Dilatation of the constricted human airway by tidal expansion of lung parenchyma.
BACKGROUND
In the normal lung, breathing and deep inspirations potently antagonize bronchoconstriction, but in the asthmatic lung this salutary effect is substantially attenuated or even reversed. To explain these findings, the prevailing hypothesis focuses on contracting airway smooth muscle and posits a nonlinear dynamic interaction between actomyosin binding and the tethering forces imposed by tidally expanding lung parenchyma.


OBJECTIVE
This hypothesis has never been tested directly in bronchial smooth muscle embedded within intraparenchymal airways. Our objective here is to fill that gap.


METHODS
We designed a novel system to image contracting intraparenchymal human airways situated within near-normal lung architecture and subjected to dynamic parenchymal expansion that simulates breathing.


RESULTS
Reversal of bronchoconstriction depended on the degree to which breathing actually stretched the airway, which in turn depended negatively on severity of constriction and positively on the depth of breathing. Such behavior implies positive feedbacks that engender airway instability.


CONCLUSIONS
These findings help to explain heterogeneity of airflow obstruction as well as why, in people with asthma, deep inspirations are less effective in reversing bronchoconstriction.
Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
Tera L
TL
Lavoie
Ramaswamy
R
Krishnan
Harrison R
HR
Siegel
Essence D
ED
Maston
Jeffrey J
JJ
Fredberg
Julian
J
Solway
Maria L
ML
Dowell
D000109:Acetylcholine; D000328:Adult; D000368:Aged; D001249:Asthma / Q000503:physiopathology / Q000628:therapy; D016084:Bronchoconstriction; D002102:Cadaver; D004106:Dilatation / Q000379:methods*; D005260:Female; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012119:Respiration; D013990:Tidal Volume; D014665:Vasodilator Agents
D014665:Vasodilator Agents; D000109:Acetylcholine