Respiratory syncytial virus prevention and asthma in healthy preterm infants: a randomised controlled trial.

Background Respiratory syncytial virus (RSV) infection is associated with subsequent wheeze and asthma. We previously reported on the causal relationship between prevention of RSV infection during infancy and reduced frequency of subsequent wheeze using a double-blind, randomised, placebo-controlled trial (MAKI). We continued follow-up and analysed the effect of RSV prevention during infancy on asthma and lung function at age 6 years. Methods We studied 429 infants born at 32-35 weeks of gestation between 2008-10 who had randomly received either palivizumab for RSV immunoprophylaxis or placebo during the RSV season of their first year of life. After the first year of follow-up, single, assessor-blind follow-up of children continued until they were aged 6 years. Primary outcomes were parent-reported current asthma and forced expiratory volume in 0.5 s (FEV0.5). The trial is registered in the ISRCTN registry, number ISRCTN73641710. Findings 395 (92%) of 429 participants completed this 6-year follow-up study. Parent-reported current asthma was reported in 28 (14.1%) of 199 children in the RSV prevention group and 47 (24.0%) of 196 children in the placebo group (absolute risk reduction [ARR] 9.9%, 95% CI 2.2 to 17.6). The difference in current asthma, which was a composite endpoint, was due to a difference in infrequent wheeze (one to three episodes in the past year; 12 [6.0%] of 199 vs 26 [13.4%] of 194, ARR 7.4%, 95% CI 1.5 to 13.2). FEV 0.5 percentage predicted values were similar between the RSV prevention group (89.1% [SD 10.6]) and placebo group (90.1% [11.1]), with a mean difference of 1.0 (95% CI -1.3 to 3.3). The proportion of children with current physician-diagnosed asthma was similar between the RSV prevention group (19 [10.3%] of 185) and placebo group (18 [9.9%] of 182), with an ARR of -0.4 (95% CI -6.5 to 5.8). Interpretation In otherwise healthy preterm infants, this single-blind, randomised, placebo-controlled trial showed that RSV prevention did not have a major effect on current asthma or lung function at age 6 years. Future research will inform on the effect of RSV prevention on asthma at school age in the general population.