The Canadian Lung Outcomes in Users of Vaping Devices (CLOUD) Study: protocol for a prospective, observational cohort study.

INTRODUCTION: The rapid growth in popularity of e-cigarettes over the past decade has prompted concerns about their impact on long-term respiratory health. Small airway injury is suspected to be a direct consequence of e-cigarette use and may be quantifiable by novel structural and functional diagnostic modalities.

METHODS AND ANALYSIS: In a multicentre observational longitudinal study, participants will be enrolled in either an adolescent (ages ≥12 and <19 years) or an adult arm (≥19 years old) and followed over 3 years across three time points (baseline, 18 months and 36 months). In the adolescent arm, a total of 50 e-cigarette and 50 non-e-cigarette users will be enrolled across 4 sites. In the adult arm, a total of 100 e-cigarette users, 100 non-e-cigarette users, and an additional 100 combustible cigarette-only users and 100 dual combustible cigarette-e-cigarette users will be enrolled across 5 sites. Participants will undergo respiratory questionnaires, pulmonary function tests, oscillometry, cardiopulmonary exercise testing, hyperpolarised 129-xenon gas MRI and blood collection. In adolescent participants only, multiple breath washout and induced sputum collection will be performed. Adult participants will also undergo inspiratory/expiratory chest CT and bronchoscopy. The primary endpoint will be a composite of small airway dysfunction according to oscillometry, cardiopulmonary testing and/or chest imaging parameters.

ETHICS AND DISSEMINATION: This protocol has been approved by The University of British Columbia-Providence Health Care Research Ethics Board (Certificate H24-00374). The use of hyperpolarised 129-xenon gas in this study has been approved by Health Canada (Certificate HC6-024-c291776). Written documentation of informed consent will be required prior to study initiation. We will seek to enrol adolescent participants who are capable of providing informed consent with an optional support statement from a parent encouraged but not required. Study findings will be disseminated to medical/scientific audiences through scientific conferences and published manuscripts respecting the Strengthening the Reporting of Observational Studies in Epidemiology statement, to youths through outreach events at high schools and community programmes and through social media, and to adults through lung health community events.

TRIAL REGISTRATION NUMBER: NCT06819969.