Critical roles of airway smooth muscle in mediating deep-inspiration-induced bronchodilation: a big stretch?

Abstract

Background: Deep inspiration (DI) has been shown to induce bronchodilation and bronchoprotection in bronchochallenged healthy subjects, but not in asthmatics. Strain-induced relaxation of airway smooth muscle (ASM) is considered one of the factors responsible for these effects. Other factors include the release or redistribution of pulmonary surfactant, alteration in mucus plugs, and changes in airway heterogeneity.

Main body: The present review is focused on the DI effect on ASM function, based on recent findings from ex vivo sheep lung experiments showing a large change in airway diameter during a DI. The amount of stretch on the airways, when applied to isolated airway rings in vitro, caused a substantial decrease in ASM contractility that takes many minutes to recover. When challenged with a bronchoconstrictor, the increase in pulmonary resistance in the ex vivo ovine lungs is mostly due to the increase in airway resistance.

Conclusions: Although non-ASM related factors cannot be excluded, the large strain on the airways associated with a DI substantially reduces ASM contractility and thus can account for most of the bronchodilatory and bronchoprotective effects of DI.

Keywords: Airway smooth muscle; Bronchodilation; Bronchoprotection; Ex vivo lung mechanics; Lung volume and airway diameter; Strain-induced airway dilation.

Fig. 1

The fractional change in intralobular airway diameter at different lung volumes corresponding to transpulmonary pressures from 5 to 30 cmH₂O in ex vivo sheep lungs. The airways are grouped into 3 sizes in terms of their diameters, small (< 3 mm), medium (between 3–4 mm), and large (> 4 mm). Reproduced from Dong et al. [24] with permission

Fig. 2

Active force generated by bronchial rings after 3 consecutive stretches at a frequency of 0.25 Hz and strain amplitude of 46% that matched the airway strain observed in intact lungs during a DI. The oscillatory strain was applied just before time zero. *P < 0.05 and **P < 0.01 indicate statistical difference from the maximum isometric force before oscillation (F_max). Reproduced from Dong et al. [24] with permission

Fig. 3

Length relaxation of bronchial rings during an isotonic contraction after 3 cycles of force oscillation (0.25 Hz). The dashed horizontal line represents acetylcholine (ACh)-induced shortening of the ring preparation maintained over time (time control) without interruption by the force oscillation. The oscillation was applied during an isotonic contraction at three different times (5, 15, and 60 min) after the onset of contraction. The solid black symbols represent measurements that are significantly different from the time control with a P value < 0.01, and the gray symbols represent measurements that are significantly different from the time control with a P value < 0.05. The open symbols indicate no difference from time control. Reproduced from Dong et al. [24] with permission

Fig. 4

A hypothetical airway-centric view of how a DI, taken after or before bronchochallenge, leads to bronchodilation (A) and bronchoprotection (B), respectively