Can Less Frequent Deep Breaths Be Protective in Asthma?
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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Can Less Frequent Deep Breaths Be Protective in Asthma?
- 1. Can Less Frequent Deep Breaths Be Protective in Asthma? Amir H. Golnabi, R. Scott Harris, Jose G. Venegas, and Tilo Winkler Pulmonary Imaging and Bioengineering Lab Massachusetts General Hospital, Harvard Medical School Boston, MA Biomedical Engineering Society Annual Meeting Seattle, WA September 25-28, 2013
- 2. Airway constriction in asthma Deep breaths (DBs) and their bronchodilatory effects http://www.webmd.com/asthma/ss/slideshowasthma-overview
- 3. Integrative computational model of bronchoconstriction* * Venegas and Winkler et al, Nature 434: 777–782, 2005.
- 4. Effects of DBs on bronchoconstriction* * Golnabi et al, ATS 2013 Annual International Conference.
- 5. Effects of DBs on bronchoconstriction* * Golnabi et al, ATS 2013 Annual International Conference.
- 6. Synergistic effect of frequency and volume of DBs on bronchoconstriction* Time intervals with one DB and normal tidal breaths in between Average Fc over the last complete DB cycle Relative tidal volume of DBs (VTDB / mean VT) * Golnabi et al, ATS 2013 Annual International Conference.
- 7. Synergistic effect of frequency and volume of DBs on bronchoconstriction* Fc vs. time (800 breaths) * Golnabi et al, ATS 2013 Annual International Conference.
- 8. Synergistic effect of frequency and volume of DBs on bronchoconstriction* Normalized Airway Radius vs. time (last 100 breaths) * Golnabi et al, ATS 2013 Annual International Conference.
- 9. Effect of lower frequency (extended time gap in between) and higher volume of DBs on the emergence of ventilation defects Fc vs. time (800 breaths) Time intervals with one DB and normal tidal breaths in between Average Fc over the last complete DB cycle Relative tidal volume of DBs (VTDB / mean VT) Relative tidal volume of DBs (VTDB / mean VT)
- 10. Effect of lower frequency (extended time gap in between) and higher volume of DBs on the emergence of ventilation defects Time intervals with one DB and normal tidal breaths in between Normalized Airway Radius vs. time (800 breaths) Relative tidal volume of DBs (VTDB / mean VT)
- 11. Thank you!
Editor's Notes
- Excessive broncoconstriction or airway narrowing is a characteristic feature of asthma. As we can see here, in a normal airway, the smooth muscle tone around the airways can constrict them, but such constriction is disproportionate in asthmatics during an asthma attach. It is well known that deep breaths or also known as deep inspirations or sighs have a bronchodilatory effect. Many experimental studies have shown that such effect is variable in asthmatics. However, all these studies have been trying to answer whether DBs are effective in asthmatics in a qualitative matter. And DBs are not well characterized, in terms of their size or volume and their frequency of occurrence.
- In order to study the effects of different size and frequency of DBs on bronchoconstriction, we have recently analyzed a wide range of breathing, using our integrative model of bronchoconstriction. This model published by our lab in 2005, consists of a 12-generation symmetric bronchial tree. The model estimates several parameters for each individual airway over time. These parameters include: airflow, pressure, airway size, tidal expansion, parenchymal forces, and airway smooth muscle behavior.
- Using our model, we studied the synergistic effect of frequency and volume of DBs on bronchoconstriction and emergence of ventilation defects, which are regions with very low ventilation or complete gas trapping. Before looking at the results, I would like to explain a little bit about two types of plots that are going to be used. The first one is the fraction of closed or hypoventilated terminal units, Fc over time. As you can see in this example, no airways are closed at the beginning of the simulation, and as the time goes on, more of them hypoventilated.
- The second plot is the normalized airway radius plot vs. time. In this plot, for visualization purpose, only 256 randomly selected airways are presented. Again, at the beginning, all airways are fully dilated, and as the time progresses some airways hypoventilate, while others are dilated. You can see the effects of deep breaths on the airway size.
- So, we looked at a range of breathing conditions for the size and frequency of DBs. The results are shown in a matrix format, where in the x-direction the size of DBs increases, while in the y-direction the time gap between consecutive DBs increases. We can see a synergistic effect between the volume and frequency of DBs. As the size increases, less frequent DBs can be tolerated without the emergence of ventilation defects.
- If we look at the Fc values versus time, the same synergistic effect can be seen. An interesting observation is the decrease in Fc values, as the volume and frequency of DBs increases.
- In order to understand the effects of DBs on areas with no ventilation defects, we looked at the airway radius plots during the last 100 breaths. There are two interesting observations here: One is the increase in the dynamic equilibrium as the size of DBs increases. The second one is the regional distension of airways as the time gap between DBs increases. So airways dilate to a greater extension, however, since the following DB does not happen quickly enough, the dilatory effect of DB is gone. So the question we asked at this point was: Is there a threshold after which, this synergistic effect is gone? What if we increase both the size and time interval between DBs? Can DBs still be effective in that case?
- And here is the answer: Lower frequency DBs (160 and 320 breaths intervals) ultimately lead to hypoventilation. Intermittent DBs with relative tidal volumes in the range of 3 to 6 temporarily re-opened all terminal units. However, due to a time lag between subsequent DBs, the activated smooth muscles re-constricted airways, and as a result, a portion of the units were closed back again before the next DB.
- We can see the temporary effect of DBs in the radius plots as well: Airways are fully dilated, but since the next DB does not happen quickly enough, the dilatory effect is gone and airways are closed back. So we see here that DBs can fail and their bronchodilatory effect can be gone if the time gap between them are too long. This raises a couple of interesting question for us: In the literature, there is not a good measure of the volume and frequency of DBs in normal and asthmatics. In experimental studies, people have considered different breathing conditions and our results show a systematic effect between the size and frequency of DBs, that can reach a plateau at lower frequencies. Are we missing anything in our model? What about different breathing patterns of with multiple and non-uniform DBs? Those are areas that we still need to investigate and understand.