# Immunosuppressive injurious effects of e-cigarettes on human lung parenchyma

> **NIH NIH R01** · NATIONAL JEWISH HEALTH · 2021 · $465,888

## Abstract

Project Summary/Abstract
The goal of this two PI research proposal is to determine the immunosuppressive and injurious effects of e-
cigarettes on human distal lung structural cells (i.e. small airway epithelial cells and lung microvascular
endothelial cells) that are critical to the pathogenesis of chronic obstructive pulmonary disease (COPD), typically
induced by tobacco cigarette smoke exposure. The use of e-cigarettes is rapidly increasing in the US youth
population, but its health effects on distal lungs have not been investigated. We have found that inhaling e-
cigarette vapor (ECVap) can reach small airways to cause distal lung injury. Specifically, we have demonstrated
that exposures to ECVap constituents, including nicotine, significantly weaken distal lung (e.g. small airway)
innate immunity against influenza A virus infection and microvascular endothelial barrier function, and enhance
lung inflammation. We will test the hypothesis that e-cigarettes impair the antiviral immunity, causing increased
neutrophilic inflammation and distal lung structural cell (small airway and microvascular endothelial cell) injury
by proposing three specific aims. In Aim 1, we will identify the mechanisms whereby ECVap impairs the antiviral
immunity of human distal lungs by performing RNA sequencing in precision-cut human (15 to 25 years old) lung
slices exposed to ECVap and influenza A viruses (IAV), and carrying out human primary small airway epithelial
cell air-liquid interface culture in the presence or absence of ECVap and IAV. In Aim 2, we will determine how
ECVap enhances neutrophilic inflammatory response to IAV infection of the human distal lung by using the
human lung slices and the co-culture system of human microvascular endothelial cells and neutrophils. In Aim
3, we will determine how ECVap increases distal lung injury following IAV infection by testing if ECVap exposure
reduces sphingolipid pro-survival signaling and subsequently increases the vulnerability of small airway epithelial
and endothelial cells to virus-induced injury. Research findings from our proposed studies will significantly
improve our understanding about the distal lung health effects of e-cigarette use in youth, and inform policies of
e-cigarette regulation.

## Key facts

- **NIH application ID:** 10241973
- **Project number:** 5R01HL144396-04
- **Recipient organization:** NATIONAL JEWISH HEALTH
- **Principal Investigator:** Hong W Chu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $465,888
- **Award type:** 5
- **Project period:** 2018-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241973

## Citation

> US National Institutes of Health, RePORTER application 10241973, Immunosuppressive injurious effects of e-cigarettes on human lung parenchyma (5R01HL144396-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241973. Licensed CC0.

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