The role of early-life viral respiratory illness in development of childhood asthma endotypes: the primero II study

Active Project Grant Awarded Last action

Award ID
R01HL138626
Recipient
Awarding agency
Obligated
$1,319,983

Award facts

Assistance listing
93.837 Cardiovascular Diseases Research
Completion date 65% complete
Place of performance
San Francisco, CA 94143, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Childhood asthma is the most common chronic illness in children, driven by complex gene- environment interactions. Among environmental factors, severe lower respiratory tract illnesses (slris) in infancy-particularly from respiratory syncytial virus (RSV) and human rhinovirus (HRV)-are among the strongest predictors of asthma. Yet whether slris play a causal role or merely unmask a pre-existing susceptibility remains unresolved. The primero birth cohort was established to address this critical GAP by prospectively enrolling 2,100 children and capturing airway biosamples from birth through early childhood. By integrating dense viral surveillance, genetic profiling, and airway transcriptomics at birth, illness, and follow-up, primero offers a uniquely powerful platform to disentangle the relationship between slris and asthma. Preliminary findings support the hypothesis that slris both reveal and reshape asthma risk. Infants who later developed HRV-slris-but not RSV-slris-showed strong downregulation of immune-related genes at birth. In contrast, RSV-slris were associated with a high risk of slris VS. Upper RIS regardless of birth expression. A primero transcriptome-wide association study (twas) identified 130 genes whose genetically regulated airway expression conferred slri risk, including established asthma loci (tslp, IL1RL1, FADS2). Children with prior slris also showed persistent airway changes at age 2-downregulation of ciliated-cell genes and upregulation of multiple inflammatory networks-implicating slri-driven remodeling in asthma pathogenesis. Based on these data, we hypothesize that asthma endotypes arise through distinct but overlapping mechanisms-(1) inborn epithelial or immune dysfunction, (2) slri-driven airway remodeling, and (3) genetic modulation of these processes. Aim 1 will test whether birth airway dysfunction predisposes to asthma, and whether slris mediate this effect. Aim 2 will define how slri-induced airway remodeling leads to asthma endotypes. Aim 3 will determine how genetic risk converges with slris to drive asthma through molecular regulation. These studies will define causal mechanisms linking early infection and genetic risk to asthma, enabling novel strategies for early-life prediction, prevention, and intervention.

Subawards

Subrecipient Amount Awarded
National Jewish Health The Role of Early-Life Viral Respiratory Illness in Development of Childhood Asthma Endotypes: the PRIMERO II study $494,993

Quick answers

Who received award R01HL138626?

R01HL138626 was awarded to The Regents Of The University Of California. San Francisco by National Heart Lung and Blood Institute (National Institutes of Health) on September 24, 2018.

How much is award R01HL138626 worth?

$1,319,983 has been obligated on R01HL138626.

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