Distinct 'Immuno-Allertypes' of Disease and High Frequencies of Sensitisation in Non-Cystic-Fibrosis Bronchiectasis

Micheál Mac Aogáin; Pei Yee Tiew; Albert Yick Hou Lim; Teck Boon Low; Gan Liang Tan; Tidi Hassan; Thun How Ong; Sze Lei Pang; Zi Yang Lee; Xiao Wei Gwee; Christopher Martinus; Yang Yie Sio; Sri Anusha Matta; Tan Ching Ong; Yuen Seng Tiong; Kang Ning Wong; Sriram Narayanan; Veonice Bijin Au; Damien Marlier; Holly R. Keir; Augustine Tee; John Arputhan Abisheganaden; Mariko Siyue Koh; De Yun Wang; John E. Connolly; Fook Tim Chew; James D. Chalmers; Sanjay H. Chotirmall

doi:10.1164/rccm.201807-1355OC

Distinct 'Immuno-Allertypes' of Disease and High Frequencies of Sensitisation in Non-Cystic-Fibrosis Bronchiectasis

Micheál Mac Aogáin, Pei Yee Tiew, Albert Yick Hou Lim, Teck Boon Low, Gan Liang Tan, Tidi Hassan, Thun How Ong, Sze Lei Pang, Zi Yang Lee, Xiao Wei Gwee, Christopher Martinus, Yang Yie Sio, Sri Anusha Matta, Tan Ching Ong, Yuen Seng Tiong, Kang Ning Wong, Sriram Narayanan, Veonice Bijin Au, Damien Marlier, Holly R. KeirAugustine Tee, John Arputhan Abisheganaden, Mariko Siyue Koh, De Yun Wang, John E. Connolly, Fook Tim Chew, James D. Chalmers, Sanjay H. Chotirmall (Lead / Corresponding author)

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Abstract

Rationale: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease and cystic fibrosis however its presence, frequency and clinical significance in non-CF bronchiectasis remain unclear.

Objective: To determine the frequency and geographic variability that exists in sensitization pattern to common and specific allergens including house dust mite and fungi and, to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis.

Methods: Patients with bronchiectasis were recruited in Asia (Singapore & Malaysia) and the United Kingdom (Scotland) (n=238) forming the Cohort of Asian and Matched European Bronchiectasis (CAMEB) which matched recruited patients on age, gender and bronchiectasis severity. Specific-IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters based on sensitization pattern and airway immune profiles ("immuno-allertypes") were determined.

Measurements and main results: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n=149). Sensitization associated with poor clinical outcomes including decreased pulmonary function and more severe disease. 'Sensitized-bronchiectasis' was classified into two 'immuno-allertypes': one fungal-driven and pro-inflammatory versus house dust mite-driven, chemokine-dominant with the former demonstrating poorer clinical outcome.

Conclusion: Allergic sensitization occurs at high frequency in bronchiectasis patients recruited from different global centres. Improving endo-phenotyping of 'sensitized-bronchiectasis', a clinically significant state, and 'treatable trait' permits therapeutic intervention in appropriate patients and may allow improved stratification in future bronchiectasis research and clinical trials.

Original language	English
Pages (from-to)	842-853
Number of pages	12
Journal	American Journal of Respiratory and Critical Care Medicine
Volume	199
Issue number	7
Early online date	28 Sept 2018
DOIs	https://doi.org/10.1164/rccm.201807-1355OC
Publication status	Published - 1 Apr 2019

Keywords

Bronchiectasis
Sensitization
Allergy
House dust-mite
Aspergillus

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Mac Aogáin, M., Tiew, P. Y., Lim, A. Y. H., Low, T. B., Tan, G. L., Hassan, T., Ong, T. H., Pang, S. L., Lee, Z. Y., Gwee, X. W., Martinus, C., Sio, Y. Y., Matta, S. A., Ong, T. C., Tiong, Y. S., Wong, K. N., Narayanan, S., Bijin Au, V., Marlier, D., ... Chotirmall, S. H. (2019). Distinct 'Immuno-Allertypes' of Disease and High Frequencies of Sensitisation in Non-Cystic-Fibrosis Bronchiectasis. American Journal of Respiratory and Critical Care Medicine, 199(7), 842-853. https://doi.org/10.1164/rccm.201807-1355OC

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title = "Distinct 'Immuno-Allertypes' of Disease and High Frequencies of Sensitisation in Non-Cystic-Fibrosis Bronchiectasis",

abstract = "Rationale: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease and cystic fibrosis however its presence, frequency and clinical significance in non-CF bronchiectasis remain unclear.Objective: To determine the frequency and geographic variability that exists in sensitization pattern to common and specific allergens including house dust mite and fungi and, to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis.Methods: Patients with bronchiectasis were recruited in Asia (Singapore & Malaysia) and the United Kingdom (Scotland) (n=238) forming the Cohort of Asian and Matched European Bronchiectasis (CAMEB) which matched recruited patients on age, gender and bronchiectasis severity. Specific-IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters based on sensitization pattern and airway immune profiles ({"}immuno-allertypes{"}) were determined.Measurements and main results: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n=149). Sensitization associated with poor clinical outcomes including decreased pulmonary function and more severe disease. 'Sensitized-bronchiectasis' was classified into two 'immuno-allertypes': one fungal-driven and pro-inflammatory versus house dust mite-driven, chemokine-dominant with the former demonstrating poorer clinical outcome.Conclusion: Allergic sensitization occurs at high frequency in bronchiectasis patients recruited from different global centres. Improving endo-phenotyping of 'sensitized-bronchiectasis', a clinically significant state, and 'treatable trait' permits therapeutic intervention in appropriate patients and may allow improved stratification in future bronchiectasis research and clinical trials.",

keywords = "Bronchiectasis, Sensitization, Allergy, House dust-mite, Aspergillus",

author = "{Mac Aog{\'a}in}, Miche{\'a}l and Tiew, {Pei Yee} and Lim, {Albert Yick Hou} and Low, {Teck Boon} and Tan, {Gan Liang} and Tidi Hassan and Ong, {Thun How} and Pang, {Sze Lei} and Lee, {Zi Yang} and Gwee, {Xiao Wei} and Christopher Martinus and Sio, {Yang Yie} and Matta, {Sri Anusha} and Ong, {Tan Ching} and Tiong, {Yuen Seng} and Wong, {Kang Ning} and Sriram Narayanan and {Bijin Au}, Veonice and Damien Marlier and Keir, {Holly R.} and Augustine Tee and Abisheganaden, {John Arputhan} and Koh, {Mariko Siyue} and Wang, {De Yun} and Connolly, {John E.} and Chew, {Fook Tim} and Chalmers, {James D.} and Chotirmall, {Sanjay H.}",

note = " This research is supported by the Singapore Ministry of Health{\textquoteright}s National Medical Research Council under its Transition Award (NMRC/TA/0048/2016) (S.H.C) and the Changi General Hospital Research Grant (CHF2016.03-P) (T.B.L). The work performed at NUS was supported by the Singapore Ministry of Education Academic Research Fund, SIgN, and the National Medical Research Council: N-154-000-038-001, R-154-000-404-112, R154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154- 000-A27-597, SIgN-06-006, SIgN-08-020 and NMRC/1150/2008 (F.T.C.). JDC is supported by the GSK/British Lung Foundation Chair of Respiratory Research. ",

year = "2019",

month = apr,

day = "1",

doi = "10.1164/rccm.201807-1355OC",

language = "English",

volume = "199",

pages = "842--853",

journal = "American Journal of Respiratory and Critical Care Medicine",

issn = "1073-449X",

publisher = "American Thoracic Society",

number = "7",

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Mac Aogáin, M, Tiew, PY, Lim, AYH, Low, TB, Tan, GL, Hassan, T, Ong, TH, Pang, SL, Lee, ZY, Gwee, XW, Martinus, C, Sio, YY, Matta, SA, Ong, TC, Tiong, YS, Wong, KN, Narayanan, S, Bijin Au, V, Marlier, D, Keir, HR, Tee, A, Abisheganaden, JA, Koh, MS, Wang, DY, Connolly, JE, Chew, FT, Chalmers, JD & Chotirmall, SH 2019, 'Distinct 'Immuno-Allertypes' of Disease and High Frequencies of Sensitisation in Non-Cystic-Fibrosis Bronchiectasis', American Journal of Respiratory and Critical Care Medicine, vol. 199, no. 7, pp. 842-853. https://doi.org/10.1164/rccm.201807-1355OC

TY - JOUR

T1 - Distinct 'Immuno-Allertypes' of Disease and High Frequencies of Sensitisation in Non-Cystic-Fibrosis Bronchiectasis

AU - Mac Aogáin, Micheál

AU - Tiew, Pei Yee

AU - Lim, Albert Yick Hou

AU - Low, Teck Boon

AU - Tan, Gan Liang

AU - Hassan, Tidi

AU - Ong, Thun How

AU - Pang, Sze Lei

AU - Lee, Zi Yang

AU - Gwee, Xiao Wei

AU - Martinus, Christopher

AU - Sio, Yang Yie

AU - Matta, Sri Anusha

AU - Ong, Tan Ching

AU - Tiong, Yuen Seng

AU - Wong, Kang Ning

AU - Narayanan, Sriram

AU - Bijin Au, Veonice

AU - Marlier, Damien

AU - Keir, Holly R.

AU - Tee, Augustine

AU - Abisheganaden, John Arputhan

AU - Koh, Mariko Siyue

AU - Wang, De Yun

AU - Connolly, John E.

AU - Chew, Fook Tim

AU - Chalmers, James D.

AU - Chotirmall, Sanjay H.

N1 - This research is supported by the Singapore Ministry of Health’s National Medical Research Council under its Transition Award (NMRC/TA/0048/2016) (S.H.C) and the Changi General Hospital Research Grant (CHF2016.03-P) (T.B.L). The work performed at NUS was supported by the Singapore Ministry of Education Academic Research Fund, SIgN, and the National Medical Research Council: N-154-000-038-001, R-154-000-404-112, R154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154- 000-A27-597, SIgN-06-006, SIgN-08-020 and NMRC/1150/2008 (F.T.C.). JDC is supported by the GSK/British Lung Foundation Chair of Respiratory Research.

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Rationale: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease and cystic fibrosis however its presence, frequency and clinical significance in non-CF bronchiectasis remain unclear.Objective: To determine the frequency and geographic variability that exists in sensitization pattern to common and specific allergens including house dust mite and fungi and, to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis.Methods: Patients with bronchiectasis were recruited in Asia (Singapore & Malaysia) and the United Kingdom (Scotland) (n=238) forming the Cohort of Asian and Matched European Bronchiectasis (CAMEB) which matched recruited patients on age, gender and bronchiectasis severity. Specific-IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters based on sensitization pattern and airway immune profiles ("immuno-allertypes") were determined.Measurements and main results: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n=149). Sensitization associated with poor clinical outcomes including decreased pulmonary function and more severe disease. 'Sensitized-bronchiectasis' was classified into two 'immuno-allertypes': one fungal-driven and pro-inflammatory versus house dust mite-driven, chemokine-dominant with the former demonstrating poorer clinical outcome.Conclusion: Allergic sensitization occurs at high frequency in bronchiectasis patients recruited from different global centres. Improving endo-phenotyping of 'sensitized-bronchiectasis', a clinically significant state, and 'treatable trait' permits therapeutic intervention in appropriate patients and may allow improved stratification in future bronchiectasis research and clinical trials.

AB - Rationale: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease and cystic fibrosis however its presence, frequency and clinical significance in non-CF bronchiectasis remain unclear.Objective: To determine the frequency and geographic variability that exists in sensitization pattern to common and specific allergens including house dust mite and fungi and, to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis.Methods: Patients with bronchiectasis were recruited in Asia (Singapore & Malaysia) and the United Kingdom (Scotland) (n=238) forming the Cohort of Asian and Matched European Bronchiectasis (CAMEB) which matched recruited patients on age, gender and bronchiectasis severity. Specific-IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters based on sensitization pattern and airway immune profiles ("immuno-allertypes") were determined.Measurements and main results: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n=149). Sensitization associated with poor clinical outcomes including decreased pulmonary function and more severe disease. 'Sensitized-bronchiectasis' was classified into two 'immuno-allertypes': one fungal-driven and pro-inflammatory versus house dust mite-driven, chemokine-dominant with the former demonstrating poorer clinical outcome.Conclusion: Allergic sensitization occurs at high frequency in bronchiectasis patients recruited from different global centres. Improving endo-phenotyping of 'sensitized-bronchiectasis', a clinically significant state, and 'treatable trait' permits therapeutic intervention in appropriate patients and may allow improved stratification in future bronchiectasis research and clinical trials.

KW - Bronchiectasis

KW - Sensitization

KW - Allergy

KW - House dust-mite

KW - Aspergillus

U2 - 10.1164/rccm.201807-1355OC

DO - 10.1164/rccm.201807-1355OC

M3 - Article

C2 - 30265843

SN - 1073-449X

VL - 199

SP - 842

EP - 853

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

IS - 7

ER -

Distinct 'Immuno-Allertypes' of Disease and High Frequencies of Sensitisation in Non-Cystic-Fibrosis Bronchiectasis

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Keywords

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