Diagnosis and Treatment Options for T2-Low Asthma

Type 2 (T2)-low asthma is characterized by the absence of T2-mediated eosinophilic airway inflammation. The diagnosis and prevalence of T2-low asthma are complicated by the absence of specific biomarkers, varied cutoffs of existing biomarkers, and biomarker suppression by corticosteroids. The substantial disease burden of T2-low asthma can be attributed to comorbidities, including obesity. Type 2-low asthma phenotypes include late-onset, aging-related, obesity-related, as well as neutrophilic and paucigranulocytic subtypes. Emerging evidence suggests that T2-low asthma may be more prevalent in mild to moderate asthma compared to severe asthma. Furthermore, the exacerbation phenotype in most patients with severe T2-low asthma may change to T2-high during an exacerbation, whereas the long-term prognosis in T2-low severe asthma remains unclear. Clinical management strategies for T2-low asthma include addressing comorbidities and risk factors, optimizing inhaled or oral corticosteroid dose, and considering other potential add-on therapies, including azithromycin, anti-thymic stromal lymphopoietin therapy, and bronchial thermoplasty. Azithromycin is a promising treatment option, showing potential to induce clinical remission in up to 50% of patients with T2-low uncontrolled asthma, and it demonstrates the therapeutic potential of targeting microbial dysbiosis in T2-low asthma. Future directions include biologics targeting IL-33 pathways, and glucagon-like peptide 1 and gastric inhibitory polypeptide receptor agonists in obesity-related T2-low asthma. Further research is needed to optimize management strategies for T2-low asthma phenotypes.