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

Official title

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

Overview

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

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.

Interventions

• Diagnostic test Hyperpolarized Xenon-129 MRI of the lungs
  Participants will be imaged using MRI using hyperpolarized xenon-129 gas as a contrast gas
• Diagnostic test Computed Tomography (CT)
  Participants will undergo a CT scan of the thoracic cavity
• Diagnostic test Pulmonary Function Tests (PFT)
  Participants will have their lung function evaluated using PFT
• Diagnostic test Cardiopulmonary exercise testing (CPET)
  Participants will perform cardiopulmonary exercise testing as a measure of exercise capacity
• Diagnostic test Sputum analysis
  Participants will provide a sputum sample that will be analysed for eosinophils
• Diagnostic test Blood analysis
  Participants will have their blood drawn and analysed for eosinophil count.
• Other Questionnaires
  Participants will complete questionnaires to assess activity related dyspnea, respiratory symptoms and health status impairment and respiratory related quality of life.

Primary outcome measures

• Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report pulmonary imaging abnormalities. [Time frame: 12 weeks following enrollment]
• Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report pulmonary imaging abnormalities. [Time frame: 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. [Time frame: 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. [Time frame: 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. [Time frame: 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. [Time frame: 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. [Time frame: 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. [Time frame: 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. [Time frame: 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. [Time frame: 12 weeks following enrollment]

Secondary outcome measures (12)

• Differences in airways between e-cigarette-only smokers and both e-cigarette and c-cigarette smokers. [Time frame: 5 years]
• Differences in airways between e-cigarette-only smokers and never smokers. [Time frame: 5 years]
• Differences in parenchyma between e-cigarette-only smokers and both e-cigarette and c-cigarette smokers. [Time frame: 5 years]
• Differences in parenchyma between e-cigarette-only smokers and never smokers. [Time frame: 5 years]
• Changes in airways of e-cigarette smokers over time. [Time frame: 5 years]
• Changes in parenchyma of e-cigarette smokers over time. [Time frame: 5 years]
• Changes in lung function of e-cigarette smokers over time as measured by FEV1. [Time frame: 5 years]
• Changes in lung function of e-cigarette smokers over time as measured by FVC. [Time frame: 5 years]
• Changes in lung function of e-cigarette smokers over time as measured by TLC. [Time frame: 5 years]
• Changes in lung function of e-cigarette smokers over time as measured by FRC. [Time frame: 5 years]
• Changes in lung function of e-cigarette smokers over time as measured by RV. [Time frame: 5 years]
• Changes in lung function of e-cigarette smokers over time as measured by FOT. [Time frame: 5 years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

Canada · 1 center

• Robarts Research Institute; The University of Western Ontario; London Health Sciences Cent — London

Publications

• Hua M, Alfi M, Talbot P. Health-related effects reported by electronic cigarette users in online forums. J Med Internet Res. 2013 Apr 8;15(4):e59. doi: 10.2196/jmir.2324. PMID 23567935
• Wang MP, Ho SY, Leung LT, Lam TH. Electronic Cigarette Use and Respiratory Symptoms in Chinese Adolescents in Hong Kong. JAMA Pediatr. 2016 Jan;170(1):89-91. doi: 10.1001/jamapediatrics.2015.3024. No abstract available. PMID 26551991
• McConnell R, Barrington-Trimis JL, Wang K, Urman R, Hong H, Unger J, Samet J, Leventhal A, Berhane K. Electronic Cigarette Use and Respiratory Symptoms in Adolescents. Am J Respir Crit Care Med. 2017 Apr 15;195(8):1043-1049. doi: 10.1164/rccm.201604-0804OC. PMID 27806211
• Cho JH, Paik SY. Association between Electronic Cigarette Use and Asthma among High School Students in South Korea. PLoS One. 2016 Mar 4;11(3):e0151022. doi: 10.1371/journal.pone.0151022. eCollection 2016. PMID 26942764
• Schweitzer RJ, Wills TA, Tam E, Pagano I, Choi K. E-cigarette use and asthma in a multiethnic sample of adolescents. Prev Med. 2017 Dec;105:226-231. doi: 10.1016/j.ypmed.2017.09.023. Epub 2017 Sep 28. PMID 28964850
• Layden JE, Ghinai I, Pray I, Kimball A, Layer M, Tenforde MW, Navon L, Hoots B, Salvatore PP, Elderbrook M, Haupt T, Kanne J, Patel MT, Saathoff-Huber L, King BA, Schier JG, Mikosz CA, Meiman J. Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report. N Engl J Med. 2020 Mar 5;382(10):903-916. doi: 10.1056/NEJMoa1911614. Epub 2019 Sep 6. PMID 31491072
• Henry TS, Kanne JP, Kligerman SJ. Imaging of Vaping-Associated Lung Disease. N Engl J Med. 2019 Oct 10;381(15):1486-1487. doi: 10.1056/NEJMc1911995. Epub 2019 Sep 6. No abstract available. PMID 31491070
• Maddock SD, Cirulis MM, Callahan SJ, Keenan LM, Pirozzi CS, Raman SM, Aberegg SK. Pulmonary Lipid-Laden Macrophages and Vaping. N Engl J Med. 2019 Oct 10;381(15):1488-1489. doi: 10.1056/NEJMc1912038. Epub 2019 Sep 6. No abstract available. PMID 31491073

Identifiers

NCT: NCT04616313 · ROB0048

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗