Thicker Is Better: How Surfactant Viscosity Governs Uniform Surfactant Lung Delivery
Abstract
Surfactant Replacement Therapy (SRT) is a well-established intervention for Neonatal Respiratory DistressSyndrome, 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 nearcomplete 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.
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BibTeX
@misc{beuzelin2026thicker,
title = {{Thicker Is Better: How Surfactant Viscosity Governs Uniform Surfactant Lung Delivery}},
author = {Tristan Beuzelin and Matthieu Labousse and Marcel Filoche},
howpublished = {HAL},
year = {2026},
month = sep,
doi = {10.48550/arxiv.2609.18450},
eprint = {2609.18450},
archivePrefix = {arXiv},
url = {https://hal.science/hal-05751812v1},
note = {CC BY 4.0},
}
RIS
TY - UNPB
TI - Thicker Is Better: How Surfactant Viscosity Governs Uniform Surfactant Lung Delivery
AU - Tristan Beuzelin
AU - Matthieu Labousse
AU - Marcel Filoche
PY - 2026
DA - 2026/09/16
PB - HAL
DO - 10.48550/arxiv.2609.18450
UR - https://hal.science/hal-05751812v1
AB - Surfactant Replacement Therapy (SRT) is a well-established intervention for Neonatal Respiratory DistressSyndrome, 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 nearcomplete 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.
ER -