COPD Cohort Research Articles

20-year trends in excess costs of COPD.

Several major risk factors for COPD, such as population ageing, 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 (in 2020 Canadian dollars (CAD)) were estimated by analysing hospital records, outpatient services, medications and community care services. Comorbidity classes were assessed using International Classification of Diseases codes. Excess COPD costs were estimated as the adjusted difference in direct medical costs between the 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 CAD 9224 per patient-year compared to CAD 3396 per patient-year for non-COPD, giving rise to excess costs of CAD 5828 (95% CI 5759-5897) per patient-year. Excess costs increased by 48% over the study period. Excess costs due to comorbidities were CAD 3588 (95% CI 3554-3622) per patient-year, with cardiovascular-related conditions alone exceeding the costs attributed to COPD (CAD 1375 versus 904 per patient-year). 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.

Relationship between Respiratory Microbiome and Systemic Inflammatory Markers in COPD: A Pilot Study.

The respiratory microbiome may influence the development and progression of COPD by modulating local immune and inflammatory events. We aimed to investigate whether relative changes in respiratory bacterial abundance are also associated with systemic inflammation, and explore their relationship with the main clinical COPD phenotypes. Multiplex analysis of inflammatory markers and transcript eosinophil-related markers were analyzed on peripheral blood in a cohort of stable COPD patients (n = 72). Respiratory microbiome composition was analyzed by 16S rRNA microbial sequencing on spontaneous sputum. Spearman correlations were applied to test the relationship between the microbiome composition and systemic inflammation. The concentration of the plasma IL-8 showed an inverted correlation with the relative abundance of 17 bacterial genera in the whole COPD cohort. COPD patients categorized as eosinophilic showed positive relationships with blood eosinophil markers and inversely correlated with the degree of airway obstruction and the number of exacerbations during the previous year. COPD patients categorized as frequent exacerbators were enriched with the bacterial genera Pseudomonas which, in turn, was positively associated with the severity of airflow limitation and the prior year's exacerbation history. The associative relationships of the sputum microbiome with the severity of the disease emphasize the relevance of the interaction between the respiratory microbiota and systemic inflammation.

Influenza and pneumococcal vaccination in patients with COPD from 3 French cohorts: Insufficient coverage and associated factors

BackgroundLow vaccination rates against influenza and Streptococcus (S.) pneumoniae infections in COPD could impair outcomes. Understanding underlying factors could help improving implementation. ObjectivesTo describe vaccination rates at inclusion in COPD cohorts and analyze associated factors. MethodsBetween 2012 and 2018, 5927 patients with sufficient data available were recruited in 3 French COPD cohorts (2566 in COLIBRI-COPD, 2653 in PALOMB and 708 in Initiatives BPCO). Data at inclusion were pooled to describe vaccination rates and analyze associated factors. ResultsMean age was 66 years, 34 % were women, 35 % were current smokers, mean FEV1 was 58 % predicted, 22 % reported ≥2 exacerbations in the year prior to inclusion, mMRC dyspnea grade was ≥2 in 59 %, 52 % had cardiovascular comorbidities and 9 % a history of asthma. Vaccinations rates in the year prior to study entry were 34.4 % for influenza + S. pneumoniae, 17.5 % for influenza alone and 8.9 % for S. pneumoniae alone. In multivariate analyses, influenza vaccination rate was greater in older age, smoking status, low FEV1, exacerbation history, mMRC dyspnea>2, asthma history, hypertension, diabetes mellitus, and the year of inclusion. SP vaccination was associated with type of practice of the respiratory physician, age, smoking status, FEV1, exacerbation history, dyspnea grade, asthma history and the year of inclusion. ConclusionRates of vaccination against influenza and S. pneumoniae infection at inclusion in COPD cohorts remain insufficient and vaccination appears restricted to patients with specific features especially regarding severity and comorbidities, which is not consistent with current recommendations.

Application of the Lancet Commission COPD classification to COPD Cohort Population in South Korea

The Lancet Commissions on COPD recommended a new classification based on five main risk factors.Patients with COPD were prospectively enrolled in a Korean COPD subgroup study cohort between April 2012 and June 2022. Patients were classified according to the etiologies (Type 1: Genetically determined (COPD-G), Type 2: Abnormal lung development (COPD-D), Type 3: Infections (COPD-I), Type 4: Cigarette smoking (COPD-C), Type 5: Biomass and pollution (COPD-P)).The database enrolled 3476 patients. Among 3392 patients, 52 (2 %), 1339 (39 %), 2930 (86 %), and 2221 (65 %) were compatible with type 2 (COPD-D), 3 (COPD-I), 4 (COPD-C), and 5 (COPD-P), respectively. Most patients (71 %, 2405) had multiple risk factors contributing to their COPD. However, 93, 712, and 182 patients had only type 3 (COPD-I), 4 (COPD-C), and 5 (COPD-P), respectively. Type 3 (COPD-I) only patients were significantly younger, more often female, and had lower lung function. Both the rate and frequency of severe exacerbations were significantly higher in type 3 (COPD-I) only patients (p = 0.038 and p = 0.048, respectively). Compared with type 5 (COPD-P) only, type 3 (COPD-I) only was significantly associated with the risk of severe exacerbation (Odds ratio, 5.7 [95 % CI, 1.0–32.4]; P = 0.049, incident rate ratio, 8.7 [95 % CI, 1.7–44.0]; P = 0.009).Many patients were affected by multiple factors. Therefore, it is important to consider not only smoking history, but also other potential risk factors when evaluating patients with COPD. Further research is needed to explore the implications of this new COPD classification system for clinical practice and treatment strategies.

Statins did not reduce the frequency of exacerbations in individuals with COPD and cardiovascular comorbidities in the COSYCONET cohort

BackgroundThe evidence regarding effects of statins on exacerbation risk in COPD remains controversial. Previous studies often excluded patients with cardiovascular comorbidities despite their high prevalence in COPD and role for exacerbations. Based on the cardioprotective properties of statins, we hypothesised that statins may reduce the risk of exacerbations especially in patients with cardiovascular comorbidities.MethodsOne thousand eight hundred eighty seven patients of the German COPD cohort COSYCONET (COPD and Systemic Consequences Comorbidities Network) of GOLD grades 1–4 (37.8% female, mean age 64.78 ± 8.3) were examined at baseline and over a period of 4.5 years for the occurrence of at least one exacerbation or severe exacerbation per year in cross-sectional and longitudinal analyses adjusted for age, gender, BMI, GOLD grade and pack-years. Due to their collinearity, various cardiovascular diseases were tested in separate analyses, whereby the potential effect of statins in the presence of a specific comorbidity was tested as interaction between statins and comorbidity. We also identified patients who never took statins, always took statins, or initiated statin intake during the follow-up.ResultsOne thousand three hundred six patients never took statins, 31.6% were statin user, and 12.9% initiated statins during the follow-up. Most cardiovascular diseases were significantly (p < 0.05)may associated with an increased risk of COPD exacerbations, but in none of them the intake of statins was a significant attenuating factor, neither overall nor in modulating the increased risk linked to the specific comorbidities. The results of the cross-sectional and longitudinal analyses were consistent with each other, also those regarding at least 1 exacerbation or at least 1 severe exacerbation per year.ConclusionThese findings complement the existing literature and may suggest that even in patients with COPD, cardiovascular comorbidities and a statin therapy that targets these comorbidities, the effects of statins on exacerbation risk are either negligible or more subtle than a reduction in exacerbation frequency.Trial registrationTrial registration ClinicalTrials.gov, Identifier: NCT01245933.Other Study ID (BMBF grant): 01GI0881, registered 18 November 2010, study start 2010–11, primary completion 2013–12, study completion 2023–09.https://clinicaltrials.gov/study/NCT01245933?cond=COPD&term=COSYCONET&rank=3

Expression of intramuscular extracellular matrix proteins in vastus lateralis muscle fibres between atrophic and non-atrophic COPD.

Extracellular matrix (ECM) proteins are the major constituents of the muscle cell micro-environment, imparting instructive signalling, steering cell behaviour and controlling muscle regeneration. ECM remodelling is among the most affected signalling pathways in COPD and aged muscle. As a fraction of COPD patients present muscle atrophy, we questioned whether ECM composition would be altered in patients with peripheral muscle wasting (atrophic COPD) compared to those without muscle wasting (non-atrophic COPD). A set of ECM molecules with known impact on myogenesis were quantified in vastus lateralis muscle biopsies from 29 COPD patients (forced expiratory volume in 1 s 55±12% predicted) using ELISA and real-time PCR. COPD patients were grouped to atrophic or non-atrophic based on fat-free mass index (<17 or ≥17 kg·m-2). Atrophic COPD patients presented a lower average vastus lateralis muscle fibre cross-sectional area (3872±258 μm2) compared to non-atrophic COPD (4509±198 μm2). Gene expression of ECM molecules was found significantly lower in atrophic COPD compared to non-atrophic COPD for collagen type I alpha 1 chain (COL1A1), fibronectin (FN1), tenascin C (TNC) and biglycan (BGN). In terms of protein levels, there were no significant differences between the two COPD cohorts for any of the ECM molecules tested. Although atrophic COPD presented decreased contractile muscle tissue, the differences in ECM mRNA expression between atrophic and non-atrophic COPD were not translated at the protein level, potentially indicating an accumulation of long-lived ECM proteins and dysregulated proteostasis, as is typically observed during deconditioning and ageing.

PROGNOSTIC VALUE OF THE TRIGLYCERIDE-GLUCOSE INDEX IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE, ASTHMA AND THEIR OVERLAP

Considering that patients with concurrent COPD and asthma frequently have metabolic disorders, special attention should be given to their detection and subsequent correction, as their presence triggers mechanisms of mutual exacerbation, and their progression worsens the prognosis.The goal is to study the correlation between the triglyceride-glucose index, bioimpedance analysis parameters, and spirometry in patients with chronic obstructive pulmonary disease, asthma, asthma-COPD overlap, and comorbid type 2 diabetes.Materials and methods. 25 patients with COPD, 23 with asthma, 25 with asthma-COPD overlap (ACO), and 33 patients with ACO and diabetes mellitus type 2 were examined. The average age of patients was 57[52;67] in the COPD cohort, 52[50;65] for asthma, 51[43;52] for asthma-COPD overlap (ACO), and 60[53.5;65] for ACO with diabetes mellitus type 2. The parameters of external respiration were determined using the BTL 08 SpiroPRO spirometer (UK), bioimpedance analysis was carried out using the portable TANITA BC-601 device (Japan). The level of triglycerides (mmol/L) was determined by the colorimetric method, and fasting glucose was determined by the glucose oxidase method. The triglyceride-glucose index was calculated using the formula: TyG index = ln [fasting TG (mg/dL) x fasting glucose (mg/dL) / 2].Results. The following correlations were established: BMI and FEV1/FVC before bronchodilation (r = 0.23, p = 0.02) and SVC (r = -0.24, p = 0.01); % fat and FVC before bronchodilation (r = -0.23, p = 0.01), as well as SVC (r = -0.21, p = 0.03); visceral fat levels with FEV1 before and after bronchodilation (r = -0.36, p &lt; 0.001 and r = -0.35, p &lt; 0.001) and FVC before and after bronchodilation (r = -0.32, p &lt; 0.001 and r = -0.30, p &lt; 0.001) and SVC (r = -0.33, p &lt; 0.001); TyG and FEV1 before and after the bronchodilation test (r = -0.25, p = 0.01 and r = -0.28, p = 0.005), as well as FVC only after the use of bronchodilator (r = -0.25, p = 0.02).Conclusions. The bioimpedance analysis and TyG index correlate with pulmonary function test parameters (FEV1, FVC, FEV1/FVC ratio, SVC, MVV) in examined patients with COPD, asthma, ACO, and the combination of ACO and type 2 diabetes. Further research prospects. Further studies are needed to clarify the possibility of using the TyG index in clinical practice not only as an alternative indicator of insulin resistance but also as a marker of deteriorating lung function in case of airflow obstruction.

Characteristics and phenotypes of a COPD cohort from referral hospital clinics in Uganda

IntroductionChronic obstructive pulmonary disease (COPD) is a heterogeneous condition with varied clinical and pathophysiological characteristics. Although there is increasing evidence that COPD in low-income and middle-income countries may have different...

Accelerated Lung Function Decline and Mucus-Microbe Evolution in Chronic Obstructive Pulmonary Disease.

Rationale: Progressive lung function loss is recognized in chronic obstructive pulmonary disease (COPD); however, no study concurrently evaluates how accelerated lung function decline relates to mucus properties and the microbiome in COPD. Objectives: Longitudinal assessment of mucus and microbiome changes accompanying accelerated lung function decline in patients COPD. Methods: This was a prospective, longitudinal assessment of the London COPD cohort exhibiting the greatest FEV1 decline (n = 30; accelerated decline; 156 ml/yr FEV1 loss) and with no FEV1 decline (n = 28; nondecline; 49 ml/yr FEV1 gain) over time. Lung microbiomes from paired sputum (total 116 specimens) were assessed by shotgun metagenomics and corresponding mucus profiles evaluated for biochemical and biophysical properties. Measurements and Main Results: Biochemical and biophysical mucus properties are significantly altered in the accelerated decline group. Unsupervised principal component analysis showed clear separation, with mucus biochemistry associated with accelerated decline, whereas biophysical mucus characteristics contributed to interindividual variability. When mucus and microbes are considered together, an accelerated decline mucus-microbiome association emerges, characterized by increased mucin (MUC5AC [mucin 5AC] and MUC5B [mucin 5B]) concentration and the presence of Achromobacter and Klebsiella. As COPD progresses, mucus-microbiome shifts occur, initially characterized by low mucin concentration and transition from viscous to elastic dominance accompanied by the commensals Veillonella, Gemella, Rothia, and Prevotella (Global Initiative for Chronic Obstructive Lung Disease [GOLD] A and B) before transition to increased mucus viscosity, mucins, and DNA concentration together with the emergence of pathogenic microorganisms including Haemophilus, Moraxella, and Pseudomonas (GOLD E). Conclusions: Mucus-microbiome associations evolve over time with accelerated lung function decline, symptom progression, and exacerbations affording fresh therapeutic opportunities for early intervention.

Multimorbidities in COPD are Associated With Increased Exacerbations and Health Care Resource Utilization in Real-World Patients from a U.S. Database.

Patients with chronic obstructive pulmonary disease (COPD) often develop other morbidities, suggesting a systemic component to this disease. This retrospective noninterventional cohort study investigated relationships between multimorbidities in COPD and their impact on COPD exacerbations and COPD-related health care resource utilization (HCRU) using real-world evidence from Optum's de-identified Clinformatics® Data Mart Database. Demographic and clinical characteristics were assessed. Overall comorbidity burden and proportion of individuals with gastroesophageal reflux disease (GERD), diabetes, or osteoporosis/osteopenia were compared in age-matched COPD versus non-COPD cohorts using descriptive statistics. COPD exacerbations and COPD-related HCRU (hospitalizations and emergency department visits) were compared between age-matched cohorts of COPD patients with and without specific common morbidities (GERD, diabetes, and osteoporosis/osteopenia). Additional weight-matching was performed for matched cohorts of COPD patients with and without diabetes, and with and without osteoporosis/osteopenia. The follow-up period was 5 years. Age-matched cohorts with and without COPD each comprised 158,106 patients. Morbidities were more common in the COPD cohort than the cohort without COPD (GERD: 44.9% versus 27.8%; diabetes: 40.8% versus 31.1%; osteoporosis/osteopenia: 18.8% versus 14.1%, respectively). Compared with matched cohorts with COPD only, cohorts of COPD patients with either GERD, diabetes, or osteoporosis/osteopenia experienced increased risk of severe exacerbations (odds ratio [OR]=1.819, OR=1.119, and OR=1.373, respectively), moderate exacerbations (OR=1.699, OR=1.102, and OR=1.322, respectively), or any exacerbations (OR=1.848, OR=1.099, and OR=1.384, respectively, p<0.001 for all comparisons) and increased risk of COPD-related HCRU (emergency department visits: OR=1.983, OR=1.098, and OR=1.343, respectively; hospitalization visits: OR=2.222, OR=1.26, and OR=1.368, respectively; p<0.001 for all comparisons). These real-world data confirm that GERD, diabetes, and osteoporosis are common morbidities in patients with COPD and, moreover, that they affect frequency of exacerbation and HCRU. Determining and addressing the mechanisms behind the systemic effects of COPD may be beneficial for COPD patients and may also help reduce COPD exacerbations.

Increased Burden of Pertussis Among Adolescents and Adults With Asthma or COPD in the United States, 2007 to 2019

Individuals with chronic respiratory illnesses may be at higher risk of pertussis infection and severe pertussis than those without. What is the incidence of pertussis and pertussis complications in cohorts with preexisting asthma or COPD vsage- and sex-matched control patients from the general population in the United States? This observational, retrospective study included individualsaged ≥ 10 years from an administrative health claims system between 2007 and 2019. Individuals with preexisting asthma or COPD were matched with control patients from the general population. The incidence of pertussis infections and pertussis-related complications were assessed overall and by age. The incidence of asthma or COPD exacerbations was also assessed before and after diagnosis of pertussis. In the general population, incidence per 100,000 person-years of pertussis infection ranged from 5.33 in 2007 to 13.04 in 2012, with highest (all years) in those aged 10 to 17 years. The risk of pertussis was higher for the asthma (rate ratio, 3.57; 95%CI, 3.25-3.92) and COPD cohorts (rate ratio, 1.83; 95%CI, 1.57-2.12) than the general population. Those with asthma or COPD had a 4.12-fold (95%CI, 3.16-5.38) and 2.82-fold (95%CI, 2.14-3.27) increased risk of pertussis with complications than the general population, respectively. Exacerbations were most frequent 30days before pertussis diagnosis (incidence rate [IR], 25%) in the asthma cohort and 30days before (IR, 26%) and after (IR, 22%) pertussis diagnosis, remaining elevated for 180days after diagnosis, in the COPD cohort. Among these insured individuals, asthma or COPD increased the risk for pertussis disease and complications vsthe general population. COPD and asthma exacerbations were observed most frequently within 30days of receiving a pertussis diagnosis and remained elevated, suggesting a long-term effect of pertussis in the COPD cohort.

Plasma metabolomics and quantitative interstitial abnormalities in ever-smokers

BackgroundQuantitative interstitial abnormalities (QIA) are an automated computed tomography (CT) finding of early parenchymal lung disease, associated with worse lung function, reduced exercise capacity, increased respiratory symptoms, and death. The metabolomic perturbations associated with QIA are not well known. We sought to identify plasma metabolites associated with QIA in smokers. We also sought to identify shared and differentiating metabolomics features between QIA and emphysema, another smoking-related advanced radiographic abnormality.MethodsIn 928 former and current smokers in the Genetic Epidemiology of COPD cohort, we measured QIA and emphysema using an automated local density histogram method and generated metabolite profiles from plasma samples using liquid chromatography–mass spectrometry (Metabolon). We assessed the associations between metabolite levels and QIA using multivariable linear regression models adjusted for age, sex, body mass index, smoking status, pack-years, and inhaled corticosteroid use, at a Benjamini–Hochberg False Discovery Rate p-value of ≤ 0.05. Using multinomial regression models adjusted for these covariates, we assessed the associations between metabolite levels and the following CT phenotypes: QIA-predominant, emphysema-predominant, combined-predominant, and neither- predominant. Pathway enrichment analyses were performed using MetaboAnalyst.ResultsWe found 85 metabolites significantly associated with QIA, with overrepresentation of the nicotinate and nicotinamide, histidine, starch and sucrose, pyrimidine, phosphatidylcholine, lysophospholipid, and sphingomyelin pathways. These included metabolites involved in inflammation and immune response, extracellular matrix remodeling, surfactant, and muscle cachexia. There were 75 metabolites significantly different between QIA-predominant and emphysema-predominant phenotypes, with overrepresentation of the phosphatidylethanolamine, nicotinate and nicotinamide, aminoacyl-tRNA, arginine, proline, alanine, aspartate, and glutamate pathways.ConclusionsMetabolomic correlates may lend insight to the biologic perturbations and pathways that underlie clinically meaningful quantitative CT measurements like QIA in smokers.

Using an electronic diary and wristband accelerometer to detect exacerbations and activity levels in COPD: a feasibility study.

Early and accurate identification of acute exacerbations of COPD may lead to earlier treatment and prevent hospital admission. Electronic diaries have been developed for symptom monitoring and accelerometers to monitor activity. However, it is unclear whether this technology is usable in the COPD population. This study aimed to assess the feasibility of an electronic diary (eDiary) for symptom reporting using the MoreCare app and activity monitoring with the Garmin Vivofit 2 in COPD. Participants were recruited from the London COPD Cohort. Participants were provided a Garmin Vivofit 2 activity monitor and an android tablet with the MoreCare app for a period of 3 months. 25 COPD patients were recruited (mean±sd age 70.8±7.1 years, forced expiratory volume in 1 s (FEV1) 49.8±14.8% predicted). Age, gender, disease severity and exacerbation frequency had no impact on eDiary compliance. There was a moderate positive correlation between median daily very active minutes and FEV1 % pred (ρ=0.62, p=0.005). Daily step counts decreased during the initial 7 days of exacerbation and recovery compared to a pre-exacerbation baseline. A decision-tree model identified change in sputum colour, change in step count, severity of cold, exacerbation history and use of rescue medication as the most important predictors of acute exacerbations of COPD in this cohort. Symptom and activity monitoring using digital technology is feasible in COPD. Further large-scale digital health studies are needed to assess whether eDiaries can be used to identify patients at risk of exacerbation and guide early intervention.

Impact of the COVID-19 pandemic on COPD patients: a nationwide mortality study in France

Abstract Background Chronic obstructive pulmonary disease (COPD) patients are a vulnerable population with an increased risk of death from COVID-19 if infected. To date, a reduction in hospitalizations for acute exacerbations of COPD has been reported in various contexts, but large population-based studies with mortality follow-up are lacking. We investigated the mortality patterns of COPD patients in France relative to a control population, comparing year 2020 to pre-pandemic years 2017-2019. Methods COPD patients were identified in the French National Health Data System based on their healthcare use. Four COPD cohorts were created, and followed for one year in 2017, 2018, 2019 and 2020, respectively. Corresponding control cohorts (without COPD) were created, matched on sex, age and residence, with a ratio of two controls per case. Survival was analyzed using Cox regressions and standardized rates. Results The four COPD cohorts included about a million and a half individuals each. All-cause mortality increased in 2020 compared to 2019 in the COPD population (hazard ratio (HR) [95% confidence interval]: 1.04 [1.03-1.05]), but to a lesser extent than in the control population (HR: 1.10 [1.08-1.11]). Non-COVID-19 mortality decreased to a greater extent in COPD patients (HR: 0.95 [0.94-0.96]) than in the controls (HR: 0.98 [0.97-0.99]). Death rate from COVID-19 was twice as high in the COPD population relative to the control population (547 vs 279 per 100,000 person-years). Conclusions The direct impact of the pandemic in terms of deaths from COVID-19 was much greater in the COPD population than in the control population. However, the larger decline in non-COVID-19 mortality in COPD patients could reflect a specific protective effect of the containment measures on this population, counterbalancing the direct impact they had been experiencing. Key messages • During the COVID-19 pandemic, COPD patients experienced a slight increase in all-cause mortality, but relatively less than the rest of the population of the same age and sex structure. • In 2020, relative to a control population, COPD patients experienced substantially higher COVID-19 mortality and, at the same time, a greater reduction in non-COVID-19 mortality.

Impact of Applying the Global Lung Initiative Criteria for Airway Obstruction in GOLD Defined COPD Cohorts: The BODE and CHAIN Experience

IntroductionThe Global Lung Function Initiative (GLI) has proposed new criteria for airflow limitation (AL) and recommends using these to interpret spirometry. The objective of this study was to explore the impact of the application of the AL GLI criteria in two well characterized GOLD-defined COPD cohorts. MethodsCOPD patients from the BODE (n=360) and the COPD History Assessment In SpaiN (CHAIN) cohorts (n=722) were enrolled and followed. Age, gender, pack-years history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, history of exacerbations and survival were recorded. CT-detected comorbidities were registered in the BODE cohort. The proportion of subjects without AL by GLI criteria was determined in each cohort. The clinical, CT-detected comorbidity, and overall survival of these patients were evaluated. ResultsIn total, 18% of the BODE and 15% of the CHAIN cohort did not meet GLI AL criteria. In the BODE and CHAIN cohorts respectively, these patients had a high clinical burden (BODE≥3: 9% and 20%; mMRC≥2: 16% and 45%; exacerbations in the previous year: 31% and 9%; 6MWD<350m: 15% and 19%, respectively), and a similar prevalence of CT-diagnosed comorbidities compared with those with GLI AL. They also had a higher rate of long-term mortality – 33% and 22% respectively. ConclusionsAn important proportion of patients from 2 GOLD-defined COPD cohorts did not meet GLI AL criteria at enrolment, although they had a significant burden of disease. Caution must be taken when applying the GLI AL criteria in clinical practice.

The modified Borg/6-min walk distance ratio: a method to assess exertional breathlessness and leg discomfort using the 6-min walk test.

The 6-min walk test (6MWT) is widely used to assess exercise capacity across chronic health conditions, but is currently not useful to assess symptoms, as the scores do not account for the 6-min walk distance (6MWD). We aimed to 1) develop normative reference equations for breathlessness and leg discomfort intensity expressed as modified Borg (mBorg)/6MWD ratios; and 2) validate the equations in people with COPD. Analysis of people aged ≥40 years who performed two 6MWTs (on a 20-m course) in the Canadian Cohort Obstructive Lung Disease (CanCOLD) study: a healthy cohort (n=291; mean±sd age 67.5±9.4 years; 54% male) with normal 6MWD and lung function, and a COPD cohort (n=156; age 66.2±9.0 years; 56% male; forced expiratory volume in 1 s (FEV1)/forced vital capacity 56.6±8.2%; FEV1 74.4±18.6% pred). The mBorg score was calculated as the Borg 0-10 category ratio intensity rating of breathlessness or leg discomfort recorded at the end of the 6MWT +1 (range 1-11), to avoid zeros and yield ratios proportional to the symptom score and 6MWD-1. Using data from the healthy cohort, sex-specific normative reference equations for breathlessness and leg discomfort mBorg/6MWD ratios were developed using multivariable linear regression, accounting for age, and body mass or body mass index. In the COPD cohort, abnormal breathlessness and leg discomfort (mBorg/6MWD>upper limit of normal) showed strong concurrent validity with worse airflow limitation, Medical Research Council breathlessness and COPD Assessment Test scores. Normative references for the mBorg/6MWD ratio are presented to assess breathlessness and leg discomfort responses to the 6MWT in COPD.

Physical Activity Estimated by the Wearable Device in Lung Disease Patients: Exploratory Analyses of Prospective Observational Study.

Background. Physical activity is a potential parameter to assess the severity or prognosis of lung disease. However, the differences in physical activity between healthy individuals and patients with lung disease remain unclear. Methods. The analyses in this report are a combined analysis of four cohorts, including a healthy control cohort, in a prospective study designed to evaluate wearable device-estimated physical activity in three cohorts: the lung cancer cohort, the interstitial pneumonia cohort, and the COPD cohort (UMIN000047834). In this report, physical activity in the lung disease cohort was compared with that in the healthy cohort. Subgroup analyses were performed based on age, sex, duration of wearable device use, and lung disease subtype. Results. A total of 238 cases were analyzed, including 216 patients with lung disease and 22 healthy cases. Distance walked and number of steps were significantly lower in the patient group compared to the healthy control group. ROC analysis for the diagnostic value of lung disease by mean distance walked and mean number of steps showed AUC of 0.764 (95%CI, 0.673 to 0.856) and 0.822 (95%CI, 0.740 to 0.905), respectively. There was a significant difference in physical activity by age, but not by gender nor by duration based on the threshold of 7 days of wearing the device. Conclusions. Lung disease decreases physical activity compared to healthy subjects, and aging may bias the estimation of physical activity. The distance walked or number of steps is recommended as a measure of physical activity, with a period of approximately one week and adjusted for age for future investigation.

The Effect of Inhaled Corticosteroids on Pneumonia Risk in Patients With COPD-Bronchiectasis Overlap: A UK Population-Based Case-Control Study

Inhaled corticosteroids (ICS) increase the risk of pneumonia in COPD and commonly are used in patients with COPD-bronchiectasis overlap. Is the risk of pneumonia associated with ICS further heightened in COPD-bronchiectasis? Electronic health care records (from 2004-2019) were used to obtain a cohort of patients with COPD and a nested case-control group (age and sex matched 1:4). Analyses were conducted to determine the risk of hospitalization for pneumonia in COPD associated with ICS use in those with bronchiectasis. Findings were confirmed by several sensitivity analyses. Additionally, a smaller nested case-control group containing only patients with COPD-bronchiectasis overlap and those with recent blood eosinophil counts (BECs) was used to determine any association with BEC. Three hundred sixteen thousand six hundred sixty-three patients were eligible for the COPD cohort; bronchiectasis significantly increased the risk of pneumonia (adjusted hazard ratio, 1.24; 95%CI, 1.15-1.33). In the first nested case-control group of 84,316 patients with COPD, ICS was found to increase the odds of pneumonia (adjusted OR [AOR], 1.26; 95%CI, 1.19-1.32) only if used in the previous 180days. However, bronchiectasis was a significant modifier such that ICS use did not augment further the already elevated bronchiectasis-associated pneumonia risk (COPD-bronchiectasis: AOR, 1.01; 95%CI, 0.8-1.28; no bronchiectasis: AOR, 1.27; 95%CI, 1.20-1.34). Several sensitivity analyses and a second smaller nested case-control group confirmed these findings. Finally, we found that BEC modified the ICS-associated pneumonia risk in COPD-bronchiectasis overlap, where lower BEC was associated significantly with pneumonia (BEC≤ 3× 109/L: AOR, 1.56; 95%CI, 1.05-2.31; BEC > 3× 109/L: AOR, 0.89; 95%CI, 0.53-1.24). ICS use does not augment further the already increased risk of hospitalization for pneumonia associated with concomitant bronchiectasis in patients with COPD.

Pre- and post-vaccination characteristics and risk factors for COVID-19 outcomes in a Swedish population-based cohort of COPD patients.

Evidence on risk factors for Coronavirus disease 2019 (COVID-19) outcomes among patients with COPD in relation to COVID-19 vaccination remains limited. The objectives of the present study were to characterise determinants of COVID-19 infection, hospitalisation, intensive care unit (ICU) admission and death in COPD patients in their unvaccinated state compared to when vaccinated. We included all COPD patients in the Swedish National Airway Register (SNAR). Events of COVID-19 infection (test and/or healthcare encounter), hospitalisation, ICU admission and death were identified from 1 January 2020 to 30 November 2021. Using adjusted Cox regression, associations between baseline sociodemographics, comorbidities, treatments, clinical measurements and COVID-19 outcomes, during unvaccinated and vaccinated follow-up time, were analysed. The population-based COPD cohort included 87 472 patients, among whom 6771 (7.7%) COVID-19 infections, 2897 (3.3%) hospitalisations, 233 (0.3%) ICU admissions and 882 (1.0%) COVID-19 deaths occurred. During unvaccinated follow-up, risk of COVID-19 hospitalisation and death increased with age, male sex, lower education, non-married status and being foreign-born. Comorbidities increased risk of several outcomes, e.g. respiratory failure for infection and hospitalisation (adjusted hazard ratios (HR) 1.78, 95% CI 1.58-2.02 and 2.51, 2.16-2.91, respectively), obesity for ICU admission (3.52, 2.29-5.40) and cardiovascular disease for mortality (2.80, 2.16-3.64). Inhaled COPD therapy was associated with infection, hospitalisation and death. COPD severity was also associated with COVID-19, especially hospitalisation and death. Although the risk factor panorama was similar, COVID-19 vaccination attenuated HRs for some risk factors. This study provides population-based evidence on predictive risk factors for COVID-19 outcomes and highlights the positive implications of COVID-19 vaccination for COPD patients.

Stronger Associations of Centrilobular Than Paraseptal Emphysema With Longitudinal Changes in Diffusing Capacity and Mortality in COPD

The factors associated with longitudinal changes in diffusing capacity remain unclear among patients with COPD. Centrilobular emphysema (CLE) and paraseptal emphysema (PSE) are major emphysema subtypes that may have distinct clinical-physiological impacts in these patients. Are CLE and PSE differently associated with longitudinal changes in diffusing capacity and mortality in patients with COPD? This pooled analysis included 399 patients with COPD from two prospective observational COPD cohorts. CLE and PSE were visually assessed on CT scan according to the Fleischner Society statement. The diffusing capacity and transfer coefficient of the lung for carbon monoxide (Dlco and KCO) and FEV1 were evaluated at least annually over a 5-year period. Mortality was recorded over 10 years. Longitudinal changes in FEV1, Dlco, and KCO and mortality were compared between mild or less severe and moderate or more severe CLE and between present and absent PSE in each Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. The Dlco and KCO decline was weakly associated with FEV1 and greater in GOLD stage 3 or higher than in GOLD stages 1 and 2. Furthermore, moderate or more severe CLE, but not present PSE, was associated with steeper declines in Dlco for GOLD stages 1 and 3 or higher and KCO for all GOLD stages independent of age, sex, height, and smoking history. The moderate or more severe CLE, but not present PSE, was associated with additional FEV1 decline and higher 10-year mortality among patients with GOLD stage 3 or higher. A CT scan finding of moderate or more severe CLE, but not PSE, was associated with a subsequent accelerated impairment in diffusing capacity and higher long-term mortality in severe GOLD stage among patients with COPD.