Mechanisms and therapeutic strategies for non-T2 asthma

Non-T2 asthma is traditionally defined as asthma without features of T2 asthma. The definition is arbitrary and is generally based on the presence of neutrophils in sputum, or the absence (or normal levels) of eosinophils or other T2 markers in sputum (paucigranulocytic), airway biopsies or in blood. This definition may be imprecise as we gain more knowledge from applying transcriptomics and proteomics to blood and airway samples. The prevalence of non-T2 asthma is also difficult to estimate as most studies are cross-sectional and influenced by concomitant treatment with glucocorticosteroids, and by the presence of recognized or unrecognized airway infections. No specific therapies have shown any clinical benefits in patients with asthma that is associated with a non-T2 inflammatory process. It remains to be seen if such an endotype truly exists and to identify treatments to target that endotype. Meanwhile, identifying intense airway neutrophilia as an indicator of airway infection and airway hyperresponsiveness as an indicator of smooth muscle dysfunction, and treating them appropriately, and not increasing glucocorticosteroids in patients who do not have obvious T2 inflammation, seem reasonable.