Advances in Non-Type 2 Asthma in the Severe Cases: from molecular insights to novel treatment strategies

Asthma is a prevalent pulmonary disease that affects nearly 300 million people worldwide and imposes a substantial economic burden. While medication can effectively control symptoms in some patients, severe asthma attacks, driven by airway-inflammation induced by environmental and infectious exposures, continue to be a major cause of asthma-related mortality. Heterogenous phenotypes of asthma include type 2 (T2) and non-T2 asthma. Non-T2 asthma is often observed in patients with severe and/or steroid-resistant asthma. This review will cover the molecular mechanisms, clinical phenotypes, causes and promising treatment of non-T2 severe asthma. Specifically, we will discuss the signaling pathways for non-T2 asthma including the activation of inflammasomes, interferon responses, and IL-17 pathways, and their contributions to the subtypes, progression, and severity of non-T2 asthma. Understanding the molecular mechanisms and genetic determinants underlying non-T2 asthma could form the basis for precision medicine in severe asthma treatment.