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Airway hyperresponsiveness is a characteristic feature of asthma and consists of an excessive airway narrowing to bronchoconstrictor stimuli. It is well-recognized that the response of the airways to deep breaths (DBs) is different between asthmatic and normal lungs, but the reason is still not well-understood. In healthy individuals, DBs have a potent ability to prevent more severe bronchoconstrictions. However, this bronchoprotective effect of DBs seems to be absent in asthmatics. We have recently analyzed a wide range of breathing conditions in order to study the synergistic effect of frequency and volume of DBs on bronchoconstriction, and also on the emergence of ventilation defects (VDefs), which are regions with very low ventilation or complete gas trapping. Our results indicated that there is a direct relationship between the frequency and volume of DB and occurrence of VDefs as well as their size and the time of emergence. Surprisingly, when we reviewed the literature, we did not find a well-established understanding of such relationship among experimental study groups who had evaluated the effects of DBs in asthmatics. Our data proved that the time-window between two subsequent DBs is essential, because a DB potentially dilates constricted airways, but the activated smooth muscles slowly re-constrict them as the time progresses. As a result, if the next DB does not occur quickly enough, as some values from the literature suggest, the hypoventilation can take place. Based on these observations, we hypothesized that the synergistic effect of frequency and volume of DBs reaches a plateau at long time-windows between DBs. In other words, if there are no DBs for a significantly long time, even the largest possible volume (i.e. total lung capacity – TLC) cannot prevent the intermediate occurrence of VDefs. The synergistic effect of DB volume and frequency on bronchoconstriction and on the emergence of VDefs reached a plateau when there was a significant delay between subsequent DBs. In such scenario, even the largest volume of DB at TLC could not prevent the emergence of VDefs. We believe our findings can establish a clear basis for understanding the relationship between the volume and frequency of the DBs in airway hyperresponsiveness. The results presented here did not include variability over time. Future studies may evaluate the behavior of the model with different patterns of breathing, including multiple and non-uniform DBs.
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