Publications by authors named "Jean Bourbeau"

232 Publications

Dyspnoea and symptom burden in mild-moderate COPD: the Canadian Cohort Obstructive Lung Disease Study.

ERJ Open Res 2021 Apr 19;7(2). Epub 2021 Apr 19.

Division of Respiratory Medicine, Dept of Medicine, McGill University Health Centre, Montreal, QC, Canada.

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 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 men (MRC2 1; OR (95% CI) 3.70 (2.23-6.14)); people with, without, physician-diagnosed COPD (MRC2 1; OR (95% CI) 3.27 (1.71-6.23)), and people with without recent exacerbations (MRC2 1; ≥2 0 exacerbations: OR (95% CI) 3.62 (1.02-12.86); MRC ≥3 1; 1 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.
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http://dx.doi.org/10.1183/23120541.00960-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053913PMC
April 2021

Mechanisms associated with increased physical activity in patients undergoing self-management behaviour modification in the randomised PHYSACTO trial.

ERJ Open Res 2021 Jan 29;7(1). Epub 2021 Mar 29.

University of Québec at Montréal/CIUSSS-NIM - Hôpital du Sacré-Coeur de Montréal, Montréal, Canada.

Introduction: In this analysis of the PHYSACTO® study, we assessed the efficacy of a self-management behaviour modification (SMBM) programme to improve physical activity (PA) levels, and the extent to which effects were mediated by readiness to change, motivation and confidence.

Methods: PHYSACTO® was a randomised, partially double-blind, parallel-group, 12-week trial to evaluate the effects of treatment on exercise capacity and PA. COPD patients received placebo, tiotropium 5 µg or tiotropium/olodaterol 5/5 µg, with or without exercise training, all with an SMBM intervention (the Living Well with COPD programme). Changes were assessed in readiness to change (stage of change visual analogue scale [VAS]), motivation (Treatment Self-Regulation Questionnaire [TSRQ]) and confidence (Perceived Competence Scale [PCS]) to engage in PA.

Results: PA was increased in all patients with complete PA data at Week 12 (n=262; +6038 steps·week, p<0.001). Significant increases were observed in patients' readiness to change (VAS 0.7 [0.6-0.8]), autonomous regulation (TRSQ 0.2 [0.1-0.3]) and confidence (PCS 0.5 [0.3-0.6]) (all p<0.01). Of note, 23% of the total effect of SMBM on steps·week was found to be mediated by increases in readiness to change, 5% by TSRQ autonomous regulation and 12% by PCS.

Conclusion: Our study demonstrated that an SMBM programme delivered to COPD patients increased PA, mediated by an improvement of three key hypothesised mechanisms of change: readiness to change, autonomous motivation and confidence. For the first time, this study shows that an SMBM programme can be successful in altering the mechanisms of change targeted by the intervention.
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http://dx.doi.org/10.1183/23120541.00533-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005679PMC
January 2021

Benefit/Risk Profile of Single-Inhaler Triple Therapy in COPD.

Int J Chron Obstruct Pulmon Dis 2021 1;16:499-517. Epub 2021 Mar 1.

University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, UK.

Chronic obstructive pulmonary disease (COPD) is associated with major healthcare and socioeconomic burdens. International consortia recommend a personalized approach to treatment and management that aims to reduce both symptom burden and the risk of exacerbations. Recent clinical trials have investigated single-inhaler triple therapy (SITT) with a long-acting muscarinic antagonist (LAMA), long-acting β-agonist (LABA), and inhaled corticosteroid (ICS) for patients with symptomatic COPD. Here, we review evidence from randomized controlled trials showing the benefits of SITT and weigh these against the reported risk of pneumonia with ICS use. We highlight the challenges associated with cross-trial comparisons of benefit/risk, discuss blood eosinophils as a marker of ICS responsiveness, and summarize current treatment recommendations and the position of SITT in the management of COPD, including potential advantages in terms of improving patient adherence. Evidence from trials of SITT versus dual therapies in symptomatic patients with moderate to very severe airflow limitation and increased risk of exacerbations shows benefits in lung function and patient-reported outcomes. Moreover, the key benefits reported with SITT are significant reductions in exacerbations and hospitalizations, with data also suggesting reduced all-cause mortality. These benefits outweigh the ICS-class effect of higher incidence of study-reported pneumonia compared with LAMA/LABA. Important differences in trial design, baseline population characteristics, such as exacerbation history, and assessment of outcomes, have significant implications for interpreting data from cross-trial comparisons. Current understanding interprets the blood eosinophil count as a continuum that can help predict response to ICS and has utility alongside other clinical factors to aid treatment decision-making. We conclude that treatment decisions in COPD should be guided by an approach that considers benefit versus risk, with early optimization of treatment essential for maximizing long-term benefits and patient outcomes.
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http://dx.doi.org/10.2147/COPD.S291967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935340PMC
March 2021

Aryl hydrocarbon receptor deficiency causes the development of chronic obstructive pulmonary disease through the integration of multiple pathogenic mechanisms.

FASEB J 2021 Mar;35(3):e21376

Research Institute of the McGill University Health Centre, Montreal, QC, Canada.

Emphysema, a component of chronic obstructive pulmonary disease (COPD), is characterized by irreversible alveolar destruction that results in a progressive decline in lung function. This alveolar destruction is caused by cigarette smoke, the most important risk factor for COPD. Only 15%-20% of smokers develop COPD, suggesting that unknown factors contribute to disease pathogenesis. We postulate that the aryl hydrocarbon receptor (AHR), a receptor/transcription factor highly expressed in the lungs, may be a new susceptibility factor whose expression protects against COPD. Here, we report that Ahr-deficient mice chronically exposed to cigarette smoke develop airspace enlargement concomitant with a decline in lung function. Chronic cigarette smoke exposure also increased cleaved caspase-3, lowered SOD2 expression, and altered MMP9 and TIMP-1 levels in Ahr-deficient mice. We also show that people with COPD have reduced expression of pulmonary and systemic AHR, with systemic AHR mRNA levels positively correlating with lung function. Systemic AHR was also lower in never-smokers with COPD. Thus, AHR expression protects against the development of COPD by controlling interrelated mechanisms involved in the pathogenesis of this disease. This study identifies the AHR as a new, central player in the homeostatic maintenance of lung health, providing a foundation for the AHR as a novel therapeutic target and/or predictive biomarker in chronic lung disease.
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http://dx.doi.org/10.1096/fj.202002350RDOI Listing
March 2021

The Prevalence of Chronic Obstructive Pulmonary Disease (COPD) and the Heterogeneity of Risk Factors in the Canadian Population: Results from the Canadian Obstructive Lung Disease (COLD) Study.

Int J Chron Obstruct Pulmon Dis 2021 12;16:305-320. Epub 2021 Feb 12.

Centre for Heart Lung Innovation, St Pauls Hospital, The University of British Columbia, Vancouver, BC, Canada.

Purpose: To determine the spirometric-based prevalence of COPD across different regions in Canada and to evaluate the site heterogeneity of risk factors.

Patients And Methods: In this cross-sectional, population-based study, random samples of non-institutionalized adults aged ≥40 years were generated by random digit dialling. Participants answered an interviewer-administered questionnaire and performed spirometry before and after bronchodilator administration. COPD was defined as post-bronchodilator FEV/FVC <0.70 (fixed ratio, FR) and as FEV/FVC <5th percentile (lower limits of normal, LLN). Separate logistic regression models were used to compute the risk (adjusted odds ratio, aOR) for COPD. I and Tau analyses were used to evaluate heterogeneity.

Results: Out of 5176 (95%) participants, 4893 (47% male with mean age 56.6 years (95% confidence interval, 56.0-57.2)) had spirometry that satisfied ATS criteria. The population prevalence of COPD was 16.2% (95% CI, 14.5-17.8) by FR and 11.2% (95% CI, 9.7-12.6) by LLN. Male predominance in prevalence was shown by FR but not by LLN criteria. Patient characteristics associated with an increased risk of COPD included: age (OR 1.56; 95% CI 1.33-1.84); history of physician-diagnosed asthma (OR 3.30; 95% CI 2.42-4.49); and childhood hospitalization for respiratory illness (OR 1.81; 95% CI 1.17-2.80). In terms of smoking-related risk factors, current smoking status had the highest odds ratio (OR 3.49; 95% CI 2.55-4.80). Variance in prevalence among sites was significantly reduced by adjusting for risk factors in Tau analyses. Higher odds of exposure for each risk factor was found in more severe COPD, suggesting that a higher risk could be linked to the development of severe disease.

Conclusion: This study reports the population prevalence of COPD in nine urban cities which collectively represent the majority of the Canadian population and demonstrates that heterogeneity in prevalence among sites is substantially explained by variation in associated risk factors for COPD.
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http://dx.doi.org/10.2147/COPD.S285338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886112PMC
February 2021

Ambient air pollution exposure and chronic bronchitis in the Lifelines cohort.

Thorax 2021 Jan 28. Epub 2021 Jan 28.

Centre for Environmental Health and Sustainability, University of Leicester, Leicester, UK.

Background: Few large studies have assessed the relationship of long-term ambient air pollution exposure with the prevalence and incidence of symptoms of chronic bronchitis and cough.

Methods: We leveraged Lifelines cohort data on 132 595 (baseline) and 65 009 (second assessment) participants linked to ambient air pollution estimates. Logistic regression models adjusted for sex, age, educational attainment, body mass index, smoking status, pack-years smoking and environmental tobacco smoke at home were used to assess associations of air pollution with prevalence and incidence of chronic bronchitis (winter cough and sputum almost daily for ≥3 months/year), chronic cough (winter cough almost daily for ≥3 months/year) and prevalence of cough and sputum symptoms, irrespective of duration.

Results: Associations were seen for all pollutants for prevalent cough or sputum symptoms. However, for prevalent and incident chronic bronchitis, statistically significant associations were seen for nitrogen dioxide (NO) and black carbon (BC) but not for fine particulate matter (PM). For prevalent chronic bronchitis, associations with NO showed OR: 1.05 (95% CI: 1.02 to 1.08) and with BC OR: 1.06 (95% CI: 1.03 to 1.09) expressed per IQR; corresponding results for incident chronic bronchitis were NO OR: 1.07 (95% CI: 1.02 to 1.13) and BC OR: 1.07 (95% CI: 1.02 to 1.13). In subgroup analyses, slightly stronger associations were observed among women, never smokers and younger individuals.

Conclusion: This is the largest analysis to date to examine cross-sectional and longitudinal associations between ambient air pollution and chronic bronchitis. NO and BC air pollution was associated with increased odds of prevalent and incident chronic bronchitis.
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http://dx.doi.org/10.1136/thoraxjnl-2020-216142DOI Listing
January 2021

Investigating the effect of pretreatment with azithromycin on inflammatory mediators in bronchial epithelial cells exposed to cigarette smoke.

Exp Lung Res 2021 Feb-Mar;47(2):98-109. Epub 2020 Dec 18.

Respiratory Epidemiology and Clinical Research Unit, Research Institute of McGill University Health Center, McGill University, Montréal, Canada.

Macrolide therapy is effective in reducing chronic obstructive pulmonary disease (COPD) exacerbations. Our recent study has shown the effectiveness of taking azithromycin in COPD patients, not only ex-smokers but also current smokers. Beyond their anti-microbial effects, macrolides have anti-inflammatory and immunomodulatory properties. The aim of this study was to determine if pretreatment with azithromycin modulates cigarette smoke-induced inflammation in airway epithelial cells. We hypothesized that pretreatment with azithromycin decreases exacerbation frequency by modulating inflammation in human airway epithelial cells exposed to cigarette smoke. BEAS-2B bronchial epithelial cells were incubated with 5% cigarette smoke extract (CSE) for 3 h, 6 h, and 24 h. Then, airway epithelial cells were pretreated with azithromycin and exposed to 5% CSE. In each stage, the expression and release of IL-6 and IL-8 mRNA were analyzed by quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. There was a significant increase of IL-6 and IL-8 mRNA, as well as an increase in extracellular IL-8 protein following exposure to 5% CSE. When cells were pretreated with azithromycin and exposed to 5% CSE for 3 h, there was a significant dose-dependent decrease in the expression of IL-6 mRNA. A final concentration of 9 µg/mL of azithromycin was sufficient to decrease IL-6, IL-8 mRNA, and extracellular IL-8 levels. Pretreatment with azithromycin decreased the expression of IL-6 and IL-8 mRNA and the release of IL-8 in bronchial epithelial cells exposed to cigarette smoke. These results demonstrate the direct effect of azithromycin on inflammatory mediators in bronchial epithelial cells exposed to cigarette smoke.
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http://dx.doi.org/10.1080/01902148.2020.1857470DOI Listing
December 2020

Diaphragm Morphology Assessed by Computed Tomography in Chronic Obstructive Pulmonary Disease.

Ann Am Thorac Soc 2020 Dec 15. Epub 2020 Dec 15.

McGill University, 5620, Medicine, Montreal, Quebec, Canada.

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with abnormal skeletal muscle morphology and function.

Objectives: We hypothesized that diaphragm muscle morphology assessed by computed tomography (CT) would be associated with COPD severity, exacerbations, health status, and exercise capacity.

Methods: The COPD Morphometry Study is a cross-sectional study that enrolled a clinical sample of smokers with COPD. Spirometry was performed and COPD severity defined according to guidelines. Three-dimensional left hemi-diaphragm morphology was segmented from contiguous axial CT images acquired at maximal inspiration, yielding quantitative measures of diaphragm CT density in Hounsfield units (HU), dome height, and muscle volume. Exacerbations prompting pharmacotherapy or hospitalization in the preceding 12-months and St. George's Respiratory Questionnaire for COPD (SGRQ-C) were assessed. Incremental symptom-limited cycle ergometry quantified peak oxygen uptake (V̇O). Associations were adjusted for age, gender, body height, body mass index, and smoking status.

Results: Among 65 smokers with COPD (75% male; [mean±SD] 56±26 pack-years; FEVpercent predicted 55±23%), mean diaphragm CT density was 3.1±10 HU, dome height was 5.2±1.3 cm, and muscle volume was 57±24 cm. A 1-SD decrement in diaphragm CT density was associated with: 8.3% lower FEV, 3.27-fold higher odds of exacerbation history, 9.7 point higher SGRQ-C, and 2.5 mL∕kg∕min lower V̇O. A 1-SD decrement in dome height was associated with 11% lower FEV, and 1.3 mL∕kg∕min lower V̇O. No associations with diaphragm volume were observed.

Conclusions: CT-assessed diaphragm morphology was associated with COPD severity, exacerbations, impaired health status, and exercise intolerance. The mechanisms and functional impact of lower diaphragm CT density merit investigation.
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http://dx.doi.org/10.1513/AnnalsATS.202007-865OCDOI Listing
December 2020

High eosinophil counts predict decline in FEV: Results from the CanCOLD study.

Eur Respir J 2020 Dec 10. Epub 2020 Dec 10.

Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.

Introduction: The aim of this study was to examine the association between blood eosinophil (EOS) levels and the decline in lung function in individuals over the age of 40 from the general population.

Methods: The study evaluated the EOS 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 EOS levels and decline in forced expiratory volume in 1 s (FEV) were performed using random mixed effects regression models with adjustments for demographics, smoking, baseline FEV, ever-asthma and history of exacerbations in the previous 12 months. CT measurements were compared between EOS subgroups using an analysis of variance.

Results: Participants who had a peripheral EOS count of ≥300 cells·µL (n=273) had a greater decline in FEV compared with those with EOS counts of <150 cells·µL (n=430) [p=0.003] (reference group) and 150 to <300 cells·µL (n=417) [p=0.003]. The absolute change in FEV was -32.99 mL·year for participants with EOS counts <150 cells·µL; -38.78 mL·year for those with 150 to <300 cells·µL; and -67.30 mL·year for participants with ≥300 cells·µL. In COPD, higher EOS count was associated with quantitative CT measurements reflecting both small and large airway abnormalities.

Conclusion: A blood EOS count of ≥300 cells·µL is an independent risk factor for accelerated lung function decline in older adults and is related to undetected structural airway abnormalities.
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http://dx.doi.org/10.1183/13993003.00838-2020DOI Listing
December 2020

Normative Cardiopulmonary Exercise Test Responses at the Ventilatory Threshold in Canadian Adults 40 to 80 Years of Age.

Chest 2021 May 18;159(5):1922-1933. Epub 2020 Nov 18.

Clinical Exercise and Respiratory Physiology Laboratory, Department of Kinesiology and Physical Education, Faculty of Education, McGill University, Montréal; Division of Respiratory Medicine, Faculty of Medicine, McGill University, Montréal; Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montréal.

Background: Physiologic and symptom responses at the ventilatory threshold (Tvent) during incremental cardiopulmonary exercise testing (CPET) can provide important prognostic information.

Research Question: This study aimed to develop an updated normative reference set for physiologic and symptom responses at Tvent during cycle CPET (primary aim) and to evaluate previously recommended reference equations from a 1985 study for predicting Tvent responses (secondary aim).

Study Design And Methods: Participants were adults 40 to 80 years of age who were free of clinically relevant disease from the Canadian Cohort Obstructive Lung Disease. Rate of oxygen consumption (V˙O) at Tvent was identified by two independent raters; physiologic and symptom responses corresponding to V˙O at Tvent were identified by linear interpolation. Reference ranges (5th-95th percentiles) for responses at Tvent were calculated according to participant sex and age for 29 and eight variables, respectively. Prediction models were developed for nine variables (oxygen pulse, V˙O, rate of CO production, minute ventilation, tidal volume, inspiratory capacity, end-inspiratory lung volume [in liters and as percentage of total lung capacity], and end-expiratory lung volume) using quantile regression, estimating the 5th (lower limit of normal), 50th (normal), and 95th (upper limit of normal) percentiles based on readily available participant characteristics. The two one-sided test of equivalence for paired samples evaluated the measured and 1985-predicted V˙O at Tvent for equivalence.

Results: Reference ranges and equations were developed based on 96 participants (49% men) with a mean ± SD age of 63 ± 9 years. Mean V˙O at Tvent was 50% of measured V˙O peak; the normal range was 33% to 66%. The 1985 reference equations overpredicted V˙O at Tvent: mean difference in men, -0.17 L/min (95% CI, -0.25 to -0.09 L/min); mean difference in women, -0.19 L/min (95% CI, -0.27 to -0.12 L/min).

Interpretation: A contemporary reference set of CPET responses at Tvent from Canadian adults 40 to 80 years of age is presented that differs from the previously recommended and often used reference set from 1985.

Trial Registry: ClinicalTrials.gov; No.: NCT00920348; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2020.11.009DOI Listing
May 2021

Accelerated Epigenetic Aging and Methylation Disruptions Occur in Human Immunodeficiency Virus Infection Prior to Antiretroviral Therapy.

J Infect Dis 2020 Sep 22. Epub 2020 Sep 22.

Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC.

Background: Whether accelerated aging develops over the course of chronic HIV infection or can be observed prior to significant immunosuppression on is unknown. We studied DNA methylation in blood to estimate cellular aging in persons living with HIV (PLWH) prior to the initiation of antiretroviral therapy.

Methods: 378 antiretroviral therapy-naïve PLWH with CD4 T cell counts >500 cells/mm 3 enrolled in the Strategic Timing of Antiretroviral Therapy trial (Pulmonary Substudy) were compared to 34 HIV-negative controls. DNA methylation was performed using the Illumina MethylationEPIC BeadChip. Differentially methylated positions (DMPs) and regions (DMRs) in PLWH compared to controls were identified using a robust linear model. Methylation age was calculated using a previously described epigenetic clock.

Results: There were a total of 56,639 DMPs and 6,103 DMRs at a false discovery rate<0.1. The top 5 DMPs corresponded to genes NLRC5, VRK2, B2M, and GPR6 and were highly enriched for cancer-related pathways. PLWH had significantly higher methylation age compared to HIV-negative controls (p=0.001), with black race, low CD4, high CD8 T cell counts, and duration of HIV being risk factors for age acceleration.

Conclusions: PLWH prior to the initiation of antiretroviral therapy and with preserved immune status show evidence of advanced methylation aging.
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http://dx.doi.org/10.1093/infdis/jiaa599DOI Listing
September 2020

Randomized Trial of Nocturnal Oxygen in Chronic Obstructive Pulmonary Disease.

N Engl J Med 2020 09;383(12):1129-1138

From Institut Universitaire de Cardiologie et de Pneumologie de Québec-Université Laval, Quebec, QC (Y.L., F.S., S.B., F.M.), Centre Hospitalier Affilié Universitaire de Trois-Rivières, Trois-Rivières, QC (F.C.), Mount Sinai Hospital, McGill University (M.B.), and Montreal Chest Institute, Research Institute of the McGill University Health Centre and McGill University (J.B.), Montreal, Centre Intégré de Santé et de Services Sociaux de Laval, Laval, QC (B.P.), and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa (S.D.A.) - all in Canada; Hospital Pedro Hispano-Unidade Local de Saúde de Matosinhos, Matosinhos (P.S.), and Centro Hospitalar Vila Nova de Gaia-Espinho, Vila Nova de Gaia (M.G.) - both in Portugal; and Hospital Universitario de Getafe, Getafe (A.A.F.), and Hospital Galdakao, Servicio Vasco de Salud-Osakidetza, Bizkaia (C.E.) - both in Spain.

Background: Long-term oxygen therapy improves survival in patients with chronic obstructive pulmonary disease (COPD) and chronic severe daytime hypoxemia. However, the efficacy of oxygen therapy for the management of isolated nocturnal hypoxemia is uncertain.

Methods: We designed this double-blind, placebo-controlled, randomized trial to determine, in patients with COPD who have nocturnal arterial oxygen desaturation without qualifying for long-term oxygen therapy, whether nocturnal oxygen provided for a period of 3 to 4 years would decrease mortality or the worsening of disease such that patients meet current specifications for long-term oxygen therapy. Patients with an oxygen saturation of less than 90% for at least 30% of the recording time on nocturnal oximetry were assigned, in a 1:1 ratio, to receive either nocturnal oxygen or ambient air from a sham concentrator (placebo). The primary outcome was a composite of death from any cause or a requirement for long-term oxygen therapy as defined by the Nocturnal Oxygen Therapy Trial (NOTT) criteria in the intention-to-treat population.

Results: Recruitment was stopped prematurely because of recruitment and retention difficulties after 243 patients, of a projected 600, had undergone randomization at 28 centers. At 3 years of follow-up, 39.0% of the patients assigned to nocturnal oxygen (48 of 123) and 42.0% of those assigned to placebo (50 of 119) met the NOTT-defined criteria for long-term oxygen therapy or had died (difference, -3.0 percentage points; 95% confidence interval, -15.1 to 9.1).

Conclusions: Our underpowered trial provides no indication that nocturnal oxygen has a positive or negative effect on survival or progression to long-term oxygen therapy in patients with COPD. (Funded by the Canadian Institutes of Health Research; INOX ClinicalTrials.gov number, NCT01044628.).
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http://dx.doi.org/10.1056/NEJMoa2013219DOI Listing
September 2020

Description of Participation in Daily and Social Activities for Individuals with COPD.

COPD 2020 10 18;17(5):543-556. Epub 2020 Aug 18.

Department of Kinesiology and Physical Education, McGill University, Montreal, Quebec, Canada.

This study described the participation in daily and social activities and the perceived barriers and facilitators to participation of individuals with chronic obstructive pulmonary disease (COPD). Individuals, recruited from outpatient clinics, responded to a survey on their participation in, and barriers and facilitators towards, 26 daily and social activities, divided into 3 categories: (1) physical activity and movement (PAM); (2) self-care; and (3) social engagement. For each activity, chi-square analyses were used to examine participation differences by individuals': quartiles of airflow obstruction [percent predicted forced expiratory volume in 1 second (FEV1%predicted)] and breathlessness burden and exacerbation risk. Of the 200 participants (47% women; mean ± standard deviation age = 68 ± 9 years), most wanted to increase their participation in PAM activities (range 21-75%) and significant differences were found in 5/10 PAM activities for individuals' breathlessness burden and exacerbation risk (e.g., more individuals than expected in group A (modified Medical Research Council breathlessness score <2 and 0-1 exacerbations in past 12 months) as much as they wanted (χ=20.43, Cramer's =.23)). Regardless of the degree of airflow obstruction or breathlessness burden and exacerbation risk, the most common barrier to participation was breathlessness (<.001, η=.86) and the most common facilitator was engaging as part of their routine (<.001, η=.75). Individuals with COPD want to increase their participation in daily and social activities but are limited by breathlessness. Strategies to alleviate breathlessness should be identified/prioritized and incorporated into individuals' daily routines to meet their self-reported participation objectives in daily and social activities.
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http://dx.doi.org/10.1080/15412555.2020.1798373DOI Listing
October 2020

Pulmonary Rehabilitation.

Clin Chest Med 2020 09;41(3):513-528

Respiratory Epidemiology and Clinical Research Unit, Montréal Chest Institute, McGill University Health Centre, 5252 De Maisonneuve, Room 3D.62, Montréal, Québec H4A 3S5, Canada.

Pulmonary rehabilitation (PR) is an essential intervention in the management of patients with chronic obstructive pulmonary disease. To guide health care professionals in the implementation and evaluation of a PR program, this article discusses the current key concepts regarding exercise testing, prescription, and training, as well as self-management intervention as essential parts of PR and post-rehabilitation maintenance. Moreover, new approaches (alternative forms of organization and delivery, tele-rehabilitation, exercise adjuncts) and unique and challenging situations (patients experiencing acute exacerbations, advanced disease) are thoroughly reviewed. Finally, validated point-of-care resources and online tools are provided.
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http://dx.doi.org/10.1016/j.ccm.2020.06.003DOI Listing
September 2020

Normative Peak Cardiopulmonary Exercise Test Responses in Canadian Adults Aged ≥40 Years.

Chest 2020 Dec 14;158(6):2532-2545. Epub 2020 Jul 14.

Clinical Exercise and Respiratory Physiology Laboratory, Department of Kinesiology and Physical Education, Faculty of Education, McGill University, Montréal, QC, Canada; Division of Respiratory Medicine, Faculty of Medicine, McGill University, Montréal, QC, Canada; Research Centre for Physical Activity and Health, Faculty of Education, McGill University, Montréal, QC, Canada; Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montréal, QC, Canada.

Background: Up-to-date normative reference sets for cardiopulmonary exercise testing (CPET) are important to aid in the accurate interpretation of CPET in clinical or research settings.

Research Question: This study aimed to (1) develop and externally validate a contemporary reference set for peak CPET responses in Canadian adults identified with population-based sampling; and (2) evaluate previously recommended reference equations for predicting peak CPET responses.

Study Design And Methods: Participants were healthy adults who were ≥40 years old from the Canadian Cohort Obstructive Lung Disease who completed an incremental cycle CPET. Prediction models for peak CPET responses were estimated from readily available participant characteristics (age, sex, height, body mass) with the use of quantile regression. External validation was performed with a second convenience sample of healthy adults. Peak CPET parameters that were measured and predicted in the validation cohort were assessed for equivalence (two one-sided tests of equivalence for paired-samples and level of agreement (Bland-Altman analyses). Two one-sided tests of equivalence for paired samples assessed differences between responses in the derivation cohort using previously recommended reference equations.

Results: Normative reference ranges (5th-95th percentiles) for 28 peak CPET parameters and prediction models for 8 peak CPET parameters were based on 173 participants (47% male) who were 64 ± 10 years old. In the validation cohort (n = 84), peak CPET responses that were predicted with the newly generated models were equivalent to the measured values. Peak cardiac parameters predicted by the previously recommended reference equations by Jones and colleagues and Hansen and colleagues were significantly higher.

Interpretation: This study provides reference ranges and prediction models for peak cardiac, ventilatory, operating lung volume, gas exchange, and symptom responses to incremental CPET and presents the most comprehensive reference set to date in Canadian adults who were ≥40 years old to be identified with population-based sampling.
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http://dx.doi.org/10.1016/j.chest.2020.06.074DOI Listing
December 2020

Predicting the rate of oxygen consumption during the 3-minute constant-rate stair stepping and shuttle tests in people with chronic obstructive pulmonary disease.

J Thorac Dis 2020 May;12(5):2489-2498

Clinical Exercise and Respiratory Physiology Laboratory, Department of Kinesiology and Physical Education, Faculty of Education, McGill University, Montréal, Canada.

Background: The 3-minute constant-rate stair stepping (3-min CRSST) and constant-speed shuttle tests (3-min CSST) were developed to assess breathlessness in response to a standardized exercise stimulus. Estimating the rate of oxygen consumption (V'O) during these tests would assist clinicians to relate the stepping/shuttle speeds that elicit breathlessness to daily physical activities with a similar metabolic demand. This study: (I) developed equations to estimate the V'O of these tests in people with chronic obstructive pulmonary disease (COPD); and (II) compared the newly developed and American College of Sports Medicine (ACSM) metabolic equations for estimating the V'O of these tests.

Methods: This study was a retrospective analysis of people with COPD who completed a 3-min CRSST (n=98) or 3-min CSST (n=69). Multivariate linear regression estimated predictors (alpha <0.05) of V'O to construct COPD-specific metabolic equations. The mean squared error (MSE) of the COPD-specific and ACSM equations was calculated and compared. Bland-Altman analyses evaluated level of agreement between measured and predicted V'O using each equation; limits of agreement (LoA) and patterns of bias were compared.

Results: Stepping rate/shuttle speed and body mass were identified as significant predictors of V'O. The MSE of the COPD-specific equations was 0.05 L·min for both tests. Mean difference between measured and predicted V'O was 0.00 L·min (95% LoA -0.46, 0.46) and 0.00 L·min (95% LoA -0.44, 0.44) for the 3-min CRSST and 3-min CSST, respectively. For the ACSM metabolic equations, the MSE was 0.10 L·min and 0.18 L·min for the 3-min CRSST and 3-min CSST, respectively. The ACSM metabolic equations underestimated V'O of the 3-min CRSST by -0.18 L·min (95% LoA -0.68, 0.32), and overestimated V'O of the 3-min CSST by 0.35 L·min (95% LoA -0.14, 0.84).

Conclusions: This study presents metabolic equations to predict V'O2 of the 3-min CRSST and 3-min CSST for people with COPD that are more accurate than the ACSM metabolic equations.
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http://dx.doi.org/10.21037/jtd.2020.03.13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330369PMC
May 2020

Fractional Exhaled Nitric Oxide as an Inflammatory Biomarker in Chronic Obstructive Pulmonary Disease (COPD) with or without Concurrent Diagnosis of Asthma: The Canadian Cohort Obstructive Lung Disease (CanCOLD).

COPD 2020 08 25;17(4):355-365. Epub 2020 Jun 25.

Respiratory Epidemiology and Clinical Research Unit, Research Institute of McGill University Health Centre, McGill University, Montreal, Canada.

We studied whether fractional exhaled nitric oxide () can differentiate chronic obstructive pulmonary disease (COPD) with concurrent diagnosis of asthma from COPD-only as well as its ability to predict disease severity and progression. This study was embedded in the Canadian Cohort Obstructive Lung Disease (CanCOLD). Subjects of ≥40 years old completed measurements were subdivided into four groups, including COPD ( = 86 [COPD-only ( = 35) and COPD with concurrent diagnosis of asthma ( = 51)], healthy ( = 72), and at risk ( = 151). Three of the most common clinical definitions were used for characterizing COPD with concurrent diagnosis of asthma: 1) atopy and self-reported physician diagnosis of asthma, 2) ≥12% and ≥200 ml post-bronchodilator FEV1; 3) self-reported physician diagnosis of asthma. values were classified using quartiles and the American Thoracic Society (ATS) guideline 2011. Compared to COPD-only, more COPD with concurrent diagnosis of asthma had a significant level of [Formula: see text] 33.5 ppb (fourth quartile) than COPD-only ( = 0.045, 0.011, and 0.006, for definition 1, 2, and 3, respectively). Considering the ATS guideline 2011, fewer COPD with concurrent diagnosis of asthma had < 25 than COPD-only, which was statistically significant with definition 1 and 3 ( = 0.038 and 0.026, respectively). as a biomarker has the potential to be used as a complementary value for differentiating COPD with concurrent diagnosis of asthma from COPD-only. Further studies should be conducted on validated definitions of COPD with concurrent diagnosis of asthma, which may include a reference to the type of airway inflammation in addition to the clinical definition.
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http://dx.doi.org/10.1080/15412555.2020.1779681DOI Listing
August 2020

Association of Dysanapsis With Chronic Obstructive Pulmonary Disease Among Older Adults.

JAMA 2020 06;323(22):2268-2280

Department of Medicine, Columbia University Medical Center, New York, New York.

Importance: Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD), yet much of COPD risk remains unexplained.

Objective: To determine whether dysanapsis, a mismatch of airway tree caliber to lung size, assessed by computed tomography (CT), is associated with incident COPD among older adults and lung function decline in COPD.

Design, Setting, And Participants: A retrospective cohort study of 2 community-based samples: the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study, which involved 2531 participants (6 US sites, 2010-2018) and the Canadian Cohort of Obstructive Lung Disease (CanCOLD), which involved 1272 participants (9 Canadian sites, 2010-2018), and a case-control study of COPD: the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which involved 2726 participants (12 US sites, 2011-2016).

Exposures: Dysanapsis was quantified on CT as the geometric mean of airway lumen diameters measured at 19 standard anatomic locations divided by the cube root of lung volume (airway to lung ratio).

Main Outcomes And Measures: Primary outcome was COPD defined by postbronchodilator ratio of forced expired volume in the first second to vital capacity (FEV1:FVC) less than 0.70 with respiratory symptoms. Secondary outcome was longitudinal lung function. All analyses were adjusted for demographics and standard COPD risk factors (primary and secondhand tobacco smoke exposures, occupational and environmental pollutants, and asthma).

Results: In the MESA Lung sample (mean [SD] age, 69 years [9 years]; 1334 women [52.7%]), 237 of 2531 participants (9.4%) had prevalent COPD, the mean (SD) airway to lung ratio was 0.033 (0.004), and the mean (SD) FEV1 decline was -33 mL/y (31 mL/y). Of 2294 MESA Lung participants without prevalent COPD, 98 (4.3%) had incident COPD at a median of 6.2 years. Compared with participants in the highest quartile of airway to lung ratio, those in the lowest had a significantly higher COPD incidence (9.8 vs 1.2 cases per 1000 person-years; rate ratio [RR], 8.12; 95% CI, 3.81 to 17.27; rate difference, 8.6 cases per 1000 person-years; 95% CI, 7.1 to 9.2; P < .001) but no significant difference in FEV1 decline (-31 vs -33 mL/y; difference, 2 mL/y; 95% CI, -2 to 5; P = .30). Among CanCOLD participants (mean [SD] age, 67 years [10 years]; 564 women [44.3%]), 113 of 752 (15.0%) had incident COPD at a median of 3.1 years and the mean (SD) FEV1 decline was -36 mL/y (75 mL/y). The COPD incidence in the lowest airway to lung quartile was significantly higher than in the highest quartile (80.6 vs 24.2 cases per 1000 person-years; RR, 3.33; 95% CI, 1.89 to 5.85; rate difference, 56.4 cases per 1000 person-years; 95% CI, 38.0 to 66.8; P<.001), but the FEV1 decline did not differ significantly (-34 vs -36 mL/y; difference, 1 mL/y; 95% CI, -15 to 16; P=.97). Among 1206 SPIROMICS participants (mean [SD] age, 65 years [8 years]; 542 women [44.9%]) with COPD who were followed up for a median 2.1 years, those in the lowest airway to lung ratio quartile had a mean FEV1 decline of -37 mL/y (15 mL/y), which did not differ significantly from the decline in MESA Lung participants (P = .98), whereas those in highest quartile had significantly faster decline than participants in MESA Lung (-55 mL/y [16 mL/y ]; difference, -17 mL/y; 95% CI, -32 to -3; P = .004).

Conclusions And Relevance: Among older adults, dysanapsis was significantly associated with COPD, with lower airway tree caliber relative to lung size associated with greater COPD risk. Dysanapsis appears to be a risk factor associated with COPD.
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http://dx.doi.org/10.1001/jama.2020.6918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284296PMC
June 2020

Granularity of alleles by DNA sequencing in CanCOLD.

Eur Respir J 2020 10 15;56(4). Epub 2020 Oct 15.

Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC, Canada.

DNA sequencing of the gene to detect α-antitrypsin (AAT) deficiency (AATD) may provide a better appreciation of the individual and cumulative impact of genetic variants on AAT serum levels and COPD phenotypes.AAT serum level and DNA sequencing of the coding regions of were performed in 1359 participants of the Canadian Cohort Obstructive Lung Disease (CanCOLD) study. Clinical assessment for COPD included questionnaires, pulmonary function testing and computed tomography (CT) imaging. Phenotypes were tested for association with genotypes collated into four groups: normal (MM), mild (MS and MI), intermediate (heterozygote MZ, non-S/non-Z/non-I, compound IS, and homozygote SS) and severe (ZZ and SZ) deficiency. Smoking strata and MZ-only analyses were also performed.34 genetic variants were identified including 25 missense mutations. Overall, 8.1% of alleles in this Canadian cohort were deficient and 15.5% of 1359 individuals were carriers of at least one deficient allele. Four AATD subjects were identified and had statistically lower diffusion capacity and greater CT-based emphysema. No COPD phenotypes were associated with mild and intermediate AATD in the overall cohort or stratified by smoking status. MZ heterozygotes had similar CT-based emphysema, but lowered diffusion capacity compared with normal and mild deficiency.In this Canadian population-based cohort, comprehensive genetic testing for AATD reveals a variety of deficient alleles affecting 15.5% of subjects. COPD phenotype was demonstrated in severe deficiency and MZ heterozygotes. This study shows the feasibility of implementing a diagnostic test for AATD using DNA sequencing in a large cohort.
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http://dx.doi.org/10.1183/13993003.00958-2020DOI Listing
October 2020

A frame of reference for assessing the intensity of exertional dyspnoea during incremental cycle ergometry.

Eur Respir J 2020 10 1;56(4). Epub 2020 Oct 1.

Laboratory of Clinical Exercise Physiology and Respiratory Investigation Unit, Queen's University and Kingston General Hospital, Kingston, ON, Canada.

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 (). 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 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- 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, 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.
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http://dx.doi.org/10.1183/13993003.00191-2020DOI Listing
October 2020

Inhalation Toxicology of Vaping Products and Implications for Pulmonary Health.

Int J Mol Sci 2020 May 15;21(10). Epub 2020 May 15.

Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.

E-cigarettes have a liquid that may contain flavors, solvents, and nicotine. Heating this liquid generates an aerosol that is inhaled into the lungs in a process commonly referred to as vaping. E-cigarette devices can also contain cannabis-based products including tetrahydrocannabinol (THC), the psychoactive component of cannabis (marijuana). E-cigarette use has rapidly increased among current and former smokers as well as youth who have never smoked. The long-term health effects are unknown, and emerging preclinical and clinical studies suggest that e-cigarettes may not be harmless and can cause cellular alterations analogous to traditional tobacco smoke. Here, we review the historical context and the components of e-cigarettes and discuss toxicological similarities and differences between cigarette smoke and e-cigarette aerosol, with specific reference to adverse respiratory outcomes. Finally, we outline possible clinical disorders associated with vaping on pulmonary health and the recent escalation of acute lung injuries, which led to the declaration of the vaping product use-associated lung injury (EVALI) outbreak. It is clear there is much about vaping that is not understood. Consequently, until more is known about the health effects of vaping, individual factors that need to be taken into consideration include age, current and prior use of combustible tobacco products, and whether the user has preexisting lung conditions such as asthma and chronic obstructive pulmonary disease (COPD).
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http://dx.doi.org/10.3390/ijms21103495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278963PMC
May 2020

Critically appraised paper: In people hospitalised with chronic obstructive pulmonary disease, a combined transition and self-management program increased healthcare utilisation [commentary].

J Physiother 2020 04 11;66(2):128. Epub 2020 Apr 11.

Respiratory Epidemiology and Clinical Research Unit, Research Institute of the McGill University Health Centre, McGill University, Montreal, Canada.

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http://dx.doi.org/10.1016/j.jphys.2020.02.002DOI Listing
April 2020

Metabolic profiles among COPD and controls in the CanCOLD population-based cohort.

PLoS One 2020 10;15(4):e0231072. Epub 2020 Apr 10.

Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Canada.

A high prevalence of intermediate cardiometabolic risk factors and obesity in chronic obstructive pulmonary disease (COPD) has suggested the existence of pathophysiological links between hypertriglyceridemia, insulin resistance, visceral adiposity, and hypoxia or impaired pulmonary function. However, whether COPD contributes independently to the development of these cardiometabolic risk factors remains unclear. Our objective was to compare ectopic fat and metabolic profiles among representative individuals with COPD and control subjects and to evaluate whether the presence of COPD alters the metabolic risk profile. Study participants were randomly selected from the general population and prospectively classified as non-COPD controls and COPD, according to the Global Initiative for Chronic Obstructive Lung Disease classification. The metabolic phenotype, which consisted of visceral adipose tissue area, metabolic markers including homeostasis model assessment of insulin resistance (HOMA-IR), and blood lipid profile, was obtained in 144 subjects with COPD and 119 non-COPD controls. The metabolic phenotype was similar in COPD and controls. The odds ratios for having pathologic values for HOMA-IR, lipids and visceral adipose tissue area were similar in individuals with COPD and control subjects in multivariate analyses that took into account age, sex, body mass index, tobacco status and current medications. In a population-based cohort, no difference was found in the metabolic phenotype, including visceral adipose tissue accumulation, between COPD and controls. Discrepancies between the present and previous studies as to whether or not COPD is a risk factor for metabolic abnormalities could be related to differences in COPD phenotype or disease severity of the study populations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231072PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147771PMC
July 2020

Impact of marijuana smoking on lung function in older persons.

Eur Respir J 2020 02 20;55(2). Epub 2020 Feb 20.

The University of British Columbia, Center for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada.

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http://dx.doi.org/10.1183/13993003.02390-2019DOI Listing
February 2020

Identification and definition of asthma-COPD overlap: The CanCOLD study.

Respirology 2020 08 16;25(8):836-849. Epub 2020 Feb 16.

Respiratory Epidemiology and Clinical Research Unit, Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada.

Background And Objective: Lack of consensus on diagnosis of ACO limits our understanding of the impact, management and outcomes of ACO. The present observational study aims to describe the prevalence, clinical characteristics and course of individuals with ACO based on various definitions used in clinical practice.

Methods: We included individuals with COPD from the prospective, multisite CanCOLD study and defined subjects with ACO using seven definitions commonly used in the literature.

Results: Data including questionnaires, lung function and CT scans were analysed from 522 individuals with COPD who were randomly recruited from the population. Among them, 264 fulfilled at least one of the seven definitions of ACO. Prevalence of ACO varied from 3.8% to 31%. Regardless of the definition, individuals with ACO had worse outcomes (lung function and higher percentage of fast decliners, symptoms and exacerbations, health-related quality of life and comorbidities) than the remaining patients with COPD. Conversely, patients with non-ACO had higher emphysema and bronchiolitis scores. The three definitions that included atopy and/or physician diagnosis of asthma identified subjects who differed significantly from patients with COPD. The two ACO definitions with post-bronchodilator reversibility were concordant with COPD and were the least stable, with less than 50% of the patients from each group maintaining reversibility over visits.

Conclusion: Atopy and physician-diagnosed asthma are more distinguishing characteristics to identify ACO. This finding needs to be validated using measures of airway inflammation and other specific biomarkers.
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http://dx.doi.org/10.1111/resp.13780DOI Listing
August 2020