New insights into the pathophysiology and therapeutic targets of asthma and comorbid chronic rhinosinusitis with or without nasal polyposis

Author:

Striz Ilja123ORCID,Golebski Kornel4,Strizova Zuzana5,Loukides Stelios6,Bakakos Petros7,Hanania Nicola A.8,Jesenak Milos91011,Diamant Zuzana12131415ORCID

Affiliation:

1. 1Department of Clinical and Transplant Immunology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

2. 2Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University, Prague, Czech Republic

3. 3Subdivision of Allergology and Clinical Immunology, Institute for Postgraduate Education in Medicine, Prague, Czech Republic

4. 4Department of Pulmonary Medicine, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands

5. 5Institute of Immunology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic

6. 6Department of Respiratory Medicine, National and Kapodistrian University of Athens, Athens, Greece

7. 7First Respiratory Medicine Department, National and Kapodistrian University of Athens, Athens, Greece

8. 8Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USA

9. 9Department of Pulmonology and Phthisiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, University Hospital in Martin, Slovakia

10. 10Department of Pediatrics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, University Hospital in Martin, Slovakia

11. 11Department of Clinical Immunology and Allergology, University Hospital in Martin, Slovakia

12. 12Department of Microbiology Immunology and Transplantation, KU Leuven, Catholic University of Leuven, Belgium

13. 13Department of Respiratory Medicine and Allergology, Institute for Clinical Science, Skane University Hospital, Lund University, Lund, Sweden

14. 14Department of Respiratory Medicine, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic

15. 15Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

Abstract

Abstract Asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) or without (CRSsNP) are chronic respiratory diseases. These two disorders often co-exist based on common anatomical, immunological, histopathological, and pathophysiological basis. Usually, asthma with comorbid CRSwNP is driven by type 2 (T2) inflammation which predisposes to more severe, often intractable, disease. In the past two decades, innovative technologies and detection techniques in combination with newly introduced targeted therapies helped shape our understanding of the immunological pathways underlying inflammatory airway diseases and to further identify several distinct clinical and inflammatory subsets to enhance the development of more effective personalized treatments. Presently, a number of targeted biologics has shown clinical efficacy in patients with refractory T2 airway inflammation, including anti-IgE (omalizumab), anti-IL-5 (mepolizumab, reslizumab)/anti-IL5R (benralizumab), anti-IL-4R-α (anti-IL-4/IL-13, dupilumab), and anti-TSLP (tezepelumab). In non-type-2 endotypes, no targeted biologics have consistently shown clinical efficacy so far. Presently, multiple therapeutical targets are being explored including cytokines, membrane molecules and intracellular signalling pathways to further expand current treatment options for severe asthma with and without comorbid CRSwNP. In this review, we discuss existing biologics, those under development and share some views on new horizons.

Publisher

Portland Press Ltd.

Subject

General Medicine

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