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

Award Number: R01AI143671
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Estimating the risk for and severity of respiratory infections attributable to CFTR heterozygosity - 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 we develop will have 29 broad implications for other diseases beyond respiratory infections.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $744,239 )
2025	2025	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	000	5	3/28/2025	NON-COMPETING CONTINUATION	$744,239
														Subtotal = $744,239

Issue Date FY: 2024 ( Subtotal = $764,865 )
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	000	4	3/15/2024	NON-COMPETING CONTINUATION	$764,865
														Subtotal = $764,865

Issue Date FY: 2023 ( Subtotal = $736,630 )
2023	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	000	3	3/7/2023	NON-COMPETING CONTINUATION	$736,630
														Subtotal = $736,630

Issue Date FY: 2022 ( Subtotal = $730,966 )
2022	2022	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	000	2	3/16/2022	NON-COMPETING CONTINUATION	$730,966
														Subtotal = $730,966

Issue Date FY: 2021 ( Subtotal = $743,016 )
2021	2021	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Allergy and Infectious Diseases Research	000	1	3/25/2021	NEW	$743,016
														Subtotal = $743,016

Grand Total All Awards = $3,719,716

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

Award Number: R01AI143671

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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