Ventilation and Pulmonary Endothelium Toxicities of E-cigarettes: A Randomized Crossover Pilot Study
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Chronic Obstructive Pulmonary Disease, Pulmonary |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 21 - 35 |
| Updated: | 1/10/2019 |
| Start Date: | March 1, 2017 |
| End Date: | January 2019 |
Ventilation and Pulmonary Endothelium Toxicities (VaPE-Tox) of E-cigarettes: A Randomized Crossover Pilot Study
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.
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.
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.
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.
Inclusion Criteria:
- current use of e-cigarettes (>1x/month but <4 days/week)
Exclusion Criteria:
- 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)
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