Airway microbiota in young people across four continents differ by country, asthma status and inflammatory phenotype

BackgroundAsthma is an umbrella diagnosis encompassing distinct pathophysiological mechanisms. While a global problem, our understanding of the interplay between respiratory microbiology and airway inflammation is largely from populations in high income settings. As a result, treatment approaches align poorly with asthma characteristics in less studied populations. ObjectiveTo identify conserved and geographically distinct relationships between airway inflammation and microbiota characteristics in young people with asthma. MethodsWe conducted a cross-sectional study performing inflammatory phenotyping, microbiota analysis, and enumeration of total bacteria, Haemophilus influenzae and Moraxella catarrhalis on 488 induced sputum samples from Brazil (n=68), Ecuador (n=119), Uganda (n=69), New Zealand (n=187), and the United Kingdom (n=45). Microbiological characteristics were compared by country, asthma status, and inflammatory characteristics, adjusting for age and sex. ResultsInflammatory phenotypes and airway microbiota differed between countries, with Uganda characterised by greater neutrophil%, microbial diversity, and bacterial load. Across all countries, microbiota similarity differed by asthma status (P=0.012). Within participants with asthma, microbiota similarity for neutrophilic and eosinophilic phenotypes differed from paucigranulocytic (P<0.001 and P=0.020, respectively) and from each other (P<0.001). Neutrophil% was strongly associated with microbiota composition (P<0.001) and positively associated with bacterial load and opportunistic pathogens (P<0.05). In contrast, eosinophil% was less strongly associated with microbiota similarity (P=0.033), positively associated with Streptococcus (P=0.0009), but not associated with bacterial load (P=0.787). Country-specific associations between sputum inflammation and microbiology were evident. ConclusionBoth airway inflammation and microbiology varied geographically in young people with asthma. Associations between microbiota characteristics and neutrophilic phenotype were conserved. Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIAsthma treatment response and severity are associated with airway inflammation and microbiology. C_LIO_LIMost asthma research is performed in high income countries and the generalisability in other settings is unclear. C_LI What this study addsO_LIAsthma inflammatory phenotypes and airway microbiota vary across high income (New Zealand and the United Kingdom) and low to middle income (Brazil, Ecuador, Uganda) countries. C_LIO_LIThe association between airway microbiota and neutrophilic and eosinophilic inflammation is complex and varied between countries. C_LI How this study might affect research, practice or policyO_LIUnderstanding variation in underlying pathophysiology between countries can inform improved deployment of maintenance asthma therapies, such as macrolides and inhaled corticosteroids, that target specific inflammatory pathways. C_LI