Thicker Is Better: How Surfactant Viscosity Governs Uniform Surfactant Lung Delivery

Abstract

Surfactant Replacement Therapy (SRT) is a well-established intervention for Neonatal Respiratory Distress Syndrome, yet its translation to adults with Acute Respiratory Distress Syndrome (ARDS) has yielded inconsistent results in clinical trials. Using a three-dimensional, zero-dimensional biomechanical model of surfactant bolus transport through the pulmonary airway tree, we demonstrate that, while the tree-like branching architecture of the lung gives rise to discrete flow regimes that result in spatially heterogeneous and inefficient drug delivery, surfactant viscosity is a key determinant of delivery homogeneity: below an analytically derived critical viscosity, gravity causes complete surfactant exclusion from entire lung subregions regardless of dose volume. A clinically compatible tenfold to thirtyfold increase in viscosity above current formulations drives all bifurcation splitting factors toward the ideal even-split value of 0.5, enabling near-complete and spatially uniform coverage of terminal bronchioles in both infant and adult lung models. Principal component analysis across approximately 24 million simulations confirms that viscosity exerts the strongest positive influence on delivery homogeneity among all injection parameters, with dose volume being the primary determinant of efficiency. These findings provide a mechanistic rationale for reformulating exogenous surfactants with higher viscosity to improve SRT outcomes in adults.