Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease

• Authors: Merin Kuruvilla, Emory University; Frances Lee, Emory University; Gerald Lee, Emory University
• Journal Title: Clinical Reviews in Allergy and Immunology
• Volume: Volume 56, Number 2
• Publisher: Humana Press | 2019-04-01, Pages 219-233
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1007/s12016-018-8712-1
• Subjects: Health Sciences, Immunology; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Allergy; Immunology; Asthma; Phenotypes; Endotypes; T2 disease; Non-T2 disease; BRONCHIAL EPITHELIAL-CELLS; INNATE LYMPHOID-CELLS; GENE-EXPRESSION; MAST-CELL; AIRWAY INFLAMMATION; CLUSTER-ANALYSIS; EOSINOPHILS; ACTIVATION; BASOPHILS; CYTOKINE

Abstract

The model of asthma as a single entity has now been replaced by a much more complex biological network of distinct and interrelating inflammatory pathways. The term asthma is now considered an umbrella diagnosis for several diseases with distinct mechanistic pathways (endotypes) and variable clinical presentations (phenotypes). The precise definition of these endotypes is central to asthma management due to inherent therapeutic and prognostic implications. This review presents the molecular mechanisms behind the heterogeneity of airway inflammation in asthmatic patients. Asthma endotypes may be broadly regarded as type 2 (T2) high or T2-low. Several biologic agents have been approved for T2-high asthma, with numerous other therapeutics that are incipient and similarly targeted at specific molecular mechanisms. Collectively, these advances have shifted existing paradigms in the approach to asthma to tailor novel therapies.