# Early Origins of Chronic Lung Disease: Outcomes into the Fifth Decade of Life

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2021 · $1,473,403

## Abstract

Asthma, chronic obstructive pulmonary disease (COPD) and a restrictive spirometry pattern (RSP) are strongly
associated with increased morbidity and mortality burden. Recent discoveries strongly suggest that the roots of
many cases of asthma, COPD and RSP in adulthood can be found during early life. Prevention of these
heterogeneous conditions, for which no cure currently exists, requires a thorough understanding of the natural
history and mechanistic pathways that underlie their distinct clinical phenotypes. The Tucson Children's
Respiratory Study (TCRS) has already made major contributions to our understanding of the natural history of
asthma and of lung function trajectories and, as its participants are entering their fifth decade, is now poised to
investigate, prospectively, the early risk factors for asthma, COPD and RSP as well as the molecular basis of
their distinct clinical phenotypes. While the origins of atopic asthma (T2) are well established, the origins of
non-T2 asthma, which is overrepresented among severe asthmatics and for which no efficacious treatment is
available, are less well known. We recently showed that both high serum insulin and non-atopic rhinitis at the
age of six years are strong, separate predictors of asthma from childhood up to age 36 years. These findings
offer exciting new avenues to understand the pathogenesis of non-T2 asthma based on its natural history.
Here, we propose to use state-of-the-art single-cell epigenetic and gene expression technologies to compare
the cell type distribution in sputum of participants with and without these two early life risk factors. Regarding
COPD, our recent findings suggest that at least half of all patients diagnosed with the disease do not show
accelerated lung function decline during adult life, suggesting that airflow limitation had its origins in low airway
function trajectories starting in childhood. We now propose to use CT imaging to determine the anatomical
features of the persistently low airway function trajectory. In addition, we showed that smokers who had
confirmed lower respiratory tract illnesses due to respiratory syncytial virus (RSV) in early life are at increased
risk of having chronic respiratory symptoms in the third decade of life. We now propose to use data into the
fifth decade of life to ascertain if the RSV-smoking interaction explains why only a minority of smokers develop
COPD. Finally, we will investigate the hypothesis that major risk factors for RSP are nutritional problems in-
utero and during childhood. We will address 3 specific aims: 1. To assess the cellular and molecular endotypes
and the continued influence of early life risk factors on phenotypes of asthma from childhood into mid-adult life.
2. To assess the continued influence of early life risk factors and the clinical, physiological, and airway
structural alterations of incipient early COPD in mid-adult life. 3. To assess the influence of early life risk factors
on plethysmography-de...

## Key facts

- **NIH application ID:** 10136679
- **Project number:** 5R01HL132523-06
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Stefano Guerra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,473,403
- **Award type:** 5
- **Project period:** 2016-06-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136679

## Citation

> US National Institutes of Health, RePORTER application 10136679, Early Origins of Chronic Lung Disease: Outcomes into the Fifth Decade of Life (5R01HL132523-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10136679. Licensed CC0.

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