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In asthma positive phase III slopes result from structural heterogeneity of the bronchial tree.

We have previously identified bronchial generations 5-7 as the locus of maximum contribution to the convective portion of the phase III slope in CT-based lung models of asthma patients. In the present study, we examined how exactly phase III slope is generated locally, by specifically interrogating at individual branch points, the necessary condition for a phase III slope to occur : some degree of convective flow sequencing between any two daughter branches that have a heterogeneity in gas washout concentration between them. Flow sequencing at individual branch points showed a wide range of values, including branch points where flow sequencing was such that phase III slopes were negative locally. Yet, the net effect in the 24 bronchial trees that we studied was that flow sequencing between least and best ventilated units was of the correct sign to generate a positive phase III slope in generations 5-7. By investigating the link of local flow sequencing between any two daughter branches to the corresponding heterogeneity of mechanical lung properties, heterogeneity of compliance was seen to be a major determinant of flow sequencing. In these structures bronchial structures, compliance heterogeneity was essentially brought about by volume asymmetry resulting from terminating pathways within the 3D confines of the lung contours. We conclude that the serial and parallel combination of lung mechanical properties at individual branch points in an asymmetrical branching network generate flow sequencing in mid-range conductive airways, so as to obtain positive at-mouth phase III slopes.