# Transitions from Impaired Respiratory Health to Lung Disease

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $127,875

## Abstract

Project Summary/Abstract
The respiratory community has traditionally defined respiratory health as the absence of lung disease. This
definition results in early lung disease being defined as the first appearance of abnormal respiratory physiology,
a paradigm that does not acknowledge that the transition from health to chronic lung disease develops over
years, a period of time when lung disease interception strategies could be most efficacious. A public health
strategy for chronic lung disease focused on disease interception mandates the detection of impaired respiratory
health before chronic lung disease becomes clinically apparent. Our group has investigated the predictors and
consequences of lung function decline in the Coronary Artery Risk Development in Young Adults (CARDIA)
study, a longitudinal cohort aged 18-30 at inception in 1985. We have identified features of impaired respiratory
health that precede the development of chronic lung disease. These include: lower peak lung function in young
adulthood, accelerated age-related decline in lung function, elevations in systemic inflammatory biomarkers, and
the presence of respiratory symptoms. While we have documented the clinical relevance of impaired respiratory
health, our work to-date does not provide a set of targets for the interception of chronic lung disease. We now
propose to take advantage of CARDIA's unique platform to study the transition from impaired respiratory health
to lung disease. In this renewal application to the CARDIA Lung study, we will build upon our work which has
determined phenotypes of impaired lung health by collecting lung CT scans, pulmonary function, and nasal
epithelial gene expression at the CARDIA year 35 examination. We will seek to validate phenotypes and identify
endotypes of impaired respiratory health. We will test the hypothesis that imaging, blood, and nasal biomarkers
serve as useful phenotypes and endotypes of impaired lung health and are associated with transitions to chronic
lung disease through the following specific aims: (1) Determine multidimensional (integrating both longitudinal
measures of lung function and CT lung injury) lifecourse trajectories associated with the future development of
emphysema and interstitial change, (2) Using a proteomic discovery-platform, determine whether blood
biomarkers predict divergent phenotypic manifestations of lung disease (emphysema vs. interstitial change) in
the transition from impaired respiratory health to lung disease, (3) Determine whether CT lung injury,
emphysema, and interstitial change are associated with altered gene expression in the nasal respiratory
epithelium. This study will investigate factors associated with susceptibility versus resilience to lung disease and
the pathobiologic changes associated with impaired lung health, and in doing so, will contribute to a foundation
for the future interception of chronic lung disease.

## Key facts

- **NIH application ID:** 10654083
- **Project number:** 3R01HL122477-08S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** RAVI KALHAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $127,875
- **Award type:** 3
- **Project period:** 2014-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10654083

## Citation

> US National Institutes of Health, RePORTER application 10654083, Transitions from Impaired Respiratory Health to Lung Disease (3R01HL122477-08S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10654083. Licensed CC0.

---

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