Clinical trial NCT06819969: The Canadian Lung Outcomes in Users of Vaping Devices Study
Official title: The Canadian Lung Outcomes in Users of Vaping Devices (CLOUD) Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Small Airways Diseases
Vaping
Vaping Related Disorder
Vaping Teens
Vaping Behavior
Keywords: CLOUD
small airway injury
vaping
vape
e-cigarette
oscillometry
multiple breath washout
chest computed tomography
chest CT
hyperpolarized 129-xenon
MRI
CPET
bronchoscopy
transcriptomics
epigenetics
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: BC Children's Hospital Research Institute
name: Providence Healthcare
name: British Columbia Cancer Agency
name: University of Alberta
name: McMaster University
name: University of Ottawa
name: Université de Sherbrooke
name: University of Toronto
First posted: 2025-02-11
Enrollment: 500
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will enroll both adolescent (ages ≥12 and \<19 years) and adult (≥19 years) e-cigarette and non-e-cigarette users in six academic hospital centres across Canada.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

Adolescent arm:

* Aged ≥12 and \<19 years old
* Either 1) use neither combustible cigarettes nor e-cigarettes or 2) use e-cigarettes exclusively

Adult arm:

* Aged ≥19 years old
* Fall into one of the following categories: 1) use neither combustible cigarettes nor e-cigarettes; 2) use combustible cigarettes exclusively, never using e-cigarettes; 3) use e-cigarettes exclusively, never using combustible cigarettes; or 4) use both combustible cigarettes and e-cigarettes currently

Exclusion Criteria:

Adolescent arm:

* Contraindication to pulmonary function testing and cardiopulmonary exercise testing
* Have smoked combustible cannabis within the last month and/or have a combustible cannabis smoking history of \>1 joint-year
* Have smoked combustible cigarettes within the last 6 months
* Have a physician-diagnosed chronic lung disease (such as asthma, cystic fibrosis, or bronchopulmonary dysplasia)
* Inability to provide written informed consent

Adult arm:

* Contraindication to pulmonary function testing and cardiopulmonary exercise testing
* Have smoked combustible cannabis within the last month and/or have a combustible cannabis smoking history of \>1 joint-year
* Currently undergoing treatment for lung cancer
* Inability to provide written informed consent

No limitations will be placed on the type of e-liquids used by participants; e.g., e-cigarette users of nicotine, tetrahydrocannabinol, and cannabidiol will be all enrolled.

Primary outcomes:
measure: Composite Measure of Small Airways Dysfunction
timeFrame: From enrollment (Baseline) to the end of study participation (36 Months).
Secondary outcomes:
measure: FEV1
timeFrame: 36 Months
measure: FVC
timeFrame: 36 Months
measure: FEV1/FVC
timeFrame: 36 Months
measure: FEV3/FEV6
timeFrame: 36 Months
measure: Total Lung Capacity
timeFrame: 36 Months
measure: Diffusion Capacity
timeFrame: 36 Months
measure: Small Airways Resistance R5-R20
timeFrame: 36 Months
measure: Ventilation Defect Percent
timeFrame: 36 Months
measure: RBC to Membrane Ratio
timeFrame: 36 Months
measure: Membrane to Gas Ratio
timeFrame: 36 Months
measure: Apparent Diffusion Coefficient
timeFrame: 36 Months
measure: Peak VO2 %predicted
timeFrame: 36 Months
measure: VE/VCO2 nadir
timeFrame: 36 Months
measure: Epigenetic Age (Blood Methylation)
timeFrame: 36 Months
measure: Differentially Methylated Genes (Blood Methylation)
timeFrame: 36 Months
measure: Differentially Expressed Genes (Blood Transcriptome)
timeFrame: 36 Months
measure: Epigenetic Age (Induced Sputum Methylation)
timeFrame: 36 Months
measure: Differentially Methylated Genes (Induced Sputum Methylation)
timeFrame: 36 Months
measure: Differentially Expressed Genes (Induced Sputum Transcriptome)
timeFrame: 36 Months
measure: Epigenetic Age (Bronchial Epithelial Cell and Bronchoalveolar Lavage Methylation)
timeFrame: 36 Months
measure: Differentially Methylated Genes (Bronchial Epithelial Cell and Bronchoalveolar Lavage Methylation)
timeFrame: 36 Months
measure: Differentially Expressed Genes (Bronchial Epithelial Cell and Bronchoalveolar Lavage Transcriptome)
timeFrame: 36 Months
measure: Lung Clearance Index
timeFrame: 36 Months
measure: DPM fSAD
timeFrame: 36 Months
measure: LAA856
timeFrame: 36 Months
measure: LAA950 (Quantitative Emphysema)
timeFrame: 36 Months
measure: Qualitative Emphysema
timeFrame: 36 Months
measure: Pulmonary Vascular Volume
timeFrame: 36 Months
measure: Mucus Score
timeFrame: 36 Months
measure: Total Airway Counts
timeFrame: 36 Months
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta (Clinical Sciences Building)
state: Alberta
city: Vancouver
country: Canada
facility: BC Cancer Agency
state: British Columbia
city: Vancouver
country: Canada
facility: BC Children's Hospital Research Institute
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Hamilton
country: Canada
facility: McMaster University (Research Institute of St. Joe's Hamilton)
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa (The Ottawa Hospital General Campus)
state: Ontario
city: Toronto
country: Canada
facility: University of Toronto (The Hospital for Sick Children)
state: Ontario
city: Sherbrooke
country: Canada
facility: Université de Sherbrooke
state: Quebec
Study officials:
affiliation: University of British Columbia
name: Janice Leung, MD
role: PRINCIPAL_INVESTIGATOR
References: