Characterization of asthma endotypes: implications for therapy

Objective: To describe the concept of precision medicine in treating severe asthma and the utility of relevant biomarkers. Data Sources: PubMed was searched for published articles on human clinical trials using biologics for T-helper type 2 cell (T(H)2)-low and T(H)2-high asthma. Study Selections: Studies were selected if they were double-masked, randomized, placebo-controlled trials published in peer-reviewed journals and relevant to the topic. Results: Multiple immune response modifiers have been evaluated in T(H)2-high asthma geared at blocking interleukin (IL)-5, IL-13, immunoglobulin E, prostaglandin D-2, and other pathways. Currently, 3 immune response modifiers approved by the Food and Drug Administration are available for treating severe T(H)2-high asthma (1 anti-immunoglobulin E and 2 antieIL-5 monoclonal antibodies) and other T(H)2-high therapies are in various stages of clinical development. Thus far, many of the T(H)2-high therapies have shown better efficacy when certain biomarkers are elevated, especially blood eosinophils. The T(H)2-low endotype does not have any readily available point-of-care biomarkers, so T(H)2-low asthma is often diagnosed based on a lack of T(H)2-high biomarkers. These patients tend to have greater resistance to steroids and the development of therapies has lagged behind that for T(H)2-high asthma. Conclusion: Two major endotypes for asthma have been described, T(H)2-high, manifested by increased eosinophils in the sputum and airways of patients, and T(H)2-low, with increased neutrophils or a pauci-granulocytic profile. Using these classifications and specific biomarkers has led to promising new therapeutics, especially for T(H)2-high asthma. (C) 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.