Deep inspiration prior to bronchoconstrictor challenge has beneficial and detrimental effects on lung mechanics in mice

Background: In healthy humans, deep inspiration (DI) prior to bronchoconstrictor challenge attenuates the fall in FEV1, a phenomenon dubbed ‘bronchoprotection’.

Aim: To assess whether the effects of DI prior to bronchoconstrictor challenge are due to: (1) reduced airway narrowing; (2) reduced airway closure; and/or (3) enhanced bronchodilation to DI preceding maximal expiration.

Methods: Anaesthetized and mechanically ventilated mice (BALB/c) received two single-dose methacholine (MCh) challenges (30 mg/mL) that were either preceded by 5 DIs, or by 20 minutes of ventilation without DI. In a separate group of mice, DI was also induced at the peak of constriction after challenge to assess changes in the bronchodilatory response to DI. DI was simulated by mechanical infl ation to a transrespiratory pressure of 30 cmH2O. Airway narrowing and bronchodilation to DI were assessed from changes in airway resistance, and airway closure from the change in tissue elastance, measured by the forced oscillation technique.

Results: MCh challenge produced an increase in airway resistance (i.e. airway narrowing) which was enhanced when challenge was preceded by DI (p < 0.001, n = 8). In contrast, MCh had no effect on tissue elastance after either challenge, suggesting that airway closure did not occur irrespective of the challenge protocol. DI induced after challenge produced immediate bronchodilation which was greater when challenge was preceded by DI (p < 0.05, n = 8).

Conclusions: DI prior to bronchoconstrictor challenge has both beneficial and detrimental effects on lung function in mice. Findings support the possibility that the benefi cial effects of prior DI in healthy humans are related to enhanced bronchodilation to DI preceding maximal expiration.