Different endotypes and phenotypes drive the heterogeneity in severe asthma

Abstract

The identification of sputum eosinophilia indicating corticosteroid responsiveness in subjects with severe asthma heralded the beginning of phenotyping asthmatic subjects based on airways inflammation. Since then, the heterogeneity of severe asthma has been explored and the importance of immunobiology has come sharply into focus with the identification of the key type‐2 cytokine pathways driving eosinophilic inflammation. The development of molecules targeting these type‐2 pathways has transformed severe asthma treatment, but necessitates robust clinical evaluation, biomarker profiling and assessment of comorbid factors to identify subjects most likely to benefit from these therapies. It has also become clear that targeting these pathways does not eradicate asthma symptoms and exacerbation risk; further work is needed to clarify underlying non‐type‐2 mechanisms in severe asthma pathways and possible therapeutic targets. This review addresses progress to date in clinical assessment and management of severe asthma and some of the challenges and unmet needs in severe asthma to achieve the goal of delivering individualized patient care.

Efficacy and safety of treatment with dupilumab for severe asthma: A systematic review of the EAACI guidelines—Recommendations on the use of biologicals in severe asthma

“…IL‐4 and IL‐13 are key cytokines in driving the initiation and chronicity of type 2 (T2) inflammation, an important inflammatory pathway in severe asthma 9‐11 . Dupilumab is a fully human anti‐IL‐4 receptor α (IL‐4Rα) monoclonal antibody that blocks both IL‐4‐ and IL‐13‐mediated signalling pathways.…”

Monoclonal antibodies for the treatment of severe asthma

“…Multiple phenotypes of severe asthma have been described, emphasising the importance of tailoring treatment to individual need . This includes the use of biomarkers of type 2 inflammation such as serum levels of IgE, peripheral eosinophils and fractional exhaled nitric oxide (FeNO) to identify phenotypes most likely to respond to targeted interventions such as monoclonal antibodies …”

Sirtuin 1: Endocan and Sestrin 2 in Different Biological Samples in Patients with Asthma. Does Severity Make the Difference?

“…Inflammation and structural and functional abnormalities within the airways are key features of asthma [1]. Distinct molecular mechanisms and biomarkers in different biological samples have been identified and linked to clinical asthma phenotypes [2]. Although these processes are well-documented, their expressions vary across the heterogeneous spectrum of asthma severity.…”