# R01- Mapping environmental contributions to rapid lung disease progression in cystic fibrosis

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2022 · $465,922

## Abstract

PROJECT SUMMARY/ABSTRACT
Progressive lung disease is the leading cause of death in individuals with cystic fibrosis (CF). Rapid decline,
characterized by accelerated loss of lung function, is common for CF patients, and cannot be explained or
predicted by CFTR/gene dysfunction alone. Mapping the environmental exposures and community
characteristics (geomarkers) that predict patient-specific rapid decline and providing tools for earlier detection
and monitoring at the center level are essential to transforming the precision of CF clinical care, and offer an
opportunity to adjust interventions to prevent irreversible lung damage. The translation of these tools into
practice is further hindered by continued use of antiquated statistical methods that ignore the interplay between
nonlinear lung function and recurrent pulmonary exacerbations in the clinical course of CF, disregard known
mortality biases that can lead to inaccurate projections of rapid decline, and do not leverage extant geographic
data on geomarkers, such as air quality or neighborhood socioeconomic conditions, to improve prediction of
rapid decline. In this proposal, we will utilize comprehensive geocoding algorithms, novel statistical methods
and powerful computational medicine tools for integration into clinical algorithms for the detection to drive early
intervention of rapid lung disease progression. The overall objective of this research is to leverage a rich CF
registry, extant national and local environmental data sources and prospectively collected study data to
accurately forecast the onset of rapid decline in individual patients, and to develop a feasible medical-
monitoring tool that positively impacts CF point-of-care decision-making. Our overarching hypothesis is that
interactive computational medicine tools for dynamic prediction and clinical surveillance of rapid pulmonary
decline in CF will enhance local disease monitoring. This will be accomplished by incorporating both
established and novel environmental exposures and community characteristics of CF patients. Our specific
aims are to 1) phenotype patients who experience early, rapid pulmonary decline informed by environmental
exposures; 2) transform dynamic prediction of rapid lung-function decline and exacerbations in CF patients
through high-dimensional, multi-level joint model mapping with environmental factors; 3) design and implement
decision support capabilities that monitor real-time lung-function decline and risk of exacerbations for
personalized, center-specific CF patient management. Once systems to accurately and precisely predict rapid
decline are in place, better prospective treatment decisions will become possible, resulting in better patient
outcomes and improved precision medicine/care.

## Key facts

- **NIH application ID:** 10321559
- **Project number:** 5R01HL141286-04
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Rhonda Szczesniak
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $465,922
- **Award type:** 5
- **Project period:** 2019-01-18 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10321559

## Citation

> US National Institutes of Health, RePORTER application 10321559, R01- Mapping environmental contributions to rapid lung disease progression in cystic fibrosis (5R01HL141286-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10321559. Licensed CC0.

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