Patients with severe asthma are at increased risk for a decreased quality of life, fixed airway obstruction, hospitalization, and death. Biologics may be required to reduce the disease burden. This review discusses the mechanisms, efficacy, and safety of biologics for severe asthma. 

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Biologic Therapies for Severe Asthma

The enigmatic eosinophil has emerged as an exciting component of the immune system, involved in a plethora of homeostatic and inflammatory responses. Substantial progress has been achieved through experimental systems manipulating eosinophils in vivo, initially in mice and more recently in humans. Researchers using eosinophil knockout mice have identified a contributory role for eosinophils in basal and inflammatory processes and protective immunity. Primarily fueled by the purported proinflammatory role of eosinophils in eosinophil-associated diseases, a series of anti-eosinophil therapeutics have emerged as a new class of drugs. These agents, which dramatically deplete eosinophils, provide a valuable opportunity to characterize the consequences of eosinophil knockout humans. Herein, we comparatively describe mouse and human eosinophil knockouts. We put forth the view that human eosinophils negatively contribute to a variety of diseases and, unlike mouse eosinophils, do not yet have an identified role in physiological health; thus, clarifying all roles of eosinophils remains an ongoing pursuit.

/pdf/eosinophil-knockout-humans-uncovering-the-role-of-4dvi8g5mo3.pdf

Eosinophil Knockout Humans: Uncovering the Role of Eosinophils Through Eosinophil-Directed Biological Therapies.

Defining a Severe Asthma Super-Responder: Findings from a Delphi Process.

Last year brought a significant advance in asthma management, unyielding to the pressure of the pandemics. Novel key findings in asthma pathogenesis focus on the resident cell compartment, epigenetics and the innate immune system. The precision immunology unbiased approach was supplemented with novel tools and greatly facilitated by the use of artificial intelligence. Several randomised clinical trials and good quality real-world evidence shed new light on asthma treatment and supported the revision of several asthma guidelines (GINA, Expert Panel Report 3, ERS/ATS guidelines on severe asthma) and the conception of new ones (EAACI Guidelines for the use of biologicals in severe asthma). Integrating asthma management within the broader context of Planetary Health has been put forward. In this review, recently published articles and clinical trials are summarised and discussed with the goal to provide clinicians and researchers with a concise update on asthma research from a translational perspective.

Advances and highlights in asthma in 2021.

Supplement to: Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. Elisabeth Bel;Sally Wenzel;Philip Thompson;Charlene Prazma;Oliver Keene;Steven Yancey;Hector Ortega;Ian Pavord; The New England Journal of Medicine

Supplement to: Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma.

Real-World Effectiveness of Benralizumab in Severe Eosinophilic Asthma.

10. Ricciardolo FLM, Petecchia L, Sorbello V, et al. Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics: the role of NF-kB. Clin Exp Allergy. 2016;46:428-438. 11. Kang JY, Kim JW, Kim JS, et al. Inhibitory effects of anti-immunoglobulin E antibodies on airway remodeling in a murine model of chronic asthma. J Asthma. 2010;47:374-380. SUPPORTING INFORMATION Additional supporting information may be found online in the Supporting Information section.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/all.14693

Brian D. Kent

Papers

Real-World Effectiveness of Benralizumab in Severe Eosinophilic Asthma.

Benralizumab after sub‐optimal response to mepolizumab in severe eosinophilic asthma

The relationship between FeNO and effectiveness of mepolizumab and benralizumab in severe eosinophilic asthma

Real-World Effectiveness of Anti-IL-5/5R Therapy in Severe Atopic Eosinophilic Asthma with Fungal Sensitization.

Adherence to inhaled corticosteroids and clinical outcomes following a year of benralizumab therapy for severe eosinophilic asthma.