Increased chitotriosidase is associated with aspergillus and frequent exacerbations in south-east Asians with bronchiectasis

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and Research Question: Chitinase activity is an important innate immune defence mechanism against infection including fungi. The two human chitinases: chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase) are associated to allergy, asthma and chronic obstructive pulmonary disease (COPD), however, their role in bronchiectasis and bronchiectasis-COPD overlap (BCO) is unknown STUDY DESIGN AND METHODS: A prospective cohort of n=463 individuals were recruited across five hospital sites in three countries (Singapore, Malaysia and Scotland) including non-diseased (n=35), severe asthma (n=54), COPD (n=90), bronchiectasis (n=241) and BCO (n=43). Systemic Chitinase levels were assessed, and, for bronchiectasis and BCO related to clinical outcomes, airway Aspergillus status and underlying pulmonary mycobiome profiles RESULTS: Systemic chitinase activity is significantly elevated in bronchiectasis and BCO exceeding that 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/year). 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 including Macroventuria, Curvularia and Sarocladium. These taxa, enriched in frequently exacerbating South-East Asians 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.and Research Question: Chitinase activity is an important innate immune defence mechanism against infection including fungi. The two human chitinases: chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase) are associated to allergy, asthma and chronic obstructive pulmonary disease (COPD), however, their role in bronchiectasis and bronchiectasis-COPD overlap (BCO) is unknown STUDY DESIGN AND METHODS: A prospective cohort of n=463 individuals were recruited across five hospital sites in three countries (Singapore, Malaysia and Scotland) including non-diseased (n=35), severe asthma (n=54), COPD (n=90), bronchiectasis (n=241) and BCO (n=43). Systemic Chitinase levels were assessed, and, for bronchiectasis and BCO related to clinical outcomes, airway Aspergillus status and underlying pulmonary mycobiome profiles RESULTS: Systemic chitinase activity is significantly elevated in bronchiectasis and BCO exceeding that 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/year). 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 including Macroventuria, Curvularia and Sarocladium. These taxa, enriched in frequently exacerbating South-East Asians 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.and Research Question: Chitinase activity is an important innate immune defence mechanism against infection including fungi. The two human chitinases: chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase) are associated to allergy, asthma and chronic obstructive pulmonary disease (COPD), however, their role in bronchiectasis and bronchiectasis-COPD overlap (BCO) is unknown STUDY DESIGN AND METHODS: A prospective cohort of n=463 individuals were recruited across five hospital sites in three countries (Singapore, Malaysia and Scotland) including non-diseased (n=35), severe asthma (n=54), COPD (n=90), bronchiectasis (n=241) and BCO (n=43). Systemic Chitinase levels were assessed, and, for bronchiectasis and BCO related to clinical outcomes, airway Aspergillus status and underlying pulmonary mycobiome profiles RESULTS: Systemic chitinase activity is significantly elevated in bronchiectasis and BCO exceeding that 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/year). 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 including Macroventuria, Curvularia and Sarocladium. These taxa, enriched in frequently exacerbating South-East Asians 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.



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