A clinical and canine experimental study in small-airway response to bronchial thermoplasty: Role of the neuronal effect.

Abstract Background The effects of bronchial thermoplasty (BT) on smooth muscle (SM) and nerves in small airways are unclear. Methods We recruited 15 patients with severe refractory asthma, who received BT treatment. Endobronchial optical-coherence tomography (EB-OCT) was performed at baseline, 3 weeks' follow-up and 2 years' follow-up to evaluate the effect of BT on airway structure. In addition, we divided 12 healthy beagles into a sham group and a BT group, the latter receiving BT on large airways (inner diameter >3 mm) of the lower lobe. The dogs’ lung lobes were resected to evaluate histological and neuronal changes of the treated large airways and untreated small airways 12 weeks after BT. Results Patients receiving BT treatment had significant improvement in Asthma Control Questionnaire (ACQ) scores and significant reduction in asthma exacerbations. EB-OCT results demonstrated a notable increase in inner-airway area (Ai) and decrease in airway wall area percentage (Aw%) in both large (3rd-to 6th-generation) and small (7th-to 9th-generation) airways. Furthermore, the animal study showed a significant reduction in the amount of SM in BT-treated large airways but not in untreated small airways. Protein gene product 9.5 (PGP9.5)–positive nerves and muscarinic receptor 3 (M3 receptor) expression in large and small airways were both markedly decreased throughout the airway wall 12 weeks after BT treatment. Conclusions BT significantly reduced nerves, but not SM, in small airways, which might shed light on the mechanism of lung denervation by BT.