Type-2-low severe asthma endotypes for new treatments: the new asthma frontier. Issue 3 (12th June 2023)

• Record Type: Journal Article
• Authors: Chung, Kian Fan
• Is Part Of: Current opinion in allergy and clinical immunology. Volume 23:Issue 3(2023)
• Page Start: 199
• Page End: 204
• Publication Date: 2023-06-12
• Subjects: eosinophil -- neutrophil -- precision medicine -- severe asthma -- type-2 inflammation; Allergy -- Periodicals; Clinical immunology -- Periodicals; Hypersensitivity; Immunity; Immune System Diseases; Allergy and Immunology; 616.079
• DOI: 10.1097/ACI.0000000000000899
• Languages: English
• ISSNs: 1528-4050

Abstract

Abstract : Purpose of review: Type-2 (T2)-high asthma represents a well defined group of severe eosinophilic asthma for which there are now effective biologic therapies targetting the interleukins (ILs) 4, 5 and 13, and Immunoglobulin E. T2-low asthma detected in the clinic by a low blood eosinophil count remains ill-defined and is the focus of this review. Recent findings: By analysing transcriptomic and proteomic expression in sputum samples in U-BIOPRED cohort, both T2-high and -low molecular phenotypes have been described. Using clustering approaches, a neutrophilic-predominant cluster associated with activation markers of neutrophilic and inflammasome activation with interferon and tumour necrosis factor expression, together with a cluster of paucigranulocytic inflammation linked to oxidative phosphorylation and senescence pathways have been described. Using gene set variation analysis, specific molecular phenotypes driven by IL-6 trans-signalling pathway, or those by IL-6, IL-17 and IL-22 pathways were identified linked to a mixed granulocytic or neutrophilic inflammation. Summary: Previous trials of antineutrophilic agents in asthma have failed because enrolled patients were not specifically chosen for these targeted treatments. Although the T2-low molecular pathways should be validated in other cohorts, the availability of targeted therapies indicated for other autoimmune conditions should encourage a trial of these respective biological therapies for these specific molecular phenotypes.