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

Award Number: R01HL132523
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2016
PERIOD OF PERFORMANCE END DATE: 03/31/2025

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Early Origins of Chronic Lung Disease: Outcomes into the Fifth Decade of Life - 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-defined lung restriction in mid-adult life. As the only birth cohort with hundreds of non- selected participants followed from birth into the fifth decade of life, the TCRS offers a unique opportunity to investigate the potential disease mechanisms for the early origins of asthma, COPD, and RSP in adult life.


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 = $0 )
2025	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Lung Diseases Research	000	8	10/26/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $1,519,797 )
2023	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Lung Diseases Research	000	8	3/30/2023	NON-COMPETING CONTINUATION	$1,519,797
														Subtotal = $1,519,797

Issue Date FY: 2022 ( Subtotal = $1,517,972 )
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Lung Diseases Research	001	7	6/14/2022	NON-COMPETING CONTINUATION	$151,800
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Lung Diseases Research	000	7	4/15/2022	NON-COMPETING CONTINUATION	$1,366,172
														Subtotal = $1,517,972

Issue Date FY: 2021 ( Subtotal = $1,473,403 )
2021	2021	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Lung Diseases Research	000	6	5/14/2021	NON-COMPETING CONTINUATION	$1,473,403
														Subtotal = $1,473,403

Issue Date FY: 2020 ( Subtotal = $1,519,158 )
2020	2020	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Lung Diseases Research	002	5	9/18/2020	COMPETING CONTINUATION	$291,471
2020	2020	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Lung Diseases Research	000	5	4/1/2020	COMPETING CONTINUATION	$1,519,158
2020	2019	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Lung Diseases Research	001	4	9/18/2020	NON-COMPETING CONTINUATION	-$291,471
														Subtotal = $1,519,158

Issue Date FY: 2019 ( Subtotal = $1,376,435 )
2019	2019	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Lung Diseases Research	001	4	4/27/2019	NON-COMPETING CONTINUATION	$1,376,435
2019	2018	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Lung Diseases Research	000	3	12/18/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,376,435

Issue Date FY: 2018 ( Subtotal = $1,376,435 )
2018	2018	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Lung Diseases Research	000	3	3/26/2018	NON-COMPETING CONTINUATION	$1,348,905
2018	2018	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Lung Diseases Research	001	3	6/9/2018	NON-COMPETING CONTINUATION	$27,530
														Subtotal = $1,376,435

Issue Date FY: 2017 ( Subtotal = $1,376,435 )
2017	2017	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Lung Diseases Research	000	2	3/16/2017	NON-COMPETING CONTINUATION	$1,376,435
														Subtotal = $1,376,435

Issue Date FY: 2016 ( Subtotal = $1,408,546 )
2016	2016	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722		USA	Lung Diseases Research	000	1	5/25/2016	NEW	$1,408,546
														Subtotal = $1,408,546

Grand Total All Awards = $11,568,181

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

Award Number: R01HL132523

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2016

PERIOD OF PERFORMANCE END DATE: 03/31/2025

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