BACKGROUND 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.

中文翻译：

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增加的壳三糖苷酶与曲霉和支气管扩张的东南亚人的频繁恶化有关

背景与研究问题：几丁质酶活性是一种重要的先天免疫防御机制，可以抵御真菌等感染。两种人类几丁质酶：壳三糖苷酶 (CHIT1) 和酸性哺乳动物几丁质酶 (AMCase) 与过敏、哮喘和慢性阻塞性肺病 (COPD) 相关，然而，它们在支气管扩张和支气管扩张-COPD 重叠 (BCO) 中的作用尚不清楚。方法：在三个国家（新加坡、马来西亚和苏格兰）的五个医院地点招募了一个由 n=463 个人组成的前瞻性队列，包括未患病（n=35）、严重哮喘（n=54）、COPD（n=90） , 支气管扩张 (n=241) 和 BCO (n=43)。评估了全身几丁质酶水平，对于与临床结果、气道曲霉状态和潜在肺真菌组谱相关的支气管扩张和 BCO 结果：支气管扩张和 BCO 的全身几丁质酶活性显着升高，超过其他气道疾病。CHIT1 活性强烈预测支气管扩张恶化，并且与气道中至少一种曲霉属物种的存在和频繁恶化（> 3 次恶化/年）有关。亚组分析揭示了东南亚患者的 CHIT1 活性与“频繁恶化者”表型之间的关联，这些患者的气道真菌组谱表明存在新的真菌类群，包括大文丘菌、弯孢菌和肉孢菌。这些富含 CHIT1 频繁恶化的东南亚人的分类群可能在支气管扩张恶化中具有潜在作用 解释：系统性 CHIT1 活性可能代表一种有用的临床工具，用于识别真菌驱动的