A simulation study of diffusion-convection interaction and its effect on multiple breath washout indices

Experimental studies of acinar ventilation heterogeneity (S_acin) derived from the multiple breath washout have shown the potential of S_acin to pick up structural change in lung disease. Recent S_acin data suggest that even when intra-acinar structure is unaltered, the combination of convection, diffusion and number of acini fed by patent terminal bronchioles can modify S_acin. We show here how S_acin is affected by structural features such as the secondary alveolar septa, intra-acinar ramification and number of ventilated acini. The simulations also predict relationships between respective alterations in S_acin and washout indices such as lung clearance index (LCI) and alveolar mixing efficiency (AME). This was verified experimentally, with highly significant correlations between S_acin and LCI (r = +0.85;p < 0.001) and between S_acin and AME (r = - 0.92; p < 0.001). We have shown how acinar ventilation heterogeneity can be affected by a reduction of number of ventilated acini, a change in overall alveolization or in intra-acinar alveolization pattern, via their impact on the balance between convection and diffusion at acinar level.