Increased heterogeneity of the lung disturbs pulmonary gas exchange. During bronchoconstriction, inflammation of lung parenchyma or acute respiratory distress syndrome, inhomogeneous lung ventilation can become bimodal and increase the risk of ventilator-induced lung injury during mechanical ventilation. A simple index sensitive to ventilation heterogeneity would be very useful in clinical practice. In the case of bimodal ventilation, the index (H) can be defined as the ratio between the longer and shorter time constant characterising regions of contrary mechanical properties. These time constants can be derived from the Otis model fitted to input impedance (Z in ) measured using forced oscillations. In this paper we systematically investigated properties of the aforementioned approach. The research included both numerical simulations and real experiments with a dual-lung simulator. Firstly, a computational model mimicking the physical simulator was derived and then used as a forward model to generate synthetic flow and pressure signals. These data were used to calculate the input impedance and then the Otis inverse model was fitted to Z in by means of the Levenberg–Marquardt (LM) algorithm. Finally, the obtained estimates of model parameters were used to compute H. The analysis of the above procedure was performed in the frame of Monte Carlo simulations. For each selected value of H, forward simulations with randomly chosen lung parameters were repeated 1000 times. Resulting signals were superimposed by additive Gaussian noise. The estimated values of H properly indicated the increasing level of simulated inhomogeneity, however with underestimation and variation increasing with H. The main factor responsible for the growing estimation bias was the fixed starting vector required by the LM algorithm. Introduction of a correction formula perfectly reduced this systematic error. The experimental results with the dual-lung simulator confirmed potential of the proposed procedure to properly deduce the lung heterogeneity level. We conclude that the heterogeneity index H can be used to assess bimodal ventilation imbalances in cases when this phenomenon dominates lung properties, however future analyses, including the impact of lung tissue viscoelasticity and distributed airway or tissue inhomogeneity on H estimates, as well as studies in the time domain, are advisable. 
Analysis of the method for ventilation heterogeneity assessment using the Otis model and forced oscillations