Dynamic changes in airway caliber after bronchodilation
In Study 2, compared with baseline levels, salbutamol inhalation led to a significant improvement not only in FEV1, FVC and FEV1/FVC, but also the small-airway spirometric parameters such as MMEF in 32 patients with moderate-to-severe asthma (all P <0.05, Table E6) . Both the Ai/BSA in medium-sized (the 3rd-6thgeneration) and small airways (the 7th-9th generation) increased substantially after salbutamol inhalation in 30 (93.8%) patients (Figure 3 and Figure 4 ). The Ai/BSA3-6 progressively increased by 14.3%, 20.1%, and 22.0% at 5 min, 10 min and 15 min post-bronchodilation compared with baseline (Figure 5 ). Meanwhile, Ai/BSA7-9 increased by 11.0%, 22.0% and 38.0% at 5 min, 10 min and 15 min post-bronchodilation compared with baseline. The Aw% of medium-sized and small airways did not change significantly at 15 min after bronchodilation. The EB-OCT assessement of dynamic changes in the medium-sized and small airways caliber within 15 min after salbutamol inhalation was shown in Video 1 .
The improvement of spirometric parameters and the airway structure in moderate asthma did not differ significantly from those of severe asthma (all P> 0.05, Table E6 and Table E7 ). Importantly, the magnitude of increase in Ai/BSA3-6, but not Ai/BSA7-9, Aw%3-6 or Aw%7-9, correlated positively with the improvement in FEV1 (r=0.636, P =0.001), FVC (r=0.506, P =0.003) and MMEF (r=0.391, P =0.027) at 15 min after salbutamol inhalation (Table 2 ).