RSV Infection in Infancy Linked to Increased Risk of Childhood Asthma

A study published by The Lancet found that children who contracted respiratory syncytial virus (RSV) in their first year of life had an increased risk of developing childhood asthma compared with those who did not contract the virus.

RSV is a seasonal virus that causes significant morbidity and mortality in infants younger than 12 months. Although previous studies have linked RSV bronchiolitis to childhood asthma, bronchiolitis is much more severe than a normal RSV infection. The current study, the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure study (INSPIRE), aimed to assess whether RSV infection without bronchilitis, which is more common, was also associated with childhood infection to determine whether clinical action should be implemented early in an infant’s life.

Researchers tested for an association between RSV infection and asthma in a cohort of healthy children who were born at term and not underweight. Children were enrolled if they were aged between birth and 4 months of age and were recruited from 11 pediatric practices in middle Tennessee.

Passive and active surveillance were conducted during the first RSV season for each child to assess RSV infection. Parents were reminded to call the researchers when the child had an onset of respiratory symptoms. Parents were also contacted every other week by phone, email, or in person. All children who attended a pediatric practice for an unscheduled visit were also approached.

A respiratory illness assessment was conducted if a child met prespecified criteria for an acute respiratory infection. Assessments involved a parental questionnaire, a physical examination, a medical chart review, and a nasal wash. The Respiratory Severity Score (RSS) was used to assess the severity of the RSV infection on a scale of 0 to 12.

There were 1946 children who were eligible for the study, of which 1760 completed a 1-year follow-up and 1371 completed a 5-year follow-up. A total of 944 children had RSV infection during infancy (54%; 95% CI, 52-57), of which 47 (5%) had a nasal wash positive only, 583 (62%) had a positive RSV serology, and 314 (33%) had both.

There were 238 children of 1309 who had available follow-up data on 5-year current asthma. The proportion of those with 5-year current asthma was lower in children with no RSV infection during infancy (91 [16%] of 587 infants) compared with infants with an RSV infection (139 [21%] of 670 infants).

Children had a 26% lower risk of developing 5-year current asthma if they were not infected with RSV in infancy compared with those who were infected (adjusted relative risk, 0.74; 95% CI, 0.58-0.94). Approximately 15% of 5-year current asthma cases could be prevented by avoiding infection of RSV (95% CI, 2.2%-26.8%).

A total of 256 (15%) of 1749 children aged 1 year had recurrent wheeze, as did 258 (15%) of 1706 children aged 2 years, 195 (13%) of 1465 aged 3 years, and 177 (12%) of 151 aged 4 years. A lower proportion of children were found to have recurrent wheeze if they had no RSV infection in their infancy compared with those who did; this was found at each of the measured timepoints.

Limitations included the potentiatl misclassification of children that were categorized as not having RSV infection, as well as possible asymptomatic or paucisymptomatic RSV infections that were not caught through serology. A standard definition of childhood asthma does not exist, which also could have led to misclassification. Additionally, confounders could have affected the relationship between being infected with RSV and childhood asthma. These results may not be generalizable to other populations.

The researchers concluded that children who were not infected with RSV in their first year of life had a reduced risk of developing childhood asthma. "However, to definitively establish causality, the effect of interventions that prevent, delay, or decrease the severity of the initial RSV infection on childhood asthma will need to be studied," the authors concluded.

Reference

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