Novel Pulmonary Imaging of Lung Structure and Function in E-cigarette Smokers

Study Overview
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Brief Summary
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This is a longitudinal study of the long-term health impact of e-cigarette smoking on the lungs. Participants will be followed over a period of 5 years, and impacts of e-cigarette smoking on the lungs will be measured with magnetic resonance imaging (MRI) using hyperpolarized xenon-129 gas, pulmonary function tests, exercise capacity, computed tomography images and questionnaires.

Detailed Description
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This is a 5-year longitudinal study of the long-term lung health impact of e-cigarette smoking. Participants with a history of e-cigarette smoking age ≥ 16 years will be recruited from within 2 hours of London, ON through local family and tertiary care physicians, emergency departments and community and social media advertisements. Asymptomatic age and sex-matched participants who have never smoked e- or c-cigarettes will be recruited through community advertisement, media and social media. Participants must satisfy all inclusion and exclusion criteria in order to participate in the study. We will compare lung health of participants at baseline, 12 weeks, 24 weeks and 48 weeks, 3 years, 4 years and 5 years with an asymptomatic control group with no history of e-cigarette or c-cigarette use. The study will involve 6 in-person visits and 1 telephone call for a health update. All measurements will be made with at least 4 hours after the last cigarette and/or vape to provide a way to practically focus on chronic and not acute effects. Pulmonary function and imaging measurements will be made before and after bronchodilator administration. At Visit 1, informed consent will be obtained before any study related assessments or procedures are performed. Eligibility criteria will be reviewed. Safety assessments including vital signs, pulmonary function testing, hematology, sputum sampling, exercise testing, and respiratory questionnaires will be completed. Visit 2 will take place 12 weeks after visit 1 and will include vital signs, pre and post bronchodilator pulmonary function testing, pre and post bronchodilator MRI imaging, chest CT scan, exercise testing, and questionnaires. Visit 3 will take place at 24 weeks and will involve a telephone call to update health information as well as questionnaires. Visit 4 will take place at 48 weeks and will involve vital signs, pre and post bronchodilator pulmonary function testing, pre and post bronchodilator MRI imaging, hematology, blood chemistry, sputum analysis, exercise testing, and questionnaires. Visit 5 will take place at year 3 and will involve vital signs, pre and post bronchodilator pulmonary function testing, pre and post bronchodilator MRI imaging, blood draw, sputum induction and analysis, exercise testing and questionnaires. Visit 6 will take place at year 4 and will involve vital signs, pre and post bronchodilator pulmonary function testing, pre and post bronchodilator MRI imaging, blood draw, sputum induction and analysis, exercise testing and questionnaires. Visit 7 will take place at year 5 and will involve vital signs, pre and post bronchodilator pulmonary function testing, pre and post bronchodilator MRI imaging, blood draw, sputum induction and analysis, exercise testing and questionnaires.

Official Title
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Novel Pulmonary Imaging of Lung Structure and Function in Symptomatic and Asymptomatic E-cigarette Smokers

Conditions
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E Cigarette Use

Intervention / Treatment
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* Diagnostic Test: Hyperpolarized Xenon-129 MRI of the lungs
* Diagnostic Test: Computed Tomography (CT)
* Diagnostic Test: Pulmonary Function Tests (PFT)
* Diagnostic Test: Cardiopulmonary exercise testing (CPET)
* Diagnostic Test: Sputum analysis
* Diagnostic Test: Blood analysis
* Other: Questionnaires


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be directly obtained from legally competent participants before any study-related assessment is performed. Male and female participant age ≥16 years. Participant has recently started vaping, >1 and <5 years weekly use. 70 participants will be c-cigarette never users. 70 participants will be former or current c-cigarette users. 10 asymptomatic age and sex-matched healthy people who have never used e- or c-cigarettes will be controls. Exclusion Criteria: Participants with contraindications for undergoing an MRI such as participants with MRI-sensitive implants, tattoos with MRI-sensitive dye and severe claustrophobia. Participant is, in the opinion of the investigator, mentally or legally incapacitated, preventing informed consent from being obtained, or cannot read or understand written material. Participant unable to perform spirometry or plethysmography maneuvers.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| c-cigarette never users<br>Includes 70 participants who are e-cigarette users who have never smoked combustible cigarettes. | Diagnostic Test: Hyperpolarized Xenon-129 MRI of the lungs<br>* Participants will be imaged using MRI using hyperpolarized xenon-129 gas as a contrast gas<br>* Other names: 129Xe MRI;Diagnostic Test: Computed Tomography (CT)<br>* Participants will undergo a CT scan of the thoracic cavity<br>* Other names: CT;Diagnostic Test: Pulmonary Function Tests (PFT)<br>* Participants will have their lung function evaluated using PFT<br>* Other names: PFT;Diagnostic Test: Cardiopulmonary exercise testing (CPET)<br>* Participants will perform cardiopulmonary exercise testing as a measure of exercise capacity<br>* Other names: CPET;Diagnostic Test: Sputum analysis<br>* Participants will provide a sputum sample that will be analysed for eosinophils<br>Diagnostic Test: Blood analysis<br>* Participants will have their blood drawn and analysed for eosinophil count.<br>Other: Questionnaires<br>* Participants will complete questionnaires to assess activity related dyspnea, respiratory symptoms and health status impairment and respiratory related quality of life.<br>|
| former or current c-cigarette users<br>Includes 70 participants who are e-cigarette users who are also former or current combustible cigarette smokers. | Diagnostic Test: Hyperpolarized Xenon-129 MRI of the lungs<br>* Participants will be imaged using MRI using hyperpolarized xenon-129 gas as a contrast gas<br>* Other names: 129Xe MRI;Diagnostic Test: Computed Tomography (CT)<br>* Participants will undergo a CT scan of the thoracic cavity<br>* Other names: CT;Diagnostic Test: Pulmonary Function Tests (PFT)<br>* Participants will have their lung function evaluated using PFT<br>* Other names: PFT;Diagnostic Test: Cardiopulmonary exercise testing (CPET)<br>* Participants will perform cardiopulmonary exercise testing as a measure of exercise capacity<br>* Other names: CPET;Diagnostic Test: Sputum analysis<br>* Participants will provide a sputum sample that will be analysed for eosinophils<br>Diagnostic Test: Blood analysis<br>* Participants will have their blood drawn and analysed for eosinophil count.<br>Other: Questionnaires<br>* Participants will complete questionnaires to assess activity related dyspnea, respiratory symptoms and health status impairment and respiratory related quality of life.<br>|
| never smokers<br>Includes 10 participants who have never smoked e-cigarettes or combustible cigarettes. | Diagnostic Test: Hyperpolarized Xenon-129 MRI of the lungs<br>* Participants will be imaged using MRI using hyperpolarized xenon-129 gas as a contrast gas<br>* Other names: 129Xe MRI;Diagnostic Test: Computed Tomography (CT)<br>* Participants will undergo a CT scan of the thoracic cavity<br>* Other names: CT;Diagnostic Test: Pulmonary Function Tests (PFT)<br>* Participants will have their lung function evaluated using PFT<br>* Other names: PFT;Diagnostic Test: Cardiopulmonary exercise testing (CPET)<br>* Participants will perform cardiopulmonary exercise testing as a measure of exercise capacity<br>* Other names: CPET;Diagnostic Test: Sputum analysis<br>* Participants will provide a sputum sample that will be analysed for eosinophils<br>Diagnostic Test: Blood analysis<br>* Participants will have their blood drawn and analysed for eosinophil count.<br>Other: Questionnaires<br>* Participants will complete questionnaires to assess activity related dyspnea, respiratory symptoms and health status impairment and respiratory related quality of life.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report pulmonary imaging abnormalities. | Measured using 129-Xe MRI | 12 weeks following enrollment | 
| Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report pulmonary imaging abnormalities. | Measured using computed tomography imaging | 12 weeks following enrollment | 
| Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report respiratory symptoms or abnormal pulmonary function measured by FEV1. | Measured using forced expiratory volume in one second (FEV1) | 12 weeks following enrollment | 
| Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report respiratory symptoms or abnormal pulmonary function measured by FVC. | Measured using forced vital capacity (FVC) | 12 weeks following enrollment | 
| Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report respiratory symptoms or abnormal pulmonary function measured by TLC. | Measured using total lung capacity (TLC) | 12 weeks following enrollment | 
| Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report respiratory symptoms or abnormal pulmonary function measured by FRC. | Measured using functional residual capacity (FRC) | 12 weeks following enrollment | 
| Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report respiratory symptoms or abnormal pulmonary function measured by RV. | Measured using residual volume (RV) | 12 weeks following enrollment | 
| Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report respiratory symptoms or abnormal pulmonary function measured by FOT. | Measured using forced oscillation technique (FOT) | 12 weeks following enrollment | 
| Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report respiratory symptoms or abnormal pulmonary function measured by LCI. | Measured using lung clearance index (LCI) | 12 weeks following enrollment | 
| Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report respiratory symptoms or abnormal pulmonary function measured by FeNO. | Measured using Fractional Exhaled Nitric Oxide (FeNO). | 12 weeks following enrollment | 
| Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report respiratory symptoms or abnormal pulmonary function measured by exercise capacity | Exercise capacity measured by cardio-pulmonary exercise testing (CPET) | 12 weeks following enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in airways between e-cigarette-only smokers and both e-cigarette and c-cigarette smokers. | Measured using 129-Xe MRI | 5 years | 
| Differences in airways between e-cigarette-only smokers and never smokers. | Measured using 129-Xe MRI | 5 years | 
| Differences in parenchyma between e-cigarette-only smokers and both e-cigarette and c-cigarette smokers. | Measured using 129-Xe MRI | 5 years | 
| Differences in parenchyma between e-cigarette-only smokers and never smokers. | Measured using 129-Xe MRI | 5 years | 
| Changes in airways of e-cigarette smokers over time. | Measured using Xenon-129 (129-Xe) MRI | 5 years | 
| Changes in parenchyma of e-cigarette smokers over time. | Measured using Xenon-129 (129-Xe) MRI | 5 years | 
| Changes in lung function of e-cigarette smokers over time as measured by FEV1. | Measured using forced expiratory volume in one second (FEV1). | 5 years | 
| Changes in lung function of e-cigarette smokers over time as measured by FVC. | Measured using forced vital capacity (FVC) | 5 years | 
| Changes in lung function of e-cigarette smokers over time as measured by TLC. | Measured using total lung capacity (TLC) | 5 years | 
| Changes in lung function of e-cigarette smokers over time as measured by FRC. | Measured using functional residual capacity (FRC) | 5 years | 
| Changes in lung function of e-cigarette smokers over time as measured by RV. | Measured using residual volume (RV) | 5 years | 
| Changes in lung function of e-cigarette smokers over time as measured by FOT. | Measured using forced oscillation technique (FOT). | 5 years | 
| Changes in lung function of e-cigarette smokers over time as measured by LCI. | Measured using lung clearance index (LCI) | 5 years | 
| Changes in lung function of e-cigarette smokers over time as measured by FeNO. | Measured using Fractional Exhaled Nitric Oxide (FeNO) | 5 years | 
| Changes in lung function of e-cigarette smokers over time as measured by exercise capacity. | Exercise capacity measured by cardio-pulmonary exercise testing (CPET) | 5 years | 
| Changes in lung health of e-cigarette smokers over time as measured by the mMRC dyspnea scale questionnaire. | Measured using the modified medical research council (mMRC) dyspnea scale | 5 years | 
| Changes in lung health of e-cigarette smokers over time as measured by SGRQ. | Measured using the St. George's respiratory questionnaire (SGRQ) | 5 years | 
| Changes in lung health of e-cigarette smokers over time as measured by CAT. | Measured using the COPD assessment test (CAT) | 5 years | 
| Changes in lung health of e-cigarette smokers over time as measured by IPAQ. | Measured using the International Physical Activity Questionnaire (IPAQ). | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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e-cigarette smoking, pulmonary function, Xenon-129, Magnetic Resonance Imaging