The mechanism of deep inspiration-induced bronchoprotection: evidence from a mouse model

Abstract

In healthy individuals, deep inspirations (DIs) taken prior to a bronchial challenge reduce the bronchoconstrictor response, which is termed ''bronchoprotection''. The mechanism(s) of DI-induced bronchoprotection is unclear.The forced oscillation technique was used to assess the effect of prior DI on subsequent bronchoconstriction to methacholine (MCh) in BALB/c mice. We assessed likely mechanisms for the bronchoprotective effects of DI including reduced airway narrowing (from changes in airway resistance) and/or closure (changes in tissue elastance) and enhanced bronchodilation to a subsequent DI (% reversal in airway narrowing).DI prior to MCh challenge: 1) did not reduce but instead enhanced airway narrowing (p,0.05); 2) increased ventilation heterogeneity (p,0.05); 3) enhanced the subsequent bronchodilatory response to DI (p,0.05); and 4) reduced tissue elastance (p,0.05), suggesting opening of closed airways or alveoli units.Our findings suggest that DI prior to MCh challenge may elicit a series of changes, some of which are beneficial to respiratory function (enhanced bronchodilation), while others place greater load on the system (enhanced bronchoconstriction and ventilation heterogeneity). It is proposed that the relative magnitudes of these opposing physiological and mechanical effects will determine the net effect on respiratory function in health and disease.

Does smooth muscle in an intact airway undergo length adaptation during a sustained change in transmural pressure?

“…The present lack of evidence for a dominant effect of ASM length adaption in situ is consistent with the failure of simulated DI to induce bronchoprotection in airway segments. The implication of these observations is that bronchoprotective effects of DI in vivo may instead arise from one or more mechanisms other than length adaptation, notably enhanced bronchodilatory effects to DI when bronchoconstriction is assessed by forced expiratory volume in 1 s (FEV 1 ), prevention of airway closure, or both (9,60). With respect to the bronchodilatory effects elicited by DI in airway segments (36,58), our present findings favor mechanisms other than length adaptation, such as crossbridge perturbation (16,17).…”

A Brief History of Airway Smooth Muscle’s Role in Airway Hyperresponsiveness

“…One interpretation of this discrepancy is that prior DI may not alter the initial airway narrowing produced by a constrictor but instead make the ASM more responsive to subsequent strain during the DI required to perform an FEV 1 maneuver. This potential mechanism is supported by a recent study of the effect of DI in mice [83]. …”

Variability in Tidal Volume Affects Lung and Cardiovascular Function Differentially in a Rat Model of Experimental Emphysema

“…In this line, Thammanomai et al ( 2008 ) showed that, in injured mice, variable ventilation, but not conventional ventilation with periods of large breaths, resulted in less lung inflammation. In emphysema, a substantial degree of small airway narrowing can be present (McDonough et al, 2011 ), but deep inspirations, which are present sporadically during VV, have been shown to revert this (Wong et al, 2012 ). In addition, the fact that VV applies subphysiological V T values may have helped limit hyperinflation during mechanical ventilation and promote emptying of lung regions with lower time constants.…”