Respiratory syncytial virus induced recurrent wheeze: genetic determinants and preventive glucocorticosteroid treatment

Abstract

Background Respiratory syncytial virus lower respiratory tract infection (RSV LRTI) is frequently followed by recurrent wheeze. Aims -To evaluate the effectiveness of early-initiated high-dosed inhaled cortiocosteroids to prevent wheezing following RSV LRTI. -To increase knowledge about pathofysiological mechanisms underlying wheezing following RSV LRTI. Methods -Clinical, immunological and genetic characteristics of recurrent wheezing during the first 3 years following RSV LRTI and at age were compared. -A randomised controlled trial was performed to evaluate the effect of beclomethasone on recurrent wheeze. 243 infants were randomised and treated with beclomethasone or placebo during 3 months. The occurrence of wheeze was evaluated in the year following treatment. -Genetic studies were performed to identify genetic determinants of recurrent wheeze. Results -‘Early’ and ‘late’ recurrent wheeze following RSV LRTI represent distinct entities. -High-dosed and early-initiated inhaled corticosteroids during RSV LTRI have a modest and transient beneficial effect on recurrent wheeze. This effect is observed in non-ventilated infants only. -Recurrent wheeze following RSV LRTI relates to genetic variation in IL19 en IL20 genes. Conclusion -The use of inhaled corticosteroids should not be advocated in all infants hospitalised for RSV LRTI, but may be considered in non-ventilated infants. -IL10 family cytokines appear to have a central role in virus-induced wheeze following RSV LRTI. Future research Replication and functional studies are needed to confirm the role of IL10 like cytokines in recurrent wheeze following RSV LRTI. Pharmacogenetic studies are needed to evaluate the interaction between genetic background and treatment effect of inhaled corticosteroids on infant wheeze.