Respiratory syncytial virus prophylaxis for prevention of recurrent childhood wheeze and asthma: a protocol for a systematic review

BACKGROUND: Lower respiratory tract infection (LRTI) caused by respiratory syncytial virus (RSV) has been associated with greater risk of recurrent wheezing and subsequent asthma. However, it is still unclear whether this association is causal or not. RSV-specific monoclonal antibodies have been shown to reduce RSV-related hospitalisations in high-risk infants, i.e. those born pre-term, but the longer term follow-up has given conflicting evidence for the prevention of recurrent wheeze or asthma. OBJECTIVE: We aim to perform a systematic review and meta-analysis to determine whether or not prophylaxis with a monoclonal antibody for prevention of RSV-bronchiolitis reduces the risk of subsequent recurrent wheeze or asthma. If so, this would support the hypothesis that the association between RSV and recurrent wheeze and/or asthma is causative. METHODS: To identify relevant studies, we will search a number of databases including Medline, Embase, PubMed and Web of Science and will also manually look for unpublished data by contacting the manufacturers of monoclonal antibodies. The intervention being investigated is RSV-specific monoclonal antibody prophylaxis, and the outcome being measured is recurrent wheeze and/or asthma. Studies will be screened according to inclusion/exclusion criteria, to include primary studies of any study design type. Eligible studies will then be evaluated for quality and assessed for bias independently by three reviewers using the ‘Grading of Recommendations Assessment, Development and Evaluation’ (GRADE) approach. The results of the studies will be extracted into 2 × 2 outcome tables, and a meta-analysis will be carried out to produce forest plots based on relative risk. Heterogeneity will be assessed using the I(2) statistic. The statistical software we will use is StatsDirect. DISCUSSION: This review will aid in determining if the relationship between RSV and asthma development is a causal one, by showing the effect (if any) of RSV prophylaxis on subsequent recurrent wheeze/asthma. If this study shows RSV prophylaxis to have no effect on the outcome of recurrent wheeze/asthma, the question of causality remains.