Understanding the key issues in the treatment of uncontrolled persistent asthma with type 2 inflammation

William W. Busse; Monica Kraft; Klaus F. Rabe; Yamo Deniz; Paul Rowe; Marcella Ruddy; Mario Castro

doi:10.1183/13993003.03393-2020

Abstract

Asthma is a complex respiratory disease that varies in severity and response to treatment. Several asthma phenotypes with unique clinical and inflammatory characteristics have been identified. Endotypes, based on distinct molecular profiles, help to further understand the heterogeneity within asthma. Type 2 inflammation, involving both the innate (type 2 innate lymphoid cell) and adaptive (T helper type 2 cells) immune systems, underpins the complex pathophysiology of chronic inflammation in asthma, as well as the presence of comorbid disease (such as chronic rhinosinusitis with nasal polyps, allergic rhinitis, and atopic dermatitis). Type 2 inflammation is characterised by upregulation of type 2 cytokines interleukin (IL)-4, IL-5, and IL-13, immunoglobulin E (IgE)-mediated release of immune mediators, and dysfunction of epithelial or epidermal barriers. Targeting these key proximal type 2 cytokines has shown efficacy in recent studies adopting a personalised approach to treatment using targeted biologics. Elevated levels of biomarkers downstream of type 2 cytokines, including fractional exhaled nitric oxide, serum IgE, and blood and sputum eosinophils, have been linked to mechanisms involved in type 2 inflammation, and have the potential to aid diagnosis, and predict and monitor response to treatment. The objective of this review is to summarise the current understanding of the biology of type 2 inflammation in asthma, examine its influence on type 2 inflammatory comorbidities, and discuss how type 2 inflammatory biomarkers can be harnessed to further personalise treatments in the age of biologic medicines.

Footnotes

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Conflict of interest: Dr. Busse reports personal fees from GlaxoSmithKline, personal fees from Novartis, personal fees from Regeneron Pharmaceuticals, Inc., personal fees from Sanofi, during the conduct of the study;.

Conflict of interest: Dr. Kraft reports other from American Lung Association, other from AstraZeneca, other from Chiesi, other from NIH, other from Regeneron Pharmaceuticals, Inc., other from Sanofi, during the conduct of the study; other from Elsevier, outside the submitted work;.

Conflict of interest: Dr. Rabe reports personal fees and other from AstraZeneca, personal fees and other from Boehringer Ingelheim, personal fees and other from Novartis, personal fees and other from Sanofi, personal fees and other from Teva, during the conduct of the study;.

Conflict of interest: Dr. Deniz reports personal fees and other from Regeneron Pharmaceuticals, Inc., during the conduct of the study;.

Conflict of interest: Dr. Rowe reports personal fees and other from Sanofi, during the conduct of the study;.

Conflict of interest: Dr. Ruddy reports personal fees and other from Regeneron Pharmaceuticals, Inc., during the conduct of the study;.

Conflict of interest: Dr. Castro reports other from American Lung Association, personal fees and other from AstraZeneca, personal fees and other from Boehringer Ingelheim, other from Chiesi, other from NIH, other from Novartis, other from PCORI, personal fees and other from Sanofi, other from 4D pharma, other from Aviragen Therapeutics, personal fees and other from Boston Scientific, personal fees and other from Genentech, other from Nuvaira, personal fees and other from Teva, other from Therabron Therapeutics, other from Theravance Biopharma, other from Vectura, other from Vida Pharma, personal fees from Regeneron Pharmaceuticals, Inc., other from Elsevier, during the conduct of the study;.

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