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

doi:10.1016/j.chest.2020.02.048

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 journal › Article › peer-review

16 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 language	English
Pages (from-to)	512-522
Number of pages	11
Journal	Chest
Volume	158
Issue number	2
Early online date	14 Mar 2020
DOIs	https://doi.org/10.1016/j.chest.2020.02.048
Publication status	Published - Aug 2020

Keywords

acid mammalian chitinase
bronchiectasis
chitinase
chitotriosidase
exacerbation

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine
Critical Care and Intensive Care Medicine
Cardiology and Cardiovascular Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.chest.2020.02.048Licence: Elsevier User Licence

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Poh, T. Y., Tiew, P. Y., Hou Lim, A. Y., Thng, K. X., Binte Mohamed Ali, N. A., Narayana, J. K., Aogáin, M. M., Tien, Z., Chew, W. M., Wai Chan, A. K., Keir, H. R., Dicker, A. J., Hassan, T. M., Xu, H., Tee, A. K. H., Ong, T. H., Koh, M. S., Abisheganaden, J. A., Chalmers, J. D., & Chotirmall, S. H. (2020). Increased Chitotriosidase Is Associated With Aspergillus and Frequent Exacerbations in South-East Asian Patients With Bronchiectasis. Chest, 158(2), 512-522. https://doi.org/10.1016/j.chest.2020.02.048

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

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.",

keywords = "acid mammalian chitinase, bronchiectasis, chitinase, chitotriosidase, exacerbation",

author = "Poh, {Tuang Yeow} and Tiew, {Pei Yee} and {Hou Lim}, {Albert Yick} and Thng, {Kai Xian} and {Binte Mohamed Ali}, {Nur A'tikah} and Narayana, {Jayanth Kumar} and Aog{\'a}in, {Miche{\'a}l Mac} and Zhijun Tien and Chew, {Wui Mei} and {Wai Chan}, {Adrian Kwok} and Keir, {Holly R.} and Dicker, {Alison J.} and Hassan, {Tidi Maharani} and Huiying Xu and Tee, {Augustine K. H.} and Ong, {Thun How} and Koh, {Mariko Siyue} and Abisheganaden, {John Arputhan} and Chalmers, {James D.} and Chotirmall, {Sanjay H.}",

note = "Copyright {\textcopyright} 2020. Published by Elsevier Inc.",

year = "2020",

month = aug,

doi = "10.1016/j.chest.2020.02.048",

language = "English",

volume = "158",

pages = "512--522",

journal = "Chest",

issn = "0012-3692",

publisher = "Elsevier",

number = "2",

}

Poh, TY, Tiew, PY, Hou Lim, AY, Thng, KX, Binte Mohamed Ali, NA, Narayana, JK, Aogáin, MM, Tien, Z, Chew, WM, Wai Chan, AK, Keir, HR, Dicker, AJ, Hassan, TM, Xu, H, Tee, AKH, Ong, TH, Koh, MS, Abisheganaden, JA, Chalmers, JD & Chotirmall, SH 2020, 'Increased Chitotriosidase Is Associated With Aspergillus and Frequent Exacerbations in South-East Asian Patients With Bronchiectasis', Chest, vol. 158, no. 2, pp. 512-522. https://doi.org/10.1016/j.chest.2020.02.048

TY - JOUR

T1 - Increased Chitotriosidase Is Associated With Aspergillus and Frequent Exacerbations in South-East Asian Patients With Bronchiectasis

AU - Poh, Tuang Yeow

AU - Tiew, Pei Yee

AU - Hou Lim, Albert Yick

AU - Thng, Kai Xian

AU - Binte Mohamed Ali, Nur A'tikah

AU - Narayana, Jayanth Kumar

AU - Aogáin, Micheál Mac

AU - Tien, Zhijun

AU - Chew, Wui Mei

AU - Wai Chan, Adrian Kwok

AU - Keir, Holly R.

AU - Dicker, Alison J.

AU - Hassan, Tidi Maharani

AU - Xu, Huiying

AU - Tee, Augustine K. H.

AU - Ong, Thun How

AU - Koh, Mariko Siyue

AU - Abisheganaden, John Arputhan

AU - Chalmers, James D.

AU - Chotirmall, Sanjay H.

PY - 2020/8

Y1 - 2020/8

N2 - 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.

AB - 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.

KW - acid mammalian chitinase

KW - bronchiectasis

KW - chitinase

KW - chitotriosidase

KW - exacerbation

UR - http://www.scopus.com/inward/record.url?scp=85084034697&partnerID=8YFLogxK

U2 - 10.1016/j.chest.2020.02.048

DO - 10.1016/j.chest.2020.02.048

M3 - Article

C2 - 32184111

SN - 0012-3692

VL - 158

SP - 512

EP - 522

JO - Chest

JF - Chest

IS - 2

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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