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Chronic obstructive pulmonary disease patient care must include confirming a diagnosis with postbronchodilator spirometry. Because of the clinical heterogeneity and the reality that airflow obstruction assessed by spirometry only partially reflects disease severity, a thorough clinical evaluation of the patient should include assessment of symptom burden and risk of exacerbations that permits the implementation of evidence-informed pharmacologic and nonpharmacologic interventions. This guideline provides recommendations from a comprehensive systematic review with a meta-analysis and expert-informed clinical remarks to optimize maintenance pharmacologic therapy for individuals with stable COPD, and a revised and practical treatment pathway based on new evidence since the 2019 update of the Canadian Thoracic Society (CTS) Guideline. The key clinical questions were developed using the Patients/Population (P), Intervention(s) (I), Comparison/Comparator (C), and Outcome (O) model for three questions that focuses on the outcomes of symptoms (dyspnea)/health status, acute exacerbations, and mortality. The evidence from this systematic review and meta-analysis leads to the recommendation that all symptomatic patients with spirometry-confirmed COPD should receive long-acting bronchodilator maintenance therapy. Those with moderate to severe dyspnea (modified Medical Research Council ≥ 2) and/or impaired health status (COPD Assessment Test ≥ 10) and a low risk of exacerbations should receive combination therapy with a long-acting muscarinic antagonist/long-acting ẞ2-agonist (LAMA/LABA). For those with a moderate/severe dyspnea and/or impaired health status and a high risk of exacerbations should be prescribed triple combination therapy (LAMA/LABA/inhaled corticosteroids) azithromycin, roflumilast or N-acetylcysteine is recommended for specific populations; a recommendation against the use of theophylline, maintenance systemic oral corticosteroids such as prednisone and inhaled corticosteroid monotherapy is made for all COPD patients., Competing Interests: Financial/Nonfinancial Disclosures Members of the CTS COPD Guideline Panel declared potential conflicts of interest at the time of appointment, and these were updated throughout the process in accordance with the CTS Conflict of Interest Disclosure Policy. J. B. reports grants from McGill University, the McGill University Health Centre Foundation, the Canadian Institute Health Research, Grifols, Novartis, Sanofi, and the Respiratory Health Network of the Fonds de la recherche en santé du Québec; grants and personal fees from Astra Zeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, and Trudell Canada Ltd; and personal fees from Pfizer Canada Ltd, and COVIS Pharma Canada Ltd, outside the submitted work. M. B. reports personal fees and grants outside the submitted work from AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Novartis, Sanofi-Genzyme, the Canadian Institute Health Research, CHEST, The Lung Association of Alberta, The University of Alberta Hospital Foundation, Alberta Innovates Health Solutions, Valeo, and Covis. P. H. reports grants from the Canadian Institute Health Research, the Lung Association of Nova Scotia, the Nova Scotia Health Authority Research Fund, Astra Zeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, Cyclomedica, Grifols, Respivant, and Vertex; and personal fees from Astra Zeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Janssen, Merck, Novartis, Sanofi-Aventis, and Trudell, outside the submitted work. S. D. A. receives grants from CIHR. He has received speaking honoraria or has participated on advisory boards for GSK, AZ, Chiesi, and Sanofi. M-F. B. reports grants and personal fees from the Cercle du doyen (Faculté de pharmacie, Université de Montréal) and Astra Zeneca Canada Ltd. A. D. reports receiving research, consulting and lecturing fees from GlaxoSmithkline, Sepracor, Schering Plough, Altana, Methapharma, AstraZeneca, ONO pharma, Merck Canada, Forest Laboratories, Novartis Canada/USA, Boehringer Ingelheim (Canada) Ltd, Pfizer Canada, SkyePharma, and KOS Pharmaceuticals and Almirall, Sanofigenzyme and TEVA Canada, Valeopharma Canada. F. M. reports grants from AstraZeneca and GlaxoSmithKline, Boehringer Ingelheim, GSK, Sanofi, and Novartis, and personal fees for serving on speaker bureaus and consultation panels from GlaxoSmithKline, Grifols, and Novartis. He is financially involved with Oxynov, a company which is developing an oxygen delivery system. S. M. reports grants outside the submitted work from Canadian Institute of Health Research and Canadian Lung Association in partnership with Boehringer Ingelheim Canada Ltd and Astra Zeneca Canada Ltd. E. P. reports personal fees from COVIS Pharma, Sanofi Genzyme, Boehringer Ingelheim Canada Ltd, Astra Zeneca Canada Ltd, GlaxoSmithKline Canada Ltd, and Novartis; and grants from the Canadian Institute Health Research, the Saskatchewan Research Foundation, the Respiratory Research Centre, and Astra Zeneca Canada Ltd, outside the submitted work. D. D. S. reports personal fees from GlaxoSmithKline Canada Ltd, Boehringer Ingelheim, and AstraZeneca outside of the submitted work. J. W. reports personal fees from GlaxoSmithKline Canada Ltd and Astra Zeneca Canada Ltd and a grant from Fisher & Paykel, outside the submitted work. B. L. W. reports personal fees from AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Novartis, Sanofi-Genzyme and Covis Pharma Canada, outside of the submitted work. D. D. M. reports consultancy work with Alberta Health Services, Health Canada, Lung Saskatchewan, Ontario Ministry of Health and Long-Term Care, Saskatchewan Health Authority, Saskatchewan Ministry of Health, Yukon Health and Social Services; reports grants (managed by University of Saskatchewan) from AstraZeneca, Boehringer Ingelheim, Canadian Institute of Health Research, GlaxoSmithKline, Grifols Therapeutics, Lung Saskatchewan, Novartis, Sanofi-Aventis, Saskatchewan Health Research Foundation, Syneos Health, Schering-Plough; employee/roles with University of Saskatchewan, Deputy Editor - CHEST Journal, Board Member - Saskatchewan Health Research Foundation; outside the submitted work. None declared (A. L., A. V. D., S. B. K., J. D. M.)., (Copyright © 2023 Canadian Thoracic Society and American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Infections are considered as leading causes of acute exacerbations of chronic obstructive pulmonary disease (COPD). Non-infectious risk factors such as short-term air pollution exposure may play a clinically important role. We sought to estimate the relationship between short-term air pollutant exposure and exacerbations in Canadian adults living with mild to moderate COPD., Methods: In this case-crossover study, exacerbations ('symptom based': ≥48 hours of dyspnoea/sputum volume/purulence; 'event based': 'symptom based' plus requiring antibiotics/corticosteroids or healthcare use) were collected prospectively from 449 participants with spirometry-confirmed COPD within the Canadian Cohort Obstructive Lung Disease. Daily nitrogen dioxide (NO 2 ), fine particulate matter (PM 2.5 ), ground-level ozone (O 3 ), composite of NO 2 and O 3 (O x ), mean temperature and relative humidity estimates were obtained from national databases. Time-stratified sampling of hazard and control periods on day '0' (day-of-event) and Lags ('-1' to '-6') were compared by fitting generalised estimating equation models. All data were dichotomised into 'warm' (May-October) and 'cool' (November-April) seasons. ORs and 95% CIs were estimated per IQR increase in pollutant concentrations., Results: Increased warm season ambient concentration of NO 2 was associated with symptom-based exacerbations on Lag-3 (1.14 (1.01 to 1.29), per IQR), and increased cool season ambient PM 2.5 was associated with symptom-based exacerbations on Lag-1 (1.11 (1.03 to 1.20), per IQR). There was a negative association between warm season ambient O 3 and symptom-based events on Lag-3 (0.73 (0.52 to 1.00), per IQR)., Conclusions: Short-term ambient NO 2 and PM 2.5 exposure were associated with increased odds of exacerbations in Canadians with mild to moderate COPD, further heightening the awareness of non-infectious triggers of COPD exacerbations., Competing Interests: Competing interests: BAR reports grants/contracts from the Canadian Institutes of Health Research (CIHR), Réseau de Recherche en Santé Respiratoire du Québec (RSRQ), Research Institute of the MUHC (RI MUHC), Ministère de l'Économie et de l'Innovation (MEI) Québec, McGill University Health Centre (MUHC) Foundation Grant, Fonds de Recherche Santé Québec (FRSQ), and CHEST Foundation Grant; and payments/honoraria from the Canadian Thoracic Society (CTS), CHEST/ACCP, Respiplus (non-profit), Alberta Kinesiology Association (AKA), and McGill University Continuing Professional Development (CPD). SDA reports payments/honoraria from AstraZeneca, GSK; and participation on Data Safety Monitoring/Advisory Board for AstraZeneca, GSK, and Sanofi. PH reports grants/contracts from Boehringer Ingelheim, Cyclomedica, Grifols, Vertex; consulting fees from Acceleron, AstraZeneca, Boehringer Ingelheim, Covis, GlaxoSmithKline, Janssen, Novartis, Sanofi, Teva, Takeda, Valeo; and leadership/fiduciary role in the Canadian Thoracic Society. FM reports grants/contracts from GlaxoSmithKline, AstraZeneca, Sanofi, Novartis, Boehringer Ingelheim, Grifols; consulting fees from AstraZeneca; payment/honoraria from GlaxoSmithKline, Boehringer Ingelheim, Grifols, Novartis; and stock/stock options from Oxynov. DM reports grants/contracts from AstraZeneca, Boehringer Ingelheim, Canadian Institute of Health Research, GlaxoSmithKline, Grifols, Lung Association—Saskatchewan, Novartis, Sanofi, Saskatchewan Health Research Foundation, Schering-Plough; consulting fees from Alberta Health Services, Canadian Foundation for Healthcare Improvement, Health Canada, Lung Association—Saskatchewan, Ontario Ministry of Health and Long-Term Care, Saskatchewan Health Authority, Yukon Health and Social Services; payment/honoraria from the Lung Association—Saskatchewan, American College of Chest Physicians; leadership/fiduciary role in the CHEST journal, Canadian Thoracic Society, American Thoracic Society and AARC; and is an employee of the University of Saskatchewan. DE O’D reports grants/contracts from AstraZeneca, Lung Health Foundation and Boehringer Ingelheim Canada; and payment/honoraria from GSK and Viajes Pacifico. BLW reports payment/honoraria from AstraZeneca, GSK, Sanofi; and Data Safety Monitoring/Advisory Board participation for AstraZeneca, GSK, and Sanofi. JB reports grants/contracts from the Canadian Institute of Health Research (CIHR), Réseau en santé respiratoire du FRQS, McGill University, McGill University Health Centre Foundation, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GSK, Grifols, Novartis, Sanofil, Trudell Canada Ltd; and payment/honoraria from AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GSK, Pfizer Canada Ltd, and Trudell Canada Ltd., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

Background: COPD increases susceptibility to sleep disturbances, which may in turn predispose to increased respiratory symptoms. The objective of this study was to evaluate, in a population-based sample, the relationship between subjective sleep quality and risk of COPD exacerbations., Methods: Data were obtained from the Canadian Cohort Obstructive Lung Disease (CanCOLD) study. Participants with COPD who had completed 18 months of follow-up were included. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI) and a three-factor analysis. Symptom-based (dyspnea or sputum change ≥ 48 h) and event-based (symptoms plus medication or unscheduled health services use) exacerbations were assessed. Association of PSQI with exacerbation rate was assessed by using negative binomial regression. Exacerbation-free survival was also assessed., Results: A total of 480 participants with COPD were studied, including 185 with one or more exacerbations during follow-up and 203 with poor baseline sleep quality (PSQI score > 5). Participants with subsequent symptom-based exacerbations had higher median baseline PSQI scores than those without (6.0 [interquartile range, 3.0-8.0] vs 5.0 [interquartile range, 2.0-7.0]; P = .01), and they were more likely to have baseline PSQI scores > 5 (50.3% vs 37.3%; P = .01). Higher PSQI scores were associated with increased symptom-based exacerbation risk (adjusted rate ratio, 1.09; 95% CI, 1.01-1.18; P = .02) and event-based exacerbation risk (adjusted rate ratio, 1.10; 95% CI, 1.00-1.21; P = .048). The association occurred mainly in those with undiagnosed COPD. Strongest associations were with Factor 3 (sleep disturbances and daytime dysfunction). Time to symptom-based exacerbation was shorter in participants with poor sleep quality (adjusted hazard ratio, 1.49; 95% CI, 1.09-2.03)., Conclusions: Higher baseline PSQI scores were associated with increased risk of COPD exacerbation over 18 months' prospective follow-up., (Copyright © 2019. Published by Elsevier Inc.)

Background: Patients with psychiatric disorders (depression, anxiety) are more likely to have poor health behaviours, including higher smoking and lower physical activity (PA) levels. Smoking is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD), and PA is critical for COPD management. However, no studies have assessed associations between psychological distress and these behaviours among patients with vs without COPD. This is a sub-analysis of the CanCOLD study that assessed the relationships between psychological disorders (depression, anxiety) and poor health behaviours (smoking, PA)., Methods: 717 COPD and 797 matched non-COPD individuals from the CanCOLD study, completed the Hospital Anxiety Depression Scale (HADS) to assess anxiety and depression. Smoking behaviour was self-reported pack-years smoking. The CHAMPS PA questionnaire determined calorific expenditure as a PA measure. Regressions determined relationships between anxiety/depression and health behaviours, adjusting for age, sex, BMI, GOLD stage and COPD status., Results: Across the whole sample, we observed relationships between depression (β = 1.107 ± 0.197; 95%CI = 0.691-1.462; p < .001) and anxiety (β = 0.780 ± 0.170; 95%CI = 0.446-1.114; p < .001) and pack years. Higher depression (β = -0.220 ± 0.028; 95%CI = -0.275 to -0.165; p < .001) and anxiety (β = -0.091 ± 0.025; 95%CI = -0.139 to -0.043; p < .001) scores were related to lower PA. These associations were comparable across COPD and non-COPD patients., Conclusions: Results showed that higher levels of anxiety and depression were related to higher cumulative smoking and lower levels of PA in patients with and without COPD, suggesting symptoms of psychological distress is similarly associated with poorer health behaviours in COPD and non-COPD individuals. Future studies need to determine if treating symptoms of psychological distress can improve health behaviours and outcomes in this population., (Copyright © 2018. Published by Elsevier Ltd.)

Background: The COPD Assessment Test (CAT) is a valid disease-specific questionnaire measuring health status. However, knowledge concerning its use regarding patient and disease characteristics remains limited. Our main objective was to assess the degree to which the CAT score varies and can discriminate between specific patient population groups., Methods: The Canadian Cohort Obstructive Lung Disease (CanCOLD) is a random-sampled, population-based, multicenter, prospective cohort that includes subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] classifications 1 to 3). The CAT questionnaire was administered at three visits (baseline, 1.5 years, and 3 years). The CAT total score was determined for sex, age groups, smoking status, GOLD classification, exacerbations, and comorbidities., Results: A total of 716 subjects with COPD were included in the analysis. The majority of subjects (72.5%) were not previously diagnosed with COPD. The mean FEV 1 /FVC ratio was 61.1 ± 8.1%, with a mean FEV 1 % predicted of 82.3 ± 19.3%. The mean CAT scores were 5.8 ± 5.0, 9.6 ± 6.7, and 16.1 ± 10.0 for GOLD 1, 2, and 3+ classifications, respectively. Higher CAT scores were observed in women, current smokers, ever-smokers, and subjects with a previous diagnosis of COPD. The CAT was also able to distinguish between subjects who experience exacerbations vs those who had no exacerbation., Conclusions: These results suggest that the CAT, originally designed for use in clinically symptomatic patients with COPD, can also be used in individuals with mild airflow obstruction and newly diagnosed COPD. In addition, the CAT was able to discriminate between sexes and subjects who experience frequent and infrequent exacerbations., Trial Registry: ClinicalTrials.gov; No.: NCT00920348; Study ID No.: IRO-93326., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

Acute hypoxia increases cerebral blood flow (CBF) and ventilation (V̇e). It is unknown if these responses are impacted with normal aging, or in patients with enhanced oxidative stress, such as (COPD). The purpose of the study was to 1) investigate the effects of aging and COPD on the cerebrovascular and ventilatory responses to acute hypoxia, and 2) to assess the effect of vitamin C on these responses during hypoxia. In 12 Younger, 14 Older, and 12 COPD, we measured peak cerebral blood flow velocity (V̄p; index of CBF), and V̇e during two 5-min periods of acute isocapnic hypoxia, under conditions of 1) saline-sham; and 2) intravenous vitamin C. Antioxidants [vitamin C, superoxide dismutase (SOD), glutathione peroxidase, and catalase], oxidative stress [malondialdehyde (MDA) and advanced protein oxidation product], and nitric oxide metabolism end products (NOx) were measured in plasma. Following the administration of vitamin C, vitamin C, SOD, catalase, and MDA increased, while NOx decreased. V̄p and V̇e sensitivity to hypoxia was reduced in Older by ∼60% (P < 0.02). COPD patients exhibited similar V̄p and V̇e responses to Older (P > 0.05). Vitamin C did not have an effect on the hypoxic V̇e response but selectively decreased the V̄p sensitivity in Younger only. These findings suggest a reduced integrative reflex (i.e., cerebrovascular and ventilatory) during acute hypoxemia in healthy older adults. Vitamin C does not appear to have a large influence on the cerebrovascular or ventilatory responses during acute hypoxia., (Copyright © 2015 the American Physiological Society.)