Merritt L Fajt1, Sally E Wenzel. 1. Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh Asthma Institute at UPMC/University of Pittsburgh School of Medicine.
Abstract
OBJECTIVE: Asthma is a common chronic disease with various phenotypes and therapeutic responses. Unlike other diseases, current anti-inflammatory treatment with corticosteroids does not include any reference to biological measures which may vary among different asthma phenotypes. Morbidity from uncontrolled asthma suggests a need for specific targeted treatment approaches such as biologic medications. In half of asthmatics, chronic airway inflammation may be driven by T helper (Th)-2 cells, which release pro-inflammatory cytokines, such as interleukin (IL)-4, IL-5 and IL-13, contributing to eosinophil inflammation and IgE production. Earlier studies of cytokine-targeted biologic therapy on non-phenotyped asthma patients were generally not clinically effective. METHODS: Literature published from 1958-2013 was identified through PubMed using the search terms which included asthma and therapy. A total of 32 studies were reviewed covering both pediatric and adult asthmatics and included double-blind randomized placebo-controlled trials testing efficacy of biologic agents to treat asthma. RESULTS: More recent approaches to personalized medicine with expression profiling studies, genetic analysis and clinical biomarkers of Th2 inflammation have allowed identification of asthma phenotypes including a Th2 "high" phenotype. Studies targeting IgE, IL-5, IL-13 and the IL4 receptor alpha chain have shown some efficacy in phenotyped patients. For those without evidence of Th2 inflammation, no specific therapies have been identified. CONCLUSIONS: In recent years, the identification of Type-2 cytokine "high" asthma in numerous studies has predicted the clinical response to the Th2 associated therapies. It is not yet clear whether all Type 2 high asthma will respond similarly to IL-4, 5 and 13 approaches.
OBJECTIVE:Asthma is a common chronic disease with various phenotypes and therapeutic responses. Unlike other diseases, current anti-inflammatory treatment with corticosteroids does not include any reference to biological measures which may vary among different asthma phenotypes. Morbidity from uncontrolled asthma suggests a need for specific targeted treatment approaches such as biologic medications. In half of asthmatics, chronic airway inflammation may be driven by T helper (Th)-2 cells, which release pro-inflammatory cytokines, such as interleukin (IL)-4, IL-5 and IL-13, contributing to eosinophil inflammation and IgE production. Earlier studies of cytokine-targeted biologic therapy on non-phenotyped asthmapatients were generally not clinically effective. METHODS: Literature published from 1958-2013 was identified through PubMed using the search terms which included asthma and therapy. A total of 32 studies were reviewed covering both pediatric and adult asthmatics and included double-blind randomized placebo-controlled trials testing efficacy of biologic agents to treat asthma. RESULTS: More recent approaches to personalized medicine with expression profiling studies, genetic analysis and clinical biomarkers of Th2inflammation have allowed identification of asthma phenotypes including a Th2 "high" phenotype. Studies targeting IgE, IL-5, IL-13 and the IL4 receptor alpha chain have shown some efficacy in phenotyped patients. For those without evidence of Th2inflammation, no specific therapies have been identified. CONCLUSIONS: In recent years, the identification of Type-2 cytokine "high" asthma in numerous studies has predicted the clinical response to the Th2 associated therapies. It is not yet clear whether all Type 2 high asthma will respond similarly to IL-4, 5 and 13 approaches.