Models of the respiratory system for monitoring or understanding the impact of invasive mechanical ventilation (MV) range from those that only require several equations to model and predict the lung’s mechanical response to a change in pressure, to those that use many hundreds-of-thousands of equations to simulate full air, blood, and gas exchange function in a structure-based model. Both type of model has some disadvantages that limit their application to optimizing treatment in the individual patient. However, both have distinct advantages that can be exploited by their integration. Here we present a modelling framework that exploits the advantages of each ‘level’ of model to understand the interaction between patient and MV device.