can less frequent deep breaths be protective in asthma?
DESCRIPTION
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.TRANSCRIPT
Can Less Frequent Deep Can Less Frequent Deep Breaths Be Protective in Breaths Be Protective in
Asthma?Asthma?
Amir H. Golnabi, R. Scott Harris, Jose G. Venegas,
and Tilo WinklerPulmonary Imaging and Bioengineering Lab
Massachusetts General Hospital, Harvard Medical School
Boston, MABiomedical Engineering Society Annual Meeting
Seattle, WASeptember 25-28, 2013
Airway constriction in asthma
http://www.webmd.com/asthma/ss/slideshowasthma-overview
Deep breaths (DBs) and their bronchodilatory effects
* Venegas and Winkler et al, Nature 434: 777–782, 2005.
Integrative computational model of bronchoconstriction*
Effects of DBs on bronchoconstriction*
* Golnabi et al, ATS 2013 Annual International Conference.
Effects of DBs on bronchoconstriction*
* Golnabi et al, ATS 2013 Annual International Conference.
Synergistic effect of frequency and volume of DBs on bronchoconstriction*
Tim
e in
terv
als
with
one
DB
and
no
rma
l tid
al b
rea
ths
in b
etw
een
Relative tidal volume of DBs (VTDB / mean VT)
Average Fc over the last complete DB cycle
* Golnabi et al, ATS 2013 Annual International Conference.
Synergistic effect of frequency and volume of DBs on bronchoconstriction*
Fc vs. time (800 breaths)
* Golnabi et al, ATS 2013 Annual International Conference.
* Golnabi et al, ATS 2013 Annual International Conference.
Synergistic effect of frequency and volume of DBs on bronchoconstriction*
Normalized Airway Radius vs. time (last 100
breaths)
Effect of lower frequency (extended time gap in between) and higher volume of DBs on the emergence of ventilation defects
Relative tidal volume of DBs (VTDB / mean VT)
Tim
e in
terv
als
with
one
D
B a
nd n
orm
al ti
dal
brea
ths
in b
etw
een
Relative tidal volume of DBs (VTDB / mean VT)
Fc vs. time (800 breaths)Average Fc over the last complete DB cycle
Effect of lower frequency (extended time gap in between) and higher volume of DBs on the emergence of ventilation defects
Relative tidal volume of DBs (VTDB / mean VT)
Tim
e in
terv
als
with
one
DB
and
no
rmal
tid
al b
reat
hs in
bet
wee
n Normalized Airway Radius vs. time (800
breaths)
Thank you!Thank you!