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Introduction: The chronic obstructive pulmonary disease (COPD) bacteriome associates with disease severity, exacerbations and mortality. While COPD patients are susceptible to fungal sensitisation, the role of the fungal mycobiome remains uncertain., Methods: We report the largest multicentre evaluation of the COPD airway mycobiome to date, including participants from Asia (Singapore and Malaysia) and the UK (Scotland) when stable (n=337) and during exacerbations (n=66) as well as nondiseased (healthy) controls (n=47). Longitudinal mycobiome analysis was performed during and following COPD exacerbations (n=34), and examined in terms of exacerbation frequency, 2-year mortality and occurrence of serum specific IgE (sIgE) against selected fungi., Results: A distinct mycobiome profile is observed in COPD compared with controls as evidenced by increased α-diversity (Shannon index; p<0.001). Significant airway mycobiome differences, including greater interfungal interaction (by co-occurrence), characterise very frequent COPD exacerbators (three or more exacerbations per year) (permutational multivariate ANOVA; adjusted p<0.001). Longitudinal analyses during exacerbations and following treatment with antibiotics and corticosteroids did not reveal any significant change in airway mycobiome profile. Unsupervised clustering resulted in two clinically distinct COPD groups: one with increased symptoms (COPD Assessment Test score) and Saccharomyces dominance, and another with very frequent exacerbations and higher mortality characterised by Aspergillus , Curvularia and Penicillium with a concomitant increase in serum sIgE levels against the same fungi. During acute exacerbations of COPD, lower fungal diversity associates with higher 2-year mortality., Conclusion: The airway mycobiome in COPD is characterised by specific fungal genera associated with exacerbations and increased mortality., Competing Interests: Conflict of interest: P.Y. Tiew has nothing to disclose. Conflict of interest: A.J. Dicker has nothing to disclose. Conflict of interest: H.R. Keir has nothing to disclose. Conflict of interest: M.E. Poh has nothing to disclose. Conflict of interest: S.L. Pang has nothing to disclose. Conflict of interest: M. Mac Aogáin has nothing to disclose. Conflict of interest: B.Q.Y. Chua has nothing to disclose. Conflict of interest: J.L. Tan has nothing to disclose. Conflict of interest: H. Xu has nothing to disclose. Conflict of interest: M.S. Koh has nothing to disclose. Conflict of interest: A. Tee has nothing to disclose. Conflict of interest: J.A. Abisheganaden has nothing to disclose. Conflict of interest: F.T. Chew reports personal fees for consultancy from Sime Darby Technology Centre, First Resources Ltd, Genting Plantation and Olam International, outside the submitted work. Conflict of interest: B.E. Miller is an employee and shareholder of GlaxoSmithKline. Conflict of interest: R. Tal-Singer reports personal fees from Immunomet and VOCALIS Health, outside the submitted work; and is a former employee and current shareholder of GlaxoSmithKline. Conflict of interest: J.D. Chalmers reports grants and personal fees from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, Grifols and Insmed, grants from Gilead Sciences, personal fees from Chiesi, Napp, Novartis and Zambon, outside the submitted work. Conflict of interest: S.H. Chotirmall has nothing to disclose., (Copyright ©ERS 2021.)

Introduction: Allergic sensitisation to fungi such as Aspergillus are associated to poor clinical outcomes in asthma, bronchiectasis and cystic fibrosis; however, clinical relevance in COPD remains unclear., Methods: Patients with stable COPD (n=446) and nondiseased controls (n=51) were prospectively recruited across three countries (Singapore, Malaysia and Hong Kong) and screened against a comprehensive allergen panel including house dust mites, pollens, cockroach and fungi. For the first time, using a metagenomics approach, we assessed outdoor and indoor environmental allergen exposure in COPD. We identified key fungi in outdoor air and developed specific-IgE assays against the top culturable fungi, linking sensitisation responses to COPD outcomes. Indoor air and surface allergens were prospectively evaluated by metagenomics in the homes of 11 COPD patients and linked to clinical outcome., Results: High frequencies of sensitisation to a broad range of allergens occur in COPD. Fungal sensitisation associates with frequent exacerbations, and unsupervised clustering reveals a "highly sensitised fungal predominant" subgroup demonstrating significant symptomatology, frequent exacerbations and poor lung function. Outdoor and indoor environments serve as important reservoirs of fungal allergen exposure in COPD and promote a sensitisation response to outdoor air fungi. Indoor (home) environments with high fungal allergens associate with greater COPD symptoms and poorer lung function, illustrating the importance of environmental exposures on clinical outcomes in COPD., Conclusion: Fungal sensitisation is prevalent in COPD and associates with frequent exacerbations representing a potential treatable trait. Outdoor and indoor (home) environments represent a key source of fungal allergen exposure, amenable to intervention, in "sensitised" COPD., Competing Interests: Conflict of interest: P.Y. Tiew has nothing to disclose. Conflict of interest: F.W.S. Ko has nothing to disclose. Conflict of interest: S.L. Pang has nothing to disclose. Conflict of interest: S.A. Matta has nothing to disclose. Conflict of interest: Y.Y. Sio has nothing to disclose. Conflict of interest: M.E. Poh has nothing to disclose. Conflict of interest: K.J.X. Lau has nothing to disclose. Conflict of interest: M. Mac Aogain has nothing to disclose. Conflict of interest: T.K. Jaggi has nothing to disclose. Conflict of interest: F.X. Ivan has nothing to disclose. Conflict of interest: N.E. Gaultier has nothing to disclose. Conflict of interest: A. Uchida has nothing to disclose. Conflict of interest: D.I. Drautz-Moses has nothing to disclose. Conflict of interest: H. Xu has nothing to disclose. Conflict of interest: M.S. Koh has nothing to disclose. Conflict of interest: D.S.C. Hui has nothing to disclose. Conflict of interest: A. Tee has nothing to disclose. Conflict of interest: J.A. Abisheganaden has nothing to disclose. Conflict of interest: S.C. Schuster has nothing to disclose. Conflict of interest: F.T. Chew has nothing to disclose. Conflict of interest: S.H. Chotirmall has nothing to disclose., (Copyright ©ERS 2020.)

Understanding the composition and clinical importance of the fungal mycobiome was recently identified as a key topic in a "research priorities" consensus statement for bronchiectasis.Patients were recruited as part of the CAMEB study: an international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis patients. The mycobiome was determined in 238 patients by targeted amplicon shotgun sequencing of the 18S-28S rRNA internally transcribed spacer regions ITS1 and ITS2. Specific quantitative PCR for detection of and conidial quantification for a range of airway Aspergillus species was performed. Sputum galactomannan, Aspergillus specific IgE, IgG and TARC (thymus and activation regulated chemokine) levels were measured systemically and associated to clinical outcomes.The bronchiectasis mycobiome is distinct and characterised by specific fungal genera, including Aspergillus , Cryptococcus and Clavispora Aspergillus fumigatus (in Singapore/Kuala Lumpur) and Aspergillus terreus (in Dundee) dominated profiles, the latter associating with exacerbations. High frequencies of Aspergillus- associated disease including sensitisation and allergic bronchopulmonary aspergillosis were detected. Each revealed distinct mycobiome profiles, and associated with more severe disease, poorer pulmonary function and increased exacerbations.The pulmonary mycobiome is of clinical relevance in bronchiectasis. Screening for Aspergillus -associated disease should be considered even in apparently stable patients., Competing Interests: Conflict of interest: F.T. Chew reports personal fees from Sime Darby Technology Center, Olam International and First Resources Ltd, outside the submitted work. J.D. Chalmers reports grants from AstraZeneca, grants and personal fees from GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Bayer Healthcare and Grifols, and personal fees from Napp, outside the submitted work., (Copyright ©ERS 2018.)