T2-Low Asthma in Women: A Clinically Relevant Distinct Endotype

Abstract Background Type 2 (T2)-low asthma is a heterogeneous endotype associated with neutrophilic or paucigranulocytic airway inflammation, reduced corticosteroid responsiveness, and poorer clinical outcomes. Selected T2-low-associated asthma phenotypes—particularly late-onset disease, obesity-associated asthma, and menopause-associated asthma—are more frequently observed in women, suggesting that sex-specific biological and environmental factors influence disease expression. This review synthesizes the current evidence on the determinants of T2-low asthma in women, with a focus on epidemiology, pathophysiological mechanisms, and therapeutic implications. Methods PubMed, Embase, and Scopus were searched for English-language articles published up to July 2026. Search terms included keywords related to T2-low asthma, sex differences, reproductive factors, obesity, and smoking. Results The reported prevalence of T2-low asthma varies from 14% to 50% with neutrophilic asthma accounting for 20% to 30% of patients. In women, estrogen signaling and hormonal variability across the menstrual cycle and menopause may contribute to T helper 17 (Th17)-skewed neutrophilic inflammation, while obesity and smoking may exacerbate disease severity and reduce corticosteroid sensitivity. Management includes weight reduction, smoking cessation, comorbidity optimization, and selected add-on therapies, including macrolides, long-acting muscarinic antagonists (LAMAs), tezepelumab, and novel therapies such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) in obesity-associated asthma. Conclusions The absence of validated positive biomarkers remains a critical barrier to accurate diagnosis, patient stratification, and targeted therapy development. Important limitations include heterogeneous study populations and predominantly observational data. Improved understanding of sex-specific influences on T2-low asthma may enhance recognition and guide personalized therapeutic strategies, reducing disease burden in this underserved population.