The Fungal Microbiome of the Upper Airway Is Associated With Future Loss of Asthma Control and Exacerbation Among Children With Asthma

Background: Accumulating evidence suggests that the upper airway bacterial microbiota is implicated in asthma inception, severity, and exacerbation. Unlike bacterial microbiota, the role of the upper airway fungal microbiome (mycobiome) in asthma control is poorly understood. Research Question: What are the upper airway fungal colonization patterns among children with asthma and their relationship with subsequent loss of asthma control and exacerbation of asthma? Study Design and Methods: The study was coupled with the Step Up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations (ClinicalTrials.gov Identifier: NCT02066129) clinical trial. The upper airway mycobiome was investigated using Internal transcribed spacer 1 (ITS1) sequencing of nasal blow samples collected from children with asthma when asthma was well controlled (baseline, n = 194) and during early signs of loss of asthma control (yellow zone [YZ], n = 107). Results: At baseline, 499 fungal genera were detected in the upper airway samples, with two commensal fungal species, Malassezia globosa and Malassezia restricta, being most dominant. The relative abundance of Malassezia species varies by age, BMI, and race. Higher relative abundance of M globosa at baseline was associated with lower risk of future YZ episodes (P =.038) and longer time to development of first YZ episode (P =.022). Higher relative abundance of M globosa at YZ episode was associated with lower risk of progression from YZ episode to severe asthma exacerbation (P =.04). The upper airway mycobiome underwent significant changes from baseline to YZ episode, and increased fungal diversity was correlated highly with increased bacterial diversity (ρ = 0.41). Interpretation: The upper airway commensal mycobiome is associated with future asthma control. This work highlights the importance of the mycobiota in asthma control and may contribute to the development of fungi-based markers to predict asthma exacerbation.