# Field Study to Understand Progression of Chronic Airway Infection

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $713,558

## Abstract

Abstract
A key problem in chronic infections is progressive dysfunction of the infected organ. Importantly, patients
with similar risk factors often exhibit marked variation in the rate of disease progression, as do individual
patients at different times. The chronic Pseudomonas aeruginosa (Pa) lung infections in people with cystic
fibrosis (CF) are a prime example. Pronounced variability in the rate of lung function decline is seen across
patients even when host CFTR genotype and airway microbiology are similar.
While both bacterial and host factors likely contribute to disease variation, several new findings lead us to
focus on genetic variation that evolves in infecting Pa. First, CF Pa strains have been found to genetically
diversify in vivo, producing clonally-related variants that differ markedly in virulence, and these variants can
co-exist simultaneously inside lungs. Second, our data show that the distribution of genetic variants
changes over time and the emergence of highly virulent genetic variants can be temporally associated with
changes in disease. Finally, many groups have investigated host genetic and environmental factors that
affect disease, but the effects of bacterial genetic variants on disease progression are relatively unexplored
Here we exploit unique clinical and technical resources, and our knowledge of Pa pathogenesis to test the
hypothesis that some gene variants that evolve in the Pa populations infecting CF patients increase lung
injury. We will test this hypothesis in three steps. First, will we measure Pa gene variants in sputum
collected at specific time points based on the lung disease phenotypes. Second, we will perform genetic
association analysis to delineate which variants/variant groups are most strongly associated with the
phenotypes. Third, we will investigate the functional effects of gene variants on Pa virulence, host injury,
and inflammation. This work could identify potential cause and effect relationships and provide proof of
principle for a disease progression mechanism that may operate in many chronic infections.

## Key facts

- **NIH application ID:** 10217239
- **Project number:** 5R01HL148274-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** MARY J EMOND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $713,558
- **Award type:** 5
- **Project period:** 2019-08-07 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217239

## Citation

> US National Institutes of Health, RePORTER application 10217239, Field Study to Understand Progression of Chronic Airway Infection (5R01HL148274-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10217239. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*