• Journal of Chest Surgery
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• v.42 no.1
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• pp.1-8
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• 2009

Background: The pathophysiology of acute respiratory distress syndrome with sepsis is acute lung injury (ALI) that's' caused by endotoxin (LPS). We evaluate effects of moxifloxacin on LPS-induced ALI in a rat model. Material and Method: The rats were divided into 3 groups as the control group (C), the LPS insult group (L), and the LPS+moxifloxacin treated group (L-M). ALI was induced by endotracheal instillation of E.coli LPS, then moxifloxacin was given in 30 minutes. Five hours later, we checked the lung weight/body weight ratio(the L/BW ratio), the protein & neutrophils in the bronchoalveolar lavage fluid (BALF), the myeloperoxidase (MPO) activity & the malondialdehyde (MDA) content, the expressions of cytosolic and secretory phospholipase $A_2$ (c, $sPLA_2$), and the morphology of the lung with using a light microscope. Result: The L/BW ratio, the protein content and the neutrophil count in the BALF, and the MPO activity and the MDA content in lung were significantly increased in group L compared to group C, and these factors were markedly decreased in group L-M compare to group L. The $cPLA_2$ expression and the $sPLA_2$ expression were increased in group L and the $cPLA_2$ expression was decreased in group L-M. Yet the $sPLA_2$ expression was not changed in group L-M. Morphologically, many inflammatory findings were observed in group L, but not in group L-M. Conclusion: Many of the inflammatory changes of ALI that were caused by LPS insult were ameliorated by moxifloxacin treatment.

• Tuberculosis and Respiratory Diseases
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• v.52 no.3
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• pp.251-259
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• 2002

Background : Reduced lung compliance and increased lung resistance are the primary lung mechanical abnormalities in acute respiratory distress syndrome (ARDS). Although there is little information regarding the mechanisms responsible for the increases in the respiratory resistance of ARDS, bronchodilators have been frequently administered in mechanically ventilated ARDS patients. To determine the effect of a bronchodilator on the respiratory mechanics depending on the level of applied positive end-expiratory pressure (PEEP), the changes in the respiratory mechanics by salbutamol inhalation was measured under the variable PEEP level in patients with ARDS. Materials and Methods : Fifteen mechanically ventilated paralyzed ARDS patients (14 of male, mean age 57 years) were enrolled in this study. The respiratory system compliance, and the maximum and minimum inspiratory resistance were obtained by the end-inspiratory occlusion method during constant flow inflation using the CP-100 pulmonary monitor (Bicore, Irvine, CA, USA). The measurements were performed at randomly applied 8, 10 and 12 cm $H_2O$ PEEP before and 30 mins after administrating salbutamol using a meter-dose-inhaler (100ug${\times}$6). Results : 1) The maximum inspiratory resistance of the lung was higher than the reported normal values due to an increase in the minimal inspiratory resistance & additional resistance. 2) The maximum inspiratory resistance and peak airway pressure were significantly higher at 12cm $H_2O$ of PEEP compared with those at 10cm $H_2O$ of PEEP. 3) Salbutamol induced a significant decrease in the maximum and the minimum inspiratory resistance but no significant change in the additional resistance only was observed at 12cm $H_2O$ of PEEP(from $15.66{\pm}1.99$ to $13.54{\pm}2.41$, from $10.24{\pm}2.98$ to $8.04{\pm}2.34$, and from $5.42{\pm}3.41$ to $5.50{\pm}3.58cm$ $H_2O$/L/sec, respectively). 4)The lung compliance did not change at the applied PEEP and salbutamol inhalation levels. Conclusion : The bronchodilator response would be different depending on the level of applied PEEP despite the increased respiratory resistance in patients with ARDS.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.379-390
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• 1997

Background : It has long been suggested that neutrophils and their products are implicated as the central mediators of the acute lung injuries. Contrary to the dominant role of neutrophils in ARDS, many cases of ARDS has occurred in the setting of severe neutropenia without pulmonary neutrophil infiltration. Therefore it is certain that effector cell(s) other than neutrophil play an important role in the pathogenesis of ARDS. This experiment was performed to define the mechanism of ARDS in the setting of neutropenia, 1) by comparing the severity of endotoxin-induced lung injury, 2) by measurement of hydrogen peroxide production and cytokine concentration in the bronchoalveolar lavage cells and fluids obtained from different rats with and without cyclophosphamide-pretreatment. Method : The male Sprague-Dawleys were divided into the normal control (NC)-, endotoxin (ETX)-, and cyclophosphamide (CPA)-group in which neutropenia was induced by injecting cyclophosphamide intraperitoneally. Acute lung injury was evoked by injecting lipopolysaccharide (LPS) into a tail vein. The bronchoalveolar lavage (BAL) was performed at 3 and 6 hour after administration of LPS to measure the change of cell counts and concentrations of protein and cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Hydrogen peroxide (HPO) production from BAL cells was measured at 6 hour after LPS administration by phenol red microassay with and without zymosan stimulation. Results : The results were as follows. A change of leukocyte counts in the peripheral blood after treatment with CPA : More than 95% of total leukocytes and neutrophils were reduced after CPA administration, resulting in severe neutropenia. A change of BAL cells : In the ETX-group, the number of total cells (p < 0.01) and of macrophage and neutrophil (p < 0.05) were increased at 3 and 6 hour after LPS administration compared to those of NC-group. In the CPA-group, the number of total leukocyte and macrophage were not changed after LPS administration, but neutrophil counts were significantly reduced and it took part in less than 0.1% of total BAL cells (p < 0.01 vs NC-group). BAL cells in this group were almost all macrophages (99.7%). A change of protein concentration in the BALF : In the ETX-group, protein concentration was increased at 3 hour and was more increased at 6 hour after LPS administration (p < 0.05 and < 0.01 vs NC-group, respectively). In the CPA-group, it was also significantly elevated at 3 hour after LPS administration (p < 0.05 vs NC-group), but the value was statistically not different from that of ETX-group. The value measured at 6 hour after LPS administration in the CPA-group became lower than that of ETX-group (p < 0.05), but showed still a higher value compared to that of NC-group (p < 0.05). A change of cytokine concentration in the BALF : TNF -alpha and IL-6 were elevated in the ETX - and CPA-group compared to those of NC-group at both time intervals. There was no statistical difference in the values of both cytokines between the ETX- and CPA-groups. Measurement of hydrogen peroxide production from BAL cells : There was no intergroup difference of HPO production from resting cells. HPO production after incubation with opsonized zymosan was significantly elevated in all groups. The percent increment of HPO production was highest in the ETX-group (89.0%, p < 0.0008 vs NC-group), and was 42.85 in the CPA-group (p = 0.003 vs NC-group ). Conclusion : Acute lung injury in the setting of neutropenia might be caused by functional activation of resident alveolar macrophages.

• Childhood Kidney Diseases
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• v.3 no.2
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• pp.123-129
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• 1999

Purpose: Acute poststreptococcal glomerulonephritis(APSGN) is a renal disease which is characterized by glomerular proliferation and inflammatory changes due to immune reaction. Although the 95% of patients with APSGN seems to recover fully and present as benign course, the remaining patients show poor prognosis. Therefore comparative retrograde study between APSGN with and without nephrotic syndrome was done to find out the any prognostic indicator to predict the outcome in patients with APSGN. Methods: We had retrospectively analyzed seventy-one patients who were diagnosed as APSGN clinically from Mar.1989 to Feb.1999 in Yonsei university medical center. Sixty-four of the patients was APSGN without nephrotic syndrome(Group A) and seven patients were in APSGN with nephrotic syndrome(Group B). Results: Patients who were diagnosed as APSGN with nephrotic syndrome were seven(9.9%) out of seventy-one. In the comparative study, sex ratio was 1:1 in group A and 1.9: 1 in group B, onset mean age was $8.9{\pm}2.6$ in group A and $8.8{\pm}2.6$ in group B. Following clinical profiles were compared but there were no significant difference between these two groups: WBC count($9413{\pm}2964\;vs\;9368{\pm}2650(/mm^3)$), hemoglobin($10.6{\pm}1.2\;vs\;10.0{\pm}0.9(gm/dL)$), ASO($746.1{\pm}640.7\;vs\;614.9{\pm}475.9(IU/ml)$), $C_3(20.1{\pm}17.0\;vs\;16.9{\pm}13.1(mg/dL)$), $C_4(22.8{\pm}9.5\;vs\;22.6{\pm}6.9(mg/dL)$), BUN($25.8{\pm}26.1\;vs\;28.1{\pm}14.5(mg/dL)$), creatinin($0.8{\pm}0.3\;vs\;0.8{\pm}0.3(mg/dL)$), $C_{cr}(80.6{\pm}28.8{\pm}62.4{\pm}31.4(ml/min/1.73\;m^2$)), the duration of edma, gross hematuria, and hypertension. However, we found that there were a significant difference in the duration of proteinuria($1.95{\pm}2.27\;vs\;13.3{\pm}21.1(months)$)(P<0.05), decreased $C_3$ duration($1.9{\pm}2.9\;vs\;7.3{\pm}5.0(weeks)$)(P<0.05) and especially it was proloned according to the amount of early urine protein excretion. Conclusion: Our study showed markedly prolonged duration of proteinuria and decreased $C_3$ duration in patients with APSGN with nephrotic syndrome. We were not able to find the definite prognostic factor that will guide the outcome of patients with APSGN accompaning nephrotic syndrome, but above findings seemed to represent as a relative indication of the outcome of the disease. All patients recovered completely and we did not experience any cases that progressed into the renal failure.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.529-538
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• 2002

Background : Many clinicians are reluctant to prescribe systemic corticosteroids to manage an asthmatic attack because of many complications such as osteoporosis, cushing's syndrome, diabetes, hypertension and bleeding tendency. The use of nebulized budesonide may be of value in some infants, old men, and in particular adult asthmatic patients who complain of severe dyspnea. A clinical validation and steroid-sparing effect of nebulized budesonide in asthmatic adults and COPD were evaluated, and the short-term effects of budesonide use on the HPA axis were assessed. Materials and Methods : Study A was prospectively done with 41 patients diagnosed with pure asthma and 30 patients diagnosed with COPD (including asthmatic component) in Soonchunhyang Hospital, Chunan from June. 2000 to Sep. 2001. They were treated with nebulized budesonide including systemic steroids (Group 1), a budesonide tubuhaler including a systemic steroid (Group 2), or only the systemic steroid(Group 3). The peak flow rate, arterial blood gas in room air, pulmonary function test, symptom scoring, steroid amount and hospital stay were analyzed. Study B was conducted with 19 patients to evaluate the short-term effects on the HPA axis of treatment with nebulized budesonide 1mg twice daily and a budesonide turbuhaler 5 puffs twice daily. The adrenal function was assessed prior to budesonide inhalation and after 7 days of budesonide inhalation. Results : In the pure asthmatic patients, the mean value of the symptoms (dyspnea, wheezing, cough, night asthma) or the arterial BGAs, total amounts of steroid or hospital stay and the difference in the results of the pulmonary function tests or peak expiratory flow rate were similar in the three groups. In COPD with an asthmatic component, there were no significant differences among the three groups. Although nebulized budesonide suppressed HPA function,(p=0.006) the HPA responses from the nebulized budesonide and turbuhaler budesonide were similar (p=0.288) Conclusion : This result suggests that systemic steroid should only be made available for acute asthmatic patients irrespective of the inhaled budesonides. Nebulized budesonide at the therapeutic dose has similar effects on the HPA axis compared to that of turbuhaler budesonide.

• Tuberculosis and Respiratory Diseases
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• v.60 no.4
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• pp.437-450
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• 2006

Background : Acute respiratory distress syndrome (ARDS) is characterized by severe inflammatory pulmonary edema of unknown pathogenesis. To investigate the pathogenesis of ARDS associated with neutrophilic oxidative stress, the role of phospholipase $A_2$ ($PLA_2$) was evaluated by the inhibition of calcium channel. Methods : In Sprague-Dawley rats, acute lung injury (ALI) was induced by the instillation of E.coli endotoxin (ETX) into the trachea. At the same time, diltiazem was given 60 min prior to tracheal instillation of ETX. Parameters of ALI such as lung and neutrophil $PLA_2$, lung myeloperoxidase (MPO), BAL neutrophils, protein, surfactant were measured. Production of free radicals from neutrophils was measured also. Morphological studies with light microscope and electron microscope were carried out and electron microscopic cytochemistry for detection of free radicals was performed also. Results : Diltiazem had decreased the ALI parameters effectively in ETX given rats and decreased the production of free radicals from neutrophils and lung tissues. Morphological studies denoted the protective effects of diltiazem. Conclusion : Diltiazem, a calcium channel blocker, was effective in amelioration of ALI by the suppression of neutrophilic oxidative stress mediated by $PLA_2$ activation.

• Pediatric Infection and Vaccine
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• v.29 no.2
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• pp.70-76
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• 2022

Coronavirus disease 2019 (COVID-19) in patients with underlying diseases, is associated with high infection and mortality rates, which may result in acute respiratory distress syndrome and death. Mucopolysaccharidosis (MPS) type II is a progressive metabolic disorder that stems from cellular accumulation of the glycosaminoglycans, heparan, and dermatan sulfate. Upper and lower airway obstruction and restrictive pulmonary diseases are common complaints of patients with MPS, and respiratory infections of bacterial or viral origin could result in fatal outcomes. We report a case of COVID-19 in a 16-year-old adolescent with MPS type II, who had been treated with idursulfase since 5 years of age. Prior to infection, the patient's clinical history included developmental delays, abdominal distension, snoring, and facial dysmorphism. His primary complaints at the time of admission included rhinorrhea, cough, and sputum without fever or increased oxygen demand. His heart rate, respiratory rate, and oxygen saturation were within the normal biological reference intervals, and chest radiography revealed no signs of pneumonia. Consequently, supportive therapy and quarantine were recommended. The patient experienced an uneventful course of COVID-19 despite underlying MPS type II, which may be the result of an unfavorable host cell environment and changes in expression patterns of proteins involved in interactions with viral proteins. Moreover, elevated serum heparan sulfate in patients with MPS may compete with cell surface heparan sulfate, which is essential for successful interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the host cell surface, thereby protecting against intracellular penetration by SARS-CoV-2.

• Tuberculosis and Respiratory Diseases
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• v.60 no.1
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• pp.49-56
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• 2006

배경 : 급성 폐손상은 폐내, 외의 원인질환들에 의해 폐포-모세혈관의 투과성이 증가하며, 폐부종에 의해 급성 저산소성 호흡곤란이 유발되는 증후군이다. 헤파린은 항응고작용 외에 자체적으로 항염증효과를 가지고 있으나, 염증성질환에 헤파린을 투여하면 출혈성 합병증이 발생하기 때문에 실제로 임상에서 이용하는데 제약이 있다. 하지만 헤파린에서 2-O와 3-O sulfate를 제거하면, 항응고 효과가 제거되고 항염증효과는 지니고 있는 비항응고성 헤파린 (nonanticoagulant heparin)으로 변화한다. 본 연구에서는 흰쥐에게 내독소 (LPS)를 투여하거나, 출혈성 쇼크를 일으켜서 유발된 급성폐손상에서 비항응고성 헤파린의 치료효과를 살펴보았다. 방법 : 각 군당 5 마리 이상의 흰쥐 (Balb/c mouse)를 이용하였다. 미정맥 (tail vein)을 통해 생리식염수 또는 비항응고성 헤파린 (50 mg/kg)을 투여한 직후에 내독소를 복강으로 투여하거나 (1 mg/kg), 심장천자를 통해 총 혈액의 1/3 정도로 제거하여 출혈성 쇼크를 유도하여 급성폐손상을 유발하였다. 내독소 투여 또는 출혈성 쇼크 유발 1 시간 후에 흰쥐를 희생시키고 폐를 적출하였고, 폐의 염증성 변화는 사이토카인 ($TNF-{\alpha}$, MIP-2, $IL-1{\beta}$)을 측정하여 살펴보았고, 폐손상의 정도는 myeloperoxidase (MPO) assay와 wet-to-dry weight ratio를 측정하여 알아보았다. 결 과 : 내독소를 투여한 흰쥐의 폐에서 대조군의 폐에 비해 사이토카인의 발현이 증가하고 ($TNF-{\alpha}$; $196.1{\pm}10.8$ vs $83.7{\pm}18.4pg/ml$, MIP-2; $3,000{\pm}725$ vs $187{\pm}26pg/ml$, $IL-1{\beta}$; $6,500{\pm}1167$ vs $266{\pm}25pg/ml$, p<0.05, respectively), 폐의 MPO 활성이 증가하였다 ($27.9{\pm}6.2$ vs $10.5{\pm}2.3U/g$ of lung protein, p<0.05). 출혈성 쇼크를 일으킨 흰쥐의 폐에서 대조군의 폐에 비해 사이토카인의 발현은 증가되지 않았으나, MPO 발현은 증가되었다 ($16.5{\pm}3.2$ vs $10.5{\pm}2.3U/g$ of lung protein, p<0.05). 내독소 투여 또는 출혈성 쇼크에 의해 급성폐손상이 유발된 흰쥐에서 생리적 식염수를 투여하거나 비항응고성 헤파린을 투여한 군 사이에 사이토카인의 발현이나 MPO 활성에 의미있는 차이는 관찰되지 않았다. 결론 : 이상의 결과로 비항응고성 헤파린은 내독소를 투여하거나 출혈성 쇼크를 일으키고 한 시간 뒤에 측정한 흰쥐의 급성폐손상에서 의미있는 치료효과를 보이지 않았다.

• Journal of Biomedical Engineering Research
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• v.24 no.5
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• pp.391-399
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• 2003

Intravascular oxygenation represents an attractive. alternative support modality for therapy originated with acute respiratory distress syndrome(ARDS). However. the clinical study concluded that more gas exchange was needed for intravascular oxygenation to be clinically effective in ARDS treatment. In this study, we tried to enhance gas exchange on the VIVLAD using microencapsulation of hemoglobin and perfluorocarbon emulsion(PFC emulsion). Blood gas measurements were performed by collecting blood samples from the arterial and venous sides of the circuit, and processing them in a blood/gas analyzer. The function of hemosome. blood/hemosome mixed solution. and blood/PFC emulsion mixed solution were tested by an oxygen dissociation curve using a blood/gas analyzer. As a result, it was shown that the oxygen transfer of hemosome and blood/hemosome mixed solution were higher than that of whole blood. Also. it showed that the carbon dioxide transfer of whole blood/PFC emulsion mixed solution was higher than that of others. Therefore, we determined that hemosome and PFC emulsion could increase oxygen transfer and carbon dioxide transfer. respectively.

• Tuberculosis and Respiratory Diseases
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• v.63 no.6
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• pp.497-506
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• 2007

Background: The present investigation was performed in rats and isolated human neutrophils in order to confirm the presumptive role of the positive feedback loop of cytosolic phospholipase $A_2$ ($cPLA_2$) activation by plateletactivating factor (PAF). Methods: The possible formation of the positive feedback loop of the $cPLA_2$ activation and neutrophilic respiratory burst was investigated in vivo and in vitro by measurement of the parameters denoting acute lung injury. In addition, morphological examinations and electron microscopic cytochemistry were performed for the detection of free radicals in the lung. Results: Five hours after intratracheal instillation of PAF ($5{\mu}g/rat$), the lung leak index, lung myeloperoxidase (MPO) activity, the number of neutrophils and the concentration of cytokine-induced neutrophil chemoattractant (CINC) in bronchoalveolar lavage fluid were increased by PAF as compared with those of control rats. The NBT assay and cytochrome-c reduction assay revealed an increased neutrophilic respiratory burst in isolated human neutrophils following exposure to PAF. Lung and neutrophilic $cPLA_2$ activity were increased following PAF exposure and exposure to hydrogen peroxide increased $cPLA_2$ activity in the lung. Histologically, inflammatory findings of the lung were observed after PAF treatment. Remarkably, as determined by $CeCl_3$ cytochemical electron microscopy, increased production of hydrogen peroxide was identified in the lung after PAF treatment. Conclusion: PAF mediates acute oxidative lung injury by the activation of $cPLA_2$, which may provoke the generation of free radicals in neutrophils.