Healthy full-term infants who are not infected with respiratory syncytial virus (RSV) during their first year of life have a substantially lower risk of developing childhood asthma, researchers reported in The Lancet.
The investigators assessed the relationship between RSV infection in infancy and childhood asthma through analysis of the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure (INSPIRE) cohort, a US population-based birth cohort that enrolled infants from birth to age 4 months from 11 pediatric practices in Tennessee.
All children included for analysis were healthy, born at term, had a birthweight of at least 2250 g, and were born from June to December 2012 or June to December 2013. Each child underwent passive and active surveillance during the first RSV season. The primary outcome was 5-year current asthma, which was defined as a parental report of physician-diagnosed asthma or use of asthma medications at any time before age 5 years and any of the following symptoms in the year before the 5-year well visit: asthma symptoms, asthma-related systemic steroid use, or acute health care use for asthma.
A total of 1741 (89%) of 1946 eligible children (median age, 55 [interquartile range, 16-78] days; 52% male) had available data to assess their RSV infection status during their first year of life. Of this group, 944 children had RSV infection in infancy (54%; 95% CI, 52-57). The infants with no RSV infection were more likely to be non-Hispanic White, enrolled at a younger age, born vaginally, and more likely to have not attended day care or lived with another child aged <6 years, compared with infants with RSV infection.
The number of children with available follow-up data who had 5-year current asthma was 238 of 1309 (18%). The proportion of those with 5-year current asthma was lower for children with no RSV infection during infancy (91 [16%] of 587 infants) vs infants with RSV infection (139 [21%] of 670 infants). Children who did not have RSV in infancy had a 26% reduced risk of 5-year current asthma compared with those with RSV infection during infancy (adjusted risk ratio [RR], 0.74; 95% CI, 0.58-0.94; P =.014). The estimated proportion of 5-year current asthma cases that could be prevented by avoiding RSV infection in infancy was 15% (95% CI, 2.2-26.8; preventable fraction of 0.15 [0.02-0.27]).
A sensitivity analysis of 810 children showed an almost identical effect size in a comparison of those with a positive nasal wash for RSV by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) vs those who had a negative nasal wash for RSV by RT-qPCR (adjusted RR, 0.76; 95% CI, 0.58-1.00; P =.051).
In an analysis of 237 infants with an in-person respiratory illness assessment and a positive nasal wash for RSV by RTqPCR and 5-year current asthma data, a positive association was found between RSV infection severity in infancy (as measured by the Respiratory Severity Score) and the risk of 5-year current asthma (adjusted odds ratio, 1.24; 95% CI, 1.05-1.45; P =.0092).
Of 194 children with 5-year current asthma and blood-specific IgE testing at age 3 years, 102 (53%) had atopic asthma and 92 (47%) had nonatopic asthma.
The proportion of children with recurrent wheeze was reduced in those with no RSV infection during infancy vs those with RSV infection at each of the measured timepoints between ages 1 and 4 years. Repeated outcome analyses showed that the association between RSV infection in infancy and recurrent wheeze during preschool years (ages 1-4 years) varied over time (Pinteraction =.026). When stratified by child age, infants with no RSV infection had a reduced risk of recurrent wheeze annually compared with infants with RSV infection, although it was only significant for 1-year and 2-year recurrent wheeze.
Limitations include the potential misclassification of children categorized as not infected with RSV in infancy and the lack of a standard definition of childhood asthma. Also, the relationship between being infected with RSV during infancy and childhood asthma could have been confounded by unmeasured factors.
“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,” the investigators stated.
Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Rosas-Salazar C, Chirkova T, Gebretsadik 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