# Prospective Health Outcomes and Inflammatory Biomarkers Associated with e-Cigarette Use

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $509,303

## Abstract

Project Summary. This project is designed to identify validated biomarkers for use in the assessment
of electronic nicotine delivery systems (ENDS) by the FDA. Since the introduction of ENDS, commonly
referred to as e-cigarettes, there has been a large increase in ENDS use among young adults and older
traditional cigarette smokers who also use ENDS (dual users). Since 2016, the Food and Drug Administration
(FDA) has had regulatory authority over ENDS, and there is an acute need for ENDS-related biomarkers
that can be used as validated surrogate endpoints for evaluation of new ENDS products. With the goal
of validated biomarker discovery in two independent cohorts, the COPDGene and UCSD ENDS studies, we
propose to identify ENDS-related inflammatory biomarkers in ENDS only and dual users and relate
these biomarkers to five-year lung health outcomes. COPDGene is an ongoing, longitudinal study of
>6,000 current and former traditional cigarette (t-cig) smokers enriched for chronic obstructive pulmonary
disease (COPD) with detailed longitudinal lung phenotyping data (including chest CT), genome-wide blood
RNA-seq, and proteomic data. The UCSD ENDS Study is a controlled study of young ENDS only users and
controls with detailed assessment of inflammatory biomarkers in the oropharynx, airways and blood.
 Biomarkers used as validated surrogate measures must be 1) associated with ENDS use, 2) predictive of
health outcomes, and 3) have a strong biological rationale. We hypothesize that inflammatory biomarkers
of ENDS use will be predictive of five-year lung health effects. In Aim 1 of this proposal, discovery of
inflammatory transcriptomic and proteomic biomarkers of ENDS exposure will be performed in subjects from
the COPDGene five-year study visit, and biomarkers will be validated in two independent sets of subjects
from the COPDGene ten-year visit and the UCSD ENDS Study. In Aim 2 we will identify antibody-specific
adaptive immune response biomarkers of ENDS exposure using adaptive immune receptor repertoire
sequencing (AIRR-seq). Auto-antibodies are biomarkers that are associated with the degree of lung damage
in COPD. AIRR-seq is a powerful tool for inflammatory biomarker discovery that characterizes an individual’s
decades-long history of antibody responses. In Aim 3 we will use machine learning predictive models to relate
ENDS-associated biomarker panels to five-year lung health outcomes from COPDGene. The investigative
team for this grant is well-positioned to identify novel inflammatory biomarkers of ENDS use. The COPDGene
and UCSD cohorts have the detailed lung phenotyping and molecular characterization necessary to discover
and clinically validate biomarkers in two important populations of ENDS users, i.e. ENDS only and dual users.

## Key facts

- **NIH application ID:** 10018099
- **Project number:** 5R01HL147326-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Peter Castaldi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $509,303
- **Award type:** 5
- **Project period:** 2019-09-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018099

## Citation

> US National Institutes of Health, RePORTER application 10018099, Prospective Health Outcomes and Inflammatory Biomarkers Associated with e-Cigarette Use (5R01HL147326-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10018099. Licensed CC0.

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