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

Background Asthma 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. Objective To identify conserved and geographically distinct relationships between airway inflammation and microbiota characteristics in young people with and without asthma. Methods We 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 participants from Brazil (asthma: 68; non-asthma: 8), Ecuador (asthma: 89; non-asthma: 30), Uganda (asthma: 61; non-asthma: 8), New Zealand (asthma: 129; non-asthma: 58) and the UK (asthma: 25; non-asthma: 20). Microbiota characteristics were compared by country, asthma status and inflammatory characteristics, adjusting for age and sex. Results Asthma inflammatory phenotypes and microbiology differed between countries, with Uganda characterised by higher neutrophils, microbial diversity and bacterial abundance. Comparison of airway inflammation with microbiota characteristics showed conserved relationships across centres, with airway neutrophil proportion explaining variance in microbiota Bray-Curtis dissimilarity (p<0.001) and being positively associated with bacterial abundance, including H. influenzae and M. catarrhalis load (all p<0.05). In contrast, eosinophil proportion was less strongly associated with microbiota dissimilarity (p=0.033) and only associated with Streptococcus abundance. Country-specific associations between airway inflammation and microbiology were evident. Conclusion Both airway inflammation and microbiology varied geographically in young people with asthma. Associations between microbiota characteristics and neutrophilic phenotype were conserved.