• Tuberculosis and Respiratory Diseases
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• v.69 no.5
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• pp.337-347
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• 2010

Background: Transglutaminase-2 (TG-2) has been reported to play an important role in the process of fibrosis. However, TG-2 studies on fibroproliferation of acute lung injury (ALI) are absent. The purpose of this study was to investigate the role of TG-2 in the fibroproliferation of lipopolysaccharide (LPS)-induced ALI. Methods: The male C57BL/6 mice of 5 weeks age were divided into 3 groups; control group (n=30) in which $50{\mu}L$ of saline was given intratracheally (IT), LPS group (n=30) in which LPS 0.5 mg/kg/$50{\mu}L$ of saline was given IT, and LPS+Cyst group treated with intraperitoneal 200 mg/kg of cystamine, competitive inhibitor of TG-2, after induction of ALI by LPS. TG-2 activity and nuclear factor $(NF)-{\kappa}B$ were measured in lung tissue homogenate. Tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, IL-6, myeloperoxidase (MPO), and transforming growth factor (TGF)-${\beta}1$ were measured using bronchoalveolar lavage fluids. Histopathologic ALI score and Mallory's phosphotunistic acid hematoxylin (PTAH) for collagen and fibronectin deposition were performed. Results: The TG-2 activities in the LPS group were significantly higher than the control and LPS+Cyst groups (p<0.05). The TNF-${\alpha}$ and IL-$1{\beta}$ concentrations and $NF-{\kappa}B$ activity were lower in the LPS+Cyst group than the LPS group (p<0.05). The LPS+Cyst group showed lower MPO, ALI score, TGF-${\beta}1$ concentration, and Mallory's PTAH stain than the LPS group, but the differences were not significant (p>0.05). Conclusion: Inhibition of TG-2 activity in the LPS-induced ALI prevented early inflammatory parameters, but had limited effects on late ALI and fibroproliferative parameters.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.519-528
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• 2002

Background : Steroid therapy has been shown to improve the clinical outcome in acute respiratory distress syndrome (ARDS) patients with histological evidence of fibroproliferation in the lung tissue and no identifiable source of infection. Because the histopathological features of acute interstitial pneumonia(AIP) are identical with that of ARDS, early steroid therapy was used in AIP patients who had histological evidence of fibroproliferation in the lung tissue and no identifiable source of infection. We analyzed seven years of our experience to evaluate the efficacy of early steroid therapy in AIP. Materials and Methods : A retrospective review was performed on AIP patients who received steroid therapy within 7 days of mechanical ventilatory support in Dankook university Hospital between May 1995 and May 2002. AIP was diagnosed clinically by ARDS without a known cause of the etiology and pathologically by a lung biopsy showing a fibroproliferative stage of diffuse alveolar damage. The clinical response and physiologic parameters were evaluated during steroid therapy. Results : Five AIP patients received intravenous methylprednisolone (1-2 mg/kg every 6 hours) after $0.6{\pm}1.7$ days of mechanical ventilatory support. Lung biopsies were performed after $1.8{\pm}1.4$ days of mechanical ventilatory support. Four patients(80%) survived and were extubated after $2.8{\pm}0.4$ days of steroid therapy with improvement in the $PaO_2/FiO_2$ ratio ($127.4{\pm}10.0$ at day 0 to $223.8{\pm}37.6$ at day 7) by steroid therapy. However, one patient(20%) died of respiratory failure after 15 days of steroid therapy. Conclusion : Early steroid therapy sppears to be beneficial in AIP patients without evidence of infection. However, as our study group was too small, further large scale studies to define the effectiveness of steroids are required.

• Tuberculosis and Respiratory Diseases
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• v.52 no.4
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• pp.376-384
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• 2002

Background : The mortality from acute respiratory distress syndrome(ARDS) in the late stage, which is characterized by progressive pulmonary fibroproliferation, is ${\geq}80%$. Although previous prospective trials failed to show a survival benefit of steroid therapy in early ARDS, recently, a few of reports have described the survival benefit of the long-term use of steroid in patients with late ARDS. In this study, we analyzed the effect of steroid therapy on patients with late ARDS retrospectively in a single. Medral intensive care unit (MICU). Methods : Over a 3-year period, the medical records of 48 ARDS patients who had been on mechanical ventilation more than 8 days were reviewed. 14 patients were treated by the long-term use of methylprednisolone and another 34 patients served as a control. Both groups were comparable regarding clinical and physiologic data lung injury score(LIS), multiple organ failure score, APACHE III and SAPS II score. Because steroid was instituted after 8 days of advanced mechanical ventilatory support in average, we arbitrarily defined the $8^{th}$ day of ARDS as first day of the study. Results : Initially, the groups had similar PF($PaO_2/FiO_2$) ratio, LIS, APACHE III and SAPS II score. By 7th day after the start of steroid therapy, there were significant improvements in PF ratio, LIS, APACHE III and SAPS II score. The mortality in the steroid treated group was significantly lower(42.9% vs 73.5%, p<0.05). Conclusion : Although the data of this study was retrospective and was not randomized, in order to improve the patient's outcomes, steroid therapy should be considered in late ARDS patients. However, prospective trials are needed to define the indication and the effect of steroid therapy in late ARDS.