Should antifungal agents be prescribed to asthmatic children with ABPA? A systematic review and evidence-based guideline recommendation

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a complication of bronchial asthma. Many physicians routinely administer antifungal agents along with corticosteroids to children with ABPA, based on a few adult studies. Objective: We examined the evidence on efficacy and safety of antifungal agents in asthmatic patients with ABPA, to develop a guideline recommendation. Methods: Our research question was: What is the efficacy of antifungal agents in asthmatic children with ABPA, on various clinical outcomes? We conducted a systematic review (SR), with a stepwise evidence search for any preexisting guidelines whose recommendations could be adopted or adapted; followed by a search for existing SRs, followed by randomized controlled trials (RCTs). The evidence was collated, critically appraised, and synthesized. We then worked through the Evidence to Decision (EtD) framework, to formulate recommendations, using the Grading of Recommendations Assessment, Development and Evaluation approach. Results: There were no preexisting evidence-based guidelines or SRs addressing our question. Our new SR identified five RCTs in adults. These, had different designs, were limited in methodological quality, and examined different interventions. The body of evidence suggested that antifungal agents alone may not be efficacious in adults with ABPA. The certainty of evidence had to be downgraded for methodological limitations and indirectness for almost all outcomes in the five trials. Based on the considerations in the EtD framework, we were unable to formulate an evidence-based recommendation, either in favor of, or against, the intervention. Therefore, individual clinicians need not consider a change in their existing practice, i.e., those using antifungals may continue to do so and vice versa (until additional evidence becomes available). Conclusion: We offer a conditional recommendation that antifungal agents may or may not be added to steroid therapy in asthmatic children with ABPA (low certainty of evidence).