• Journal of Ginseng Research
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• v.45 no.4
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• pp.482-489
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• 2021

Background: Asthma is an incurable hyper-responsive disease of the pulmonary system that is caused by various allergens, including indoor and outdoor stimulators. According to the Global Asthma Network, 339 million people suffered from asthma in 2018, with particularly severe forms in children. Numerous treatments for asthma are available; however, they are frequently associated with adverse effects such as growth retardation, neurological disorders (e.g., catatonia, poor concentration, and insomnia), and physiological disorders (e.g., immunosuppression, hypertension, hyperglycemia, and osteoporosis). Methods: Korean Red Ginseng has long been used to treat numerous diseases in many countries, and we investigated the anti-asthmatic effects and mechanisms of action of Korean Red Ginseng. Eighty-four BALB/c mice were assigned to 6 treatment groups: control, ovalbumin-induced asthma group, dexamethasone treatment group, and 3 groups treated with Korean Red Ginseng water extract (KRGWE) at 5, 25, or 50 mg/kg/day for 5 days. Anti-asthmatic effects of KRGWE were assessed based on biological changes, such as white blood cell counts and differential counts in the bronchoalveolar lavage fluid, serum IgE levels, and histopathological changes in the lungs, and by examining anti-asthmatic mechanisms, such as the cytokines associated with Th1, Th2, and Treg cells and inflammation pathways. Results: KRGWE affected ovalbumin-induced changes, such as increased white blood cell counts, increased IgE levels, and morphological changes (mucous hypersecretion, epithelial cell hyperplasia, inflammatory cell infiltration) by downregulating cytokines such as IL-12, IL-4, and IL-6 via GATA-3 inactivation and suppression of inflammation via NF-κB/COX-2 and PGE₂ pathways. Conclusion: KRGWE is a promising drug for asthma treatment.

• Pediatric Infection and Vaccine
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• v.29 no.2
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• pp.77-83
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• 2022

A small proportion of children with coronavirus disease 2019 (COVID-19) develop severe pneumonia. We reported the severe COVID-19 pneumonia in children aged <18 years with COVID-19 treated with remdesivir and dexamethasone from August 2021 to November 2021 by a retrospective review of their medical records. Eight children were included (5 males and 3 females). Their median age was 16 years (range: 9 to 17 years) and their median body mass index was 30.5 kg/m² (range: 22.8-38.5 kg/m²). All patients had fever and dyspnea with hypoxia. Chest radiographic findings were variable and included diffuse or multifocal consolidation, nodules, and ground-glass opacities in the lungs. After receiving intravenous remdesivir and dexamethasone, 7 of the 8 children experienced an improvement in their symptoms within 2 days. In our case series, obesity was present in 6 out of 8 children with severe COVID-19 pneumonia.

• Journal of Environmental Health Sciences
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• v.49 no.2
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• pp.108-117
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• 2023

Background: When particles are absorbed into the human body, they penetrate deep into the lungs and interact with the tissues of the body. Heavy metals in PM_2.5 can cause various diseases. The main source of PM_2.5 emissions in South Korea's atmosphere has been surveyed to be places of business. Objectives: The concentration of heavy metals in PM_2.5 near the Ulsan Industrial Complex was measured and a health risk assessment was performed for residents near the industrial complex for exposure to heavy metals in PM_2.5. Methods: Concentrations of heavy metals in PM_2.5 were measured at four measurement sites (Ulsan, Mipo, Onsan, Maegok) near the industrial complexes. Heavy metals were analyzed according to the Air Pollution Monitoring Network Installation and Operation Guidelines presented by the National Institute of Environmental Research. Among them, only five substances (Mn, Ni, As, Cd, Cr⁶⁺) were targeted. The risk assessment was conducted on inhalation exposure for five age groups, and the excess cancer risk and hazard quotient were calculated. Results: In the risk assessment of exposure to heavy metals in PM_2.5, As, Cd, and Cr⁶⁺ exceeded the risk tolerance standard of 10^-6 for carcinogenic hazards. The highest hazard levels were observed in Onsan and Mipo industrial complexes. In the case of non-carcinogenic hazards, Mn was identified as exceeding the hazard tolerance of 1, and it showed the highest hazard in the Ulsan Industrial Complex. Conclusions: This study presented a detailed health risk from exposure to heavy metals in PM_2.5 by industrial complexes located in Ulsan among five age groups. It is expected to be utilized as the basis for preparing damage control and industrial emission reduction measures against PM_2.5 exposure at the Ulsan Industrial Complex.

• Tuberculosis and Respiratory Diseases
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• v.49 no.1
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• pp.37-48
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• 2000

Backgrounds : The pathophysiology of chronic airflow obstruction, such as bronchial asthma, is characterized by mucus hypersecretion, goblet cell hyperplasia(GCH), smooth muscle hypertrophy, and inflammatory cells infiltration. In fatal asthma patients, one distinct findings is mucus hypersecretion due to GCH. However, the mechanisms of GCH in these hypersecretory diseases remain still unknown. In this study, a rat model was rapidly induced with GCH by instillation of $TiO_2$, intratracheally. We intend to confirm GCH and association of concomitant inflammatory cells infiltration and to observe the effect of potent antiinflammatory agent, that is dexamethasone, on GCH with inflammatory cells. Methods : Twenty-one 8-weeks-old male Sprague-Dawley rats were divided into three groups. Endotoxinfree water was instilled intratracheally in group 1(control) ; $TiO_2$, was instilled in the group 2 ; and dexamethasone was injected intraperitoneally to group 3 before $TiO_2$ instillation. After 120 hours, all rats were sacrificed, and trachea, bronchi, and lungs were resected respectively. These tissues were made as paraffin blocks and stained as PAS for goblet cells and Luna stain for eosinophils. We calculated the ratio of goblet cell to respiratory epithelium and number of infiltrated eosinophils from each tissue. Results : (1) Fraction of goblet cells was significantly increased in group 2 than in group 1 in the trachea and in the main bronchus. (10.19$\pm$11.33% vs 4.09$\pm$8.28%, p<0.01 and 34.09$\pm$23.91% vs 3.61$\pm$4.84%, p<0.01, respectively). (2) Eosinophils were significantly increased in the airway of group 2 than that of group 1. (5.43$\pm$3.84% vs 0.17$\pm$0.47 in trachea and 47.71$\pm$16.91 vs 2.71$\pm$1.96 in main bronchi). (3) There was a positive correlation between goblet cells and eosinophils(r=0.719, p=0.001). (4) There was significant difference in the decrease of goblet cells after dexamethasone injection between group 2 and group 3 (p<0.01). Also, infiltration of eosinophils was suppressed by dexamethasone. Conclusion : We made an animal model of $TiO_2$-induced goblet cell hyperplasia. GCH was observed mainly in the main bronchi with concomitant eosinophilic infiltration. Both goblet cell hyperplasia and eosinophilic infiltration were suppressed by dexamethasone. This animal model may serve as a useful tool in understanding of the mechanism of GCH in chronic airway diseases.

• Tuberculosis and Respiratory Diseases
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• v.60 no.5
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• pp.516-522
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• 2006

Background : In contrast to tuberculous pleurisy, tuberculous empyema is a chronic active infectious disease of the pleural cavity that is frequently accompanied by cavitary or advanced pulmonary lesions. The condition requires long-term anti-tuberculous medication with external drainage. The clinical features and treatment outcome of tuberculous empyema are unclear despite the high prevalence of tuberculosis in Korea. Methods : From January 1991 through April 2004, 17 patients diagnosed with tuberculous empyema in Kyungpook National University Hospital were enrolled in this study. Their medical records and chest radiographs were reviewed. Results : Twelve patients(71%) had a history of tuberculosis and six of the 12 patients were under current anti-tuberculous medication. Productive cough, fever, and dyspnea were the main complaints. There was no predominance between the right and left lungs. Nine patients(53%) had far-advanced pulmonary tuberculosis, two(12%) had a cavitary lesion, and seven(41%) had a pyopneumothorax on the chest radiograph. All eight cases in whom the data of pleural fluid WBC differential count was available showed polymorphonuclear leukocyte predominance. Eight patients(47%) had other bacterial infections as well. The overall rates of a positive sputum AFB smear and culture for M. tuberculosis were 71% and 64%, respectively. The positive AFB smear and culture rates for M. tuberculosis from the pleural fluid were 33% and 36%, respectively. Twelve of the 16 patients(75%) were treated successfully. Three underwent additional surgical intervention. Two patients (12%) died during treatment. Conclusion : Tuberculous empyema is frequently accompanied by advanced pulmonary lesions, and polymorphonuclear leukocytes are predominant in the pleural fluid. Other accompanying bacterial infections in the pleural cavity are also common in tuberculous empyema patients. Therefore, tuberculous empyema should be considered in differential diagnosis of patients with polymorphonuclear leukocyte-predominant pleural effusion. In addition, more active effort will be needed to achieve a bacteriological diagnosis in the pleural fluid.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.246-259
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• 2000

Background: As one of the etiologies of acute respiratory distress syndrome(ARDS), sepsis is one of the morbid causes of this cryptogenic malady. Even though many documents on the role of endotoxin(ETX) in the pathogenesis of ARDS have been issued, still the underlying mechanism associated with oxidative stress and activation of $PLA_2$ has been controversial. In the present study, the role of phospholipase $A_2(PLA_2)$ in the neutrophilic respiratory burst, which is presumed to cause acute lung injury during sepsis, was probed. Method: In glutathione-depleted Sprague-Dawley rats, lung leak, infiltration of neutrophils, $PLA_2$ activity and lipid peroxidation in the lung were measured after intratracheal instillation of endotoxin(delete). In addition, gamma glutamyl transferase(GGT) activity and the amount of pulmonary surfactant were measured. Morphologically, the changes in ultrastructure and cytochemical demonstration of oxidants were presented to confirm the neutrophilic oxidative stress and to elucidate the effects of $PLA_2$ activation on(delete) oxidative stress. Results: Instillation of ETX to glutathione-depleted rats intensified lung leak and lipid peroxidation when compared with non-glutathione depleted rats treated with the endotoxin. Moreover, oxidative stress was confirmed by the assay of GGT and malondialdehyde. Functionally, the depletion of glutathione altered the secretion of pulmonary surfactant from alveolar type II cells. Ultrastructurally and cytochemicaliy, oxidative stress was also confirmed after treatment of with ETX and diethylmaleate(DEM). Conclusion: The endotoxin-induced acute lung injury was mediated by oxidative stress, which in turn was provoked by the neutrophilic respiratory burst. The activation of $PLA_2$ in the lung seems to playa pivotal role in the oxidative stress of the lung.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.547-557
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• 1996

Background : An excessive accumulation of neutrophils in lung tissue has been known to play an important role in mediating the tissue injury among the adult respiratory distress syndrome, idiopathic pulmonary fibrosis and cystic fibrosis by releasing toxic oxygen radicals and proteolytic enzymes. Therefore, it is important to understand a possible mechanism of neutrophil accumulation in lung tissue. In many species, exposure to hyperoxic stimuli can cause changes of lung tissues very similar to human adult respiratory distress syndrome and neutrophils are also functioning as the main effector cells in hyperoxic lung injury. The purpose of the present study was to examine whether neutrophils function as a key effector cell and to study the nature of possible neutrophil chemotactic factors found in bronchoalveolar lavage fluid from the hyperoxia exposed rats. Methods : We exposed the rats to the more than 95% oxygen for 24, 48, 60 arid 72 hours and bronchoalveolar lavage(BAL) was performed. Neutrophil chemotactic activity was measured from the BAT- fluid of each experimental groups. We also evaluated the molecular weight of neutrophil chemotactic tractors using fast performance liquid chromatography and characterized the substances by dialyzer membrane and heat treatment. Results : 1) The neutrophil proportions in bronchoalveolar lavage fluid began to rise from 48 hours after oxygen exposure, and continued to be significantly increased with exposure times. 2) chemotactic index for neutrophils in lung lavages from rats exposed to hyperoxia was significantly higher in 48 hours group than in control group, and was significantly increased with exposure time. 3) No deaths occured until after 48 hours of exposure. However, mortality rates were increased to 33.3 % in 60 hours group and 81.3 % in 72 fours group. 4) Gel filtration using fast performance liquid chromatography disclosed two peaks of neutrophil chemotactic activity in molecular weight of 104,000 and 12,000 daltons. 5) Chemotactic indices of bronchoalveolar lavage fluid were significantly deceased when bronchoalveolar lavage fluid was treated with heat ($56^{\circ}C$ for 30 min or $100^{\circ}C$ for 10 min) or dialyzed (dialyzer membrane molecular weight cut off : 12,000 daltons). Conclusion : These results suggested that the generation of neutrophil chemotactic factor and subsequent neutrophil influx into the lungs are playing an important roles in hyperoxia-induced acute lung injury. Neutrophil chemotactic factor in the lung lavage fluids consisted of several distinct components having different molecular weight and different physical characteristics.

• Tuberculosis and Respiratory Diseases
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• v.43 no.1
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• pp.54-62
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• 1996

Background: $^{99m}Tc$ MIBI(Methoxyisobutylisonitrile complex), a member of the isonitrile class of coordination compounds, is a lipophilic cation presently under investigation for clinical use as myocardial perfusion imaging agent and is widely used to detect myocardial infarction. Preliminary reports indicate that $T_1$-201 accumulate in human neoplasm and several authors reported $^{99m}Tc$ MIBI may also localized in primary malignant tumor and metastatic deposits from lung cancer. We evaluated the uptake of $^{99m}Tc$ MIBI in lung cancer and localization of mediastinal and other site metastasis, and compared the benign lesion of the lung. Method: Thirty four patients of lung cancer and ten patients of benign lung lesion were studied with chest CT and $^{99m}Tc$ MIBI Lung SPECT. $^{99m}Tc$ MIBI uptake ratio was assessed by TR/NL(Lung lesion/ Normal area), HT/NL (Heart/Normal area) and HT/TR(Heart/Lung lesion). Results: 1) All lung cancer patients showed increased uptakes of $^{99m}Tc$ MIBI in malignant lung lesion and Tc-99m MIBI uptake was also increased in mediastinal and lymph node metastasis except two cases. 2) There was significant different ratio of TR/NL between malignant and benign lesion, $3.79{\pm}1.82$ and $1.67{\pm}0.63$ on planar images, respectively(p<0.001). 3) There was no significant difference of $^{99m}Tc$ MIBI uptake ratio between squamous cell carcinoma, small cell carcinoma and adeno carcinoma($3.64{\pm}1.66$, $3.57{\pm}0.72$, $4.31{\pm}2.28$ respectively). Conclusion: $^{99m}Tc$ MIBI lung SPECT was useful in the localization of tumor and mediastinal or other site metastatic lesion in lung cancer and also in the differential diagnosis between benign and malignant lesion.

• Tuberculosis and Respiratory Diseases
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• v.52 no.3
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• pp.219-229
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• 2002

Background : Sepsis-induced acute lung injury (ALI) is caused by many cellular and humoral mediators induced by an endotoxin. Histamine, which is widely distributed in the lungs and has been considered as an important mediator of sepsis. It increases P-selectin expression on the endothelial cell surfaces and induces IL-8 secretion. Therefore, an endotoxin-induced histamine may be related to neutrophil-mediated ALI by inducing the migration and activation of neutrophils in the lung tissue. However, the role of endogenous histamine in endotoxin ALI has not been clarified. The purpose of this study was to investigate how endotoxin-induced ALI is influenced by endogenous histamine and to identify the possible mechanism of action. Materials and Methods : The study consisted of 4 groups using Sprague-Dawley rats : 1) control group, where the rats were infused intratracheally by normal saline, 2) an endotoxin group, where lipopolysaccharide (LPS) was administered intratracheally 3) the $H_2$ receptor antagonist-treated group ($H_2$ group) and 4) the $H_1$ receptor antagonist-treated group ($H_1$ group), where $H_2$-receptor blocker (ranitidine) and $H_1$-receptor blocker(pyrilamine) were co-treated intravenously with the intratracheal administration of an endotoxin. The lung leak index using $I^{125}$-BSA, the total protein and LDH concentration in the lung lavage fluid, myeloperoxidase(MPO) activity in the lung tissue, the pathologic score and the total number of neutrophils, TNF-$\alpha$, IL-$1{\beta}$ and IL-10 in lung lavage (BAL) fluid were measured in each group as the indices of lung injury. Results : Compared to the control group, the endotoxin group exhibited significant increases in all lung injury indices. Significant reductions in the endotoxin-mediated increases in lung leak index (p<0.05) were observed in both the $H_1$ and $H_2$ groups. In addition the total protein (p<0.05) and LDH concentration (p<0.05) in the BAL fluid were also lower in the $H_2$ group compared to the endotoxin group. However, there was no change in the MPO activity in the lung tissue, the pathologic score and the total number of neutrophils in the BAL fluid in both the $H_2$ and $H_1$ groups compared to the endotoxin group. The increases in TNF-$\alpha$ IL-$1{\beta}$ and IL-10 concentrations in the BAL fluid observed in the endotoxin group were not reduced in the $H_2$ and $H_1$ groups. Conclusion : Antihistamine attenuated the enhanced alveolar-capillary permeability induced by the endotoxin via the $H_2$ receptor. However the attenuating mechanism may not be related to the pathogenesis of neutrophil dependent lung injury.

• Tuberculosis and Respiratory Diseases
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• v.79 no.3
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• pp.143-152
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• 2016

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor ${\beta}1$ (TGF-${\beta}1$)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-${\beta}1$-induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-${\beta}1$ with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and ${\alpha}$-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-${\beta}1$ receptor type 1 ($T{\beta}RI$) and type 2 ($T{\beta}RII$) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-${\beta}1$-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-${\beta}1$-induced change of the EMT phenotype. ApoA1 inhibited the TGF-${\beta}1$-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-${\beta}1$-induced increase in $T{\beta}RI$ and $T{\beta}RII$ expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-${\beta}1$-induced EMT in experimental lung fibrosis.