Frank JA, Briot R, Lee JW, Ishizaka A, Uchida T, Matthay MA. Physiological and biochemical markers of alveolar epithelial barrier dysfunction in perfused human lungs. Am J Physiol Lung Cell Mol Physiol 293: L52-L59, 2007. First published March 9, 2007; doi:10.1152/ajplung.00256.2006.-To study air space fluid clearance (AFC) under conditions that resemble the clinical setting of pulmonary edema in patients, we developed a new perfused human lung preparation. We measured AFC in 20 human lungs rejected for transplantation and determined the contribution of AFC to lung fluid balance. AFC was then compared with air space and perfusate levels of a biological marker of epithelial injury. The majority of human lungs rejected for transplant had intact basal (75%) and 2-adrenergic agonist-stimulated (70%) AFC. For lungs with both basal and stimulated AFC, the basal AFC rate was 19 Ϯ 10%/h, and the 2-adrenergic-stimulated AFC rate was 43 Ϯ 13%/h. Higher rates of AFC were associated with less lung weight gain (Pearson coefficient Ϫ0.90, P Ͻ 0.0001). Air space and perfusate levels of the type I pneumocyte marker receptor for advanced glycation end products (RAGE) were threefold and sixfold higher, respectively, in lungs without basal AFC compared with lungs with AFC (P Ͻ 0.05). These data show that preserved AFC is a critical determinant of favorable lung fluid balance in the perfused human lung, raising the possibility that 2-agonist therapy to increase edema fluid clearance may be of value for patients with acute lung injury and pulmonary edema. Also, although additional studies are needed, a biological marker of alveolar epithelial injury may be useful clinically in predicting preserved AFC. alveolar epithelial fluid transport; acute lung injury; acute respiratory distress syndrome; lung transplantation; biological markers; pulmonary edema; primary graft failure; air space fluid clearance POSTLUNG TRANSPLANT REPERFUSION PULMONARY EDEMA is a form of acute lung injury that contributes to early mortality in lung transplant patients (6 -8, 37). Acute lung injury is characterized by the loss of alveolar epithelial barrier function, including increased permeability to protein and decreased fluid transport from the air spaces, resulting in pulmonary edema (6 -8, 37). Removal of edema fluid from the air spaces, or distal air space fluid clearance (AFC), is dependent on a transepithelial sodium concentration gradient established by basolateral sodium-potassium ATPase (19,20). The basal rate of alveolar epithelial ion and fluid transport can be increased by  2 -adrenergic agonists (15,17,20,22). Edema fluid cleared from the distal air spaces into the interstitial space is transported from the lungs primarily by direct absorption into the pulmonary venous circulation, but also by pulmonary lymphatic drainage and clearance into the pleural space (20,30). Lung fluid balance is the sum of edema formation and lung fluid clearance.Data from nonperfused human lungs obtained from donated organs rejected for transplant (39) and from p...
Detection and analysis of volatile compounds in exhaled breath represents an attractive tool for monitoring the metabolic status of a patient and disease diagnosis, since it is non-invasive and fast. Numerous studies have already demonstrated the benefit of breath analysis in clinical settings/applications and encouraged multidisciplinary research to reveal new insights regarding the origins, pathways, and pathophysiological roles of breath components. Many breath analysis methods are currently available to help explore these directions, ranging from mass spectrometry to laser-based spectroscopy and sensor arrays. This review presents an update of the current status of optical methods, using near and mid-infrared sources, for clinical breath gas analysis over the last decade and describes recent technological developments and their applications. The review includes: tunable diode laser absorption spectroscopy, cavity ring-down spectroscopy, integrated cavity output spectroscopy, cavity-enhanced absorption spectroscopy, photoacoustic spectroscopy, quartz-enhanced photoacoustic spectroscopy, and optical frequency comb spectroscopy. A SWOT analysis (strengths, weaknesses, opportunities, and threats) is presented that describes the laser-based techniques within the clinical framework of breath research and their appealing features for clinical use.
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