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In the lungs, the Laplace pressure, Δ P = 2 γ / R , would be higher in smaller alveoli than larger alveoli unless the surface tension, γ decreases with alveolar interfacial area, A , such that 2ε > γ in which ε = A (d γ /d A ) is the dilatational modulus. In Acute Respiratory Distress Syndrome (ARDS), lipase activity due to the immune response to an underlying trauma or disease causes single chain lysolipid concentrations to increase in the alveolar fluids via hydrolysis of double-chain phospholpids in bacterial, viral, and normal cell membranes. Increasing lysolipid concentrations decrease the dilatational modulus dramatically at breathing frequencies if the soluble lysolipid has sufficient time to diffuse off the interface, causing 2 ε < γ , thereby potentially inducing the “Laplace Instability”, in which larger alveoli have a lower internal pressure than smaller alveoli. This can lead to uneven lung inflation, alveolar flooding, and poor gas exchange, typical symptoms of ARDS. While the ARDS lung contains a number of lipid and protein species in the alveolar fluid in addition to lysolipids, the surface activity and frequency dependent dilatational modulus of lysolipid suggest how inflammation may lead to the lung instabilities associated with ARDS. At high frequencies, even at high lysolipid concentrations, 2 ε − γ > 0, which may explain the benefits ARDS patients receive from high frequency oscillatory ventilation.