S58 Viral infection perturbs the respiratory mycobiome in COPD

Introduction Molecular studies have recently revealed that the lower respiratory tract harbours a microbiome consisting of bacteria, fungi, and viruses. Emerging evidence indicates that commensal bacteria (‘bacteriome’) can modulate host immunity but very little is known about commensal fungi (‘mycobiome’). Mycobiome perturbations have been reported in stable COPD but the role they play in driving susceptibility to infectious exacerbations are unknown. An emerging paradigm of exacerbation pathogenesis argues that consideration of the bacteriome alone may be an over-simplification in understanding drivers of these heterogenous episodes. We therefore sought to understand how the mycobiome changes and relates to inflammatory responses during virus-exacerbated COPD. Methods We analysed samples collected during carefully controlled studies of rhinovirus challenge in COPD (n=9) and healthy controls (n=12). Sputum was analysed at baseline (pre-infection) and at days 5, 12 and 42 following rhinovirus inoculation. ITS2 sequencing was used to profile the mycobiome and correlations with cytokine measurements by MSD were assessed. Results Changes in fungal genera occurring during the infection course in COPD and healthy subjects are shown in figure 1A. Rhinovirus infection led to a trend towards increased alpha diversity in COPD subjects (P=0.129) at day 12 post-infection, an effect not observed in healthy controls. Bray-Curtis dissimilarity showed separation between the COPD and healthy groups at day 5 post-infection (P=0.068) (figure 1B). Mycobiome changes during infection broadly showed inter-subject heterogeneity (figure 1C). Significant expansion of Cladosporium was observed in COPD subjects from baseline to day 12 post-infection (P=0.004) (figure 1C). In COPD patients, early expansion of Candida (day 5 post-infection) correlated with sputum concentrations of pro-inflammatory (MIP-1beta, P<0.01) and type 2 cytokines (IL-13, P<0.05). The most prominent correlations in the healthy participants occurred at day 12, where Candida and Cladosporium abundance correlated with a range of pro-inflammatory and type 2 cytokines. Conclusion The respiratory mycobiome is perturbed during respiratory viral infection with heterogenous changes seen in COPD and healthy individuals. Correlations between fungal genera and inflammation raise the possibility that these commensals directly influence immune responses during exacerbations but functional studies would be required for further confirmation.