Association of Rhinovirus C Bronchiolitis and Immunoglobulin E Sensitization During Infancy With Development of Recurrent Wheeze

To evaluate whether bronchiolitis in infancy caused by rhinovirus C is a stronger risk factor for recurrent wheeze than bronchiolitis caused by respiratory syncytial virus (RSV) or rhinovirus A or B.

716 infants in a multi-center prospective cohort study who were hospitalized for bronchiolitis due to rhinovirus and/or RSV from November 2011 – April 2014.

The primary exposure of interest was viral infection (RSV, rhinovirus A, B or C) based on PCR of nasopharyngeal samples. The primary outcome was recurrent wheeze by age 3 years (according to 2007 NIH asthma guidelines: 2 exacerbations in 6 months with corticosteroids or at least 4 wheezing episodes in 1 year). Cox proportional hazards models were used to account for varying length of follow-up. Authors investigated effect modification by allergic sensitization (presence of IgE to specific foods and aeroallergens).

The median age at admission was 2.9 months. Participants were followed for up to 36 months and were 60% male, with diverse race/ethnicity (45% non-Hispanic white, 23% non-Hispanic Black, 28% Hispanic, and 4% other). Viral bronchiolitis was caused by: RSV (76%), rhinovirus A (12%), rhinovirus B (2%), and rhinovirus C (11%); 14% had RSV/rhinovirus coinfection. Compared with infections caused by other viral species, patients with infection caused by rhinovirus C were significantly older, heavier and more likely to have a history of breathing problems. Over the follow-up period, recurrent wheeze developed in 32% of the sample. Bronchiolitis due to rhinovirus C was associated with risk of recurrent wheeze (hazard ratio (HR) = 1.58, 95% CI = 1.08–2.32) compared with other viral species. There was effect modification: the association was only seen among children with IgE sensitization (HR = 3.03, 95% CI = 1.20–7.61). Associations were not driven by RSV co-infection.

Infants with bronchiolitis caused by rhinovirus C had a higher risk of recurrent wheeze than those with bronchiolitis caused by rhinovirus A, B or RSV. The highest risk was observed among infants with IgE sensitization.

Bronchiolitis is an important risk factor for recurrent wheeze, a predictor of asthma in childhood, and this study adds to recent data highlighting an important role of rhinovirus C infection. This may contribute to an enhanced understanding of the underlying pathogenesis and ultimately guide more individualized management of bronchiolitis with a goal of preventing long-term sequelae and identifying children at elevated risk who would benefit from monitoring and intervention. The study raises important questions, including whether results can be generalized to populations with less-severe cases of bronchiolitis (that do not require hospitalization), as well as whether the important clinical and demographic differences seen among patients with rhinovirus C infection are antecedent factors that may explain some of the observed associations.