# Deep Functional Phenotyping of the ALA Lung Health Cohort

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2024 · $772,943

## Abstract

Project Summary/Abstract
An individual can progress from ideal lung health, to an intermediate phenotype of impaired lung health, to
chronic respiratory disease, yet this transition is poorly understood. A consequence of this knowledge gap is the
lack of robust strategies to prevent chronic lung disease. The Lung Health Cohort (LHC) study (NHLBI
5U01HL146408) will recruit healthy participants across the US to have their lung health evaluated through
questionnaires, biospecimen analysis, spirometry, and computerized tomography (CT), and relate these features
to an array of anthropomorphic and environmental factors thought to influence lung health. In this Ancillary study
application, we propose to extend the phenotyping of the LHC to include detailed measures of lung
structure and function to obtain a more robust understanding of the influence of modifiable exposures
and risk factors on lung health. We postulate that a key aspect of both current and future lung health is
“dysanapsis”, which is thought to occur when dyssynchronous growth of airways and lung parenchyma such that
the airways are small relative to lung size. Dysanapsis has been associated in children with obesity, airways
hyperresponsiveness and asthma, and in adults, with COPD; however, a comprehensive characterization and
validation of dysanapsis by both more specific functional and structural measures has not been assessed in
healthy young adults nor shown to be a longitudinal risk factor. Our timely and innovative approach will combine
structural information by CT with functional, state-of the-art assessment of spirometry, lung volumes, and
oscillometry and gas exchange. We hypothesize that modifiable exposures and risk factors influence lung
health by their effects on structural and functional dysanapsis of the airway, parenchyma and pulmonary
vasculature and gas exchange. In particular, we will assess the associations of modifiable environmental
factors such as tobacco, air pollution, marijuana and electronic cigarettes, in addition to age, sex, ethnicity, BMI,
prematurity, allergic rhinitis, and history of COVID-19, as these factors relate to airway and vascular dysanapsis,
cardiac morphology and gas exchange. The plausible mechanistic hypothesis that underlies the proposal is that
there is mismatching of airways and blood vessels to parenchyma both in terms of structure (CT) and function
(PFTs); we posit that this dysanapsis is a silent marker of early and progressive lung disease. This ancillary
study will leverage the infrastructure and endpoints of the parent LHC study, as we will extend the LHC
investigation in a number of significant ways to fill knowledge gaps that determine both the reserve and
susceptibility of the lung to disease. This “deep phenotyping” of the baseline lung function and cardiac and
pulmonary vascular structure will provide a more detailed understanding of the influence of modifiable exposures
and risk factors of both current and future lung disease.

## Key facts

- **NIH application ID:** 10896464
- **Project number:** 5R01HL161220-03
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Charles G Irvin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $772,943
- **Award type:** 5
- **Project period:** 2022-08-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896464

## Citation

> US National Institutes of Health, RePORTER application 10896464, Deep Functional Phenotyping of the ALA Lung Health Cohort (5R01HL161220-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10896464. Licensed CC0.

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