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In this article, we have described a computational framework for multiscale simulation of gas flow in subject-specific airway models of the human lung. The framework consists of five major components: accurate extraction of airway geometry from MDCT image data sets, geometrical modeling of airway trees, novel 3-D and 1-D coupled mesh generation, 3-D high-fidelity CFD techniques for turbulent and transitional flow, and CT-derived subject-specific physiological boundary conditions. This work demonstrates the importance of multi-scale simulation of pulmonary gas flow for accurate prediction of flow characteristics at large and small airways and their interactions. The multiscale simulation presented here can be further applied to other healthy and diseased human subjects for intra- and intersubject analyses to better understand the lung flow-structure relationship, the progression of lung diseases, and the correlation between inhaled pharmaceutical drug aerosols or air pollutants with airway structure.