Asthma Phenotypes as a Guide for Current and Future Biologic Therapies
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Asthma Phenotypes as a Guide for Current and Future Biologic Therapies Daniel Hamilton 1 & Heather Lehman 2
# Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract Asthma has been increasingly recognized as being a heterogeneous disease with multiple distinct mechanisms and pathophysiologies. Evidence continues to build regarding the existence of different cell types, environmental exposures, pathogens, and other factors that produce a similar set of symptoms known collectively as asthma. This has led to a movement from a “one size fits all” symptom-based methodology to a more patient-centered, individualized approach to asthma treatment targeting the underlying disease process. A significant contributor to this shift to more personalized asthma therapy has been the increasing availability of numerous biologic therapies in recent years, providing the opportunity for more targeted treatments. When targeted biologics began to be developed for treatment of asthma, the hope was that distinct biomarkers would become available, allowing the clinician to determine which biologic therapy was best suited for which patients. Presence of certain biomarkers, like eosinophilia or antigen-specific IgE, is important features of specific asthma phenotypes. Currently available biomarkers can help with decision making about biologics, but are generally too broad and non-specific to clearly identify an asthma phenotype or the single biologic best suited to an asthmatic. Identification of further biomarkers is the subject of intense research. Yet, identifying a patient’s asthma phenotype can help in predicting disease course, response to treatment, and biologic therapies to consider. In this review, major asthma phenotypes are reviewed, and the evidence for the utility of various biologics, both those currently on the market and those in the development process, in each of these phenotypes is explored. Keywords Asthma . Endotypes . Eosinophils . IgE . IL-5 . IL-4 . IL-13 . Thymic stromal lymphopoietin (TSLP)
Introduction Asthma is a heterogeneous disease, with variable symptomatology, pathophysiology, and response to medications. The current paradigm underlying the approach to study of asthma therapeutics, especially biologics, is that asthma should not be considered a single uniform disease, but rather many different disease sub-entities with different etiologies and pathophysiologies. Asthma has been divided into multiple phenotypes, defined as “the visible characteristics of an organism resulting from the interaction between its genetic makeup and the environment” [1]. Subsequently, the term “endotype” was
* Heather Lehman [email protected] 1
SUNY Upstate Medical University College of Medicine, Syracuse, NY, USA
2
Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, 1001 Main Street, Buffalo, NY 14203, USA
coined to delineate distinct subtypes of asthma; an “endotype” specifically is as “a subtype of a condi
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