Cytokine Responses to Rhinovirus and Development of Asthma, Allergic Sensitization, and Respiratory Infections during Childhood

Abstract

Early-onset troublesome asthma with early-life sensitization, later-onset milder allergic asthma, and disease protection are each associated with different patterns of rhinovirus-induced immune responses.

Differential associations of allergic disease genetic variants with developmental profiles of eczema, wheeze and rhinitis

“…with transient wheeze when defined as high probability of wheeze within the first 5 years, with remission by age 8 years, and a very low probability of eczema and rhinitis throughout childhood. Given that early-life wheeze in the absence of other allergic symptoms (such as eczema) is mostly virus-induced, our results are in agreement with observations from recent studies which provided evidence that polymorphisms on chromosome 17q21 regulate ICAM1 expression and thus may affect the frequency and severity of rhinovirus infection and early childhood wheezing illness, 28 that impaired anti-virus immunity is associated with early-life wheezing, 29 and that early-life antibiotic use (a proxy for impaired innate anti-virus immunity) is associated with 17q21 polymorphisms. 30…”

Longitudinal trajectories of severe wheeze exacerbations from infancy to school age and their association with early‐life risk factors and late asthma outcomes

“…We have observed a relatively high frequency of rhinitis in early school age among all children with physician‐confirmed wheezing, with the proportion of subjects with rhinitis steadily increasing from those with no exacerbations (30%), to those in infrequent (37%) and frequent exacerbations trajectories (50%), compared to only 17% among children who have never wheezed. This extends recent findings that childhood rhinitis confers significant risk for asthma development and suggests that both allergic non‐allergic mechanisms are important for susceptibility to frequent exacerbations …”

“…This extends recent findings that childhood rhinitis confers significant risk for asthma development 40 and suggests that both allergic non-allergic mechanisms are important for susceptibility to frequent exacerbations. 41 The proportion of children with more severe asthma in our cohort was highest among children who had frequent exacerbations.…”

Association of type 2 cytokines in severe rhinovirus bronchiolitis during infancy with risk of developing asthma: A multicenter prospective study

“…In the sensitivity analysis using normalized cytokine levels and the subgroup analysis excluding infants with a breathing problem prior to enrollment, the results were similar These findings are concordant with previous cross-sectional and retrospective studies that suggested potential interrelations between RV infection, type 2 cytokines (eg, IL-4, IL-5, IL-13, TSLP), and asthmatic airway inflammation. [2][3][4] The current prospective study builds on these earlier reports and extends them by demonstrating the prospective association between type 2 cytokine levels in the airway of infants with solo RV bronchiolitis and the risk of developing asthma. The mechanisms underlying these findings warrant further investigation.…”

“…Experimental models and human (cross-sectional and retrospective) studies have reported that RV infection may induce type 2 cytokines (eg, interleukin [IL]-4, IL-5, IL-13, thymic stromal lymphopoietin [TSLP]) and that the levels of these cytokines are elevated in the asthmatic airway. [2][3][4] However, no prospective study has investigated the longitudinal relation of type 2 airway inflammation in children-let alone infants with bronchiolitis-to the development of childhood asthma. To address this knowledge gap, we prospectively examined the association of nasopharyngeal cytokines in infants with RV bronchiolitis with the risk of developing childhood asthma, by using data from a multicenter cohort of infants with severe bronchiolitis.…”