Background
Asthma is a long-term condition affecting the lungs. It is the most common long-term condition affecting children. One in 11 children in the United Kingdom have asthma. People with asthma can experience asthma 'attacks' of coughing, wheezing, and difficulty breathing.
Each year there is a peak in asthma attacks after school restarts in autumn. The likely reason for this is that children are exposed to more viruses that can trigger asthma. Children may also have taken their regular medication less consistently with the break in routine over the summer.
As this increase in attacks at the start of the school year is predictable, and the reason for it is somewhat understood, it might be preventable. Approaches to reducing autumn asthma attacks include using extra medications when school restarts or medication reminders during the school holiday.
Main findings
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.
Limitations
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.
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.
Asthma exacerbations in school-aged children peak in autumn, shortly after children return to school following the summer holiday. This might reflect a combination of risk factors, including poor treatment adherence, increased allergen and viral exposure, and altered immune tolerance. Since this peak is predictable, interventions targeting modifiable risk factors might reduce exacerbation-associated morbidity and strain upon health resources. The peak occurs in September in the Northern Hemisphere and in February in the Southern Hemisphere.
To assess the effects of pharmacotherapy and behavioural interventions enacted in anticipation of school return during autumn that are designed to reduce asthma exacerbations in children during this period.
We searched the Cochrane Airways Group Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, reference lists of primary studies and existing reviews, and manufacturers’ trial registries (Merck, Novartis and Ono Parmaceuticals). We searched databases from their inception to 1 December 2017, and imposed no restriction on language of publication.
We included all randomised controlled trials comparing interventions aimed specifically at reducing autumn exacerbations with usual care, (no systematic change in management in preparation for school return). We included studies providing data on children aged 18 years or younger.
We used standard methodological procedures expected by Cochrane. Two review authors independently screened records identified by the search and then extracted data and assessed bias for trials meeting the inclusion criteria. A third review author checked for accuracy and mediated consensus on disagreements. The primary outcome was proportion of children experiencing one or more asthma exacerbations requiring hospitalisation or oral corticosteroids during the autumn period.
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.