Publications by authors named "François Maltais"

271 Publications

Efficacy and Safety of Umeclidinium/Vilanterol in Current and Former Smokers with COPD: A Prespecified Analysis of The EMAX Trial.

Adv Ther 2021 Aug 4. Epub 2021 Aug 4.

Altitude Clinical Consulting and Clinical Research Institute of Southern Oregon, Medford, OR, USA.

Introduction: Smoking may reduce the efficacy of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD), but its impact on bronchodilator efficacy is unclear. This analysis of the EMAX trial explored efficacy and safety of dual- versus mono-bronchodilator therapy in current or former smokers with COPD.

Methods: The 24-week EMAX trial evaluated lung function, symptoms, health status, exacerbations, clinically important deterioration, and safety with umeclidinium/vilanterol, umeclidinium, and salmeterol in symptomatic patients at low exacerbation risk who were not receiving ICS. Current and former smoker subgroups were defined by smoking status at screening.

Results: The analysis included 1203 (50%) current smokers and 1221 (50%) former smokers. Both subgroups demonstrated greater improvements from baseline in trough FEV at week 24 (primary endpoint) with umeclidinium/vilanterol versus umeclidinium (least squares [LS] mean difference, mL [95% CI]; current: 84 [50, 117]; former: 49 [18, 80]) and salmeterol (current: 165 [132, 198]; former: 117 [86, 148]) and larger reductions in rescue medication inhalations/day over 24 weeks versus umeclidinium (LS mean difference [95% CI]; current: - 0.42 [- 0.63, - 0.20]; former: - 0.25 - 0.44, - 0.05]) and salmeterol (current: - 0.28 [- 0.49, - 0.06]; former: - 0.29 [- 0.49, - 0.09]). Umeclidinium/vilanterol increased the odds (odds ratio [95% CI]) of clinically significant improvement at week 24 in Transition Dyspnea Index versus umeclidinium (current: 1.54 [1.16, 2.06]; former: 1.32 [0.99, 1.75]) and salmeterol (current: 1.37 (1.03, 1.82]; former: 1.60 [1.20, 2.13]) and Evaluating Respiratory Symptoms-COPD versus umeclidinium (current: 1.54 [1.13, 2.09]; former: 1.50 [1.11, 2.04]) and salmeterol (current: 1.53 [1.13, 2.08]; former: 1.53 [1.12, 2.08]). All treatments were well tolerated in both subgroups.

Conclusions: In current and former smokers, umeclidinium/vilanterol provided greater improvements in lung function and symptoms versus umeclidinium and salmeterol, supporting consideration of dual-bronchodilator therapy in symptomatic patients with COPD regardless of their smoking status.
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http://dx.doi.org/10.1007/s12325-021-01855-yDOI Listing
August 2021

Acute Cardiopulmonary and Muscle Oxygenation Responses to Normocapnic Hyperpnea Exercise in COPD.

Med Sci Sports Exerc 2021 Jul 30. Epub 2021 Jul 30.

Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec, Canada.

Purpose: To investigate cardiorespiratory responses and intercostal muscle oxygenation during normocapnic hyperpnea exercise in COPD.

Methods: Twenty-two patients with COPD performed a cardiopulmonary cycling exercise test to assess peak oxygen consumption (V˙O2peak) and minute ventilation (V˙Epeak). They also performed a normocapnic hyperpnea exercise alone, at 50-60% of V˙Epeak to exhaustion, using a respiratory device (Spirotiger) connected to a gas analyzer to monitor V˙O2, V˙E and end-tidal CO2 partial pressure (PETCO2). Cardiac output (CO), intercostal and vastus lateralis muscle oxygenation were continuously measured during exercise using finger photoplethysmography and near-infrared spectroscopy, respectively. Arterial blood gases (PaCO2) and inspiratory capacity (IC) were obtained at rest and at the end of hyperpnea exercise.

Results: The hyperpnea exercise lasted 576 ± 277 s at a V˙E of 34.5 ± 12.1 L•min-1 (58 ± 6% of V˙Epeak), a respiratory rate of 22 ± 4 breath•min-1 and a tidal volume of 1.43 ± 0.43 L. From rest to the end of hyperpnea exercise, V˙O2 increased by 0.35 ± 0.16 L•min-1 (p < 0.001), while PETCO2 and PaCO2 decreased by ~2 mm Hg (p = 0.031), and ~ 5 mm Hg (p = 0.002, n = 13), respectively. Moreover, IC fell from 2.44 ± 0.84 L at rest to 1.96 ± 0.59 L (p = 0.002). During the same period, heart rate and CO increased from 69 ± 12 bpm and 4.94 ± 1.15 L•min-1 at rest to 87 ± 17 bpm (p = 0.002) and 5.92 ± 1.58 L•min-1 (p = 0.007), respectively. During hyperpnea exercise, intercostal deoxyhemoglobin and total hemoglobin increased by 14.26 ± 13.72% (p = 0.001) and 8.69 ± 12.49% (p = 0.003) compared to their resting value. However, during the same period, vastus lateralis oxygenation remained stable (p > 0.05).

Conclusion: In patients with COPD, normocapnic hyperpnea exercise provided a potent cardiorespiratory physiological stimulus, including dynamic hyperinflation, and increased intercostal deoxyhemoglobin consistent with enhanced requirement for muscle O2 extraction.
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http://dx.doi.org/10.1249/MSS.0000000000002760DOI Listing
July 2021

Dysanapsis and the Spirometric Response to Inhaled Bronchodilator.

Am J Respir Crit Care Med 2021 Jul 15. Epub 2021 Jul 15.

McGill University, Respiratory Medicine, Montreal, Quebec, Canada;

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http://dx.doi.org/10.1164/rccm.202107-1574LEDOI Listing
July 2021

Dual Bronchodilator Therapy as First-Line Treatment in Maintenance-Naïve Patients with Symptomatic COPD: A Pre-Specified Analysis of the EMAX Trial.

Int J Chron Obstruct Pulmon Dis 2021 28;16:1939-1956. Epub 2021 Jun 28.

Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Member of the German Center for Lung Research (DZL), Marburg, Germany.

Introduction: Limited prospective evidence is available to guide selection of first-line maintenance therapy in patients with COPD. This pre-specified analysis of the EMAX trial explored the efficacy and safety of dual- versus mono-bronchodilator therapy in maintenance-naïve and maintenance-treated patients.

Methods: The 24-week EMAX trial evaluated lung function, symptoms (including rescue medication use), exacerbations, and safety with umeclidinium/vilanterol, umeclidinium, and salmeterol in symptomatic patients at low exacerbation risk who were not receiving inhaled corticosteroids. Maintenance-naïve and maintenance-treated subgroups were defined by maintenance bronchodilator use 30 days before screening.

Results: The analysis included 749 (31%) maintenance-naïve and 1676 (69%) maintenance-treated patients. For both subgroups, improvements from baseline in trough FEV at Week 24 (primary endpoint) were greater with umeclidinium/vilanterol versus umeclidinium (mean difference [95% CI]; maintenance-naïve: 44 mL [1, 87]; maintenance-treated: 77 mL [50, 104]), and salmeterol (maintenance-naïve: 128 mL [85, 171]; maintenance-treated: 145 mL [118, 172]), and in rescue medication inhalations/day over 24 weeks versus umeclidinium (maintenance-naïve: -0.44 [-0.73, -0.16]; maintenance-treated: -0.28 [-0.45, -0.12]) and salmeterol (maintenance-naïve: -0.37 [-0.66, -0.09]; maintenance-treated: -0.25 [-0.41, -0.08]). In maintenance-naïve patients, umeclidinium/vilanterol numerically improved scores at Week 24 for Transition Dyspnea Index versus umeclidinium (0.37 [-0.21, 0.96]) and versus salmeterol (0.47 [-0.10, 1.05]) and Evaluating Respiratory Symptoms-COPD versus umeclidinium (-0.26 [-1.04, 0.53]) and versus salmeterol (-0.58 [-1.36, 0.20]), with similar improvements seen in maintenance-treated patients. All treatments were well tolerated across both subgroups.

Conclusion: Similar to maintenance-treated patients, maintenance-naïve patients receiving umeclidinium/vilanterol showed greater improvements in lung function and symptoms compared with patients receiving umeclidinium or salmeterol. These findings provide support for the consideration of dual bronchodilator treatment in symptomatic maintenance-naïve patients with COPD.
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http://dx.doi.org/10.2147/COPD.S291751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254100PMC
June 2021

Update on Asthma-COPD Overlap (ACO): A Narrative Review.

Int J Chron Obstruct Pulmon Dis 2021 17;16:1783-1799. Epub 2021 Jun 17.

Pneumology Department, Hospital Universitari Vall d´Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.

Although chronic obstructive pulmonary disease (COPD) and asthma are well-characterized diseases, they can coexist in a given patient. The term asthma-COPD overlap (ACO) was introduced to describe patients that have clinical features of both diseases and may represent around 25% of COPD patients and around 20% of asthma patients. Despite the increasing interest in ACO, there are still substantial controversies regarding its definition and its position within clinical guidelines for patients with obstructive lung disease. In general, most definitions indicate that ACO patients must present with non-reversible airflow limitation, significant exposure to smoking or other noxious particles or gases, together with features of asthma. In patients with a primary diagnosis of COPD, the identification of ACO has therapeutic implication because the asthmatic component should be treated with inhaled corticosteroids and some studies suggest that the most severe patients may respond to biological agents indicated for severe asthma. This manuscript aims to summarize the current state-of-the-art of ACO. The definitions, prevalence, and clinical manifestations will be reviewed and some innovative aspects, such as genetics, epigenetics, and biomarkers will be addressed. Lastly, the management and prognosis will be outlined as well as the position of ACO in the COPD and asthma guidelines.
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http://dx.doi.org/10.2147/COPD.S312560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216660PMC
June 2021

Exploring PI3Kδ Molecular Pathways in Stable COPD and Following an Acute Exacerbation, Two Randomized Controlled Trials.

Int J Chron Obstruct Pulmon Dis 2021 3;16:1621-1636. Epub 2021 Jun 3.

Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK.

Background: Inhibition of phosphoinositide 3-kinase δ (PI3Kδ) exerts corrective effects on the dysregulated migration characteristics of neutrophils isolated from patients with chronic obstructive pulmonary disease (COPD).

Objective: To develop novel, induced sputum endpoints to demonstrate changes in neutrophil phenotype in the lung by administering nemiralisib, a potent and selective inhaled PI3Kδ inhibitor, to patients with stable COPD or patients with acute exacerbation (AE) of COPD.

Methods: In two randomized, double-blind, placebo-controlled clinical trials patients with A) stable COPD (N=28, randomized 3:1) or B) AECOPD (N=44, randomized 1:1) received treatment with inhaled nemiralisib (1mg). Endpoints included induced sputum at various time points before and during treatment for the measurement of transcriptomics (primary endpoint), inflammatory mediators, functional respiratory imaging (FRI), and spirometry.

Results: In stable COPD patients, the use of nemiralisib was associated with alterations in sputum neutrophil transcriptomics suggestive of an improvement in migration phenotype; however, the same nemiralisib-evoked effects were not observed in AECOPD. Inhibition of sputum inflammatory mediators was also observed in stable but not AECOPD patients. In contrast, a placebo-corrected improvement in forced expiratory volume in 1 sec of 136 mL (95% Credible Intervals -46, 315mL) with a probability that the true treatment ratio was >0% (Pr(θ>0)) of 93% was observed in AECOPD. However, FRI endpoints remained unchanged.

Conclusion: We provide evidence for nemiralisib-evoked changes in neutrophil migration phenotype in stable COPD but not AECOPD, despite improving lung function in the latter group. We conclude that induced sputum can be used for measuring evidence of alteration of neutrophil phenotype in stable patients, and our study provides a data set of the sputum transcriptomic changes during recovery from AECOPD.
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http://dx.doi.org/10.2147/COPD.S309303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184158PMC
June 2021

Isotonic quadriceps endurance is better associated with daily physical activity than quadriceps strength and power in COPD: an international multicentre cross-sectional trial.

Sci Rep 2021 Jun 2;11(1):11557. Epub 2021 Jun 2.

Department of Community Medicine and Rehabilitation, Physiotherapy, Umeå University , Umeå, Sweden.

Knowledge about modifiable determinants of daily physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) is crucial to design effective PA interventions. The present study aimed to determine the contribution of quadriceps strength, power and endurance to daily PA in COPD. Additionally, for quadriceps endurance, we also aimed to determine to what extent the association varies according to the mode of movement (isotonic, isometric, or isokinetic). Using a multicentre cross-sectional trial design we determined the contribution of quadriceps function to daily PA (steps, sedentary time and time spent doing moderate-to-very-vigorous physical activity [MVPA]) using bivariate and partial Pearson correlation analysis (r) and multiple linear regression models (ΔR). Pre-determined controlling factors were sex, age, body mass index (BMI), COPD-assessment test, forced expiratory volume in one second in percent of the predicted value (FEV), and distance walked on the 6-minute walk test. Eighty-one patients with COPD (mean ± SD: age 67 ± 8 years, FEV 57 ± 19%, daily steps 4968 ± 3319, daily sedentary time 1016 ± 305 min, and MVPA time 83 ± 45 min) were included. Small to moderate bivariate correlations (r = .225 to .452, p < .05) were found between quadriceps function and measures of PA. The best multiple linear regression models explained 38-49% of the variance in the data. Isotonic endurance was the only muscle contributor that improved all PA models; daily steps (ΔR = .04 [relative improvement 13%] p = .026), daily sedentary time (ΔR = .07 [23%], p = .005) and MVPA-minutes (ΔR = .08 [20%], p = .001). Isotonic endurance was also independently associated with most PA variables, even when controlling for strength, power or isometric-isokinetic endurance properties of the muscle (r = .246 to .384, p < .05). In contrast, neither strength, power, isometric-or isokinetic endurance properties of the muscle was independently associated with PA measures when controlling for isotonic endurance (r = .037 to .219, p > .05). To conclude, strength, power, and endurance properties of the quadriceps were low to moderately associated with PA in patients with COPD. Isotonic quadriceps endurance was the only quadriceps property that was independently associated with the different measures of PA after controlling for a basic set of known determinants of PA, quadriceps strength or power, or isometric or isokinetic quadriceps endurance. Future longitudinal studies should investigate its potential as a modifiable determinant of PA.
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http://dx.doi.org/10.1038/s41598-021-90758-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172909PMC
June 2021

Indoor air quality assessment in dwellings with different ventilation strategies in Nunavik and impacts on bacterial and fungal microbiota.

Indoor Air 2021 May 28. Epub 2021 May 28.

Département de Biochimie, Microbiologie et Bio-Informatique, Université Laval, Québec, Qc, Canada.

Indoor air quality is a major issue for public health, particularly in northern communities. In this extreme environment, adequate ventilation is crucial to provide a healthier indoor environment, especially in airtight dwellings. The main objective of the study is to assess the impact of ventilation systems and their optimization on microbial communities in bioaerosols and dust in 54 dwellings in Nunavik. Dwellings with three ventilation strategies (without mechanical ventilators, with heat recovery ventilators, and with energy recovery ventilators) were investigated before and after optimization of the ventilation systems. Indoor environmental conditions (temperature, relative humidity) and microbiological parameters (total bacteria, Aspergillus/Penicillium, endotoxin, and microbial biodiversity) were measured. Dust samples were collected in closed face cassettes with a polycarbonate filter using a micro-vacuum while a volume of 20 m of bioaerosols were collected on filters using a SASS3100 (airflow of 300 L/min). In bioaerosols, the median number of copies was 4.01 × 10 copies/m of air for total bacteria and 1.45 × 10 copies/m for Aspergillus/Penicillium. Median concentrations were 5.13 × 10 copies/mg of dust, 5.07 × 10 copies/mg, 9.98 EU/mg for total bacteria, Aspergillus/Penicillium and endotoxin concentrations, respectively. The main microorganisms were associated with human occupancy such as skin-related bacteria or yeasts, regardless of the type of ventilation.
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http://dx.doi.org/10.1111/ina.12857DOI Listing
May 2021

Physical Frailty in COPD Patients with Chronic Respiratory Failure.

Int J Chron Obstruct Pulmon Dis 2021;16:1381-1392. Epub 2021 May 17.

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

Background: The prevalence of physical frailty and its clinical characteristics in advanced chronic obstructive pulmonary disease (COPD) is unknown, as well as the usefulness of functional capacity tests to screen for physical frailty. The aim of the study was to evaluate the proportion and clinical portrait of COPD patients with chronic respiratory failure exhibiting physical frailty at the time of referral to home-based pulmonary rehabilitation. We also evaluate the usefulness of the short physical performance battery (SPPB) and timed-up and go (TUG) as potential screening tools for physical frailty. Finally, we evaluated the specific contribution of gait speed to the frailty Fried total score.

Methods: This was a prospective observational study in which physical frailty was defined using Fried criteria (body mass loss, exhaustion, low physical activity, slower walking and weakness). Clinical portrait was documented from daily physical activity, exercise tolerance, functional capacity, anxiety and depressive symptoms, health-related quality of life, and fatigue scores. The ability of the SPPB and TUG to predict physical frailty was investigated using receiver operating characteristic curves. Contribution of each Fried criteria was evaluated with a principal component analysis (PCA).

Results: Amongst the 44 included participants (FEV, 33 ± 13% of predicted), 19 were physically frail. Frail individuals had lower daily steps number, exercise tolerance and functional capacity, and higher fatigue, anxiety, and depressive symptom scores (p<0.05) compared to non-frail individuals. SPPB and TUG did not have an acceptable detection accuracy for screening physical frailty. PCA indicated that gait speed was the main contributor to the Fried total score of physical frailty.

Conclusion: Physical frailty affects a large proportion of COPD patients with chronic respiratory failure starting a home-based intervention and was associated with worse clinical status. Although the present results need to be confirmed by adequately powered studies, gait speed seems to have the potential to become a simple screening tool for physical frailty in this population.
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http://dx.doi.org/10.2147/COPD.S295885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144849PMC
July 2021

The Biobanque québécoise de la COVID-19 (BQC19)-A cohort to prospectively study the clinical and biological determinants of COVID-19 clinical trajectories.

PLoS One 2021 19;16(5):e0245031. Epub 2021 May 19.

Department of Human Genetics, Faculty of Medicine, McGill University, Montreal, QC, Canada.

SARS-CoV-2 infection causing the novel coronavirus disease 2019 (COVID-19) has been responsible for more than 2.8 million deaths and nearly 125 million infections worldwide as of March 2021. In March 2020, the World Health Organization determined that the COVID-19 outbreak is a global pandemic. The urgency and magnitude of this pandemic demanded immediate action and coordination between local, regional, national, and international actors. In that mission, researchers require access to high-quality biological materials and data from SARS-CoV-2 infected and uninfected patients, covering the spectrum of disease manifestations. The "Biobanque québécoise de la COVID-19" (BQC19) is a pan-provincial initiative undertaken in Québec, Canada to enable the collection, storage and sharing of samples and data related to the COVID-19 crisis. As a disease-oriented biobank based on high-quality biosamples and clinical data of hospitalized and non-hospitalized SARS-CoV-2 PCR positive and negative individuals. The BQC19 follows a legal and ethical management framework approved by local health authorities. The biosamples include plasma, serum, peripheral blood mononuclear cells and DNA and RNA isolated from whole blood. In addition to the clinical variables, BQC19 will provide in-depth analytical data derived from the biosamples including whole genome and transcriptome sequencing, proteome and metabolome analyses, multiplex measurements of key circulating markers as well as anti-SARS-CoV-2 antibody responses. BQC19 will provide the scientific and medical communities access to data and samples to better understand, manage and ultimately limit, the impact of COVID-19. In this paper we present BQC19, describe the process according to which it is governed and organized, and address opportunities for future research collaborations. BQC19 aims to be a part of a global communal effort addressing the challenges of COVID-19.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245031PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133500PMC
June 2021

Treatment of COPD with Long-Acting Bronchodilators: Association Between Early and Longer-Term Clinically Important Improvement.

Int J Chron Obstruct Pulmon Dis 2021;16:1215-1226. Epub 2021 May 3.

Global Specialty & Primary Care, GSK, Brentford, Middlesex, UK.

Introduction: This post hoc analysis of the "Early MAXimization of bronchodilation for improving COPD stability" (EMAX) trial investigated whether patients achieving early clinically important improvement (CII) sustained longer-term improvements and lower risk of clinically important deterioration (CID).

Methods: Patients were randomized to umeclidinium/vilanterol, umeclidinium, or salmeterol for 24 weeks. The patient-reported outcomes (PROs) Transition Dyspnea Index (TDI), Evaluating Respiratory Symptoms, St George's Respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) were assessed. CII, defined as attaining minimum clinically important differences (MCID) in ≥2 PROs, was assessed at Weeks 4, 12 and 24. CID was defined as a deterioration in CAT, SGRQ, TDI by the MCID and/or a moderate/severe exacerbation from Day 30.

Results: Of 2425 patients, 50%, 53% and 51% achieved a CII at Weeks 4, 12 and 24, respectively. Patients with a CII at Week 4 versus those without had significantly greater odds of achieving a CII at Weeks 12 and 24 (odds ratio: 5.57 [95% CI: 4.66, 6.66]; 4.09 [95% CI: 3.44, 4.86]). The risk of a CID was higher in patients who did not achieve a CII at Week 4 compared with patients who did (hazard ratio [95% CI]: 2.09 [1.86, 2.34]). Patients treated with umeclidinium/vilanterol versus either monotherapy had significantly greater odds of achieving CII at Weeks 4, 12 and 24.

Conclusion: Achieving a CII at Week 4 was associated with longer-term improvement in PROs and a reduced risk of deterioration. Further research is required to investigate the importance of an early response to treatment on the long-term disease course.
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http://dx.doi.org/10.2147/COPD.S295835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106450PMC
July 2021

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

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;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
June 2021

Specific Contribution of Quadriceps Muscle Strength, Endurance, and Power to Functional Exercise Capacity in People With Chronic Obstructive Pulmonary Disease: A Multicenter Study.

Phys Ther 2021 Jun;101(6)

Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, 2725 Chemin Sainte-Foy, Québec, G1V 4G5, Canada.

Objective: Various functional muscle properties affect different aspects of functional exercise capacity in people with chronic obstructive pulmonary disease (COPD). The purpose of this study was to investigate the contribution of quadriceps muscle strength, endurance, and power to 6-Minute Walking Distance (6MWD) and 1-minute sit-to-stand test (1STS) performance in people with COPD.

Methods: The study was a prospective, multicenter, cross-sectional study. Anthropometrics, Medical Research Council dyspnea scale, lung function, 6MWD, and 1STS number of repetitions were assessed. Isometric quadriceps strength and endurance, isotonic quadriceps endurance, isokinetic quadriceps strength, and power were assessed on a computerized dynamometer while functional quadriceps power was determined during 5 sit-to-stand repetitions. Univariate and multivariate analyses were performed to determine the contribution of functional muscle properties to the 6MWD and the 1STS number of repetitions.

Results: The study included 70 people with COPD (mean % predicted forced expiratory volume in 1 second = 58.9 [SD = 18.2]). The 6MWD correlated with each functional muscle property except the isometric quadriceps endurance. The number of repetitions during the 1STS correlated with each functional muscle property except isometric measurements. Multivariate models explained 60% and 39% of the variance in the 6MWD and 1STS number of repetitions, respectively, with quadriceps power determined during 5 sit-to-stand repetitions being the muscle functional property with the strongest contribution to the models.

Conclusion: Except for isometric endurance, quadriceps strength, endurance, and power were associated with functional exercise capacity in people with moderate COPD. Among these functional muscle properties, muscle power contributed the most to the 6MWD and 1STS number of repetitions, suggesting that muscle power is more relevant to functional exercise capacity than muscle strength or endurance in people with COPD.

Impact: Understanding the individual contribution of muscle properties to functional status is important to designing interventions. This study provides the guidance that muscle power may be more important to functional exercise capacity than muscle strength or endurance in people with COPD.
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http://dx.doi.org/10.1093/ptj/pzab052DOI Listing
June 2021

Randomized Trial of Nocturnal Oxygen in Chronic Obstructive Pulmonary Disease. Reply.

N Engl J Med 2021 01;384(1):86

Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, QC, Canada

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http://dx.doi.org/10.1056/NEJMc2032006DOI Listing
January 2021

Effects of Low-Load/High-Repetition Resistance Training on Exercise Capacity, Health Status, and Limb Muscle Adaptation in Patients With Severe COPD: A Randomized Controlled Trial.

Chest 2021 May 13;159(5):1821-1832. Epub 2020 Dec 13.

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

Background: Training volume is paramount in the magnitude of physiological adaptations following resistance training. However, patients with severe COPD are limited by dyspnea during traditional two-limb low-load/high-repetition resistance training (LLHR-RT), resulting in suboptimal training volumes. During a single exercise session, single-limb LLHR-RT decreases the ventilatory load and enables higher localized training volumes compared with two-limb LLHR-RT.

Research Question: Does single-limb LLHR-RT lead to more profound effects compared with two-limb LLHR-RT on exercise capacity (6-min walk distance [6MWD]), health status, muscle function, and limb adaptations in patients with severe COPD?

Study Design And Methods: Thirty-three patients (mean age 66 ± 7 years; FEV 39 ± 10% predicted) were randomized to 8 weeks of single- or two-limb LLHR-RT. Exercise capacity (6MWD), health status, and muscle function were compared between groups. Quadriceps muscle biopsy specimens were collected to examine physiological responses.

Results: Single-limb LLHR-RT did not further enhance 6MWD compared with two-limb LLHR-RT (difference, 14 [-12 to 39 m]. However, 73% in the single-limb group exceeded the known minimal clinically important difference of 30 m compared with 25% in the two-limb group (P = .02). Health status and muscle function improved to a similar extent in both groups. During training, single-limb LLHR-RT resulted in a clinically relevant reduction in dyspnea during training compared with two-limb LLHR-RT (-1.75; P = .01), but training volume was not significantly increased (23%; P = .179). Quadriceps muscle citrate synthase activity (19%; P = .03), hydroxyacyl-coenzyme A dehydrogenase protein levels (32%; P < .01), and capillary-to-fiber ratio (41%; P < .01) were increased compared with baseline after pooling muscle biopsy data from all participants.

Interpretation: Single-limb LLHR-RT did not further increase mean 6MWD compared with two-limb LLHR-RT, but it reduced exertional dyspnea and enabled more people to reach clinically relevant improvements in 6MWD. Independent of execution strategy, LLHR-RT improved exercise capacity, health status, muscle endurance, and enabled several physiological muscle adaptations, reducing the negative consequences of limb muscle dysfunction in COPD.

Clinical Trial Registration: ClinicalTrials.gov; No.: NCT02283580; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2020.12.005DOI Listing
May 2021

Effects of Tiotropium/Olodaterol on Activity-Related Breathlessness, Exercise Endurance and Physical Activity in Patients with COPD: Narrative Review with Meta-/Pooled Analyses.

Adv Ther 2021 02 11;38(2):835-853. Epub 2020 Dec 11.

Kingston General Hospital, Kingston, ON, Canada.

One of the most debilitating symptoms of chronic obstructive pulmonary disease (COPD) is breathlessness, which leads to avoidance of physical activities in daily living and hastens clinical deterioration. Treatment of patients with COPD with inhaled long-acting muscarinic antagonist (LAMA)/long-acting β-agonist (LABA) combination therapy improves airflow limitation, reduces breathlessness compared with LAMA or LABA monotherapies, and improves health status and quality of life. A large clinical trial programme focusing on the effects of tiotropium/olodaterol combination therapy demonstrated that this LAMA/LABA combination improves lung function and reduces hyperinflation (assessed by serial inspiratory capacity measurements) compared with either tiotropium alone or placebo in patients with COPD. Tiotropium/olodaterol also increases exercise endurance capacity and improves patient perception of the intensity of breathlessness compared with placebo. In this narrative review, we focus on the relationship between improving symptoms during activity, the ability to remain active in daily life and how this may impact quality of life. We consider the benefits of therapy optimisation by means of dual bronchodilation with tiotropium/olodaterol, and present new data from meta-analyses/pooled analyses showing that tiotropium/olodaterol improves inspiratory capacity compared with placebo and tiotropium and improves exercise endurance time compared with placebo after 6 weeks of treatment. We also discuss the importance of taking a holistic approach to improving physical activity, including pulmonary rehabilitation and exercise programmes in parallel with bronchodilator therapy and psychological programmes to support behaviour change.
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http://dx.doi.org/10.1007/s12325-020-01557-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889690PMC
February 2021

Asthma with Irreversible Airway Obstruction in Smokers and Nonsmokers: Links between Airway Inflammation and Structural Changes.

Respiration 2020 Dec 8:1-11. Epub 2020 Dec 8.

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

Background: The development of irreversible airway obstruction (IRAO) in asthma is related to lung/airway inflammatory and structural changes whose characteristics are likely influenced by exposure to tobacco smoke.

Objective: To investigate the interplay between airway and lung structural changes, airway inflammation, and smoking exposure in asthmatics with IRAO.

Methods: We studied asthmatics with IRAO who were further classified according to their smoking history, those with ≥20 pack-years of tobacco exposure (asthmatics with smoking-related IRAO [AwS-IRAO]) and those with <5 pack-years of tobacco exposure (asthmatics with nonsmoking-related IRAO [AwNS-IRAO]). In addition to recording baseline clinical and lung function features, all patients had a chest computed tomography (CT) from which airway wall thickness was measured and quantitative and qualitative assessment of emphysema was performed. The airway inflammatory profile was documented from differential inflammatory cell counts on induced sputum.

Results: Ninety patients were recruited (57 AwS-IRAO and 33 AwNS-IRAO). There were no statistically significant differences in the extent of emphysema and gas trapping between groups on quantitative chest CT analysis, although Pi10, a marker of airway wall thickness, was significantly higher in AwS-IRAO (p = 0.0242). Visual analysis showed a higher prevalence of emphysema (p = 0.0001) and higher emphysema score (p < 0.0001) in AwS-IRAO compared to AwNS-IRAO and distribution of emphysema was different between groups. Correlations between radiological features and lung function were stronger in AwS-IRAO. In a subgroup analysis, we found a correlation between airway neutrophilia and emphysematous features in AwS-IRAO and between eosinophilia and both airway wall thickness and emphysematous changes in AwNS-IRAO.

Conclusions: Although bronchial structural changes were relatively similar in smoking and nonsmoking patients with asthma and IRAO, emphysematous changes were more predominant in smokers. However, neutrophils in AwS-IRAO and eosinophils in AwNS-IRAO were associated with lung and airway structural changes.
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http://dx.doi.org/10.1159/000508163DOI Listing
December 2020

Long-term safety of tiotropium/olodaterol in older patients with moderate-to-very-severe COPD in the TONADO® studies.

NPJ Prim Care Respir Med 2020 12 4;30(1):53. Epub 2020 Dec 4.

Pulmonary Department, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, D-55131, Mainz, Germany.

Older patients with chronic obstructive pulmonary disease (COPD) may be at increased risk of adverse events (AEs) due to decreased protective organ function and increased comorbidities. TONADO® 1 + 2 were replicate, randomized, double-blind, parallel-group, 52-week, Phase III trials comparing the efficacy and safety of tiotropium/olodaterol (5/5 µg) versus the monocomponents via the Respimat® inhaler in patients with moderate-to-very-severe COPD. In this prespecified safety analysis, patients were grouped by age. Of 3100 patients, 1585 (51.1%) were aged <65 years, 1198 (38.7%) 65-<75 years, 309 (10.0%) 75-<85 years, and eight (0.3%) ≥85 years. At baseline, 23.4% had a pre-existing cardiac disorder, 45.6% had hypertension, and 13.3% had glucose metabolism disorders, including diagnosed diabetes. Overall, there was no increase in major adverse cardiac events, other AEs, or serious AEs with tiotropium/olodaterol versus the monocomponents in any age group, supporting the safety of tiotropium/olodaterol in older patients with COPD.
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http://dx.doi.org/10.1038/s41533-020-00212-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719164PMC
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

Impact of baseline COPD symptom severity on the benefit from dual mono-bronchodilators: an analysis of the EMAX randomised controlled trial.

Ther Adv Respir Dis 2020 Jan-Dec;14:1753466620968500

Centre de Pneumologie, Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec, Québec, Canada.

Rationale: Symptom relief is a key treatment goal in patients with chronic obstructive pulmonary disease (COPD). However, there are limited data available on the response to bronchodilator therapy in patients at low risk of exacerbations with different levels of symptom severity. This study compared treatment responses in patients with a range of symptom severities as indicated by baseline COPD assessment test (CAT) scores.

Methods: The 24-week EMAX trial evaluated the benefits of umeclidinium/vilanterol umeclidinium or salmeterol in symptomatic patients at low exacerbation risk who were not receiving inhaled corticosteroids. This analysis assessed lung function, symptoms, health status, and short-term deterioration outcomes in subgroups defined by a baseline CAT score [<20 () and ⩾20 (pre-specified)]. Outcomes were also assessed using fractional polynomial modelling with continuous transformations of baseline CAT score covariates.

Results: Of the intent-to-treat population ( = 2425), 56% and 44% had baseline CAT scores of <20 and ⩾20, respectively. Umeclidinium/vilanterol demonstrated favourable improvements compared with umeclidinium and salmeterol for the majority of outcomes irrespective of the baseline CAT score, with the greatest improvements generally observed in patients with CAT scores <20. Fractional polynomial analyses revealed consistent improvements in lung function, symptoms and reduction in rescue medication use with umeclidinium/vilanterol umeclidinium and salmeterol across a range of CAT scores, with the largest benefits seen in patients with CAT scores of approximately 10-21.

Conclusions: Patients with symptomatic COPD benefit similarly from dual bronchodilator treatment with umeclidinium/vilanterol. Fractional polynomial analyses demonstrated the greatest treatment differences favouring dual therapy in patients with a CAT score <20, although benefits were seen up to scores of 30. This suggests that dual bronchodilation may be considered as initial therapy for patients across a broad range of symptom severities, not only those with severe symptoms (CAT ⩾20). NCT03034915, 2016-002513-22 (EudraCT number).
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http://dx.doi.org/10.1177/1753466620968500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659027PMC
November 2020

The Clinical Utility of Determining the Allelic Background of Mutations Causing Alpha-1 Antitrypsin Deficiency: The Case with the Null Variant Q0(Mattawa)/Q0(Ourém).

Chronic Obstr Pulm Dis 2021 Jan;8(1)

Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Québec, QC, Canada.

Background: Alpha-1 antitrypsin deficiency (AATD) is caused by genetic variants in the gene conferring risk of developing emphysema. The clinical expression of AATD-related emphysema mostly occurs in carriers of 2 deficient alleles. By DNA sequencing of , numerous rare variants have been identified. Clarifying whether 2 mutations observed in 1 patient are on the same or distinct alleles has obvious clinical implications.

Methods: We studied 7 carriers of a rare variant, Leu353Phe_fsTer24, known to lead to undetectable serum levels of AAT. Two of them were also carriers of the S or Z allele. We developed an allele-specific DNA sequencing method to characterize the allelic background of the Leu353Phe_fsTer24 variant.

Results: The Leu353Phe_fsTer24 variant was transmitted on the same allele as the M3 variant (E376D) in all patients. This mutation is thus named Q0 on the conventional PI system. We demonstrated that individuals harboring the E264V (S) and E342K (Z) mutations had them on distinct alleles from Q0 and are, thus, compound heterozygotes. The 7 Q0 carriers had AAT levels ranging from 0.18g/l to 0.82g/l. The lowest AAT serum levels were observed in compound heterozygotes (S/Q0 and Z/Q0) suggesting higher risk of developing emphysema.

Conclusion: For the 7 patients, Leu353Phe_fsTer24 is transmitted on the M3 background and they are, thus, carriers of the Q0 allele. Allele-specific DNA sequencing was useful to distinguish 1 or 2 deficient alleles in carriers of 2 mutations. In rare cases, this method is important to understand the clinical significance of genetic variants found in .
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http://dx.doi.org/10.15326/jcopdf.8.1.2020.0168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047621PMC
January 2021

Long-Term Effectiveness of a Home-Based Pulmonary Rehabilitation in Older People with Chronic Obstructive Pulmonary Disease: A Retrospective Study.

Int J Chron Obstruct Pulmon Dis 2020 15;15:2505-2514. Epub 2020 Oct 15.

FormAction Santé, Pérenchies, France.

Background: Long-term effectiveness of pulmonary rehabilitation (PR) is still uncertain in older people with severe chronic obstructive pulmonary disease (COPD). The objective was to compare the effects of home-based PR in people with COPD above and below the age of 70 years.

Methods: In this retrospective study, 480 people with COPD were recruited and divided into those ≤70 (n=341) and those >70 years of age (n=139). All participants underwent an 8 weeks of home-based PR, consisting of a weekly supervised 90-minute home session. Six-minute stepper test (6MST), timed-up and go test (TUG), Hospital Anxiety and Depression Scale, and Visual Simplified Respiratory Questionnaire (VSRQ) were assessed at baseline (M0), at 2 (M2), 8 (M8), 14 (M14) months after baseline.

Results: The older group was described by fewer current smokers (p <0.001), more long-term oxygen therapy use (p = 0.024), higher prevalence of comorbidities (p<0.001), lower 6MST score and higher TUG score (p<0.001), compared to the younger group. Both groups improved every outcome at M2 compared to baseline. At M2, 88% of people ≤70 years of age and 79% of those above 70 were considered as responders in at least one evaluated parameter (p = 0.013). Both groups maintained the benefits at M14, except for the VSRQ score and the number of responders to this outcome in the older group.

Conclusion: Regardless of the age, personalized home-based PR was effective for people with COPD in the short term. Above 70 years, an ageing effect appeared on the long-term effectiveness of quality of life benefit.
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http://dx.doi.org/10.2147/COPD.S268901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571583PMC
June 2021

Effect of once-daily fluticasone furoate/vilanterol vilanterol alone on bone mineral density in patients with COPD: a randomized, controlled trial.

Ther Adv Respir Dis 2020 Jan-Dec;14:1753466620965145

Research and Development, GlaxoSmithKline plc., Research Triangle Park, NC, USA.

Background: The relationship between inhaled corticosteroids and bone mineral density (BMD) remains uncertain despite extensive research.

Methods: This was an international, multicenter, randomized, double-blind, parallel-group, 3-year noninferiority study. Patients with chronic obstructive pulmonary disease (COPD) (⩾40 years of age; smoking history ⩾10 pack years) and at least one native hip evaluable for BMD were enrolled and randomized 1:1, stratified by sex, to treatment with vilanterol (VI) 25 µg or fluticasone furoate/vilanterol (FF/VI) 100 µg/25 µg. BMD measurements were taken dual-energy X-ray absorptiometry every 6 months. The primary endpoint was assessment of the noninferiority of change from baseline in total hip BMD per year at the -1% noninferiority level. Change from baseline in BMD at the lumbar spine and BMD measurements by sex were secondary endpoints. Incidences of COPD exacerbations and bone fractures throughout the study were also recorded.

Results: Of 283 randomized patients, 170 (60%) completed the study. Noninferiority was demonstrated for FF/VI VI with regards to change from baseline in total hip BMD per year, with changes of -0.27% and 0.18%, respectively, and a treatment difference of -0.46% per year [95% confidence interval (CI) -0.97 to 0.06]. The treatment difference for FF/VI VI regarding lumbar spine BMD was -0.51% per year (95% CI -1.11 to 0.10). COPD exacerbations and bone fracture rates were similar between treatment groups.

Conclusion: FF/VI showed noninferiority to VI for change from baseline in total hip BMD per year, when assessed at the -1% noninferiority margin in a combined sample of men and women with COPD.
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http://dx.doi.org/10.1177/1753466620965145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798365PMC
October 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

Relieving exertional dyspnea during the 3-min constant speed shuttle test in patients with COPD with indacaterol/glycopyrronium tiotropium: the RED trial.

Ther Adv Respir Dis 2020 Jan-Dec;14:1753466620939507

Centre de pneumologie, Institut universitaire de cardiologie et de pneumologie de Québec, 2725 chemin Ste-Foy, QC G1V 4G5, Canada.

Background: Exertional dyspnea is a cardinal feature of chronic obstructive pulmonary disease (COPD) and a major cause of activity limitation. Although dual bronchodilation is more effective than bronchodilator monotherapy at improving resting pulmonary function, it is unclear to which extent this translates into superior relief of exertional dyspnea.

Methods: We conducted a randomized controlled, double-blind, cross-over trial comparing indacaterol 110 µg/glycopyrronium 50 µg once daily (OD) with tiotropium 50 µg OD in patients with moderate to severe COPD and resting hyperinflation (functional residual capacity >120% of predicted value). The primary outcome was Borg dyspnea score at the end of a 3-min constant speed shuttle test after 3 weeks of treatment. Secondary outcomes included changes in Borg dyspnea score after the first dose of study medication, expiratory flows and lung volumes. Statistical analysis was conducted using a cross-over analysis of variance model with repeated measurements.

Results: A total of 50 patients with COPD and a mean forced expiratory volume in 1 s of 54 ± 11% (mean ± SEM) predicted participated in the cross-over phase of the trial. Compared with baseline, there was a decrease in dyspnea after the first dose of medication with indacaterol/glycopyrronium [mean -1.00, 95% confidence interval (CI) -1.49 to -0.52] but not with tiotropium alone (mean -0.36, 95% CI -0.81 to 0.08). The reduction in dyspnea after the first dose was statistically significant between the two treatments (mean difference of -0.64, 95% CI -1.11 to -0.17). Despite indacaterol/glycopyrronium providing further bronchodilation and lung deflation throughout the trial, the reduction in dyspnea was not sustained at 3 weeks of treatment (mean between-treatment difference at 3 weeks of 0.09, 95% CI -0.44 to 0.61).

Conclusion: In comparison with bronchodilator monotherapy, indacaterol/glycopyrronium provided greater immediate exertional dyspnea relief, although this difference was not sustained after 3 weeks of therapy despite evidence of further bronchodilation and lung deflation.
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http://dx.doi.org/10.1177/1753466620939507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361488PMC
July 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

Validation and Cardiorespiratory Response of the 1-Min Sit-to-Stand Test in Interstitial Lung Disease.

Med Sci Sports Exerc 2020 12;52(12):2508-2514

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

Purpose: To assess the 1-min sit-to-stand test (1STS) test-retest reliability and construct validity and its associated cardiorespiratory response in comparison to the 6-min walk test (6MWT) and symptom-limited cycling cardiopulmonary exercise test (CPET) in people with interstitial lung disease (ILD).

Methods: Fifteen participants with ILD performed two 1STS tests, a 6MWT and a CPET. The three tests were administered on three separate visits, and cardiorespiratory parameters were continuously recorded during the tests.

Results: The number of repetitions during both 1STS tests was 22 ± 4 and 22 ± 4 (mean difference of 0.53 ± 2.00 repetitions, P = 0.32) with an intraclass correlation of 0.937 (95% confidence interval, 0.811-0.979]) and a minimal detectable change of 2.9 repetitions. The number of 1STS repetitions was highly correlated with the 6MWT distance (r = 0.823, P < 0.001) and with the peak cycling power output expressed in % predicted values (r = 0.706, P < 0.003). Oxygen consumption (V˙O2) peak during the 1STS reached 83% and 78% of V˙O2 peak during 6MWT and CPET, respectively. Peak 1STS HR, minute ventilation (V˙E,), V˙O2 values, as well as nadir SpO2 were achieved during the recovery phase of the test, whereas peak 6MWT and CPET HR, V˙E, V˙O2 and nadir SpO2 always occurred at the end of the test. The three tests elicited a similar fall in SpO2 ranging between 8% and 12%. Symptom scores after the 1STS were similar to those seen at the end of the 6MWT but lower than those of CPET.

Conclusions: The 1STS showed excellent test-retest reliability in patients with ILD in whom it elicited a substantial, but submaximal cardiorespiratory response. Our data also support the construct validity of the 1STS to assess functional exercise capacity in patients with ILD and to detect exercise-induced O2 desaturation.
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http://dx.doi.org/10.1249/MSS.0000000000002423DOI Listing
December 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
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