# Airway pH regulation in asthma

> **NIH NIH P01** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $396,250

## Abstract

PROJECT SUMMARY/ABSTRACT
Project 2
The airway epithelium, like the renal tubular epithelium, expresses proteins that regulate luminal pH. For
example, glutaminase regulates ammonia production; it is inhibited by Th1 cytokines, acidifying the airway.
Cystic fibrosis transmembrane regulatory protein regulates outward HCO3- transit, and its absence results in
luminal acidification. Decreased airway lining fluid pH can promote airway inflammation as well as viral and
bacterial replication. We hypothesize that the distal airway epithelial surface is acidic, both because of high CO2
levels and low- pH lamellar bodies; that pH increases as airway lining fluid is swept proximally; and that impaired
airway luminal buffering can contribute to the pathophysiology of asthma. In particular, there is evidence that
acute asthma exacerbations are associated with a fall in airway luminal pH; an effect reversed by glucocorticoids.
Further, some asthma patients have a low luminal pH at baseline. Here, we will study the cellular determinants
of airway pH regulation. We will make use of the effect of airway pH to alter airway NO metabolism and
bioactivities (Project 1) to map the location and effects of low pH in the asthmatic airway in vivo. We will study
the recently discovered effects of androgens (Project 3) to promote the expression of beneficial pH regulatory
enzymes in asthma. Finally, we will study the potential benefit of inhaled buffer in asthma patients with
exacerbations. Specifically, we will carry out three aims.
In Aim 1, we will characterize the cellular determinants of airway pH. In Aim 2, we will map the epithelial pH of
the normal and asthmatic airway. In Aim 3, we will measure the effect of inhaled buffer on inflammation and
response to β2 agonists in asthma. At the end of the project, we anticipate having mapped both the cellular
regulation of airway epithelial pH and the anatomic variations in airway pH in health and in asthma; and we will
have developed a new, personalized approach to target pH abnormalities in patients with asthma exacerbations.

## Key facts

- **NIH application ID:** 10457997
- **Project number:** 5P01HL158507-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Benjamin Gaston
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $396,250
- **Award type:** 5
- **Project period:** 2021-08-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10457997

## Citation

> US National Institutes of Health, RePORTER application 10457997, Airway pH regulation in asthma (5P01HL158507-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10457997. Licensed CC0.

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