Distinct "immunoallertypes" of disease and high frequencies of sensitization in non-cystic fibrosis bronchiectasis

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–cystic fibrosis bronchiectasis remain unclear. Objectives: To determine the frequency...

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Main Authors: Mac Aogáin, Micheál, Tiew, Pei Yee, Lim, Albert Yick Hou, Low, Teck Boon, Tan, Gan Liang, Hassan, Tidi, Ong, Thun How, Pang, Sze Lei, Lee, Zi Yang, Gwee, Xiao Wei, Martinus, Christopher, Sio, Yang Yie, Matta, Sri Anusha, Ong, Tan Ching, Tiong, Yuen Seng, Wong, Kang Ning, Narayanan, Sriram, Au, Veonice Bijin, Marlier, Damien, Keir, Holly R., Tee, Augustine, Abisheganaden, John Arputhan, Koh, Mariko Siyue, Wang, De Yun, Connolly, John E., Chew, Fook Tim, Chalmers, James D., Chotirmall, Sanjay Haresh
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2020
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Online Access:https://hdl.handle.net/10356/145453
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Institution: Nanyang Technological University
Language: English
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Summary: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–cystic fibrosis bronchiectasis remain unclear. Objectives: To determine the frequency and geographic variability that exists in a 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 and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, 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 (“immunoallertypes”), 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 was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. “Sensitized bronchiectasis” was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome. Conclusions: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a “treatable trait” permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials.