RSV Infection During Infancy Linked to Higher Risk of Asthma in Childhood

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While respiratory syncytial virus (RSV) infection in the first year of life was associated with a greater risk for childhood asthma in a new study, the authors highlight equally the finding that infants who were not infected during this vulnerable period had a substantial 26% reduced risk of asthma at age 5.

In addition, authors of the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure (INSPIRE) study also found that the estimated proportion of 5-year current asthma cases that could be prevented by avoiding RSV infection during infancy was 15% (95% CI 2.19-26.84).

"In this large, population-based birth cohort of healthy infants born at term, we showed that infants without RSV infection have a substantially reduced risk of developing childhood asthma compared with infants with RSV infection," wrote researchers in the study published in The Lancet. "To our knowledge, INSPIRE is the first study specifically designed to test the hypothesis that not being infected with RSV during infancy decreases the risk of childhood asthma."

While early-life severe RSV infection has been shown to be associated with the onset of childhood wheezing illnesses, the relationship between RSV infection during infancy and the development of asthma in childhood is less clear.

“For 60 years investigators have repeatedly identified the link between severe RSV and asthma; however, we’ve shown that this link is explained in part by shared heredity to both severe RSV and asthma,” said principal investigator and senior author Tina Hartert, MD, MPH, of Vanderbilt University Medical Center in Nashville, Tennessee, in a university press release. “The solution in our study was to understand the link between RSV and asthma by ensuring all RSV infections would be captured using molecular techniques and post-season serology.”

Infants with non-low birthweight born at term between June and December 2012 or between June and December 2013 were recruited from 11 pediatric practices across middle Tennessee. Hartert and colleagues ascertained RSV infection status in the first year of life via passive and active surveillance. Parents were contacted regularly, and infants underwent nasal washes and blood sampling at some health care encounters.

Participants were followed up prospectively for the primary outcome of 5-year current asthma, which researchers analyzed in all participants who completed the 5-year follow-up. Secondary outcomes included recurrent wheeze and 5-year current asthma inflammatory subtype, according to the study.

A total of 1946 children (48% girls; median age, 55 days) were enrolled in INSPIRE, of whom 1741 (89%) had available data to analyze RSV infection status in the first year of life. Among the 1741 participants with available RSV infection data, 54% (n=944) had been infected during infancy.

Investigators observed that the proportion of children with 5-year current asthma was lower among those without RSV infection during infancy (91 [16%] of 587) than those infected with RSV during infancy (139 [21%] of 670; p=0.016).

Participants who were not infected with RSV during infancy had a 26% lower risk of 5-year current asthma compared to those who were infected during infancy (adjusted rate ratio [aRR] 0.74, 95% CI 0.58-0.94; P=.014).

Results showed the proportion of children with recurrent wheeze was lower among those with no RSV infection during infancy than those with RSV infection. Also, compared with participants with RSV infection during infancy, a lower proportion of infants without RSV infection had 5-year current nonatopic asthma, “but this finding was not significant for 5-year current atopic asthma,” wrote Hartert et al.

"It is important to recognize that although our findings suggest a causal association, because of the observational design, our study can never definitively establish causality," noted investigators. "Instead, our results highlight the need for long-term follow-up of common respiratory outcomes among children participating in ongoing and future clinical trials of agents for RSV immunoprophylaxis."

Researchers also acknowledged possible misclassification of RSV in some patients, where infants that did have RSV were not officially diagnosed, as well as a lack of applicability to others outside the study population.

Reference: Hartert TV, Rosas-Salazar C, Chirkova T, et al. Respiratory syncytial virus infection during infancy and asthma during childhood in the USA (INSPIRE): A population-based, prospective birth cohort study. Lancet. Published online April 19, 2023. doi:10.1016/S0140-6736(23)00811-5.