Computational modeling of the obstructive lung diseases asthma and COPD.
Bottom Line: Computational modeling offers a powerful approach for investigating this relationship between imaging measurements and disease severity, and understanding the effects of different disease subtypes, which is key to developing improved diagnostic methods.Gaining an understanding of a system as complex as the respiratory system is difficult if not impossible via experimental methods alone.We discuss application of modeling techniques to obstructive lung diseases, namely asthma and emphysema and the use of models to predict response to therapy.
Asthma and chronic obstructive pulmonary disease (COPD) are characterized by airway obstruction and airflow imitation and pose a huge burden to society. These obstructive lung diseases impact the lung physiology across multiple biological scales. Environmental stimuli are introduced via inhalation at the organ scale, and consequently impact upon the tissue, cellular and sub-cellular scale by triggering signaling pathways. These changes are propagated upwards to the organ level again and vice versa. In order to understand the pathophysiology behind these diseases we need to integrate and understand changes occurring across these scales and this is the driving force for multiscale computational modeling. There is an urgent need for improved diagnosis and assessment of obstructive lung diseases. Standard clinical measures are based on global function tests which ignore the highly heterogeneous regional changes that are characteristic of obstructive lung disease pathophysiology. Advances in scanning technology such as hyperpolarized gas MRI has led to new regional measurements of ventilation, perfusion and gas diffusion in the lungs, while new image processing techniques allow these measures to be combined with information from structural imaging such as Computed Tomography (CT). However, it is not yet known how to derive clinical measures for obstructive diseases from this wealth of new data. Computational modeling offers a powerful approach for investigating this relationship between imaging measurements and disease severity, and understanding the effects of different disease subtypes, which is key to developing improved diagnostic methods. Gaining an understanding of a system as complex as the respiratory system is difficult if not impossible via experimental methods alone. Computational models offer a complementary method to unravel the structure-function relationships occurring within a multiscale, multiphysics system such as this. Here we review the currentstate-of-the-art in techniques developed for pulmonary image analysis, development of structural models of therespiratory system and predictions of function within these models. We discuss application of modeling techniques to obstructive lung diseases, namely asthma and emphysema and the use of models to predict response to therapy. Finally we introduce a large European project, AirPROM that is developing multiscale models toinvestigate structure-function relationships in asthma and COPD.
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Mentions: The main focus of the modeling within AirPROM is predicting ventilation and the impact of pathophysiological changes on resultant ventilation and lung function. The AirPROM workflow (Figure 3) includes data and models for both the large and small airways. State-of-the-art software (Mimics®, Materialise NV, Belgium; Airways, Institut Telecom, France) is being developed to enable automatic extraction of the morphological properties of central airways and lobes from patient CT data. High-resolution computational meshes of the central airways and lung surface are generated for use in 3D CFD (FRI) simulation studies using the ANSYS software. 1D airway models are generated down to the gas exchange level using the VFB algorithm (see Figure 4). Functional models that predict ventilation and impedance within the 1D networks have been developed. Correlation of model predictions with imaging and measures at the mouth will be used for model validation. At least 70 patient specific models will be analyzed in this pipeline. So far 24 patients within the AirPROM database have been analyzed using FRI, results have shown a good correlation with PFT measurements .