Background: Adherence rates among asthma patients are generally low and decrease during adolescence, resulting in poorly controlled asthma. The aim of our study was to evaluate the effectiveness of the ADolescent Adherence Patient Tool (ADAPT), an interactive mobile health (mHealth) intervention, in supporting selfmanagement and improving inhaled corticosteroid adherence in adolescents with asthma. Methods: We conducted a cluster randomized controlled trial in 66 Dutch community pharmacies. Asthma patients aged 12-18 years were invited to participate, based on pharmacy medication refill records. The main study outcome was self-reported medication adherence, measured with the Medication Adherence Report Scale (MARS). Secondary outcomes were asthma control and quality of life. Outcomes were measured at start (t = 0 months) and at the end of follow-up (t = 6 months). Mixed-effects models were used to analyze the effect. Results: In total, 234 adolescents (147 in the control group and 87 in the intervention group) completed the study; mean age 15.1 ± 1.9 years and 52.6% females. Adherence rates of patients with low baseline adherence (MARS scores ≤19; n = 76) increased with 1.42 points in the intervention group (n = 26). Adherence rates of patients in the control group (n = 50) decreased with 0.70 points. Thus there was a positive effect of the intervention on medication adherence (MARS +2.12, p = 0.04). This effect was stronger (MARS +2.52, p = 0.02) in poor adherent adolescents with uncontrolled asthma (n = 74). No effect of the intervention was observed on asthma control or quality of life. Conclusions: The ADAPT intervention increases medication adherence in adolescents with asthma having poor adherence rates at baseline. Healthcare providers should consider a tailored mHealth approach to improve the asthma treatment.

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Montelukast, a selective leukotriene receptor antagonist, is recommended in guidelines for the treatment of asthma in both children and adults. However, its effectiveness is debated, and recent studies have reported several adverse events such as neuropsychiatric disorders and allergic granulomatous angiitis. This study aims to obtain more insight into the safety profile of montelukast and to provide prescribing physicians with an overview of relevant adverse drug reactions in both children and adults. We retrospectively studied all adverse drug reactions on montelukast in children and adults reported to the Netherlands Pharmacovigilance Center Lareb and the WHO Global database, VigiBase® until 2016. Depression was reported most frequently in the whole population to the global database VigiBase® (reporting odds ratio (ROR) 6.93; 95% CI: 6.5–7.4). In the VigiBase®, aggression was reported the most in children (ROR, 29.77; 95% CI: 27.5–32.2). Headaches were reported the most frequently to the Dutch database (ROR, 2.26; 95% CI: 1.61–3.19). Furthermore, nightmares are often reported for both children and adults to the Dutch and the global database. Eight patients with allergic granulomatous angiitis were reported to the Dutch database and 563 patients in the VigiBase®. These data demonstrate that montelukast is associated with neuropsychiatric adverse drug reactions such as depression and aggression. Especially in children nightmares are reported frequently. Allergic granulomatous angiitis is also reported, a causal relationship has not been established.

Forgetfulness is a major reason for non-adherence in adolescents. Furthermore, our results suggest use of peer support may be helpful in promoting good medication use. Future interventions should be aimed at providing practical reminders and should be modifiable to individual preferences.

Antibiotic use in the third trimester of pregnancy was associated with a small increased risk of asthma in preschool children. This association was robust to time-invariant confounding or exposure time trends, further supporting the important role for early-life intestinal microbiota in the development of childhood asthma.