# Pulmonary cell fate and lung repair in rodent and porcine models of chlorine and phosgene inhalation injuries

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $482,024

## Abstract

Reactive chemicals such as chlorine and phosgene pose a grave threat to respiratory health. These agents
were used in warfare, with a significant risk of diversion for terrorist attacks, and frequently cause injuries
due to accidental release. Little progress has been made in developing countermeasures, with supportive
treatment remaining standard of care.
In this application, we hypothesize that inhalation of chlorine and phosgene damage different subsets of
pulmonary cells critical for maintenance of epithelial and endothelial barriers, gas exchange, and tissue
recovery. Our hypothesis is based on preliminary studies in rodent and porcine chlorine exposure models in
which we discovered a novel lung repair mechanism relying on submucosal lung cells that repopulate and
differentiate into new epithelia. In contrast to chlorine, phosgene initially spares upper airway cells and
primarily damages pulmonary endothelial cells, including newly discovered alveolar endothelial cell
subtypes, specialized aerocytes (“aCap”) and general capillary (“gCap”). Comparing mice and pigs, we noted
that the identity and location of cell populations in the pig lung more closely resemble the human anatomy.
The following specific aims are designed to comprehensively analyze the short- and long-term effects of
chlorine and phosgene on lung cell populations in rodents and pigs: Aim 1. Monitor molecular identities and
temporal dynamics of pulmonary cell populations after exposures to chlorine or phosgene and during
recovery; Aim 2. Visualize pulmonary epithelial and alveolar cells and structures after chlorine or phosgene
injury using thick slice microscopy; Aim 3. Compare effects of ventilator and oxygenation support and
positional maneuvers on pulmonary cell survival after phosgene or chlorine exposure

## Key facts

- **NIH application ID:** 10506127
- **Project number:** 1R01ES034387-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Satyanarayana Achanta
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $482,024
- **Award type:** 1
- **Project period:** 2022-09-02 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10506127

## Citation

> US National Institutes of Health, RePORTER application 10506127, Pulmonary cell fate and lung repair in rodent and porcine models of chlorine and phosgene inhalation injuries (1R01ES034387-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10506127. Licensed CC0.

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