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Background: Recent advances in texture-based computed tomography (CT) radiomics have demonstrated its potential for classifying COPD., Methods: Participants from the Canadian Cohort Obstructive Lung Disease (CanCOLD) study were evaluated. A total of 108 features were included: eight quantitative CT (qCT), 95 texture-based radiomic and five demographic features. Machine-learning models included demographics along with texture-based radiomics and/or qCT. Combinations of five feature selection and five classification methods were evaluated; a training dataset was used for feature selection and to train the models, and a testing dataset was used for model evaluation. Models for classifying COPD status and severity were evaluated using the area under the receiver operating characteristic curve (AUC) with DeLong's test for comparison. SHapely Additive exPlanations (SHAP) analysis was used to investigate the features selected., Results: A total of 1204 participants were evaluated (n=602 no COPD; n=602 COPD). There were no differences between the groups for sex (p=0.77) or body mass index (p=0.21). For classifying COPD status, the combination of demographics, texture-based radiomics and qCT performed better (AUC=0.87) than the combination of demographics and texture-based radiomics (AUC=0.81, p<0.05) or qCT alone (AUC=0.84, p<0.05). Similarly, for classifying COPD severity, the combination of demographics, texture-based radiomics and qCT performed better (AUC=0.81) than demographics and texture-based radiomics (AUC=0.72, p<0.05) or qCT alone (AUC=0.79, p<0.05). Texture-based radiomics and qCT features were among the top five features selected (15th percentile of the CT density histogram, CT total airway count, pack-years, CT grey-level distance zone matrix zone distance entropy, CT low-attenuation clusters) for classifying COPD status., Conclusion: Texture-based radiomics and conventional qCT features in combination improve machine‑learning models for classification of COPD status and severity., Competing Interests: Conflict of interest: We would like to note that there is no overlap with our study and other previously published CanCOLD studies. Further, there are no conflicts of interest or industry support in relation to this project for any of the authors. M. Kirby is a consultant for VIDA Diagnostics Inc. (Coralville, IA, USA)., (Copyright ©The authors 2024.)

Background: Computed tomography (CT) visual emphysema score is a better predictor of mortality than single quantitative CT emphysema measurements in COPD, but there are numerous CT measurements that reflect COPD-related disease features. The purpose of this study was to determine if linear combinations of quantitative CT measurements by principal component analysis (PCA) have a greater association with forced expiratory volume in 1 s (FEV 1 ) lower limit of normal (LLN) annualised change (ΔFEV 1 ) than visual emphysema score in COPD., Methods: In this retrospective, longitudinal study, demographic, spirometry and CT images were acquired. CT visual emphysema score and quantitative analysis were performed; low attenuation area <950 HU (LAA 950 ) and 12 other quantitative CT measurements were investigated. PCA was used for CT feature extraction. Multiple linear regression models for baseline FEV 1 LLN and 6-year ΔFEV 1 were used to determine associations with visual emphysema score and CT measurements. A total of 725 participants were analysed (n=299 never-smokers, n=242 at-risk and n=184 COPD)., Results: Quantitative CT measures (LAA 950 and PCA components) were independently statistically significant (p<0.05) in predicting baseline FEV 1 LLN, whereas visual emphysema score was not statistically significant in any baseline model. When predicting 6-year ΔFEV 1 , only visual emphysema score was significant (p<0.05) in models with LAA 950 and PCA combination of emphysema measurements. In the model with PCA using all CT measurements predicting 6-year ΔFEV 1 , visual emphysema score (p=0.021) along with one PCA component (p=0.004) were statistically significant., Conclusions: PCA with a combination of CT measurements reflecting several different COPD-related disease features independently predicted baseline lung function and increased the relative importance of quantitative CT compared with visual emphysema score for predicting lung function decline., Competing Interests: Conflict of Interest: All authors have nothing to disclose., (Copyright ©The authors 2023.)

Rationale: Peripheral airway obstruction is a key feature of chronic obstructive pulmonary disease (COPD), but the mechanisms of airway loss are unknown. This study aims to identify the molecular and cellular mechanisms associated with peripheral airway obstruction in COPD., Methods: Ten explanted lung specimens donated by patients with very severe COPD treated by lung transplantation and five unused donor control lungs were sampled using systematic uniform random sampling (SURS), resulting in 240 samples. These samples were further examined by micro-computed tomography (CT), quantitative histology and gene expression profiling., Results: Micro-CT analysis showed that the loss of terminal bronchioles in COPD occurs in regions of microscopic emphysematous destruction with an average airspace size of ≥500 and <1000 µm, which we have termed a "hot spot". Based on microarray gene expression profiling, the hot spot was associated with an 11-gene signature, with upregulation of pro-inflammatory genes and downregulation of inhibitory immune checkpoint genes, indicating immune response activation. Results from both quantitative histology and the bioinformatics computational tool CIBERSORT, which predicts the percentage of immune cells in tissues from transcriptomic data, showed that the hot spot regions were associated with increased infiltration of CD4 and CD8 T-cell and B-cell lymphocytes., Interpretation: The reduction in terminal bronchioles observed in lungs from patients with COPD occurs in a hot spot of microscopic emphysema, where there is upregulation of IFNG signalling, co-stimulatory immune checkpoint genes and genes related to the inflammasome pathway, and increased infiltration of immune cells. These could be potential targets for therapeutic interventions in COPD., Competing Interests: Conflict of interest: F. Xu has nothing to disclose. Conflict of interest: D.M. Vasilescu has nothing to disclose. Conflict of interest: D. Kinose has nothing to disclose. Conflict of interest: N. Tanabe has nothing to disclose. Conflict of interest: K.W. Ng has nothing to disclose. Conflict of interest: H.O. Coxson has nothing to disclose. Conflict of interest: J.D. Cooper has nothing to disclose. Conflict of interest: T-L. Hackett has nothing to disclose. Conflict of interest: S.E. Verleden has nothing to disclose. Conflict of interest: B.M. Vanaudenaerde has nothing to disclose. Conflict of interest: C.S. Stevenson reports other (salary) from Johnson and Johnson, outside the submitted work. Conflict of interest: M.E. Lenburg reports grants from Genentech, during the conduct of the study and other (stock) from Metera Pharmaceuticals, outside the submitted work. Conflict of interest: A. Spira is an employee of Johnson and Johnson. Conflict of interest: W.C. Tan reports personal fees for advisory board work from GlaxoSmithKline, Canada, and AstraZenenca, Canada, outside the submitted work. Conflict of interest: D.D. Sin reports grants and personal fees for lectures from AstraZeneca and personal fees for lectures from Boehringer Ingelheim, outside the submitted work. Conflict of interest: R.T. Ng has nothing to disclose. Conflict of interest: J.C. Hogg reports grants from Genentech, Johnson and Johnson Corporation, Canadian Institute of Health Research, US National Institutes of Health, Katholieke Universiteit Leuven, Parker B Francis Foundation, St Paul's Hospital Foundation, BCLUNG Association and BC Heart and Stroke Foundation, during the conduct of the study., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

There is limited understanding of how to identify people at high risk of developing COPD. Our objective was to investigate the association between computed tomography (CT) total airway count (TAC) and incident COPD over 3 years among ever-smokers from the population-based Canadian Cohort Obstructive Lung Disease (CanCOLD) study. CT and spirometry were acquired in ever-smokers at baseline; spirometry was repeated at 3-year follow-up. CT TAC was generated by summing all airway segments in the segmented airway tree (VIDA Diagnostics, Inc.). CT airway wall area, wall thickness for a theoretical airway with 10 mm perimeter (Pi10), and low attenuation areas below -856 HU (LAA 856 ) were also measured. Logistic and mixed effects regression models were constructed to determine the association for CT measurements with development of COPD and forced expiratory volume in 1 s/forced vital capacity (FEV 1 /FVC) decline, respectively. Among 316 at-risk participants evaluated at baseline (65±9 years, 40% female, 18±19 pack-years), incident COPD was detected in 56 participants (18%) over a median 3.1±0.6 years of follow-up. Among CT measurements, only TAC was associated with incident COPD (p=0.03), where a 1-sd decrement in TAC increased the odds ratio for incident COPD by a factor of two. In a multivariable linear regression model, reduced TAC was significantly associated with greater longitudinal FEV 1 /FVC decline (p=0.03), but no other measurements were significant. CT TAC predicts incident COPD in at-risk smokers, indicating that smokers exhibit early structural changes associated with COPD prior to abnormal spirometry., Competing Interests: Conflict of interest: M. Kirby reports consultancy for VIDA Diagnostics Inc., outside the submitted work. Conflict of interest: B.M. Smith reports grants from the Canadian Institutes of Health Research (CIHR), the National Institutes of Health (USA), the McGill Interdisciplinary Initiative in Infection and Immunity (MI4), the Research Institute of the McGill University Health Centre (MUHC), the Quebec Lung Association, and the Quebec Health Research Fund, outside the submitted work. Conflict of interest: N. Tanabe reports grants from FUJIFILM, and personal fees from AstraZeneca, Boehringer Ingelheim and GlaxoSmithKline, outside the submitted work. Conflict of interest: J.C. Hogg has nothing to disclose. Conflict of interest: H.O. Coxson has nothing to disclose. Conflict of interest: D.D. Sin reports personal fees from AstraZeneca, Boehringer Ingelheim and Grifols, outside the submitted work. Conflict of interest: J. Bourbeau reports grants from CIHR and the Canadian Respiratory Research Network, personal fees from the Canadian Thoracic Society and CHEST, grants from the Foundation of the MUHC and Aerocrine, and grants and personal fees from AstraZeneca, Boehringer Ingelheim, Grifols, GlaxoSmithKline, Novartis and Trudell, outside the submitted work. Conflict of interest: W.C. Tan reports grants from the CIHR (CIHR/Rx&D Collaborative Research Program Operating Grants, 93326) with industry partners AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc., Nycomed Canada Inc. and Pfizer Canada Ltd, during the conduct of the study; and personal fees from GlaxoSmithKline, Canada, and AstraZeneca, Canada, outside the submitted work., (Copyright ©The authors 2021.)

Introduction: The aim of this study was to examine the association between blood eosinophil levels and the decline in lung function in individuals aged >40 years from the general population., Methods: The study evaluated the eosinophil counts from thawed blood in 1120 participants (mean age 65 years) from the prospective population-based Canadian Cohort of Obstructive Lung Disease (CanCOLD) study. Participants answered interviewer-administered respiratory questionnaires and performed pre-/post-bronchodilator spirometric tests at 18-month intervals; computed tomography (CT) imaging was performed at baseline. Statistical analyses to describe the relationship between eosinophil levels and decline in forced expiratory volume in 1 s (FEV 1 ) were performed using random mixed-effects regression models with adjustments for demographics, smoking, baseline FEV 1 , ever-asthma and history of exacerbations in the previous 12 months. CT measurements were compared between eosinophil subgroups using ANOVA., Results: Participants who had a peripheral eosinophil count of ≥300 cells·µL -1 (n=273) had a greater decline in FEV 1 compared with those with eosinophil counts of <150 cells·µL -1 (n=430; p=0.003) (reference group) and 150-<300 cells·µL -1 (n=417; p=0.003). The absolute change in FEV 1 was -32.99 mL·year -1 for participants with eosinophil counts <150 cells·µL -1 ; -38.78 mL·year -1 for those with 150-<300 cells·µL -1 and -67.30 mL·year -1 for participants with ≥300 cells·µL -1 . In COPD, higher eosinophil count was associated with quantitative CT measurements reflecting both small and large airway abnormalities., Conclusion: A blood eosinophil count of ≥300 cells·µL -1 is an independent risk factor for accelerated lung function decline in older adults and is related to undetected structural airway abnormalities., Competing Interests: Conflict of interest: W.C. Tan reports grants from Canadian Institute of Heath Research (CIHR/Rx&D Collaborative Research Program, operating grants 93326) with industry partners AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc., Nycomed Canada Inc. and Pfizer Canada Ltd, during the conduct of the study. Conflict of interest: J. Bourbeau reports funding for the current study from GlaxoSmithKline; grants from CIHR, Canadian Respiratory Research Network (CRRN), Foundation of the MUHC and Aerocrine, personal fees for consultancy and lectures from Canadian Thoracic Society and Chest, grants and personal fees for advisory board work and lectures from AstraZeneca, Boehringer Ingelheim, Grifols, GlaxoSmithKline, Novartis and Trudell, outside the submitted work. Conflict of interest: G. Nadeau was an employee of and held shares in a pharmaceutical company at the time of the study. Conflict of interest: W. Wang has nothing to disclose. Conflict of interest: N. Barnes was an employee of and held shares in a pharmaceutical company at the time of the study. Conflict of interest: S.H. Landis held stocks and shares in GlaxoSmithKline, during the conduct of the study. Conflict of interest: M. Kirby is a consultant for VIDA Diagnostics Inc., outside the submitted work. Conflict of interest: J.C. Hogg has nothing to disclose. Conflict of interest: D.D. Sin reports grants from Merck, personal fees for advisory board work from Sanofi-Aventis and Regeneron, grants and personal fees for research from Boehringer Ingelheim, grants and personal fees for advisory board work and lectures from AstraZeneca, personal fees for advisory board work and lectures from Novartis, outside the submitted work., (Copyright ©ERS 2021.)

Studies assessing dyspnoea and health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD) have focussed on patients in clinical settings, not the general population. The aim of this analysis was to compare the prevalence and severity of dyspnoea and impaired HRQoL in individuals with and without COPD from the general population, focussing on mild-moderate COPD. Analysis of the 3-year Canadian Cohort Obstructive Lung Disease (CanCOLD) study included four subgroups: mild COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1); moderate COPD (GOLD 2); non-COPD smokers; and non-COPD never-smokers. The primary outcome was dyspnoea (Medical Research Council (MRC) scale), and the secondary outcome was HRQoL (COPD Assessment Test (CAT) score; Saint George's Respiratory Questionnaire (SGRQ) score). Subgroups were analysed by sex, physician-diagnosed COPD status and exacerbations. 1443 participants (mild COPD (n=397); moderate COPD (n=262(; smokers (n=449) and never-smokers (n=335)) were studied. People with mild COPD were more likely to report more severe dyspnoea (MRC 2 versus 1) than those without COPD (OR (95% CI) 1.42 (1.05-1.91)), and non-COPD never-smokers (OR (95%CI) 1.64 (1.07-2.52)). Among people with mild COPD, more severe dyspnoea was reported in women versus men (MRC2 versus 1; OR (95% CI) 3.70 (2.23-6.14)); people with, versus without, physician-diagnosed COPD (MRC2 versus 1; OR (95% CI) 3.27 (1.71-6.23)), and people with versus without recent exacerbations (MRC2 versus 1; ≥2 versus 0 exacerbations: OR (95% CI) 3.62 (1.02-12.86); MRC ≥3 versus 1; 1 versus 0 exacerbation: OR (95% CI): 9.24 (2.01-42.42)). Similar between-group differences were obtained for CAT and SGRQ scores. Careful assessment of dyspnoea and HRQoL could help identify individuals for earlier diagnosis and treatment., Competing Interests: Conflict of interest: M. Cherian reports the study is currently funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd and Novartis. Previous study funding partners were the Respiratory Health Network of the Fonds de la recherche en santé du Québec, the Foundation of the McGill University Health Centre, Almirall, Merck, Nycomed, Pfizer Canada Ltd and Theratechnologies. Medical writing support provided by Fishawack Communications Ltd was funded by GSK. Conflict of interest: D. Jensen reports the study is currently funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd and Novartis. Previous study funding partners were the Respiratory Health Network of the Fonds de la recherche en santé du Québec, the Foundation of the McGill University Health Centre, Almirall, Merck, Nycomed, Pfizer Canada Ltd and Theratechnologies. Medical writing support provided by Fishawack Communications Ltd was funded by GSK. He also reports grants and personal fees from AstraZeneca, and grants from Boehringer Ingelheim, Novartis and Tilray, outside the submitted work. Conflict of interest: W.C. Tan reports the study is currently funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd and Novartis. Previous study funding partners were the Respiratory Health Network of the Fonds de la recherche en santé du Québec, the Foundation of the McGill University Health Centre, Almirall, Merck, Nycomed, Pfizer Canada Ltd and Theratechnologies. Medical writing support provided by Fishawack Communications Ltd was funded by GSK. Conflict of interest: S. Mursleen reports the study is currently funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd and Novartis. Previous study funding partners were the Respiratory Health Network of the Fonds de la recherche en santé du Québec, the Foundation of the McGill University Health Centre, Almirall, Merck, Nycomed, Pfizer Canada Ltd and Theratechnologies. Medical writing support provided by Fishawack Communications Ltd was funded by GSK. S. Mursleen is an employee of and holds shares/options in GSK. Conflict of interest: E.C. Goodall reports the study is currently funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd and Novartis. Previous study funding partners were the Respiratory Health Network of the Fonds de la recherche en santé du Québec, the Foundation of the McGill University Health Centre, Almirall, Merck, Nycomed, Pfizer Canada Ltd and Theratechnologies. Medical writing support provided by Fishawack Communications Ltd was funded by GSK. E.C. Goodall is an employee of GSK. Conflict of interest: G.A. Nadeau reports the study is currently funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd and Novartis. Previous study funding partners were the Respiratory Health Network of the Fonds de la recherche en santé du Québec, the Foundation of the McGill University Health Centre, Almirall, Merck, Nycomed, Pfizer Canada Ltd and Theratechnologies. Medical writing support provided by Fishawack Communications Ltd was funded by GSK. G.A. Nadeau was an employee of and held shares/options in GSK at the time of the analysis. Conflict of interest: A.M. Awan reports the study is currently funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd and Novartis. Previous study funding partners were the Respiratory Health Network of the Fonds de la recherche en santé du Québec, the Foundation of the McGill University Health Centre, Almirall, Merck, Nycomed, Pfizer Canada Ltd and Theratechnologies. Medical writing support provided by Fishawack Communications Ltd was funded by GSK. A.M. Awan is an employee of GlaxoSmithKline. Conflict of interest: D.D. Marciniuk reports the study is currently funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd and Novartis. Previous study funding partners were the Respiratory Health Network of the Fonds de la recherche en santé du Québec, the Foundation of the McGill University Health Centre, Almirall, Merck, Nycomed, Pfizer Canada Ltd and Theratechnologies. Medical writing support provided by Fishawack Communications Ltd was funded by GSK. He also reports consultancy fees and research funding (managed by University of Saskatchewan) from AstraZeneca and Boehringer Ingelheim; consultancy fees from the Canadian Foundation for Healthcare Improvement, and the Chinese Committee of Health and Family Planning; consultancy fees and research funding (managed by University of Saskatchewan) from GSK; consultancy fees from Health Canada; consultancy fees and research funding (managed by University of Saskatchewan) from the Lung Association of Saskatchewan; consultancy fees from Mylan; consultancy fees and research funding (managed by University of Saskatchewan) from Novartis; consultancy fees from the Saskatchewan Ministry of Health, Saskatchewan Health Authority, and Yukon Health and Social Services; research funding (managed by University of Saskatchewan) from Canada Health Infoway, the Canadian Institute of Health Research, the Lung Health Institute of Canada, Sanofi, the Saskatchewan Health Research Foundation and Schering-Plough; and is a spokesperson on behalf of the Canadian Thoracic Society, outside the submitted work. Conflict of interest: B.L. Walker reports the study is currently funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd and Novartis. Previous study funding partners were the Respiratory Health Network of the Fonds de la recherche en santé du Québec, the Foundation of the McGill University Health Centre, Almirall, Merck, Nycomed, Pfizer Canada Ltd and Theratechnologies. Medical writing support provided by Fishawack Communications Ltd was funded by GSK. She also reports advisory board and speaker fees from AstraZeneca and GSK, outside the submitted work. Conflict of interest: S.D. Aaron reports the study is currently funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd and Novartis. Previous study funding partners were the Respiratory Health Network of the Fonds de la recherche en santé du Québec, the Foundation of the McGill University Health Centre, Almirall, Merck, Nycomed, Pfizer Canada Ltd, and Theratechnologies. Medical writing support provided by Fishawack Communications Ltd was funded by GSK. Conflict of interest: D.E. O'Donnell reports the study is currently funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd and Novartis. Previous study funding partners were the Respiratory Health Network of the Fonds de la recherche en santé du Québec, the Foundation of the McGill University Health Centre, Almirall, Merck, Nycomed, Pfizer Canada Ltd, and Theratechnologies. Medical writing support provided by Fishawack Communications Ltd was funded by GSK. Conflict of interest: K.R. Chapman reports the study is currently funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd and Novartis. Previous study funding partners were the Respiratory Health Network of the Fonds de la recherche en santé du Québec, the Foundation of the McGill University Health Centre, Almirall, Merck, Nycomed, Pfizer Canada Ltd, and Theratechnologies. Medical writing support provided by Fishawack Communications Ltd. was funded by GSK. He also reports grants from Bayer, grants and personal fees from CSL Behring, grants from Grifols, grants and personal fees from Takeda, grants from Vertex, grants and personal fees from Mereo Biopharma, and grants and personal fees from Sanofi, during the conduct of the study. Conflict of interest: F. Maltais reports the study is currently funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd and Novartis. Previous study funding partners were the Respiratory Health Network of the Fonds de la recherche en santé du Québec, the Foundation of the McGill University Health Centre, Almirall, Merck, Nycomed, Pfizer Canada Ltd, and Theratechnologies. Medical writing support provided by Fishawack Communications Ltd. was funded by GSK. He also reports research grants paid to his institution from AstraZeneca, GSK and Sanofi, a research grant and fees for speaker bureaus/consultancy from Novartis, grants and personal fees from Boehringer Ingelheim, and a research grant paid to his institution and fees for speaker bureaus/consultancy from Grifols, outside the submitted work. Conflict of interest: P. Hernandez reports the study is currently funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd and Novartis. Previous study funding partners were the Respiratory Health Network of the Fonds de la recherche en santé du Québec, the Foundation of the McGill University Health Centre, Almirall, Merck, Nycomed, Pfizer Canada Ltd, and Theratechnologies. Medical writing support provided by Fishawack Communications Ltd. was funded by GSK. He also reports honoraria for a medical advisory board from Actelion; honoraria for a medical advisory board and speaker fees for continuing health education, and funding to his institution for conduct of clinical trials from AstraZeneca and Boehringer Ingelheim; funding to his institution for conduct of clinical trials from Cyclomedica; honoraria for medical advisory boards from GlaxoSmithKline and Novartis; funding to his institution for conduct of clinical trials Respivant and Grifols; honoraria for medical advisory boards from Sanofi and Teva; and funding to his institution for conduct of clinical trials from Vertex, all outside the submitted work. Conflict of interest: D.D. Sin reports the study is currently funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd and Novartis. Previous study funding partners were the Respiratory Health Network of the Fonds de la recherche en santé du Québec, the Foundation of the McGill University Health Centre, Almirall, Merck, Nycomed, Pfizer Canada Ltd, and Theratechnologies. Medical writing support provided by Fishawack Communications Ltd. was funded by GSK. He also reports an honorarium for speaking engagement from AstraZeneca and one for attending an advisory board from Boehringer Ingelheim, outside the submitted work. Conflict of interest: A. Benedetti reports the study is currently funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd and Novartis; grants, and lecture and advisory board fees from AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd and GlaxoSmithKline Canada Ltd; grants from Canadian Institutes of Health Research and the Respiratory Health Network of the Fonds de la recherche en santé du Québec; medical writing support provided by Fishawack Communications Ltd funded by GSK; grants from Novartis; and grants from Almirall, Merck, Nycomed, Pfizer Canada Ltd, Theratechnologies and The Foundation of the McGill University Health Centre, all during the conduct of the study. Conflict of interest: J. Bourbeau reports the study is currently funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd and Novartis; grants, and lecture and advisory board fees from AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd and GlaxoSmithKline Canada Ltd; grants from Canadian Institutes of Health Research and the Respiratory Health Network of the Fonds de la recherche en santé du Québec; medical writing support provided by Fishawack Communications Ltd funded by GSK; grants from Novartis; and grants from Almirall, Merck, Nycomed, Pfizer Canada Ltd, Theratechnologies and The Foundation of the McGill University Health Centre, all during the conduct of the study; and consultancy and lecture fees from the Canadian Thoracic Society and CHEST; grants from the Foundation of the MUHC and Aerocrine; grants, and lecture and advisory board fees from Grifols, Novartis and Trudell, and grants from Canadian Institutes of Health Research, all outside the submitted work., (©The authors 2021.)

Assessment of dyspnoea severity during incremental cardiopulmonary exercise testing (CPET) has long been hampered by the lack of reference ranges as a function of work rate (WR) and ventilation ( V' E ). This is particularly relevant to cycling, a testing modality which overtaxes the leg muscles leading to a heightened sensation of leg discomfort.Reference ranges based on dyspnoea percentiles (0-10 Borg scale) at standardised work rates and V' E were established in 275 apparently healthy subjects aged 20-85 years (131 men). They were compared with values recorded in a randomly selected "validation" sample (n=451; 224 men). Their usefulness in properly uncovering the severity of exertional dyspnoea were tested in 167 subjects under investigation for chronic dyspnoea ("testing sample") who terminated CPET due to leg discomfort (86 men).Iso-work rate and, to a lesser extent, iso- V' E reference ranges (5th-25th, 25th-50th, 50-75th and 75th-95th percentiles) increased as a function of age, being systematically higher in women (p<0.01). There were no significant differences in percentiles distribution between "reference" and "validation" samples (p>0.05). Submaximal dyspnoea-work rate scores fell within the 75th-95th or >95th percentiles in 108 out of 118 (91.5%) subjects of the "testing" sample who showed physiological abnormalities known to elicit exertional dyspnoea, i.e. ventilatory inefficiency and/or critical inspiratory constraints. In contrast, dyspnoea scores typically fell in the 5th-50th range in subjects without those abnormalities (p<0.001).This frame of reference might prove useful to uncover the severity of exertional dyspnoea in subjects who otherwise would be labelled as "non-dyspnoeic" while providing mechanistic insights into the genesis of this distressing symptom., Competing Interests: Conflict of interest: J.A. Neder has nothing to disclose. Conflict of interest: D.C. Berton has nothing to disclose. Conflict of interest: L.E. Nery has nothing to disclose. Conflict of interest: W.C. Tan reports grants from Canadian Respiratory Research Network, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Novartis, Canadian Institutes of Health Research, Respiratory Health Network of the Fonds de la recherche en santé du Québec, Merck, Nycomed, Pfizer Canada Ltd and Theratechnologies, during the conduct of the study. Conflict of interest: J. Bourbeau reports grants from CIHR, Canadian Respiratory Research Network (CRRN), Foundation of the MUHC and Aerocrine, personal fees for consultancy and lectures from Canadian Thoracic Society and CHEST, grants and personal fees for advisory board work and lectures from AstraZeneca, Boehringer Ingelheim, Grifols, GlaxoSmithKline, Novartis and Trudell, outside the submitted work. Conflict of interest: D.E. O'Donnell has nothing to disclose., (Copyright ©ERS 2020.)

Background: Previous studies have associated marijuana exposure with increased respiratory symptoms and chronic bronchitis among long-term cannabis smokers. The long-term effects of smoked marijuana on lung function remain unclear., Methods: We determined the association of marijuana smoking with the risk of spirometrically defined chronic obstructive pulmonary disease (COPD) (post-bronchodilator forced expiratory volume in 1 s (FEV 1 )/forced vital capacity ratio <0.7) in 5291 population-based individuals and the rate of decline in FEV 1 in a subset of 1285 males and females, aged ≥40 years, who self-reported use (or non-use) of marijuana and tobacco cigarettes and performed spirometry before and after inhaled bronchodilator on multiple occasions. Analysis for the decline in FEV 1 was performed using random mixed effects regression models adjusted for age, sex and body mass index. Heavy tobacco smoking and marijunana smoking was defined as >20 pack-years and >20 joint-years, respectively., Results: ∼20% of participants had been or were current marijuana smokers with most having smoked tobacco cigarettes in addition (83%). Among heavy marijuana users, the risk of COPD was significantly increased (adjusted OR 2.45, 95% CI 1.55-3.88). Compared to never-smokers of marijuana and tobacco, heavy marijuana smokers and heavy tobacco smokers experienced a faster decline in FEV 1 by 29.5 mL·year -1 (p=0.0007) and 21.1 mL·year -1 (p<0.0001), respectively. Those who smoked both substances experienced a decline of 32.31 mL·year -1 (p<0.0001)., Interpretation: Heavy marijuana smoking increases the risk of COPD and accelerates FEV 1 decline in concomitant tobacco smokers beyond that observed with tobacco alone., Competing Interests: Conflict of interest: W.C. Tan reports grants from Canadian Institute of Heath Research (CIHR/Rx&D Collaborative Research Program Operating Grants-93326) with industry partners AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc., Nycomed Canada Inc., Pfizer Canada Ltd, during the conduct of the study. Conflict of interest: J. Bourbeau reports grants from Canadian Institute of Heath Research (CIHR/Rx&D Collaborative Research Program Operating Grants-93326) with industry partners AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc., Nycomed Canada Inc., Pfizer Canada Ltd, during the conduct of the study. Conflict of interest: S.D. Aaron has nothing to disclose. Conflict of interest: J.C. Hogg has nothing to disclose. Conflict of interest: F. Maltais has nothing to disclose. Conflict of interest: P. Hernandez reports grants from Canadian Institute Health Research, during the conduct of the study; grants and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis and Takeda, personal fees from Merck, Grifols, Pfizer and Almirall, grants from CSL Behring, outside the submitted work. Conflict of interest: D.D. Marciniuk has nothing to disclose. Conflict of interest: K.R. Chapman reports grants from Novartis, Almirall, Boehringer Ingelheim, Forest, GSK, AstraZeneca, Amgen, Roche, CSL Behring, Grifols, Genentech and Kamada, during the conduct of the study; UHN administered personal support from CIHR (GSK Research Chair in Respiratory Health Care Delivery), outside the submitted work. Conflict of interest: T. To has nothing to disclose. Conflict of interest: J.M. FitzGerald has nothing to disclose. Conflict of interest: B.L. Walker reports grants from Canadian Institute of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada, GlaxoSmithKline Canada and Novartis, during the conduct of the study; grants from Respiratory Health Strategic Clinical Network Alberta, personal fees from AstraZeneca, GlaxoSmithKline and Novartis, outside the submitted work. Conflict of interest: J. Road has nothing to disclose. Conflict of interest: L. Zheng has nothing to disclose. Conflict of interest: G. Zhou has nothing to disclose. Conflict of interest: T. Yau has nothing to disclose. Conflict of interest: A. Benedetti has nothing to disclose. Conflict of interest: D. O'Donnell has nothing to disclose. Conflict of interest: D.D. Sin reports grants from Merck, personal fees for advisory board work from Sanofi-Aventis and Regeneron, grants and personal fees from Boehringer Ingelheim, grants and personal fees for lectures and advisory board work from AstraZeneca, personal fees for lectures and advisory board work from Novartis, outside the submitted work., (Copyright ©ERS 2019.)

We aimed to examine associations between chronic airflow obstruction (CAO) and unemployment across the world.Cross-sectional data from 26 sites in the Burden of Obstructive Lung Disease (BOLD) study were used to analyse effects of CAO on unemployment. Odds ratios for unemployment in subjects aged 40-65 years were estimated using a multilevel mixed-effects generalised linear model with study site as random effect. Site-by-site heterogeneity was assessed using individual participant data meta-analyses.Out of 18 710 participants, 11.3% had CAO. The ratio of unemployed subjects with CAO divided by subjects without CAO showed large site discrepancies, although these were no longer significant after adjusting for age, sex, smoking and education. The site-adjusted odds ratio (95% CI) for unemployment was 1.79 (1.41-2.27) for CAO cases, decreasing to 1.43 (1.14-1.79) after adjusting for sociodemographic factors, comorbidities and forced vital capacity. Of other covariates that were associated with unemployment, age and education were important risk factors in high-income sites (4.02 (3.53-4.57) and 3.86 (2.80-5.30), respectively), while female sex was important in low- to middle-income sites (3.23 (2.66-3.91)).In the global BOLD study, CAO was associated with increased levels of unemployment, even after adjusting for sociodemographic factors, comorbidities and lung function., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

In small studies and cases series, a history of tuberculosis has been associated with both airflow obstruction, which is characteristic of chronic obstructive pulmonary disease, and restrictive patterns on spirometry. The objective of the present study was to assess the association between a history of tuberculosis and airflow obstruction and spirometric abnormalities in adults.The study was performed in adults, aged 40 years and above, who took part in the multicentre, cross-sectional, general population-based Burden of Obstructive Lung Disease study, and had provided acceptable post-bronchodilator spirometry measurements and information on a history of tuberculosis. The associations between a history of tuberculosis and airflow obstruction and spirometric restriction were assessed within each participating centre, and estimates combined using meta-analysis. These estimates were stratified by high- and low/middle-income countries, according to gross national income.A self-reported history of tuberculosis was associated with airflow obstruction (adjusted odds ratio 2.51, 95% CI 1.83-3.42) and spirometric restriction (adjusted odds ratio 2.13, 95% CI 1.42-3.19).A history of tuberculosis was associated with both airflow obstruction and spirometric restriction, and should be considered as a potentially important cause of obstructive disease and low lung function, particularly where tuberculosis is common., (Copyright ©ERS 2015.)

This study aimed to compare strategies for chronic obstructive pulmonary disease (COPD) case finding using data from the Burden of Obstructive Lung Disease study. Population-based samples of adults aged ≥40 yrs (n = 9,390) from 14 countries completed a questionnaire and spirometry. We compared the screening efficiency of differently staged algorithms that used questionnaire data and/or peak expiratory flow (PEF) data to identify persons at risk for COPD and, hence, needing confirmatory spirometry. Separate algorithms were fitted for moderate/severe COPD and for severe COPD. We estimated the cost of each algorithm in 1,000 people. For moderate/severe COPD, use of questionnaire data alone permitted high sensitivity (97%) but required confirmatory spirometry in 80% of participants. Use of PEF necessitated confirmatory spirometry in only 19-22% of subjects, with 83-84% sensitivity. For severe COPD, use of PEF achieved 91-93% sensitivity, requiring confirmatory spirometry in <9% of participants. Cost analysis suggested that a staged screening algorithm using only PEF initially, followed by confirmatory spirometry as needed, was the most cost-effective case-finding strategy. Our results support the use of PEF as a simple, cost-effective initial screening tool for conducting COPD case-finding in adults aged ≥40 yrs. These findings should be validated in real-world settings such as the primary care environment.

Chronic obstructive pulmonary disease (COPD) is predicted to become the third most common cause of death and disability worldwide by 2020. The prevalence of COPD defined by the lower limit of normal was estimated using high-quality spirometry in surveys of 14 populations aged ≥ 40 yrs. The strength and consistency of associations were assessed using random effects meta-analysis. Pack-years of smoking were associated with risk of COPD at each site. After adjusting for this effect, we still observed significant associations of COPD risk with age (OR 1.52 for a 10 yr age difference, 95% CI 1.35-1.71), body mass index in obese compared with normal weight (OR 0.50, 95% CI 0.37-0.67), level of education completed (OR 0.76, 95% CI 0.67-0.87), hospitalisation with a respiratory problem before age 10 yrs (OR 2.35, 95% CI 1.42-3.91), passive cigarette smoke exposure (OR 1.24, 95% CI 1.05-1.47), tuberculosis (OR 1.78, 95%CI 1.17-2.72) and a family history of COPD (OR 1.50, 95% CI 1.19-1.90). Although smoking is the most important risk factor for COPD, other risk factors are also important. More research is required to elucidate relevant risk factors in low- and middle-income countries where the greatest impact of COPD will occur.