Trait profiles in difficult‐to‐treat asthma: Clinical impact and response to systematic assessment
Tiffany Lin, Jonathan Pham, Eve Denton, Joy Lee, Fiona Hore‐Lacy, Asger Sverrild, Stephanie Stojanovic, Tunn Ren Tay, Kavitha Garuna Murthee, Naghmeh Radhakrishna, Monique Dols, Janet Bondarenko, Janine Mahoney, Robyn E. O’Hehir, Eli Dabscheck, Mark Hew
Abstract
Abstract Background 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. Methods 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, FEV 1 , exacerbation frequency, and maintenance oral corticosteroid (mOCS) dose, at baseline and following systematic assessment. Results Among 241 patients, two airway‐centric profiles were characterized by early‐onset with allergic rhinitis ( n = 46) and adult onset with eosinophilia/chronic rhinosinusitis ( 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 < .001) and AQLQ (3.8 vs. 4.5, p < .001) scores. Following systematic assessment, the cohort showed overall improvements across all outcomes. However, airway‐centric profiles had more FEV 1 improvement (5.6% vs. 2.2% predicted, p < .05) while non‐airway‐centric profiles trended to greater exacerbation reduction (1.7 vs. 1.0, p = .07); mOCS dose reduction was similar (3.1 mg vs. 3.5 mg, p = .782). Conclusion 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.