Chronic Obstructive Pulmonary Disease Cohort Research Articles

Twenty-year trends in excess costs of chronic obstructive pulmonary disease.

Several major risk factors for chronic obstructive pulmonary disease (COPD), such as population aging, smoking rates, and air pollution levels are rapidly changing, causing inevitable changes in the population burden of COPD. We determined the excess direct costs of COPD and their trend from 2001 to 2020. Using administrative health data from British Columbia, Canada, we created a retrospective matched cohort of physician-diagnosed COPD patients and non-COPD individuals. Excess direct medical costs (2020 $CAD) were estimated by analysing hospital records, outpatient services, medications, and community-care services. Comorbidity classes were assessed using the International Classification of Diseases codes. Excess COPD costs were estimated as the adjusted difference in direct medical costs between COPD and non-COPD cohorts. There were 208 554 and 404 703 individuals in the COPD and non-COPD cohorts, respectively (47.8% female; mean baseline age 69.1 and 68.2 years, respectively). Direct medical costs for COPD were $9224 per patient-year (/PY), compared to $3396/PY for non-COPD, giving rise to excess costs of $5828/PY (95% confidence interval [CI] 5759-5897). Excess costs increased by 48% over the study period. Excess costs due to comorbidities were $3588/PY (95% CI 3554-3622), with cardiovascular-related conditions alone exceeding the costs attributed to COPD ($1375/PY versus $904/PY). Despite multifaceted prevention and management initiatives, COPD-related economic burden is increasing, with the majority of costs due to comorbid conditions. Rising per-patient costs, combined with the flat or increasing prevalence of COPD in many jurisdictions, indicates a significant increase in COPD burden.

Detection of chronic obstructive pulmonary disease and frequency of cardiopulmonary events in patients with a significant smoking history hospitalised for acute myocardial infarction

Abstract Background Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and also myocardial infarction (MI). Patients with COPD are more likely to have MI than those without and adequately treating COPD might improve cardiovascular outcomes. Reliable diagnosis is important for appropriate treatment. Prevalence of COPD in those hospitalised for MI has not been accurately established. Blood eosinophil count is an important guide to the benefit of inhaled corticosteroid (ICS) treatment in COPD. We aimed to accurately characterise lung function, symptom burden, eosinophil count and cardiopulmonary events in those with a significant smoking history hospitalised for acute MI. Methods Participants (n=216) with a smoking history of ≥10 pack-years currently hospitalised for acute MI were recruited at a single UK centre. Microspirometry and completion of the COPD Assessment Test (CAT) questionnaire were performed at enrolment. Presence and severity of COPD was graded using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. A high burden of COPD symptoms was defined as a CAT score of >10. Repeat CAT and assessment for relevant cardiopulmonary events was undertaken at 3 months and 1 year after enrolment. Results In the enrolled cohort, median age was 60 years (IQR 53-67), 26% were female, 57% were current smokers and median pack-year history was 32 (23-45). 41 of 216 (19 %, [95% CI 14-25]) had evidence of COPD, defined as FEV1/FEV6 <0.7 on best-attempt microspirometry, with 39 (95%) being GOLD2 or greater. Of the 41 with detected COPD, only 15 (37%, [22-53]) had a prior diagnosis. In those with evidence of COPD, a high burden of COPD symptoms was present in 63% of participants at enrolment, 40% at 3 months and 45% at 1 year. 20% [9-35] were receiving inhaled corticosteroids at enrolment. 63% [47-78] had eosinophil count ≥100 cells/mm3 and 17% [7-32] ≥300 cells/mm3. Among those with detected COPD, after 1 year 19.5% (95% CI 9-35%) had suffered a respiratory illness requiring prescription of medication, which was numerically but not statistically significantly higher than those without detected COPD (14.3% [10-20%]). In the COPD cohort, death, infection requiring hospitalisation, MI or unplanned coronary revascularisation, and bleeding requiring hospitalisation each occurred on two occasions (4.9%). Conclusions Based on these data, the prevalence of microspirometry-diagnosed COPD of any severity in patients with significant smoking history hospitalised for MI is around 19%. There is a high rate of undiagnosed and untreated disease, a significant burden of symptoms, including during convalescence, and around a 20% incidence of respiratory illness requiring medical treatment at 1 year. Gathering accurate data from this group is helpful in planning research and service improvement. Increasing detection of COPD in patients with MI would lead to improved cardiopulmonary outcomes.

Diffusion capacity and static hyperinflation as markers of disease progression predict 3-year mortality in COPD: Results from COSYCONET.

Chronic obstructive pulmonary disease (COPD) exhibits diverse patterns of disease progression, due to underlying disease activity. We hypothesized that changes in static hyperinflation or KCO % predicted would reveal subgroups with disease progression unidentified by preestablished markers (FEV1, SGRQ, exacerbation history) and associated with unique baseline biomarker profiles. We explored 18-month measures of disease progression associated with 18-54-month mortality, including changes in hyperinflation parameters and transfer factor, in a large German COPD cohort. Analysing data of 1364 patients from the German observational COSYCONET-cohort, disease progression and improvement patterns were assessed for their impact on mortality via Cox hazard regression models. Association of biomarkers and COPD Assessment test items with phenotypes of disease progression or improvement were evaluated using logistic regression and random forest models. Increased risk of 18-54-month mortality was linked to decrease in KCO % predicted (7.5% increments) and FEV1 (20 mL increments), increase in RV/TLC (2% increments) and SGRQ (≥6 points), and an exacerbation grade of 2 at 18 months. Decrease in KCO % predicted ≥7.5% and an increase of RV/TLC ≥2% were the most frequent measures of 18-month disease progression occurring in ~52% and ~46% of patients, respectively. IL-6 and CRP thresholds exhibited significant associations with medium- and long-term disease measures. In a multicentric cohort of COPD, new markers of current disease activity predicted mid-term mortality and could not be anticipated by baseline biomarkers.

HHIP's Dynamic Role in Epithelial Wound Healing Reveals a Potential Mechanism of COPD Susceptibility.

A genetic variant near HHIP has been consistently identified as associated with increased risk for Chronic Obstructive Pulmonary Disease (COPD), the third leading cause of death worldwide. However HHIP's role in COPD pathogenesis remains elusive. Canonically, HHIP is a negative regulator of the hedgehog pathway and downstream GLI1 and GLI2 activation. The hedgehog pathway plays an important role in wound healing, specifically in activating transcription factors that drive the epithelial mesenchymal transition (EMT), which in its intermediate state (partial EMT) is necessary for the collective movement of cells closing the wound. Herein, we propose a mechanism to explain HHIP's role in faulty epithelial wound healing, which could contribute to the development of emphysema, a key feature of COPD. Using two different Boolean models compiled from the literature, we show dysfunctional HHIP results in a lack of negative feedback on GLI, triggering a full EMT, where cells become mesenchymal and do not properly close the wound. We validate these Boolean models with experimental evidence gathered from published scientific literature. We also experimentally test if low HHIP expression is associated with EMT at the edge of wounds by using a scratch assay in a human lung epithelial cell line. Finally, we show evidence supporting our hypothesis in bulk and single cell RNA-Seq data from different COPD cohorts. Overall, our analyses suggest that aberrant wound healing due to dysfunctional HHIP, combined with chronic epithelial damage through cigarette smoke exposure, may be a primary cause of COPD-associated emphysema.

Biological Age, Chronological Age, and Survival in Pulmonary Fibrosis: A Causal Mediation Analysis.

Rationale: Accelerated biological aging has been implicated in the development of interstitial lung disease (ILD) and other diseases of aging but remains poorly understood. Objectives: To identify plasma proteins that mediate the relationship between chronological age and survival association in patients with ILD. Methods: Causal mediation analysis was performed to identify plasma proteins that mediated the chronological age-survival relationship in an idiopathic pulmonary fibrosis discovery cohort. Proteins mediating this relationship after adjustment for false discovery were advanced for testing in an independent ILD validation cohort and explored in a chronic obstructive pulmonary disease cohort. A proteomic-based measure of biological age was constructed and survival analysis performed, assessing the impact of biological age and peripheral blood telomere length on the chronological age-survival relationship. Measurements and Main Results: Twenty-two proteins mediated the chronological age-survival relationship after adjustment for false discovery in the idiopathic pulmonary fibrosis discovery cohort (n = 874), with 19 remaining significant mediators of this relationship in the ILD validation cohort (n = 983) and one mediating this relationship in the chronic obstructive pulmonary disease cohort. Latent transforming growth factor-β binding protein 2 and ectodysplasin A2 receptor showed the strongest mediation across cohorts. A proteomic measure of biological age completely attenuated the chronological age-survival association and better discriminated survival than chronological age. Results were robust to adjustment for peripheral blood telomere length, which did not mediate the chronological age-survival relationship. Conclusions: Molecular measures of aging completely mediate the relationship between chronological age and survival, suggesting that chronological age has no direct effect on ILD survival.

Associations Between Chronic Rhinosinusitis and the Development of Non–Cystic Fibrosis Bronchiectasis

BackgroundStudies have shown an association between chronic rhinosinusitis (CRS) and non-cystic fibrosis (CF) bronchiectasis. ObjectiveWe aimed to determine if CRS increases the risk of developing non-CF bronchiectasis. MethodsA retrospective analysis was conducted utilizing electronic medical records from an academic center. Patients with CRS without bronchiectasis, with at least one chest computed tomography (CT) performed after the diagnosis of CRS, were identified between January 2006 and December 2015. Charts were reviewed until May 2022. The control group was age, sex, and race matched, and included patients without CRS, asthma, or chronic obstructive pulmonary disease (COPD) who had at least one chest CT. Bronchiectasis was identified by chest CT radiology reports. The odds of developing bronchiectasis were analyzed in patients with CRS without asthma or COPD (Cohort 1) and patients with CRS with asthma or COPD (Cohort 2). ResultsThe odds of developing bronchiectasis were significantly higher in patients with CRS (139/1594, 8.7%) compared to patients in the control group (443/7992 [5.5%], OR 1.63 [1.34-1.99]). Furthermore, the odds of developing bronchiectasis were higher in Cohort 1 (63/863 [7.3%], OR 1.34 [1.02-1.76]) and Cohort 2 (76/731 [10.4%], OR 1.98 [1.53-2.55]) versus the control group. After adjusting for confounding diseases, the association was attenuated in Cohort 1 (OR 1.22 [0.92-1.61]) but remained significant in Cohort 2 (OR 1.78 [1.37-2.31]). ConclusionsCRS is associated with the future development of non-CF bronchiectasis. Patients with CRS, especially those with asthma or COPD, have a higher likelihood of developing bronchiectasis than patients without CRS.

Automated evaluation of diaphragm configuration based on chest CT in COPD patients

BackgroundSevere chronic obstructive pulmonary disease (COPD) often results in hyperinflation and flattening of the diaphragm. An automated computed tomography (CT)-based tool for quantifying diaphragm configuration, a biomarker for COPD, was developed in-house and tested in a large cohort of COPD patients.MethodsWe used the LungQ platform to extract the lung-diaphragm intersection, as direct diaphragm segmentation is challenging. The tool computed the diaphragm index (surface area/projected surface area) as a measure of diaphragm configuration on inspiratory scans in a COPDGene subcohort. Visual inspection of 250 randomly selected segmentations served as a quality check. Associations between the diaphragm index, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages, forced expiratory volume in 1 s (FEV1) % predicted, and CT-derived emphysema scores were explored using analysis of variance and Pearson correlation.ResultsThe tool yielded incomplete segmentation in 9.2% (2.4% major defect, 6.8% minor defect) of 250 randomly selected cases. In 8431 COPDGene subjects (4240 healthy; 4191 COPD), the diaphragm index was increasingly lower with higher GOLD stages (never-smoked 1.83 ± 0.16; GOLD-0 1.79 ± 0.18; GOLD-1 1.71 ± 0.15; GOLD-2: 1.67 ± 0.16; GOLD-3 1.58 ± 0.14; GOLD-4 1.54 ± 0.11) (p < 0.001). Associations were found between the diaphragm index and both FEV1% predicted (r = 0.44, p < 0.001) and emphysema score (r = −0.36, p < 0.001).ConclusionWe developed an automated tool to quantify the diaphragm configuration in chest CT. The diaphragm index was associated with COPD severity, FEV1%predicted, and emphysema score.Relevance statementDue to the hypothesized relationship between diaphragm dysfunction and diaphragm configuration in COPD patients, automatic quantification of diaphragm configuration may prove useful in evaluating treatment efficacy in terms of lung volume reduction.Key PointsSevere COPD changes diaphragm configuration to a flattened state, impeding function.An automated tool quantified diaphragm configuration on chest-CT providing a diaphragm index.The diaphragm index was correlated to COPD severity and may aid treatment assessment.Graphical

Autoimmune diseases and COPD risk: A Mendelian randomization study

BackgroundStudies in epidemiology have indicated a link between chronic obstructive pulmonary disease (COPD) and various autoimmune conditions.This study aimed to investigate the potential causal link between nine autoimmune diseases with a genetic basis and COPD using a two-sample Mendelian randomization (MR) analysis. MethodTo test the impact of susceptibility to immune-related outcomes on genetic prediction of COPD risk, we used pooled statistics from the largest genome-wide association study (GWAS) in Europe in a two-sample MR setting.Genetic data for type 1 diabetes, hypothyroidism, systemic lupus erythematosus, and primary biliary cirrhosis were obtained from the European Bioinformatics Institute (EBI), while data for multiple sclerosis and primary sclerosing cholangitis were extracted from the Integrative Epidemiology Unit (IEU) database. Additionally, genetic data for ulcerative colitis, rheumatoid arthritis, and celiac disease were also collected.These nine autoimmune diseases and the COPD cohort from the UK Biobank (1605 cases and 461,328 controls) were analyzed separately as exposure and outcome.Our primary method for the initial screening was inverse variance weighting (IVW).The MR-Egger regression test assessed multivariate validity, while the Cochran’s Q test examined heterogeneity.To ensure the reliability of the findings, a leave-one-out analysis was conducted. ResultIVW discovered proof of type 1 diabetes (OR = 1.0003; 95 % CI = 1.0000–1.0005; P = 0.046), hypothyroidism (OR = 1.0004; 95 % CI = 1.0001–1.0008; P = 0.0263), celiac disease (OR = 1.0002; 95 % CI = 1.0000–1.0004; P = 0.0168) and systemic lupus erythematosus (OR = 1.0002; 95 % CI = 1.0000–1.0004; P = 0.049) were significantly linked to the heightened risk of COPD with no signs of variation or pleiotropy.Even after accounting for potential confounding factors like smoking, the correlation remained robust.Additionally, our research found that the IVW method did not indicate any causal link between COPD and multiple sclerosis, ulcerative colitis, rheumatoid arthritis, primary biliary cirrhosis, or primary sclerosing cholangitis (all P >0.05). ConclusionThis research discovered that individuals with type 1 diabetes, hypothyroidism, celiac disease, and systemic lupus erythematosus have a higher likelihood of developing COPD.Additionally, this research revealed no connection between COPD and multiple sclerosis, ulcerative colitis, rheumatoid arthritis, primary biliary cirrhosis, or primary sclerosing cholangitis.

Computed tomography mucus plugs and airway tree structure in patients with chronic obstructive pulmonary disease: Associations with airflow limitation, health-related independence and mortality.

Mucus plugs and underlying airway tree structure can affect airflow limitation and prognosis in patients with chronic obstructive pulmonary disease (COPD), but their relative roles are unclear. This study used two COPD cohorts to examine whether mucus plugs on computed tomography (CT) were associated with airflow limitation and clinical outcomes independent of other airway structural changes and emphysema. Based on visual CT assessment, patients with mucus plugs in 0, 1-2 and ≥3 lung segments were assigned to no-, low- and high-mucus groups. Loss of health-related independence and mortality were prospectively recorded for 3 and 10 years in the Kyoto-Himeji and Hokkaido cohorts, respectively. The percentages of the wall area of the central airways (WA%), total airway count (TAC) and emphysema were quantified on CT. Of 199 and 96 patients in the Kyoto-Himeji and Hokkaido cohorts, 34% and 30%, respectively, had high mucus scores. In both cohorts, TAC was lower in the high-mucus group than in the no-mucus group, whereas their emphysema severity did not differ. High mucus score and low TAC were independently associated with airflow limitation after adjustment for WA% and emphysema. In multivariable models adjusted for WA% and emphysema, TAC, rather than mucus score, was associated with a greater rate of loss of independence, whereas high mucus score, rather than TAC, was associated with increased mortality. Mucus plugs and lower airway branch count on CT had distinct roles in airflow limitation, health-related independence and mortality in patients with COPD.

The Usefulness of the C2HEST Score in Predicting the Clinical Outcomes of COVID-19 in COPD and Non-COPD Cohorts.

Patients with chronic obstructive pulmonary disease (COPD) infected with SARS-CoV-2 indicate a higher risk of severe COVID-19 course, which is defined as the need for hospitalization in the intensive care unit, mechanical ventilation, or death. However, simple tools to stratify the risk in patients with COPD suffering from COVID-19 are lacking. The current study aimed to evaluate the predictive value of the C2HEST score in patients with COPD. A retrospective analysis of medical records from 2184 patients hospitalized with COVID-19 at the University Hospital in Wroclaw from February 2020 to June 2021, which was previously used in earlier studies, assessed outcomes such as mortality during hospitalization, all-cause mortality at 3 and 6 months, non-fatal discharge, as well as adverse clinical incidents. This re-analysis specifically examines the outcomes using a COPD split. In the COPD group, 42 deaths were recorded, including 18 in-hospital deaths. In-hospital mortality rates at 3 and 6 months did not significantly differ among C2HEST strata, nor did their impact on subsequent treatment. However, a notable association between the C2HEST score and prognosis was observed in the non-COPD cohort comprising 2109 patients. The C2HEST score's predictive ability is notably lower in COPD patients compared to non-COPD subjects, with COPD itself indicating a high mortality risk. However, C2HEST effectively identifies patients at high risk of cardiac complications during COVID-19, especially in non-COPD cases.

Clinical significance of chronic bronchitis in different racial groups

BackgroundsLimited data are available on racial differences in the clinical features of chronic bronchitis (CB) patients with chronic obstructive pulmonary disease (COPD). In this study, we aimed to compare clinical features among CB patients of different races. We also analyzed the clinical significance of CB, defined classically and based on the COPD Assessment Test (CAT), to validate the CAT-based definition.MethodsWe analyzed patient data extracted from the Korean COPD Subgroup Study (KOCOSS) cohort (2012–2021) and US Genetic Epidemiology of COPD (COPDGene) study (2008–2011). We compared clinical characteristics among CB and non-CB patients of three different races using two CB definitions.ResultsIn this study, 3,462 patients were non-Hispanic white (NHW), 1,018 were African American (AA), and 1,793 were Asian. The proportions of NHW, AA, and Asian patients with CB according to the classic definition were 27.4%, 20.9%, and 10.7%, compared with 25.2%, 30.9%, and 23.0% according to the CAT-based definition, respectively. The risk of CB prevalence was highest in NHW and lowest in Asian COPD patients. Among all races, CB patients were more likely to be current smokers, have worse respiratory symptoms and poorer health-related quality of life (HrQoL), and to have decreased lung function and exercise capacity. Most of these characteristics showed similar associations with the outcomes between the two definitions of CB. A binominal regression model revealed that CB patients of all races had an increased risk of future exacerbations according to both CB definitions, except for Asian patients with classically defined CB.ConclusionsThe presence of CB was associated with worse respiratory symptoms, HrQoL, exercise capacity and lung function, and more exacerbations, regardless of race or CB definition. The CAT-based definition may be more useful for assessing the risk of future exacerbations in Asian COPD patients.

Evaluating the clinical utility of small airway function assessment for early diagnosis of GOLD stage 0 chronic obstructive pulmonary disease

Objective To investigate the clinical utility of small airway function indices for early identification of GOLD stage 0 chronic obstructive pulmonary disease (COPD). Methods This retrospective study enrolled 137 participants at our institution between January 2017 and December 2018, comprising 40 healthy controls, 46 individuals with GOLD stage 0 COPD, and 51 patients with established COPD. Pulmonary function was assessed using the PowerCube spirometry system (GANSHORN, Germany). Parameters evaluated included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, and small airway function indicators. Results The COPD cohort exhibited significantly lower values across all lung function measures compared to the other two groups, particularly for dynamic lung volume parameters such as FEV1%predicted and FEV1/FVC%. Small airway function indices, including FEV3%predicted, FEF75%predicted, FEF50%predicted, FEF25%predicted, and MMEF%predicted, were markedly decreased in the COPD group (all p-values <0.001). Receiver operating characteristic (ROC) curve analysis demonstrated that MMEF/FVC% and FEV3/FVC% had high diagnostic accuracy for COPD, with MMEF/FVC% exhibiting the optimal sensitivity and specificity. Conclusion Small airway function indices, especially MMEF/FVC%, can serve as effective tools for early identification of GOLD stage 0 COPD. Incorporation of these findings into clinical practice may facilitate early diagnosis and intervention, thereby improving treatment outcomes and patient quality of life.

Motivation and Confidence about Physical Activity in Chronic Obstructive Pulmonary Disease Patients: Health Benefits Matter to Patients

Introduction: Physical activity (PA) has shown great benefits in patients with chronic obstructive pulmonary disease (COPD); however, their PA is below average. Motivational factors associated with PA in COPD have not been widely studied and could be a target for improving adherence to PA. The objective of our study was to identify and understand the different motivational and confidence factors related to low levels of PA in a COPD cohort. Method: Observational, prospective, multicenter study of COPD patients. Sociodemographic data, respiratory symptoms, comorbidities, spirometry, and exercise capacity were collected. PA was measured using the Dynaport accelerometer and patient motivation and confidence in PA were assessed by a questionnaire previously used in a COPD population in the USA. Results: Eighty six COPD patients were included, 68.6% being male, with a mean (SD) age of 66.6 (8.5) years and a mean forced expiratory volume in the first second (%) of 50.9% (17.3%). The mean walking time was 82.8 (37.8) minutes/day. Questions related to health benefits and enjoying exercise were ranked highest in the motivation questionnaire and statistically significant differences were found in PA measures between patients with low and high motivation. A lack of confidence regarding hot weather and health-related issues significantly influenced PA levels. Advice from third parties, including healthcare providers, was not associated with higher PA levels. Conclusions: Improving the health of COPD patients is their main motivation to perform PA. Lack of confidence when it is hot or when they fear for their health is related to low levels of PA. Advice from third parties, including healthcare professionals, is not associated with higher PA. These results are relevant for developing strategies to increase the adherence of COPD patients to PA programs.

Clinical features and 1-year outcomes of variable obstruction in participants with preserved spirometry: results from the ECOPD study in China

BackgroundThere are limited data on the clinical features and longitudinal prognosis of variable obstruction, particularly among never smokers and different variable obstruction types. Therefore, we aimed to evaluate the clinical...

A Harmonised Approach to Curating Research-Ready Datasets for Asthma, Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Lung Disease (ILD) in England, Wales and Scotland Using Clinical Practice Research Datalink (CPRD), Secure Anonymised Information Linkage (SAIL) Databank and DataLoch.

Electronic healthcare records (EHRs) are an important resource for health research that can be used to improve patient outcomes in chronic respiratory diseases. However, consistent approaches in the analysis of these datasets are needed for coherent messaging, and when undertaking comparative studies across different populations. We developed a harmonised curation approach to generate comparable patient cohorts for asthma, chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) using datasets from within Clinical Practice Research Datalink (CPRD; for England), Secure Anonymised Information Linkage (SAIL; for Wales) and DataLoch (for Scotland) by defining commonly derived variables consistently between the datasets. By working in parallel on the curation methodology used for CPRD, SAIL and DataLoch for asthma, COPD and ILD, we were able to highlight key differences in coding and recording between the databases and identify solutions to enable valid comparisons. Codelists and metadata generated have been made available to help re-create the asthma, COPD and ILD cohorts in CPRD, SAIL and DataLoch for different time periods, and provide a starting point for the curation of respiratory datasets in other EHR databases, expediting further comparable respiratory research.

Clinical characterization and outcomes of impulse oscillometry-defined bronchodilator response: an ECOPD cohort-based study

BackgroundThe clinical significance of the impulse oscillometry-defined small airway bronchodilator response (IOS-BDR) is not well-known. Accordingly, this study investigated the clinical characteristics of IOS-BDR and explored the association between lung function decline, acute respiratory exacerbations, and IOS-BDR.MethodsParticipants were recruited from an Early Chronic Obstructive Pulmonary Disease (ECOPD) cohort subset and were followed up for two years with visits at baseline, 12 months, and 24 months. Chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio < 0.70. IOS-BDR was defined as meeting any one of the following criteria: an absolute change in respiratory system resistance at 5 Hz ≤ − 0.137 kPa/L/s, an absolute change in respiratory system reactance at 5 Hz ≥ 0.055 kPa/L/s, or an absolute change in reactance area ≤ − 0.390 kPa/L. The association between IOS-BDR and a decline in lung function was explored with linear mixed-effects model. The association between IOS-BDR and the risk of acute respiratory exacerbations at the two-year follow-up was analyzed with the logistic regression model.ResultsThis study involved 466 participants (92 participants with IOS-BDR and 374 participants without IOS-BDR). Participants with IOS-BDR had higher COPD assessment test and modified Medical Research Council dyspnea scale scores, more severe emphysema, air trapping, and rapid decline in FVC than those without IOS-BDR over 2-year follow-up. IOS-BDR was not associated with the risk of acute respiratory exacerbations at the 2-year follow-up.ConclusionsThe participants with IOS-BDR had more respiratory symptoms, radiographic structural changes, and had an increase in decline in lung function than those without IOS-BDR.Trial registrationChinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July, 2019.

Real-World Effectiveness of Single-Inhaler Triple Therapy for COPD: Impact of Diabetes Comorbidity

Background Type 2 diabetes is a frequent comorbidity in chronic obstructive pulmonary disease (COPD) patients, with the GOLD treatment recommendations asserting that the presence of diabetes be disregarded in the choice of treatment. Methods In a cohort of COPD patients with frequent exacerbations, initiators of single-inhaler triple therapy or dual bronchodilators were compared on the incidence of COPD exacerbation and pneumonia over one year, adjusted by propensity score weighting and stratified by type 2 diabetes. Results The COPD cohort included 1,114 initiators of triple inhalers and 4,233 of dual bronchodilators (28% with type 2 diabetes). The adjusted hazard ratio (HR) of exacerbation with triple therapy was 1.04 (95% CI: 0.86–1.25) among COPD patients with type 2 diabetes and 0.74 (0.65–0.85) in those without. The incidence of severe pneumonia was elevated with triple therapy among patients with type 2 diabetes (HR 1.77; 1.14–2.75). Conclusion Triple therapy in COPD is effective among those without, but not those with, type 2 diabetes. Future therapeutic trials in COPD should consider diabetes comorbidity.

Effects of triple therapy on disease burden in patients of GOLD groups C and D: results from the observational COPD cohort COSYCONET

BackgroundRandomized controlled trials described beneficial effects of inhaled triple therapy (LABA/LAMA/ICS) in patients with chronic obstructive pulmonary disease (COPD) and high risk of exacerbations. We studied whether such effects were also detectable under continuous treatment in a retrospective observational setting.MethodsData from baseline and 18-month follow-up of the COPD cohort COSYCONET were used, including patients categorized as GOLD groups C/D at both visits (n = 258). Therapy groups were defined as triple therapy at both visits (triple always, TA) versus its complement (triple not always, TNA). Comparisons were performed via multiple regression analysis, propensity score matching and inverse probability weighting to adjust for differences between groups. For this purpose, variables were divided into predictors of therapy and outcomes.ResultsIn total, 258 patients were eligible (TA: n = 162, TNA: n = 96). Without adjustments, TA patients showed significant (p < 0.05) impairments regarding lung function, quality of life and symptom burden. After adjustments, most differences in outcomes were no more significant. Total direct health care costs were reduced but still elevated, with inpatient costs much reduced, while costs of total and respiratory medication only slightly changed.ConclusionWithout statistical adjustment, patients with triple therapy showed multiple impairments as well as elevated treatment costs. After adjusting for differences between treatment groups, differences were reduced. These findings are compatible with beneficial effects of triple therapy under continuous, long-term treatment, but also demonstrate the limitations encountered in the comparison of controlled intervention studies with observational studies in patients with severe COPD using different types of devices and compounds.

Effectiveness, Safety, and Costs of Thromboprophylaxis with Enoxaparin or Unfractionated Heparin Among Medical Inpatients With Chronic Obstructive Pulmonary Disease or Heart Failure

Background: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are risk factors for venous thromboembolism (VTE). Enoxaparin and unfractionated heparin (UFH) help prevent hospital-associated VTE, but few studies have compared them in COPD or HF. Objectives: To compare effectiveness, safety, and costs of enoxaparin vs UFH thromboprophylaxis in medical inpatients with COPD or HF. Methods: This retrospective cohort study included adults with COPD or HF from the Premier PINC AI Healthcare Database. Included patients received prophylactic-dose enoxaparin or UFH during a &gt;6-day index hospitalization (the first visit/admission that met selection criteria during the study period) between January 1, 2010, and September 30, 2016. Multivariable regression models assessed independent associations between exposures and outcomes. Hospital costs were adjusted to 2017 US dollars. Patients were followed 90 days postdischarge (readmission period). Results: In the COPD cohort, 114 174 (69%) patients received enoxaparin and 51 011 (31%) received UFH. Among patients with COPD, enoxaparin recipients had 21%, 37%, and 10% lower odds of VTE, major bleeding, and in-hospital mortality during index admission, and 17% and 50% lower odds of major bleeding and heparin-induced thrombocytopenia (HIT) during the readmission period, compared with UFH recipients (all P &lt;.006). In the HF cohort, 58 488 (58%) patients received enoxaparin and 42 726 (42%) received UFH. Enoxaparin recipients had 24% and 10% lower odds of major bleeding and in-hospital mortality during index admission, and 13%, 11%, and 51% lower odds of VTE, major bleeding, and HIT during readmission (all P &lt;.04) compared with UFH recipients. Enoxaparin recipients also had significantly lower total hospital costs during index admission (mean reduction per patient: COPD, $1280; HF, $2677) and readmission (COPD, $379; HF, $1024). Among inpatients with COPD or HF, thromboprophylaxis with enoxaparin vs UFH was associated with significantly lower odds of bleeding, mortality, and HIT, and with lower hospital costs. Conclusions: This study suggests that thromboprophylaxis with enoxaparin is associated with better outcomes and lower costs among medical inpatients with COPD or HF based on real-world evidence. Our findings underscore the importance of assessing clinical outcomes and side effects when evaluating cost-effectiveness.

Effectiveness, Safety, and Costs of Thromboprophylaxis with Enoxaparin or Unfractionated Heparin Among Medical Inpatients With Chronic Obstructive Pulmonary Disease or Heart Failure.

Background: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are risk factors for venous thromboembolism (VTE). Enoxaparin and unfractionated heparin (UFH) help prevent hospital-associated VTE, but few studies have compared them in COPD or HF. Objectives: To compare effectiveness, safety, and costs of enoxaparin vs UFH thromboprophylaxis in medical inpatients with COPD or HF. Methods: This retrospective cohort study included adults with COPD or HF from the Premier PINC AI Healthcare Database. Included patients received prophylactic-dose enoxaparin or UFH during a >6-day index hospitalization (the first visit/admission that met selection criteria during the study period) between January 1, 2010, and September 30, 2016. Multivariable regression models assessed independent associations between exposures and outcomes. Hospital costs were adjusted to 2017 US dollars. Patients were followed 90 days postdischarge (readmission period). Results: In the COPD cohort, 114 174 (69%) patients received enoxaparin and 51 011 (31%) received UFH. Among patients with COPD, enoxaparin recipients had 21%, 37%, and 10% lower odds of VTE, major bleeding, and in-hospital mortality during index admission, and 17% and 50% lower odds of major bleeding and heparin-induced thrombocytopenia (HIT) during the readmission period, compared with UFH recipients (all P <.006). In the HF cohort, 58 488 (58%) patients received enoxaparin and 42 726 (42%) received UFH. Enoxaparin recipients had 24% and 10% lower odds of major bleeding and in-hospital mortality during index admission, and 13%, 11%, and 51% lower odds of VTE, major bleeding, and HIT during readmission (all P <.04) compared with UFH recipients. Enoxaparin recipients also had significantly lower total hospital costs during index admission (mean reduction per patient: COPD, 2677) and readmission (COPD, 1024). Among inpatients with COPD or HF, thromboprophylaxis with enoxaparin vs UFH was associated with significantly lower odds of bleeding, mortality, and HIT, and with lower hospital costs. Conclusions: This study suggests that thromboprophylaxis with enoxaparin is associated with better outcomes and lower costs among medical inpatients with COPD or HF based on real-world evidence. Our findings underscore the importance of assessing clinical outcomes and side effects when evaluating cost-effectiveness.