α- and β-diversity
Difference in airway microbiome was observed across cohorts at species level in both α-diversity (p = 0.001, Figure 1B ) and β-diversity (p ≤0.002, Figure 1C ). Although the levels of α-diversity in SAn and SAs/ex were comparable, SAs/ex exhibited lower α-diversity compared to MMA and HC. α-diversity of SAn was lower than that of MMA while there was no difference between MMA and HC (Figure 1B ). α-diversity was inversely correlated with sputum neutrophils in SAn, neutrophilic and paucigranulocytic inflammation groups, and in TAC1 and TAC3 (Figure S3). There was no positive association between α-diversity and exacerbations in the previous year or pack-years of smoking, but there was a positive correlation between α-diversity, and FEV1 (% predicted) in neutrophilic inflammation and in TAC2 (Figure S3 ).
Compared to HC, α-diversity was reduced in eosinophilic (p<0.05), neutrophilic (p<0.05) and mixed granulocytic (p<0.001) (Figure 2B ). Differences in β-diversity based on Bray-Curtis dissimilarity were observed across the inflammatory groups using PERMANOVA (p<0.001) and ordination using principal coordinate analysis (Figure 2C) .
α-diversity in TAC1 and TAC2 was lower than in TAC3 and HC (p<0.001) (Figure 3B) . Differences in β-diversity based on Bray-Curtis dissimilarity were also observed across the TACs (p<0.001) (Figure 3C) .