Trait profiles in difficult-to-treat asthma: clinical impact and response to systematic assessment.

Abstract

Multidisciplinary systematic assessment improves outcomes in difficult-to-treat asthma, but without clear response predictors. Using a treatable-traits framework, we stratified patients by trait profile, examining clinical impact and treatment responsiveness to systematic assessment. We performed latent class analysis using 12 traits on difficult-to-treat asthma patients undergoing systematic assessment at our institution. We examined Asthma Control Questionnaire (ACQ-6) and Asthma Quality of Life Questionnaire (AQLQ) scores, FEV1 , exacerbation frequency, and maintenance oral corticosteroid (mOCS) dose, at baseline and following systematic assessment. Among 241 patients; two airway-centric profiles were characterised by early-onset with allergic rhinitis (n=46) and adult-onset with eosinophilia/chronic rhino-sinusitis (n=60)), respectively, with minimal comorbid or psychosocial traits; three non-airway centric profiles exhibited either comorbid (obesity, vocal cord dysfunction, dysfunctional breathing) dominance (n=51), psychosocial (anxiety, depression, smoking, unemployment) dominance (n=72), or multi-domain impairment (n=12). Compared to airway-centric profiles, non-airway centric profiles had worse baseline ACQ-6 (2.7 vs 2.2, p<0.001) and AQLQ (3.8 vs 4.5, p<0.001) scores. Following systematic assessment, the cohort showed overall improvements across all outcomes. However, airway-centric profiles had more FEV1 improvement (5.6% vs 2.2% predicted, p<0.05) while non-airway centric profiles trended to greater exacerbation reduction (1.7 vs 1.0, p=0.07); mOCS dose reduction was similar (3.1mg vs 3.5mg, p=0.782). Distinct trait profiles in difficult-to-treat asthma are associated with different clinical outcomes and treatment responsiveness to systematic assessment. These findings yield clinical and mechanistic insights into difficult-to-treat asthma, offer a conceptual framework to address disease heterogeneity, and highlight areas responsive to targeted intervention.