Abstract: Our searches returned 546 trials, of which five met our inclusion criteria. These studies randomised 14,252 children to receive either an intervention or usual care. All studies were conducted in the Northern Hemisphere. Three interventions used a leukotriene receptor antagonist, one used omalizumab or a boost of inhaled corticosteroids, and the largest study, (12,179 children), used a medication reminder letter. Whilst the risk of bias within individual studies was generally low, we downgraded the evidence quality due to imprecision associated with low participant numbers, poor consistency between studies, and indirect outcome ascertainment. A US study of 513 children with mild/severe asthma and allergic sensitisation was the only study to provide data for our primary outcome. In this study, the proportion of participants experiencing an exacerbation requiring oral corticosteroids or hospital admission in the 90 days after school return was significantly reduced to 11.3% in those receiving omalizumab compared to 21.0% in those receiving placebo (odds ratio 0.48, 95% confidence interval 0.25 to 0.92, moderate-quality evidence). The remaining studies used alternative exacerbation definitions. When data from two leukotriene receptor antagonist studies with comparable outcomes were combined in a random-effects model, there was no evidence of an effect upon exacerbations. There was no evidence that a seasonal medication reminder letter decreased unscheduled contacts for a respiratory diagnosis between September and December. Four studies recorded adverse events. There was no evidence that the proportion of participants experiencing at least one adverse event differed between intervention and usual care groups. Lack of data prevented planned subgroup and sensitivity analyses. Seasonal omalizumab treatment from four to six weeks before school return might reduce autumn asthma exacerbations. We found no evidence that this strategy is associated with increased adverse effects other than injection site pain, but it is costly. There were no data upon which to judge the effect of this or other seasonal interventions on asthma control, quality of life, or asthma-related death. In future studies definitions of exacerbations should be provided, and standardised where possible. To investigate possible differential effects according to subgroup, participants in future trials should be well characterised with respect to baseline asthma severity and exacerbation history in addition to age and gender.

Plain-language summary: Our searches found 546 trials, of which five were relevant. In total, 14,252 children were randomly assigned to receive either an intervention targeting autumn asthma attacks or usual care. Four small studies (approximately 200 to 1200 children in each) gave children extra asthma medication; these additional medications were omalizumab, leukotriene receptor antagonist tablets, or increased doses of inhaled steroids. One study sent a medication reminder letter over the summer holidays to parents of children with asthma. One trial gave children either omalizumab or placebo. Omalizumab is an antibody designed to alter the immune response. It was given by injection regularly over four to six weeks before school return (i.e. over the bulk of the summer holidays). The children in this study had known allergic asthma. The study showed that omalizumab might reduce autumn attacks. Eleven per cent of those receiving omalizumab had an asthma attack during the first 90 days compared to 21% of those receiving placebo. Three studies used leukotriene receptor antagonist tablets, either montelukast or pranlukast. Although the results of one study suggested that seasonal montelukast might reduce autumn attacks, there was no evidence of reduced attacks in the other two later trials, including a second larger trial of montelukast. There was no evidence that sending a reminder letter reduces the number of children requiring an unplanned healthcare contact. No study provided evidence that the total number of children experiencing adverse events was greater in the intervention than in the usual care group. Our findings were limited by the small numbers of studies identified and because these studies used different interventions and definitions of asthma exacerbations. Further research is needed to better understand how to prevent seasonal attacks, including interventions suitable for children with mild asthma, where expensive and painful treatments are not justified.