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J Appl Physiol (October 16, 2008). doi:10.1152/japplphysiol.90576.2008
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Submitted on April 27, 2008
Revised on October 7, 2008
Accepted on October 8, 2008

Assessment of heterogeneous airway constriction in dogs: A structure-function analysis

David W. Kaczka1*, Robert H. Brown2, and Wayne Mitzner3

1 The Johns Hopkins University
2 John Hopkins University
3 Johns Hopkins University

* To whom correspondence should be addressed. E-mail: dkaczka1{at}jhmi.edu.

Obstructive lung diseases are often characterized by heterogeneous patterns of bronchoconstriction, although specific relationships between structural heterogeneity and lung function have yet to be established. We measured respiratory input impedance (Zrs) in eight anesthetized dogs using broadband forced oscillations at baseline and during intravenous methacholine (MCh) infusion. We also obtained high resolution computed tomographic (HRCT) scans in four of the dogs and identified 20-30 individual airway segments in each animal. The Zrs spectra and HRCT images were obtained before and five minutes following a deep inspiration (DI) to 35 cm H2O. Each Zrs spectrum was fitted with two different models of the respiratory system: 1) a lumped airways model consisting of a single airway compartment, and 2) a distributed airways model incorporating a continuous distribution of airway resistances. For the latter, we found that the mean level and spread of airway resistances increased with MCh dose. While a DI had no effect on average airway resistance during MCh infusion, it did increase the level of airway heterogeneity. At baseline and low-to-moderate doses of MCh, the lumped airways model was statistically more appropriate to describe Zrs, while the distributed airways model was superior at the highest doses of MCh. There was a significant correlation between heterogeneity assessed with inverse modeling and the standard deviation of airway diameters obtained from HRCT. These data demonstrate that increases in airway heterogeneity as assessed with forced oscillations and inverse modeling can be linked to specific structural alterations in airway diameters.







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