Sex differences in difficult asthma; findings in the WATCH cohort

Background: Difficult asthma is comprised of many phenotypes, but how sex influences such patterns of disease remains unclear. Aims: To assess how the nature of difficult asthma seen in clinical practice differs between males and females. Methods: We studied patients enrolled (n=380) from a tertiary difficult asthma clinic (Southampton, UK) into a longitudinal Wessex AsThma CoHort (WATCH) assessing comparisons of core features stratified by sex. Results: Two thirds of subjects were female. Male participants were significantly older (median age 59.5 years v 48; p<0.001), and were also older at diagnosis, (median age of 31.0 years v 15; p<0.001). Males were less likely to have a smoking history (p=0.003), more likely to have a history of non-CF bronchiectasis (p=0.003), and demonstrated a higher peripheral eosinophil count (p=0.018). Females were more likely to be salicylate sensitive (33.5% v 13.3%, p<0.001), and had higher obesity prevalence (52.3% v 36.8%, p=0.017). Females had poorer asthma control assessed by ACQ6 (p=0.010) and were more likely to have depression (42% v 27%; p=0.006), anxiety (36 % v 25%; p=0.039), dysfunctional breathing (60% v 42%; p=0.001) and vocal cord dysfunction (20% v 10%; p=0.023). FeNO, atopy, total IgE and fungal sensitisation did not differ by sex. Males demonstrated a greater reduction in FEV1 (p=0.029). Post bronchodilator spirometry was obstructive in males (post BD FEV1/FVC 62.05) but not females (post BD FEV1/FVC 70.68) (p<0.001), with greater small airways obstruction (Post BD FEF 25-75%= 41.95% predicted in males v 55.40 in females; p<0.001). Conclusion: Some core characteristics of difficult asthma differ by sex supporting the need for sex-specific stratified treatment approaches