New Perspectives on Difficult Asthma; Sex and Age of Asthma-Onset Based Phenotypes.

ABSTRACT Background Asthma is a diverse condition that differs with age and sex. However, it remains unclear how sex, age of asthma-onset, and/or their interaction, influence clinical expression of more problematic adult “difficult” asthma. Objectives To better understand the clinical features of difficult asthma within a real-world clinical setting using novel phenotypic classification, stratifying subjects by sex and age of asthma-onset. Methods Participants in a longitudinal difficult asthma clinical cohort study (Wessex AsThma CoHort of difficult asthma; WATCH), United Kingdom, (n=501) were stratified into 4 difficult asthma phenotypes based on sex and age of asthma-onset (early Results The cohort had more female participants (65%) but had similar proportions of participants with early or adult-onset disease. Early-onset female disease was commonest (35%), highly atopic, with good spirometry and strong associations to some physical comorbidities but highest psychophysiologic comorbidities. Adult-onset females also had considerable psychophysiologic comorbidities, highest obesity, and were least atopic. Amongst male subjects, proportionately more had adult-onset disease. Early-onset male disease was rarest (14%) but associated with worst lung function, high smoking, atopy and fungal sensitisation. Despite shortest disease duration, adult-onset males had highest use of maintenance oral corticosteroid, poor lung function and highest FeNO in spite of highest smoking prevalence. Conclusion This study shows that sex, age of asthma-onset, and their interactions influence different clinical manifestations of difficult asthma and identifies a greater risk for lung function loss and oral corticosteroid dependency associated with smoking in adult-onset male subjects.