RSV infections in infants increase the likelihood of asthma in children

In a recent study published in The Lancetresearchers are exploring the correlation between respiratory syncytial virus (RSV) infection in infancy and the development of childhood asthma.

Study: Respiratory syncytial virus infection in infancy and childhood asthma in the United States (INSPIRE): a prospective population-based birth cohort study. Image Credit: Alexander Ishchenko / Shutterstock.com

What is RSV?

RSV is a common respiratory virus that is seasonal and causes significant illness and death in infants worldwide. RSV bronchiolitis has been consistently associated with childhood asthma in observational studies.

Previous studies have also indicated that the correlation between childhood asthma and RSV bronchiolitis may be influenced by the common genetic predisposition to severe RSV infection in early life and wheezing phenotypes in children. Determining whether preventing RSV infection in early childhood can reduce the risk of childhood asthma is crucial for developing effective primary prevention methods, reducing respiratory morbidity in children, and establishing health policies.

About the study

The INSPIRE (Infant Susceptibility to Pulmonary Infections and Asthma After RSV Exposure) study is a population-based birth cohort that aims to test the hypothesis that RSV infection during infancy increases the likelihood of asthma infant. Children who met the eligibility criteria were enrolled within the first four months of birth.

The recruitment process was conducted at 11 pediatric practices located in central Tennessee. The inclusion criteria for the study were healthy children without significant cardiovascular, pulmonary or neurological diseases, born at term with a birth weight of 2250 g or more, and born between June and December 2012 or June and December 2013.

For children who met specific criteria for acute respiratory infection, the team conducted an in-person assessment that included a parental questionnaire, physical examination, nasal wash collection, and structured medical record review in people who had received health care. RSV was detected molecularly using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Blood samples were taken from all children at one year of age and serum RSV antibody titers were measured using an enzyme immunoassay (ELISA).

During the first year of life, children were classified as RSV-negative or RSV-positive. The Respiratory Severity Score (RSS) was used to assess the severity of RSV infection in infants who underwent an in-person respiratory disease assessment.

The primary outcome of the study was current asthma for five years, which was determined by parental diagnosis of physician-diagnosed asthma or use of asthma medication before age five, as well as than any of the following symptoms in the 12 months prior to the five-year visit, including asthma symptoms, use of acute health care for asthma, or use of systemic steroids related to asthma asthma. Secondary outcomes included recurrent wheezing and current asthma inflammatory subtype over five years.

Study results

Of a total of 1,952 children enrolled in INSPIRE, 1,946 met the eligibility criteria, of whom 1,220 underwent an in-person examination for respiratory disease and 1,709 provided a blood sample at the age of one year. Of the 1,946 children enrolled, 2,093 in-person assessments were completed to assess respiratory disease.

Children who completed their five-year visit had higher birth weight, increased likelihood of having private insurance, breastfeeding in infancy, attending daycare in infancy, and reduced exposure to second-hand smoke during infancy or in utero compared to those who had none completing their five-year visit.

Of the 1,220 children who underwent an in-person respiratory disease assessment, 361 tested positive for RSV by RT-qPCR in at least one nasal wash. The peak rate of RSV-positive nasal washouts, as determined by RT-qPCR testing, was noted in January of the 2012–2013 RSV season and December of the 2013–2014 RSV season. Of the 1,220 children evaluated for respiratory disease, the median age of initial RSV infection was 20.29 weeks, while the median RSS was three.

The prevalence of RSV infection in early childhood was 944 out of 1741 children. Of 944 infants infected with RSV, 47 tested positive by nasal washout using RT-qPCR exclusively, 583 tested positive for RSV serology at one year of age exclusively, and 314 tested positive for both. Infants uninfected with RSV were more likely to be born vaginally, recruited at a younger age, and non-Hispanic Caucasian than their RSV-infected counterparts.

Of the 1,309 children with follow-up data, 238 had had current asthma for five years. Children who did not have RSV infection during infancy had a lower five-year prevalence of current asthma compared to those who had RSV infection during infancy.

Children uninfected with RSV in infancy had a 26% reduced likelihood of current asthma over five years compared to their RSV-infected counterparts. RSV infection in infancy could prevent 15% of current asthma cases over five years.

Children without RSV infection during infancy had a lower proportion of recurrent wheezing compared to those with RSV infection at each measured time point from age one to four years. The relationship between RSV infection in infancy and recurrent wheezing in preschool children showed temporal variability in repeated analyzes of the results.

Infants without RSV infection had a lower annual risk of recurrent wheeze compared with those infected with RSV, according to age-stratified models. However, statistical significance was only observed for recurrent wheeze at one and two years.

conclusion

The absence of RSV infection during the first year of life is linked to a significant decrease in the likelihood of developing childhood asthma. This correlation is influenced by age and severity.

The study results also indicate the need to investigate interventions that can prevent, delay, or lessen the severity of first RSV infection as a potential strategy to reduce the prevalence of childhood asthma in the population.

The current study also underscores the need for expanded surveillance of prevalent respiratory outcomes in children enrolled in current and upcoming clinical trials of therapies for RSV immunoprophylaxis.