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

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.

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.

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 <18 years or adult ≥18 years) and characterized in relation to clinical and pathophysiological features.

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 with some physical comorbidities but highest psychophysiologic comorbidities. Adult-onset females also had considerable psychophysiologic comorbidities and 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 sensitization. Despite shortest disease duration, adult-onset males had highest use of maintenance oral corticosteroid, poor lung function, and highest fractional exhaled nitrogen oxide in spite of highest smoking prevalence.

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 dependence associated with smoking in adult-onset male subjects.