Partitioning of lung tissue response and inhomogeneous airway constriction at the airway opening

During a bronchial challenge, much of the observed response of lung tissues is an artifactual consequence of inhomogeneous airway constriction. Inhomogeneities, in the sense of time constant inequalities, are an inherently linear phenomenon. Conversely, if lung tissues respond to a bronchoagonist, they become more nonlinear. On the basis of these distinct responses, we present an approach to separate real tissue changes from airway inhomogeneities. We developed a lung model that includes airway inhomogeneities in the form of a continuous distribution of airway resistances and nonlinear viscoelastic tissues. Because time domain data are dominated by nonlinearities, whereas frequency domain data are most sensitive to inhomogeneities, we apply a combined time-frequency domain identification scheme. This model was tested with simulated data from a morphometrically based airway model mimicking gross peripheral airway inhomogeneities and shown capable of recovering all tissue parameters to within 15% error. Application to our previously measured data suggests that in dogs during histamine infusion 1) the distribution of airway resistances increases widely and 2) lung tissues do respond but less so than previously reported. This approach, then, is unique in its ability to differentiate between airway and tissue responses to an agonist from a single broadband measurement made at the airway opening.