Abstract
Deep inspirations (DIs) have a dilatory effect on airway smooth muscle (ASM) that helps to prevent or reduce more severe bronchoconstriction in healthy individuals. However, this bronchodilation appears to fail in some asthmatic patients or under certain conditions, and the reason is unclear. Additionally, quantitative effects of the frequency and magnitude of DIs on bronchodilation are not well understood. In the present study, we used a computational model of bronchoconstriction to study the effects of DI volumes, time intervals between intermittent DIs, relative speed of ASM constriction, and ASM activation on bronchoconstriction and the emergence of ventilation defects (VDefs). Our results showed a synergistic effect between the volume of DIs and the time intervals between them on bronchoconstriction and VDefs. There was a domain of conditions with sufficiently large volumes of DIs and short time intervals between them to prevent VDefs. Among conditions without VDefs, larger volumes of DIs resulted in greater airway dilation. Similarly, the time interval between DIs, during which the activated ASM re-constricts, affected the amplitude of periodic changes in airway radii. Both the relative speed of ASM constriction and ASM activation affected what volume of DIs and what time interval between them could prevent the emergence of VDefs. In conclusion, quantitative characteristics of DIs, such as their volume and time interval between them, affect bronchoconstriction and may contribute to difficulties in asthma. Better understanding of the quantitative aspects of DIs may result in novel or improved therapeutic approaches.
Highlights
Deep inspirations (DIs) can be an effective bronchodilator and protect against bronchoconstriction
We discovered that the computational model demonstrated some intuitive findings that fit with clinical data such as the synergistic nature of increasing volume and frequency of DI’s on reducing ventilation defects (VDefs), but that the model revealed counter-intuitive findings such as the worsening of VDefs with insufficient volume or frequency of DIs and the ability to predict the efficacy of DI’s based on a single parameter derived from the rate of airway smooth muscle contraction
The model predictions were virtually identical because DIs fully dilated the airways., which is consistent with the non-significant difference between experimental data points of that range
Summary
Deep inspirations (DIs) can be an effective bronchodilator and protect against bronchoconstriction. These beneficial effects are reduced or completely absent in patients with asthma, and the reasons for that are still unclear. Unknown are the effects of DIs on the heterogeneity in airway narrowing during bronchoconstriction that causes patchy ventilation defects (VDefs). That model was based on an airway tree network where interactions among the airways of the tree led to the emergence of heterogeneous constriction and VDefs. Such emergent behavior in complex systems is linked to critical points or boundaries between domains with very different behaviors [5]. Complex systems are very sensitive to external stimuli so that
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