Airway remodelling rather than cellular infiltration characterises both type2 cytokine biomarker‐high and ‐low severe asthma

Khalfaoui, L. et al. (2022) Airway remodelling rather than cellular infiltration characterises both type2 cytokine biomarker‐high and ‐low severe asthma. Allergy, 77(10), pp. 2974-2986. (doi: 10.1111/all.15376) (PMID:35579040)

Abstract

Background: The most recognizable phenotype of severe asthma comprises people who are blood eosinophil and FeNO-high, driven by type-2 (T2) cytokine biology which responds to targeted biological therapies. However, in many people with severe asthma, these T2 biomarkers are suppressed but poorly controlled asthma persists. The mechanisms driving asthma in the absence of T2 biology are poorly understood. Objectives: To explore airway pathology in T2 biomarker-high and -low severe asthma. Methods: T2 biomarker-high severe asthma (T2-high, n=17) was compared to biomarker-intermediate (T2-intermediate, n=21) and biomarker-low (T2-low, n=20) severe asthma, and healthy controls (n=28). Bronchoscopy samples were processed for immunohistochemistry, and sputum for cytokines, PGD2 and LTE4 measurements. Results: Tissue eosinophil, neutrophil and mast cell counts were similar across severe asthma phenotypes and not increased when compared to healthy controls. In contrast, the remodeling features of airway smooth muscle mass and MUC5AC expression were increased in all asthma groups compared to health, but similar across asthma subgroups. Submucosal glands were increased in T2-intermediate and T2-low asthma. In spite of similar tissue cellular inflammation, sputum IL-4, IL-5, and CCL26 were increased in T2-high versus T2-low asthma, and several further T2-associated cytokines, PGD2 and LTE4, were increased in T2-high and T2-intermediate asthma compared to healthy controls. Conclusions: Eosinophilic tissue inflammation within proximal airways is suppressed in T2 biomarker-high and T2-low severe asthma, but inflammatory and structural cell activation is present, with sputum T2-associated cytokines highest in T2 biomarker-high patients. Airway remodeling persists, and may be important for residual disease expression beyond eosinophilic exacerbations.

• Item Type: Articles
• Additional Information: This paper was supported by an MRC Stratified Medicine Grant MR/M016579/1, and in part by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre (Respiratory). Additional funding was received from Genentech to the University Hospitals of Leicester NHS Trust to support this study. SJF is supported by the NIHR Manchester Biomedical Research Centre.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Chaudhuri, Dr Rekha and Bicknell, Dr Steve
• Authors: Khalfaoui, L., Symon, F. A., Couillard, S., Hargadon, B., Chaudhuri, R., Bicknell, S., Mansur, A. H., Shrimanker, R., Hinks, T. S. C., Pavord, I. D., Fowler, S. J., Brown, V., McGarvey, L. P., Heaney, L. G., Austin, C. D., Howarth, P. H., Arron, J. R., Choy, D. F., and Bradding, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Allergy
• Publisher: Wiley
• ISSN: 0105-4538
• ISSN (Online): 1398-9995
• Published Online: 17 May 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Allergy 77(10): 2974-2986
• Publisher Policy: Reproduced under a Creative Commons License