Increased permeability of the alveolar-capillary membrane results in diffuse alveolar damage that leads to non-cardiogenic low-pressure pulmonary edema. Clinically, this is referred to as acute lung injury (ALI). The well-described phenomenon of acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury, often associated with a high mortality rate in the critical care population. Currently, there are very few practical techniques available to provide a rapid and direct measure of pulmonary microvascular permeability in the critical care setting. In this study, a novel diagnostic technique involving the administration of hydroxyethyl starches (HES) to patients with ALI/ARDS is introduced. The infrared (IR) spectroscopic determination of hydroxyethyl starch-based macromolecules in patient's bronchial washing fluids is used to assess the pulmonary alveolar-capillary permeability in acute lung injury. Hydroxyethyl starches are used clinically as colloid plasma expanders. The large size of infused HES, under normal circumstances, restricts these molecules to the intravascular space. Under conditions of increased pulmonary vascular permeability, high molecular weight fractions of the polymer with plasma protein components and water will leak into the pulmonary interstitium. The leakage of plasma protein and water result in pulmonary interstitial edema. IR spectroscopy and IR microscopy were applied to animal injury experiments for pulmonary permeability assessment. From the baseline study, two groups were recognized as "leak" and "non-leak" based on the spectral signature of HES in bronchial washing fluid. By applying a spectral pattern recognition methodology a training set was constructed based on a set of bronchial washings for leak and non-leak groups. Autopsy tissue from a patient with acute lung injury confirmed that investigation of a patient's bronchial washing fluid is able to provide an e rly diagnosis of ARDS. A prospective randomized study on an injured patient population was also conducted. The experimental and clinical investigations demonstrate that IR spectroscopy provides a direct measure of capillary-alveolar membrane permeability in acute lung injury. This technique is advantageous because no radioactive tracers are employed and little sample preparation is required. It is a rapid, simple, and a minimally invasive technique with high sensitivity for diagnosing ARDS. Furthermore, the assay method is very specific in evaluating pulmonary vascular permeability in acute lung injury cases. The simplicity of this method makes it convenient to use and applicable to the critical care environment. This study of the use of IR spectroscopy in the assessment of capillary-alveolar membrane permeability in acute lung injury patients representsa new and significant application of this technique to clinical sciences. (Abstract shortened by UMI.)
