4.7 Article

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

Journal

Publisher

AMER THORACIC SOC
DOI: 10.1164/rccm.201807-1355OC

Keywords

bronchiectasis; sensitization; allergy; house dust mite; Aspergillus

Funding

  1. Singapore Ministry of Health's National Medical Research Council [NMRC/TA/0048/2016]
  2. Changi General Hospital Research grant [CHF2016.03-P]
  3. Singapore Ministry of Education Academic Research Fund
  4. SIgN
  5. National Medical Research Council [N-154-000-038-001, R-154-000-404-112, R-154-000-553-112, 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, NMRC/1150/2008]
  6. GSK/British Lung Foundation Chair of Respiratory Research

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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.

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