# Estimating the risk for and severity of respiratory infections attributable to CFTR heterozygosity

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2024 · $764,865

## Abstract

Project Summary/Abstract
 1 Cystic fibrosis is one of the most common autosomal regressive genetic disorders in the United States:
 2 approximately 1 out of 32 Caucasians and 1 out of 61 African Americans is a CF carrier. A hallmark of this
 3 disease is recurrent respiratory infections. However, cystic fibrosis requires two copies of the CFTR
 4 mutation. Traditionally, one non-mutated CFTR gene was thought to be sufficient for maintaining health.
 5 However, a few small studies and preliminary work by our group have demonstrated that CF carriers may
 6 be at increased risk for respiratory infections, including recurrent sinusitis, pneumonia, and atypical
 7 mycobacterial infections, than non-CF carriers. Given an estimated population of 15 million CF carriers in
 8 the United States, if carriers are more likely to acquire respiratory infections, the attributable burden of
 9 respiratory infections and corresponding antimicrobial use attributable to the CF-carrier state may be
10 substantial. Thus, there is a critical need for population-based investigations to precisely determine the
11 attributable risk of the CF-carrier state for respiratory infections.
12 The goal of our research is to determine the role of the CF-carrier state on the risk for acquiring respiratory
13 infections. Due to the frequency of genetic testing for CFTR mutations for genetic counseling, it is possible
14 to identify CF carriers in some existing population-based data sets. Our group has recently demonstrated
15 that CF carriers are at significantly greater risk for respiratory infections compared to age and sex matched
16 controls. However, more work is needed that considers other patient characteristics as well as patients'
17 specific CF mutations. In addition, the biological plausibility of these findings needs to be established. Thus,
18 we will determine the natural history of respiratory infections for CF carriers using administrative claims
19 data; determine the risk for respiratory infections among CF carriers in a genotyped cohort using data from
20 electronic medical records, and assess airway epithelial function in CF carriers compared to non-carriers.
21 This work is significant because respiratory infections are a major cause of morbidity and mortality; CF
22 carriers are common and can be identified by current genetic counseling methods; and there are CFTR-
23 modulating therapies available that may be cost-effective treatments for CF carriers with excessive
24 respiratory infections. This work is innovative because all previous work in this area has been done using
25 small cohorts of patients, and we will have access to a large cohort of CF carriers and controls. Also, we will
26 be able to identify the CF carriers using diagnosis and procedure codes in administrative data and the
27 medical record an in one cohort we will be able to identify specific CFTR mutations.
28 Given the number of CF carriers in the general population, the methods and models ...

## Key facts

- **NIH application ID:** 10805471
- **Project number:** 5R01AI143671-04
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** PHILIP M POLGREEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $764,865
- **Award type:** 5
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10805471

## Citation

> US National Institutes of Health, RePORTER application 10805471, Estimating the risk for and severity of respiratory infections attributable to CFTR heterozygosity (5R01AI143671-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10805471. Licensed CC0.

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