RSV prevention in infancy and asthma in later life

In the Lancet Respiratory Medicine, Scheltema and colleagues¹ report the results of a single-blind extension of the randomised, placebo-controlled MAKI trial (https://doi.org/10.1186/ISRCTN73641710 [accessed 04/05/2018]), which investigated the effect of respiratory syncytial virus (RSV) immunoprophylaxis in late preterm infants on parent-reported current asthma at age 6 years. Investigation of this outcome is important because wheeze and asthma cause substantial respiratory morbidity in children, and primary prevention strategies are needed.

Odds ratios (ORs) from observational studies implicating lower respiratory tract infection caused by RSV as a risk factor for asthma have been consistent with two meta-analyses providing a summary OR of 3.84 (95% CI 3.23–4.58).^2,3 Although confounding by indication is a problem in observational studies, we have provided fairly convincing evidence that at least part of this association is causal.^4,5 In particular, the association between infant age at the annual peak of RSV infection and subsequent asthma is hard to explain through non-causal mechanisms.^4,5

The study by Scheltema and colleagues is one of two extended randomised controlled trials (https://doi.org/10.1186/ISRCTN73641710 ([accessed 04/05/2018], https://clinicaltrials.gov/ct2/show/NCT00121108 [accessed 04/05/2018]) to ever have addressed the important question of whether prevention of RSV infection during infancy prevents either early childhood wheeze or childhood asthma. Both studies used an innovative, time-efficient, and cost-efficient design of following up trials in infants to assess wheeze and asthma outcomes in childhood. However, the primary outcome of both trials was an infant outcome. To have sufficient power to show causality between RSV infection prophylaxis in infancy and the less common outcomes of medically attended wheeze or asthma in childhood, a much larger number of infants and longer-term follow-up data are needed.

Although randomised controlled trials are the gold standard for assessing the efficacy of new treatments, they are not always feasible or necessary. If randomised trials of new, inexpensive interventions, such as vaccinating pregnant women, can show a reduction in serious RSV outcomes in infants, then this endpoint alone should be sufficient to justify the use of these strategies. The possible additional benefit of reducing long-term respiratory morbidity increases the importance of preventing RSV infections in infants, even if a benefit on asthma development in later childhood has not been shown unequivocally in an adequately designed and powered randomised trial. The magnitude of the effect of asthma, a lifelong chronic disease, is sufficiently large that even a small reduction in true asthma incidence would have major public health implications.