (HADS).,Inter-rater and intra-rater reliability was excellent (intraclass correlation coefficient [ICC] = 0.96; 95% CI: 0.93-0.97; p < 0.001; and ICC = 0.98; 95% CI: 0.96-0.98; p < 0.001, respectively).,Bland Altman plots showed good test-retest reliability.,The CAT total score correlated significantly with spirometry results, 6MWT distance, SGRQ scores, MMRC dyspnea scale scores, and HADS-depression scores.,The Portuguese-language version of the CAT is a valid, reproducible, and reliable instrument for evaluating patients with COPD in Brazil.,Realizar a validação e verificar a reprodutibilidade da versão em português do Brasil do COPD Assessment Test (CAT).,Estudo multicêntrico, no qual foram selecionados pacientes com DPOC estável em dois hospitais de ensino na cidade de Fortaleza, CE.,A versão do CAT foi aplicada duas vezes a 50 pacientes com DPOC por dois observadores independentes no mesmo dia.,Após uma semana, esse mesmo questionário foi aplicado novamente aos mesmos pacientes por um dos observadores.,No primeiro dia, os pacientes foram submetidos à prova de função pulmonar e ao teste de caminhada de seis minutos (TC6) e responderam as versões validadas de qualidade de vida relacionada à saúde (QVRS).,(SGRQ), escala de dispneia Modified Medical Research Council (MMRC) e hospital anxiety and depression scale (HADS).,As reprodutibilidades interobservador e intraobservador foram excelentes (coeficiente de correlação intraclasse [CCI] = 0,96; IC95%: 0,93-0,97; p < 0,001; e CCI = 0,98; IC95%: 0,96-0,98; p < 0,001, respectivamente).,As disposições gráficas de Bland Altman demonstraram boa confiabilidade teste-reteste.,Houve correlações significativas do escore total do CAT com os resultados de espirometria, TC6, SGRQ, escala de dispneia MMRC e HADS-depressão.,A versão brasileira do CAT é um instrumento válido, reprodutível e confiável para a avaliação dos pacientes com DPOC na população brasileira. | The GOLD 2011 document proposed a new classification system for COPD combining symptom assessment by COPD assessment test (CAT) or modified Medical Research Council (mMRC) dyspnea scores, and exacerbation risk.,We postulated that classification of COPD would be different by the symptom scale; CAT vs mMRC.,Outpatients with COPD were enrolled from January to June in 2012.,The patients were categorized into A, B, C, and D according to the GOLD 2011; patients were categorized twice with mMRC and CAT score for symptom assessment, respectively.,Additionally, correlations between mMRC scores and each item of CAT scores were analyzed.,Classification of 257 patients using the CAT score vs mMRC scale was as follows.,By using CAT score, 60 (23.3%) patients were assigned to group A, 55 (21.4%) to group B, 21 (8.2%) to group C, and 121 (47.1%) to group D.,On the basis of the mMRC scale, 97 (37.7%) patients were assigned to group A, 18 (7.0%) to group B, 62 (24.1%) to group C, and 80 (31.1%) to group D.,The kappa of agreement for the GOLD groups classified by CAT and mMRC was 0.510.,The mMRC score displayed a wide range of correlation with each CAT item (r = 0.290 for sputum item to r = 0.731 for dyspnea item, p < 0.001).,The classification of COPD produced by the mMRC or CAT score was not identical.,Care should be taken when stratifying COPD patients with one symptom scale versus another according to the GOLD 2011 document. | 1 |
Background and objectives: Exertional desaturation (ED) is often overlooked in chronic obstructive pulmonary disease (COPD).,We aim to investigate the impact of ED on mortality and the predictors of ED in COPD.,Materials and methods: A cohort of COPD patients with clinically stable, widely ranging severities were enrolled.,ED is defined as oxyhemoglobin saturation by pulse oximetry (SpO2) < 90% or a drop of ΔSpO2 ≥ 4% during a six-minute walk test (6MWT).,Cox regression analysis is used to estimate the hazard ratio (HR) for three-year mortality.,Results: A total of 113 patients were studied, including ED (N = 34) and non-ED (N = 79) groups.,FVC (% of predicted value), FEV1/FVC (%), FEV1 (% of predicted value), DLCO (%), maximal inspiratory pressure, SpO2 during the 6MWT, GOLD stage, and COPD severity were significantly different between the ED and non-ED groups in univariate analysis.,Low minimal SpO2 (p < 0.001) and high maximal heart rate (p = 0.04) during the 6MWT were significantly related to ED in multivariate analysis.,After adjusting for age, gender, body mass index, 6MWD, FEV1, mMRC, GOLD staging, exacerbation, hs-CRP, and fibrinogen, the mortality rate of the ED group was higher than that of the non-ED group (p = 0.012; HR = 4.12; 95% CI 1.37-12.39).,For deaths, the average survival time of ED was shorter than that of the non-ED group (856.4 days vs.,933.8 days, p = 0.033).,Conclusions: ED has higher mortality than non-ED in COPD.,COPD should be assessed for ED, especially in patients with low minimal SpO2 and high maximal HR during the 6MWT. | The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised many questions about the management of patients with chronic obstructive pulmonary disease (COPD) and whether modifications of their therapy are required.,It has raised questions about recognizing and differentiating coronavirus disease (COVID-19) from COPD given the similarity of the symptoms.,The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Science Committee used established methods for literature review to present an overview of the management of patients with COPD during the COVID-19 pandemic.,It is unclear whether patients with COPD are at increased risk of becoming infected with SARS-CoV-2.,During periods of high community prevalence of COVID-19, spirometry should only be used when it is essential for COPD diagnosis and/or to assess lung function status for interventional procedures or surgery.,Patients with COPD should follow basic infection control measures, including social distancing, hand washing, and wearing a mask or face covering.,Patients should remain up to date with appropriate vaccinations, particularly annual influenza vaccination.,Although data are limited, inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should continue to be used as indicated for stable COPD management.,Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications.,Differentiating symptoms of COVID-19 infection from chronic underlying symptoms or those of an acute COPD exacerbation may be challenging.,If there is suspicion for COVID-19, testing for SARS-CoV-2 should be considered.,Patients who developed moderate-to-severe COVID-19, including hospitalization and pneumonia, should be treated with evolving pharmacotherapeutic approaches as appropriate, including remdesivir, dexamethasone, and anticoagulation.,Managing acute respiratory failure should include appropriate oxygen supplementation, prone positioning, noninvasive ventilation, and protective lung strategy in patients with COPD and severe acute respiratory distress syndrome.,Patients who developed asymptomatic or mild COVID-19 should be followed with the usual COPD protocols.,Patients who developed moderate or worse COVID-19 should be monitored more frequently and accurately than the usual patients with COPD, with particular attention to the need for oxygen therapy. | 1 |
CD8 cells may contribute towards an autoimmune process in COPD.,Down regulation of T cell receptor (TCR) signalling molecules occurs in autoimmune diseases with consequent T cell dysfunction.,We hypothesise that TCR signalling is abnormal in COPD pulmonary CD8 cells.,Micro-array gene expression analysis of blood and pulmonary COPD CD8 samples was performed and compared to pulmonary CD8 cells from smoker controls (S).,We focused on the TCR signalling pathway, with validation of key findings using polymerase chain reaction and immunofluorescence.,TCR signalling molecules in COPD pulmonary CD8 cells were down regulated compared to blood CD8 cells (CD247: fold change (FC) −2.43, Q = 0.001; LCK: FC −2.25, Q = 0.01).,Micro-array analysis revealed no significant differences between COPD and S pulmonary CD8 cells.,However, PCR revealed significantly lower gene expression levels of CD247 (FC −1.79, p = 0.04) and LCK (FC −1.77, p = 0.01) in COPD compared to S pulmonary CD8 cells.,CD247 down regulation in COPD CD8 cells was confirmed by immunofluorescent staining of bronchoalveolar lavage cells: Significantly fewer COPD CD8 cells co-expressed CD247 compared to healthy non-smoker CD8 cells (mean 88.9 vs 75.2%, p<0.05) There is down regulation of TCR signalling molecules in COPD pulmonary CD8 cells.,This may cause T cell dysfunction. | Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible chronic inflammatory disease of the lung.,The nature of the immune reaction in COPD raises the possibility that IL-17 and related cytokines may contribute to this disorder.,This study analyzed the expression of IL-17A and IL-17F as well as the phenotype of cells producing them in bronchial biopsies from COPD patients.,Bronchoscopic biopsies of the airway were obtained from 16 COPD subjects (GOLD stage 1-4) and 15 control subjects.,Paraffin sections were used for the investigation of IL-17A and IL-17F expression in the airways by immunohistochemistry, and frozen sections were used for the immunofluorescence double staining of IL-17A or IL-17F paired with CD4 or CD8.,In order to confirm the expression of IL-17A and IL-17F at the mRNA level, a quantitative RT-PCR was performed on the total mRNA extracted from entire section or CD8 positive cells selected by laser capture microdissection.,IL-17F immunoreactivity was significantly higher in the bronchial biopsies of COPD patients compared to control subjects (P < 0.0001).,In the submucosa, the absolute number of both IL-17A and IL-17F positive cells was higher in COPD patients (P < 0.0001).,After adjusting for the total number of cells in the submucosa, we still found that more cells were positive for both IL-17A (P < 0.0001) and IL-17F (P < 0.0001) in COPD patients compared to controls.,The mRNA expression of IL-17A and IL-17F in airways of COPD patients was confirmed by RT-PCR.,The expression of IL-17A and IL-17F was co-localized with not only CD4 but also CD8, which was further confirmed by RT-PCR on laser capture microdissection selected CD8 positive cells.,These findings support the notion that Th17 cytokines could play important roles in the pathogenesis of COPD, raising the possibility of using this mechanism as the basis for novel therapeutic approaches. | 1 |
Individuals with COPD may present reduced peripheral muscle strength, leading to impaired mobility.,Comprehensive pulmonary rehabilitation (PR) should include strength training, in particular to lower limbs.,Furthermore, simple tools for the assessment of peripheral muscle performance are required.,To assess the peripheral muscle performance of COPD patients by the sit-to-stand test (STST), as compared to the one-repetition maximum (1-RM), considered as the gold standard for assessing muscle strength in non-laboratory situations, and to evaluate the responsiveness of STST to a PR program.,Sixty moderate-to-severe COPD inpatients were randomly included into either the specific strength training group or into the usual PR program group.,Patients were assessed on a 30-second STST and 1-minute STST, 1-RM, and 6-minute walking test (6MWT), before and after PR.,Bland-Altman plots were used to evaluate the agreement between 1-RM and STST.,The two groups were not different at baseline.,In all patients, 1-RM was significantly related to the 30-second STST (r=0.48, P<0.001) and to 1-minute STST (r=0.36, P=0.005).,The 30-second STST was better tolerated in terms of the perceived fatigue (P=0.002) and less time consuming (P<0.001) test.,In the specific strength training group significant improvements were observed in the 30-second STST (P<0.001), 1-minute STST (P=0.005), 1-RM (P<0.001), and in the 6MWT (P=0.001).,In the usual PR program group, significant improvement was observed in the 30-second STST (P=0.042) and in the 6MWT (P=0.001).,Our study shows that in stable moderate-to-severe inpatients with COPD, STST is a valid and reliable tool to assess peripheral muscle performance of lower limbs, and is sensitive to a specific PR program. | Functional activities, such as the sit-to-stand-to-sit (STSTS) task, are often impaired in individuals with chronic obstructive pulmonary disease (COPD).,The STSTS task places a high demand on the postural control system, which has been shown to be impaired in individuals with COPD.,It remains unknown whether postural control deficits contribute to the decreased STSTS performance in individuals with COPD.,Center of pressure displacement was determined in 18 individuals with COPD and 18 age/gender-matched controls during five consecutive STSTS movements with vision occluded.,The total duration, as well as the duration of each sit, sit-to-stand, stand and stand-to-sit phase was recorded.,Individuals with COPD needed significantly more time to perform five consecutive STSTS movements compared to healthy controls (19±6 vs. 13±4 seconds, respectively; p = 0.001).,The COPD group exhibited a significantly longer stand phase (p = 0.028) and stand-to-sit phase (p = 0.001) compared to the control group.,In contrast, the duration of the sit phase (p = 0.766) and sit-to-stand phase (p = 0.999) was not different between groups.,Compared to healthy individuals, individuals with COPD needed significantly more time to complete those phases of the STSTS task that require the greatest postural control.,These findings support the proposition that suboptimal postural control is an important contributor to the decreased STSTS performance in individuals with COPD. | 1 |
Sputum and blood eosinophil counts predict corticosteroid effects in COPD patients.,Bacterial infection causes increased airway neutrophilic inflammation.,The relationship of eosinophil counts with airway bacterial load in COPD patients is uncertain.,We tested the hypothesis that bacterial load and eosinophil counts are inversely related.,COPD patients were seen at stable state and exacerbation onset.,Sputum was processed for quantitative polymerase chain reaction detection of the potentially pathogenic microorganisms (PPM) H. influenzae, M. catarrhalis and S. pneumoniae.,PPM positive was defined as total load ≥1 × 104copies/ml.,Sputum and whole blood were analysed for differential cell counts.,At baseline, bacterial counts were not related to blood eosinophils, but sputum eosinophil % was significantly lower in patients with PPM positive compared to PPM negative samples (medians: 0.5% vs.,1.25% respectively, p = 0.01).,Patients with PPM positive samples during an exacerbation had significantly lower blood eosinophil counts at exacerbation compared to baseline (medians: 0.17 × 109/L vs.,0.23 × 109/L respectively, p = 0.008), while no blood eosinophil change was observed with PPM negative samples.,These findings indicate an inverse relationship between bacterial infection and eosinophil counts.,Bacterial infection may influence corticosteroid responsiveness by altering the profile of neutrophilic and eosinophilic inflammation.,The online version of this article (doi:10.1186/s12931-017-0570-5) contains supplementary material, which is available to authorized users. | We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.,Three studies of ≥1-year duration met the inclusion criteria.,Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%).,At baseline, 57-75% of patients had ≥2% blood eosinophils.,Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.,For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001).,No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively).,In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo).,No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.,Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. | 1 |
Nighttime symptoms can negatively impact the quality of life of patients with chronic obstructive pulmonary disease (COPD).,The Nighttime Symptoms of COPD Instrument (NiSCI) was designed to measure the occurrence and severity of nighttime symptoms in patients with COPD, the impact of symptoms on nighttime awakenings, and rescue medication use.,The objective of this study was to explore item reduction, inform scoring recommendations, and evaluate the psychometric properties of the NiSCI.,COPD patients participating in a Phase III clinical trial completed the NiSCI daily.,Item analyses were conducted using weekly mean and single day scores.,Descriptive statistics (including percentage of respondents at floor/ceiling and inter-item correlations), factor analyses, and Rasch model analyses were conducted to examine item performance and scoring.,Test-retest reliability was assessed for the final instrument using the intraclass correlation coefficient (ICC).,Correlations with assessments conducted during study visits were used to evaluate convergent and known-groups validity.,Data from 1,663 COPD patients aged 40-93 years were analyzed.,Item analyses supported the generation of four scores.,A one-factor structure was confirmed with factor analysis and Rasch analysis for the symptom severity score.,Test-retest reliability was confirmed for the six-item symptom severity (ICC, 0.85), number of nighttime awakenings (ICC, 0.82), and rescue medication (ICC, 0.68) scores.,Convergent validity was supported by significant correlations between the NiSCI, St George’s Respiratory Questionnaire, and Exacerbations of Chronic Obstructive Pulmonary Disease Tool-Respiratory Symptoms scores.,The results suggest that the NiSCI can be used to determine the severity of nighttime COPD symptoms, the number of nighttime awakenings due to COPD symptoms, and the nighttime use of rescue medication.,The NiSCI is a reliable and valid instrument to evaluate these concepts in COPD patients in clinical trials and clinical practice.,Scoring recommendations and steps for further research are discussed. | “Physical inactivity” and “sedentary lifestyles” are phrases often used when describing lifestyles of people with chronic obstructive pulmonary disease (COPD).,Evidence suggests activity types, independent of energy expenditure, influence health outcomes, so understanding patterns of time use is important, particularly in chronic disease.,We aimed to identify reports of time use in people with COPD.,Predefined search strategies were used with six electronic databases to identify individual activity reports (including frequencies and/or durations) in which community-dwelling people with COPD engaged.,Eligible studies were assessed independently against predefined criteria and data were extracted by two reviewers.,Data synthesis was achieved by aggregating activity reports into activity domains (sports/exercise, screen time, transport, quiet time, self-care, sociocultural, work/study, chores, and sleep).,Twenty-six publications reported 37 specific daily activities.,People with COPD were found to spend extended periods in sedentary behaviors (eg, standing [194 min/day]; sitting [359 min/day]; lying [88 min/day]), have limited engagement in physical activity (eg, walking [51 min/day]; exercising [1.2 episodes per week {ep/w}, 13 min/day]), have high health care needs (medical appointments [1.0 ep/w]), and experience difficulties associated with activities of daily living (eg, showering [2.5 ep/w, 60 minutes per episode]; preparing meals [4.7 ep/w]).,Little data could be found describing how people with COPD use their time, and data synthesis was problematic because of variations in methodologies, population differences, and research emphases.,Identified data largely referred to posture and were skewed according to country, assessment methods, and disease severity.,Comparisons with age-matched population data showed people with COPD spent less time engaged in personal-care activities (self-care and sleeping) and chores than people in similar age groups.,The incorporation of time-use outcomes in future research designs should be encouraged.,Ideally, these tools should use consistent frameworks and comparable outcome measures in order to provide clearer descriptions of time use in chronic disease. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities.,The main cause is smoking tobacco, but other factors have been identified.,Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli.,The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both.,Comorbidities include ischaemic heart disease, diabetes, and lung cancer.,Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids).,Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification.,Future research should be directed towards the development of agents that notably affect the course of disease. | Oxidative stress occurs when free radicals and other reactive species overwhelm the availability of antioxidants.,Reactive oxygen species (ROS), reactive nitrogen species, and their counterpart antioxidant agents are essential for physiological signaling and host defense, as well as for the evolution and persistence of inflammation.,When their normal steady state is disturbed, imbalances between oxidants and antioxidants may provoke pathological reactions causing a range of nonrespiratory and respiratory diseases, particularly chronic obstructive pulmonary disease (COPD).,In the respiratory system, ROS may be either exogenous from more or less inhalative gaseous or particulate agents such as air pollutants, cigarette smoke, ambient high-altitude hypoxia, and some occupational dusts, or endogenously generated in the context of defense mechanisms against such infectious pathogens as bacteria, viruses, or fungi.,ROS may also damage body tissues depending on the amount and duration of exposure and may further act as triggers for enzymatically generated ROS released from respiratory, immune, and inflammatory cells.,This paper focuses on the general relevance of free radicals for the development and progression of both COPD and pulmonary emphysema as well as novel perspectives on therapeutic options.,Unfortunately, current treatment options do not suffice to prevent chronic airway inflammation and are not yet able to substantially alter the course of COPD.,Effective therapeutic antioxidant measures are urgently needed to control and mitigate local as well as systemic oxygen bursts in COPD and other respiratory diseases.,In addition to current therapeutic prospects and aspects of genomic medicine, trending research topics in COPD are presented. | 1 |
Chronic obstructive pulmonary disease (COPD) is a multicomponent condition that is characterised by airflow obstruction that is not fully reversible and is a major global cause of morbidity and mortality.,The most widely used marker of disease severity and progression is FEV1.,However, FEV1 correlates poorly with both symptoms and other measures of disease progression and thus there is an urgent need for other biological markers to better characterise individuals with COPD.,Fibrinogen is an acute phase plasma protein that has emerged as a promising biomarker in COPD.,Here we review the current clinical evidence linking fibrinogen with COPD and its associated co-morbidities and discuss its potential utility as a biomarker.,Searches for appropriate studies were undertaken on PubMed using search terms fibrinogen, COPD, emphysema, chronic bronchitis, FEV1, cardiovascular disease, exacerbation and mortality.,There is strong evidence of an association between fibrinogen and the presence of COPD, the presence and frequency of exacerbations and with mortality.,Fibrinogen is associated with disease severity but does not predict lung function decline, a measure used as a surrogate for disease activity.,The role of fibrinogen in identifying inflammatory co morbidities, particularly cardiovascular disease, remains unclear.,Fibrinogen is reduced by p38 mitogen-activated protein kinase inhibitors in individuals with stable disease and by oral corticosteroids during exacerbations.,Fibrinogen is likely to be a useful biomarker to stratify individuals with COPD into those with a high or low risk of future exacerbations and may identify those with a higher risk of mortality. | Elevated circulating levels of several inflammatory biomarkers have been described in selected patient populations with COPD, although less is known about their population-based distribution.,The aims of this study were to compare the levels of several systemic biomarkers between stable COPD patients and healthy subjects from a population-based sample, and to assess their distribution according to clinical variables.,This is a cross-sectional study design of participants in the EPI-SCAN study (40-80 years of age).,Subjects with any other condition associated with an inflammatory process were excluded.,COPD was defined as a post-bronchodilator FEV1/FVC < 0.70.,The reference group was made of non-COPD subjects without respiratory symptoms, associated diseases or prescription of medication.,Subjects were evaluated with quality-of-life questionnaires, spirometry and 6-minute walk tests.,Serum C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukins (IL-6 and IL-8), alpha1-antitrypsin, fibrinogen, albumin and nitrites/nitrates (NOx) were measured.,We compared 324 COPD patients and 110 reference subjects.,After adjusting for gender, age, BMI and tobacco consumption, COPD patients showed higher levels of CRP (0.477 ± 0.023 vs.,0.376 ± 0.041 log mg/L, p = 0.049), TNF-α (13.12 ± 0.59 vs.,10.47 ± 1.06 pg/mL, p = 0.033), IL-8 (7.56 ± 0.63 vs.,3.57 ± 1.13 pg/ml; p = 0.033) and NOx (1.42 ± 0.01 vs.,1.36 ± 0.02 log nmol/l; p = 0.048) than controls.,In COPD patients, serum concentrations of some biomarkers were related to severity and their exercise tolerance was related to serum concentrations of CRP, IL-6, IL-8, fibrinogen and albumin.,Our results provide population-based evidence that COPD is independently associated with low-grade systemic inflammation, with a different inflammatory pattern than that observed in healthy subjects. | 1 |
Chronic obstructive pulmonary disease (COPD) was the fourth leading cause of death worldwide in 2015.,Current treatments for patients ease discomfort and help decrease disease progression; however, none improve lung function or change mortality.,COPD is heterogeneous in its molecular and clinical presentation, making it difficult to understand disease aetiology and define robust therapeutic strategies.,Given the complexity of the disease we propose a precision medicine approach to understanding and better treating COPD.,It is possible that multiOMICs can be used as a tool to integrate data from multiple fields.,Moreover, analysis of electronic medical records could aid in the treatment of patients and in the predictions of outcomes.,The Precision Medicine Initiative created in 2015 has made precision medicine approaches to treat disease a reality; one of these diseases being COPD. | Grouping COPD subjects into clinical phenotypes might be useful for the management of the disease, but the clinical implications of such classification are still not totally clear, especially regarding prognosis.,The primary objective of this study was to assess whether the mortality rates were different between four predefined clinical phenotypes.,This is a retrospective, observational study carried out at the COPD clinic of a University Hospital.,A total of 891 COPD patients were classified, according to the Spanish COPD guidelines, into the following four phenotypes: asthma-COPD overlap (ACO; 75 subjects), nonexacerbator (NONEX; 531 subjects), exacerbator with chronic bronchitis (EXCB; 194 subjects), and exacerbator with emphysema (EXEMPH; 91 subjects).,We compared the mortality outcomes between the phenotypes.,After a follow-up of 48.4±25.2 months, there were 194 deaths (21.8%).,There were significant differences in all-cause mortality between phenotypes.,The ACO phenotype had the best long-term prognosis, whereas EXEMPH had the highest risk of death.,NONEX and EXCB mortality figures were in between the other two groups.,We also found some differences in the causes of death, and patients with EXEMPH were at a higher risk of dying because of COPD itself.,The differences in mortality did not seem related to the classification into phenotypes in itself but to disparities in COPD severity and comorbidity load between groups.,Classifying COPD patients according to several predefined clinical phenotypes can identify clusters of subjects with different mortality outcomes.,Some phenotypes are associated with a specific cause of death.,The mechanisms that underlie these differences seem to be related to COPD severity and comorbidities. | 1 |
Previous studies suggest that gender differences exist in COPD diagnosis and symptoms; these differences may be more pronounced in younger adults.,Our objective was to explore age-associated gender differences across a range of COPD severities.,A total of 4,484 current and former smokers with COPD from the Genetic Epidemiology of COPD cohort were investigated using regression modeling to explore the association between gender, age, disease severity, and the contributing elements of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification system (symptoms, exacerbation risk, airflow limitation).,The age-gender interaction was observed across multiple age categories.,Compared to men with COPD, younger women with COPD had a greater likelihood of more severe dyspnea, airflow limitation, greater risk for exacerbations, and categorization in GOLD groups B and D.,These differences were less pronounced in older women with COPD.,However, older women remained more likely to experience severe dyspnea and to manifest more severe COPD (B vs A) than older men, despite lower pack-years of smoking.,These data demonstrate the significant symptom burden of COPD in women, especially younger women.,More research is needed to understand the pathogenesis of increased severity of COPD in women and to develop gender-targeted clinical assessment and management approaches to improve outcomes for women and men with COPD at all ages. | To investigate the respiratory infectious phenotypes and their impact on length of stay (LOS) and the COPD Assessment Test (CAT) Scale in acute exacerbation of COPD (AECOPD).,We categorized 81 eligible patients into bacterial infection, viral infection, coinfection, and non-infectious groups.,The respiratory virus examination was determined by a liquid bead array xTAG Respiratory Virus Panel in pharyngeal swabs, while bacterial infection was studied by conventional sputum culture.,LOS and CAT as well as demographic information were recorded.,Viruses were detected in 38 subjects, bacteria in 17, and of these, seven had both.,Influenza virus was the most frequently isolated virus, followed by enterovirus/rhinovirus, coronavirus, bocavirus, metapneumovirus, parainfluenza virus types 1, 2, 3, and 4, and respiratory syncytial virus.,Bacteriologic analyses of sputum showed that Pseudomonas aeruginosa was the most common bacteria, followed by Acinetobacter baumannii, Klebsiella, Escherichia coli, and Streptococcus pneumoniae.,The longest LOS and the highest CAT score were detected in coinfection group.,CAT score was positively correlated with LOS.,Respiratory infection is a common causative agent of exacerbations in COPD.,Respiratory coinfection is likely to be a determinant of more severe acute exacerbations with longer LOS.,CAT score may be a predictor of longer LOS in AECOPD. | 1 |
Blood eosinophil counts and history of exacerbations have been proposed as predictors of patients with chronic obstructive pulmonary disease (COPD) who may benefit from triple therapy (inhaled corticosteroid, long-acting β2-agonist and long-acting muscarinic antagonist).,In a retrospective cohort analysis we examined the profiles of COPD patients from the UK Clinical Practice Research Datalink (CPRD) and US Optum Clinformatics™ Data Mart (Optum) databases with reference to exacerbation frequency and blood eosinophil distribution.,Of the 31,437 (CPRD) and 383,825 (Optum) patients with COPD, 15,364 (CPRD) and 139,465 (Optum) met the eligibility criteria and were included.,Among patients with ≥2 exacerbations and available eosinophil counts in the baseline period (CPRD, n = 3089 and Optum, n = 13414), 17.0 and 13.3% respectively had eosinophil counts ≥400 cells/μL.,Patients with ≥2 exacerbations or eosinophil count ≥400 cells/μL during first year, exacerbated at least once (CPRD, 82.8% vs Optum, 80.6%) or continued to have eosinophil count ≥300 cells/μL (76.8% vs 76.5%), respectively in the follow-up year.,In both years, a higher variability in the number of exacerbations and eosinophil count was observed in patients with one exacerbation and eosinophil counts between 300 and 400 cells/μL; patients with eosinophil count < 150 cells/μL had the lowest variability.,Approximately 10% patients had both ≥2 exacerbations and eosinophil count ≥300 cells/μL across the databases.,A high variability in blood eosinophil counts over two consecutive years was observed in UK and US patients with COPD and should be considered while making treatment decisions.,A small proportion of COPD patients had frequent exacerbations and eosinophil count ≥300 cells/μL.,The online version of this article (10.1186/s12931-019-1130-y) contains supplementary material, which is available to authorized users. | 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 |
Chronic obstructive pulmonary disease (COPD) is set to become the third most frequent cause of death and also the third largest cause of global morbidity by 2020.,In China, where the population is aging rapidly, COPD has become one of the leading causes of disability and a large economic burden.,An epidemiological assessment of the COPD in China is required, with a focus on the number of cases living with disease, main determinants of the disease and time trends.,We systematically searched large Chinese bibliographic databases and English databases to identify spirometry-based epidemiological studies of the prevalence of COPD in China diagnosed according to GOLD criteria.,We estimated age- and gender-specific prevalence of COPD using a multilevel mixed-effect logistic regression.,We also presented the time trends of COPD between 1990 and 2010 by age, gender and setting (urban vs rural).,In 1990, the prevalence of COPD ranged from 0.49% (95% CI = 0.29-0.85) in <20 years group to 20.95% (95% CI = 14.04-27.04) in> = 80 years group, and the crude prevalence for China was 2.70% (95% CI = 1.86-3.51).,In 2010, the prevalence in <20 years was 0.55% (95% CI = 0.37-1.04) and in> = 80 years was 22.89% (95% CI = 18.13-28.96), with the crude prevalence for China of 3.84% (95% CI = 3.30-4.77).,The COPD prevalence in males was about two-fold higher than in females, and it increased with increasing age.,Between 1990-2010, the total number of Chinese people living with COPD increased by 66.73%, from 30.90 million (95% CI = 21.28-40.02) in 1990 to 51.52 million (95% CI = 44.26-63.93) in 2010.,This increase was most striking in middle age, and greater in females than in males from 30 years up to 64 years.,Our estimates, which used an independent approach to acquiring data and development of analytical methods, and were based on a more complete data set, are remarkably similar to those produced recently by the GBD 2013 collaboration, differing by only about 5% in the estimated number of COPD cases in 1990 and by 1% in 2010.,COPD is a highly prevalent disease in China and its importance is growing steadily.,The number of people living with COPD has increased substantially between 1990 and 2010.,COPD is more frequent in males and in rural areas.,Optimised primary and secondary prevention and treatment is urgently needed to counter this growing trend.,Improved epidemiological studies will be required to assist development of more effective strategies of prevention and treatment of COPD in China in the next decade and beyond. | There is increasing interest in the earlier detection of, and intervention in, patients at highest risk of developing chronic obstructive pulmonary disease (COPD).,The objective of this research was to develop and validate a risk prediction model for general practitioner (GP)-recorded diagnosis of COPD.,We used data from 239 Scottish GP practices; two-thirds were randomly allocated to a derivation cohort and the other third to a validation cohort.,We included patients aged 35-74 years at the cohort entry date, and excluded patients with a recorded diagnosis of COPD prior to the entry date and with missing data on smoking status.,There were 480,903 patients in the derivation cohort and 247,755 in the validation cohort.,The incidence of COPD in the total cohort was 5.53/1,000 patient-years of follow-up (95% confidence interval (CI), 5.46-5.60).,In the derivation cohort, the COPD risk for ever- versus never-smokers was substantially higher in women (hazard ratio (HR)=9.61, 95% CI, 8.92-10.34) than in men (HR=6.72, 95% CI, 6.19-7.30).,Other risk factors for both sexes were level of deprivation and a previously recorded asthma diagnosis.,In the validation cohort, the model discriminated well between patients who did and those who did not develop COPD: area under the receiver operating characteristics curve=0.845 (95% CI, 0.840-0.850) for females and 0.832 (95% CI, 0.827-0.837) for males.,We have developed and validated the first risk prediction model for COPD, which has the major advantage of being populated entirely by routinely collected data and consequently may be used for clinical practice. | 1 |
Genetic variation in the cluster on chromosome 15, encoding the nicotinic acetylcholine receptor subunits (CHRNA5‐CHRNA3‐CHRNB4), has shown strong associations with tobacco consumption and an additional risk increase in smoking‐related diseases such as chronic obstructive pulmonary disease (COPD), peripheral artery disease and lung cancer.,To test whether rs1051730 (C/T), a tag for multiple variants in the CHRNA5‐CHRNA3‐CHRNB3 cluster, is associated with a change in risk of smoking‐related mortality and morbidity in the Malmö Diet and Cancer study, a population‐based prospective cohort study.,At baseline participants were classified as current (n = 6951), previous (n = 8426) or never (n = 9417) smokers.,Cox‐proportional hazards models were used to determine the correlation between rs1051730 and incidence of first COPD, tobacco‐related cancer, other cancer and cardiovascular disease (CVD), and total mortality due to these causes, during approximately 14 years of follow‐up.,Amongst current smokers there were 480 first incident COPD events, 852 tobacco‐related cancers, 810 other cancers and 1022 CVD events.,A total of 1508 deaths occurred, including 500 due to CVD, 102 due to respiratory diseases and 677 due to cancer.,In adjusted additive models, an increasing number of T alleles were associated with a gradual increase in total mortality, incident COPD and tobacco‐related cancer, even after adjustment for smoking quantity.,No significant associations were observed amongst never smokers.,Our data suggest that gene variance in the CHRNA5‐CHRNA3‐CHRNB4 cluster is associated with an increased risk of death, incidence of COPD and tobacco‐related cancer in smokers.,These findings indicate an individual susceptibility to tobacco use and its complications; this may be important when targeting and designing smoking cessation therapies. | There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD).,The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1-2% of individuals with COPD.,We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study.,The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population.,Logistic regression models with adjustments of covariates were used to analyze the case-control populations.,Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations.,Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study.,They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730).,Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations.,The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%.,The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels.,Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429).,The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD.,CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer. | 1 |
The efficacy of inhaled corticosteroids (ICSs)/long-acting beta2-agonist (LABA) treatment in patients with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) compared to patients with COPD alone has rarely been examined.,This study aimed to evaluate the clinical efficacy for the improvement of lung function after ICS/LABA treatment in patients with ACOS compared to COPD alone patients.,Patients with stable COPD were selected from the Korean Obstructive Lung Disease (KOLD) cohort.,Subjects began a 3-month ICS/LABA treatment after a washout period.,ACOS was defined when the patients had 1) a personal history of asthma, irrespective of age, and wheezing in the last 12 months in a self-reported survey and 2) a positive bronchodilator response.,Among 152 eligible COPD patients, 45 (29.6%) fulfilled the criteria for ACOS.,After a 3-month treatment with ICS/LABA, the increase in forced expiratory volume in 1 second (FEV1) was significantly greater in ACOS patients than in those with COPD alone (240.2±33.5 vs 124.6±19.8 mL, P=0.002).,This increase in FEV1 persisted even after adjustment for confounding factors (adjusted P=0.002).,According to severity of baseline FEV1, the ACOS group showed a significantly greater increase in FEV1 than the COPD-alone group in patients with mild-to-moderate airflow limitation (223.2±42.9 vs 84.6±25.3 mL, P=0.005), whereas there was no statistically significant difference in patients with severe to very severe airflow limitation.,This study provides clinical evidence that ACOS patients with mild-to-moderate airflow limitation showed a greater response in lung function after 3 months of ICS/LABA combination treatment. | 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 |
Circulating markers of inflammation in chronic obstructive pulmonary disease (COPD) may correlate to disease progression and extrapulmonary complications such as malnourishment.,However, surprisingly little is known about gender-related differences for circulating inflammatory markers in COPD.,To characterize differences in circulating markers of inflammation in malnourished female and male patients with COPD.,Thirty female and 11 male patients with a clinical diagnosis of COPD and malnourishment were examined.,A group of control subjects without evidence of COPD was recruited for comparison of some variables.,Blood samples were drawn, and the following parameters were studied: leukocytes and differential counts, C-reactive protein (CRP), tumor necrosis factor-α, interleukin (IL)-6 and IL-8, myeloperoxidase (MPO), neutrophil elastase (NE), intracellular adhesion molecule-1, vascular endothelial adhesion molecule-1, and E-selectin.,The mean neutrophil concentration was significantly (P = 0.019) higher in female (4.5 × 109/L) than in male patients with COPD (3.5 × 109/L) and significantly higher than in female control subjects (3.1 × 109/L) (P < 0.01, n = 85).,The mean CRP values were considerably higher in female (4.9 mg/mL) than in male patients with COPD (1.5 mg/mL), but the difference was not statistically significant (P = 0.20).,The mean concentrations of IL-6 and IL-8 tended to be higher in female than in male patients with COPD, but these differences did not reach statistical significance either (P > 0.05).,Confounding factors (smoking, medication) could not explain the gender differences noted.,The concentrations of MPO and NE displayed a strong correlation (r = 0.89; P < 0.01, n = 41) but revealed no gender differences.,The latter was true for concentrations of adhesion molecules as well.,Our study puts forward evidence of a gender-related difference in systemic inflammation in malnourished patients with COPD in terms of circulating neutrophils being more abundant in female patients.,Among these female patients, there was also a trend toward an increase in two neutrophil-mobilizing cytokines.,New and better-powered studies are warranted to confirm and characterize this potentially important phenomenon in greater detail. | Smoking activates and recruits inflammatory cells and proteases to the airways.,Matrix metalloproteinase (MMP)-12 may be a key mediator in smoke induced emphysema.,However, the influence of smoking and its cessation on airway inflammation and MMP-12 expression during COPD is still unknown.,We aimed to analyse airway inflammatory cell patterns in induced sputum (IS) and bronchoalveolar lavage (BAL) from COPD patients who are active smokers and who have ceased smoking >2 years ago.,39 COPD outpatients - smokers (n = 22) and ex-smokers (n = 17) were studied. 8 'healthy' smokers and 11 healthy never-smokers were tested as the control groups.,IS and BAL samples were obtained for differential and MMP-12+-macrophages count analysis.,The number of IS neutrophils was higher in both COPD groups compared to both controls.,The amount of BAL neutrophils was higher in COPD smokers compared to healthy never-smokers.,The number of BAL MMP-12+-macrophages was higher in COPD smokers (1.6 ± 0.3 × 106/ml) compared to COPD ex-smokers, 'healthy' smokers and healthy never-smokers (0.9 ± 0.4, 0.4 ± 0.2, 0.2 ± 0.1 × 106/ml respectively, p < 0.05).,The lower amount of BAL neutrophils in COPD ex-smokers, compared to COPD smokers, suggests positive alterations in alveolar compartment after smoking cessation.,Smoking and disease itself may stimulate MMP-12 expression in airway compartments (IS and BAL) from COPD patients. | 1 |
Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition associated with high morbidity and mortality.,This study aimed to use weighted gene co-expression network analysis (WGCNA) to explore the molecular pathogenesis of the emphysema phenotype of COPD.,After obtaining lung mRNA expression profiles from ten patients with the emphysema phenotype of COPD and eight controls, emphysema-associated gene modules were identified with WGCNA.,Among 13 distinct modules, the green-yellow and brown modules showed the strongest correlations with emphysema severity and lung function and were thus selected as hub modules.,On gene ontology analysis, these two modules were mainly enriched in immune response, B cell receptor (BCR) signaling pathway, extracellular matrix (ECM) organization, and collagen fibril organization.,Pathway analysis primarily showed enrichment in BCR signaling pathways, ECM receptor interaction, and NF-κB and TGF-β signaling pathways for the two hub modules.,Several genes, including FCRLA, MS4A1, CD19, FKBP10, C1S and HTRA1, among others, were identified as hub genes.,Our results shed light on the potential genetic mechanisms underlying the pathogenesis of the emphysema phenotype of COPD.,However, further research will be needed to confirm the involvement of the identified genes and to determine their therapeutic relevance. | Many lung diseases are associated with changes in autophagic activity.,The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway plays a key regulatory role in autophagy.,Our aim was to explore the function of PI3K/AKT/mTOR pathway on autophagy in chronic obstructive pulmonary disease (COPD) caused by particulate matter with a diameter <2.5 µm (PM2.5).,Male C57BL/6 mice were randomly divided into sham, model, and PI3K inhibitor groups.,Mice were exposed to PM2.5 for 4 weeks to establish an in vivo COPD model.,Alveolar epithelial cells were stimulated with PM2.5 to establish an in vitro COPD model.,In mice with COPD induced by PM2.5, the PI3K inhibitor PF-04979064 suppressed protein expression of PI3K, p-AKT, and p-mTOR to increase apoptosis of alveolar epithelial cells and reduce autophagy.,Short interfering PI3K suppressed the PI3K/AKT/mTOR pathway to induce apoptosis and reduce autophagy of alveolar epithelial cells in an in vitro model of COPD.,Activation of PI3K induced the PI3K/AKT/mTOR pathway to reduce apoptosis of alveolar epithelial cells in the in vitro model of COPD by promoting autophagy.,These data demonstrate that PI3K/AKT/mTOR pathway regulates autophagy to induce apoptosis of alveolar epithelial cells in COPD. | 1 |
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. | The assessment of symptoms of chronic obstructive pulmonary disease (COPD) is important for monitoring and managing the disease and for evaluating outcomes of interventions.,COPD patients experience symptoms during the day and night, and symptoms experienced at night often disturb sleep.,The aim of this paper is to describe methods used to develop a patient-reported outcome (PRO) instrument for evaluating nighttime symptoms of COPD, and to document evidence for the content validity of the instrument.,Literature review and clinician interviews were conducted to inform discussion guides to explore patients’ nighttime COPD symptom experience.,Data from focus groups with COPD patients was used to develop a conceptual framework and the content of a new PRO instrument.,Patient understanding of the new instrument was assessed via cognitive interviews with COPD patients.,The literature review confirmed that there is no instrument with evidence of content validity currently available to assess nighttime symptoms of COPD.,Additionally, the literature review and clinician interviews suggested the need to understand patients’ experience of specific symptoms in order to evaluate nighttime symptoms of COPD.,Analyses of patient focus group data (N = 27) supported saturation of concepts and aided in development of a conceptual framework.,Items were generated using patients’ terminology to collect data on concepts in the framework including the occurrence and severity of COPD symptoms, use of rescue medication at night, and nocturnal awakening.,Response options were chosen to reflect concepts that were salient to patients.,Subsequent cognitive interviewing with ten COPD patients demonstrated that the items, response options, recall period, and instructions were understandable, relevant, and interpreted as intended.,A new PRO instrument, the Nighttime Symptoms of COPD Instrument (NiSCI), was developed with documented evidence of content validity.,The NiSCI is ready for empirical testing, including item reduction and evaluation of psychometric properties. | 1 |
All‐trans retinoic acid (ATRA) or mesenchymal stem cells (MSCs) have been shown to promote lung tissue regeneration in animal models of emphysema.,However, the reparative effects of the combination of the two and the role of p70S6 kinase‐1 (p70S6k1) activation in the repair process have not been defined.,Twenty‐one days after intratracheal instillation of porcine pancreatic elastase (PPE), MSC and/or 10 days of ATRA treatment was initiated.,Thirty‐two days later, static lung compliance (Cst), mean linear intercepts (MLIs), and alveolar surface area (S) were measured.,After PPE, mice demonstrated increased values of Cst and MLI, and decreased S values.,Both ATRA and MSC transfer were individually effective in improving these outcomes while the combination of ATRA and MSCs was even more effective.,The combination of p70S6k1−/− MSCs transfer followed by ATRA demonstrated only modest effects, and rapamycin treatment of recipients with wild‐type (WT) MSCs and ATRA failed to show any effect.,However, transfer of p70S6k1 over‐expressing‐MSCs together with ATRA resulted in further improvements over those seen following WT MSCs together with ATRA.,ATRA activated p70S6k1 in MSCs in vitro, which was completely inhibited by rapamycin.,Tracking of transferred MSCs following ATRA revealed enhanced accumulation and extended survival of MSCs in recipient lungs following PPE but not vehicle instillation.,These data suggest that in MSCs, p70S6k1 activation plays a critical role in ATRA‐enhanced lung tissue repair, mediated in part by prolonged survival of transferred MSCs. p70S6k1‐activated MSCs may represent a novel therapeutic approach to reverse the lung damage seen in emphysema. stem cells translational medicine 2018;7:551-558 | Abnormal immune responses are believed to be highly relevant in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Dendritic cells provide a critical checkpoint for immunity by their capacity to both induce and suppress immunity.,Although evident that cigarette smoke, the primary cause of COPD, significantly influences dendritic cell functions, little is known about the roles of dendritic cells in the pathogenesis of COPD.,The extent of dendritic cell infiltration in COPD tissue specimens was determined using immunohistochemical localization of CD83+ cells (marker of matured myeloid dendritic cells), and CD1a+ cells (Langerhans cells).,The extent of tissue infiltration with Langerhans cells was also determined by the relative expression of the CD207 gene in COPD versus control tissues.,To determine mechanisms by which dendritic cells accumulate in COPD, complimentary studies were conducted using monocyte-derived human dendritic cells exposed to cigarette smoke extract (CSE), and dendritic cells extracted from mice chronically exposed to cigarette smoke.,In human COPD lung tissue, we detected a significant increase in the total number of CD83+ cells, and significantly higher amounts of CD207 mRNA when compared with control tissue.,Human monocyte-derived dendritic cells exposed to CSE (0.1-2%) exhibited enhanced survival in vitro when compared with control dendritic cells.,Murine dendritic cells extracted from mice exposed to cigarette smoke for 4 weeks, also demonstrated enhanced survival compared to dendritic cells extracted from control mice.,Acute exposure of human dendritic cells to CSE induced the cellular pro-survival proteins heme-oxygenase-1 (HO-1), and B cell lymphoma leukemia-x(L) (Bcl-xL), predominantly through oxidative stress.,Although activated human dendritic cells conditioned with CSE expressed diminished migratory CCR7 expression, their migration towards the CCR7 ligand CCL21 was not impaired.,These data indicate that COPD is associated with increased numbers of cells bearing markers associated with Langerhans cells and mature dendritic cells, and that cigarette smoke promotes survival signals and augments survival of dendritic cells.,Although CSE suppressed dendritic cell CCR7 expression, migration towards a CCR7 ligand was not diminished, suggesting that reduced CCR7-dependent migration is unlikely to be an important mechanism for dendritic cell retention in the lungs of smokers with COPD. | 1 |
The coexistence of gastroesophageal reflux disease (GERD) and COPD has been recognized, but there has been no comprehensive evaluation of the impact of GERD on COPD-related health status and patient-centered outcomes.,Cross-sectional and longitudinal study of 4,483 participants in the COPDGene cohort who met GOLD criteria for COPD.,Physician-diagnosed GERD was ascertained by questionnaire.,Clinical features, spirometry and imaging were compared between COPD subjects without versus with GERD.,We evaluated the relationship between GERD and symptoms, exacerbations and markers of microaspiration in univariate and multivariate models.,Associations were additionally tested for the confounding effect of covariates associated with a diagnosis of GERD and the use of proton-pump inhibitor medications (PPIs).,To determine whether GERD is simply a marker for the presence of other conditions independently associated with worse COPD outcomes, we also tested models incorporating a GERD propensity score.,GERD was reported by 29% of subjects with female predominance.,Subjects with GERD were more likely to have chronic bronchitis symptoms, higher prevalence of prior cardiovascular events (combined myocardial infarction, coronary artery disease and stroke 21.3% vs.,13.4.0%, p < 0.0001).,Subjects with GERD also had more severe dyspnea (MMRC score 2.2 vs.,1.8, p < 0.0001), and poorer quality of life (QOL) scores (St.,George’s Respiratory Questionnaire (SGRQ) total score 41.8 vs.,34.9, p < 0.0001; SF36 Physical Component Score 38.2 vs.,41.4, p < 0.0001).,In multivariate models, a significant relationship was detected between GERD and SGRQ (3.4 points difference, p < 0.001) and frequent exacerbations at baseline (≥2 exacerbation per annum at inclusion OR 1.40, p = 0.006).,During a mean follow-up time of two years, GERD was also associated with frequent (≥2/year exacerbations OR 1.40, p = 0.006), even in models in which PPIs, GERD-PPI interactions and a GERD propensity score were included.,PPI use was associated with frequent exacerbator phenotype, but did not meaningfully influence the GERD-exacerbation association.,In COPD the presence of physician-diagnosed GERD is associated with increased symptoms, poorer QOL and increased frequency of exacerbations at baseline and during follow-up.,These associations are maintained after controlling for PPI use.,The PPI-exacerbations association could result from confounding-by-indication. | Mortality rate is high in patients with chronic obstructive pulmonary disease (COPD).,Our aim was to investigate long-term mortality and associated risk factors in COPD patients previously hospitalized for a COPD exacerbation.,A total of 256 patients from the Nordic countries were followed for 8.7 ± 0.4 years after the index hospitalization in 2000-2001.,Prior to discharge, the St George’s Respiratory Questionnaire was administered and data on therapy and comorbidities were obtained.,Information on long-term mortality was obtained from national registries in each of the Nordic countries.,In total, 202 patients (79%) died during the follow up period, whereas 54 (21%) were still alive.,Primary cause of death was respiratory (n = 116), cardiovascular (n = 43), malignancy (n = 28), other (n = 10), or unknown (n = 5).,Mortality was related to older age, with a hazard risk ratio (HRR) of 1.75 per 10 years, lower forced expiratory volume in 1 second (FEV1) (HRR 0.80), body mass index (BMI) <20 kg/m2 (HRR 3.21), and diabetes (HRR 3.02).,Older age, lower BMI, and diabetes were related to both respiratory and cardiovascular mortality.,An association was also found between lower FEV1 and respiratory mortality, whereas mortality was not significantly associated with therapy, anxiety, or depression.,Almost four out of five patients died within 9 years following an admission for COPD exacerbation.,Increased mortality was associated with older age, lower lung function, low BMI, and diabetes, and these factors should be taken into account when making clinical decisions about patients who have been admitted to hospital for a COPD exacerbation. | 1 |
Fatigue is the second most common symptom in patients with chronic obstructive pulmonary disease (COPD).,Despite its high prevalence, fatigue is often ignored in daily practice.,For this reason, little is known about the underlying determinants of fatigue in patients with COPD.,The primary objectives of this study are to chart the course of fatigue in patients with COPD, to identify the physical, systemic, psychological and behavioural factors that precipitate and perpetuate fatigue in patients with COPD, to evaluate the impact of exacerbation-related hospitalisations on fatigue and to better understand the association between fatigue and 2-year all-cause hospitalisation and mortality in patients with COPD.,The secondary aim is to identify diurnal differences in fatigue by using ecological momentary assessment (EMA).,This manuscript describes the protocol of the FAntasTIGUE study and gives an overview of the possible strengths, weaknesses and clinical implications.,A 2-year longitudinal, observational study, enrolling 400 patients with clinically stable COPD has been designed.,Fatigue, the primary outcome, will be measured by the subjective fatigue subscale of the Checklist Individual Strength (CIS-Fatigue).,The secondary outcome is the day-to-day/diurnal fatigue, registered in a subsample (n=60) by EMA.,CIS-Fatigue and EMA will be evaluated at baseline, and at 4, 8 and 12 months.,The precipitating and perpetuating factors of fatigue (physical, psychological, behavioural and systemic) will be assessed at baseline and at 12 months.,Additional assessments will be conducted following hospitalisation due to an exacerbation of COPD that occurs between baseline and 12 months.,Finally, at 18 and 24 months the participants will be followed up on their fatigue, number of exacerbations, exacerbation-related hospitalisation and survival.,This protocol was approved by the Medical research Ethics Committees United, Nieuwegein, the Netherlands (NL60484.100.17).,NTR6933; Pre-results. | Symptoms, particularly dyspnea, and activity limitation, have an impact on the health status and the ability to function normally in patients with chronic obstructive pulmonary disease (COPD).,To develop an electronic patient diary (eDiary), qualitative patient interviews were conducted from 2009 to 2010 to identify relevant symptoms and degree of bother due to symptoms.,The eDiary was completed by a subset of 209 patients with moderate-to-severe COPD in the 26-week QVA149 SHINE study.,Two morning assessments (since awakening and since the last assessment) and one evening assessment were made each day.,Assessments covered five symptoms (“shortness of breath,” “phlegm/mucus,” “chest tightness,” “wheezing,” and “coughing”) and two impact items (“bothered by COPD” and “difficulty with activities”) and were scored on a 10-point numeric scale.,Patient compliance with the eDiary was 90.4% at baseline and 81.3% at week 26.,Correlations between shortness of breath and impact items were >0.95.,Regression analysis showed that shortness of breath was a highly significant (P<0.0001) predictor of impact items.,Exploratory factor analysis gave a single factor comprising all eDiary items, including both symptoms and impact items.,Shortness of breath, the total score (including five symptoms and two impact items), and the five-item symptom score from the eDiary performed well, with good consistency and reliability.,The eDiary showed good sensitivity to change, with a 0.6 points reduction in the symptoms scores (on a 0-10 point scale) representing a meaningful change.,The eDiary was found to be valid, reliable, and responsive.,The high correlations obtained between “shortness of breath” and the ratings of “bother” and “difficulty with activities” confirmed the relevance of this symptom in patients with COPD.,Future studies will be required to explore further psychometric properties and their ability to differentiate between COPD treatments. | 1 |
The traditional classification of COPD, which relies solely on spirometry, fails to account for the complexity and heterogeneity of the disease.,Phenotyping is a method that attempts to derive a single or combination of disease attributes that are associated with clinically meaningful outcomes.,Deriving phenotypes entails the use of cluster analyses, and helps individualize patient management by identifying groups of individuals with similar characteristics.,We aimed to systematically review the literature for studies that had derived such phenotypes using unsupervised methods.,Two independent reviewers systematically searched multiple databases for studies that performed validated statistical analyses, free of definitive pre-determined hypotheses, to derive phenotypes among patients with COPD.,Data were extracted independently.,9156 citations were retrieved, of which, 8 studies were included.,The number of subjects ranged from 213 to 1543.,Most studies appeared to be biased: patients were more likely males, with severe disease, and recruited in tertiary care settings.,Statistical methods used to derive phenotypes varied by study.,The number of phenotypes identified ranged from 2 to 5.,Two phenotypes, with poor longitudinal health outcomes, were common across multiple studies: young patients with severe respiratory disease, few cardiovascular co-morbidities, poor nutritional status and poor health status, and a phenotype of older patients with moderate respiratory disease, obesity, cardiovascular and metabolic co-morbidities.,The recognition that two phenotypes of COPD were often reported may have clinical implications for altering the course of the disease.,This review also provided important information on limitations of phenotype studies in COPD and the need for improvement in future studies.,The online version of this article (doi:10.1186/s12931-015-0208-4) contains supplementary material, which is available to authorized users. | Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies.,To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).,Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years.,We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation.,Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs.,0.9 (1.1) per year, p<0.001) compared to non-inflamed ones.,As a descriptive study our results show associations but do not prove causality.,Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.,Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment. | 1 |
Chronic obstructive pulmonary disease (COPD) is a major cause of mortality.,Patients with advanced disease often have a poor quality of life, such that guidelines recommend providing palliative care in their last year of life.,Uptake and use of palliative care in advanced COPD is low; difficulty in predicting 1-year mortality is thought to be a major contributing factor.,We identified two primary care COPD cohorts using UK electronic healthcare records (Clinical Practice Research Datalink).,The first cohort was randomised equally into training and test sets.,An external dataset was drawn from a second cohort.,A risk model to predict mortality within 12 months was derived from the training set using backwards elimination Cox regression.,The model was given the acronym BARC based on putative prognostic factors including body mass index and blood results (B), age (A), respiratory variables (airflow obstruction, exacerbations, smoking) (R) and comorbidities (C).,The BARC index predictive performance was validated in the test set and external dataset by assessing calibration and discrimination.,The observed and expected probabilities of death were assessed for increasing quartiles of mortality risk (very low risk, low risk, moderate risk, high risk).,The BARC index was compared to the established index scores body mass index, obstructive, dyspnoea and exacerbations (BODEx), dyspnoea, obstruction, smoking and exacerbations (DOSE) and age, dyspnoea and obstruction (ADO).,Fifty-four thousand nine hundred ninety patients were eligible from the first cohort and 4931 from the second cohort.,Eighteen variables were included in the BARC, including age, airflow obstruction, body mass index, smoking, exacerbations and comorbidities.,The risk model had acceptable predictive performance (test set: C-index = 0.79, 95% CI 0.78-0.81, D-statistic = 1.87, 95% CI 1.77-1.96, calibration slope = 0.95, 95% CI 0.9-0.99; external dataset: C-index = 0.67, 95% CI 0.65-0.7, D-statistic = 0.98, 95% CI 0.8-1.2, calibration slope = 0.54, 95% CI 0.45-0.64) and acceptable accuracy predicting the probability of death (probability of death in 1 year, n high-risk group, test set: expected = 0.31, observed = 0.30; external dataset: expected = 0.22, observed = 0.27).,The BARC compared favourably to existing index scores that can also be applied without specialist respiratory variables (area under the curve: BARC = 0.78, 95% CI 0.76-0.79; BODEx = 0.48, 95% CI 0.45-0.51; DOSE = 0.60, 95% CI 0.57-0.61; ADO = 0.68, 95% CI 0.66-0.69, external dataset: BARC = 0.70, 95% CI 0.67-0.72; BODEx = 0.41, 95% CI 0.38-0.45; DOSE = 0.52, 95% CI 0.49-0.55; ADO = 0.57, 95% CI 0.54-0.60).,The BARC index performed better than existing tools in predicting 1-year mortality.,Critically, the risk score only requires routinely collected non-specialist information which, therefore, could help identify patients seen in primary care that may benefit from palliative care.,The online version of this article (10.1186/s12916-019-1310-0) contains supplementary material, which is available to authorized users. | Our aim was to assess the impact of comorbidities on existing COPD prognosis scores.,A total of 543 patients with COPD (FEV1 <80% and FEV1/FVC <70%) were included between January 2003 and January 2004.,Patients were stable for at least 6 weeks before inclusion and were followed for 5 years without any intervention by the research team.,Comorbidities and causes of death were established from medical reports or information from primary care medical records.,The GOLD system and the body mass index, obstruction, dyspnea and exercise (BODE) index were used for COPD classification.,Patients were also classified into four clusters depending on the respiratory disease and comorbidities.,Cluster analysis was performed by combining multiple correspondence analyses and automatic classification.,Receiver operating characteristic curves and the area under the curve (AUC) were calculated for each model, and the DeLong test was used to evaluate differences between AUCs.,Improvement in prediction ability was analyzed by the DeLong test, category-free net reclassification improvement and the integrated discrimination index.,Among the 543 patients enrolled, 521 (96%) were male, with a mean age of 68 years, mean body mass index 28.3 and mean FEV1% 55%.,A total of 167 patients died during the study follow-up.,Comorbidities were prevalent in our cohort, with a mean Charlson index of 2.4.,The most prevalent comorbidities were hypertension, diabetes mellitus and cardiovascular diseases.,On comparing the BODE index, GOLDABCD, GOLD2017 and cluster analysis for predicting mortality, cluster system was found to be superior compared with GOLD2017 (0.654 vs 0.722, P=0.006), without significant differences between other classification models.,When cardiovascular comorbidities and chronic renal failure were added to the existing scores, their prognostic capacity was statistically superior (P<0.001).,Comorbidities should be taken into account in COPD management scores due to their prevalence and impact on mortality. | 1 |
The burden of chronic obstructive pulmonary disease (COPD) is high.,Health benefits can be gained in primary care by early detection and preventive measures.,To compare the effectiveness of two strategies for population-based early detection of COPD, taking into account different socioeconomic status (SES) settings.,Practices were randomised on strategy and stratified on SES setting.,The Respiratory Health Screening Questionnaire (RHSQ) was distributed to all participants.,In the practice-managed condition, the practice was responsible for the whole procedure, while in the patient-managed condition, patients were responsible for calculating their RHSQ risk score and applying for a spirometry test.,The main outcome measure was the rate of COPD diagnoses after screening.,More new COPD patients were detected in the practice-managed condition (36%) than in the patient-managed condition (18%).,In low SES practices, more high-risk patients were found (16%) than in moderate-to-high SES practices (9%).,Recalculated for a standard Dutch practice (2,350 patients), the yield would be 8.9 new COPD diagnoses, which is a 20% increase of known cases.,The practice-managed variant of this screening procedure shows a substantial yield of new COPD diagnoses for both low and moderate-to-high SES practices. | Chronic obstructive pulmonary disease (COPD) is underdiagnosed in general practice.,Our aim was to implement a population-based approach for the early detection of COPD and to assess its impact on primary care workload and costs, and the influence of socioeconomic status (SES).,An observational study with mixed methods was performed in 10 Dutch general practices of either low or moderate to high SES.,The Respiratory Health Screening Questionnaire was posted during a three-month period to all persons aged 45, 55, and 65 years (one age group per month).,The practices calculated the risk, and patients at high risk of COPD were invited for spirometry at the practice.,The general practitioner used the spirometric results and a consultation to establish a clinical diagnosis.,Qualitative and quantitative data on workload, cost, and barriers were evaluated.,Ten practices returned 293 (35.3%) COPD risk tests for the three age groups.,Participants from low SES practices responded better than those from moderate to high SES practices (40.8% vs.,30.5%).,In practices with low SES 17.9% of the tests indicated high risk compared with 16.1% in practices with moderate to high SES.,Nine patients (23%) were newly diagnosed with COPD.,The healthcare providers' extra workload averaged 18.5 hours during the three months for one standard practice.,The average cost of this survey programme (three age groups in three months) was 荤520 for low SES practices and 荤398 for moderate to high SES practices.,All healthcare providers affirmed that the extra workload in this survey model is acceptable and feasible when finances are compensated.,Early detection of COPD is feasible in daily life primary care.,In moderate to high SES practices the costs of detecting COPD were less than in low SES practices. | 1 |
Depression is a common and mostly undertreated problem in patients with chronic diseases.,However, population-based studies on the association between chronic obstructive pulmonary disease (COPD) and subsequent depression are limited in Asian populations.,This study evaluated the incidence and risk factors of depression for patients with COPD in Taiwan.,Using the claims data from the National Health Insurance of Taiwan, we identified 38,010 COPD patients newly diagnosed in 2000-2004 and 38,010 subjects without COPD frequency, matched by sex, age and index date.,The incidence rate and hazard ratio for depression were estimated by the end of 2008.,The incidence rate of depression was 1.88 folds higher in the COPD cohort than in the non-COPD cohort (12.2 versus 6.47 per 1,000 person-years, p < 0.0001).,The depression risk was the greatest within the first year following COPD diagnosis and tended to decline with follow-up time.,Among COPD patients, multivariate analysis showed that younger women and low-income patients were at higher risk of depression.,Hospitalization and comorbidities such as hypertension, arthritis, cancer, and heart disease were also significant predictors for depression risk.,This population-based cohort study demonstrated a strong relationship between COPD and subsequent depression.,These findings could assist healthcare providers to pinpoint individuals with a higher predisposition to having depression, which could then facilitate the provision of culturally appropriate rehabilitation within the first year after the diagnosis of COPD. | Hospital readmission for acute exacerbation of COPD (AECOPD) occurs in up to 30% of patients, leading to excess morbidity and poor survival.,Physiological risk factors predict readmission, but the impact of modifiable psychosocial risk factors remains uncertain.,We aimed to evaluate whether psychosocial risk factors independently predict readmission for AECOPD in patients referred to early discharge services (EDS).,This prospective cohort study included 79 patients with AECOPD cared for by nurse led EDS in the UK, and followed up for 12 months.,Data on lung function, medical comorbidities, previous hospital admissions, medications, and sociodemographics were collected at baseline; St George's Respiratory Questionnaire (SGRQ), Hospital Anxiety and Depression Scale (HADS), and social support were measured at baseline, 3 and 12-months.,Exploratory multivariate models were fitted to identify psychosocial factors associated with readmission adjusted for known confounders.,26 patients were readmitted within 90 days and 60 patients were readmitted at least once during follow-up.,Depression at baseline predicted readmission adjusted for sociodemographics and forced expiratory volume in 1 second (odds ratio 1.30, 95% CI 1.06 to 1.60, p = 0.013).,Perceived social support was not significantly associated with risk of readmission.,Home ownership was associated with the total number of readmissions (B = 0.46, 95% CI -0.86 to -0.06, p = 0.024).,Compared with those not readmitted, readmitted patients had worse SGRQ and HADS scores at 12 months.,Depressive symptoms and socioeconomic status, but not perceived social support, predict risk of readmission and readmission frequency for AECOPD in patients cared for by nurse-led EDS.,Future work on reducing demand for unscheduled hospital admissions could include the design and evaluation of interventions aimed at optimising the psychosocial care of AECOPD patients managed at home. | 1 |
The objective of this study was to identify the necessary features of pulmonary telerehabilitation (P-TR) from the perspectives of individuals living with chronic lung disease and health care professionals (HCPs) who deliver pulmonary rehabilitation (PR).,Focus groups were carried out with patients (n = 26) and HCPs (n = 26) to elicit and explore their opinions about the critical elements of in-person PR and ideas for how these elements could be supported using technology.,A questionnaire was used to assess technology use, PR experience, and general health status.,Four key elements of PR were identified as critical to P-TR: the social aspect of PR; communicating with HCPs for education and support; using biosensors for monitoring and promoting self-knowledge; and the evolution of support with progress over time.,A range of technology-enabled devices and programs were suggested as means to recreate aspects of these integral elements.,Consultations with patients and HCPs suggest that users are interested in technology and want to ensure it recreates the important aspects of PR.,Patients and HCPs identified similar key elements for P-TR.,The opinions and suggestions of patients and HCPs should be the driving force of innovation if P-TR is to succeed in improving health outcomes. | Most guidelines recommend pulmonary rehabilitation (PR) for patients with chronic obstructive pulmonary disease (COPD) and modified Medical Research Council dyspnea scale (mMRC) levels ≥2, but the effectiveness of PR in patients with less advanced disease is not well established.,Our aim was to investigate the effects of PR in patients with COPD and mMRC ≤1.,The methodology was developed as a part of evidence-based guideline development and is in accordance with the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group.,We identified randomized controlled trials (RCTs) through a systematic, multidatabase literature search and selected RCTs comparing the effects of PR with usual care in patients with COPD and mMRC ≤1.,Predefined critical outcomes were health-related quality of life (HRQoL), adverse effects and mortality, while walking distance, maximal exercise capacity, muscle strength, and dropouts were important outcomes.,Two authors independently extracted data, assessed trial eligibility and risk of bias, and graded the evidence.,Meta-analyses were performed when deemed feasible.,Four RCTs (489 participants) were included.,On the basis of moderate-quality evidence, we found a clinically and statistically significant improvement in short-term HRQoL of 4.2 units (95% confidence interval [CI]: [−4.51 to −3.89]) on St George’s Respiratory Questionnaire, but not at the longest follow-up.,We also found a statistically significant improvement of 25.71 m (95% CI: [15.76-35.65]) in the 6-minute walk test with PR; however, this improvement was not considered clinically relevant.,No difference was found for mortality, and insufficient data prohibited meta-analysis for muscle strength and maximal exercise capacity.,No adverse effects were reported.,We found a moderate quality of evidence suggesting a small, significant improvement in short-term HRQoL and a clinically nonsignificant improvement in walking distance following PR in patients with COPD and mild symptoms.,This resulted in a weak recommendation of routine PR in these patients using the GRADE approach. | 1 |
Readmission following COPD exacerbation is a common and challenging clinical problem.,New approaches to predicting readmissions are required to help mitigate risk and develop novel interventions.,We conducted a prospective cohort study in 82 COPD patients admitted due to an exacerbation of COPD.,Lung function measures [spirometry, forced oscillation technique (FOT) indices and peak inspiratory flow rate (PIFR)], inflammatory biomarkers and patient-reported outcomes including previous exacerbation history, breathlessness, quality of life and frailty were measured at admission and discharge.,We prospectively followed patients for 30 and 90 days to identify predictors for readmission.,The readmission rate within 30 days was 38%, and 56% within 90 days.,Previous exacerbations, higher COPD Assessment Test score at discharge, frailty, reduced PIFR and increased length of stay were significantly associated with 30-day readmission.,PIFR at discharge and frailty had the highest predictive ability for 30-day readmission using area under receiver operating characteristic curves (AUC 0.86, 95% CI 0.78-0.95, p < 0.001 and AUC 0.81, 95% CI 0.71-0.90, p < 0.001, respectively).,Ninety-day readmissions were significantly associated with previous exacerbations and hospitalisations, higher CAT score at discharge, frailty, depression, lower PIFR and greater expiratory flow limitation (EFL) in the supine position.,The best predictive variable in multivariable analysis for both 30- and 90-day readmission was PIFR at discharge.,PIFR, CAT score, frailty, and EFL were found to be associated with 30- and 90-day readmission following COPD exacerbation.,These findings help identify those at highest risk and to optimise care prior to discharge. | In the Withdrawal of Inhaled Steroids during Optimized Bronchodilator Management (WISDOM) trial, inhaled corticosteroid (ICS) withdrawal in patients with chronic obstructive pulmonary disease receiving triple therapy (long-acting β2-agonist+long-acting muscarinic antagonist+ICS) did not change moderate/severe exacerbation risk.,However, many patients were not taking triple therapy before study participation.,This analysis was conducted to eliminate the impact of non-ICS users on WISDOM results by re-analyzing the data using only the subset of patients who were taking triple therapy at screening.,The effect of ICS withdrawal on moderate/severe exacerbation risk in the subgroup of WISDOM patients taking triple therapy before enrolling in the study was evaluated in this post hoc analysis.,Additionally, the effect of ICS withdrawal in patients with a history of ≥2 exacerbations in the previous year and various blood eosinophil counts was assessed.,Overall, 39.0% (n=970: ICS continuation, 479; ICS withdrawal, 491) of the WISDOM trial population were taking triple therapy at screening.,Baseline characteristics were generally similar between groups.,Moderate/severe exacerbation risk between the ICS withdrawal and continuation groups (hazard ratio [HR], 1.05; 95% confidence interval [CI]: 0.89-1.25) was not increased in patients taking triple therapy at screening versus the overall trial population (HR [95% CI]: 1.06 [0.94-1.19]).,However, in patients with a history of ≥2 exacerbations, exacerbation risk (HR [95% CI]) increased nominally with blood eosinophil count from 1.07 [0.81-1.41] (≥100 cells/μL) to 1.45 [0.58-3.60] (≥400 cells/μL).,Consistent with results from the overall WISDOM trial population, ICS withdrawal did not increase exacerbation risk in patients taking triple therapy at screening.,Patients with a history of frequent exacerbations and higher blood eosinophil counts could benefit from continuation of ICS-based therapy.,Point your SmartPhone at the code above.,If you have a QR code reader the video abstract will appear.,Or use:,https://youtu.be/q_gF6ypMYJw | 1 |
Guidelines now call for a thorough and comprehensive description of the development of healthcare interventions to aid evaluation and understanding of the processes of change.,This was the primary aim of this study but we also recognised that effective interventions are commonly not implemented in clinical practice.,It is suggested that insufficient attention is given to the implementation process at the development phase of interventions.,This study outlines the 5 step iterative process we adopted for considering both implementation and effectiveness issues from the outset of intervention development.,We use the development of a complex intervention Tailored intervention for ANxiety and DEpression Management (TANDEM) in patients with chronic obstructive pulmonary disease to illustrate this process.,Intervention development built upon the Medical Research Council framework for developing complex interventions and the person-based approach for development of behavioural interventions.,Building an expert team, specifying theory, qualitative data collection and pre-piloting were all critical steps in our intervention development and are described here.,Contact with experts in the field, and explicitly building on previous work, ensured efficiency of design.,Qualitative work suggested guiding principles for the intervention such as introducing mood in relation to breathlessness, and providing flexible tailoring to patients’ needs, whilst implementation principles focused on training selected respiratory professionals and requiring supervision to ensure standards of care.,Subsequent steps of intervention development, pre-piloting and intervention refinement led to an intervention that was deemed acceptable and if successful will be ready for implementation.,The TANDEM study was developed efficiently by building on previous work and considering implementation issues from the outset, with the aim that if shown to be effective it will have more rapid translation in to the health care system with accelerated patient benefits.,ISRCTN ISRCTN59537391.,Registered on 20 March 2017.,Protocol version 6.0, 22 April 2018.,The online version contains supplementary material available at 10.1186/s13063-021-05203-x. | 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 |
Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg has been shown to improve lung function and health status, and reduce exacerbations, versus budesonide/formoterol in patients with chronic obstructive pulmonary disease (COPD).,We evaluated the non-inferiority of single-inhaler FF/UMEC/VI versus FF/VI + UMEC using two inhalers.,Eligible patients with COPD (aged ≥40 years; ≥1 moderate/severe exacerbation in the 12 months before screening) were randomized (1:1; stratified by the number of long-acting bronchodilators [0, 1 or 2] per day during run-in) to receive 24-week FF/UMEC/VI 100/62.5/25 μg and placebo or FF/VI 100/25 μg + UMEC 62.5 μg; all treatments/placebo were delivered using the ELLIPTA inhaler once-daily in the morning.,Primary endpoint: change from baseline in trough forced expiratory volume in 1 s (FEV1) at Week 24.,The non-inferiority margin for the lower 95% confidence limit was set at − 50 mL.,A total of 1055 patients (844 [80%] of whom were enrolled on combination maintenance therapy) were randomized to receive FF/UMEC/VI (n = 527) or FF/VI + UMEC (n = 528).,Mean change from baseline in trough FEV1 at Week 24 was 113 mL (95% CI 91, 135) for FF/UMEC/VI and 95 mL (95% CI 72, 117) for FF/VI + UMEC; the between-treatment difference of 18 mL (95% CI -13, 50) confirmed FF/UMEC/VI’s was considered non-inferior to FF/VI + UMEC.,At Week 24, the proportion of responders based on St George’s Respiratory Questionnaire Total score was 50% (FF/UMEC/VI) and 51% (FF/VI + UMEC); the proportion of responders based on the Transitional Dyspnea Index focal score was similar (56% both groups).,A similar proportion of patients experienced a moderate/severe exacerbation in the FF/UMEC/VI (24%) and FF/VI + UMEC (27%) groups; the hazard ratio for time to first moderate/severe exacerbation with FF/UMEC/VI versus FF/VI + UMEC was 0.87 (95% CI 0.68, 1.12).,The incidence of adverse events was comparable in both groups (48%); the incidence of serious adverse events was 10% (FF/UMEC/VI) and 11% (FF/VI + UMEC).,Single-inhaler triple therapy (FF/UMEC/VI) is non-inferior to two inhalers (FF/VI + UMEC) on trough FEV1 change from baseline at 24 weeks.,Results were similar on all other measures of efficacy, health-related quality of life, and safety.,GSK study CTT200812; ClinicalTrials.gov NCT02729051 (submitted 31 March 2016). | Real-world prescription pathways leading to triple therapy (TT) (inhaled corticosteroid [ICS] plus long-acting β2-agonist bronchodilator [LABA] plus long-acting muscarinic antagonist) differ from Global initiative for chronic Obstructive Lung Disease [GOLD] and National Institute for Health and Care Excellence treatment recommendations.,This study sets out to identify COPD patients without asthma receiving TT, and determine the pathways taken from diagnosis to the first prescription of TT.,This was a historical analysis of COPD patients without asthma from the Optimum Patient Care Research Database (387 primary-care practices across the UK) from 2002 to 2010.,Patient disease severity was classified using GOLD 2013 criteria.,Data were analyzed to determine prescribing of TT before, at, and after COPD diagnosis; the average time taken to receive TT; and the impact of lung function grade, modified Medical Research Council dyspnea score, and exacerbation history on the pathway to TT.,During the study period, 32% of patients received TT.,Of these, 19%, 28%, 37%, and 46% of patients classified as GOLD A, B, C, and D, respectively, progressed to TT after diagnosis (P<0.001).,Of all patients prescribed TT, 25% were prescribed TT within 1 year of diagnosis, irrespective of GOLD classification (P=0.065).,The most common prescription pathway to TT was LABA plus ICS.,It was observed that exacerbation history did influence the pathway of LABA plus ICS to TT.,Real life UK prescription data demonstrates the inappropriate prescribing of TT and confirms that starting patients on ICS plus LABA results in the inevitable drift to overuse of TT.,This study highlights the need for dissemination and implementation of COPD guidelines to physicians, ensuring that patients receive the recommended therapy. | 1 |
Co-morbidities are common in chronic obstructive pulmonary disease (COPD).,We assessed the contribution of common co-morbidities on health related quality of life (HRQoL) among COPD patients.,Using both generic (15D) and respiratory-specific (AQ20) instruments, HRQoL was assessed in a hospital based COPD population (N = 739, 64% males, mean age 64 years, SD 7 years) in this observational study with inferential analysis.,The prevalence of their co-morbidities was compared with those of 5000 population controls.,The patients represented all severity stages of COPD and the patterns of common concomitant disorders differed between patients.,Co-morbidities such as psychiatric conditions, alcohol abuse, cardiovascular diseases, and diabetes were more common among COPD patients than in age and gender matched controls.,Psychiatric conditions and alcohol abuse were the strongest determinants of HRQoL in COPD and could be detected by both 15D (Odds Ratio 4.7 and 2.3 respectively) and AQ20 (OR 2.0 and 3.0) instruments.,Compared to respiratory specific AQ20, generic 15D was more sensitive to the effects of comorbidities while AQ20 was slightly more sensitive for the low FEV1.,FEV1 was a strong determinant of HRQoL only at more severe stages of disease (FEV1 < 40% of predicted).,Poor HRQoL also predicted death during the next five years.,The results suggest that co-morbidities may impair HRQoL at an early stage of the disease, while bronchial obstruction becomes a significant determinant of HRQoL only in severe COPD. | The purpose of our study was to examine the association of prior outpatient use of statins and angiotensin converting enzyme (ACE) inhibitors on mortality for subjects ≥ 65 years of age hospitalized with acute COPD exacerbations.,We conducted a retrospective national cohort study using Veterans Affairs administrative data including subjects ≥65 years of age hospitalized with a COPD exacerbation.,Our primary analysis was a multilevel model with the dependent variable of 90-day mortality and hospital as a random effect, controlling for preexisting comorbid conditions, demographics, and other medications prescribed.,We identified 11,212 subjects with a mean age of 74.0 years, 98% were male, and 12.4% of subjects died within 90-days of hospital presentation.,In this cohort, 20.3% of subjects were using statins, 32.0% were using ACE inhibitors or angiotensin II receptor blockers (ARB).,After adjusting for potential confounders, current statin use (odds ratio 0.51, 95% confidence interval 0.40-0.64) and ACE inhibitor/ARB use (0.55, 0.46-0.66) were significantly associated with decreased 90-day mortality.,Use of statins and ACE inhibitors prior to admission is associated with decreased mortality in subjects hospitalized with a COPD exacerbation.,Randomized controlled trials are needed to examine whether the use of these medications are protective for those patients with COPD exacerbations. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) exhibit dominant features of chronic bronchitis, emphysema, and/or asthma, with a common phenotype of airflow obstruction.,COPD pulmonary physiology reflects the sum of pathological changes in COPD, which can occur in large central airways, small peripheral airways, and the lung parenchyma.,Quantitative or high-resolution computed tomography is used as a surrogate measure for assessment of disease progression.,Different biological or molecular markers have been reported that reflect the mechanistic or pathogenic triad of inflammation, proteases, and oxidants and correspond to the different aspects of COPD histopathology.,Similar to the pathogenic triad markers, genetic variations or polymorphisms have also been linked to COPD-associated inflammation, protease-antiprotease imbalance, and oxidative stress.,Furthermore, in recent years, there have been reports identifying aging-associated mechanistic markers as downstream consequences of the pathogenic triad in the lungs from COPD patients.,For this review, the authors have limited their discussion to a review of mechanistic markers and genetic variations and their association with COPD histopathology and disease status. | Chronic obstructive pulmonary disease (COPD) is associated with increased oxidative and nitrosative stress.,The aim of our study was to assess the importance of these factors in the airways of healthy smokers and symptomatic smokers without airway obstruction, i.e. individuals with GOLD stage 0 COPD.,Exhaled NO (FENO) and induced sputum samples were collected from 22 current smokers (13 healthy smokers without any respiratory symptoms and 9 with symptoms i.e. stage 0 COPD) and 22 healthy age-matched non-smokers (11 never smokers and 11 ex-smokers).,Sputum cell differential counts, and expressions of inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE) were analysed from cytospins by immunocytochemistry.,Eosinophil cationic protein (ECP) and lactoferrin were measured from sputum supernatants by ELISA.,FENO was significantly decreased in smokers, mean (SD) 11.0 (6.7) ppb, compared to non-smokers, 22.9 (10.0), p < 0.0001.,Induced sputum showed increased levels of neutrophils (p = 0.01) and elevated numbers of iNOS (p = 0.004), MPO (p = 0.003), nitrotyrosine (p = 0.003), and 4-HNE (p = 0.03) positive cells in smokers when compared to non-smokers.,Sputum lactoferrin levels were also higher in smokers than in non-smokers (p = 0.02).,Furthermore, we noted four negative correlations between FENO and 1) total neutrophils (r = -0.367, p = 0.02), 2) positive cells for iNOS (r = -0.503, p = 0.005), 3) MPO (r = -0.547, p = 0.008), and 4) nitrotyrosine (r = -0.424, p = 0.03).,However, no major differences were found between never smokers and ex-smokers or between healthy smokers and stage 0 COPD patients.,Our results clearly indicate that several markers of oxidative/nitrosative stress are increased in current cigarette smokers compared to non-smokers and no major differences can be observed in these biomarkers between non-symptomatic smokers and subjects with GOLD stage 0 COPD. | 1 |
Long-term use of macrolide antibiotics is effective to prevent exacerbations in chronic obstructive pulmonary disease (COPD).,As risks and side effects of long-term intervention outweigh the benefits in the general COPD population, the optimal dose, duration of treatment, and target population are yet to be defined.,Hospitalization for an acute exacerbation (AE) of COPD may offer a targeted risk group and an obvious risk period for studying macrolide interventions.,Patients with COPD, hospitalized for an AE, who have a smoking history of ≥10 pack-years and had ≥1 exacerbation in the previous year will be enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (NCT02135354).,On top of a standardized treatment of systemic corticosteroids and antibiotics, subjects will be randomized to receive either azithromycin or placebo during 3 months, at an uploading dose of 500 mg once a day for 3 days, followed by a maintenance dose of 250 mg once every 2 days.,The primary endpoint is the time-to-treatment failure during the treatment phase (ie, from the moment of randomization until the end of intervention).,Treatment failure is a novel composite endpoint defined as either death, the admission to intensive care or the requirement of additional systemic steroids or new antibiotics for respiratory reasons, or the diagnosis of a new AE after discharge.,We investigate whether azithromycin initiated at the onset of a severe exacerbation, with a limited duration and at a low dose, might be effective and safe in the highest risk period during and immediately after the acute event.,If proven effective and safe, this targeted approach may improve the treatment of severe AEs and redirect the preventive use of azithromycin in COPD to a temporary intervention in the subgroup with the highest unmet needs. | Twenty per cent of chronic obstructive pulmonary disease (COPD) patients are readmitted for acute exacerbation (AECOPD) within 30 days of discharge.,The prognostic significance of early readmission is not fully understood.,The objective of our study was to estimate the mortality risk associated with readmission for acute exacerbation within 30 days of discharge in COPD patients.,The cohort (n = 378) was divided into patients readmitted (n = 68) and not readmitted (n = 310) within 30 days of discharge.,Clinical, laboratory, microbiological, and severity data were evaluated at admission and during hospital stay, and mortality data were recorded at four time points during follow-up: 30 days, 6 months, 1 year and 3 years.,Patients readmitted within 30 days had poorer lung function, worse dyspnea perception and higher clinical severity.,Two or more prior AECOPD (HR, 2.47; 95% CI, 1.51-4.05) was the only variable independently associated with 30-day readmission.,The mortality risk during the follow-up period showed a progressive increase in patients readmitted within 30 days in comparison to patients not readmitted; moreover, 30-day readmission was an independent risk factor for mortality at 1 year (HR, 2.48; 95% CI, 1.10-5.59).,In patients readmitted within 30 days, the estimated absolute increase in the mortality risk was 4% at 30 days (number needed to harm NNH, 25), 17% at 6-months (NNH, 6), 19% at 1-year (NNH, 6) and 24% at 3 years (NNH, 5).,In conclusion a readmission for AECOPD within 30 days is associated with a progressive increased long-term risk of death. | 1 |
Fresh peripheral blood (PB) samples from 432 outpatients with stable chronic obstructive pulmonary disease (COPD) were examined.,Patients were classified into Group A (large SRA+ cells were undetected) and Group B (large SRA+ cells were detected) and followed‐up for 1 year.,Patients were further subdivided according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage.,Cox proportional hazard model had shown that Gold, Group, home oxygen therapy (HOT), and treatment were significant predictors of severe exacerbation.,Six of 353 patients in Group A and 29 of 79 in Group B developed severe exacerbation.,The rates of severe exacerbation were significantly higher in Group B patients, GOLD stage 2 than Group A, GOLD stage 2; in Group B, GOLD stage 3 than Group A, GOLD stage 3; and in all of Group B compared with in all of Group A.,The Kaplan‐Meier curves of Group B, GOLD stages 1-4, and of all of Group B showed significantly worse rates of severe exacerbation than those of Group A, Gold 1-4, and all of Group A, respectively.,The appearance of large SRA+ cells in the PB of patients with stable COPD may represent a useful biomarker for severe COPD exacerbation. | A multidimensional assessment of COPD was recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) in 2013 and revised in 2017.,We examined the ability of the GOLD 2017 and the new 16 subgroup (1A-4D) classifications to predict clinical outcomes, including exacerbation and mortality, and compared them with the GOLD 2013 classifications.,Patients with COPD were recruited from January 2006 to December 2017.,The predictive abilities of grades 1-4 and groups A-D were examined through a logistic regression analysis with receiver operating curve estimations and area under the curve (AUC).,A total of 553 subjects with COPD were analyzed.,The mortality rate was 48.6% during a median follow-up period of 5.2 years.,Both the GOLD 2017 and the 2013 group A-D classifications had good predictive ability for total and severe exacerbations, for which the AUCs were 0.79 vs 0.77 and 0.79 vs 0.78, respectively.,The AUCs for the GOLD 2017 groups A-D, grades 1-4, and the GOLD 2013 group A-D classifications were 0.70, 0.66, and 0.70 for all-cause mortality and 0.73, 0.71, and 0.74 for respiratory cause mortality, respectively.,Combining the spirometric staging with the grouping for the GOLD 2017 subgroups (1A-4D), the all-cause mortality rate for group B and D patients was significantly increased from subgroups 1B-4B (27.7%, 50.6%, 53.3%, and 69.2%, respectively) and groups 1D-4D (55.0%, 68.8%, 82.1%, and 90.5%, respectively).,The AUCs of subgroups (1A-4D) were 0.73 and 0.77 for all-cause and respiratory mortality, respectively; the new classification was determined more accurate than the GOLD 2017 for predicting mortality (P<0.0001).,The GOLD 2017 classification performed well by identifying individuals at risk of exacerbation, but its predictive ability for mortality was poor among COPD patients.,Combining the spirometric staging with the grouping increased the predictive ability for all-cause and respiratory mortality.,We validate the ability of the GOLD 2017 and 16 subgroup (1A-4D) classifications to predict clinical outcome for COPD patients.,The GOLD 2017 classification performed well by identifying individuals at risk of exacerbation, but its predictive ability for mortality was poor.,The new 16 subgroup (1A-4D) classification combining the spirometric 1-4 staging and the A-D grouping increased the predictive ability for mortality and was better than the GOLD 2017 for predicting all-cause and respiratory mortality among COPD patients. | 1 |
The natural disease course of chronic obstructive pulmonary disease (COPD) is often punctuated by exacerbations: acute events of symptom worsening associated with significant morbidity and healthcare resource utilization; reduced quality of life; and increased risk of hospitalization and death.,The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommend that patients at risk of exacerbations (GOLD Groups C and D) receive a long-acting muscarinic antagonist (LAMA) or a long-acting β2-agonist (LABA)/LAMA combination, respectively, as preferred initial treatments.,The latter recommendation is based on recent trial evidence demonstrating the superior efficacy of a fixed-dose LABA/LAMA over an inhaled corticosteroid (ICS)/LABA in exacerbation prevention.,ICS in combination with a LABA is also indicated for prevention of exacerbations, but the use of ICS is associated with an increased risk of adverse events such as pneumonia, and offers limited benefits beyond those provided by LABA or LAMA monotherapy.,In this review, we examine evidence from a number of pivotal studies of LABAs and LAMAs, administered as monotherapy or as part of dual or triple combination therapy, with a specific focus on their effect on exacerbations.,We also discuss a new proposed treatment paradigm for the management of COPD that takes into account this recent evidence and adopts a more cautious approach to the use of ICS.,In alignment with GOLD 2017, we suggest that ICS should be reserved for patients with concomitant asthma or in whom exacerbations persist despite treatment with LABA/LAMA. | 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. | 1 |
The quality of care can be improved by the development and implementation of evidence-based treatment guidelines.,Different national guidelines for chronic obstructive pulmonary disease (COPD) exist in Europe and relevant differences may exist among them.,This was an evaluation of COPD treatment guidelines published in Europe and Russia in the past 7 years.,Each guideline was reviewed in detail and information about the most important aspects of patient diagnosis, risk stratification and pharmacotherapy was extracted following a standardised process.,Guidelines were available from the Czech Republic, England and Wales, Finland, France, Germany, Italy, Poland, Portugal, Russia, Spain and Sweden.,The treatment goals, criteria for COPD diagnosis, consideration of comorbidities in treatment selection and support for use of long-acting bronchodilators, were similar across treatment guidelines.,There were differences in measures used for stratification of disease severity, consideration of patient phenotypes, criteria for the use of inhaled corticosteroids and recommendations for other medications (e.g. theophylline and mucolytics) in addition to bronchodilators.,There is generally good agreement on treatment goals, criteria for diagnosis of COPD and use of long-acting bronchodilators as the cornerstone of treatment among guidelines for COPD management in Europe and Russia.,However, there are differences in the definitions of patient subgroups and other recommended treatments.,There are important differences between European national COPD guidelineshttp://ow.ly/U2P4y | The coexistence of COPD and asthma is widely recognized but has not been well described.,This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma.,We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study.,119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma.,These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001).,More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001).,Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001).,Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT.,There were no differences in spirometry or CT measurements of emphysema or airway wall thickness.,Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life.,They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history.,ClinicalTrials.gov: NCT00608764 | 1 |
Endpoints that evaluate deterioration rather than improvement of disease may have clinical utility in COPD.,In this analysis, we compared the effects of different maintenance treatments on the prevention of clinically important deterioration (CID) in moderate-to-severe COPD patients.,Data were analyzed from three 26-week studies comparing indacaterol/glycopyrronium (IND/GLY) with tiotropium (TIO) or salmeterol/fluticasone (SFC).,Two definitions of CID were used; each was a composite of three outcome measures typically associated with COPD.,Definition 1 (D1) comprised a ≥100 mL decrease in forced expiratory volume in 1 second (FEV1), a ≥4-unit increase in St George’s Respiratory Questionnaire, and a moderate-to-severe COPD exacerbation.,In Definition 2 (D2), a ≥1-unit decrease in transition dyspnea index replaced FEV1.,Using D1, IND/GLY significantly reduced the risk of first or sustained CID versus either TIO (hazard ratio 0.72 [0.61, 0.86], P=0.0003 and 0.73 [0.61, 0.89], P=0.001) or SFC (0.67 [0.57, 0.80] and 0.63 [0.52, 0.77], both P<0.0001).,With D2, IND/GLY significantly reduced the risk of first, but not sustained, CID versus TIO (0.80 [0.64 to 0.99], P=0.0359 and 0.85 [0.66, 1.10], P=0.2208) and both first and sustained CID versus SFC (0.73 [0.61, 0.88], P=0.001 and 0.72 [0.58, 0.90], P=0.0036).,These data confirm the utility of the CID endpoint as a means of monitoring COPD worsening in patients with moderate-to-severe COPD.,Using the CID measure, we demonstrated that dual bronchodilation with IND/GLY significantly reduced the risk of CID versus either long-acting muscarinic antagonist or long-acting β2-agonist/inhaled corticosteroid treatment, providing further evidence for the benefit of dual bronchodilation in this patient population. | Dual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits in lung function and health status versus monotherapy.,The aim of this study was to determine whether early initiation of a dual bronchodilator versus monotherapy reduced the risk of deterioration in COPD.,This post hoc pooled analysis investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared with tiotropium (TIO) 18 mcg/day in a maintenance-naïve (MN) subgroup of patients relative to the intent-to-treat (ITT) population from three 6-month active comparator studies (n = 1747).,Other treatment arms (UMEC/VI 125/25, VI 25 and UMEC 125) comprised 850 patients in total but were not included in this analysis.,The primary endpoint was trough forced expiratory volume in 1 s (FEV1).,St George’s Respiratory Questionnaire (SGRQ) score, rescue medication use, and a novel composite endpoint of short-term clinically important deterioration (CID; ≥100 ml decrease in trough FEV1, ≥4-unit increase in SGRQ score, or a COPD exacerbation) were also assessed.,UMEC/VI improved trough FEV1 versus TIO at day 169 [least squares mean (95% confidence interval): MN: 146 ml (102-189) and ITT: 95 ml (71-118); both P < 0.001].,Both UMEC/VI and TIO improved SGRQ and rescue use in the two populations, with greater improvements in rescue use with UMEC/VI versus TIO.,UMEC/VI reduced the risk of short-term clinically important deterioration versus TIO [hazard ratio; 95% confidence interval: MN: 0.66 (0.51-0.85); ITT: 0.62 (0.54-0.71), both P ≤ 0.001].,Adverse events were similar across both populations and treatments.,Early use of dual-bronchodilator therapy has superior efficacy on lung function and may reduce the risk of short-term deterioration compared to monotherapy in symptomatic patients with COPD.,Clinical trial registration: GSK analysis 202066 (NCT01316900/DB2113360, NCT01316913/DB2113374, NCT01777334/ZEP117115).,Funding: This study was funded by GSK.,The online version of this article (doi:10.1007/s12325-016-0430-6) contains supplementary material, which is available to authorized users. | 1 |
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised many questions about the management of patients with chronic obstructive pulmonary disease (COPD) and whether modifications of their therapy are required.,It has raised questions about recognizing and differentiating coronavirus disease (COVID-19) from COPD given the similarity of the symptoms.,The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Science Committee used established methods for literature review to present an overview of the management of patients with COPD during the COVID-19 pandemic.,It is unclear whether patients with COPD are at increased risk of becoming infected with SARS-CoV-2.,During periods of high community prevalence of COVID-19, spirometry should only be used when it is essential for COPD diagnosis and/or to assess lung function status for interventional procedures or surgery.,Patients with COPD should follow basic infection control measures, including social distancing, hand washing, and wearing a mask or face covering.,Patients should remain up to date with appropriate vaccinations, particularly annual influenza vaccination.,Although data are limited, inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should continue to be used as indicated for stable COPD management.,Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications.,Differentiating symptoms of COVID-19 infection from chronic underlying symptoms or those of an acute COPD exacerbation may be challenging.,If there is suspicion for COVID-19, testing for SARS-CoV-2 should be considered.,Patients who developed moderate-to-severe COVID-19, including hospitalization and pneumonia, should be treated with evolving pharmacotherapeutic approaches as appropriate, including remdesivir, dexamethasone, and anticoagulation.,Managing acute respiratory failure should include appropriate oxygen supplementation, prone positioning, noninvasive ventilation, and protective lung strategy in patients with COPD and severe acute respiratory distress syndrome.,Patients who developed asymptomatic or mild COVID-19 should be followed with the usual COPD protocols.,Patients who developed moderate or worse COVID-19 should be monitored more frequently and accurately than the usual patients with COPD, with particular attention to the need for oxygen therapy. | Chronic obstructive pulmonary disease (COPD) has become a global epidemic and is the third leading cause of death worldwide.,COPD is characterized by chronic airway inflammation, loss of alveolar-capillary units, and progressive decline in lung function.,Major risk factors for COPD are cigarette smoking and aging.,COPD-associated pathomechanisms include multiple aging pathways such as telomere attrition, epigenetic alterations, altered nutrient sensing, mitochondrial dysfunction, cell senescence, stem cell exhaustion and chronic inflammation.,In this review, we will highlight the current literature that focuses on the role of age and aging-associated signaling pathways as well as their impact on current treatment strategies in the pathogenesis of COPD.,Furthermore, we will discuss established and experimental COPD treatments including senolytic and anti-aging therapies and their potential use as novel treatment strategies in COPD. | 1 |
Chronic obstructive pulmonary disease is generally progressive and associated with reduced physical activity.,Both pharmacological therapy and exercise training can improve exercise capacity; however, these are often not sufficient to change the amount of daily physical activity a patient undertakes.,Behaviour-change self-management programmes are designed to address this, including setting motivational goals and providing social support.,We present and discuss the necessary methodological considerations when integrating behaviour-change interventions into a multicentre study.,PHYSACTO is a 12-week phase IIIb study assessing the effects on exercise capacity and physical activity of once-daily tiotropium+olodaterol 5/5 µg with exercise training, tiotropium+olodaterol 5/5 µg without exercise training, tiotropium 5 µg or placebo, with all pharmacological interventions administered via the Respimat inhaler.,Patients in all intervention arms receive a behaviour-change self-management programme to provide an optimal environment for translating improvements in exercise capacity into increases in daily physical activity.,To maximise the likelihood of success, special attention is given in the programme to: (1) the Site Case Manager, with careful monitoring of programme delivery; (2) the patient, incorporating patient-evaluation/programme-evaluation measures to guide the Site Case Manager in the self-management intervention; and (3) quality assurance, to help identify and correct any problems or shortcomings in programme delivery and ensure the effectiveness of any corrective steps.,This paper documents the comprehensive methods used to optimise and standardise the behaviour-change self-management programme used in the study to facilitate dialogue on the inclusion of this type of programme in multicentre studies.,The study has been approved by the relevant Institutional Review Boards, Independent Ethics Committee and Competent Authority according to national and international regulations.,The results of this study will be disseminated through relevant, peer-reviewed journals and international conference presentations.,NCT02085161. | Physical inactivity is a cardinal feature of chronic obstructive pulmonary disease (COPD), and is associated with increased morbidity and mortality.,Pedometers, which have been used in healthy populations, might also increase physical activity in patients with COPD.,COPD patients taking part in a 3-month individualised programme to promote an increase in their daily physical activity were randomised to either a standard programme of physical activity encouragement alone, or a pedometer-based programme.,Assessments were performed by investigators blinded to treatment allocation.,Change in average 1-week daily step count, 6-min walking distance (6MWD), modified Medical Research Council scale, St George’s respiratory questionnaire (SGRQ) and COPD assessment test (CAT) were compared between groups.,102 patients were recruited, of whom 97 completed the programme (pedometer group: n=50; control group: n=47); 60.8% were male with a mean±sd age of 68.7±8.5 years, and forced expiratory volume in 1 s (FEV1) 66.1±19.4% and FEV1/forced vital capacity 55.2±9.5%.,Both groups had comparable characteristics at baseline.,The pedometer group had significantly greater improvements in: physical activity 3080±3254 steps·day−1versus 138.3±1950 steps·day−1 (p<0.001); SGRQ −8.8±12.2 versus −3.8±10.9 (p=0.01); CAT score −3.5±5.5 versus −0.6±6.6 (p=0.001); and 6MWD 12.4±34.6 versus −0.7±24.4 m (p=0.02) than patients receiving activity encouragement only.,A simple physical activity enhancement programme using pedometers can effectively improve physical activity level and quality of life in COPD patients.,Pedometer-based programme produced clinically important improvements in physical activity and health status in COPDhttp://ow.ly/AmcCO | 1 |
COPD exacerbations occur more frequently with disease progression and are associated with worse prognosis and higher healthcare expenditure.,To utilize a networked system, optimized with statistical process control (SPC), for remote patient monitoring (RPM) and to identify potential predictors of COPD exacerbations.,Seventeen subjects, mean (SD) age of 69.7 (7.2) years, with moderate to severe COPD received RPM.,Over 2618 patient-days (7.17 patient-years) of monitoring, we obtained daily symptom scores, treatment adherence, self-reported activity levels, daily spirometry (SVC, FEV1, FVC, PEF), inspiratory capacity (IC), and oxygenation (SpO2).,These data were used to identify predictors of exacerbations defined using Anthonisen and other criteria.,After implementation of SPC, concordance analysis showed substantial agreement between FVC (decrease below the 7-day rolling average minus 1.645 SD) and self-reported healthcare utilization events (κ=0.747, P<0.001) as well as between increased use of inhaled short-acting bronchodilators and exacerbations defined by two Anthonisen criteria (κ=0.611, P<0.001) or modified Anthonisen criteria (κ=0.622, P<0.001).,There was a moderate agreement between FEV1 (decrease >1.645 SD below the 7-day rolling average) and self-reported healthcare utilization events (κ=0.475, P<0.001) and between SpO2 less than 90% and exacerbations defined by two Anthonisen criteria (κ=0.474, P<0.001) or modified Anthonisen criteria (κ=0.564, P<0.001).,Exacerbations were best predicted by FVC and FEV1 below the one-sided 95% confidence interval derived from SPC but also by increased use of inhaled short-acting bronchodilators and fall in oxygen saturation.,An RPM program that captures these parameters may be used to guide appropriate interventions aimed at reducing healthcare utilization in COPD patients. | Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death. | 1 |
Factors associated with reduced daily physical activity (DPA) in patients with COPD are still controversial.,Physical inactivity in COPD increases risk of cardiovascular disease, frequent exacerbations, reduced health status, and increased symptoms.,We hypothesised that reduced DPA in patients with COPD is independent of traditional risk factors including age and spirometry.,In this cross-sectional study, DPA (over 7 days) was assessed on 88 community stable patients with COPD and 40 controls free from cardiorespiratory disease.,Spirometry, body composition, number of exacerbations, handgrip strength (HGS), modified Medical Research Council (mMRC), arterial stiffness, 6-min walking distance (6MWD) and BODE index were also determined.,Frequent exacerbation was defined as ≥2 and non-frequent exacerbation < 2.,Patients with COPD had reduced DPA and exercise capacity compared with controls similar in age, BMI and gender, p < 0.001.,Frequent exacerbators had less DPA than infrequent exacerbators and both less than controls, p < 0.001.,Patients with higher BODE index were less active than those with lower index.,Time spent on moderate activity was related to cardiovascular risk factors including arterial stiffness.,The DPA in patients was independent of age, gender, spirometry, body composition and HGS, p > 0.05.,The level of breathlessness was superior to lung function in predicting the level of DPA.,The level of DPA in COPD was independent of traditional risk factors.,Breathlessness score is a better predictor of the DPA than lung function and handgrip strength. | Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms and pathological consequences.,Although primarily viewed as a respiratory disease, COPD has both pulmonary and extrapulmonary effects, which have an impact on many aspects of physical, emotional, and mental well-being.,Traditional assessment of COPD relies heavily on measuring lung function, specifically forced expiratory volume in 1 second (FEV1).,However, the evidence suggests that FEV1 is a relatively poor correlate of symptoms such as breathlessness and the impact of COPD on daily life.,Furthermore, many consequences of the disease, including anxiety and depression and the ability to perform daily activities, can only be described and reported reliably by the patient.,Thus, in order to provide a comprehensive view of the effects of interventions in clinical trials, it is essential that spirometry is accompanied by assessments using patient-reported outcome (PRO) instruments.,We provide an overview of patient-reported outcome concepts in COPD, such as breathlessness, physical functioning, and health status, and evaluate the tools used for measuring these concepts.,Particular attention is given to the newly developed instruments emerging in response to recent regulatory guidelines for the development and use of PROs in clinical trials.,We conclude that although data from the development and validation of these new PRO instruments are emerging, to build the body of evidence that supports the use of a new instrument takes many years.,Furthermore, new instruments do not necessarily have better discriminative or evaluative properties than older instruments.,The development of new PRO tools, however, is crucial, not only to ensure that key COPD concepts are being reliably measured but also that the relevant treatment effects are being captured in clinical trials.,In turn, this will help us to understand better the patient’s experience of the disease. | 1 |
The aim of this study was to explore to what extent a combined counselling and pulmonary rehabilitation program (PR) influences the perception of physical activity (PA) and motivation for behavioral change in PA in individuals with COPD.,The results of previous quantitative trial that investigated the effect of this combined treatment on daily PA were inconclusive.,It is conjectured that a more targeted tailoring of the counselling and PR intervention could improve its effectiveness.,Eighteen individuals with COPD (median age 69, 8 females) who had participated in the PneumoReha program were interviewed twice (following PR and at three-month follow-up).,These interviews were transcribed and analyzed thematically.,Based on the codes thus identified, three categories ‘perception of PA intensity’, ‘quality of motivation to perform PA’, and ‘strategies to cope with barriers’ were used to differentiate ‘types’ of participants.,Four different types of COPD individuals were distinguished.,Study findings indicate that those individuals who participated in the PR program combined with embedded counselling tended to be more active and intrinsically motivated.,A typology of four types of people with COPD was developed, characterized by their perception of activity, individual motivation and strategies for managing barriers.,The patients’ physical activity level might be influenced by their concept of physical activity and the quality of motivation.,Recognizing patients’ different activity behaviors is important for improving the quality of outpatient PR programs and developing tailored (according to each type) counselling interventions embedded in outpatient PR programs.,The study was registered on the website of https://www.clinicaltrials.gov/ with the identifier NCT02455206 (27/05/2015), as well as on the Swiss National Trails Portal SNCTP000001426 (05/21/2015). | Pulmonary rehabilitation has short-term benefits on dyspnea, exercise capacity and quality of life in COPD, but evidence suggests these do not always translate to increased daily physical activity on a patient level.,This is attributed to a limited understanding of the determinants of physical activity maintenance following pulmonary rehabilitation.,This systematic review of qualitative research was conducted to understand COPD patients’ perceived facilitators and barriers to physical activity following pulmonary rehabilitation.,Electronic databases of published data, non-published data, and trial registers were searched to identify qualitative studies (interviews, focus groups) reporting the facilitators and barriers to physical activity following pulmonary rehabilitation for people with COPD.,Thematic synthesis of qualitative data was adopted involving line-by-line coding of the findings of the included studies, development of descriptive themes, and generation of analytical themes.,Fourteen studies including 167 COPD patients met the inclusion criteria.,Seven sub-themes were identified as influential to physical activity following pulmonary rehabilitation.,These included: intentions, self-efficacy, feedback of capabilities and improvements, relationship with health care professionals, peer interaction, opportunities following pulmonary rehabilitation and routine.,These encapsulated the facilitators and barriers to physical activity following pulmonary rehabilitation and were identified as sub-themes within the three analytical themes, which were beliefs, social support, and the environment.,The findings highlight the challenge of promoting physical activity following pulmonary rehabilitation in COPD and provide complementary evidence to aid evaluations of interventions already attempted in this area, but also adds insight into future development of interventions targeting physical activity maintenance in COPD. | 1 |
The mechanisms underlying airflow obstruction in COPD cannot be distinguished by standard spirometry.,We ascertain whether mathematical modeling of airway biomechanical properties, as assessed from spirometry, could provide estimates of emphysema presence and severity, as quantified by computed tomography (CT) metrics and CT-based radiomics.,We quantified presence and severity of emphysema by standard CT metrics (VIDA) and co-registration analysis (ImbioLDA) of inspiratory-expiratory CT in 194 COPD patients who underwent pulmonary function testing.,According to percentages of low attenuation area below − 950 Hounsfield Units (%LAA-950insp) patients were classified as having no emphysema (NE) with %LAA-950insp < 6, moderate emphysema (ME) with %LAA-950insp ≥ 6 and < 14, and severe emphysema (SE) with %LAA-950insp ≥ 14.,We also obtained stratified clusters of emphysema CT features by an automated unsupervised radiomics approach (CALIPER).,An emphysema severity index (ESI), derived from mathematical modeling of the maximum expiratory flow-volume curve descending limb, was compared with pulmonary function data and the three CT classifications of emphysema presence and severity as derived from CT metrics and radiomics.,ESI mean values and pulmonary function data differed significantly in the subgroups with different emphysema degree classified by VIDA, ImbioLDA and CALIPER (p < 0.001 by ANOVA).,ESI differentiated NE from ME/SE CT-classified patients (sensitivity 0.80, specificity 0.85, AUC 0.86) and SE from ME CT-classified patients (sensitivity 0.82, specificity 0.87, AUC 0.88).,Presence and severity of emphysema in patients with COPD, as quantified by CT metrics and radiomics can be estimated by mathematical modeling of airway function as derived from standard spirometry.,The online version of this article (10.1186/s12931-019-1049-3) contains supplementary material, which is available to authorized users. | To determine whether visually assessed patterns of emphysema at CT might provide a simple assessment of mortality risk among cigarette smokers.,Of the first 4000 cigarette smokers consecutively enrolled between 2007 and 2011 in this COPDGene study, 3171 had data available for both visual emphysema CT scores and survival.,Each CT scan was retrospectively visually scored by two analysts using the Fleischner Society classification system.,Severity of emphysema was also evaluated quantitatively by using percentage lung volume occupied by low-attenuation areas (voxels with attenuation of −950 HU or less) (LAA-950).,Median duration of follow-up was 7.4 years.,Regression analysis for the relationship between imaging patterns and survival was based on the Cox proportional hazards model, with adjustment for age, race, sex, height, weight, pack-years of cigarette smoking, current smoking status, educational level, LAA-950, and (in a second model) forced expiratory volume in 1 second (FEV1).,Observer agreement in visual scoring was good (weighted κ values, 0.71-0.80).,There were 519 deaths in the study cohort.,Compared with subjects who did not have visible emphysema, mortality was greater in those with any grade of emphysema beyond trace (adjusted hazard ratios, 1.7, 2.5, 5.0, and 4.1, respectively, for mild centrilobular emphysema, moderate centrilobular emphysema, confluent emphysema, and advanced destructive emphysema, P < .001).,This increased mortality generally persisted after adjusting for LAA-950.,The visual presence and severity of emphysema is associated with significantly increased mortality risk, independent of the quantitative severity of emphysema.,Online supplemental material is available for this article. | 1 |
To assess the comparative efficacy of short-acting muscarinic antagonists (SAMAs), long-acting muscarinic antagonists (LAMAs), LAMA in combination with long-acting beta-agonists (LABAs; LAMA/LABAs) and inhaled corticosteroids (ICS) in combination with LABA (ICS/LABAs) for the maintenance treatment of COPD.,We systematically reviewed 74 randomized controlled trials (74,832 participants) published up to 15 November 2017, which compared any of the interventions (SAMA [ipratropium], LAMA [aclidinium, glycopyrronium, tiotropium, umeclidinium], LAMA/LABA [aclidinium/formoterol, indacaterol/glycopyrronium, tiotropium/olodaterol, umeclidinium/vilanterol] and ICS/LABA [fluticasone/vilanterol, budesonide/formoterol, salmeterol/fluticasone]) with each other or with placebo.,A random-effects network meta-analysis combining direct and indirect evidence was conducted to examine the change from baseline in trough FEV1, transition dyspnea index, St George’s Respiratory Questionnaire and frequency of adverse events at weeks 12 and 24.,Inconsistency models were not statistically significant for all outcomes.,LAMAs, LAMA/LABAs and ICS/LABAs led to a significantly greater improvement in trough FEV1 compared with placebo and SAMA monotherapy at weeks 12 and 24.,All LAMA/LABAs, except aclidinium/formoterol, were statistically significantly better than LAMA monotherapy and ICS/LABAs in improving trough FEV1.,Among the LAMAs, umeclidinium showed statistically significant improvement in trough FEV1 at week 12 compared to tiotropium and glycopyrronium, but the results were not clinically significant.,LAMA/LABAs had the highest probabilities of being ranked the best agents in FEV1 improvement.,Similar trends were observed for the transition dyspnea index and St George’s Respiratory Questionnaire outcomes.,There were no significant differences in the incidences of adverse events among all treatment options.,LAMA/LABA showed the greatest improvement in trough FEV1 at weeks 12 and 24 compared with the other inhaled drug classes, while SAMA showed the least improvement.,There were no significant differences among the LAMAs and LAMA/LABAs within their respective classes. | Dual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits in lung function and health status versus monotherapy.,The aim of this study was to determine whether early initiation of a dual bronchodilator versus monotherapy reduced the risk of deterioration in COPD.,This post hoc pooled analysis investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared with tiotropium (TIO) 18 mcg/day in a maintenance-naïve (MN) subgroup of patients relative to the intent-to-treat (ITT) population from three 6-month active comparator studies (n = 1747).,Other treatment arms (UMEC/VI 125/25, VI 25 and UMEC 125) comprised 850 patients in total but were not included in this analysis.,The primary endpoint was trough forced expiratory volume in 1 s (FEV1).,St George’s Respiratory Questionnaire (SGRQ) score, rescue medication use, and a novel composite endpoint of short-term clinically important deterioration (CID; ≥100 ml decrease in trough FEV1, ≥4-unit increase in SGRQ score, or a COPD exacerbation) were also assessed.,UMEC/VI improved trough FEV1 versus TIO at day 169 [least squares mean (95% confidence interval): MN: 146 ml (102-189) and ITT: 95 ml (71-118); both P < 0.001].,Both UMEC/VI and TIO improved SGRQ and rescue use in the two populations, with greater improvements in rescue use with UMEC/VI versus TIO.,UMEC/VI reduced the risk of short-term clinically important deterioration versus TIO [hazard ratio; 95% confidence interval: MN: 0.66 (0.51-0.85); ITT: 0.62 (0.54-0.71), both P ≤ 0.001].,Adverse events were similar across both populations and treatments.,Early use of dual-bronchodilator therapy has superior efficacy on lung function and may reduce the risk of short-term deterioration compared to monotherapy in symptomatic patients with COPD.,Clinical trial registration: GSK analysis 202066 (NCT01316900/DB2113360, NCT01316913/DB2113374, NCT01777334/ZEP117115).,Funding: This study was funded by GSK.,The online version of this article (doi:10.1007/s12325-016-0430-6) contains supplementary material, which is available to authorized users. | 1 |
The topic of 24-hour management of COPD is related to day-to-night symptoms management, specific follow-up and patients’ adherence to therapy.,COPD symptoms strongly vary during day and night, being worse in the night and early morning.,This variability is not always adequately considered in the trials.,Night-time symptoms are predictive of higher mortality and more frequent exacerbations; therefore, they should be a target of therapy.,During night-time, in COPD patients the supine position is responsible for a different thoracic physiology; moreover, during some sleep phases the vagal stimulation determines increased bronchial secretions, increased blood flow in the bronchial circulation (enhancing inflammation) and increased airway resistance (broncho-motor tone).,Moreover, in COPD patients the circadian rhythm may be impaired.,The role of pharmacotherapy in this regard is still poorly investigated.,Symptoms can be grossly differentiated according to the different phenotypes of the disease: wheezing recalls asthma, while dyspnea is strongly related to emphysema (dynamic hyperinflation) or obstructive bronchiolitis (secretions).,Those symptoms may be different targets of therapy.,In this regard, GOLD recommendations for the first time introduced the concept of phenotype distinction suggesting the use of inhaled corticosteroids (ICS) particularly when an asthmatic pattern or eosiophilic inflammations are present, and hypothesized different approaches to target symptoms (ie, dyspnea) or exacerbations.,Pharmacotherapy should be evaluated and possibly directed on the basis of circadian variations, for instance, supporting the use of twice-daily rapid-action bronchodilators and evening dose of ICS.,Recommendations on day and night symptoms monitoring strategies and choice of the specific drug according to patient’s profile are still not systematically investigated or established.,This review is the summary of an advisory board on the topic “24-hour control of COPD and role of pharmacotherapy”, held by five pulmonologists, experts in respiratory pathophysiology, pharmacology and sleep medicine.,Point your SmartPhone at the code above.,If you have a QR code reader the video abstract will appear.,Or use:,https://youtu.be/RlA6NHUbnFY | To identify factors that hinder discussions regarding chronic obstructive pulmonary disease (COPD) between primary care physicians (PCPs) and their patients in Sweden.,Primary health care centres (PHCCs) in Stockholm, Sweden.,A total of 59 PCPs.,Semi-structured individual and focus-group interviews between 2012 and 2014.,Data were analysed inspired by grounded theory methods (GTM).,Time-pressured patient-doctor consultations lead to deprioritization of COPD.,During unscheduled visits, deprioritization resulted from focusing only on acute health concerns, while during routine care visits, COPD was deprioritized in multi-morbid patients.,The reasons PCPs gave for deprioritizing COPD are: “Not becoming aware of COPD”, “Not becoming concerned due to clinical features”, “Insufficient local routines for COPD care”, “Negative personal attitudes and views about COPD”, “Managing diagnoses one at a time”, and “Perceiving a patient’s motivation as low’’.,De-prioritization of COPD was discovered during PCP consultations and several factors were identified associated with time constraints and multi-morbidity.,A holistic consultation approach is suggested, plus extended consultation time for multi-morbid patients, and better documentation and local routines.,Key pointsUnder-diagnosis and insufficient management of chronic obstructive pulmonary disease (COPD) are common in primary health care.,A patient-doctor consultation offers a key opportunity to identify and provide COPD care.,Time pressure, due to either high number of patients or multi-morbidity, leads to omission or deprioritization of COPD during consultation.Deprioritization occurs due to lack of awareness, concern, and local routines, negative personal views, non-holistic consultation approach, and low patient motivation.Better local routines, extended consultation time, and a holistic approach are needed when managing multi-morbid patients with COPD.,Under-diagnosis and insufficient management of chronic obstructive pulmonary disease (COPD) are common in primary health care.,A patient-doctor consultation offers a key opportunity to identify and provide COPD care.,Time pressure, due to either high number of patients or multi-morbidity, leads to omission or deprioritization of COPD during consultation.Deprioritization occurs due to lack of awareness, concern, and local routines, negative personal views, non-holistic consultation approach, and low patient motivation.Better local routines, extended consultation time, and a holistic approach are needed when managing multi-morbid patients with COPD.,Time pressure, due to either high number of patients or multi-morbidity, leads to omission or deprioritization of COPD during consultation.,Deprioritization occurs due to lack of awareness, concern, and local routines, negative personal views, non-holistic consultation approach, and low patient motivation.,Better local routines, extended consultation time, and a holistic approach are needed when managing multi-morbid patients with COPD. | 1 |
The duration of antibiotic treatment of exacerbations of COPD (ECOPD) is controversial.,Serum procalcitonin (PCT) is a biomarker of bacterial infection used to identify the cause of ECOPD.,We investigated whether a PCT-guided plan would allow a shorter duration of antibiotic treatment in patients with severe ECOPD.,For this multicenter, randomized, non-inferiority trial, we enrolled 184 patients hospitalized with ECOPD from 18 hospitals in Italy.,Patients were assigned to receive antibiotics for 10 days (standard group) or for either 3 or 10 days (PCT group).,The primary outcome was the rate of ECOPD at 6 months.,Having planned to recruit 400 patients, we randomized only 183: 93 in the PCT group and 90 in the standard group.,Thus, the completed study was underpowered.,The ECOPD rate at 6 months between PCT-guided and standard antibiotic treatment was not significant (% difference, 4.04; 90% confidence interval [CI], −7.23 to 15.31), but the CI included the non-inferiority margin of 15.,In the PCT-guided group, about 50% of patients were treated for 3 days, and there was no difference in primary or secondary outcomes compared to patients treated for 10 days.,Although the primary and secondary clinical outcomes were no different for patients treated for 3 or 10 days in the PCT group, the conclusion that antibiotics can be safely stopped after 3 days in patients with low serum PCT cannot be substantiated statistically.,Thus, the results of this study are inconclusive regarding the noninferiority of the PCT-guided plan compared to the standard antibiotic treatment.,The study was funded by Agenzia Italiana del Farmaco (AIFA-FARM58J2XH).,Clinical trial registered with www.clinicaltrials.gov (NCT01125098).,ClinicalTrials.gov NCT01125098 | Serum procalcitonin levels have been used as a biomarker of invasive bacterial infection and recently have been advocated to guide antibiotic therapy in patients with chronic obstructive pulmonary disease (COPD).,However, rigorous studies correlating procalcitonin levels with microbiologic data are lacking.,Acute exacerbations of COPD (AECOPD) have been linked to viral and bacterial infection as well as noninfectious causes.,Therefore, we evaluated procalcitonin as a predictor of viral versus bacterial infection in patients hospitalized with AECOPD with and without evidence of pneumonia.,Adults hospitalized during the winter with symptoms consistent with AECOPD underwent extensive testing for viral, bacterial, and atypical pathogens.,Serum procalcitonin levels were measured on day 1 (admission), day 2, and at one month.,Clinical and laboratory features of subjects with viral and bacterial diagnoses were compared.,In total, 224 subjects with COPD were admitted for 240 respiratory illnesses.,Of these, 56 had pneumonia and 184 had AECOPD alone.,A microbiologic diagnosis was made in 76 (56%) of 134 illnesses with reliable bacteriology (26 viral infection, 29 bacterial infection, and 21 mixed viral bacterial infection).,Mean procalcitonin levels were significantly higher in patients with pneumonia compared with AECOPD.,However, discrimination between viral and bacterial infection using a 0.25 ng/mL threshold for bacterial infection in patients with AECOPD was poor.,Procalcitonin is useful in COPD patients for alerting clinicians to invasive bacterial infections such as pneumonia but it does not distinguish bacterial from viral and noninfectious causes of AECOPD. | 1 |
Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death. | 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 |
The obesity paradox in COPD describes protective effects of obesity on lung pathology and inflammation.,However, the underlying relationships between obesity, diet and disease outcomes in COPD are not fully understood.,In this study we measured the response to dietary fatty acids upon markers of inflammation and remodelling in human lung cells from people with and without COPD.,Pulmonary fibroblasts were challenged with ω-3 polyunsaturated fatty acids (PUFAs), ω-6 PUFAs, saturated fatty acids (SFAs) or the obesity-associated cytokine TNFα.,After 48-72 h release of the pro-inflammatory cytokines interleukin (IL)-6 and CXCL8 was measured using ELISA and mRNA expression and deposition of the extracellular matrix (ECM) proteins fibronectin, type I collagen, tenascin and perlecan were measured using qPCR or ECM ELISA, respectively.,Challenge with the ω-6 PUFA arachidonic acid (AA), but not ω-3 PUFAs or SFAs, resulted in increased IL-6 and CXCL8 release from fibroblasts, however IL-6 and CXCL8 release was reduced in COPD (n = 19) compared to non-COPD (n = 36).,AA-induced cytokine release was partially mediated by downstream mediators of cyclooxygenase (COX)-2 in both COPD and non-COPD.,In comparison, TNFα-induced IL-6 and CXCL8 release was similar in COPD and non-COPD, indicating a specific interaction of AA in COPD.,In patients with or without COPD, regression analysis revealed no relationship between BMI and cytokine release.,In addition, AA, but not SFAs or ω-3 PUFAs reduced the basal deposition of fibronectin, type I collagen, tenascin and perlecan into the ECM in COPD fibroblasts.,In non-COPD fibroblasts, AA-challenge decreased basal deposition of type I collagen and perlecan, but not fibronectin and tenascin.,This study shows that AA has disease-specific effects on inflammation and ECM protein deposition.,The impaired response to AA in COPD might in part explain why obesity appears to have less detrimental effects in COPD, compared to other lung diseases.,The online version of this article (10.1186/s12931-018-0919-4) contains supplementary material, which is available to authorized users. | The study aimed to determine the relationship between throat microbiome and COPD.,Sixty-five Chinese males (n=20, smokers without COPD; n=45 smokers with COPD) were included.,Nonmetric multidimensional scaling indicated differences of microbiome between COPD and controls, but no difference was observed between COPD patients with differing degrees of lung function or disease severity.,Rarefaction analyses suggested that operational taxonomic units (OTUs, species-level) richness decreased in COPD.,The dominant taxa between COPD and controls were similar, but the proportions of taxonomic distribution were different.,The dominant phyla were Bacteroidetes, Proteobacteria, Firmicutes and Fusobacteria.,The dominant genera were Haemophilus, Leptotrichia, Porphyromonas, Fusobacterium, Veillonella, Streptococcus, Neisseria and Prevotella.,Two dominant OTUs, otu3 (Veillonella_dispar) and otu4 (Streptococcus_unclassified), were identified.,Otu3 and its father-level taxa, which were negatively correlated with predicted percent of forced expiratory volume in a second (FEV1%pred), were increased in COPD.,By contrast, otu4 and its father-level taxa, which were positively correlated with FEV1%pred, were decreased in COPD.,Otu4 also showed a slight potential as a COPD biomarker.,To conclude, the throat microbiome was different between smokers with or without COPD, which is similar to findings from the lower respiratory tract.,This study may strengthen our understanding of the relationship between microbiomes of different airway sites and COPD. | 1 |
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. | 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 |
Vertebral compression fractures (VCF) are common in COPD patients, with osteoporosis being the main cause.,The clinical impact of VCF derives mostly from both pain and chest deformity, which may lead to ventilatory and physical activity limitations.,Surprisingly, the consequences of VCF on the quality outcomes of hospital care are poorly known.,To assess these indicators in patients hospitalized due to a COPD exacerbation (ECOPD) who also have VCF.,Clinical characteristics and quality care indicators were assessed in two one-year periods, one retrospective (exploratory) and one prospective (validation), in all consecutive patients hospitalized for ECOPD.,Diagnosis of VCF was based on the reduction of >20% height of the vertebral body evaluated in standard lateral chest X-ray (three independent observers).,From the 248 patients admitted during the exploratory phase, a third had at least one VCF.,Underdiagnosis rate was 97.6%, and patients with VCF had more admissions (normalized for survival), longer hospital stays, and higher mortality than patients without (4 [25th-75th percentiles, 2-8] vs 3 [1-6] admissions, P<0.01; 12 [6-30] vs 9 [6-18] days, P<0.05; and 50 vs 32.1% deaths, P<0.01, respectively).,The risk of dying in the two following years was also higher in VCF patients (odds ratio: 2.11 [1.2-3.6], P<0.01).,The validation cohort consisted of 250 patients who showed very similar results.,The logistic regression analysis indicated that both VCF and age were factors independently associated with mortality.,Although VCF is frequently underdiagnosed in patients hospitalized for ECOPD, it is strongly associated with a worse prognosis and quality care outcomes. | The purpose of our study was to examine the association of prior outpatient use of statins and angiotensin converting enzyme (ACE) inhibitors on mortality for subjects ≥ 65 years of age hospitalized with acute COPD exacerbations.,We conducted a retrospective national cohort study using Veterans Affairs administrative data including subjects ≥65 years of age hospitalized with a COPD exacerbation.,Our primary analysis was a multilevel model with the dependent variable of 90-day mortality and hospital as a random effect, controlling for preexisting comorbid conditions, demographics, and other medications prescribed.,We identified 11,212 subjects with a mean age of 74.0 years, 98% were male, and 12.4% of subjects died within 90-days of hospital presentation.,In this cohort, 20.3% of subjects were using statins, 32.0% were using ACE inhibitors or angiotensin II receptor blockers (ARB).,After adjusting for potential confounders, current statin use (odds ratio 0.51, 95% confidence interval 0.40-0.64) and ACE inhibitor/ARB use (0.55, 0.46-0.66) were significantly associated with decreased 90-day mortality.,Use of statins and ACE inhibitors prior to admission is associated with decreased mortality in subjects hospitalized with a COPD exacerbation.,Randomized controlled trials are needed to examine whether the use of these medications are protective for those patients with COPD exacerbations. | 1 |
Lung disease in cystic fibrosis (CF) involves excessive inflammation, repetitive infections and development of bronchiectasis.,Recently, literature on emphysema in CF has emerged, which might become an increasingly important disease component due to the increased life expectancy.,The purpose of this study was to assess the presence and extent of emphysema in endstage CF lungs.,In explanted lungs of 20 CF patients emphysema was semi-quantitatively assessed on histology specimens.,Also, emphysema was automatically quantified on pre-transplantation computed tomography (CT) using the percentage of voxels below -950 Houndfield Units and was visually scored on CT.,The relation between emphysema extent, pre-transplantation lung function and age was determined.,All CF patients showed emphysema on histological examination: 3/20 (15%) showed mild, 15/20 (75%) moderate and 2/20 (10%) severe emphysema, defined as 0-20% emphysema, 20-50% emphysema and >50% emphysema in residual lung tissue, respectively.,Visually upper lobe bullous emphysema was identified in 13/20 and more diffuse non-bullous emphysema in 18/20.,Histology showed a significant correlation to quantified CT emphysema (p = 0.03) and visual emphysema score (p = 0.001).,CT and visual emphysema extent were positively correlated with age (p = 0.045 and p = 0.04, respectively).,In conclusion, this study both pathologically and radiologically confirms that emphysema is common in end-stage CF lungs, and is age related.,Emphysema might become an increasingly important disease component in the aging CF population. | Smoking and COPD are associated with decreased mucociliary clearance, and healthy smokers have shorter cilia in the large airway than nonsmokers.,We hypothesized that changes in cilia length are consistent throughout the airway, and we further hypothesized that smokers with COPD have shorter cilia than healthy smokers.,Because intraflagellar transport (IFT) is the process by which cilia of normal length are produced and maintained, and alterations in IFT lead to short cilia in model organisms, we also hypothesized that smoking induces changes in the expression of IFT-related genes in the airway epithelium of smokers and smokers with COPD.,To assess these hypotheses, airway epithelium was obtained via bronchoscopic brushing.,Cilia length was assessed by measuring 100 cilia (10 cilia on each of 10 cells) per subject and Affymetrix microarrays were used to evaluate IFT gene expression in nonsmokers and healthy smokers in 2 independent data sets from large and small airway as well as in COPD smokers in a data set from the small airway.,In the large and small airway epithelium, cilia were significantly shorter in healthy smokers than nonsmokers, and significantly shorter in COPD smokers than in both healthy smokers and nonsmokers.,The gene expression data confirmed that a set of 8 IFT genes were down-regulated in smokers in both data sets; however, no differences were seen in COPD smokers compared to healthy smokers.,These results support the concept that loss of cilia length contributes to defective mucociliary clearance in COPD, and that smoking-induced changes in expression of IFT genes may be one mechanism of abnormally short cilia in smokers.,Strategies to normalize cilia length may be an important avenue for novel COPD therapies. | 1 |
Osteoporosis is a common complication of chronic obstructive pulmonary disease (COPD).,Recent clinical and biological researches have increasingly delineated the biomolecular pathways of bone metabolism regulation in COPD.,We extended this work by examining the specific association and potential contribution of the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis to the pathogenesis of osteoporosis in advanced COPD.,The aim of this study was to assess the relationships of serum OPG, RANKL, and tumor necrosis factor-alpha (TNF-α) with bone turnover in men with very severe COPD.,Pulmonary function, T-score at the lumbar spine (LS) and femoral neck (FN), serum OPG, RANKL, soluble receptor of tumor necrosis factor-alpha-I and II (sTNFR-I, sTNFR-II), osteocalcin (OC), and β-CrossLaps (βCL) levels were measured in 45 men with very severe stage COPD and 36 male non-COPD volunteers.,COPD patients and healthy controls were compared using an independent t-test and Mann-Whitney U-test.,The Pearson coefficient was used to assess the relationships between variables.,OPG and OC were lower in male COPD patients than in control subjects whereas RANKL, serum βCL, TNF-α, and its receptors were higher.,OPG directly correlated with forced expiratory volume in 1 s (FEV1) % predicted (r = 0.46, P < 0.005), OC (r = 0.34, P < 0.05), LS (r = 0.56, P < 0.001), and FN T-score (r = 0.47, P < 0.01).,In contrast, serum RANKL inversely associated with LS and FN T-score (r = −0.62, P < 0.001 and r = −0.48, P < 0.001) but directly correlated with βCL (r = 0.48, P < 0.001).,In addition, OPG was inversely correlated with RANKL (r = −0.39, P < 0.01), TNF-α (r = −0.56, P < 0.001), and sTNFR-I (r = −0.40, P < 0.01).,Our results suggest that serum OPG and RANKL levels are inversely associated with bone loss in men with advanced stage COPD. | The prescription of physical activity for hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) can be complicated by the presence of comorbidities.,The current research aimed to synthesize the relevant literature on the benefits of exercise for people with multimorbidities who experience an AECOPD, and ask: What are the parameters and outcomes of exercise in AECOPD and in conditions that are common comorbidities as reported by systematic reviews (SRs)?,An SR was performed using the Cochrane Collaboration protocol.,Nine electronic databases were searched up to July 2011.,Articles were included if they (1) described participants with AECOPD, chronic obstructive pulmonary disease (COPD), or one of eleven common comorbidities, (2) were an SR, (3) examined aerobic training (AT), resistance training (RT), balance training (BT), or a combination thereof, (4) included at least one outcome of fitness, and (5) compared exercise training versus control/sham.,This synthesis examined 58 SRs of exercise training in people with AECOPD, COPD, or eleven chronic conditions commonly associated with COPD.,Meta-analyses of endurance (aerobic or exercise capacity, 6-minute walk distance - 6MWD) were shown to significantly improve in most conditions (except osteoarthritis, osteoporosis, and depression), whereas strength was shown to improve in five of the 13 conditions searched: COPD, older adults, heart failure, ischemic heart disease, and diabetes.,Several studies of different conditions also reported improvements in quality of life, function, and control or prevention outcomes.,Meta-analyses also demonstrate that exercise training decreases the risk of mortality in older adults, and those with COPD or ischemic heart disease.,The most common types of training were AT and RT.,BT and functional training were commonly applied in older adults.,The quality of the SRs for most conditions was moderate to excellent (>65%) as evaluated by AMSTAR scores.,In summary, this synthesis showed evidence of significant benefits from exercise training in AECOPD, COPD, and conditions that are common comorbidities.,A broader approach to exercise and activity prescription in pulmonary rehabilitation may induce therapeutic benefits to ameliorate clinical sequelae associated with AECOPD and comorbidities such as the inclusion of BT and functional training. | 1 |
Poor treatment adherence in patients with chronic obstructive pulmonary disease (COPD) or asthma is a global public health concern with severe consequences in terms of patient health and societal costs.,A potentially promising tool for addressing poor compliance is eHealth.,This review investigates the effects of eHealth interventions on medication adherence in patients with COPD or asthma.,A systematic literature search was conducted in the databases of Cochrane Library, PsycINFO, PubMed, and Embase for studies with publication dates between January 1, 2000, and October 29, 2020.,We selected randomized controlled trials targeting adult patients with COPD or asthma, which evaluated the effectiveness of an eHealth intervention on medication adherence.,The risk of bias in the included studies was examined using the Cochrane Collaboration’s risk of bias tool.,The results were narratively reviewed.,In total, six studies focusing on COPD and seven focusing on asthma were analyzed.,Interventions were mostly internet-based or telephone-based, and could entail telemonitoring of symptoms and medication adherence, education, counseling, consultations, and self-support modules.,Control groups mostly comprised usual care conditions, whereas a small number of studies used a face-to-face intervention or waiting list as the control condition.,For COPD, the majority of eHealth interventions were investigated as an add-on to usual care (5/6 studies), whereas for asthma the majority of interventions were investigated as a standalone intervention (5/7 studies).,Regarding eHealth interventions targeting medication adherence for COPD, two studies reported nonsignificant effects, one study found a significant effect in comparison to usual care, and three reported mixed results.,Of the seven studies that investigated eHealth interventions targeting medication adherence in asthma, three studies found significant effects, two reported nonsignificant effects, and two reported mixed effects.,The mixed results on the effectiveness of eHealth interventions in improving treatment adherence for asthma and COPD are presumably related to the type, context, and intensity of the interventions, as well as to differences in the operationalization and measurement of adherence outcomes.,Much remains to be learned about the potential of eHealth to optimize treatment adherence in COPD and asthma. | The burden of chronic obstructive pulmonary disease (COPD) to patients and health services is steadily increasing.,Self-management supported by mobile device applications could improve outcomes for people with COPD.,Our aim was to synthesize evidence on the effectiveness of mobile health applications compared with usual care.,A systematic review was conducted to identify randomized controlled trials.,Outcomes of interest included exacerbations, physical function, and Quality of Life (QoL).,Where possible, outcome data were pooled for meta-analyses.,Of 1709 citations returned, 13 were eligible trials.,Number of exacerbations, quality of life, physical function, dyspnea, physical activity, and self-efficacy were reported.,Evidence for effectiveness was inconsistent between studies, and the pooled effect size for physical function and QoL was not significant.,There was notable variation in outcome measures used across trials.,Developing a standardized outcome-reporting framework for digital health interventions in COPD self-management may help standardize future research. | 1 |
Chronic respiratory diseases (CRD) are common among patients with coronavirus disease 2019 (COVID-19).,We sought to determine the association between CRD (including disease overlap) and the clinical outcomes of COVID-19.,Data of diagnoses, comorbidities, medications, laboratory results, and clinical outcomes were extracted from the national COVID-19 reporting system.,CRD was diagnosed based on International Classification of Diseases-10 codes.,The primary endpoint was the composite outcome of needing invasive ventilation, admission to intensive care unit, or death within 30 days after hospitalization.,The secondary endpoint was death within 30 days after hospitalization.,We included 39,420 laboratory-confirmed patients from the electronic medical records as of May 6, 2020.,Any CRD and CRD overlap was present in 2.8% and 0.2% of patients, respectively.,Chronic obstructive pulmonary disease (COPD) was most common (56.6%), followed by bronchiectasis (27.9%) and asthma (21.7%).,COPD-bronchiectasis overlap was the most common combination (50.7%), followed by COPD-asthma (36.2%) and asthma-bronchiectasis overlap (15.9%).,After adjustment for age, sex, and other systemic comorbidities, patients with COPD (odds ratio [OR]: 1.71, 95% confidence interval [CI]: 1.44-2.03) and asthma (OR: 1.45, 95% CI: 1.05-1.98), but not bronchiectasis, were more likely to reach to the composite endpoint compared with those without at day 30 after hospitalization.,Patients with CRD were not associated with a greater likelihood of dying from COVID-19 compared with those without.,Patients with CRD overlap did not have a greater risk of reaching the composite endpoint compared with those without.,CRD was associated with the risk of reaching the composite endpoint, but not death, of COVID-19. | The aim was to determine the clinical characteristics of COVID-19 patients because the SARS-CoV-2 virus continues to circulate in the population.,This is a retrospective, multicentre, cohort study.,Adult COVID-19 cases from four hospitals in Zhejiang were enrolled and clustered into three groups based on epidemiological history.,First-generation patients had a travel history to Hubei within 14 days before disease onset; second-generation patients had a contact history with first-generation patients; third-generation patients had a contact history with second-generation patients.,Demographic, clinical characteristics, clinical outcomes and duration of viral shedding were analysed.,A total of 171 patients were enrolled, with 83, 44 and 44 patients in the first-, second-, and third-generation, respectively.,Compared with the first and second generations, third-generation patients were older (61.3 vs.,48.3 and 44.0 years, p < 0.001) and had more coexisting conditions (56.8% vs.,36.1% and 27.3%, p 0.013).,At 7 ± 1 days from illness onset, third-generation patients had lower lymphocyte (0.6 vs.,0.8 and 0.8 × 109/L, p 0.007), higher C-reactive protein (29.7 vs.,17.1 and 13.8 mg/L, p 0.018) and D-dimer (1066 vs.,412.5 and 549 μg/L, p 0.002) and more lesions involving the pulmonary lobes (lobes ≥5, 81.8% vs.,53.0% and 34.1%, p < 0.001).,The proportions of third-generation patients developing severe illness (72.7% vs.,32.5% and 27.3%, p < 0.001), critical illness (38.6% vs.,10.8% and 6.8%, p < 0.001) and receiving endotracheal intubation (20.5% vs.,3.6% and 2.3%, p 0.002) were higher than in the other two groups.,Third-generation patients were older, had more underlying comorbidities and had a higher proportion of severe or critical illness than first- and second-generation patients. | 1 |
The combination of the inhaled muscarinic antagonist umeclidinium (UMEC) with the long-acting β2-agonist vilanterol (VI) has been shown to provide significant improvements in lung function compared with UMEC, VI, or placebo (PBO) in patients with chronic obstructive pulmonary disease (COPD).,This study was specifically designed to support these findings by assessing health-related quality of life and symptomatic outcomes in a similar population.,This was a 12-week multicenter, randomized, double-blind, parallel-group, placebo-controlled study.,Eligible patients were randomized 1:1 to receive once-daily UMEC/VI 62.5/25 μg (via ELLIPTA® dry powder inhaler) or PBO for 12 weeks.,The primary endpoint was St George’s Respiratory Questionnaire (SGRQ) total score at day 84.,Secondary efficacy endpoints included rescue albuterol use (puffs/day) over weeks 1-12 and trough forced expiratory volume in 1 second on day 84.,Adverse events were also assessed.,A total of 496 patients were included in the intent-to-treat population in the UMEC/VI (n=248) and PBO (n=248) treatment groups.,UMEC/VI 62.5/25 μg provided a significant and clinically meaningful improvement in SGRQ total score at day 84 versus PBO (difference between treatments in SGRQ total score change from baseline: −4.03 [95% confidence interval {CI}: −6.28, −1.79]; P<0.001).,UMEC/VI 62.5/25 μg resulted in a statistically significant reduction in rescue albuterol use versus PBO (−0.7 puffs/day [95% CI: −1.1, −0.4]; P<0.001).,UMEC/VI 62.5/25 μg provided a significant and clinically meaningful improvement in trough forced expiratory volume in 1 second on day 84 versus PBO (122 mL [95% CI: 71, 172]; P<0.001).,The incidence of adverse events was similar between treatments (32% and 30% of patients in the UMEC/VI 62.5/25 μg and PBO groups, respectively).,The results of this study demonstrate that treatment with UMEC/VI 62.5/25 μg provides clinically important improvements in SGRQ and rescue medication use versus PBO in patients with moderate-to-very-severe COPD. | Combining bronchodilators with different mechanisms of action may improve efficacy and reduce risk of side effects compared to increasing the dose of a single agent in chronic obstructive pulmonary disease (COPD).,We investigated this by combining two long-acting bronchodilators: once-daily muscarinic antagonist tiotropium and once-daily β2-agonist olodaterol.,Two replicate, double-blind, randomized, 12-week studies (ANHELTO 1 [NCT01694771] and ANHELTO 2 [NCT01696058]) evaluated the efficacy and safety of olodaterol 5 μg once daily (via Respimat®) combined with tiotropium 18 μg once daily (via HandiHaler®) versus tiotropium 18 μg once daily (via HandiHaler®) combined with placebo (via Respimat®) in patients with moderate to severe COPD.,Primary efficacy end points were area under the curve from 0-3 hours of forced expiratory volume in 1 second (FEV1 AUC0-3) and trough FEV1 after 12 weeks (for the individual trials).,A key secondary end point was health status by St George’s Respiratory Questionnaire (SGRQ) total score (combined data set).,Olodaterol + tiotropium resulted in significant improvements over tiotropium + placebo in FEV1 AUC0-3 (treatment differences: 0.117 L [P<0.001], ANHELTO 1; 0.106 L [P<0.001], ANHELTO 2) and trough FEV1 (treatment differences: 0.062 L [P<0.001], ANHELTO 1; 0.040 L [P=0.0029], ANHELTO 2); these were supported by secondary end points.,These effects translated to improvements in SGRQ total scores (treatment difference −1.85; P<0.0001).,The tolerability profile of olodaterol + tiotropium was similar to tiotropium monotherapy.,These studies demonstrated that olodaterol (Respimat®) and tiotropium (HandiHaler®) provided bronchodilatory effects above tiotropium alone in patients with COPD.,In general, both treatments were well tolerated. | 1 |
Chronic obstructive lung disease (COPD) is a common cause of death in industrialized countries often induced by exposure to tobacco smoke.,A substantial number of patients with COPD also suffer from pulmonary hypertension that may be caused by hypoxia or other hypoxia-independent stimuli - inducing pulmonary vascular remodeling.,The Ca2+ binding protein, S100A4 is known to play a role in non-COPD-driven vascular remodeling of intrapulmonary arteries.,Therefore, we have investigated the potential involvement of S100A4 in COPD induced vascular remodeling.,Lung tissue was obtained from explanted lungs of five COPD patients and five non-transplanted donor lungs.,Additionally, mice lungs of a tobacco-smoke-induced lung emphysema model (exposure for 3 and 8 month) and controls were investigated.,Real-time RT-PCR analysis of S100A4 and RAGE mRNA was performed from laser-microdissected intrapulmonary arteries.,S100A4 immunohistochemistry was semi-quantitatively evaluated.,Mobility shift assay and siRNA knock-down were used to prove hypoxia responsive elements (HRE) and HIF binding within the S100A4 promoter.,Laser-microdissection in combination with real-time PCR analysis revealed higher expression of S100A4 mRNA in intrapulmonary arteries of COPD patients compared to donors.,These findings were mirrored by semi-quantitative analysis of S100A4 immunostaining.,Analogous to human lungs, in mice with tobacco-smoke-induced emphysema an up-regulation of S100A4 mRNA and protein was observed in intrapulmonary arteries.,Putative HREs could be identified in the promoter region of the human S100A4 gene and their functionality was confirmed by mobility shift assay.,Knock-down of HIF1/2 by siRNA attenuated hypoxia-dependent increase in S100A4 mRNA levels in human primary pulmonary artery smooth muscle cells.,Interestingly, RAGE mRNA expression was enhanced in pulmonary arteries of tobacco-smoke exposed mice but not in pulmonary arteries of COPD patients.,As enhanced S100A4 expression was observed in remodeled intrapulmonary arteries of COPD patients, targeting S100A4 could serve as potential therapeutic option for prevention of vascular remodeling in COPD patients.,The online version of this article (doi:10.1186/s12931-015-0284-5) contains supplementary material, which is available to authorized users. | This study compared reticular basement membrane (Rbm) and vascular remodelling within the bronchial mucosa of subjects with chronic obstructive pulmonary disease (COPD) with those from patients with asthma, to test the ‘Dutch hypothesis’ of whether these are essentially the same or different pathological conditions.,Bronchoscopic biopsies were stained with anti-collagen IV antibody; 18 current smoking COPD, 10 symptomatic asthmatics and 13 healthy non-smoking controls were studied.,The Rbm in COPD was fragmented, non-homogeneous, variable in thickness and hypervascular, whereas in asthma the Rbm was compact and homogeneous with no evidence of increased vascularity compared to controls.,Length of Rbm splitting presented as percentage of Rbm length was used to measure fragmentation; it was greater in COPD than in controls and asthmatics [median (range) 20.7% (0.4-68.5) versus 5.3% (0.0-21.7) versus 1.5% (0.0-15.1), P < 0.001].,The number of Rbm vessels/mm Rbm [median (range) 10.1 (1.6-23.0) versus 4.5 (0.0-26.4) versus 4.4 (0.4-8.1), P < 0.01] and area of Rbm vessels, μm2/mm Rbm [median (range) 953 (115-2456) versus 462 (0-3263) versus 426 (32-2216), P < 0.05] was also increased in COPD compared to normal subjects and asthmatics.,The characteristics of Rbm remodelling are quite different in asthma and COPD. | 1 |
Natural history of chronic obstructive pulmonary disease (COPD) is punctuated by exacerbations; however, little is known about prognosis of the first-ever COPD exacerbation and variables predicting its outcomes.,A population-based cohort study among COPD patients with their first-ever exacerbations requiring hospitalizations was conducted.,Main outcomes were in-hospital mortality and one-year mortality after discharge.,Demographics, comorbidities, medications and in-hospital events were obtained to explore outcome predictors.,The cohort comprised 4204 hospitalized COPD patients, of whom 175 (4%) died during the hospitalization.,In-hospital mortality was related to higher age (odds ratio [OR]: 1.05 per year; 95% confidence interval [CI]: 1.03-1.06) and Charlson comorbidity index score (OR: 1.08 per point; 95% CI: 1.01-1.15); angiotensin II receptor blockers (OR: 0.61; 95% CI: 0.38-0.98) and β blockers (OR: 0.63; 95% CI: 0.41-0.95) conferred a survival benefit.,At one year after discharge, 22% (871/4029) of hospital survivors were dead.,On multivariate Cox regression analysis, age and Charlson comorbidity index remained independent predictors of one-year mortality.,Longer hospital stay (hazard ratio [HR] 1.01 per day; 95% CI: 1.01-1.01) and ICU admission (HR: 1.33; 95% CI: 1.03-1.73) during the hospitalization were associated with higher mortality risks.,Prescription of β blockers (HR: 0.79; 95% CI: 0.67-0.93) and statins (HR: 0.66; 95% CI: 0.47-0.91) on hospital discharge were protective against one-year mortality.,Even the first-ever severe COPD exacerbation signifies poor prognosis in COPD patients.,Comorbidities play a crucial role in determining outcomes and should be carefully assessed.,Angiotensin II receptor blockers, β blockers and statins may, in theory, have dual cardiopulmonary protective properties and probably alter prognosis of COPD patients.,Nevertheless, the limitations inherent to a claims database study, such as the diagnostic accuracy of COPD and its exacerbation, should be born in mind. | Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients.,Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype.,This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.,These patients are therefore a priority for research and treatment.,The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection.,Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment.,Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.,This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.,The online version of this article (doi:10.1186/1741-7015-11-181) contains supplementary material, which is available to authorized users. | 1 |
Psychological morbidity is common in chronic respiratory diseases.,The diagnostic accuracy of the Hospital Anxiety and Depression Scale (HADS) and risk factors for comorbid depression in chronic obstructive pulmonary disease (COPD) are addressed.,Consecutive COPD patients (GOLD stage I-IV, 40-75 years old) were enrolled in a multicentre, cross-sectional cohort study.,Diagnosis of depression was ascertained through clinical records.,Lung function, HADS score, 6-minute walking test (6-MWT), MRC dyspnoea score, and COPD Assessment Test (CAT) were evaluated.,Two hundred fifty-nine COPD patients (mean age 62.5 years; 32% female; mean FEV1 48% predicted) were included.,Patients diagnosed with depression (29/259; 11.2%) had significantly higher HADS-D and HADS-Total scores than nondepressed patients (median (quartiles) HADS-D 6 [4; 9] versus 4 [2; 7], median HADS-Total 14 [10; 20] versus 8 [5; 14]).,Receiver-operating characteristic plots showed moderate accuracy for HADS-D, AUC 0.662 (95%CI 0.601-0.719), and HADS-Total, AUC 0.681 (95%CI 0.620-0.737), with optimal cut-off scores of >5 and >9, respectively.,Sensitivity and specificity were 62.1% and 62.6% for HADS-D compared to 75.9% and 55.2% for HADS-Total.,Age, comorbidities, sex, and lower airflow limitation predicted depression.,The HADS exhibits low diagnostic accuracy for depression in COPD patients.,Younger men with comorbidities are at increased risk for depression. | Health status provides valuable information, complementary to spirometry and improvement of health status has become an important treatment goal in COPD management.,We compared the usefulness and validity of the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ), two simple questionnaires, in comparison with the St.,George Respiratory Questionnaire (SGRQ).,We administered the CAT, CCQ and SGRQ in patients with COPD stage I-IV during three visits.,Spirometry, 6 MWT, MRC scale, BODE index, and patients perspectives on questionnaires were recorded in all visits.,Standard Error of Measurement (SEM) was used to calculate the Minimal Clinical Important Difference (MCID) of all questionnaires.,We enrolled 90 COPD patients.,Cronbach's alpha for both CAT and CCQ was high (0.86 and 0.89, respectively).,Patients with severe COPD reported worse health status compared to milder subgroups.,CAT and CCQ correlated significantly (rho =0.64, p < 0.01) and both with the SGRQ (rho = 0.65; CAT and rho = 0.77; CCQ, p < 0.01).,Both questionnaires exhibited a weak correlation with lung function (rho = −0.35;CAT and rho = −0.41; CCQ, p < 0.01).,Their reproducibility was high; CAT: ICC = 0.94 (CI 0.92-0.96), total CCQ ICC = 0.95 (0.92-0.96) and SGRQ = 0.97 (CI 0.95-0.98).,The MCID calculated using the SEM method showed results similar to previous studies of 3.76 for the CAT, 0.41 for the CCQ and 4.84 for SGRQ.,Patients suggested both CAT and CCQ as easier tools than SGRQ in terms of complexity and time considerations.,More than half of patients preferred CCQ instead of CAT.,The CAT and CCQ have similar psychometric properties with a slight advantage for CCQ based mainly on patients’ preference and are both valid and reliable questionnaires to assess health status in COPD patients. | 1 |
The pathogenesis of chronic obstructive pulmonary disease (COPD) is characterized by an interaction of environmental influences, particularly cigarette smoking, and genetic determinants.,Given the global increase in COPD, research on the genomic variants that affect susceptibility to this complex disorder is reviving.,In the present study, we investigated whether single nucleotide polymorphisms in 'a disinter-grin and metalloprotease' 33 (ADAM33) are associated with the development and course of COPD.,We genotyped 150 German COPD patients and 152 healthy controls for the presence of the F+1 and S_2 SNPs in ADAM 33 that lead to the base pair exchange G to A and C to G, respectively.,To assess whether these genetic variants are influential in the course of COPD, we subdivided the cohort into two subgroups comprising 60 patients with a stable and 90 patients with an unstable course of disease.,In ADAM33, the frequency of the F+1 A allele was 35.0% among stable and 43.9% among unstable COPD subjects, which was not significantly different from the 35.5% found in the controls (P = 0.92 and P = 0.07, respectively).,The frequency of the S_2 mutant allele in subjects with a stable COPD was 23.3% (P = 0.32), in subjects with an unstable course 30.6% (P = 0.47).,The study shows that there is no significant difference in the distribution of the tested SNPs between subjects with and without COPD.,Furthermore, these polymorphisms appear to have no consequences for the stability of the disease course. | There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD).,The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1-2% of individuals with COPD.,We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study.,The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population.,Logistic regression models with adjustments of covariates were used to analyze the case-control populations.,Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations.,Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study.,They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730).,Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations.,The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%.,The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels.,Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429).,The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD.,CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer. | 1 |
Combined pulmonary fibrosis and emphysema (CPFE) is an underrecognized syndrome characterized by chronic, progressive disease with a dismal prognosis.,Frequent co-morbidities with a higher incidence than in idiopathic pulmonary fibrosis or emphysema alone are pulmonary hypertension (WHO group 3) in 47-90% of the patients and lung cancer in 46.8% of the patients.,Review current evidence and knowledge concerning diagnosis, risk factors, disease evolution and treatment options of CPFE.,We searched studies reporting CPFE in original papers, observational studies, case reports, and meta-analyses published between 1990 and August 2020, in the PubMed, Embase, Cochrane Library, Wiley Online Library databases and Google Scholar using the search terms [CPFE], [pulmonary fibrosis] OR [IPF] AND [emphysema].,Bibliographies of retrieved articles were searched as well.,Further inclusion criteria were publications in English, French, German and Italian, with reference to humans.,In vitro data and animal data were not considered unless they were mentioned in studies reporting predominantly human data.,Between May 1, 1990, and September 1, 2020, we found 16 studies on CPFE from the online sources and bibliographies.,A total of 890 patients are described in the literature.,Although male/female ratio was not reported in all studies, the large majority of patients were male (at least 78%), most of them were current or former heavy smokers.,CPFE is a syndrome presenting with dyspnea on exertion followed by disruptive cough and recurrent exacerbations.,The disease may progress rapidly, be aggravated by pulmonary hypertension WHO group 3 and is associated with an increased risk of lung cancer.,Smoking and male sex are important risk factors.,There is a need for more research on CPFE especially relating to etiology, influence of genetics, treatment and prevention options.,Antifibrotic therapy might be an interesting treatment option for these patients. | Some have suggested that chronic obstructive pulmonary disease (COPD) is a disease of accelerated aging.,Aging is characterized by shortening of telomeres.,The relationship of telomere length to important clinical outcomes such as mortality, disease progression and cancer in COPD is unknown.,Using quantitative polymerase chain reaction (qPCR), we measured telomere length of peripheral leukocytes in 4,271 subjects with mild to moderate COPD who participated in the Lung Health Study (LHS).,The subjects were followed for approximately 7.5 years during which time their vital status, FEV1 and smoking status were ascertained.,Using multiple regression methods, we determined the relationship of telomere length to cancer and total mortality in these subjects.,We also measured telomere length in healthy “mid-life” volunteers and patients with more severe COPD.,The LHS subjects had significantly shorter telomeres than those of healthy “mid-life” volunteers (p<.001).,Compared to individuals in the 4th quartile of relative telomere length (i.e. longest telomere group), the remaining participants had significantly higher risk of cancer mortality (Hazard ratio, HR, 1.48; p = 0.0324) and total mortality (HR, 1.29; p = 0.0425).,Smoking status did not make a significant difference in peripheral blood cells telomere length.,In conclusion, COPD patients have short leukocyte telomeres, which are in turn associated increased risk of total and cancer mortality.,Accelerated aging is of particular relevance to cancer mortality in COPD. | 1 |
An extrafine formulation of the long-acting muscarinic antagonist glycopyrronium bromide (GB) is in development for chronic obstructive pulmonary disease (COPD), in combination with beclometasone dipropionate and formoterol fumarate - a “fixed triple”.,This two-part study was randomized, double blind, placebo controlled in patients with moderate-to-severe COPD: Part 1: single-dose escalation, GB 12.5, 25, 50, 100 or 200 μg versus placebo; Part 2: repeat-dose (7-day), four-period crossover, GB 12.5, 25 or 50 μg twice daily (BID) versus placebo, with an open-label extension in which all patients received tiotropium 18 μg once daily.,On the morning of Day 8 in all five periods, patients also received formoterol 12 μg.,In study Part 1, 27 patients were recruited.,All GB doses significantly increased from baseline forced expiratory volume in 1 second (FEV1) area under the curve (AUC0-12h) and peak FEV1, with a trend toward greater efficacy with higher GB dose.,All adverse events were mild-moderate in severity, with a lower incidence with GB than placebo and no evidence of a dose-response relationship.,In study Part 2, of 38 patients recruited, 34 completed the study.,Adjusted mean differences from placebo in 12 h trough FEV1 on Day 7 (primary) were 115, 142 and 136 mL for GB 12.5, 25 and 50 μg BID, respectively (all P<0.001).,GB 25 and 50 μg BID were superior (P<0.05) to GB 12.5 μg BID for pre-dose morning FEV1 on Day 8.,For this endpoint, GB 25 and 50 μg BID were also superior to tiotropium.,Compared with Day 7, addition of formoterol significantly increased Day 8 FEV1 peak and AUC0-12h with all GB doses and placebo (all P<0.001).,All adverse events were mild-moderate in severity and there was no indication of a dose-related relationship.,This study provides initial evidence on bronchodilation, safety and pharmacokinetics of extrafine GB BID.,Overall, the results suggest that GB 25 μg BID is the optimal dose in patients with COPD. | 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 |
The therapeutic value of inhaled corticosteroids (ICSs) for COPD is limited.,In published RCTs, ICS could be withdrawn in COPD patients without increasing exacerbation risk when bronchodilator treatment is optimized.,Here we report on the feasibility and risks of ICS withdrawal in Dutch general practice for COPD patients without an indication for ICSs.,In our pragmatic trial, general practitioners decided autonomously which of their COPD patients on ICS treatment could stop this, how this was done, and whether additional bronchodilator therapy was needed.,We recruited 62 COPD patients (58 analysed) who were eligible for ICS withdrawal in 79 practices.,In 32 patients (55.2%, 95% CI: 42.5-67.3%) ICS was withdrawn successfully, 19 (32.8%, 95% CI: 22.1-45.6%) restarted ICS treatment within six months, 12 patients (20.7%, 95% CI: 12.3-32.8%) had a moderate exacerbation, and one patient had a severe exacerbation.,ICS withdrawal was successful in just over half of the patients with COPD without an indication for ICS. | Alpha-1-Antitrypsin Deficiency (AATD) is an economically unexplored genetic disease.,Direct and indirect costs (based on self-reported information on healthcare utilization) and health-related quality of life (HRQL, as assessed by SGRQ, CAT, and EQ-5D-3 L) were compared between 131 AATD patients (106 with, 25 without augmentation therapy (AT)) and 2,049 COPD patients without AATD participating in the COSYCONET COPD cohort.,The medication costs of AT were excluded from all analyses to reveal differences associated with morbidity profiles.,The association of AATD (with/without AT) with costs or HRQL was examined using generalized linear regression modelling (GLM) adjusting for age, sex, GOLD grade, BMI, smoking status, education and comorbidities.,Adjusted mean direct annual costs were €6,099 in AATD patients without AT, €7,117 in AATD patients with AT (excluding costs for AT), and €7,460 in COPD patients without AATD.,AATD with AT was significantly associated with higher outpatient (+273%) but lower inpatient (−35%) and medication costs (−10%, disregarding AT) compared with COPD patients without AATD.,There were no significant differences between groups regarding indirect costs and HRQL.,Apart from AT costs, AATD patients tended to have lower, though not significant, overall costs and similar HRQL compared to COPD patients without AATD.,AT was not associated with lower costs or higher HRQL.,NCT01245933,The online version of this article (doi:10.1186/s12931-017-0543-8) contains supplementary material, which is available to authorized users. | 1 |
There is increasing focus on understanding the nature of chronic obstructive pulmonary disease (COPD) during the earlier stages.,Mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1 or the now-withdrawn GOLD stage 0) represents an early stage of COPD that may progress to more severe disease.,This review summarises the disease burden of patients with mild COPD and discusses the evidence for treatment intervention in this subgroup.,Overall, patients with mild COPD suffer a substantial disease burden that includes persistent or potentially debilitating symptoms, increased risk of exacerbations, increased healthcare utilisation, reduced exercise tolerance and physical activity, and a higher rate of lung function decline versus controls.,However, the evidence for treatment efficacy in these patients is limited due to their frequent exclusion from clinical trials.,Careful assessment of disease burden and the rate of disease progression in individual patients, rather than a reliance on spirometry data, may identify patients who could benefit from earlier treatment intervention.,The online version of this article (10.1186/s12931-019-1108-9) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is a common cause of suffering and death.,Evidence-based management of COPD by general practitioners (GPs) is crucial for decreasing the impact of the disease.,Efficient strategies include early diagnosis, smoking cessation and multimodal treatment.,To describe knowledge about and skills for managing COPD in GPs in Sweden.,Prior to COPD education (the PRIMAIR Study), GPs at primary health care centers (PHCCs) in Stockholm replied to 13 written, patient-case based, multiple choice and free-text questions about COPD.,Their knowledge and practical management skills were assessed by assigned points that were analyzed with non-parametric tests.,Overall, 250 GPs at 34 PHCCs replied (89% response rate).,Total mean score was 9.9 (maximum 26).,Scores were highest on ‘management of smoking cessation’, ‘follow-up after exacerbation’ and ‘diagnostic procedures’.,Spirometry was used frequently, although interpretation skills were suboptimal.,‘Management of maintenance therapy’, ‘management of multimorbidity’ and ‘interprofessional cooperation’ had mediocre scores.,Scores were unrelated to whether there was a nurse-led asthma/COPD clinic at the PHCC.,Swedish GPs’ knowledge of COPD and adherence to current guidelines seem insufficient.,A nurse-led asthma/COPD clinic at the PHCC does not correlate with sufficient COPD skills in the GPs.,The relevance of this study to participants’ actual clinical practice and usefulness of easy-to-access clinical guides are interesting topics for future investigation.,To identify problem areas, we suggest using questionnaires prior to educational interventions.,General practitioners (GPs) play a crucial role in providing evidence-based care for patients with chronic obstructive pulmonary disease (COPD) who are treated in primary care.,Swedish GPs’ knowledge about COPD and adherence to current guidelines seem insufficient.,Areas in greatest need of improvement are spirometry interpretation, management of maintenance therapy, management of multimorbidity in patients with COPD and interprofessional cooperation. | 1 |
The purpose of this study was to assess the relationship of smoking duration with respiratory symptoms and history of chronic obstructive pulmonary disease (COPD) in the South Carolina Behavioral Risk Factor Surveillance System survey in 2012.,Data from 4,135 adults aged ≥45 years with a smoking history were analyzed using multivariable logistic regression that accounted for sex, age, race/ethnicity, education, and current smoking status, as well as the complex sampling design.,The distribution of smoking duration ranged from 19.2% (1-9 years) to 36.2% (≥30 years).,Among 1,454 respondents who had smoked for ≥30 years, 58.3% were current smokers, 25.0% had frequent productive cough, 11.2% had frequent shortness of breath, 16.7% strongly agreed that shortness of breath affected physical activity, and 25.6% had been diagnosed with COPD.,Prevalence of COPD and each respiratory symptom was lower among former smokers who quit ≥10 years earlier compared with current smokers.,Smoking duration had a linear relationship with COPD (P<0.001) and all three respiratory symptoms (P<0.001) after adjusting for smoking status and other covariates.,While COPD prevalence increased with prolonged smoking duration in both men and women, women had a higher age-adjusted prevalence of COPD in the 1-9 years, 20-29 years, and ≥30 years duration periods.,These state population data confirm that prolonged tobacco use is associated with respiratory symptoms and COPD after controlling for current smoking behavior. | Chronic respiratory diseases are a significant cause of morbidity and mortality worldwide.,We sought to evaluate the impact of asthma, chronic bronchitis and allergic rhinitis on all-cause hospitalizations and limitations in daily activities in adults.,In the Gene Environment Interactions in Respiratory Diseases study (2007/2010), a screening questionnaire was mailed to 9,739 subjects aged 20-44 (response rate: 53.0%) and to 3,480 subjects aged 45-64 (response rate: 62.3%), who were randomly selected from the general population in Italy.,The questionnaire was used to: identify the responders who had asthma, chronic bronchitis, allergic rhinitis or asthma-like symptoms/dyspnoea/other nasal problems; evaluate the total burden [use of hospital services (at least one ED visit and/or one hospital admission) and number of days with reduced activities (lost working days and days with limited, not work related activities) due to any health problems (apart from accidents and injuries) in the past three months]; evaluate the contribution of breathing problems to the total burden (hospitalizations and number of days with reduced activities specifically due to breathing problems).,At any age, the all-cause hospitalization risk was about 6% among the subjects without any respiratory conditions, it increased to about 9-12% among the individuals with allergic rhinitis or with asthma-like symptoms/dyspnoea/other nasal problems, and it peaked at about 15-18% among the asthmatics with chronic bronchitis aged 20-44 and 45-64, respectively.,The expected number of days with reduced activities due to any health problems increased from 1.5 among the subjects with no respiratory conditions in both the age classes, to 6.3 and 4.6 among the asthmatics with chronic bronchitis aged 20-44 and 45-64, respectively.,The contribution of breathing problems to the total burden was the highest among the asthmatics with chronic bronchitis (23-29% of the hospitalization risk and 39-50% of the days with reduced activities, according to age).,The impact of asthma, chronic bronchitis and allergic rhinitis on all-cause hospitalizations and limitations in daily activities is substantial, and it is markedly different among adults from the general population in Italy.,The contribution of breathing problems to the total burden also varies according to the respiratory condition. | 1 |
Tiotropium Safety and Performance in Respimat® (TIOSPIR®) compared the safety and efficacy of tiotropium Respimat® and tiotropium HandiHaler® in patients with chronic obstructive pulmonary disease (COPD).,A prespecified spirometry substudy compared the lung function efficacy between treatment groups.,TIOSPIR® was a large-scale, long-term (2.3-year), event-driven, randomized, double-blind, parallel-group trial of 17,135 patients with COPD.,In the spirometry substudy, trough forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured at baseline and every 24 weeks for the duration of the trial.,The substudy included 1370 patients who received once-daily tiotropium Respimat® 5 μg (n = 461), 2.5 μg (n = 464), or tiotropium HandiHaler® 18 μg (n = 445).,Adjusted mean trough FEV1 (average 24-120 weeks) was 1.285, 1.258, and 1.295 L in the Respimat® 5 μg, 2.5 μg, and HandiHaler® 18 μg groups (difference versus HandiHaler® [95 % CI]: −10 [−38, 18] mL for Respimat® 5 μg and, −37 [−65, −9] mL for Respimat® 2.5 μg); achieving noninferiority to tiotropium HandiHaler® 18 μg for tiotropium Respimat® 5 but not for 2.5 μg (prespecified analysis).,Adjusted mean trough FVC was 2.590, 2.544, and 2.593 L in the Respimat® 5 μg, 2.5 μg, and HandiHaler® 18 μg groups.,The rates of FEV1 decline over 24 to 120 weeks were similar for the three treatment arms (26, 40, and 34 mL/year for the tiotropium Respimat® 5-μg, 2.5-μg, and HandiHaler® 18-μg groups).,The rate of FEV1 decline in GOLD I + II patients was greater than in GOLD III + IV patients (46 vs. 23 mL/year); as well as in current versus ex-smokers, in patients receiving combination therapies at baseline versus not, and in those experiencing an exacerbation during the study versus not.,The TIOSPIR® spirometry substudy showed that tiotropium Respimat® 5 μg was noninferior to tiotropium HandiHaler® 18 μg for trough FEV1, but Respimat® 2.5 μg was not.,Tiotropium Respimat® 5 μg provides similar bronchodilator efficacy to tiotropium HandiHaler® 18 μg with comparable rates of FEV1 decline.,The rate of FEV1 decline varied based on disease severity, with a steeper rate of decline observed in patients with moderate airway obstruction.,NCT01126437.,The online version of this article (doi:10.1186/s12931-015-0269-4) contains supplementary material, which is available to authorized users. | Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users. | 1 |
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