Environmental fungal sensitisation associates with poorer clinical outcomes in COPD

Introduction: Allergic sensitization 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 non-diseased 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 assess outdoor and indoor environmental allergen exposure in COPD. We identify key fungi in outdoor air and develop specific-IgE assays against the top culturable fungi, linking sensitization responses to COPD outcomes. Indoor air and surface allergens were prospectively evaluated by metagenomics in the homes of n=11 COPD patients and linked to clinical outcome. Results: High frequencies of sensitization to a broad range of allergens occurs in COPD. Fungal sensitization associates with frequent exacerbations, and, unsupervised clustering reveals a „highly sensitized fungal predominant‟ sub-group 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 sensitization 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 sensitization 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 „sensitized‟ COPD.