• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.846-860
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• 1998

Background: Endotoxin (LPS : lipopolysaccharide), a potent activator of immune system, can induce acute and chronic inflammation through the production of cytokines by a variety of cells, such as monocytes, endothelial cells, lymphocytes, eosinophils, neutrophils and fibroblasts. LPS stimulate the mononucelar cells by two different pathway, the CD14 dependent and independent way, of which the former has been well documented, but not the latter. LPS binds to the LPS-binding protein (LBP), in serum, to make the LPS-LBP complex which interacts with CD14 molecules on the mononuclear cell surface in peripheral blood or is transported to the tissues. In case of high concentration of LPS, LPS can stimulate directly the macrophages without LBP. We investigated to detect the generation of proinflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-$\alpha$ and fibrogenic cytokine, TGF-$\beta$, by peripheral blood mononuclear cells (PBMC) after LPS stimulation under serum-free conditions, which lacks LBPs. Methods : PBMC were obtained by centrifugation on Ficoll Hypaque solution of peripheral venous bloods from healthy normal subjects, then stimulated in the presence of LPS (0.1 ${\mu}g/mL$ to 100 ${\mu}g/mL$ ). The activities of IL-1, IL-6, TNF, and TGF-$\beta$ were measured by bioassaies using cytokines - dependent proliferating or inhibiting cell lines. The cellular sources producing the cytokines was investigated by immunohistochemical stains and in situ hybridization. Results : PBMC started to produce IL-6, TNF-$\alpha$ and TGF-$\beta$ in 1 hr, 4 hrs and 8hrs, respectively, after LPS stimulation. The production of IL-6, TNF-$\alpha$ and TGF-$\beta$ continuously increased 96 hrs after stimulation of LPS. The amount of production was 19.8 ng/ml of IL-6 by $10^5$ PBMC, 4.1 ng/mL of TNF by $10^6$ PBMC and 34.4 pg/mL of TGF-$\beta$ by $2{\times}10^6$ PBMC. The immunoreactivity to IL-6, TNF-$\alpha$ and TGF-$\beta$ were detected on monocytes in LPS-stimulated PBMC. Some of lymphocytes showed positive immunoreactivity to TGF-$\beta$. Double immunohistochemical stain showed that IL-1$\beta$, IL-6, TNF-$\alpha$ expression was not associated with CD14 postivity on monocytes. IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$mRNA expression were same as observed in immunoreactivity for each cytokines. Conclusion: When monocytes are stimulated with LPS under serum-free conditions, IL-6 and TNF-$\alpha$ are secreted in early stage of inflammation. In contrast, the secretion of TGF-$\beta$ arise in the late stages and that is maintained after 96 hrs. The main cells releasing IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ are monocytes, but also lymphocytes can secret TGF-$\beta$.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.861-869
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• 1998

Backgrounds: The injury of a tissue results in the infalmmation, and the imflammed tissue is replaced by the normal parenchymal cells during the process of repair. But, constitutional or repetitive damage of a tissue causes the deposition of collagen resulting in the loss of its function. These lesions are found in the lung of patients with idiopathic pulmonary fibrosis, complicated fibrosis after diffuse alveolar damage (DAD) and inorganic dust-induced lung fibrosis. The tissue from lungs of patients undergoing episodes of active and/or end-stage pulmonary fibrosis shows the accumulation of inflammatory cells, such as mononuclear cells, neutrophils, mast cells and eosinophils, and fibroblast hyperplasia. In this regard, it appears that the inflammation triggers fibroblast activation and proliferation with enhanced matrix synthesis, stimulated by inflammatory mediators such as interleukin-1 (IL-1) and/or tumor necrosis factor (TNF). It has been well known that TGF-$\beta$ enhance the proliferation of fibroblasts and the production of collagen and fibronectin, and inhibit the degradation of collagen. In this regard, It is likely that TGF-$\beta$ undergoes important roles in the pathogenesis of pulmonary fibrosis. Nevertheless, this single cytokine is not the sole regulator of the pulmonary fibrotic response. It is likely that the balance of many cytokines including TGF-$\beta$, IL-1, IL-6 and TNF-$\alpha$ regulates the pathogenesis of pulmonary fibrosis. In this study, we investigate the interaction of TGF-$\beta$, IL-1$\beta$, IL-6 and TNF-$\alpha$ and their effect on the proliferation of fibroblasts. Methods: We used a human fibroblast cell line, MRC-5 (ATCC). The culture of MRC-5 was confirmed by immunofluorecent staining. First, we determined the concentration of serum in cuture medium, in which the proliferation of MRC-5 is supressed but the survival of MRC-5 is retained. Second, we measured optical density after staining the cytokine-stimulated cells with 0.5% naphthol blue black in order to detect the effect of cytokines on the proliferation of MRC-5. Result: In the medium containing 0.5% fetal calf serum, the proliferation of MRC-5 increased by 50%, and it was maintained for 6 days. IL-1$\beta$, TNF-$\alpha$ and IL-6 induced the proliferation of MRC-5 by 45%, 160% and 120%, respectively. IL-1$\beta$ and TNF-$\alpha$ enhanced TGF-$\beta$-induced proliferation of MRC-5 by 64% and 159%, but IL-6 did not affect the TGF-$\beta$-induced proliferation. And lNF-$\alpha$-induced proliferation of MRC-5 was reduced by IL-1$\beta$ in 50%. TGF-$\beta$, TNF-$\alpha$ and both induced the proliferation of MRC-5 to 89%, 135% and 222%, respectively. Conclusions: TNF-$\alpha$, TGF-$\beta$ and IL-1$\beta$, in the order of the effectiveness, showed the induction of MRC-5 proliferation of MRC-5. TNF-$\alpha$ and IL-1$\beta$ enhance the TGF-$\beta$-induced proliferation of MRC-5, but IL-6 did not have any effect TNF-$\alpha$-induced proliferation of MRC-5 is diminished by IL-1, and TNF-$\alpha$ and TGF-$\beta$ showed a additive effect.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.360-378
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• 1997

Background : Severe acute lung injury(ALI), also known as the adult respiratory distress syndrome(ARDS), is a heterogenous nature of dynamic and explosive clinical synrome that exacts a mortality of approximately 50%. Endotoxin(ETX) is an abundant component of the outer membrane of gram-negative bacteria capable of inducing severe lung injury in gram-negative sepsis and gram-negative bacterial pneumonia, which are among the most common predisposing causes of ARDS. The influx of PMNs into airway tissue is a pathological hallmark of LPS-induced lung injury. And there is a substantial evidence suggesting that cytokines are important mediators of lung injury in gram-negative sepsis. However, the kinetics of phagocytes and cytokines by an exact time sequence and their respective pathogenic importance remain to be elucidated. This study was performed to investigate the role of phagocytes and proinflammatory cytokines in ETX-induced ALI through a time course of changes in the concentration of protein, $TNF{\alpha}$ and IL-6, and counts of total and its differential cells in BALF. The consecutive histologic findings were also evaluated. Method : The experimental animals, healthy male Sprague-Dawley, weighted $200{\pm}50g$, were divided into control- and ALI- group. ALI was induced by an intravenous administration of ETX, 5mg/kg. Above mentioned all parameters were examined at 0(control), 3, 6, 24, 72 h after administration of ETX. $TNF{\alpha}$ and IL-6 cone. in BALF were measured by a bioassay. Results : The protein concentration and total leukocyte count(TC) in BALF was significantly increased at 3h compared to controls(p < 0.05). The protein conc. was significantly elavated during observation period, but TC was significantly decreased at 72h(p < 0.05 vs. 24h). There was a close relationship between TC and protein cone. in BALF(r = 0.65, p < 0.001). The PMN and monocyte count was well correlated with TC in BALF, and the correlation of PMN(r = 0.97, p < 0.001) appeared to be more meaningful than that of monocyte(r = 0.61, p < 0.001). There was also a significant correlation between protein cone. and PMN or monocyte count in BALF(PMN vs. monocyte : r = 0.55, p < 0.005 vs. r = 0.64, p < 0.001). The count of monocyte was significantly elavated during observation period though a meaningful reduction of PMN count in BALF at 72h, this observation suggested that monocyte may, at least, partipate in the process of lung injury steadly. In this study, there was no relationship between IL-6 and $TNF{\alpha}$ cone., and $TNF{\alpha}$ but not IL-6 was correlated with TC(r = 0.61, p < 0.05) and monocyte(r = 0.67, p < 0.05) in BALF only at 3, 6h after ETX introduced. In particular, the IL-6 cone. increased earlier and rapidly peaked than $TNF{\alpha}$ cone. in BALF. In histologic findings, the cell counts of lung slices were increased from 3 to 72h(p < 0.001 vs. NC). Alveolar wall-thickness was increased from 6 to 24h(p < 0.001 vs. NC). There was a significant correlation between the cell counts of lung slices and alveolar wall-thickness(r= 0.61, p < 0.001). This result suggested that the cellular infiltrations might be followed by the alterations of interstitium, and the edematous change of alveolar wall might be most rapidly recovered to its normal condition in the process of repair. Conclusion : We concluded that although the role of PMN is partly certain in ETX-induced ALI, it is somewhat inadequate to its known major impact on ALL Alveolar macrophage and/or non-immune cells such as pulmonary endothelial or epithelial cells, may be more importantly contributed to the initiation and perpetual progression of ETX-induced ALI. The IL-6 in ETX-induced ALI was independent to $TNF{\alpha}$, measured by a bioassay in BALF. The early rise in IL-6 in BALF implies multiple origins of the IL-6.

• Tuberculosis and Respiratory Diseases
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• v.47 no.3
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• pp.356-364
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• 1999

Backgrounds: Previous reports have revealed a high morbidity and mortality in fatal asthma patients, especially those treated in the medical intensive care unit(MICU). But it has not been well known about the predictable factors for the mortality of fatal asthma(F A) with acute respiratory failure. In order to define the predictable factors for the mortality of FA at the admission to MICU, we analyzed the relationship between the clinical parameters and the prognosis of FA patients. Methods: A retrospective analysis of all medical records of 59 patients who had admitted for FA to MICU at a tertiary care MICU from January 1992 to March 1997 was performed. Results: Over all mortality rate was 32.2% and 43 patients were mechanically ventilated. In uni-variate analysis, the death group had significantly older age ($66.2{\pm}10.5$ vs. $51.0{\pm}18.8$ year), lower FVC($59.2{\pm}21.1$ vs. $77.6{\pm}23.3%$) and lower $FEV_1$($41.4{\pm}18.8$ vs. $61.l{\pm}23.30%$), and longer total ventilation time ($255.0{\pm}236.3$ vs. $98.1{\pm}120.4$ hour) (p<0.05) compared with the survival group (PFT: best value of recent 1 year). At MICU admission, there were no significant differences in vital signs, $PaCO_2$, $PaO_2/FiO_2$, and $AaDO_2$, in both groups. However, on the second day of MICU, the death group had significantly more rapid pulse rate ($121.6{\pm}22.3$ vs. $105.2{\pm}19.4$ rate/min), elevated $PaCO_2$ ($50.1{\pm}16.5$ vs. $41.8{\pm}12.2 mm Hg$), lower $PaO_2/FiO_2$, ($160.8{\pm}59.8$ vs. $256.6{\pm}78.3 mm Hg$), higher $AaDO_2$ ($181.5{\pm}79.7$ vs. $98.6{\pm}47.9 mm Hg$), and higher APACHE III score ($57.6{\pm}21.1$ vs. $20.3{\pm}13.2$) than survival group (p<0.05). The death group had more frequently associated with pneumonia and anoxic brain damage at admission, and had more frequently developed sepsis during disease progression than the survival group (p<0.05). Multi-variate analysis using APACHE III score and $PaO_2/FiO_2$, ratio on first and second day, age, sex, and pneumonia combined at admission revealed that APACHE III score (40) and $PaO_2/FiO_2$ ratio (<200) on second day were regarded as predictive factors for the mortality of fatal asthma (p<0.05). Conclusions: APACHE III score ($\geq$40) and $PaO_2/FiO_2$ ratio (<200) on the second day of MICU, which might reflect the response of treatment, rather than initially presented clinical parameters would be more important predictable factors of mortality in patients with FA.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1236-1251
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• 1998

Background : TNF-$\alpha$ appears to be a central mediator of the host response to sepsis. While TNF-$\alpha$ is mainly considered a proinflammatory cytokine, it can also act as a direct cytotoxic cytokine. However, there are not so many studies about the relationship bet ween TNF-$\alpha$ level and lung injury severity in ALI, particularly regarding the case of ALI caused by direct lung injury such as diffuse pulmonary infection. Recently, a natural defense mechanism, known as the stress response or the heat shock response, has been reported in cellular or tissue injury reaction. There are a number of reports examining the protective role of pre-induced heat stress proteins on subsequent LPS-induced TNF-$\alpha$ release from monocyte or macrophage and also on subsequent LPS-induced ALI in animals. However it is not well established whether the stress protein synthesis such as HSP can be induced from rat alveolar macrophages by in vitro or in vivo LPS stimulation. Methods : We measured the level of TNF-$\alpha$, the percentage of inflammatory cells in bronchoalveolar lavage fluid, protein synthesis in alveolar macrophages isolated from rats at 1, 2, 3, 4, 6, 12, and 24 hours after intratracheal LPS instillation. We performed histologic examination and also obtained histologic lung injury index score in lungs from other rats at 1, 2, 3, 4, 6, 12, 24 h after intratracheal LPS instillation. Isolated non-stimulated macrophages were incubated for 2 h with different concentration of LPS (0, 1, 10, 100 ng/ml, 1, or 10 ${\mu}g/ml$). Other non-stimulated macrophages were exposed at $43^{\circ}C$ for 15 min, then returned to at $37^{\circ}C$ in 5% CO2-95% for 1 hour, and then incubated for 2 h with LPS (0, 1, 10, 100ng/ml, 1, or 10 ${\mu}g/ml$). Results : TNF-$\alpha$ levels began to increase significantly at 1 h, reached a peak at 3 h (P<0.0001), began to decrease at 6 h, and returned to control level at 12 h after LPS instillation. The percentage of inflammatory cells (neutrophils and alveolar macrophages) began to change significantly at 2 h, reached a peak at 6 h, began to recover but still showed significant change at 12 h, and showed insignificant change at 24 h after LPS instillation compared with the normal control. After LPS instillation, the score of histologic lung injury index reached a maximum value at 6 h and remained steady for 24 hours. 35 kDa protein band was newly synthesized in alveolar macrophage from 1 hour on for 24 hours after LPS instillation. Inducible heat stress protein 72 was not found in any alveolar macrophages obtained from rats after LPS instillation. TNF-$\alpha$ levels in supernatants of LPS-stimulated macro phages were significantly higher than those of non-stimulated macrophages(p<0.05). Following LPS stimulation, TNF-$\alpha$ levels in supernatants were significantly lower after heat treatment than in those without heat treatment (p<0.05). The inducible heat stress protein 72 was not found at any concentrations of LPS stimulation. Whereas the 35 kDa protein band was exclusively found at dose of LPS of 10 ${\mu}g/ml$. Conclusion : TNF-$\alpha$ has a direct or indirect close relationship with lung injury severity in acute lung injury or acute respiratory distress syndrome. In vivo and in vitro LPS stimulation dose not induce heat stress protein 72 in alveolar macrophages. It is likely that 35 kDa protein, synthesized by alveolar macrophage after LPS instillation, does not have a defense role in acute lung injury.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1265-1276
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• 1998

Background : Nitric oxide(NO) is an endogenously produced free radical that plays an important role in regulating vascular tone, inhibition of platelet aggregation and white blood cell adhesion to endothelial cells, and host defense against infection. The highly reactive nature of NO with oxygen radicals suggests that it may either promote or reduce oxidant-induced cell injury in several biological pathways. Oxidant injury and interactions between pulmonary vascular endothelium and leukocytes are important in the pathogenesis of acute lung injury, including acute respiratory distress syndrome(ARDS). In ARDS, therapeutic administration of NO is a clinical condition providing exogenous NO in oxidant-induced endothelial injury. The role of exogenous NO from NO donor or the suppression of endogenous NO production was evaluated in oxidant-induced endothelial injury. Method : The oxidant injury in cultured rat lung microvascular endothelial cells(RLMVC) was induced by hydrogen peroxide generated from glucose oxidase(GO). Cell injury was evaluated by $^{51}$chromium($^{51}Cr$) release technique. NO donor, such as S-nitroso-N-acetylpenicillamine(SNAP) or sodium nitroprusside(SNP), was added to the endothelial cells as a source of exogenous NO. Endogenous production of NO was suppressed with N-monomethyl-L-arginine(L-NMMA) which is an NO synthase inhibitor. L-NMMA was also used in increased endogenous NO production induced by combined stimulation with interferon-$\gamma$(INF-$\gamma$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), and lipopolysaccharide(LPS). NO generation from NO donor or from the endothelial cells was evaluated by measuring nitrite concentration. Result : $^{51}Cr$ release was $8.7{\pm}0.5%$ in GO 5 mU/ml, $14.4{\pm}2.9%$ in GO 10 mU/ml, $32.3{\pm}2.9%$ in GO 15 mU/ml, $55.5{\pm}0.3%$ in GO 20 mU/ml and $67.8{\pm}0.9%$ in GO 30 mU/ml ; it was significantly increased in GO 15 mU/ml or higher concentrations when compared with $9.6{\pm}0.7%$ in control(p < 0.05; n=6). L-NMMA(0.5 mM) did not affect the $^{51}Cr$ release by GO. Nitrite concentration was increased to $3.9{\pm}0.3\;{\mu}M$ in culture media of RLMVC treated with INF-$\gamma$ (500 U/ml), TNF-$\alpha$(150 U/ml) and LPS($1\;{\mu}g/ml$) for 24 hours ; it was significantly suppressed by the addition of L-NMMA. The presence of L-NMMA did not affect $^{51}Cr$ release induced by GO in RLMVC pretreated with INF-$\gamma$, TNF-$\alpha$ and LPS. The increase of $^{51}Cr$ release with GO(20 mU/ml) was prevented completely by adding 100 ${\mu}M$ SNAP. But the add of SNP, potassium ferrocyanate or potassium ferricyanate did not protect the oxidant injury. Nitrite accumulation was $23{\pm}1.0\;{\mu}M$ from 100 ${\mu}M$ SNAP at 4 hours in phenol red free Hanks' balanced salt solution. But nitrite was not detectable from SNP upto 1 mM The presence of SNAP did not affect the time dependent generation of hydrogen peroxide by GO in phenol red free Hanks' balanced salt solution. Conclusion : Hydrogen peroxide generated by GO causes oxidant injury in RLMVC. Exogenous NO from NO donor prevents oxidant injury, and the protective effect may be related to the ability to release NO. These results suggest that the exogenous NO may be protective on oxidant injury to the endothelium.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.140-152
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• 1998

Background: Prone position improves oxygenation in patients with ARDS probably by reducing shunt Reduction of shunt in prone position is thought to be effected by lowering of the critical opening pressure (COP) of the dorsal lung because the pleural pressure becomes less positive in prone position compared to supine position. It can then be assumed that prone position would bring about greater improvement in oxygenation when PEEP applied in supine position is just beneath COP than when PEEP is above COP. Hemodynamically, prone position is expected to attenuate the lifting of cardiac fossa induced by PEEP. Based on these backgrounds, we investigated whether the effect of prone position on oxygenation differs in magnitude according to the level of PEEP applied in supine position, and whether impaired cardiac output in supine position by PEEP can be restored in prone position. Methods: In seven mongrel dogs, $PaO_2/F_1O_2$(P/F) was measured in supine position and at prone position 30 min. Cardiac output (CO), stroke volume (SV), pulse rate (PR), and pulmonary artery occlusion pressure (PAOP) were measured in supine position, at prone position 5 min, and at prone position 30 min. After ARDS was established with warmed saline lavage(P/F ratio $134{\pm}72$ mm Hg), inflection point was measured by constant flow method($6.6{\pm}1.4cm$ $H_2O$), and the above variables were measured in supine and prone positions under the application of Low PEEP($5.0{\pm}1.2cm$ $H_2O$), and Optimal PEEP($9.0{\pm}1.2cm$ $H_2O$)(2 cm $H_2O$ below and above the inflection point, respectively) consecutively. Results : P/F ratio in supine position was $195{\pm}112$ mm Hg at Low PEEP and $466{\pm}63$ mm Hg at Optimal PEEP(p=0.003). Net increase of P/F ratio at prone position 30 min, however, was far greater at Low PEEP($205{\pm}90$ mm Hg) than at Optimal PEEP($33{\pm}33$ mm Hg)(p=0.009). Compared to CO in supine position at Optimal PEEP($2.4{\pm}0.5$ L/min), CO in prone improved to $3.4{\pm}0.6$ L/min at prone position 5 min (p=0.0180) and $3.6{\pm}0.7$ L/min at prone position 30 min (p=0.0180). Improvement in CO was attributable to the increase in SV: $14{\pm}2$ ml in supine position, $20{\pm}2$ ml at prone position 5 min (p=0.0180), and $21{\pm}2$ ml at prone position 30 min (p=0.0180), but not to change in PR or PAOP. When the dogs were turned to supine position again, MAP ($92{\pm}23$ mm Hg, p=0.009), CO ($2.4{\pm}0.5$ L/min, p=0.0277) and SV ($14{\pm}1$ ml, p=0.0277) were all decreased compared to prone position 30 min. Conclusion: Prone position in a dog with saline-lavaged acute lung injury appeared to augment the effect of relatively low PEEP on oxygenation, and also attenuate the adverse hemodynamic effect of relatively high PEEP. These findings suggest that a PEEP lower than Optimal PEEP can be adopted in prone position to achieve the goal of alveolar recruitment in ARDS avoiding the hemodynamic complications of a higher PEEP at the same time.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.987-996
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• 1996

Background : We prospectively evaluated the applicability and effect of noninvasive ventilation (NIV) in acute respiratory failure and tried to find out the parameters that could predict successful application of NIV. Methods : Twenty-six out of 106 patients with either acute ventilatory failure (VF: $PaCO_2$ > 43 mm Hg with pH < 7.35) or oxygenation failure (OF: $PaO_2/AO_2$ < 300 mm Hg with $pH{\geq}7.35$) requiring mechanical ventilation were managed by NIV (CPAP + pressure suppon, or BiPAP) with face mask. Eleven out of 19 cases with VF (57.9%) (M : F=7 : $55.4{\pm}14.6$ yrs) and 15 out of 87 cases with OF (17.2%) (M : F=12 : 3, $50.6{\pm}15.6$ yrs) were s uilable for NIY. Respiratory rates, arterial blood gases and success rate of NIV were analyzed in each group. Results: 81.8% (9/11) of YF and 40% (6/15) of OF were successfully managed on NIV and were weruled from mechanical ventilator without resorting to endotracheal intubation. Complications were noted in 2 cases (nasal skin necrosis 1, gaseous gastric distension 1). In NIV for ventilatory failure, the respiration rate was significantly decreased at 12 hour of NIV ($34{\pm}9$ /min pre-NIV, $26{\pm}6$ /min at 12 hour of NIV, p=0.045), while $PaCO_2$ ($87.3{\pm}20.6$ mm Hg pre-NIV, $81.2{\pm}9.1$ mm Hg at 24 hour of NIV) and pH ($7.26{\pm}0.04$, $7.32{\pm}0.02$, respectively, p <0.05) were both significantly decreased at 24 hour of NIV In NIV for oxygenation failure, $PaCO_2$ were not different between the successful and the failed cases at pre-NIV and till 12 hours after NIV. The $PaO_2/FIO_2$ ratio, however, significantly improved at 0.5 hour of NIV in successful cases and were maintained at around 200 mm Hg (n=6 : at baseline, 0.5h, 6h, 12h : $120.0{\pm}19.6$, $218.9{\pm}98.3$, $191.3{\pm}55.2$, $232.8{\pm}17.6$ mm Hg, respectively, p=0.0211), but it did not rise in the failed cases (n=9 : $127.9{\pm}63.0$, $116.8{\pm}24.4$, $100.6{\pm}34.6$, $129.8{\pm}50.3$ mm Hg, respectively, p=0.5319). Conclusion : From the above results we conclude that NIV is effective for hypercapnic respiratory failure and its success was heralded by reduction of respiration rale before the reduction in $PaCO_2$ level. In hypoxic respiratory failure, NIV is much less effective, and the immediate improvement of $PaO_2/FIO_2$ ratio at 0.5h after application is thought to be a predictor of successful NIV.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.535-547
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• 1995

Background: Intensive care units(ICUs) probably represent the single largest identifiable source of infection within the hospital. Although there are several studies on ICU infections in respect to their bacteriology or mortality rate for individual types of ICU, few studies have compared ICU infections between different types of ICU. The aim of this study was to identify clinical differences in bacteremia between medical ICU(MICU) and surgical ICU(SICU) patients. Methods: 256 patients with bacteremia were retrospectively evaluated. Medical records were reviewed to obtain the clinical and bacteriologic informations. Results: 1) The mean age of the patients with bacteremia of MICU($58.6{\pm}17.2\;yr$) was greater than that of all MICU patients($54.3{\pm}17.1\;yr$)(p<0.01), but there was no significant difference in SICU patients(patients with bacteremia of SICU: $56.3{\pm}18.6\;yr$, all SICU patients: $62.0{\pm}16.8$)(p>0.05). ICU stay was longer(MICU patients: $23.4{\pm}40.8$ day, SICU patients: $30.3{\pm}26.8$ day) than the mean stay of all patients($6.8{\pm}15.5$ day)(p<0.05, respectively). Bacteremia of both ICU patients developed past the average day of ICU stay(all MICU patients: 7.9 day, all SICU patients: 6.0 day, MICU bacteremia: 19th day, SICU bacteremia: 17th day of ICU stay)(p<0.05, respectively). 2) There were no significant differences in mean age, sex, and length of stay of both ICU patients with bacteremia. 3) Use of antibiotics or steroid, use of percutaneous devices and invasive procedures before development of bacteremia were more frequent in SICU patients than in MICU patients(prior antibiotics use: MICU 45%, SICU 63%, p<0.05; steroid use: MICU 14%, SICU 36%, p<0.01; use of percutaneous devices: MICU 19%, SICU 39%, p<0.01; invasive procedures: MICU 19%, SICU 61 %, p<0.01). 4) The prevalence of community acquired infections was significantly higher in MICU patients than in SICU patients(MICU 42%, SICU 9%)(p<0.01), whereas SICU patients showed higher prevalence of ICU-acquired infection than MICU patients(MICU 48%, SICU 78%)(p<0.01). 5) There were no differences in causative organisms, primary sites of infection and time interval to bacteremia between both ICUs. 6) There were no significant differences in outcome according to pathogenic organisms or primary sites of infection. 7) The mortality rate was higher in patients with bacteremia than without bacteremia(MICU mortality rate: patients with bacteremia 72.5%, patients without bacteremia 36.0%, p<0.01; SICU mortality rate: patients with bacteremia 40.3%, patients without bacteremia 8.5%, p<0.05), and the mortality rate of MICU bacteremia was significantly higher compared with that of SICU bacteremia(MICU 72.5%, SICU 40.3%)(p<0.01). Conclusion: ICU patients with bacteremia stayed longer before the development of bacteremia, and showed higher mortality than the overall ICU population. The incidence of bacteremia was higher in MICU patients than SICU patients. MICU patients with bacteremia showed higher prevalence of liver diseases and acute respiratory failure, community-acquired bacteremia and greater mortality rate than SICU patients with bacteremia. SICU patients with bacteremia, on the other hand, showed higher prevalence of trauma, prior use of immunosuppressive agents, invasive procedures, and ICU-acquired bacteremia, and lower mortality rate than MICU patients with bacteremia.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.555-568
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• 1995

Background: It is most physiologic to measure the diffusing capacity of the lung by using oxygen, but it is so difficult to measure partial pressure of oxygen in the capillary blood of the lung that in clinical practice it is measured by using carbon monoxide, and single-breath diffusing capacity method is used most widely. However, since the process of withholding the breath for 10 seconds after inspiration to the total lung capacity is very hard to practice for patients who suffer from cough, dyspnea, etc, the intra-breath lung diffusing capacity method which requires a single exhalation of low-flow rate without such process was devised. In this study, we want to know whether or not there is any significant difference in the diffusing capacity of the lung measured by the single-breath and intra-breath methods, and if any, which factors have any influence. Methods: We chose randomly 73 persons without regarding specific disease, and after conducting 3 times the flow-volume curve test, we selected forced vital capacity(FVC), percent of predicted forced vital capacity, forced expiratory volume within 1 second($FEV_1$), percent of forced expiratory volume within 1 second, the ratio of forced expiratory volume within 1 second against forced vital capacity($FEV_1$/FVC) in test which the sum of FVC and $FEV_1$ is biggest. We measured the diffusing capacity of the lung 3 times in each of the single-breath and intra-breath methods at intervals of 5 minutes, and we evaluated which factors have any influence on the difference of the diffusing capacity of the lung between two methods[the mean values(ml/min/mmHg) of difference between two diffusing capacity measured by two methods] by means of the linear regression method, and obtained the following results: Results: 1) Intra-test reproducibility in the single-breath and intra-breath methods was excellent. 2) There was in general a good correlation between the diffusing capacity of the lung measured by a single-breath method and that measured by the intra-breath method, but there was a significant difference between values measured by both methods($1.01{\pm}0.35ml/min/mmHg$, p<0.01) 3) The difference between the diffusing capacity of the lung measured by both methods was not correlated to FVC, but was correlated to $FEV_1$, percent of $FEV_1$, $FEV_1$/FVC and the gradient of methane concentration which is an indicator of distribution of ventilation, and it was found as a result of the multiple regression test, that the effect of $FEV_1$/FVC was most strong(r=-0.4725, p<0.01) 4) In a graphic view of the difference of diffusing capacity measured by single-breath and intra-breath method and $FEV_1$/FVC, it was found that the former was divided into two groups in section where $FEV_1$/FVC is 50~60%, and that there was no significant difference between two methods in the section where $FEV_1$/FVC is equal or more than 60% ($0.05{\pm}0.24ml/min/mmHg$, p>0.1), but there was significant difference in the section, less than 60%($-4.5{\pm}0.34ml/min/mmHg$, p<0.01). 5. The diffusing capacity of the lung measured by the single-breath and intra-breath method was the same in value($24.3{\pm}0.68ml/min/mmHg$) within the normal range(2%/L) of the methane gas gradient, and there was no difference depending on the measuring method, but if the methane concentration gradients exceed 2%/L, the diffusing capacity of the lung measured by single-breath method became $15.0{\pm}0.44ml/min/mmHg$, and that measured by intra-breath method, $11.9{\pm}0.51ml/min/mmHg$, and there was a significant difference between them(p<0.01). Conclusion: Therefore, in case where $FEV_1$/FVC was less than 60%, the diffusing capacity of the lung measured by intra-breath method represented significantly lower value than that by single-breath method, and it was presumed to be caused largely by a defect of ventilation-distribution, but the possibility could not be excluded that the diffusing capacity of the lung might be overestimated in the single-breath method, or the actual reduction of the diffusing capacity of the lung appeared more sensitively in the intra-breath method.