• Tuberculosis and Respiratory Diseases
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• v.41 no.5
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• pp.452-461
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• 1994

Background: Tumor necrosis factor(TNF)-$\alpha$ and Interleukin(lL)-$1{\beta}$ are thought to play a major role in the pathogenesis of the septic syndrome, which is frequently associated with adult respiratory distress syndrome(ARDS). In spite of many reports for the role of TNF-$\alpha$ in the pathogenesis of ARDS, including human studies, it has been reported that TNF-$\alpha$ is not sensitive and specific marker for impending ARDS. But there is a possibility that the results were affected by the diversity of pathogenetic mechanisms leading to the ARDS because of various underlying disorders of the study group in the previous reports. The purpose of the present study was to evaluate the roles of TNF-$\alpha$ and IL-$1{\beta}$ as a predictable marker for development of ARDS in the patients with septic syndrome, in which the pathogenesis is believed to be mainly cytokine-mediated. Methods: Thirty-six patients of the septic syndrome hospitalized in the intensive care units of the Asan Medical Center were studied. Sixteens suffered from ARDS, whereas the remaining 20 were at the risk of developing ARDS(acute hypoxemic respiratory failure, AHRF). In all patients venous blood samples were collected in heparin-coated tubes at the time of enrollment, at 24 and 72 h thereafter. TNF-$\alpha$ and IL-$1{\beta}$ was measured by an enzyme-linked immunosorbent assay (ELISA). All data are expressed as median with interquartile range. Results: 1) Plama TNF-$\alpha$ levels: Plasma TNF-$\beta$ levels were less than 10pg/mL, which is lowest detection value of the kit used in this study within the range of the $mean{\pm}2SD$, in all of the normal controls, 8 of 16 subjects of ARDS and in 8 in 20 subjects of AHRF. Plasma TNF-$\alpha$ levels from patients with ARDS were 10.26pg/mL(median; <10-16.99pg/mL, interquartile range) and not different from those of patients at AHRF(10.82, <10-20.38pg/mL). There was also no significant difference between pre-ARDS(<10, <10-15.32pg/mL) and ARDS(<10, <10-10.22pg/mL). TNF-$\alpha$ levels were significantly greater in the patients with shock than the patients without shock(12.53pg/mL vs. <10pg/mL) (p<0.01). There was no statistical significance between survivors(<10, <10-12.92pg/mL) and nonsurvivors(11.80, <10-20.8pg/mL) (P=0.28) in the plasma TNF-$\alpha$ levels. 2) Plasma IL-$1{\beta}$ levels: Plasma IL-$1{\beta}$ levels were less than 0.3ng/mL, which is the lowest detection value of the kit used in this study, in one of each patients group. There was no significant difference in IL-$1{\beta}$ levels of the ARDS(2.22, 1.37-8.01ng/mL) and of the AHRF(2.13, 0.83-5.29ng/mL). There was also no significant difference between pre-ARDS(2.53, <0.3-8.34ngfmL) and ARDS(5.35, 0.66-11.51ng/mL), and between patients with septic shock and patients without shock (2.51, 1.28-8.34 vs 1.46, 0.15-2.13ng/mL). Plasma IL-$1{\beta}$ levels were significantly different between survivors(1.37, 0.4-2.36ng/mL) and nonsurvivors(2.84, 1.46-8.34ng/mL). Conclusion: Plasma TNF-$\alpha$ and IL-$1{\beta}$ level are not a predictable marker for development of ARDS. But TNF-$\alpha$ is a marker for shock in septic syndrome. These result could not exclude a possibility of pathophysiologic roles of TNF-$\alpha$ and IL-$1{\beta}$ in acute lung injury because these cytokine could be locally produced and exert its effects within the lungs.

• Tuberculosis and Respiratory Diseases
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• v.73 no.1
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• pp.1-10
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• 2012

Care of patients with sepsis has improved over the last decade. However, in the recent two years, there was no significant progress in the development of a new drug for critically ill patients. In January 2011, it was announced that the worldwide phase 3 randomized trial of a novel anti-Toll-like receptor-4 compound, eritoran tetrasodium, had failed to demonstrate an improvement in the mortality of patients with severe sepsis. In October 2011, Xigris (drotrecogin alfa, a recombinant activated protein C) was withdrawn from the market following the failure of its worldwide trial that had attempted to demonstrate improved outcome. These announcements were disappointing. The recent failure of 2 promising drugs to further reduce mortality suggests that new approaches are needed. A study was published showing that sepsis can be associated to a state of immunosuppression and loss of immune function in human. However, the timing, incidence, and nature of the immunosuppression remain poorly characterized, especially in humans. This emphasizes the need for a better understanding of sepsis as well as new therapeutic strategies. Many clinical experiences of the extracorporeal membrane oxygenator (ECMO) treatment for adult acute respiratory distress syndrome (ARDS) patients, which is caused by the H1N1 influenza A virus, were reported. The use of ECMO in severe respiratory failure, particularly in the treatment of adult ARDS, is occurring more commonly.

• Journal of Trauma and Injury
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• v.28 no.1
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• pp.34-38
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• 2015

The case of a patient with a transfusion-related acute lung injury (TRALI) to whom extracorporeal membrane oxygenation (ECMO) had been applied is reported. A 55-year-old male injured with liver laceration (grade 3) without chest injury after car accident. He received lots of blood transfusion and underwent damage control abdominal surgery. In the immediate postoperative period, he suffered from severe hypoxia and respiratory acidosis despite of vigorous management such as 100% oxygen with mechanical ventilation, high PEEP and muscle relaxant. Finally, ECMO was applied to the patients as a last resort. Aggressive treatment with ECMO improved the oxygenation and reduced the acidosis. Unfortunately, the patient died of liver failure and infection. TRALI is a part of acute respiratory distress syndrome (ARDS). The use of ECMO for TRALI induced severe hypoxemia might be a useful option for providing time to allow the injured lung to recover.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.1
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• pp.65-70
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• 1997

In order to investigate the effect of ANP on surfactant secretion from alveolar type II cell(AT II cell) during circulatory derangement in adult respiratory distress syndrome (ARDS), the secretion of surfactant from AT II cells was evaluated in purely isolated AT II cultures from rat lungs. For the simulation of sympathetic stimulation during circulatory derangement, primary AT II cultures were incubatedwith isoproterenol and IBMX. In this isoproterenol stimulated AT II cells, ANP were added in the media for the investigation of effect of ANP on surfactant secretion from AT II cells. For the evaluation of surfactant secretion, $[^3H]-methylcholine$ was incorporated and the level of radiolabelled choline chloride secreted from the cells was determined. As previously reported, isoproterenol and IBMX stimulated surfactant secretion from AT II cells. Isoproterenol showed synergistic increase of surfactant secretion with IBMX in AT II cells. In isoproterenol stimulated AT II cells, physiological level of ANP inhibited the secretion of surfactant in primary cultures of AT II cells. On the basis of these experimental it is suggested that, in association with ciculatory change during ARDS, increased secretion of ANP by the pulmonary edema, hypoxia and congestive heart heart failure might aggravate the symptoms of ARDS by reduction of surfactant secretion from AT II cells.

• Tuberculosis and Respiratory Diseases
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• v.38 no.1
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• pp.70-73
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• 1991

We have experienced a case of lung injury caused by accidental inhalation of ammonia gas in a 34 year-old-man. By the explosion of ammonia tank in a refrigerator boat he inhaled ammonia gas. Several minutes later, he suffered from severe dyspnea and visual loss. On arrival at emergency room, analysis of arterial blood gas revealed severe hypoxemia and his chest film showed bilateral pulmonary infiltrates. Under the impression of adult respiratory distress syndrome, mechanical ventilator was applied to the patient. After recovery from ARDS and tracheal edema, he complained of some hemoptysis and productive sputum during the admission. So we checked bronchoscopy and bronchograpy which showed tracheal bullae just above carina and tubular bronchiectatic change in the right lower lobe. We report a case of lung injuries-ARDS, tracheal bullae, and bronchiectasis-caused by inhalation of ammonia gas with the review of the relevant literatures.

• The Korean Journal of Nuclear Medicine
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• v.18 no.1
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• pp.45-53
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• 1984

The purpose of this study is to observe the changes of pulmonary capillary permeability and various hemodynamic parameters before and after Positive End-Expiratory Pressure(PEEP) in Adult Respiratory Distress Syndrome (ARDS). Using a canine oleic acid induced ARDS model, we measured the pulmonary capillary permeability with a slope of lung: heart radioactivity ratio, hemodynamic parameters with Swan-Ganz catheter and blood gas tensions. 1) In normal and ARDS dogs, the PEEP didn't significantly influence the slope of lung: heart radioactivity ratio. But in ARDS group the slope index was increased compaired with that of control group (p<0.05). 2) Also in ARDS group, $PaO_2$ was significantly decreased, and $PaCO_2,\;PvCO_2$, MPAP, $AaDO_2$, Qs/Qt were significantly increased compared with those of control group (p<0.05). 3) In normal dogs, the PEEP didn't influence blood pH or gas tension, $AaDO_2$, Qs/Qt, or hemodynamics. 4) In ARDS dogs, however, the PEEP significantly increased $PaO_2$ and decreased $AaDO_2$, Qs/Qt (p<0.05).

• Tuberculosis and Respiratory Diseases
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• v.52 no.1
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• pp.62-69
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• 2002

Acute interstitial pneumonia (AIP) is a rare fulminant form of lung injury that presents acutely; usually in a previously healthy individual. It corresponds to a subset of cases of idiopathic adult respiratory distress syndrome (ARDS). Invasive pulmonary aspergillosis is a disease occuring predominantly with defects in immunity such as hematologic malignancy, influenza infection, postchemotherapy, long-term corticosteroid treatment. Invasive aspergillosis has worse prognosis and most cases are diagnosed at postmortem autopsies. We experienced a case of acute interstitial pneumonia with an invasive aspergillosis during corticosteroid treatment. Acute interstitial pneumonia with invasive aspergillosis was diagnosed by an open lung biopsy using thoracoscopy, showing fungal hyphae with sepsis and an acute angle branching invasion of the lung tissue and blood vessels. The patient was treated with IV amphotericin-B, but died due to septic shock.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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• pp.479-491
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• 1998

In order to know the pathogenesis of adult respiratory distress syndrome (ARDS) in association with the oxidative stress by neutrophils, the role of platelet activating factor (1-0-alkyl-2-acetyl-snglycero-3-phosphocholine, PAF) was investigated during acute lung injury induced by interleukin- $1{\alpha}$ (IL-1) in rats. An insufflation of IL-1 into the rat's trachea increased the acetyltransferase activity in the lung and the increase of PAF content was followed. As evidences of acute lung injury by neutrophilic respiratory burst, lung leak index, myeloperoxidase activity, numbers of neutrophils in the bronchoalveolar lavage fluid, neutrophilic adhesions to endothelial cells and NBT positive neutrophils were increased after IL-1 treatment. In addition, a direct instillation of PAF into the trachea caused acute lung leak and the experimental results showed a similar pattern in comparison with IL-1 induced acute lung injury. For the confirmation of oxidative stress during acute lung leak by IL-1 and PAF, a histochemical electron microscopy was performed. In IL-1 and PAF treated lungs of rats, the deposits of cerrous perhydroxide were found. To elucidate the role of PAF, an intravenous injection of PAF receptor antagonist, WEB 2086 was given immediately after IL-1 or PAF treatment. WEB 2086 decreased the production of hydrogen peroxide and the acute lung leak. In ultrastructural study, WEB 2086 mitigated the pathological changes induced by IL-1 or PAF. The nuclear factor kappa B (NFkB) was activated by PAF and this activation was inhibited by WEB 2086 almost completely. Based on these experimental results, it is suggested that the PAF produced in response to IL-1 through the remodeling pathway has the major role for acute lung injury by neutrophilic respiratory burst. In an additional experiment, we can also come to conclude that the activation of the NFkB by PAF is thought to be the fundamental mechanism to initiate the oxidative stress by neutrophils causing release of proinflammatory cytokines and activation of phospholipase $A_2$.

• Tuberculosis and Respiratory Diseases
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• v.40 no.1
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• pp.6-15
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• 1993

Background: Positive end, expiratory pressure (PEEP) has become one of the standard therapies for adult respiratory distress syndrome (ARDS). Total static compliance has been proposed as a guide to determine the size of PEEP ('best PEEP') which is of unproven clinical benefit and remains controversial. Besides increasing functional residual capacity and thus improving oxygenation, PEEP stimulate prostacyclin secretion and was proposed for the treatment of acute pulmonary embolism. But little is known about the effect of PEEP on hemodynamic and gas exchange disturbances in acute pulmonary embolism. Methods: To study the validity of total static compliance as a predictor of 'best PEEP' in ARDS and acute pulmonary embolism, experimental ARDS was induced in mongrel dog with oleic acid and acute pulmonary embolism with autologous blood clot. Then hemodynamic and gas exchange parameters were measured with serial increment of PEEP. Results:In ARDS group, total static compliance and oxygen transport were maximal at 5 cm$H_2O$, and decreased thereafter (p<0.05). With increment of PEEP, arterial oxygen tension ($PaO_2$) and arterial carbon dioxide tension ($PaCO_2$) increased and cardiac output and physiological shunt decreased. In pulmonary embolism group, total static compliance, oxygen transport, physiological shunt and cardiac output decreased and $PaO_2$ and $PaCO_2$ increased with increment of PEEP (p<0.05). Comparing the change induced by increment of PEEP by 1 cm$H_2O$ in ARDS group with that in pulmonary embolism group, there was no significant difference between two groups except cardiac output which decreased more in pulmonary embolism group (p<0.05). In ARDS group, oxygen transport and total static compliance increased after PEEP application, and total static compliance was maximal at the PEEP level where oxygen transport was maximal. However in pulmonary embolism group, oxygen transport and total static compliance decreased after application of PEEP. There was significant correlation between change of total static compliance and change of oxygen transport in both groups. Conclusion: In both ARDS and acute pulmonary embolism, it can be concluded that total static compliance is useful as a predictor of 'best PEEP'.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.319-327
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• 1994

Background: The pathogenetic mechanism of adult respiratory distress syndrome(ARDS) is not clearly defined yet, but it is well known that increased pulmonary capillary permeabilty is characteristic feature of ARDS. The increased alveolar-capillary permeability is usually preceded by damage of pulmonary artery endothelial cells. The released enzymes and oxygen free radicals from the activated neutrophils seem to play a predominant role in endothelial cell cytotoxicity. The activated neutrophils, however, probably are not the sole contributing factor in this type of damage because many cases of ARDS have been reported in severe neutropenia. Bacterial endotoxin perse and/or oxygen free radicals released from endothelial cells are suggested to be possible factors that contribute to the development of ARDS. The purpose of this study is to investigate the direct cytotoxicity of endotoxin and the role of oxygen free radicals released from the endothelial cells in endotoxin-induced endothelial cell cytotoxicity. Methods: First, to investigate whether endotoxin is cytotoxic to HUVE by itself, various doses of endotoxin were added to culture medium and cytotoxicity was measured. Second, to evaluate the possible role of oxygen free radical in endotoxin-induced HUVE cytotoxicity, various antioxidants were added on the endotoxin-induced HUVE cytotoxicity and cytotoxicity was measured. Third, to verify the release of oxygen free radicals from HUVE, the concentrations of hydrogen peroxide in the endotoxin-treated culture supernatant were measured. Finally, to observe the cytotoxic effect of hydrogen peroxide, HUVE cytotoxicity in the presence of various doses of hydrogen peroxide was measured. The fourth generations of subcultured HUVE from primary culture were used. The cell cytotoxicity was quantified by the chromium-51 release assay. Results: 1) Endotoxin alone showed HUVE cytotoxicity in a dose-dependent fashion. 2) Endotoxin-induced HUVE cytotoxicity was significantly attenuated by the pretreatment of catalase and DMTU. 3) Hydrogen peroxide was released from HUVE after endotoxin treatment in a dose-dependent fashion. 4) Exogenous hydrogen peroxide also showed HUVE cytotoxicity in a dose-dependent fashion. Conclusion: These results suggest that endotoxin alone can directly injure HUVE, and, oxygen-free radicals released from HUVE in response to endotoxin may also participate in the endotoxin-induced HUVE cytotoxicity.