Search

Background Allergic bronchopulmonary aspergillosis (ABPA) is associated with frequent exacerbations and poor outcomes in chronic respiratory disease, but remains underdiagnosed. The role of fungal sensitization in bronchiectasis-COPD overlap (BCO) is unknown. Research Question What is the occurrence and clinical relevance of Aspergillus sensitization and ABPA in BCO when compared with individuals with COPD or bronchiectasis without overlap? Study Design Prospective, observational, cross-sectional study. Methods We prospectively recruited 280 patients during periods of clinical stability with bronchiectasis (n = 183), COPD (n = 50), and BCO (n = 47) from six hospitals across three countries (Singapore, Malaysia, and Scotland). We assessed sensitization responses (as specific IgE) to a panel of recombinant Aspergillus fumigatus allergens and the occurrence of ABPA in relationship to clinical outcomes. Results Individuals with BCO show an increased frequency and clinical severity of ABPA compared with those with COPD and bronchiectasis without overlap. BCO-associated ABPA is associated with more severe disease, higher exacerbation rates, and lower lung function when compared with ABPA occurring in the absence of overlap. BCO with a severe bronchiectasis severity index (BSI; > 9) is associated significantly with the occurrence of ABPA that is unrelated to underlying COPD severity. Conclusions BCO demonstrates a high frequency of ABPA that is associated with a severe BSI (> 9) and poor clinical outcomes. Clinicians should maintain a high index of suspicion for the potential development of ABPA in patients with BCO with high BSI.

Background Chitinase activity is an important innate immune defence mechanism against infection that includes fungi. The 2 human chitinases: chitotriosidase (CHIT1) and acidic mammalian chitinase are associated to allergy, asthma, and COPD; however, their role in bronchiectasis and bronchiectasis-COPD overlap (BCO) is unknown. Research Question What is the association between chitinase activity, airway fungi and clinical outcomes in bronchiectasis and bronchiectasis-COPD overlap? Study Design and Methods A prospective cohort of 463 individuals were recruited across five hospital sites in three countries (Singapore, Malaysia, and Scotland) including individuals who were not diseased (n = 35) and who had severe asthma (n = 54), COPD (n = 90), bronchiectasis (n = 241) and BCO (n = 43). Systemic chitinase levels were assessed for bronchiectasis and BCO and related to clinical outcomes, airway Aspergillus status, and underlying pulmonary mycobiome profiles. Results Systemic chitinase activity is elevated significantly in bronchiectasis and BCO and exceed the activity in other airway diseases. CHIT1 activity strongly predicts bronchiectasis exacerbations and is associated with the presence of at least one Aspergillus species in the airway and frequent exacerbations (≥3 exacerbations/y). Subgroup analysis reveals an association between CHIT1 activity and the “frequent exacerbator” phenotype in South-East Asian patients whose airway mycobiome profiles indicate the presence of novel fungal taxa that include Macroventuria, Curvularia and Sarocladium. These taxa, enriched in frequently exacerbating South-East Asian patients with high CHIT1 may have potential roles in bronchiectasis exacerbations. Interpretation Systemic CHIT1 activity may represent a useful clinical tool for the identification of fungal-driven “frequent exacerbators” with bronchiectasis in South-East Asian populations.

Background The role of Candida albicans in the cystic fibrosis (CF) airway is underexplored. Considered a colonizer, few question its pathogenic potential despite high isolation frequencies from sputum culture. We evaluated the frequency and identified the strongest predictors of C albicans colonization in CF. Independent associations of colonization with clinical outcomes were determined, and the longitudinal effects of C albicans acquisition on BMI and FEV 1 were evaluated. Methods A prospective observational study of 89 patients with CF was performed (3,916 sputum samples over 11 years). Frequency of C albicans growth in sputum allowed classification of the cohort into colonizers and noncolonizers. BMI, FEV 1 , hospital-treated exacerbations, and other clinical parameters were followed throughout the study to determine association with colonization status. Multivariate regression determined the strongest predictors of colonization and for clinical effects after adjustment for confounders. Repeated-measures analysis of variance assessed the longitudinal effect of colonization on BMI and FEV 1 . Results Colonization with C albicans was frequent (49.4%) and best predicted by pancreatic insufficiency ( P = .014), osteopenia ( P = .03), and cocolonization with Pseudomonas species ( P = .002). C albicans colonization significantly predicted hospital-treated exacerbations ( P = .004) after adjustment for confounders. Exacerbation rate significantly increased in patients with chronic or intermittent colonizations following first acquisition of C albicans . Colonization accelerated rates of decline for BMI ( P 1 ( P Conclusion Airway colonization with C albicans presaged a greater rate of FEV 1 decline and hospital-treated exacerbations in CF.