Rhinovirus Type in Severe Bronchiolitis and the Development of Asthma

Respiratory syncytial virus (RSV) and rhinovirus (RV)-induced bronchiolitis are associated with increased asthma risk in children. Whether virus types have different risks associated with later development of asthma is not known. RV-A and RV-C cause more severe respiratory illness than RV-B. Cadherin-related family member 3, a receptor for RV-C, and atopy are risk factors for development of early-onset asthma. The current study investigates whether RSV or RV types are differentially associated with use of asthma medications in the 4 years following severe bronchiolitis in infancy.

Children less than 24 months of age, hospitalized for bronchiolitis over consecutive winter seasons 2008–2010 were enrolled in a prospective, 3-center, 4-year cohort follow-up study in Finland. The diagnosis of bronchiolitis was made clinically, according to the American Academy of Pediatrics guidelines. The median age at study entry for 408 patients was 7.5 months. Sixty-four percent of patients were males, 23% had parental asthma, 13% had been premature, 12% had a comorbid medical disorder, 37% had a history of wheezing, and 30% had a history of atopic dermatitis. At the time of hospitalization, 42% had RSV, 29% had RV, 2% had RSV and RV, and 27% had negative testing for both viruses. Among patients with RV, 21% had RV-C, 7% had RV-A, 3% had RV-B, and one patient had both RV-B and RV-C.

Real-time reverse transcription PCR for detection of RNA respiratory viruses was performed on nasal wash samples collected within 24 hours of arrival to the inpatient care unit. Questionnaires modified from the International Study of Asthma and Allergy in Childhood questionnaires were sent to participants 4-5 years following hospitalization. Caregivers were queried about respiratory symptoms as well as need, prescription and use of asthma medication following the index hospitalization.

Three hundred and forty-nine patients were included in the final analyses. Children with RV-A (adjusted hazard ratio, 2.3; P = .01), RV-C (adjusted hazard ratio, 3.5; P < .001), and non-RSV/-RV (adjusted hazard ratio, 2.0; P = .004) bronchiolitis started asthma control medication earlier than did children with RSV bronchiolitis. Four years after hospitalization, 47% of patients with RV, 26% of patients with non-RSV/non-RV, and 15% of patients with RSV bronchiolitis had used asthma control medication during the past year. Patients with RV-C bronchiolitis, atopic dermatitis, and fever at the time of hospitalization had the highest risk for development of asthma (adjusted odds ratio, 5.0; P = .03).

Severe bronchiolitis caused by RV-A and RV-C was associated with early initiation and prolonged use of asthma control medication. Bronchiolitis is a disease with subgroups that have different risk factors and dissimilar responses to treatment and prognoses.

Identification of viral etiologies for bronchiolitis may help to stratify risk for future development of asthma. In patients infected with viruses known to have greater risk for subsequent development of asthma, early intervention strategies could be targeted. Further, as noted by the authors, preventive strategies for high-risk viruses (such as RV-A and RV-C) might reduce the burden of childhood asthma.