Ventilation and Pulmonary Endothelium Toxicities (VaPE-Tox) of E-cigarettes: A Randomized Crossover Pilot Study
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Pulmonary Microvascular Blood Flow (PMBF), Measured on Gadolinium-enhanced MRI, Between E-cigarette Exposed and Unexposed Conditions
研究概览
简要总结
Determination of the acute pulmonary toxicities of e-cigarettes in young adults is of major public health importance, as e-cigarette vapor contains established toxicants that as hypothesized cause acute damage to the airways and the pulmonary microvasculature that may promote the development of CLD, for which there remain few effective therapies.
The study therefore propose a pilot study using a randomized crossover design in ten healthy young adults to test the acute effects of a standardized e-cigarette exposure on two sensitive, safe, non-invasive imaging measures: (1) ventilation defects on hyperpolarized helium-enhanced magnetic resonance imaging, and (2) pulmonary microvascular blood flow on gadolinium-enhanced pulmonary magnetic resonance angiography.
详细描述
Magnetic resonance imaging (MRI) and angiography (MRA) measures are promising approaches to detecting and characterizing the anticipated acute pulmonary toxicities of e-cigarettes. Hyperpolarized helium (3He)-enhanced MRI may be more sensitive than spirometry, a global lung function measure, for determination of airway toxicities. 3He-enhanced MRI has been used to demonstrate the extent of ventilation defects in healthy persons with normal spirometry; to measure ventilation changes in asthmatics pre- and post-challenge with bronchodilators and methacholine; and to predict pulmonary hospitalizations in persons with COPD. Meanwhile, until recently, non-invasive measures of pulmonary vascular toxicities were lacking. The investigators have developed an innovative measure of pulmonary microvascular blood flow on gadolinium (Gd)-enhanced MRA, which the investigators found to be markedly abnormal in early chronic obstructive pulmonary disease (COPD) and emphysema, and to be associated with increased endothelial microparticles, a marker of endothelial dysfunction. Nonetheless, neither of these sensitive, non-invasive, repeatable, and reproducible measures has ever been used to assess e-cigarette toxicities.
It is hypothesized that e-cigarette vapor inhalation will result in an acute increase in global and regional ventilation defects and an acute decrease in global and regional pulmonary microvascular perfusion.
This pilot work will provide the experience and data to support subsequent funding applications powered to definitively establish the acute toxicities of e-cigarette vapor of various compositions (e.g., with and without nicotine, with and without flavoring) in persons with and without chronic lung diseases (e.g., asthma) on pulmonary ventilation and microvascular perfusion. Furthermore, confirmation of the hypotheses in this sample would provide important preliminary evidence of e-cigarette pulmonary toxicities to inform interim regulatory decisions, as well as potentially generating vivid images of e-cigarette harms that may be meaningful to the general public and therefore suitable for use in public education campaigns.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •current use of e-cigarettes (>1x/month but <4 days/week)
排除标准
- •any chronic medical or major psychiatric problems including current asthma
- •self-reported heavy snoring/sleep apnea
- •pre-bronchodilator FEV1 or FVC <80% predicted or FEV1/FVC < lower limit of normal
- •MRI exclusions (pregnancy, claustrophobia, metal in body, gadolinium allergy, eGFR <60 mL/min/1.73m2)
- •MRI scan with contrast within the last 12 months or planned MRI with contrast in the next 6 months
- •use of any of the following in the prior 30 days: any conventional cigarettes, marijuana >10 days, any illicit drugs, any medication or inhalers (excluding hormonal contraceptives)
- •binge drinking (≥5 alcoholic beverages over 2 hours) over the prior two weeks
- •adverse symptomatic response to the study e-cigarette exposure (e.g., palpitations, shortness of breath, chest pain, headache, dizziness)
研究组 & 干预措施
E-cigarette first
Participants will undergo the e-cigarette exposure prior to the first two MRI measures, and then they will undergo the sham exposure prior to the last two MRI measures. The two MRIs performed under both experimental exposures (e-cigarette and sham) will be enhanced by (1) gadolinium and then (2) hyperpolarized 3-helium.
干预措施: E-cigarette (Device)
E-cigarette first
Participants will undergo the e-cigarette exposure prior to the first two MRI measures, and then they will undergo the sham exposure prior to the last two MRI measures. The two MRIs performed under both experimental exposures (e-cigarette and sham) will be enhanced by (1) gadolinium and then (2) hyperpolarized 3-helium.
干预措施: Sham (Other)
E-cigarette first
Participants will undergo the e-cigarette exposure prior to the first two MRI measures, and then they will undergo the sham exposure prior to the last two MRI measures. The two MRIs performed under both experimental exposures (e-cigarette and sham) will be enhanced by (1) gadolinium and then (2) hyperpolarized 3-helium.
干预措施: Hyperpolarized 3-Helium (Drug)
E-cigarette first
Participants will undergo the e-cigarette exposure prior to the first two MRI measures, and then they will undergo the sham exposure prior to the last two MRI measures. The two MRIs performed under both experimental exposures (e-cigarette and sham) will be enhanced by (1) gadolinium and then (2) hyperpolarized 3-helium.
干预措施: Gadolinium (Drug)
Sham first
Participants will undergo the sham exposure prior to the first two MRI measures, and then they will undergo the e-cigarette exposure prior to the last two MRI measures. The two MRIs performed under both experimental exposures (e-cigarette and sham) will be enhanced by (1) gadolinium and then (2) hyperpolarized 3-helium.
干预措施: E-cigarette (Device)
Sham first
Participants will undergo the sham exposure prior to the first two MRI measures, and then they will undergo the e-cigarette exposure prior to the last two MRI measures. The two MRIs performed under both experimental exposures (e-cigarette and sham) will be enhanced by (1) gadolinium and then (2) hyperpolarized 3-helium.
干预措施: Sham (Other)
Sham first
Participants will undergo the sham exposure prior to the first two MRI measures, and then they will undergo the e-cigarette exposure prior to the last two MRI measures. The two MRIs performed under both experimental exposures (e-cigarette and sham) will be enhanced by (1) gadolinium and then (2) hyperpolarized 3-helium.
干预措施: Hyperpolarized 3-Helium (Drug)
Sham first
Participants will undergo the sham exposure prior to the first two MRI measures, and then they will undergo the e-cigarette exposure prior to the last two MRI measures. The two MRIs performed under both experimental exposures (e-cigarette and sham) will be enhanced by (1) gadolinium and then (2) hyperpolarized 3-helium.
干预措施: Gadolinium (Drug)
结局指标
主要结局
Pulmonary Microvascular Blood Flow (PMBF), Measured on Gadolinium-enhanced MRI, Between E-cigarette Exposed and Unexposed Conditions
时间窗: After exposure (approximately 30 seconds)
PMBF will be measured on gadolinium-enhanced MRI after e-cigarette and sham exposures. There were four days between the measurements of PMBF (e-cigarette) and PMBF (sham). PMBF is measured in mL(blood)/min/mL(lung volume). Lower PMBF has been observed in adults with COPD and emphysema.
Ventilation Defect Percentage (VDP), Measured on Hyperpolarized 3-helium Enhanced MRI
时间窗: After exposure (approximately 30 seconds)
VDP will be measured on hyperpolarized 3Helium-enhanced MRI after e-cigarette and sham exposures. Due to limitations of prior qualitative/visual assessments of MRI, we developed and validated a new deep learning approach to the precise measurement of ventilation defects and report the percent non-fully ventilated lung using this method.
次要结局
- Regional PMBF, Measured on Gadolinium-enhanced MRI(After exposure (approximately 30 seconds))
- Regional VDP, Measured on Hyperpolarized 3-helium Enhanced MRI(After exposure (approximately 30 seconds))
- Lung Function, Measured on Spirometry(After exposure (approximately 30 seconds))
- Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)(After exposure (approximately 30 seconds))
- Cardiac Output, Measured on Cardiac MRI(After exposure (approximately 30 seconds))
研究者
Elizabeth Oelsner
Assistant Professor of Medicine
Columbia University