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Review
. 2024 Apr 18;63(4):2301619.
doi: 10.1183/13993003.01619-2023. Print 2024 Apr.

Airway remodelling in asthma and the epithelium: on the edge of a new era

Gilda Varricchi  1   2   3 , Christopher E Brightling  4   3 , Christopher Grainge  5 , Bart N Lambrecht  6 , Pascal Chanez  7
Affiliations
Review

Airway remodelling in asthma and the epithelium: on the edge of a new era

Gilda Varricchi et al. Eur Respir J. .

Abstract

Asthma is a chronic, heterogeneous disease of the airways, often characterised by structural changes known collectively as airway remodelling. In response to environmental insults, including pathogens, allergens and pollutants, the epithelium can initiate remodelling via an inflammatory cascade involving a variety of mediators that have downstream effects on both structural and immune cells. These mediators include the epithelial cytokines thymic stromal lymphopoietin, interleukin (IL)-33 and IL-25, which facilitate airway remodelling through cross-talk between epithelial cells and fibroblasts, and between mast cells and airway smooth muscle cells, as well as through signalling with immune cells such as macrophages. The epithelium can also initiate airway remodelling independently of inflammation in response to the mechanical stress present during bronchoconstriction. Furthermore, genetic and epigenetic alterations to epithelial components are believed to influence remodelling. Here, we review recent advances in our understanding of the roles of the epithelium and epithelial cytokines in driving airway remodelling, facilitated by developments in genetic sequencing and imaging techniques. We also explore how new and existing therapeutics that target the epithelium and epithelial cytokines could modify airway remodelling.

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Conflict of interest statement

Conflict of interest: G. Varricchi has received grants from AstraZeneca. C.E. Brightling has received grants and consultancy fees from 4D Pharma, AstraZeneca, Chiesi, Genentech, GSK, Mologic, Novartis, Regeneron Pharmaceuticals, Roche and Sanofi. C. Grainge has received grants from AstraZeneca and industry-sponsored grants from Boehringer Ingelheim and Cyclopharma. B.N. Lambrecht has received grants from the European Research Council, Ghent University, Research Foundation Flanders and the Flanders Institute of Biotechnology, and has received consulting fees from Argenx, AstraZeneca, GSK and Sanofi. P. Chanez has received consultancy fees from ALK, Almirall, AstraZeneca, Boehringer Ingelheim, Boston Scientific, Centocor, Chiesi, GSK, Johnson & Johnson, MSD, Novartis, Sanofi, SNCF and Teva Pharmaceuticals, has received industry-sponsored grants from ALK, AstraZeneca, Boehringer Ingelheim, Boston Scientific, Centocor, Chiesi, GSK, Novartis, Roche and Teva Pharmaceuticals, and is the president of the scientific committee for Fondation du Souffle.

Figures

FIGURE 1
FIGURE 1
Multiple pathogenic factors trigger structural alterations of a) healthy airways resulting in b) airway remodelling. Epithelial cytokines can play diverse, yet often overlapping, roles in airway remodelling in asthma. ASM: airway smooth muscle; EMT: epithelial-to-mesenchymal transition; IL: interleukin; MMP: matrix metalloproteinase; TGF: transforming growth factor; TSLP: thymic stromal lymphopoietin.
FIGURE 2
FIGURE 2
Epithelial cytokines activate immune cells that drive pathogenic airway remodelling processes in patients with severe asthma. Biologic therapies for severe asthma (approved or recently in development) that target epithelial cytokines and downstream mediators may ameliorate features of airway remodelling. EGFR: epidermal growth factor receptor; IL: interleukin; ILC2: group 2 innate lymphoid cell; R: receptor; RAGE: receptor for advanced glycation end-products; ST2: serum stimulation-2; TSLP: thymic stromal lymphopoietin.
See this image and copyright information in PMC

References

    1. Global Initiative for Asthma (GINA) . Global Strategy for Asthma Management and Prevention. 2022. Available from: http://ginasthma.org/
    1. Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 2012; 18: 716–725. doi:10.1038/nm.2678 - DOI - PubMed
    1. Kuruvilla ME, Lee F, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol 2019; 56: 219–233. doi:10.1007/s12016-018-8712-1 - DOI - PMC - PubMed
    1. Fahy JV. Type 2 inflammation in asthma – present in most, absent in many. Nat Rev Immunol 2015; 15: 57–65. doi:10.1038/nri3786 - DOI - PMC - PubMed
    1. Moore WC, Hastie AT, Li X, et al. . Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis. J Allergy Clin Immunol 2014; 133: 1557–1563. doi:10.1016/j.jaci.2013.10.011 - DOI - PMC - PubMed