Time course and calcium dependence of sustained bronchoconstriction induced by deep inhalation in asthma

We studied six asthmatic patients who showed a progressive decrease in FEV1 when successive forced expiratory maneuvers were performed at 1-min intervals. We determined the time course of changes in specific airway conductance following a single deep inhalation (DI) and the ratio of maximum expiratory flow at 40% of FVC from maximal and partial flow-volume curves (MEF40M/P) during a series of forced expiratory maneuvers. Specific airway conductance measured 3 s after DI was increased by 11 +/- 6 (SE)%, which was not significantly different from an increase of 23 +/- 8% observed in six healthy control subjects. Later (i.e., 10 to 40 s after DI) specific airway conductance was significantly less than the pre-DI value in asthmatic but not in healthy subjects. Mean FEV1 decreased significantly by 28% from the first to the eighth forced expiratory maneuver performed during a period of 15 min, whereas MEF40M/P was not significantly changed and remained always significantly greater than 1. The voltage-dependent calcium channel antagonist nifedipine significantly prevented the reduction of FEV1 without affecting MEF40M/P. We conclude that, in some asthmatic individuals, DI may induce a transient bronchodilatation followed by a calcium-dependent sustained bronchoconstriction. We suggest that the initial bronchodilatation is due to the mechanical interdependence between airways and lung parenchyma, whereas the sustained bronchoconstriction is due to contraction of the airway smooth muscle.