Vaping is increasingly popular with both adolescent and adult Canadians, but the long-term health impacts remain unknown. We believe that the tools we currently have to detect lung disease in people who vape may be insufficient and propose new ways to find lung injuries that may impact them over the course of their lives. These include exercise testing, new imaging techniques, and new breathing tests that will demonstrate how vaping may harm their lungs. We will use these tools in both adolescent and adult Canadians to give Canadians who vape important information on the consequences of vaping.
Promoted as a safer method of inhaling nicotine compared to cigarettes and as smoking cessation tools, e-cigarettes have substantially grown in popularity with rates of uptake now exceeding those of cigarette smoking. In Canada, 6% of Canadians aged 15 years and older have vaped in the past 30 days. Younger Canadians appear to be the most susceptible to these habits, with 14% of those aged 15-19 years and 18% of those aged 20-24 years reporting past 30 day use. Indigenous populations are also disproportionately affected by the spread of vaping which may place them at higher risk for potential downstream respiratory complications. As Canadians increasingly reach for e-cigarettes, especially at younger ages and not just for the purposes of smoking cessation, greater clarity into the pulmonary toxicities vaping is urgently needed. The Canadian Lung Outcomes in Users of Vaping Devices (CLOUD) Study is a pan-Canadian, multicentre, multidisciplinary, and longitudinal approach to studying vaping from cell to society. The characterization of e-cigarettes' respiratory effects remains superficial and a more comprehensive phenotyping of vaping-exposed lungs across the lifespan using novel imaging and pulmonary function techniques, dynamic exercise testing, and airway cell sequencing would significantly enhance our understanding of the potential harms. As with combustible cigarette smoking, the small airways (characterized by a diameter \<2mm) may be particularly vulnerable during vaping given their high degree of exposure to particulate matter. These regions of the lung may harbour the earliest signs of injury, ultimately setting the stage for future obstructive airways disease. Objectives The objective of the CLOUD Study is to characterize small airway injury in adolescent and adult Canadians who use e-cigarettes. Specifically, our goals are to: 1. Characterize the structural and functional disruptions associated with e-cigarette use using oscillometry, multiple breath washout, chest computed tomography, hyperpolarized 129-xenon magnetic resonance imaging, cardiopulmonary exercise testing, and bronchoscopy. 2. Determine the association between e-cigarette use and respiratory outcomes, including symptom burdens, exacerbation-like respiratory events, and school and work absences. 3. Characterize the epigenetic and transcriptomic disruptions associated with e-cigarette use in blood, sputum, airway epithelium, and lung immune cells. Methods Our observational, longitudinal cohort study encompasses six academic hospital centres across Canada (the University of British Columbia, the University of Alberta, McMaster University, the University of Ottawa, the University of Toronto, and the Université de Sherbrooke). Participants (n=100 ages \>12 and \<19 years and n=400 ages ≥19 years) will be followed over 3 years, undergoing repeat demographic and respiratory symptom questionnaires, oscillometry, pulmonary function testing, and exercise testing. Adolescent participants will additionally undergo multiple breath washout and induced sputum collection and adult participants will undergo chest CT imaging and bronchoscopy. A substudy of adolescent and adult participants undergoing pulmonary hyperpolarized 129-xenon gas magnetic resonance imaging will also be performed. Induced sputum and bronchoscopy-derived airway epithelial and bronchoalveolar lavage samples will be sequenced for methylation and transcriptomics.
Study Type
OBSERVATIONAL
Enrollment
500
University of Alberta (Clinical Sciences Building)
Edmonton, Alberta, Canada
BC Cancer Agency
Vancouver, British Columbia, Canada
BC Children's Hospital Research Institute
Vancouver, British Columbia, Canada
St. Paul's Hospital
Vancouver, British Columbia, Canada
McMaster University (Research Institute of St. Joe's Hamilton)
Hamilton, Ontario, Canada
University of Ottawa (The Ottawa Hospital General Campus)
Ottawa, Ontario, Canada
University of Toronto (The Hospital for Sick Children)
Toronto, Ontario, Canada
Université de Sherbrooke
Sherbrooke, Quebec, Canada
Composite Measure of Small Airways Dysfunction
Participants meeting at least one of the following criteria will be considered to have small airways dysfunction: For adolescent participants, these measures will include 1) a change in resistance from 5-20 Hz (R5-R20) \>upper limit of normal (ULN) on oscillometry or 2) peak oxygen consumption (VO2)\<lower limit of normal (LLN) plus a ventilatory response or minute ventilation/carbon dioxide production (VE/VCO2) nadir \>ULN. For adult participants, these measures will include 1) R5-R20 \>ULN, 2) disease probability measure functional small airways disease \>10% on chest CT, or 3) peak VO2\<84% predicted plus a VE/VCO2 nadir \>ULN. The proportion of participants meeting at least one of the criteria for small airways dysfunction at any time point will be compared between the vaping and control groups using Chi-square tests. Multivariable logistic regressions will be used to adjust for possible covariates, such as age, sex, and their interaction with vaping/smoking groups.
Time frame: From enrollment (Baseline) to the end of study participation (36 Months).
FEV1
Outcome measured in units of Liters (L) for all study participants.
Time frame: 36 Months
FVC
Outcome measured in units of Liters (L) for all study participants.
Time frame: 36 Months
FEV1/FVC
Outcome measured in units of 0-100% for all study participants.
Time frame: 36 Months
FEV3/FEV6
Outcome measured in units of 0-100% for all study participants.
Time frame: 36 Months
Total Lung Capacity
Outcome measured in units of Liters (L) for all study participants.
Time frame: 36 Months
Diffusion Capacity
Outcome measured in units of mL/min/mmHg for all study participants.
Time frame: 36 Months
Small Airways Resistance R5-R20
Outcome measured in units of kPa/l/s for all study participants.
Time frame: 36 Months
Ventilation Defect Percent
Outcomes measured in units of 0-100% for study participants in the following sites: St. Paul's Hospital (University of British Columbia), BC Children's Hospital (University of British Columbia), the Hospital for Sick Children (University of Toronto), St. Joseph's Healthcare Hamilton (McMaster University).
Time frame: 36 Months
RBC to Membrane Ratio
Outcomes measured in units of a ratio for study participants in the following sites: St. Paul's Hospital (University of British Columbia), BC Children's Hospital (University of British Columbia), the Hospital for Sick Children (University of Toronto), St. Joseph's Healthcare Hamilton (McMaster University).
Time frame: 36 Months
Membrane to Gas Ratio
Outcomes measured in units of a ratio for study participants in the following sites: St. Paul's Hospital (University of British Columbia), BC Children's Hospital (University of British Columbia), the Hospital for Sick Children (University of Toronto), St. Joseph's Healthcare Hamilton (McMaster University).
Time frame: 36 Months
Apparent Diffusion Coefficient
Outcomes measured in units of cm2/s for study participants in the following sites: St. Paul's Hospital (University of British Columbia), BC Children's Hospital (University of British Columbia), the Hospital for Sick Children (University of Toronto), St. Joseph's Healthcare Hamilton (McMaster University).
Time frame: 36 Months
Peak VO2 %predicted
Outcomes measured in units of 0-100% for all study participants.
Time frame: 36 Months
VE/VCO2 nadir
Outcomes measured in units of a ratio for all study participants.
Time frame: 36 Months
Epigenetic Age (Blood Methylation)
Outcomes measured in units of age acceleration residual for all study participants.
Time frame: 36 Months
Differentially Methylated Genes (Blood Methylation)
Outcomes measured in units of beta-values for all study participants.
Time frame: 36 Months
Differentially Expressed Genes (Blood Transcriptome)
Outcomes measured in units of transcripts per million for all study participants.
Time frame: 36 Months
Epigenetic Age (Induced Sputum Methylation)
Outcomes measured in units of age acceleration residual for adolescent study participants in the following sites: BC Children's Hospital (University of British Columbia), the Hospital for Sick Children (University of Toronto), Centre Hospitalier Universitaire de Sherbrooke (Universite de Sherbrooke).
Time frame: 36 Months
Differentially Methylated Genes (Induced Sputum Methylation)
Outcomes measured in units of beta-values for adolescent study participants in the following sites: BC Children's Hospital (University of British Columbia), the Hospital for Sick Children (University of Toronto), Centre Hospitalier Universitaire de Sherbrooke (Universite de Sherbrooke).
Time frame: 36 Months
Differentially Expressed Genes (Induced Sputum Transcriptome)
Outcomes measured in units of transcripts per million for adolescent study participants in the following sites: BC Children's Hospital (University of British Columbia), the Hospital for Sick Children (University of Toronto), Centre Hospitalier Universitaire de Sherbrooke (Universite de Sherbrooke).
Time frame: 36 Months
Epigenetic Age (Bronchial Epithelial Cell and Bronchoalveolar Lavage Methylation)
Outcomes measured in units of age acceleration residual for adult study participants in the following sites: St. Paul's Hospital (University of British Columbia), St. Joseph's Healthcare Hamilton (McMaster University), Centre Hospitalier Universitaire de Sherbrooke (Universite de Sherbrooke).
Time frame: 36 Months
Differentially Methylated Genes (Bronchial Epithelial Cell and Bronchoalveolar Lavage Methylation)
Outcomes measured in units of beta-values for adult study participants in the following sites: St. Paul's Hospital (University of British Columbia), St. Joseph's Healthcare Hamilton (McMaster University), Centre Hospitalier Universitaire de Sherbrooke (Universite de Sherbrooke).
Time frame: 36 Months
Differentially Expressed Genes (Bronchial Epithelial Cell and Bronchoalveolar Lavage Transcriptome)
Outcomes measured in units of transcripts per million for adult study participants in the following sites: St. Paul's Hospital (University of British Columbia), St. Joseph's Healthcare Hamilton (McMaster University), Centre Hospitalier Universitaire de Sherbrooke (Universite de Sherbrooke).
Time frame: 36 Months
Lung Clearance Index
Outcomes measured in counts for adolescent study participants in the following sites: BC Children's Hospital (University of British Columbia), the Hospital for Sick Children (University of Toronto).
Time frame: 36 Months
DPM fSAD
Outcomes measured in units of 0-100% for adult study participants in the following sites: St. Paul's Hospital (University of British Columbia), St. Joseph's Healthcare Hamilton (McMaster University), Centre Hospitalier Universitaire de Sherbrooke (Universite de Sherbrooke), Clinical Sciences Building (University of Alberta), Ottawa Hospital General Campus (University of Ottawa).
Time frame: 36 Months
LAA856
Outcomes measured in units of 0-100% for adult study participants in the following sites: St. Paul's Hospital (University of British Columbia), St. Joseph's Healthcare Hamilton (McMaster University), Centre Hospitalier Universitaire de Sherbrooke (Universite de Sherbrooke), Clinical Sciences Building (University of Alberta), Ottawa Hospital General Campus (University of Ottawa).
Time frame: 36 Months
LAA950 (Quantitative Emphysema)
Outcomes measured in units of 0-100% for adult study participants in the following sites: St. Paul's Hospital (University of British Columbia), St. Joseph's Healthcare Hamilton (McMaster University), Centre Hospitalier Universitaire de Sherbrooke (Universite de Sherbrooke), Clinical Sciences Building (University of Alberta), Ottawa Hospital General Campus (University of Ottawa).
Time frame: 36 Months
Qualitative Emphysema
Outcomes measured in units of 0-100% for adult study participants in the following sites: St. Paul's Hospital (University of British Columbia), St. Joseph's Healthcare Hamilton (McMaster University), Centre Hospitalier Universitaire de Sherbrooke (Universite de Sherbrooke), Clinical Sciences Building (University of Alberta), Ottawa Hospital General Campus (University of Ottawa).
Time frame: 36 Months
Pulmonary Vascular Volume
Outcomes measured in units of milliliters (mL) for adult study participants in the following sites: St. Paul's Hospital (University of British Columbia), St. Joseph's Healthcare Hamilton (McMaster University), Centre Hospitalier Universitaire de Sherbrooke (Universite de Sherbrooke), Clinical Sciences Building (University of Alberta), Ottawa Hospital General Campus (University of Ottawa).
Time frame: 36 Months
Mucus Score
Outcomes measured in counts for adult study participants in the following sites: St. Paul's Hospital (University of British Columbia), St. Joseph's Healthcare Hamilton (McMaster University), Centre Hospitalier Universitaire de Sherbrooke (Universite de Sherbrooke), Clinical Sciences Building (University of Alberta), Ottawa Hospital General Campus (University of Ottawa).
Time frame: 36 Months
Total Airway Counts
Outcomes measured in counts for adult study participants in the following sites: St. Paul's Hospital (University of British Columbia), St. Joseph's Healthcare Hamilton (McMaster University), Centre Hospitalier Universitaire de Sherbrooke (Universite de Sherbrooke), Clinical Sciences Building (University of Alberta), Ottawa Hospital General Campus (University of Ottawa).
Time frame: 36 Months
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