# Using PET to Measure Pulmonary Oxidative Stress in E-cigarette Users

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2020 · $203,125

## Abstract

Worldwide, more than 3.5 million people die annually from smoking-related lung diseases. Although public
awareness regarding smoking-related risks has increased and tobacco smoking has declined in the United
States, the use of Electronic Nicotine Delivery Systems, or ENDS (e.g., e-cigarettes, vape pens), has
dramatically increased, particularly among youth and young adults. The increased popularity of ENDS is due in
part to targeted marketing efforts asserting that these products represent a “safer alternative” to traditional
cigarettes. To date, however, there is a paucity of human data on the potential toxicity of ENDS use, particularly
relative to that of cigarette smoke. Inducible nitric oxide synthase (iNOS) is an enzyme that is constitutively
expressed in lung epithelium and is specific for inflammation, a common pathway for many types of lung disease.
We propose to measure lung inflammation using Positron Emission Tomography (PET) imaging with [18F]-6-
(1/2)(2-fluoro-propyl)-4-methylpyridin-2-amine ([18F]NOS), an exciting new PET radiotracer that targets the
inducible isoform of nitric oxide synthase. The goal of the proposed study is to leverage our experience with this
novel imaging technique to compare, for the first time, lung inflammation in ENDS users with cigarette smokers
and nonsmokers. Specifically, we will quantify, localize, and compare, for the first time, lung inflammation in
ENDS users with cigarette smokers and nonsmokers using PET lung imaging with [18F]NOS (Aim 1) and examine
and compare biomarkers of airway (fractional exhaled nitric oxide (FeNO)) and lung inflammation (i.e., pro-
inflammatory cytokines (TNF-α, IL-1β, IL-8)) and lung function (as measured by forced expiratory volume (FEV)
and forced vital capacity (FVC) using spirometry) (Aim 2). To accomplish these goals, 60 subjects [3 groups of
20: ENDS users, traditional cigarette smokers, and nonsmoking controls] will be carefully screened and smoking
status will be biochemically verified. Subjects will complete self-report measures, undergo a one-hour [18F]NOS
PET/CT (computed tomography) scan of the chest, provide a breath and blood sample for measurement of
biomarkers of airway and lung inflammation, and complete lung function tests using spirometry. The proposed
study would be the first use of [18F]NOS PET lung imaging to localize and quantify the extent of lung inflammation,
examine biomarkers of airway and lung inflammation, and lung function due to ENDS use and cigarette smoking.
By measuring specific inflammatory effects of ENDS use on lung tissue, our proposal directly supports the FDA's
goal of developing ENDS product standards to protect public health.

## Key facts

- **NIH application ID:** 10018085
- **Project number:** 5R21HL144673-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Reagan R Wetherill
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $203,125
- **Award type:** 5
- **Project period:** 2019-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018085

## Citation

> US National Institutes of Health, RePORTER application 10018085, Using PET to Measure Pulmonary Oxidative Stress in E-cigarette Users (5R21HL144673-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10018085. Licensed CC0.

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