The Complex Type 2 Endotype in Allergy and Asthma: From Laboratory to Bedside

Abstract

Better management of allergic diseases needs a sharpened understanding of disease heterogeneity and mechanisms in relation to clinically significant outcomes. Phenotypes describing observable clinical and morphologic characteristics and unique responses to treatment have been developed; however, they do not relate to disease mechanisms. Recently, extended heterogeneous and disease-related metabolic, inflammatory, immunological, and remodeling pathways have been described, and reproducible patterns are defined as disease endotypes. An endotype might consist of several intricated mechanisms that cannot be clearly separated into "pure single molecular mechanism" thus being a "complex endotype." The description of an endotype may rely on biomarkers, which can be the signature of a complex underlying pathway or a key molecule associated with or directly playing a role in a particular disease endotype. The Th2 type inflammation can be defined as a complex endotype in asthma and linked to mechanisms of disease development and response to treatment and to disease outcomes such as exacerbations and remodeling. The type 2 complex endotype in allergies and asthma includes innate lymphoid cells, T helper 2 cells, tissue eosinophilia, and IgE production. Currently, emerging endotype-driven strategies in asthma, particularly the development of biologicals that target a single molecular pathway, are being focused for solving individualized clinical problems on disease outcomes. Progress is also being made for endotyping rhinitis, chronic rhinosinusitis, and atopic dermatitis.

NK cells contribute to persistent airway inflammation and AHR during the later stage of RSV infection in mice

“…However, in the past decade, it has become clear that the innate immune cells are critical for the development of asthma and related [33][34][35]. In accordance, we observed that BALF inflammatory cells infiltration, lung tissue damage as well as AHR were significantly increased and persisted at least for 60 days in the RSV-infected nude mice.…”

Endotypes of allergic diseases and asthma: An important step in building blocks for the future of precision medicine

“…1) and heterogeneous, since not all determinants are present in all patients or, in a given patient, at all time points. 6,7 We therefore must embrace the concept of a "complex endotype" consisting of several subendotypes as opposed to an endotype that encompasses a single molecular mechanism. 7 Epigenetics and endotypes of allergy and asthma Epigenetic programming during early life influences is crucial for the development of the endotypes of allergic diseases.…”

European Symposium on Precision Medicine in Allergy and Airways Diseases: Report of the European Union Parliament Symposium (October 14, 2015)

“…• Allergies and CRDs often begin early in life and persist throughout the life cycle, affecting all age groups (12,13).…”

“…o Novel diagnostic tools are emerging, allowing better immunologic and functional endotyping of the patient (13,24). Component-resolved diagnosis (CRD) allows the evaluation of the individual sensitization pattern to environmental allergens (25,26).…”