Immuno-allertypes in non-cystic fibrosis bronchiectasis

Introduction: The role of allergy and sensitization in non-CF bronchiectasis remains unexplored. Methods: Patients with radiologically confirmed and stable bronchiectasis were enrolled from three different countries (N=238): Singapore and Malaysia (N=138) and Dundee, United Kingdom (N=100). Systemic immune and airway inflammatory profiles were determined including 41cytokines and specific IgE titres against common allergens including; house dust mite (HDM) and the fungi Alternaria alternata and Aspergillus fumigatus. Results: High frequencies of sensitization were observed in stable non-CF bronchiectasis that demonstrate geographic variation. Two distinct clinically relevant clusters (coined “immuno-allertypes”) were identified: a “fungal-driven pro-inflammatory” group characterized by sensitization to fungal allergens and a pro-inflammatory cytokine profile and a “HDM -driven chemokine dominant” group characterized by sensitization to house dust mites and enriched for chemotactic mediators and eosinophilic driven airway inflammation. The “fungal-driven” immuno-allertype associates with more severe disease (p ≤ 0.01) and poorer lung function (p ≤ 0.05) compared to the “HDM driven” group. Conclusion: Two distinct and clinically relevant immuno-allertypes of non-CF bronchiectasis were identified representing a potential ‘treatable trait’ for a disease where limited treatment options currently exist Funding: 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).