• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.487-499
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• 2000

Background : Acute lung injury is an hypoxic respiratory failure resulting from damage to the alveolar-capillary membrane, which can be developed by a variety of systemic inflammatory diseases. In this study the therapeutic effects of intra-tracheal pulmonary surfactant instillation was evaluated in the intratracheal endotoxin induced acute lung injury model of a rat. Methods : Twenty Sprague-Dawley rats were divided into 4 groups, and normal saline (2 ml/kg, for group 1) or LPS (5 mg/kg, for group 2, 3, and 4) was instilled into the trachea respectively. Either normal saline (2 ml/kg, for group 1 & 2, 30 min later) or bovine surfactant (15 mg/kg, 30 min later for group 3, 5 hr later for group 5) was instilled into the trachea. The therapeutic effect of intratracheal surfactant therapy was evaluated with one chamber body plethysmography (respiratory frequency, tidal volume and enhanced pause), ABGA, BAL fluid analysis (cell count with differential, protein concentration) and pathologic examination of the lung. Results : Intratracheal endotoxin instillation increased the respiration rate decreased the tidal volume and int creased the Penh in all group of rats. Intratracheal instillation of surfactant decreased Penh, increased arterial oxygen tension, decreased protein concentration of BAL fluid and decreased lung inflammation at both times of administration (30 minute and 5 hour after endotoxin instillation). Conclusion : Intratracheal instillation of surfactant can be a beneficial therapeutic modality as discovered in the acute lung injury model of rats induced by intratracheal LPS intillation. It deserves to be evaluated for treatment of human acute lung injury.

• Tuberculosis and Respiratory Diseases
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• v.53 no.4
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• pp.409-419
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• 2002

Background : The therapeutic effects of surfactant on acute lung injury derive not only from its recruiting action on collapsed alveoli but also from its anti-inflammatory effects. Pro-apoptotic action on alveolar neutrophils represents one of the important anti-inflammatory mechanisms of surfactant. In the present study, we evaluated the effects of sufactant on the apoptosis of human peripheral and rat alveolar neutrophils. Methods : In the (Ed- the article is not definitely needed but it helps to separate the two prepositions 'in') in vitro study, human neutrophils were collected from healthy volunteers. An equal number of neutrophils ($1{\times}10^6$) (Ed-confirm) was treated with LPS (10, 100, 1000ng/ml), surfactant (10, 100, $1000{\mu}g/ml$), or a combination of LPS (1000ng/ml) and surfactant (10, 100, $1000{\mu}g/ml$). After incubation for 24 hours, the apoptosis of neutrophils was evaluated by Annexin V method. In the in vivo study, induction of acute lung injury in SD rats by intra-tracheal instillation of LPS (5mg/kg) was followed by intra-tracheal administration of either surfactant (30mg/kg) or normal saline (5ml/kg). Tenty-four hours after LPS instillation, alveolar neutrophils were collected and the apoptotic rate was evaluated by Annexin V method. In addition, changes of the respiratory mechanics of rats (respiratory rate, tidal volume, and airway resistance) were evaluated with one chamber body plethysmography before, and 23 hours after, LPS instillation. Results : in the in vitro study, LPS treatment decreased the apoptosis of human peripheral blood neutrophils (control: $47.4{\pm}5.0%$, LPS 10ng/ml; $30.6{\pm}10.8%$, LPS 100ng/ml; $27.5{\pm}9.5%$, LPS 1000ng/ml; $24.4{\pm}7.7%$). The combination of low to moderate doses of surfactant with LPS promoted apoptosis (LPS 1000ng/ml + Surf $10{\mu}g/ml$; $36.6{\pm}11.3%$, LPS 1000ng/ml +Surf $100{\mu}g/ml$; $41.3{\pm}11.2%$). The high dose of surfactant ($1000{\mu}g/ml$) decreased apoptosis ($24.4{\pm}7.7%$) and augmented the anti-apoptotic effect of LPS (LPS 1000ng/ml + Surf $1000P{\mu}g/ml$; $19.8{\pm}5.4%$). In the in vivo study, the apoptotic rate of alveolar neutrophils of surfactant-treated rats was higher than that of normal saline-treated rats ($6.03{\pm}3.36%$ vs. $2.95{\pm}0.58%$). The airway resistance (represented by Penh) of surfactant-treated rats was lower than that of normal saline-treated rats at 23 hours after LPS injury ($2.64{\pm}0.69$ vs. $4.51{\pm}2.24$, p<0.05). Conclusion : Surfactant promotes the apoptosis of human peripheral blood and rat alveolar neutrophils. Pro-apoptotic action on neutrophils represents one of the important anti-inflammatory mechanisms of surfactant.

• Tuberculosis and Respiratory Diseases
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• v.43 no.3
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• pp.367-376
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• 1996

Background : The diagnosis of emphysema during life is based on a combination of clinical, functional, and radiographic findings, but this combination is relatively insensitive and nonspecific. The development of rapid, high-resolution third and fourth generation CT scanners has enabled us to resolve pulmonary parenchymal abnormalities with great precision. We compared the chest HRCT findings to the pulmonary function test and arterial blood gas analysis in pulmonary emphysema patients to test the ability of HRCT to quantify the degree of pulmonary emphysema. Methods : From october 1994 to october 1995, the study group consisted of 20 subjects in whom HRCT of the thorax and pulmonary function studies had been obtained at St. Mary's hospital. The analysis was from scans at preselected anatomic levels and incorporated both lungs. On each HRCT slice the lung parenchyma was assessed for two aspects of emphysema: severity and extent. The five levels were graded and scored separately for the left and right lung giving a total of 10 lung fields. A combination of severity and extent gave the degree of emphysema. We compared the HRCT quantitation of emphysema, pulmonary function tests, ABGA, CBC, and patients characteristics(age, sex, height, weight, smoking amounts etc.) in 20 patients. Results : 1) There was a significant inverse correlation between HRCT scores for emphysema and percentage predicted values of DLco(r = -0.68, p < 0.05), DLco/VA(r = -0.49, p < 0.05), FEV1(r = -0.53, p < 0.05), and FVC(r = -0.47, p < 0.05). 2) There was a significant correlation between the HRCT scores and percentage predicted values of TLC(r = 0.50, p < 0.05), RV(r = 0.64, p < 0.05). 3) There was a significant inverse correlation between the HRCT scores and PaO2(r = -0.48, p < 0.05) and significant correlation with D(A-a)O2(r = -0.48, p < 0.05) but no significant correlation between the HRCT scores and PaCO2. 4) There was no significant correlation between the HRCT scores and age, sex, height, weight, smoking amounts in patients, hemoglobin, hematocrit, and wbc counts. Conclusion : High-Resolution CT provides a useful method for early detection and quantitating emphysema in life and correlates significantly with pulmonary function tests and arterial blood gas analysis.