Larry Borish1. 1. Asthma and Allergic Disease Center, Carter Immunology Center, Departments of Medicine and Microbiology, University of Virginia Health System, Charlottesville, Virginia. Electronic address: lb4m@virginia.edu.
Abstract
OBJECTIVES: To review current thinking regarding the role of personalized phenotype-driven as opposed to broad guideline-based therapies in asthma and to speculate on the relative contributions of innate (lung) and adaptive (T and B lymphocyte) roles in asthma pathogenesis. DATA SOURCES: PubMed literature review. STUDY SELECTIONS: Articles pertaining to asthma pathogenesis, with emphasis on those that included biotherapeutic interventions. RESULTS: Current methods allow asthma to be divided into phenotypes characterized by the presence or absence of eosinophilic inflammation. Corticosteroids are likely to be only effective in the context of eosinophilic inflammation. Similarly, interventions with biotherapeutic agents currently available or in development have efficacious only when administered to patients with asthma of relevant phenotypes. CONCLUSION: The availability of biotherapeutic agents that target IgE, interleukin (IL) 5, and, in the near future, IL-13 is an exciting vindication of molecular medicine. However, these biotherapeutic agents are only effective when targeted to patients with specific asthma phenotypes. In Promising biotherapeutic targets are the airway epithelial-derived cytokines IL-25, IL-33, and thymic stromal lymphopoietin. Targeting these lung epithelial-derived mediators, instead of products of the adaptive immune system, may be more likely to improve day-to-day asthma symptoms in contrast to agents that target the adaptive immune system, approaches that primarily act to ameliorate asthma exacerbations.
OBJECTIVES: To review current thinking regarding the role of personalized phenotype-driven as opposed to broad guideline-based therapies in asthma and to speculate on the relative contributions of innate (lung) and adaptive (T and B lymphocyte) roles in asthma pathogenesis. DATA SOURCES: PubMed literature review. STUDY SELECTIONS: Articles pertaining to asthma pathogenesis, with emphasis on those that included biotherapeutic interventions. RESULTS: Current methods allow asthma to be divided into phenotypes characterized by the presence or absence of eosinophilic inflammation. Corticosteroids are likely to be only effective in the context of eosinophilic inflammation. Similarly, interventions with biotherapeutic agents currently available or in development have efficacious only when administered to patients with asthma of relevant phenotypes. CONCLUSION: The availability of biotherapeutic agents that target IgE, interleukin (IL) 5, and, in the near future, IL-13 is an exciting vindication of molecular medicine. However, these biotherapeutic agents are only effective when targeted to patients with specific asthma phenotypes. In Promising biotherapeutic targets are the airway epithelial-derived cytokines IL-25, IL-33, and thymic stromal lymphopoietin. Targeting these lung epithelial-derived mediators, instead of products of the adaptive immune system, may be more likely to improve day-to-day asthma symptoms in contrast to agents that target the adaptive immune system, approaches that primarily act to ameliorate asthma exacerbations.
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