Distinct "Immunoallertypes" of Disease and High Frequencies of Sensitization in Non-Cystic Fibrosis Bronchiectasis

Mac Aogáin M 1 , Tiew PY 1 , Lim AYH 2 , Low TB 3 , Tan GL 4 , Hassan T 5 Show all authors , Ong TH 4 , Pang SL 6 , Lee ZY 6 , Gwee XW 6 , Martinus C 6 , Sio YY 6 , Matta SA 6 , Ong TC 6 , Tiong YS 6 , Wong KN 6 , Narayanan S 7 , Au VB 7 , Marlier D 7 , Keir HR 8 , Tee A 3 , Abisheganaden JA 2 , Koh MS 4 , Wang Y 9 , Connolly JE 7 , Chew FT 6 , Chalmers JD 8 , Chotirmall SH 1

Affiliations 

  • 1 1 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
  • 2 3 Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore
  • 3 4 Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore
  • 4 2 Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore
  • 5 5 Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
  • 6 6 Department of Biological Sciences, National University of Singapore, Singapore
  • 7 8 Institute of Molecular and Cell Biology, A*STAR, Singapore
  • 8 9 University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland; and
  • 9 10 Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Am J Respir Crit Care Med, 2019 04 01;199(7):842-853.
PMID: 30265843 DOI: 10.1164/rccm.201807-1355OC

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-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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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