Abstract The bronchial tree plays a main role in the human respiratory system because the air distribution throughout the lungs and gas exchange with blood occur in the airways whose dimensions vary from several centimeters to micrometers. Organization of about 60,000 conducting airways and 33 million respiratory airways in a limited space results in a complex structure. Due to this inherent complexity and a high number of airways, using target-oriented dimensional reduction is inevitable. In addition, there is no general reduced-order model for various types of problems. This necessitates coming up with an appropriate model from a variety of different reduced-order models to solve the desired problem. Lumped formulation, trumpet, or typical path model of whole or parts of bronchial tree are frequently used reduced-order models. On the other hand, using any of these models results in underestimation of flow heterogeneity leading to inaccurate prediction of the systems whose mechanisms depend on the fluid heterogeneity. In this study, a simple robust model combining mechanistic and non-mechanistic modeling approaches of the bronchial tree is proposed which overcomes the limitations of the previous reduced-order models and gives the same results of a detailed mechanistic model for the first time. This model starts from an accurate multi-branching model of conducting and respiratory airways (i.e., the base model) and suggests a proxy model of conducting airway and reduced-order model of respiratory airways based on the base model to significantly reduce computational cost while retaining the accuracy. The combination of these models suggests various reduced-order surrogate models of the human bronchial tree for different problems. The applications and limitations of each reduced-order model are also discussed. The accuracy of the proposed model in the prediction of fluid heterogeneity has been examined by the simulation of multi-breath inert gas washout because the alveolar slope is the reflection of fluid heterogeneity where the computational time decreases from 121 h (using the base model) to 4.8 s (using the reduced-order model). A parallel strategy for solving the equations is also proposed which decreases run time by 0.18 s making the model suitable for real-time applications. Furthermore, the ability of the model has been evaluated in the modeling of asthmatic lung as an instance of abnormal lungs, and in the modeling of O2–CO2 exchange as an instance of nonlinear reacting systems. The results indicate that the proposed model outperforms previous models based on accuracy, robustness, and run time.Graphic abstract
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