# How nicotine delivered by Electronic Nicotine Delivery Systems (ENDS) affects the lung and its recovery from cigarette smoking

> **NIH VA I01** · VA SALT LAKE CITY HEALTHCARE SYSTEM · 2024 · —

## Abstract

Since their introduction to the marketplace, Electronic Nicotine Delivery Systems (ENDS) have
experienced a rapid growth in popularity as a means to deliver nicotine to the user in unprecedented high
concentrations and purity. There is little evidence pertaining to the consequences this route of nicotine self-
administration has on the health of the naïve user or those who use this product to aid in cigarette smoking (CS)
cessation. This Merit application is designed to fill gaps in our understanding of these issues. Here the focus
will be on how the lung morphology and normal gene expression including a defined response to the inhaled
house dust mite allergen is impacted by ENDS:nic exposure, especially in the lung previously exposed to
cigarette smoke. There are 3 interactive Aims to address the Project Hypothesis: The use of nicotine as delivered
by electronic nicotine delivery systems (ENDS:nic), both in the naïve lung and subsequent to cessation of
cigarette smoking (CS), impacts the morphology and immune responsiveness of the exposed lung and
complicates normal recovery processes following CS cessation. Specific Aim 1. Does ENDS:nic exposure
impact lung morphology, mucin production and fibrosis in the naïve lung and the lung previously
damaged by CS exposure? Measurement of ENDS:nic effects on the lung will include morphologic changes
in alveolar spaces, mucin production (e.g., Muc5b) and deposition, and changes to collagen deposition (fibrosis).
Results will determine how the form of nicotine (salt versus free-base) and its relative concentrations impact
these parameters. We further hypothesize that ENDS:nic exposure (and possibly carrier alone) will alter lung
morphology and that mice previously exposed to CS will not recover to the same extent as mice that are allowed
to recover in the absence of END:nic use and possibly carrier. Specific Aim 2. Does ENDS:nic impact
immune function in naïve mice and does the transition from cigarette smoke to ENDS:nic exposure
impede immune functional recovery? ENDS:Nic delivery strongly suppresses the lung eosinophil response
to inhalation of the common house dust mite (HDM) allergen. This reliable experimental measurement provides
an end-point to quantify the impact by different ionic forms of nicotine, their concentration and the associated e-
liquid carrier compounds. The focus will also be on transcriptional responsiveness to HDM by AM and specific
lung cellular signaling responses during recovery from prior CS-associated damage in the context of ENDS:nic
relative to no product use as well as the impact by ENDS:nic itself. Specific Aim 3. How are alpha7-modulated
cell-signaling mechanisms in the alveolar macrophage (AM) affected by ENDS:nic exposure? These
experiments will focus on alveolar macrophages (AM) which constitute the majority of immune cells in the
bronchial alveolar lung fluids (BALF). Newly developed methods that combine AM enrichment from the BALF of
ENDS:nic and CS exposed mice and in...

## Key facts

- **NIH application ID:** 11016905
- **Project number:** 5I01BX004637-05
- **Recipient organization:** VA SALT LAKE CITY HEALTHCARE SYSTEM
- **Principal Investigator:** Noel G. Carlson
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11016905

## Citation

> US National Institutes of Health, RePORTER application 11016905, How nicotine delivered by Electronic Nicotine Delivery Systems (ENDS) affects the lung and its recovery from cigarette smoking (5I01BX004637-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11016905. Licensed CC0.

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