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_H2)-low and T_H2-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_H2-high asthma geared at blocking interleukin (IL)-5, IL-13, immunoglobulin E, prostaglandin D₂, and other pathways. Currently, 3 immune response modifiers approved by the Food and Drug Administration are available for treating severe T_H2-high asthma (1 anti-immunoglobulin E and 2 anti–IL-5 monoclonal antibodies) and other T_H2-high therapies are in various stages of clinical development. Thus far, many of the T_H2-high therapies have shown better efficacy when certain biomarkers are elevated, especially blood eosinophils. The T_H2-low endotype does not have any readily available point-of-care biomarkers, so T_H2-low asthma is often diagnosed based on a lack of T_H2-high biomarkers. These patients tend to have greater resistance to steroids and the development of therapies has lagged behind that for T_H2-high asthma. Conclusion Two major endotypes for asthma have been described, T_H2-high, manifested by increased eosinophils in the sputum and airways of patients, and T_H2-low, with increased neutrophils or a pauci-granulocytic profile. Using these classifications and specific biomarkers has led to promising new therapeutics, especially for T_H2-high asthma.