Canadian Cohort on the Origin and Progression of Airway Disease: Physiology Platform

The Canadian Respiratory Research Network (CRRN) has recently been established to study the origins and evolution of airways disease in the population. The CRRN is funded by the Institute of Cardio-respiratory Health (ICRH), an institute of the CIHR. The Physiology platform will support the other CRRN platforms (biology, imaging, population health, knowledge transfer) by providing a comprehensive characterization of the nature and extent of physiological impairment of respiratory function in smokers at risk for airways disease and in those with early or mild airway obstruction. The planned studies of the physiology group (core sites located at Queen's University, University of British Columbia and McGill University) will initially focus on smoking-related lung injury in those at risk for COPD and in those meeting spirometric criteria for mild airway obstruction, with or without respiratory symptoms. The primary aim of this initial study is to identify and validate sensitive test(s) of peripheral airway dysfunction that may qualify as physiological biomarkers for use in future CRRN studies.

Study Overview

• Status: Completed
• Conditions: Smoking; COPD

• Study Type: Observational
• Enrollment (Actual): 99

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • University of British Columbia
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Queen's University and Kingston General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S4
      • McGill University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Subjects will include 30 participants from each of the following four subgroups: GOLD grade 1A COPD, GOLD grade 1B COPD, symptomatic smokers who do not meet spirometric criteria for COPD, and age- and sex-matched healthy non-smoking controls. Subjects will be recruited from the Canadian Chronic Obstructive Lung Disease (CanCOLD) study cohort and, once that source has been exhausted, from each site's database of previous or potential research study participants. The CanCOLD Study cohort was recruited from the COLD Study sample, which was a random sample of adults ≥40 years of age who had pre- and post-bronchodilator spirometry performed in order to estimate the prevalence of COPD in Canada.

Description

INCLUSION CRITERIA:

Stable patients with GOLD grade 1 mild COPD will be included in the study if they have: a post-bronchodilator FEV1≥80 %predicted and an FEV1/FVC ratio <0.7 and <LLN; ≥40 years of age; and a cigarette smoking history ≥10 pack-years or ≥10 years of exposure to other inhaled substances (i.e., second hand smoke and/or biomass). Symptomatic (category B) subjects will have a Baseline Dyspnea Index (BDI) total score ≤9, a modified Medical Research Council (MRC) dyspnea score ≥2, or a COPD Assessment Test (CAT) score ≥10. Asymptomatic (category A) subjects will have a BDI>9, modified MRC<2 or CAT<10, no history of seeking medical care for respiratory symptoms, and no history of using respiratory medications. Symptomatic current or ex-smokers (>10 pack-year history) who do not meet criteria for COPD (e.g., post-bronchodilator FEV1<80%predicted and FEV1/FVC<0.7, with both measurements also <LLN) and who are on no respiratory medication will be included. Symptomatic will be defined as: BDI≤9, modified MRC≥2 or CAT>10. Healthy, age- and sex-matched, non-smoking (<2 pack-year history) participants with normal spirometry will be used for comparison purposes.

EXCLUSION CRITERIA:

• presence of clinically significant comorbidities that could contribute to dyspnea or exercise limitation (i.e., unstable heart disease, a pulmonary disease other than COPD, uncontrolled diabetes, neuromuscular or orthopedic impairment);
• history/clinical evidence of asthma;
• contraindications to exercise testing;
• <40 years of age;
• body mass index <18.5 or >=35 kg/m2.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Mild COPD, symptomatic; Smokers fitting GOLD 1B criteria for COPD
Mild COPD, asymptomatic; Smokers fitting GOLD 1A criteria for COPD
Symptomatic smokers, at risk for COPD; Smokers who do not meet spirometric criteria for COPD
Healthy, non-smoking controls; Non-smokers, matched to smoking groups for age (>40 yrs of age) and gender

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Small airway function	There is no single measurement of small airway function since this study is evaluating which measurements, among a list of conventional and experimental physiological parameters, best characterize the nature and extent of impairment of respiratory function in the smoking study groups and which of these parameters best predict clinical outcome (i.e., dyspnea, exercise capacity, ventilatory capacity, health status). Assessments will include: spirometry, closing volume, impulse oscillometry, frequency dependence of dynamic lung compliance, plethysmographic lung volumes and metronome-paced dynamic hyperinflation.	1 day (Time of visit)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiopulmonary exercise test	Includes measurements of exertional dyspnea (intensity and quality), peak exercise capacity (peak oxygen uptake [VO2]) and ventilatory responses (ventilation, pulmonary gas exchange, breathing pattern, operating lung volumes and tidal flow-volume loops) during symptom-limited incremental cardiopulmonary cycle exercise testing.	1 day (Time of visit)
Clinical outcome	Includes questionnaires regarding chronic activity-related dyspnea, respiratory symptoms, health status and physical activity.	1 day (Time of visit)

Collaborators and Investigators

• Sponsor: Dr. Denis O'Donnell
• Collaborators: University of British Columbia; McGill University; Canadian Institutes of Health Research (CIHR); Ottawa Hospital Research Institute
• Investigators: Principal Investigator: Denis E O'Donnell, MD, FRCPC, Queen's University and Kingston General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): September 30, 2022

Study Registration Dates

• First Submitted: May 30, 2014
• First Submitted That Met QC Criteria: June 2, 2014
• First Posted (Estimated): June 3, 2014

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: exercise; smoking; mild COPD; dyspnea; clinical outcomes; small airway dysfunction
• Other Study ID Numbers: DMED-1674-14