Increased Chitotriosidase Is Associated With Aspergillus and Frequent Exacerbations in South-East Asian Patients With Bronchiectasis

Tuang Yeow Poh, Pei Yee Tiew, Albert Yick Hou Lim, Kai Xian Thng, Nur A'tikah Binte Mohamed Ali, Jayanth Kumar Narayana, Micheál Mac Aogáin, Zhijun Tien, Wui Mei Chew, Adrian Kwok Wai Chan, Holly R. Keir, Alison J. Dicker, Tidi Maharani Hassan, Huiying Xu, Augustine K. H. Tee, Thun How Ong, Mariko Siyue Koh, John Arputhan Abisheganaden, James D. Chalmers, Sanjay H. Chotirmall (Lead / Corresponding author)

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)512-522
Number of pages11
JournalChest
Volume158
Issue number2
Early online date14 Mar 2020
DOIs
Publication statusPublished - Aug 2020

Keywords

  • acid mammalian chitinase
  • bronchiectasis
  • chitinase
  • chitotriosidase
  • exacerbation

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