Lipid-derived free radical production in superantigen-induced interstitial pneumonia.

We studied the free radical generation involved in the development of interstitial pneumonia (IP) in an animal model of autoimmune disease. We observed an electron spin resonance (ESR) spectrum of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) radical adducts detected in the lipid extract of lungs in autoimmune-prone mice after intratracheal instillation of staphylococcal enterotoxin B. The POBN adducts detected by ESR were paralleled by infiltration of macrophages and neutrophils into the bronchoalveolar lavage fluid. To further investigate the mechanism of free radical generation, mice were pretreated with the macrophage toxicant gadolinium chloride, which significantly suppressed the radical generation. Free radical generation was also decreased by pretreatment with the xanthine oxidase (XO) inhibitor allopurinol, the iron chelator Desferal, and the inducible nitric oxide synthase (iNOS) inhibitor 1400W. Histopathologically, these drugs significantly reduced both the cell infiltration into the alveolar septal walls and the synthesis of pulmonary collagen fibers. Experiments with NADPH oxidase knockout mice showed that NADPH oxidase did not contribute to lipid radical generation. These results suggest that lipid-derived carbon-centered free radical production is important in the manifestation of IP and that a macrophage toxicant, an XO inhibitor, an iron chelator, and an iNOS inhibitor protect against both radical generation and the manifestation of IP.

Prediction of prognosis for acute respiratory distress syndrome with thin-section CT: validation in 44 cases.

PURPOSE: To retrospectively evaluate whether the thin-section computed tomographic (CT) appearance has prognostic value for prediction of mortality, number of ventilator-free days (ie, days without mechanical ventilation), and 28-day risk of barotrauma in patients with a clinically early stage of acute respiratory distress syndrome (ARDS) from diverse causes. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Two independent observers who were blinded to patient outcomes retrospectively evaluated the thin-section CT scans obtained within 7 days after clinical ARDS onset in 26 survivors and 18 nonsurvivors. Of 44 patients, there were 37 men and seven women (mean age +/- standard deviation, 61.8 years +/- 15.6). CT findings were graded on a scale of 1-6 that corresponded with consecutive pathologic phases: score of 1, normal attenuation; score of 2, ground-glass attenuation; score of 3, consolidation; score of 4, ground-glass attenuation associated with traction bronchiolectasis or bronchiectasis; score of 5, consolidation associated with traction bronchiolectasis or bronchiectasis; and score of 6, honeycombing. An overall CT score was obtained by adding the six averaged scores (three zones in each lung). Multivariate regression analysis was used to assess the independent predictive value of the CT score. RESULTS: The area of increased attenuation associated with traction bronchiolectasis or bronchiectasis (P = .002), as well as the overall CT score (P = .002), was smaller in survivors than in nonsurvivors. Results of multivariate regression analysis revealed that CT score was independently associated with mortality (P = .006). A CT score of less than 230 enabled prediction of survival with 73% sensitivity and 75% specificity and was associated with both a greater number of ventilator-free days (P = .018) and a lower incidence of barotrauma (P = .013) within 28 days after ARDS onset. CONCLUSION: Extensive thin-section CT abnormalities indicative of fibroproliferative changes were independently predictive of poor prognosis in patients with a clinically early stage of ARDS.