Acute respiratory distress syndrome (ARDS) and infant respiratory distress syndrome (IRDS) are severe pulmonary syndromes affecting approximately 190,000 in the United States with a mortality rate of 40%. During ARDS, hypoxemia can follow, which requires mechanical ventilation. This assisted ventilation can injure the lung by inducing large mechanical stresses from an air-liquid interface propagating through occlusion, and exposing the vessel wall to large mechanical stress gradients. In this study we investigate airway reopening scenarios by creating a model of terminal pulmonary airways using flexible tubing with monolayer coverage of lung epithelial cells. Specifically, we attempt to find a relationship between the state of collapse of a channel and the stress the cells undergo during the reopening event. This study is the first demonstration of an experimental tube with a tube law approximately physiological range. Our results indicated that in collapsed channels, as the velocity of reopening increases, the amount of damage to cells increases. This indicates flexibility causes an increase in cell damage which agrees with the stimulus-response behavior from prior studies. However, in fully-inflated channels, we see transitional behavior between flexible and rigid models. This research is a good starting point to investigate recruitment-derecruitment events in flexible channels, which could give a better representation of the mechanisms that cause cell damage in cases of ARDS and VILI. / 1 / Michael C Harrison

acase@tulane.edu

Acute Respiratory Distress Syndrome (ARDS) is a lung condition with a mortality rate of 40 % that affects about 225,000 individuals in the U.S. In these patients, epithelial injury can contribute to alveolar flooding and injury to type II cells by disrupting normal epithelial fluid transport, impacting the removal of edema fluid from alveolar space. Mechanical stresses associated with opening occluded airways damages the epithelial lining of the lungs. Prior studies explore the nature of the stresses and damage in straight tube models of airways. Our model presented in this work accounts for the branching in the pulmonary airways. We have developed a scalable microfluidic model of pulmonary airway bifurcations for investigation of reopening near the bifurcation as well as the macroscopic reopening pattern. We utilize a μ-PIV/Shadowgraph system to visualize the flow fields near the interface as a semi-infinite finger of air propagates through the bifurcation model. Further, we utilize μ-PIV for downstream flow-rate monitoring to examine the symmetry of reopening through bifurcating networks. In the absence of surfactant, propagation preferentially opens the low-resistance path, and leads to asymmetric reopening. However, with SDS and albumin inactivated surfactant, interfacial propagation preferentially reopens the pathway with the higher hydraulic resistance. The propagation pattern with pulmonary surfactant stabilizes the system so that the daughter branches of a nearly symmetric bifurcation open simultaneously. Our multiple generation network serves to validate the stability of the single generation. However, the second generation does not mirror the behavior of the first generation. We explore the reasons for this, and also present preliminary studies for the investigation of restoring surfactant function after deactivation by serum proteins. / acase@tulane.edu

In the reopening of fluid occluded airways, the pressure gradient due to the propagation of an air bubble causes extensive epithelial cell damage. The mechanism of cell necrosis and biotransport may be further understood by characterizing the flow fields near the tip of a semi-infinite bubble propagating through a fluid-filled bifurcation. A symmetric microfluidic pulmonary bifurcation model was fabricated for optical diagnostics with an instantaneous μ-PIV/ shadowgraphy microscopy system. Data handling and processing techniques were developed to calculate interfacial characteristics of multiphase flow from the microscopy system and accuracy was quantified through varying the apparatus set up. Differences in the interfacial geometric characteristics were quantified for changes in static and dynamic surface tension in comparisons of water, SDS, and Infasurf that may reflect changes in the mechanical stress that stimulate, and potentially damage, epithelial cells that line the airways. From these results, the asymmetrical tendencies of opening a symmetric pulmonary bifurcation model were quantified. It was found that pulmonary surfactant stabilized symmetric bifurcations that opened asymmetrically without the aid of surfactant. / acase@tulane.edu