RESEARCH Association between adherence and severe asthma exacerbation: A systematic review and meta-analysis Bunchai Chongmelaxme, Nathorn Chaiyakunapruk, Piyameth Dilokthornsakul * article info Article history: Received 1 November 2019 Accepted 10 February 2020 abstract Objective: To assess the association between adherence levels and severe asthma exacerbation. Design: A systematic search was performed from inception to November 2018 on the following databases: PubMed, CENTRAL, EMBASE, and ClinicalTrials.gov. Setting and participants: Randomized-controlled trials (RCTs) and cohort and case-control studies that investigated the impact of adherence to controller medications on severe asthma exacerbation were included in the analysis. Data extraction was undertaken by 2 re- viewers, and all studies were assessed for their qualities using the Cochrane risk of bias tool for RCT and the Newcastle-Ottawa scale for cohort and case-control studies. Random-effects model meta-analyses were performed. Outcome measures: Severe asthma exacerbation. Results: From 8061 articles, 8 studies were included in quantitative synthesis. The meta- analyses revealed that the odds of exacerbation among the patients with 80% or more adherence were lowered by 47% (odds ratio 0.53 [95% CI 0.42e0.66], P < 0.001) compared with less than 80%. When compared with less than 20% adherence, a 33% reduction in the odds (0.67 [0.53e0.86], P ¼ 0.001) was associated with the patients achieving 50% or more, whereas a decrease in exacerbation was not associated with 20% to 49% adherence (0.94 [0.85e1.04], P ¼ 0.22). In addition, a 2.4-fold increase in the odds (2.4 [2.1e2.7], P < 0.001) was associated with discontinuation of therapy. Conclusion: The highest reduction in the odds of exacerbation was associated with patients achieving 80% or more adherence, and the odds also reduced among those with 50% or more adherence, whereas a substantial increase in exacerbation was associated with discontinua- tion of therapy. © 2020 Published by Elsevier Inc. on behalf of the American Pharmacists Association. Background Asthma is one of the most common chronic respiratory diseases that affects approximately 300 million people world- wide. 1,2 Its prevalence has steadily increased over the last few decades. In 2011, it was approximately 8.2% in the United States, and it was 5.1%, 9.1%, 10.6%, and 12.2% in China, Malaysia, Singapore, and Thailand, respectively. 3,4 Asthma exacerbation is the presence of progressively worsening shortness of breath, coughing, wheezing, and chest tightness or any combination thereof and is classified as mild, moderate, and severe on the basis of the severity of the symptoms combined with the results of a lung function assessment. 1 Mild exacerbations can be managed at home, but severe cases require a more tailored treatment that often includes monitoring in the emergency department (ED) or hospital admission. 5 Current evidence showed that the mean annual exacerbation rates per patient during a 12-month period were 0.16 per year in the United States and 0.11 per year in the United Kingdom. 6 Nonadherence is a common and costly problem for the treatment of asthma. 7 Studies have shown that 50% of children and adults did not take their prescribed medications, which was associated with uncontrolled symptoms and an increase in exacerbation rates and deaths. 8 The reported rates of non- adherence to asthma medications ranged from 30% to 70%, 1,9,10 and this had a substantial economic burden due to the direct Disclosure: The authors declare no relevant conflicts of interest or financial relationships. * Correspondence: Piyameth Dilokthornsakul, PharmD, PhD, Center of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Fac- ulty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand 65000. E-mail address: piyamethd@gmail.com (P. Dilokthornsakul). Contents lists available at ScienceDirect Journal of the American Pharmacists Association journal homepage: www.japha.org https://doi.org/10.1016/j.japh.2020.02.010 1544-3191/© 2020 Published by Elsevier Inc. on behalf of the American Pharmacists Association. Journal of the American Pharmacists Association xxx (2020) 1e17 SCIENCE AND PRACTICE