Effects of increasing tidal volume and end-expiratory lung volume on induced bronchoconstriction in healthy humans.

Background: Increasing functional residual capacity (FRC) or tidal volume (V_T) reduces airway resistance and attenuates the response to bronchoconstrictor stimuli in animals and humans. What is unknown is which one of the above mechanisms is more effective in modulating airway caliber and whether their combination yields additive or synergistic effects. To address this question, we investigated the effects of increased FRC and increased V_T in attenuating the bronchoconstriction induced by inhaled methacholine (MCh) in healthy humans.

Methods: Nineteen healthy volunteers were challenged with a single-dose of MCh and forced oscillation was used to measure inspiratory resistance at 5 and 19 Hz (R₅ and R₁₉), their difference (R_5-19), and reactance at 5 Hz (X₅) during spontaneous breathing and during imposed breathing patterns with increased FRC, or V_T, or both. Importantly, in our experimental design we held the product of V_T and breathing frequency (BF), i.e, minute ventilation (V_E) fixed so as to better isolate the effects of changes in V_T alone.

Results: Tripling V_T from baseline FRC significantly attenuated the effects of MCh on R₅, R₁₉, R_5-19 and X₅. Doubling V_T while halving BF had insignificant effects. Increasing FRC by either one or two V_T significantly attenuated the effects of MCh on R_5, R₁₉, R_5-19 and X₅. Increasing both V_T and FRC had additive effects on R₅, R₁₉, R_5-19 and X₅, but the effect of increasing FRC was more consistent than increasing V_T thus suggesting larger bronchodilation. When compared at iso-volume, there were no differences among breathing patterns with the exception of when V_T was three times larger than during spontaneous breathing.

Conclusions: These data show that increasing FRC and V_T can attenuate induced bronchoconstriction in healthy humans by additive effects that are mainly related to an increase of mean operational lung volume. We suggest that static stretching as with increasing FRC is more effective than tidal stretching at constant V_E, possibly through a combination of effects on airway geometry and airway smooth muscle dynamics.