Document resource
Introduction Bronchial Thermoplasty (BT) is an available therapy for severe asthma. However, we are unable to stratify a priori clinical responders limiting its widespread adoption.Aim To establish BT’s clinical benefit and identify responder attributes to enable clinical decision-making.Methods We pooled pre/post-BT patient biopsies from 8 sites (119 patients) that were analysed for airway smooth muscle (ASM) mass, reticular basement membrane, and epithelial integrity to assess the impact on airway remodelling: biological response. Clinical response was assessed via exacerbation and hospitalisation frequency, asthma control questionnaire scores (ACT, ACQ) and asthma quality of life questionnaire score (AQLQ). To stratify patient response, we used the virtual patient 1 to create patient-specific digital avatars, simulated BT, and compared predictions vs clinical data.Results Patients showed significant reductions in ASM mass (mean±SD) 15.1±6.8% to 6.7±4.1%, basement membrane 6.4±2.5µm to 5.5±2.1µm, and improvement in epithelial integrity 30.7±19.1% to 39.9±16.9% (p<0.05 all). Annual asthma exacerbation rate decreased: 5.8±5.3 to 1.2±1.7 (p<0.001). Asthma-related hospital admissions decreased: 1.5±2.5 to 0.3±0.7 (p<0.001). ACT improved from 7.7±2.9 to 15.2±6.2, ACQ from 3.0±1.3 to 2.4±1.3, and AQLQ from 3.2±1.6 to 4.4±1.7 (p<0.05 all). The virtual patient predicted impact on airway remodelling with 90% and clinical response with 70% accuracy.Conclusions Bronchial Thermoplasty showed excellent biological and clinical response. Our computer model supports the view that BT benefits are largely an indirect vs direct result of heat-driven cell death. The model helped identify the patient profile most likely to benefit from Bronchial Thermoplasty.Reference Saunders, et al. Science Transl Med. 2019;11:eaao6451.