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

Abstract

Discoveries from basic science research in the last decade have brought significant progress in knowledge of pathophysiologic processes of allergic diseases, with a compelling impact on understanding of the natural history, risk prediction, treatment selection or mechanism-specific prevention strategies. The view of the pathophysiology of allergic diseases developed from a mechanistic approach, with a focus on symptoms and organ function, to the recognition of a complex network of immunological pathways. Several subtypes of inflammation and complex immune-regulatory networks and the reasons for their failure are now described, that open the way for the development of new diagnostic tools and innovative targeted-treatments. An endotype is a subtype of a disease condition, which is defined by a distinct pathophysiological mechanism, whereas a disease phenotype defines any observable characteristic of a disease without any implication of a mechanism. Another key word linked to disease endotyping is biomarker that is measured and evaluated to examine any biological or pathogenic processes, including response to a therapeutic intervention. These three keywords will be discussed more and more in the future with the upcoming efforts to revolutionize patient care in the direction of precision medicine and precision health. The understanding of disease endotypes based on pathophysiological principles and their validation across clinically meaningful outcomes in asthma, allergic rhinitis, chronic rhinosinusitis, atopic dermatitis and food allergy will be crucial for the success of precision medicine as a new approach to patient management.

Subtypes of asthma based on asthma control and severity: a latent class analysis

“…This is also the situation often faced in clinical work, especially in primary care, as well as in large epidemiologic studies. We also did not have the possibility to test the population for biomarkers and form endotypes out of this population, which would be the next step towards investigating whether these subtypes might influence asthma treatment in the future [39]. It is however highly likely, that behind the observed subtypes there are underlying mechanisms, for example inflammation that at least partly would explain the differences in asthma control and severity [39].…”

Study of nasal exhaled nitric oxide levels in diagnosis of allergic rhinitis in subjects with and without asthma

“…The high prevalence of AR in patients with asthma is often referred to as the one airway theory since both are characterized by influx of eosinophils, mast cell degranulation, and upregulation of Th2-related cytokine production from the lymphocytes 8. For this reason, patients with AR with or without asthma frequently are assessed for airway hyperresponsiveness (challenge with reversibility), spirometry for airway obstruction, skin testing for hypersensitivity to allergens, total and specific IgE, and fractional exhaled nitric oxide (FENO) measurement.…”

Relationship of Allergy with Asthma: There Are More Than the Allergy “Eggs” in the Asthma “Basket”

“…It is characterized by a type 2 immune response that involves Th2 cells, B cells, basophils, eosinophils, mast cells, major cytokines secreted from immune cells [interleukin (IL)-4, IL-5, IL-9, and IL-13], and others secreted from epithelial cells (IL-25, IL-31, IL-33, and TSLP) (7). This is the endotype underpinning allergic asthma and is strongly linked to atopy, IgE production, and eosinophilic inflammation (8).…”