Children with rhinovirus (RV)-induced severe early wheezing have higher risks of subsequent recurrences and asthma than those with other viral aetiologies. The immunopathogenesis of this novel association remains unclear. While all major guidelines recommend against the use of bronchodilators and corticosteroids as a treatment regimen for bronchiolitis and early wheezing, they fail to consider the emerging evidence of bronchiolitis heterogeneity. Though early RV-induced wheezing resembles recurrent wheezing and asthma, its immunopathogenesis and the efficacy of bronchodilators and corticosteroids remain poorly studied.

In this thesis we evaluated the clinical short- and long-term effectiveness of both inhaled β2-agonist with and without oral corticosteroid treatment in early wheezing, RV-affected children. Moreover, we studied the immune responses from anti-CD3/anti-CD28-stimulated peripheral blood mononuclear cells (PBMCs), and their association with short- and long-term prognoses in first-time wheezing children under different scenarios, including sole RV vs. sole respiratory syncytial virus (RSV), and sole RV vs RV while coinfecting with human bocavirus 1 (HBoV1). Lastly, the association between the initial disease severity during sole RV-associated wheezing and cytokine response from stimulated PBMCs was evaluated.

The results of this thesis support the assumption of bronchiolitis heterogeneity. Concomitant use of β2-agonist and systemic corticosteroids appears to be beneficial in children with early wheezing induced by RV. Moreover, early wheezing induced by RV and RSV result in different cytokine responses and short- and long-term prognoses, thus suggesting different immunopathology between the two primary inducers of bronchiolitis. Furthermore, HBoV1 co-infecting with RV leads to immunomodulation by suppression, indicating that coinfections during bronchiolitis may impact the overall cytokine responses. Finally, an improper balance between pro- and anti-inflammatory cytokine profiles is associated with poorer initial disease severity.

These results highlight the heterogeneity of bronchiolitis and its effect on long-term prognosis and emphasize the need for more personalised treatment strategies for children with early wheezing.