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Review
. 2019 Apr;56(2):219-233.
doi: 10.1007/s12016-018-8712-1.

Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease

Merin E Kuruvilla  1   2 , F Eun-Hyung Lee  1   3 , Gerald B Lee  4   5
Affiliations
Review

Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease

Merin E Kuruvilla et al. Clin Rev Allergy Immunol. 2019 Apr.

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The model of asthma as a single entity has now been replaced by a much more complex biological network of distinct and interrelating inflammatory pathways.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.

Keywords: Asthma; Endotypes; Non-T2 disease; Phenotypes; T2 disease.

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Conflict of interest statement

Conflict of Interest F.E.-H.L. is the founder of MicroBplex, Inc. M.E.K. and G.B.L. have no conflicts of interest.

Figures

Fig. 1
Fig. 1
T2-high inflammatory pathways in asthma. A dysregulated epithelial barrier facilitates translocation of allergens, air pollution, and viruses, leading to release of alarmins such as thymic stromal lymphopoietin (TSLP), IL-25, and IL-33. TSLP primes dendritic cells to induce the differentiation of naïve T cells into Th2 cells. Th2 cells activate B cells via IL-4 to differentiate into plasma cells that generate IgE required for mast cell responses to allergens. The alarmins IL-25 and IL-33 can activate group 2 innate lymphoid cells (ILC2s), mast cells, eosinophils, and basophils. Activated ILC2s, like Th2 cells, produce IL-5 and IL-13. IL-5 promotes eosinophil differentiation and survival. IL-13, IL-4, and inflammatory mediators from mast cells, basophils, and eosinophils have effects on airway hyperresponsiveness, smooth muscle hypertrophy, and airway remodeling. CysLT, cysteinyl leukotrienes; ECP, eosinophil cationic protein; EDN, eosinophil-derived neurotoxin; EPx, eosinophil peroxidase; MBP, major basic protein; PGD2, prostaglandin D2
See this image and copyright information in PMC

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