Lung Surfactant Dilatational Rheology and Potential Effects on Lung Stability

Abstract

Acute respiratory distress syndrome (ARDS) is a diffuse, inflammatory lung disease characterized by increased vascular permeability, decreased lung compliance, and loss of aerated tissue affecting 200,000 in.the US annually with 40% mortality. COVID-19 infections have significantly increased these numbers over the past two years with a mortality rate of nearly 70%. The mechanisms through which ARDS arises and how host factors confer an increased risk of developing severe disease remain unclear. It is known that inflammation due to underlying disease is linked to ARDS progression and severity. Phospholipase A2 catalyzed degradation of pathogen phospholipids to soluble lysolipids and free fatty acids can lead to a mechanical lung instability known as the ‘Laplace Instability’ by replacing healthy lung surfactant at the air-water interface. The intra-alveolar pressure is increased by ΔP = 2γ/R; ΔP is higher in alveoli with smaller radii, R, than larger alveoli if γ, the surface tension, is constant. This would cause smaller alveoli to deflate and fill with fluid, while the larger alveolar become distended, both symptoms of ARDS. To prevent this, the surface tension must decrease with decreasing alveolar radius such that 2E* (ω) − γ > 0 in which E* (ω) = A(ω) (∂γ/∂A) is the dilatational modulus. For healthy lung surfactant 2E* (ω) − γ > 0 and the lung is stable. However, during inflammation, lysolipid concentrations increase by orders of magnitude in the alveolar fluids. We show that lysopalmitoylphosphatidylcholine concentrations above its critical micelle concentration (CMC) cause E> (ω) of lung surfactant monolayers to decrease dramatically leading to 2E* (ω)−γ ≤ 0 at breathing frequencies, which can lead to the Laplace Instability and compromise uniform lung inflation. Theoretical models show E* decreases due to diffusive exchange of lysolipids between the monolayer and the micelles in the adjacent fluid. Surfactant adsorption to a clean interface as well as surfactant dilatational properties can be correlated with equilibrium surface concentration vs bulk concentration data using fundamental thermodynamic models of Lysolipid properties.