# Investigating the Resilient Smoker

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $77,142

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposal seeks to address a gap in knowledge about the clinical and biological factors that are associated
with resilience to the development of smoking-related lung disease and protective pathways that may be
leveraged to develop new therapies and preventative approaches for COPD. Tobacco smoke is the most
common environmental risk factor for COPD, however despite this strong association, it is estimated that only
15-25% of smokers will develop COPD when using spirometric criteria for the diagnosis. It is uncertain why
some smokers are spirometrically “resilient” to the damaging pulmonary effects of cigarette smoke. One
premise is that the traditional spirometric definition of COPD may underestimate disease and overestimate the
percentage of smokers who are truly “resilient”. Specifically, a significant proportion of smokers who do not
meet spirometric criteria for COPD still have respiratory symptoms, exacerbations, and radiographic
abnormalities, which suggests they are experiencing adverse effects from tobacco smoke exposure and
indicate they may not be truly “resilient.” One factor underlying resilience may be protective factors in the
airway epithelium since this is the first anatomic surface of the lung exposed to the highest concentration of
tobacco smoke. My long-term goal is to identify pathobiological mechanisms related to resilience as opposed
to disease onset and progression. My central hypotheses are that 1)“resilience” is better defined using multiple
clinical domains and that 2)variability in the airway epithelial response to chronic smoke exposure, as
measured by gene expression alterations, can modify disease susceptibility, and provide insight into the
mechanisms of “resilience.” I propose to test these hypotheses in two specific aims. Aim 1: Systematically
develop a new multidimensional definition of a “resilient smoker” using multiple clinical domains and determine
its prevalence and biological significance in a longitudinal study of COPD. Aim 2: Identify airway epithelial gene
expression markers associated with the “resilient smoker” using SPIROMICS, an NHLBI-funded multi-site
longitudinal cohort study of COPD which has obtained detailed clinical, radiographic, physiological data, and
bronchoscopic samples of airway epithelial cells. The public health impact of these aims is that successful
completion will identify new strategies to treat and prevent COPD. This overall approach is innovative because
most translational studies focus on pathways associated with disease rather than protection from development
of the disease. This proposal is directly responsive to NHLBI priorities because it focuses on Objective 1 the
NHLBI Strategic Vision: “Understand normal biological function and resilience”. Furthermore, this award will
have a positive impact on Dr. Anita Oh's training, as a clinical fellow at the University of California San
Francisco, by providing her with the support necessary to acquire kn...

## Key facts

- **NIH application ID:** 10221775
- **Project number:** 5F32HL149329-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Anita Oh
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $77,142
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10221775

## Citation

> US National Institutes of Health, RePORTER application 10221775, Investigating the Resilient Smoker (5F32HL149329-03). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10221775. Licensed CC0.

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