SNPs in innate immune genes are important in determining susceptibility to RSV bronchiolitis.

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BackgroundA relationship between hospitalization for respiratory syncytial virus (RSV) bronchiolitis and asthma development has been suggested in case-control studies.ObjectiveThe aim of this study was to assess the risk of current wheeze, asthma, and lung function at school age in infants previously hospitalized for RSV bronchiolitis compared to non-hospitalized children.MethodsFor this study, data from a prospective birth cohort of unselected, term-born infants (n = 553), of whom 4 (0.7%) were hospitalized for RSV bronchiolitis, and a prospective patient cohort of 155 term infants hospitalized for RSV bronchiolitis were used. Respiratory outcomes at age 6 in children hospitalized for RSV bronchiolitis were compared to non-hospitalized children.ResultsThe risk of current wheeze was higher in hospitalized patients (n = 159) compared to non-hospitalized children (n = 549) (adjusted odds ratio (OR) 3.2 (95% CI 1.2–8.1). Similarly, the risk of current asthma, defined as a doctor’s diagnosis of asthma plus current symptoms or medication use, was higher in hospitalized patients (adjusted OR 3.1 (95% CI 1.3–7.5). Compared to non-hospitalized children, RSV bronchiolitis hospitalization was associated with lower lung function (mean difference FEV1% predicted −6.8 l (95% CI (−10.2 to −3.4).Conclusions and Clinical RelevanceThis is the first study showing that hospitalization for RSV bronchiolitis during infancy is associated with increased risk of wheezing, current asthma, and impaired lung function as compared to an unselected birth cohort at age 6.

Prematurity is a risk factor for severe respiratory syncytial virus bronchiolitis. We show that genetic factors in innate immune genes (IFNA13, IFNAR2, STAT2, IL27, NFKBIA, C3, IL1RN, TLR5), in innate and adaptive immunity (IFNG), and in airway remodeling genes (ADAM33 and TGFBR1), affect disease susceptibility to a different extent in preterm children, born with underdeveloped lungs, than in term children.

Objective To determine whether early initiated anti-inflammatory therapy with prolonged high dose inhaled glucocorticoids influences the occurrence and severity of recurrent wheeze after respiratory syncytial virus related lower respiratory tract infections.Design Randomised double blind placebo controlled trial.Setting Paediatric departments of 19 Dutch clinical centres.Participants 243 previously healthy infants (126 boys, 117 girls) aged less than 13 months and admitted to hospital with respiratory syncytial virus infection.Interventions 200 μg extra fine hydrofluoroalkane (HFA) beclometasone dipropionate twice daily or matched placebo administered by a pressurised metered dose inhaler and a spacer during the first three months after hospital admission.Main outcome measure The primary outcome was the number of days with wheeze in the year after the three month intervention period.Results Of the 243 eligible infants, 119 were randomised to receive beclometasone and 124 to receive placebo. No significant difference was found in the number of days with wheeze between the two groups (total days, 1761/33 568 in the beclometasone group v 2301/36 556 in the placebo group, P=0.31) and the proportion of infants with wheeze did not differ between the groups (61% in the beclometasone group v 62% in the placebo group, P=0.90). In the predefined subgroup of infants who did not need mechanical ventilation (n=221), beclometasone reduced the number of days with wheeze by 32% (relative reduction in total days, 1315/30 405 in the beclometasone group v 2120/33 149 in the placebo group, P=0.046). This reduction was most pronounced during the first six months of the follow-up year after intervention. The proportion of infants with wheeze did not differ between the groups (59% in the beclometasone group v 60% in the placebo group, P=0.89).Conclusions Early initiated high dose extra fine HFA beclometasone to infants during the first three months after hospital admission for respiratory syncytial virus infection has no major effect on recurrent wheeze. The general use of such treatment during lower respiratory tract infection with respiratory syncytial virus should not be advocated.Trial registration Current Controlled Trials ISRCTN12352714.

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