# Establishing critical time windows of infant RSV infection in the causal relationship of RSV and childhood asthma

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $779,909

## Abstract

Project Summary
Sixty years of observational studies have consistently demonstrated an association between respiratory
syncytial virus (RSV) lower respiratory tract infection (LRTI) and asthma, the two most common respiratory
diseases of infancy and childhood, resulting in significant morbidity and mortality in the US and worldwide.
However, we have demonstrated the problem with this approach, given confounding due to shared heredity.
To overcome this, we have demonstrated in both retrospective and prospective studies that RSV infection, not
only severe infection, during a susceptible age window increases the risk of asthma development, and that
delayed primary RSV infection until after infancy is associated with a significantly decreased risk of developing
childhood asthma. Our results along with human and experimental findings, provide the preliminary data to
support that there is an age-dependent causal relationship between infant RSV infection and asthma. Key
remaining unanswered questions include determining the critical susceptibility period/timing of RSV infection
during which infection results in increased childhood asthma, establishing causality between RSV infection and
asthma, and determining if new RSV prevention products impact long-term respiratory morbidity.
We hypothesize that there is an identifiable age-dependent window during which RSV infection results in an
enhanced risk of childhood asthma, and that prevention or delay in initial infection protects from asthma
development. To test the hypotheses, we will assemble a population of over 4 million infants who were born
and enrolled in a state Medicaid program and the Department of Defense Military Healthcare System from
2003-2028. We will address the questions using 1) an instrumental variable (IV) approach and 2) the “natural
experiment” of the SARS-CoV-2 pandemic time period which resulted in more than a year during which there
was almost no RSV circulation followed by an off-season summer RSV peak and an extremely early RSV
season. The IV approach, designed to address causal questions using observational data, is a novel statistical
method that has been successfully implemented in many health outcome studies. We will also address this
question by taking advantage of the soon-to-be available RSV protection product(s) during the 2023-2028 RSV
seasons to assess if they have an impact on long-term childhood respiratory morbidities including asthma.
Establishment of an age-dependent causal relationship between RSV and asthma will be of enormous public
health importance for asthma prevention, as there is currently no effective primary prevention strategy for
asthma. Further, results of this study will be important in understanding required duration of protection during
infancy to inform RSV prevention product recommendations. Lastly, demonstrating value added long-term
benefit of RSV prevention strategies will certainly enhance the cost-benefit for uptake of RSV prevention
products...

## Key facts

- **NIH application ID:** 10860270
- **Project number:** 1R01HL173480-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Tina V Hartert
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $779,909
- **Award type:** 1
- **Project period:** 2024-06-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10860270

## Citation

> US National Institutes of Health, RePORTER application 10860270, Establishing critical time windows of infant RSV infection in the causal relationship of RSV and childhood asthma (1R01HL173480-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10860270. Licensed CC0.

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