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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: E Cigarette Use
• Intervention / Treatment: Diagnostic test: Hyperpolarized Xenon-129 MRI of the lungs; Diagnostic test: Computed Tomography (CT); Diagnostic test: Pulmonary Function Tests (PFT); Diagnostic test: Sputum analysis; Diagnostic test: Blood analysis; Other: Questionnaires; Diagnostic test: Cardiopulmonary exercise testing (CPET)

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.

• Study Type: Observational
• Enrollment (Anticipated): 150

Contacts and Locations

• Study Contact: Name: Angela Wilson, RRT; Phone Number: 24197 519-931-5777; Email: awilson@robarts.ca
• Study Contact Backup: Name: Grace E Parraga, PhD; Phone Number: 519-931-5265; Email: gparraga@robarts.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

1. e-cigarette users who did not require hospitalization, nor used c-cigarettes
2. e-cigarette users who also consumed c-cigarettes
3. never smokers

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
c-cigarette never users; Includes 70 participants who are e-cigarette users who have never smoked combustible cigarettes.	Diagnostic test: Hyperpolarized Xenon-129 MRI of the lungs; Participants will be imaged using MRI using hyperpolarized xenon-129 gas as a contrast gas; Other Names: 129Xe MRI; Diagnostic test: Computed Tomography (CT); Participants will undergo a CT scan of the thoracic cavity; Other Names: CT; Diagnostic test: Pulmonary Function Tests (PFT); Participants will have their lung function evaluated using PFT; Other Names: PFT; 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.; Diagnostic test: Cardiopulmonary exercise testing (CPET); Participants will perform cardiopulmonary exercise testing as a measure of exercise capacity; Other Names: CPET
former or current c-cigarette users; 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; Participants will be imaged using MRI using hyperpolarized xenon-129 gas as a contrast gas; Other Names: 129Xe MRI; Diagnostic test: Computed Tomography (CT); Participants will undergo a CT scan of the thoracic cavity; Other Names: CT; Diagnostic test: Pulmonary Function Tests (PFT); Participants will have their lung function evaluated using PFT; Other Names: PFT; 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.; Diagnostic test: Cardiopulmonary exercise testing (CPET); Participants will perform cardiopulmonary exercise testing as a measure of exercise capacity; Other Names: CPET
never smokers; Includes 10 participants who have never smoked e-cigarettes or combustible cigarettes.	Diagnostic test: Hyperpolarized Xenon-129 MRI of the lungs; Participants will be imaged using MRI using hyperpolarized xenon-129 gas as a contrast gas; Other Names: 129Xe MRI; Diagnostic test: Computed Tomography (CT); Participants will undergo a CT scan of the thoracic cavity; Other Names: CT; Diagnostic test: Pulmonary Function Tests (PFT); Participants will have their lung function evaluated using PFT; Other Names: PFT; 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.; Diagnostic test: Cardiopulmonary exercise testing (CPET); Participants will perform cardiopulmonary exercise testing as a measure of exercise capacity; Other Names: CPET

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Western University, Canada
• Collaborators: London Health Sciences Centre
• Investigators: Principal Investigator: Grace E Parraga, Western University - Robarts Research Institute

Publications and helpful links

General Publications

• Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. doi: 10.1183/09031936.05.00034805. No abstract available.
• Oostveen E, MacLeod D, Lorino H, Farre R, Hantos Z, Desager K, Marchal F; ERS Task Force on Respiratory Impedance Measurements. The forced oscillation technique in clinical practice: methodology, recommendations and future developments. Eur Respir J. 2003 Dec;22(6):1026-41. doi: 10.1183/09031936.03.00089403.
• Kirby M, Heydarian M, Svenningsen S, Wheatley A, McCormack DG, Etemad-Rezai R, Parraga G. Hyperpolarized 3He magnetic resonance functional imaging semiautomated segmentation. Acad Radiol. 2012 Feb;19(2):141-52. doi: 10.1016/j.acra.2011.10.007. Epub 2011 Nov 21.
• Owrangi AM, Etemad-Rezai R, McCormack DG, Cunningham IA, Parraga G. Computed tomography density histogram analysis to evaluate pulmonary emphysema in ex-smokers. Acad Radiol. 2013 May;20(5):537-45. doi: 10.1016/j.acra.2012.11.010.
• Pizzichini E, Pizzichini MM, Efthimiadis A, Evans S, Morris MM, Squillace D, Gleich GJ, Dolovich J, Hargreave FE. Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):308-17. doi: 10.1164/ajrccm.154.2.8756799.
• McGavin CR, Artvinli M, Naoe H, McHardy GJ. Dyspnoea, disability, and distance walked: comparison of estimates of exercise performance in respiratory disease. Br Med J. 1978 Jul 22;2(6132):241-3. doi: 10.1136/bmj.2.6132.241.
• Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Kline Leidy N. Development and first validation of the COPD Assessment Test. Eur Respir J. 2009 Sep;34(3):648-54. doi: 10.1183/09031936.00102509.
• Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire. Am Rev Respir Dis. 1992 Jun;145(6):1321-7. doi: 10.1164/ajrccm/145.6.1321.
• Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003 Aug;35(8):1381-95. doi: 10.1249/01.MSS.0000078924.61453.FB.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Davidson K, Brancato A, Heetderks P, Mansour W, Matheis E, Nario M, Rajagopalan S, Underhill B, Wininger J, Fox D. Outbreak of Electronic-Cigarette-Associated Acute Lipoid Pneumonia - North Carolina, July-August 2019. MMWR Morb Mortal Wkly Rep. 2019 Sep 13;68(36):784-786. doi: 10.15585/mmwr.mm6836e1.
• Landman ST, Dhaliwal I, Mackenzie CA, Martinu T, Steel A, Bosma KJ. Life-threatening bronchiolitis related to electronic cigarette use in a Canadian youth. CMAJ. 2019 Dec 2;191(48):E1321-E1331. doi: 10.1503/cmaj.191402. Epub 2019 Nov 20.

Helpful Links

• Canada, H. Canadian Tobacco, Alcohol and Drugs Survey (CTADS): summary of results for 2017

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2023
• Primary Completion (Anticipated): December 1, 2027
• Study Completion (Anticipated): December 1, 2027

Study Registration Dates

• First Submitted: November 2, 2020
• First Submitted That Met QC Criteria: November 2, 2020
• First Posted (Actual): November 4, 2020

Study Record Updates

• Last Update Posted (Actual): May 15, 2023
• Last Update Submitted That Met QC Criteria: May 12, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Xenon-129; Magnetic Resonance Imaging; pulmonary function; e-cigarette smoking
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Anesthetics, Inhalation; Xenon
• Other Study ID Numbers: ROB0048

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No