Clinical implementation of automated O2 titration in a tertiary care hospital.

Background: When treating acute respiratory failure, both hypoxemia and hyperoxemia should be avoided. SpO2 should be monitored closely and O2 flows adjusted accordingly. Achieving this goal might be easier with automated O2 titration compared to manual titration of fixed-flow O2 We evaluated the feasibility of using an automated O2 titration device in subjects treated for acute hypoxemic respiratory failure in a tertiary care hospital.Methods: Healthcare workers received education and training about oxygen therapy and were familiarized with an automated O2 titration device (FreeO2, Oxynov, Quebec City, Canada). A coordinator was available from 8 am to 5 pm during week days to provide technical assistance. The ability of the device to maintain SpO2 within the prescribed therapeutic window was recorded. Basic clinical information was recorded.Results: Subjects were enrolled from November 2020 to August 2022. We trained 508 healthcare workers on use of automated O2 titration which was finally used on 872 occasions in 763 subjects, distributed on the respiratory, COVID-19 and thoracic surgery wards and the emergency room. Clinical information could be retrieved for 609 (80%) subjects who were on the system for a median of 3 days (interquartile range: 2 to 6 days) representing 2567 subject-days of clinical experience with the device. In the 82 (14%) subjects for whom this information was available, the system maintained SpO2 within the prescribed targets 89% of the time. Ninety-six subjects experienced clinical deterioration as defined by the need to be transferred to the intensive care unit and/or requirement of high nasal flow oxygen but none of these events were judged to be related to the O2 device.Conclusions: Automated O2 titration could be successfully implemented in hospitalized subjects with hypoxemic respiratory failure from various causes. This experience should foster further improvement of the device and recommendations for an optimized utilization.

Haemodynamic compensations for exercise tissue oxygenation in early stages of COPD: an integrated cardiorespiratory assessment study.

BACKGROUND: Cardiovascular comorbidities are increasingly being recognised in early stages of chronic obstructive pulmonary disease (COPD) yet complete cardiorespiratory functional assessments of individuals with mild COPD or presenting with COPD risk factors are lacking. This paper reports on the effectiveness of the cardiocirculatory-limb muscles oxygen delivery and utilisation axis in smokers exhibiting no, or mild to moderate degrees of airflow obstruction using standardised cardiopulmonary exercise testing (CPET). METHODS: Post-bronchodilator spirometry was used to classify participants as 'ever smokers without' (n=88), with 'mild' (n=63) or 'mild-moderate' COPD (n=56). All underwent CPET with continuous concurrent monitoring of oxygen uptake (V'O2) and of bioimpedance cardiac output (Qc) enabling computation of arteriovenous differences (a-vO2). Mean values of Qc and a-vO2 were mapped across set ranges of V'O2 and Qc isolines to allow for meaningful group comparisons, at same metabolic and circulatory requirements. RESULTS: Peak exercise capacity was significantly reduced in the 'mild-moderate COPD' as compared with the two other groups who showed similar pulmonary function and exercise capacity. Self-reported cardiovascular and skeletal muscle comorbidities were not different between groups, yet disease impact and exercise intolerance scores were three times higher in the 'mild-moderate COPD' compared with the other groups. Mapping of exercise Qc and a-vO2 also showed a leftward shift of values in this group, indicative of a deficit in peripheral O2 extraction even for submaximal exercise demands. Concurrent with lung hyperinflation, a distinctive blunting of exercise stroke volume expansion was also observed in this group. CONCLUSION: Contrary to the traditional view that cardiovascular complications were the hallmark of advanced disease, this study of early COPD spectrum showed a reduced exercise O2 delivery and utilisation in individuals meeting spirometry criteria for stage II COPD. These findings reinforce the preventive clinical management approach to preserve peripheral muscle circulatory and oxidative capacities.

Airway tree caliber heterogeneity and airflow obstruction among older adults.

Smaller mean airway tree caliber is associated with airflow obstruction and chronic obstructive pulmonary disease (COPD). We investigated whether airway tree caliber heterogeneity was associated with airflow obstruction and COPD. Two community-based cohorts (MESA Lung, CanCOLD) and a longitudinal case-control study of COPD (SPIROMICS) performed spirometry and computed tomography measurements of airway lumen diameters at standard anatomical locations (trachea-to-subsegments) and total lung volume. Percent-predicted airway lumen diameters were calculated using sex-specific reference equations accounting for age, height, and lung volume. The association of airway tree caliber heterogeneity, quantified as the standard deviation (SD) of percent-predicted airway lumen diameters, with baseline forced expired volume in 1-second (FEV1), FEV1/forced vital capacity (FEV1/FVC) and COPD, as well as longitudinal spirometry, were assessed using regression models adjusted for age, sex, height, race-ethnicity, and mean airway tree caliber. Among 2,505 MESA Lung participants (means ± SD age: 69 ± 9 yr; 53% female, mean airway tree caliber: 99 ± 10% predicted, airway tree caliber heterogeneity: 14 ± 5%; median follow-up: 6.1 yr), participants in the highest quartile of airway tree caliber heterogeneity exhibited lower FEV1 (adjusted mean difference: -125 mL, 95%CI: -171,-79), lower FEV1/FVC (adjusted mean difference: -0.01, 95%CI: -0.02,-0.01), and higher odds of COPD (adjusted odds ratio: 1.42, 95%CI: 1.01-2.02) when compared with the lowest quartile, whereas longitudinal changes in FEV1 and FEV1/FVC did not differ significantly. Observations in CanCOLD and SPIROMICS were consistent. Among older adults, airway tree caliber heterogeneity was associated with airflow obstruction and COPD at baseline but was not associated with longitudinal changes in spirometry.NEW & NOTEWORTHY In this study, by leveraging two community-based samples and a case-control study of heavy smokers, we show that among older adults, airway tree caliber heterogeneity quantified by CT is associated with airflow obstruction and COPD independent of age, sex, height, race-ethnicity, and dysanapsis. These observations suggest that airway tree caliber heterogeneity is a structural trait associated with low baseline lung function and normal decline trajectory that is relevant to COPD.

Ozanimod Therapy in Patients With COVID-19 Requiring Oxygen Support: A Randomized Open-Label Pilot Trial.

BACKGROUND: Sphingosine-1-phosphate receptor ligands (SRLs) dampen immunopathologic damages in models of viral pneumonia. RESEARCH QUESTION: Is it feasible to administer an SRL therapy, here ozanimod (OZA), to acutely ill patients infected with SARS-CoV-2? STUDY DESIGN AND METHODS: The prospective randomized open-label COVID-19 Ozanimod Intervention (COZI) pilot trial was conducted in three Canadian hospitals. Patients admitted for COVID-19 requiring oxygen were eligible. Randomization was stratified for risk factors of poor outcome and oxygen needs at inclusion. Participants were allocated to standard of care or to standard of care plus OZA. OZA (oral, once daily, incremental dosage) was administered for a maximum of 14 days. Primary end point investigated for size effect and variance over time was the assessment of safety and efficacy, evaluated by the daily score on the World Health Organization-adapted six-point ordinal scale for clinical improvement analyzed under the intention-to-treat principle. RESULTS: Twenty-three patients were randomized to the standard of care arm, and 20 were randomized to the OZA arm from September 2020 to February 2022. Evaluation of efficacy showed nonsignificant reductions of median (interquartile range) duration of respiratory support (6 [3-10] vs 9 [4-12] days; P = .34), median duration of hospitalization (9 [6-12] vs 10 [6-18] days; P = .20), and median time to clinical improvement (4 [3-7] vs 7 [3-11] days; P = .12) for OZA compared with standard of care, respectively. Heart rate was significantly lower with OZA (65 [ 63-67] vs 71 [69-72] beats/min; P < .0001). However, QT and PR intervals were not affected. No severe adverse drug reaction was reported. INTERPRETATION: To our knowledge, SRL utility in severe pneumonia has never been tested in patients. This study shows for the first time that this new pharmacologic agent may safely be administered to patients hospitalized for viral pneumonia, with potential clinical benefits. Bradycardia was frequent but well tolerated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04405102; URL: www. CLINICALTRIALS: gov.

Validation of Constant Work Rate Cycling Endurance Time for Use in Chronic Obstructive Pulmonary Disease Clinical Trials.

Rationale: A COPD Foundation working group sought to identify measures of exercise endurance, a meaningful aspect of physical functioning in everyday life among patients with chronic obstructive pulmonary disease (COPD) that is not fully accepted in regulatory decision making, hampering drug development. Objectives: To demonstrate, as we previously asserted (Casaburi COPD 2022;9:252), that constant work rate cycling endurance time is an appropriate exercise endurance measure in patients with COPD. Methods: To validate this assertion, we assembled an integrated database of endurance time responses, including 8 bronchodilator (2,166 subjects) and 15 exercise training (3,488 subjects) studies (Casaburi COPD 2022;9:520). Results: Construct validity was demonstrated: 1) peak physiologic and perceptual responses were similar for constant work rate and incremental cycling; 2) after bronchodilator therapy, there were greater increases in endurance time in patients with more severe airflow limitation; 3) after exercise training, endurance time increases were similar across airflow limitation severities; and 4) there were correlations between changes in endurance time and changes in mechanistically related physiologic and perceptual variables. Test-retest reliability was demonstrated, with consistency of changes in endurance time at two time points after the intervention. Responsiveness was confirmed, with significant increases in endurance time after active (but not placebo) bronchodilator therapy, with greater increases seen with more severe airflow limitation and after exercise training. On the basis of regression analysis using multiple anchor variables, the minimum important difference for endurance time increase is estimated to be approximately 1 minute. Conclusions: Constant work rate cycling endurance time is a valid exercise endurance measure in COPD, suitable for contributing to the evaluation of treatment benefit supporting regulatory decision making and evidence-based therapeutic recommendations.

Distinctive features of the oropharyngeal microbiome in Inuit of Nunavik and correlations of mild to moderate bronchial obstruction with dysbiosis.

Inuit of Nunavik are coping with living conditions that can influence respiratory health. Our objective was to investigate associations between respiratory health in Inuit communities and their airway microbiome. Oropharyngeal samples were collected during the Qanuilirpitaa? 2017 Inuit Health Survey and subjected to metagenomic analyses. Participants were assigned to a bronchial obstruction group or a control group based on their clinical history and their pulmonary function, as monitored by spirometry. The Inuit microbiota composition was found to be distinct from other studied populations. Within the Inuit microbiota, differences in diversity measures tend to distinguish the two groups. Bacterial taxa found to be more abundant in the control group included candidate probiotic strains, while those enriched in the bronchial obstruction group included opportunistic pathogens. Crossing taxa affiliation method and machine learning consolidated our finding of distinct core microbiomes between the two groups. More microbial metabolic pathways were enriched in the control participants and these were often involved in vitamin and anti-inflammatory metabolism, while a link could be established between the enriched pathways in the disease group and inflammation. Overall, our results suggest a link between microbial abundance, interactions and metabolic activities and respiratory health in the Inuit population.

How can the findings of the EMAX trial on long-acting bronchodilation in chronic obstructive pulmonary disease be applied in the primary care setting?

This review addresses outstanding questions regarding initial pharmacological management of chronic obstructive pulmonary disease (COPD). Optimizing initial treatment improves clinical outcomes in symptomatic patients, including those with low exacerbation risk. Long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) dual therapy improves lung function versus LAMA or LABA monotherapy, although other treatment benefits have been less consistently observed. The benefits of dual bronchodilation in symptomatic patients with COPD at low exacerbation risk, and its duration of efficacy and cost effectiveness in this population, are not yet fully established. Questions remain on the impact of baseline symptom severity, prior treatment, degree of reversibility to bronchodilators, and smoking status on responses to dual bronchodilator treatment. Using evidence from EMAX (NCT03034915), a 6-month trial comparing the LAMA/LABA combination umeclidinium/vilanterol with umeclidinium and salmeterol monotherapy in symptomatic patients with COPD at low exacerbation risk who were inhaled corticosteroid-naïve, we describe how these findings can be applied in primary care.

2023 Canadian Thoracic Society Guideline on Pharmacotherapy in Patients With Stable COPD.

Chronic obstructive pulmonary disease patient care must include confirming a diagnosis with postbronchodilator spirometry. Because of the clinical heterogeneity and the reality that airflow obstruction assessed by spirometry only partially reflects disease severity, a thorough clinical evaluation of the patient should include assessment of symptom burden and risk of exacerbations that permits the implementation of evidence-informed pharmacologic and nonpharmacologic interventions. This guideline provides recommendations from a comprehensive systematic review with a meta-analysis and expert-informed clinical remarks to optimize maintenance pharmacologic therapy for individuals with stable COPD, and a revised and practical treatment pathway based on new evidence since the 2019 update of the Canadian Thoracic Society (CTS) Guideline. The key clinical questions were developed using the Patients/Population (P), Intervention(s) (I), Comparison/Comparator (C), and Outcome (O) model for three questions that focuses on the outcomes of symptoms (dyspnea)/health status, acute exacerbations, and mortality. The evidence from this systematic review and meta-analysis leads to the recommendation that all symptomatic patients with spirometry-confirmed COPD should receive long-acting bronchodilator maintenance therapy. Those with moderate to severe dyspnea (modified Medical Research Council ≥ 2) and/or impaired health status (COPD Assessment Test ≥ 10) and a low risk of exacerbations should receive combination therapy with a long-acting muscarinic antagonist/long-acting ẞ2-agonist (LAMA/LABA). For those with a moderate/severe dyspnea and/or impaired health status and a high risk of exacerbations should be prescribed triple combination therapy (LAMA/LABA/inhaled corticosteroids) azithromycin, roflumilast or N-acetylcysteine is recommended for specific populations; a recommendation against the use of theophylline, maintenance systemic oral corticosteroids such as prednisone and inhaled corticosteroid monotherapy is made for all COPD patients.

Reference equations for quadriceps strength, endurance and power: a multicentre study.

Introduction: The lack of reference values of lower-limb muscle function hinders the clinical recommendations of its measurement in patients with COPD. Therefore, this study aimed to develop reference equations to predict reference values for quadriceps strength, endurance and power and evaluate their construct validity in patients with COPD. Methods: Quadriceps strength, endurance and power were assessed in 158 healthy individuals and 87 patients with COPD. In addition, patients with COPD performed a 6-min walk test (6MWT) and a 1-min sit-to-stand test (1STS). Multiple linear regressions were performed to develop reference equations. The proportion of patients with COPD with reduced quadriceps function was determined, and correlations between quadriceps strength, endurance and power expressed in percentage of predicted values and 6MWT and 1STS performance were used to document the construct validity of the reference equation. Results: Except for quadriceps isometric endurance, the proposed reference equations explained 50-70% of the variance of the quadriceps properties in healthy individuals. All quadriceps properties were systematically reduced in a large proportion of patients with COPD compared to healthy individuals. Correlation coefficients between quadriceps properties expressed in percentage of predicted values and 6MWT and 1STS performance ranged between 0.28 and 0.49 (all p<0.05). Conclusion: In healthy individuals, age, sex, height and body mass index explained 50-70% of the variance of quadriceps strength, endurance and power. When expressed in percentage of predicted values, these quadriceps properties correlated with 6MWT and 1STS performance, suggesting construct validity of the reference values in patients with COPD.

Automated O2 Titration Alone or With High-Flow Nasal Cannula During Walking Exercise in Chronic Lung Diseases.

BACKGROUND: Exercise-induced O2 desaturation contributes to dyspnea and exercise intolerance in various respiratory diseases. This study assessed whether automated O2 titration was superior to fixed-flow O2 to improve exertional dyspnea and walking exercise endurance. We also aimed at evaluating possible additive effects of high-flow nasal cannula coupled with automated O2 titration on these outcomes. METHODS: Subjects with chronic respiratory diseases and exercise-induced desaturation performed a 3-min constant-speed shuttle test (CSST) and an endurance shuttle walking test (ESWT) with either (1) fixed-flow O2, (2) automated O2 titration targeting an SpO2 of 94% (± 2%), and (3) automated O2 titration + high-flow nasal cannula according to a randomized sequence. The main outcome was Borg dyspnea score at the end of the 3-min CSST. Secondary outcomes included endurance time and dyspnea during ESWT and oxygenation status during exercise. RESULTS: Ten subjects with COPD, 10 with interstitial lung disease, 5 with pulmonary hypertension, and 3 with cystic fibrosis completed the study. Compared to fixed-flow O2, automated O2 titration did not reduce dyspnea at the end of the 3-min CSST. Endurance time during the ESWT was prolonged with automated O2 titration (mean difference 298 [95% CI 205-391] s, P < .001), and dyspnea at isotime was reduced. No further improvement was noted when high-flow nasal cannula was added to automated O2 titration. Compared to fixed-flow O2, O2 flows were higher with automated O2 titration, resulting in better oxygenation. CONCLUSIONS: Automated O2 titration was superior to fixed-flow O2 to alleviate dyspnea and improve exercise endurance during the ESWT in subjects with a variety of chronic respiratory diseases. Adding high-flow nasal cannula to automated O2 titration provided no further benefits.

Short-term air pollution exposure and exacerbation events in mild to moderate COPD: a case-crossover study within the CanCOLD cohort.

BACKGROUND: Infections are considered as leading causes of acute exacerbations of chronic obstructive pulmonary disease (COPD). Non-infectious risk factors such as short-term air pollution exposure may play a clinically important role. We sought to estimate the relationship between short-term air pollutant exposure and exacerbations in Canadian adults living with mild to moderate COPD. METHODS: In this case-crossover study, exacerbations ('symptom based': ≥48 hours of dyspnoea/sputum volume/purulence; 'event based': 'symptom based' plus requiring antibiotics/corticosteroids or healthcare use) were collected prospectively from 449 participants with spirometry-confirmed COPD within the Canadian Cohort Obstructive Lung Disease. Daily nitrogen dioxide (NO2), fine particulate matter (PM2.5), ground-level ozone (O3), composite of NO2 and O3 (Ox), mean temperature and relative humidity estimates were obtained from national databases. Time-stratified sampling of hazard and control periods on day '0' (day-of-event) and Lags ('-1' to '-6') were compared by fitting generalised estimating equation models. All data were dichotomised into 'warm' (May-October) and 'cool' (November-April) seasons. ORs and 95% CIs were estimated per IQR increase in pollutant concentrations. RESULTS: Increased warm season ambient concentration of NO2 was associated with symptom-based exacerbations on Lag-3 (1.14 (1.01 to 1.29), per IQR), and increased cool season ambient PM2.5 was associated with symptom-based exacerbations on Lag-1 (1.11 (1.03 to 1.20), per IQR). There was a negative association between warm season ambient O3 and symptom-based events on Lag-3 (0.73 (0.52 to 1.00), per IQR). CONCLUSIONS: Short-term ambient NO2 and PM2.5 exposure were associated with increased odds of exacerbations in Canadians with mild to moderate COPD, further heightening the awareness of non-infectious triggers of COPD exacerbations.

Factors Associated with Attrition in a Longitudinal Cohort of Older Adults in the Community.

Introduction: Retaining participants in longitudinal studies increases their power. We undertook this study in a population-based longitudinal cohort of adults with COPD to determine the factors associated with increased cohort attrition. Methods: In the longitudinal population-based Canadian Cohort of Obstructive Lung Disease (CanCOLD) study, 1561 adults > 40 years old were randomly recruited from 9 urban sites. Participants completed in-person visits at 18-month intervals and also were followed up every 3 months over the phone or by email. The cohort retention for the study and the reasons for attrition were analyzed. Hazard ratios and robust standard errors were calculated using Cox regression methods to explore the associations between participants who remained in the study and those who did not. Results: The median follow-up (years) of the study is 9.0 years. The overall mean retention was 77%. Reasons for attrition (23%) were: dropout by participant (39%), loss of contact (27%), investigator-initiated withdrawal (15%), deaths (9%), serious disease (9%), and relocation (2%). Factors independently associated with attrition were lower educational attainment, higher pack-year tobacco consumption, diagnosed cardiovascular disease, and a higher Hospital Anxiety and Depression Scale score: adjusted hazard ratios (95% confidence interval) were 1.43(1.11, 1.85); 1.01(1.00, 1.01); 1.44(1.13, 1.83); 1.06(1.02, 1.10) respectively. Conclusions: Identification and awareness of risk factors for attrition could direct targeted retention strategies in longitudinal studies. Moreover, the identification of patient characteristics associated with study dropout could address any potential bias introduced by differential dropouts.

Impaired Spirometry and COPD Increase the Risk of Cardiovascular Disease: A Canadian Cohort Study.

BACKGROUND: Individuals with COPD and preserved ratio impaired spirometry (PRISm) findings in clinical settings have an increased risk of cardiovascular disease (CVD). RESEARCH QUESTION: Do individuals with mild to moderate or worse COPD and PRISm findings in community settings have a higher prevalence and incidence of CVD compared with individuals with normal spirometry findings? Can CVD risk scores be improved when impaired spirometry is added? STUDY DESIGN AND METHODS: The analysis was embedded in the Canadian Cohort Obstructive Lung Disease (CanCOLD). Prevalence of CVD (ischemic heart disease [IHD] and heart failure [HF]) and their incidence over 6.3 years were compared between groups with impaired and normal spirometry findings using logistic regression and Cox models, respectively, adjusting for covariables. Discrimination of the pooled cohort equations (PCE) and Framingham risk score (FRS) in predicting CVD were assessed with and without impaired spirometry. RESULTS: Participants (n = 1,561) included 726 people with normal spirometry findings and 835 people with impaired spirometry findings (COPD Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1 disease, n = 408; GOLD stage ≥ 2, n = 331; PRISm findings, n = 96). Rates of undiagnosed COPD were 84% in GOLD stage 1 and 58% in GOLD stage ≥ 2 groups. Prevalence of CVD (IHD or HF) was significantly higher among individuals with impaired spirometry findings and COPD compared with those with normal spirometry findings, with ORs of 1.66 (95% CI, 1.13-2.43; P = .01∗) (∗ indicates statistical significane with P < .05) and 1.55 (95% CI, 1.04-2.31; P = .033∗), respectively. Prevalence of CVD was significantly higher in participants having PRISm findings and COPD GOLD stage ≥ 2, but not GOLD stage 1. CVD incidence was significantly higher, with hazard ratios of 2.07 (95% CI, 1.10-3.91; P = .024∗) for the impaired spirometry group and 2.09 (95% CI, 1.10-3.98; P = .024∗) for the COPD group compared to individuals with normal spirometry findings. The difference was significantly higher among individuals with COPD GOLD stage ≥ 2, but not GOLD stage 1. The discrimination for predicting CVD was low and limited when impaired spirometry findings were added to either risk score. INTERPRETATION: Individuals with impaired spirometry findings, especially those with moderate or worse COPD and PRISm findings, have increased comorbid CVD compared with their peers with normal spirometry findings, and having COPD increases the risk of CVD developing.

A 37-Year-Old Man With Right Lung Consolidation.

CASE PRESENTATION: A 37-year-old man attended a medical clinic at the confluence of the Appalachian and the St. Lawrence Valley after 2 weeks of coughing greenish sputum and progressive dyspnea on exertion. In addition, he reported fatigue, fevers, and chills. He had quit smoking a year earlier and was not a drug user. He recently had spent most of his free time outdoors, mountain biking, but had not travelled outside of Canada. Medical history was unremarkable. He did not take any medication. Upper airway samples taken for SARS-CoV-2 proved negative; he was prescribed cefprozil and doxycycline for presumed community-acquired pneumonia. He returned to the emergency room 1 week later with mild hypoxemia, persisting fever, and a chest radiography consistent with lobar pneumonia. The patient was admitted to his local community hospital, and broad-spectrum antibiotics were added to the regimen. Unfortunately, his condition deteriorated over the following week, and he experienced hypoxic respiratory failure for which he required mechanical ventilation before his transfer to our medical center.

COPD: Providing the right treatment for the right patient at the right time.

Chronic Obstructive Pulmonary Disease (COPD) is a common disease associated with significant morbidity and mortality that is both preventable and treatable. However, a major challenge in recognizing, preventing, and treating COPD is understanding its complexity. While COPD has historically been characterized as a disease defined by airflow limitation, we now understand it as a multi-component disease with many clinical phenotypes, systemic manifestations, and associated co-morbidities. Evidence is rapidly emerging in our understanding of the many factors that contribute to the pathogenesis of COPD and the identification of "early" or "pre-COPD" which should provide exciting opportunities for early treatment and disease modification. In addition to breakthroughs in our understanding of the origins of COPD, we are optimizing treatment strategies and delivery of care that are showing impressive benefits in patient-centered outcomes and healthcare utilization. This special issue of Respiratory Medicine, "COPD: Providing the Right Treatment for the Right Patient at the Right Time" is a summary of the proceedings of a conference held in Stresa, Italy in April 2022 that brought together international experts to discuss emerging evidence in COPD and Pulmonary Rehabilitation in honor of a distinguished friend and colleague, Claudio Ferdinando Donor (1948-2021). Claudio was a true pioneer in the field of pulmonary rehabilitation and the comprehensive care of individuals with COPD. He held numerous leadership roles in in the field, provide editorial stewardship of several respiratory journals, authored numerous papers, statement and guidelines in COPD and Pulmonary Rehabilitation, and provided mentorship to many in our field. Claudio's most impressive talent was his ability to organize spectacular conferences and symposia that highlighted cutting edge science and clinical medicine. It is in this spirit that this conference was conceived and planned. These proceedings are divided into 4 sections which highlight crucial areas in the field of COPD: (1) New concepts in COPD pathogenesis; (2) Enhancing outcomes in COPD; (3) Non-pharmacologic management of COPD; and (4) Optimizing delivery of care for COPD. These presentations summarize the newest evidence in the field and capture lively discussion on the exciting future of treating this prevalent and impactful disease. We thank each of the authors for their participation and applaud their efforts toward pushing the envelope in our understanding of COPD and optimizing care for these patients. We believe that this edition is a most fitting tribute to a dear colleague and friend and will prove useful to students, clinicians, and researchers as they continually strive to provide the right treatment for the right patient at the right time. It has been our pleasure and a distinct honor to serve as editors and oversee such wonderful scholarly work.

Physical Activity and Symptom Burden in COPD: The Canadian Obstructive Lung Disease Study.

Background: The relationship between symptom burden and physical activity (PA) in chronic obstructive pulmonary disease (COPD) remains poorly understood with limited data on undiagnosed individuals and those with mild to moderate disease. Objective: The primary objective was to evaluate the relationship between symptom burden and moderate-to-vigorous intensity PA (MVPA) in individuals from a random population-based sampling mirroring the population at large. Methods: Baseline participants of the Canadian Cohort Obstructive Lung Disease (n=1558) were selected for this cross-sectional sub-study. Participants with mild COPD (n=406) and moderate COPD (n=331), healthy individuals (n=347), and those at risk of developing COPD (n=474) were included. The Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire was used to estimate MVPA in terms of energy expenditure. High symptom burden was classified using the COPD Assessment Test ([CAT] ≥10). Results: Significant associations were demonstrated between high symptom burden and lower MVPA levels in the overall COPD sample (ß=-717.09; 95% confidence interval [CI]=-1079.78, -354.40; p<0.001) and in the moderate COPD subgroup (ß=-694.1; 95% CI=-1206.54, -181.66; p=0.006). A total of 72% of the participants with COPD were previously undiagnosed. The undiagnosed participants had significantly higher MVPA than those with physician diagnosed COPD (ß=-592.41 95% CI=-953.11, -231.71; p=0.001). Conclusion: MVPA was found to be inversely related to symptom burden in a large general population sample that included newly diagnosed individuals, most with mild to moderate COPD. Assessment of symptom burden may help identify patients with lower MVPA, especially for moderate COPD and for relatively inactive individuals with mild COPD.

Exercise testing and postoperative complications after minimally invasive lung resection: A cohort study.

Background: Peak oxygen uptake ( V ˙ O 2 ) during cardiospulmonary exercise testing (CPET) is used to stratify postoperative risk following lung cancer resection but peak V ˙ O 2 thresholds to predict post-operative mortality and morbidity were derived mostly from patients who underwent thoracotomy. Objectives: We evaluated whether peak V ˙ O 2 or other CPET-derived variables predict post-operative mortality and cardiopulmonary morbidity after minimally invasive video-assisted thoracoscopic surgery (VATS) for lung cancer resection. Methods: A retrospective analysis of patients who underwent VATS lung resection between 2002 and 2019 and in whom CPET was performed. Logistic regression models were used to determine predictors of postoperative outcomes until 30 days after surgery. The ability of peak V ˙ O 2 to discriminate between patients with and without post-operative complications was evaluated using Receiver operating characteristic (ROC) analysis. Results: Among the 593 patients, postoperative cardiopulmonary complications occurred in 92 (15.5%) individuals, including three deaths. Mean peak V ˙ O 2 was 18.8 ml⋅kg-1⋅min-1, ranging from 7.0 to 36.4 ml⋅kg-1⋅min-1. Best predictors of postoperative morbidity and mortality were peripheral arterial disease, bilobectomy or pneumonectomy (versus sublobar resection), preoperative FEV1, peak V ˙ O 2 , and peak V ˙ E / V ˙ C O 2 . The proportion of patients with peak V ˙ O 2 of < 15 ml⋅kg-1⋅min-1, 15 to < 20 ml⋅kg-1⋅min-1 and ≥ 20 ml⋅kg-1⋅min-1 experiencing at least one postoperative complication was 23.8, 16.3 and 10.4%, respectively. The area under the ROC curve for peak V ˙ O 2 was 0.63 (95% CI: 0.57-0.69). Conclusion: Although lower peak V ˙ O 2 was a predictor of postoperative complications following VATS lung cancer resection, its ability to discriminate patients with or without complications was limited.