• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.328-338
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• 1994

Background: Effect of sulfur dioxide($SO_2$) exposure on airway is well known but little about the effect of $SO_2$ exposure on lung parenchyme. This study is to determine if short tenn exposure to $SO_2$ in concentration commonly found in industrialized environment cause potentially harmful effect on the lung parenchyme, and to evaluate the exposure time-response relationship between short tenn exposure to $SO_2$ and the inflammatory response in mouse lung. Method: 5ppm $SO_2$ gas was used and 48 mice were grouped into control(10), 30(9), 60(11), and 120 minute exposure(18) group. In each group, bronchoalveolar lavage(BAL) was done immediately after and at 1,2,3 days after exposure. Histological examination was performed in control and 120 minute exposure group. Results: 1) Cell response in bronchoalveolar lavage fluid. In 30 and 60 minute exposure group, compared to the control group, lymphocyte count has significantly increased(p<0.05) at 1 day after exposure but did not differ at 2 days after exposure. In 120 minute exposure group, also compared to the control group, there was significant increase in total cell, macrophage, and lymphocyte count at 1 day after exposure, (p<0.05) which lasted for 2 days but did not significantly differ at 3 days after exposure. 2) Histological findings in 120 minute exposure group. In the airway, mild epithelial cell damage and ciliary loss were noted but there was no evidence of inflammatory cell infiltration. Interstitial inflammatory infiltration was noted at 1 day after exposure, which lasted for 3 days after exposure and there was no evidence of edema or fibrosis in the interstitium Conclusions: These data indicate potentially noxious effect of $SO_2$ on the lung parenchyme as well as the airway at exposure level that are regarded as relatively safe, and the duration of injury depends on the exposure time.

• Journal of Life Science
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• v.19 no.6
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• pp.735-743
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• 2009

The common word flavonoids is often used to classify a family of natural compounds, highly abundant in all higher plants, that have received significant therapeutic interest in recent years. Naringin is associated with a reduced risk of heart disease, neurodegenerative disease, cancer and other chronic diseases; however the molecular basis of this effect remains to be elucidated. Thus we attempted to elucidate the anti-allergic effect of Naringin in ovalbumin (OVA)-induced asthma model mice. The OVA-induced mice showed allergic reactions in the airways. These included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung around blood vessels and airways, airway luminal narrowing, and the development of airway hyper-responsiveness (AHR). The administration of Naringin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that Naringin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of Naringin in terms of its effects on asthma in mice.

• 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.

• Applied Microscopy
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• v.34 no.1
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• pp.31-42
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• 2004

Acute respiratory distress syndrome (ARDS) is a kind of acute lung injury characterized by inflammatory disruption of alveolar-capillary barrier and notorious for its high mortality. Neutrophils cause cell damage through the production of free radicals, inflammatory mediators, and proteases in ARDS. $PLA_2$ might serve a primary regulatory role in the activation of neutrophils. This present study was performed to elucidate the effect of rutin known as $PLA_2$ inhibitor on ARDS induced by endotoxin. Endotoxin had increased lung myeloperoxidase (MPO) activity, BAL (bronchoalveolar lavage) protein content, numbers of neutrophils in BALF (bronchoalveolar lavage fluid) compared with those of control rat (p<0.001). In addition, histological evidence of lung injury was correlated with neutrophil influx into alveolar space and cerrous perhydroxide granules were found in lining of endothelial cell, alveolar type I, II cells. In contrast, pretreated group of rutin had significantly decreased all of the parameters (p<0.001). These data suggest that inhibition of $PLA_2$ is one step approach that block the process of ARDS. Accordingly, we conclude that rutin can be used as the prophylactic agent for ARDS on the bases of these experimental results.

• Tuberculosis and Respiratory Diseases
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• v.51 no.6
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• pp.540-549
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• 2001

Background : Usual interstitial pneumonia (UIP) is a progressive fibrous lung disease with occasional fatal outcomes. However, the extent and rate of progression varies markedly from one patient to another. As a result, it is difficult to determine the time of the initial treatment and assess the disease activity and course. Fibroblast foci (FF) is well known to synthesize collagen actively by their myofibroblasts component. However, the prognostic value of the FF have not been evaluated in patients with VIP. Therefore this study was undertaken to determine how the number of fibroblastic foci can reflect the disease activity and progression. Methods: Twenty patients with UIP(M : F=13 : 7), who were diagnosed by a surgical lung biopsy. The number of fibroblastic foci was analyzed in terms of its correlation with the clinical manifostations, pulmonary function test, arterial blood gas analysis, and a bronchoalveolar lavage(BAL). Results : The number of fibroblastic foci did not correlate with the various lung function tests and the other clinical parameters. Interestingly, the percentage of neutrophils in the bronchoalveolar lavage fluid did correlate with the quantity of the normalized Vv of FF(r=0.60, p<0.05). The patients were divided into 2 groups, group I and II, arbitrarily, according to the value of the normalized Vv. The clinical parameters and the PIT results were not different between the two groups. In particular, the survival rate between the two groups according to the Kaplan-Meier analysis were not different. Conclusion : A large number of FF does not imply a bad prognosis in patients with UIP.

• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.530-542
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• 2000

Background : Nonspecific interstitial pneumonia (NSIP) has been reported recently to have shown much better response to medical treatment and better prognosis compared with idiopathic UIP. However, clinical characteristics of idiopathic NSIP discriminating it from UIP have not been clearly defined. Method : Among 120 patients with biopsy-proven diffuse interstitial lung diseases admitted to the Samsung Medical Center between July 1996 and March 2000, 18 patients with idiopathic NSIP were included in this study. Retrospective chart review and radiographic analysis were performed. Results : 1) At diagnosis, 17 patients were female and the average age was $55.2{\pm}8.4$ years (44~73 years). The average duration from development of respiratory symptom to surgical lung biopsy was $9.9{\pm}17.1$ months. Increase in bronchoalveolar lavage fluid lymphocytes ($23.0{\pm}13.1%$) was noted. On HRCT, ground glass and irregular linear opacity were observed, but honeycombing was absent in all patients. 2) Corticosteroids were initially given to 13 patients, but the medication was stopped in 3 patients due to severe side effects. Further medical therapy was not possible in 1 patient who experienced streroid-induced psychosis. Herpes zoster (n=3), tuberculosis (n=1), avascular necrosis of the hip (n=1), cataract (n=2) and diabetes mellitus (n=1) developed during prolonged corticosteroid administration. Of the 7 patients receiving oral cyclophosphamide therapy, hemorrhagic cystitis hindered one patient from continuing with the medication. 3) After medical treatment, 14 of 17 patients improved, and 3 patients remained stable (mean follow-up ; $24.1{\pm}11.2$ months). FVC increased by $20.2{\pm}11.2%$ of predicted value and the extent of ground glass opacity on HRCT decreased significantly ($15.7{\pm}14.7%$). 4) Of the 14 patients who had stopped medication, 5 showed recurrence of NSIP and 2 became aggravated during steroid tapering. All patients with recurrence showed deterioration within one year after completion of initial treatment. Conclusion : Since idiopathic NSIP has unique clinical profiles and shows good prognosis, diagnosis different from UIP, and aggressive medical treatment are needed.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.795-804
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• 1998

Background: Chronic eosinophilic pneumonia(CEP) is interstitial lung disease characterized by multiple infiltration on radiographic study, accumulation of eosinophils in the alveolar space and interstitium of the lung, chronic persistent symptoms and possible relapse. Acute eosinophilic pneumonia(AEP) is a recently described illness, characterized by rapid clinical course, acute respiratory insufficiency and no relapse. Method : To better characterize acute and chronic eosinophilic pneumonia, we studied the clinical and laboratory features of 16 patients(AEP : 7 patients, CEP : 9 patients), which were clinico-pathohistologically diagnosed and not to be associated with organic disorders producing peripheral blood eosinophilia. Results: The mean age was higher for patients with CEP than for patients with AEP ($55.4{\pm}15.1$ vs. $24.6{\pm}7.9$ years, p<0.05). High fever(above $38^{\circ}C$) was presented in all patients of AEP and in one patient(11%) of CEP. All patients of AEP and eight patients (89%) of CEP showed bilateral pulmonary infiltrates, and 6 patients(86%) of AEP and 2 patients(22%) of CEP showed pleural effusion in chest radiograph. The mean white blood cell count of AEP and CEP were $17,186/mm^3$ and $12,867/mm^3$, respectively. The mean peripheral blood eosinophil count of AEP and CEP were $939/mm^3$ and $2,104/mm^3$, respectively. The mean eosinophil fraction of BAL fluid of AEP and CEP were 32.4% (range: 18~47%) and 35.8% (range: 15.3~88.2%), respectively. The mean $PaO_2$ was lower for patients with AEP than for patients with CEP ($44.1{\pm}15.5$ vs. $62.7{\pm}6.9$mmHg, p<0.05). All patients of AEP and CEP were initially treated with antibiotics. All patients of CEP and one patients of AEP were finally required systemic steroid therapy. 6 patients of AEP were improved without steroid therapy. Relapse was observed in 3 patients(33%) of CEP. Conclusion : Compair with of chronic eosinophilic pneumonia, acute eosinophilic pneumonia was characterized by relatively young age, acute onset, high fever, severe hypoxemia, diffuse pulmonary infiltrates with pleural effusion, steroid therapy is effective but spontaneous improvement with conservative therapy was frequent.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.215-228
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• 1999

Background: Sarcoidosis is a chronic granulomatous inflammatory disease of unknown etiology often involving the lungs and intrathoracic lymph nodes. The natural course of sarcoidosis is variable from spontaneous remission to significant morbidity or death. But, the mechanisms causing the variable clinical outcomes or any single parameter to predict the prognosis was not known. In sarcoidosis, the number and the activity of CD4 + lymphocytes are significantly increased at the loci of disease and their oligoclonality suggests that the CD4 + lymphocytes hyperreactivity may be caused by persistent antigenic stimulus. Recently, it has been known that CD4+ lymphocytes can be subdivided into 2 distinct population(Th1 and Th2) defined by the spectrum of cytokines produced by these cells. Th1 cells promote cellular immunity associated with delayed type hypersensitivity reactions by generating IL-2 and IFN-$\gamma$. Th2 cells playa role in allergic responses and immediate hypersensitivity reactions by secreting IL-4, IL-5, and IL-10. CD4+ lymphocytes in pulmonary sarcoidosis were reported to be mainly Th1 cells. IL-12 has been known to play an important role in differentiation of undifferentiated naive T cells to Th1 cells. And, Moller et al. observed increased IL-12 in bronchoalveolar lavage fluid(BALF) in patients with sarcoidosis. So it is possible that the elevated level of IL-12 is necessary for the continuous progression of the disease in active sarcoidosis. This study was performed to test the assumption that IL-12 can be a marker of active pulmonary sarcoidosis. Methods: We measured the concentration of IL-12 in BALF and in conditioned medium of alveolar macrophage(AM) using ELISA(enzyme-linked immunosorbent assay) method in 26 patients with pulmonary sarcoidosis(10 males, 16 females, mean age: $39.8{\pm}2.1$ years) and 11 normal control. Clinically, 14 patients had active sarcoidosis and 12 patients had inactive. Results: Total cells counts, percentage and number of lymhocytes, number of AM and CD4/CD8 lymphocyte ratio in BALF were significantly higher in patients with sarcoidosis than in control group. But none of these parameters could differentiate active sarcoidosis from inactive disease. The concentration of IL-12 in BALF was significantly increased in sarcoidosis patients ($49.3{\pm}9.2$ pg/ml) than in normal control ($2.5{\pm}0.4$ pg/ml) (p<0.001). Moreover it was significantly higher in patients with active sarcoidosis ($70.3{\pm}14.8$ pg/ml) than in inactive disease ($24.8{\pm}3.l$ pg/ml) (p=0.001). Also, the concentration of IL-12 in BALF showed significant correlation with the percentage of AM(p<0.001), percentage(p<0.001) and number of lymphocyte(p<0.001) in BALF, suggesting the close relationship between the level of IL-12 in BALF and the inflammatory cell infiltration in the lungs. Furthermore, we found a significant correlation between the level of IL-12 and the concentration of soluble ICAM-1 : in serum(p<0.001) and BALF (p=0.001), and also between IL-12 level and ICAM-1 expression of AM(p<0.001). The AM from patients with pulmonary sarcoidosis secreted significantly larger amount of IL-12 ($206.2{\pm}61.9$ pg/ml) than those of control ($68.3{\pm}43.7$ pg/ml) (p<0.008), but, there was no difference between inactive and active disease group. Conclusion : Our data suggest that the BALF IL-12 level can be used as a marker of the activity of pulmonary sarcoidosis.

• Tuberculosis and Respiratory Diseases
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• v.39 no.6
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• pp.453-473
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• 1992

Background: National survey was performed to estimate the incidence of sarcoidosis in Korea. The clinical data of confirmed cases were analysed for the practice of primary care physicians and pulmonary specialists. Methods: The period of study was from January 1991 to December 1992. Data were retrospectively collected by correspondence with physicians in departments of internal medicine, dermatology, ophthalmology and neurology of the hospitals having more than 100 beds using returning postcards. In confirmed and suspicious cases of sardoidosis, case record chart for clinical and laboratory findings were obtained in detail. Results: 1) Postcards were sent to 523 departments in 213 hospitals. Internal medicine composed 41%, dermatology 20%, ophthalmology 20% and neurology 19%. 2) Postcards were returned from 241 departments (replying rates was 48%). 3) There were 113 confirmed cases from 50 departments and 10 cases. The cases were composed from internal medicine (81%), dermatology (13%), ophthalmology (3%) and neurology (3%). 78 confirmed cases were analysed, which were composed from department of internal medicine (92%), dermatology (5%), and neurology (3%). 4) The time span for analysed cases was 1980 to 1992. one case was analysed in 1980 and the number gradually increased to 18 cases in 1991. 5) The majority of patients (84.4%) were in the age group of 20 to 49 years. 6) The ratio of male to female was 1 : 1.5. 7) The most common chief complains were respiratory symptoms, dermatologic symptoms, generalized discomforts, visual changes, arthralgia, abdominal pains, and swallowing difficulties in order. 16% of the patients were asymptomatic. 8) Mean duration between symptom onset and diagnosis was 2 months. 9) The most common symptoms were respiratory, general, dermatologic, ophthalmologic, neurologic and cardiac origin in order. 10) Hemoglobin, hematocrits and platelet were in normal range. 58% of the patients had lymphopenia measuring less than 30% of white cell count. The ratio of CD4 to CD8 lymphocytes was $1.73{\pm}1.16$ with range of 0.43 to 4.62. ESR was elevated in 43% of the cases. 11) Blood chemistry was normal in most cases. Serum angiotensin converting enzyme (S-ACE) was $66.8{\pm}58.6\;U/L$ with the range of 8.79 to 265 U /L. Proteinuria of more than 150 mg was found in 42. 9% of the patients. 12) Serum IgG was elevated in 43.5%, IgA in 45.5%, IgM in 59.1% and IgE in 46.7%. The levels of complement C3 and C4 were in the normal range. Anti-nuclear antibody was detected in 11% of the cases. Kweim test was performed in 3 cases, and in all cases the result was positive. 13) FVC was decreased in 17.3%, FEV1 in 11.5%, FEV1/FVC in 10%, TLC in 15.2%, and DLco in 64.7%. 14) PaO2 was decreased below 90 mmHg in 48.6% and PaCO2 was increased above 45 mmHg in 5.7%. 15) The percentage of macrophages in BAL fluid was $51.4{\pm}19.2%$, lymphocytes $44.4{\pm}21.1%$, and the ratio of CD4 to CD8 lymphocytes was $3.41{\pm}2.07$. 16) There was no difference in laboratory findings between male and female. 17) Hilar enlargement on chest PA was present in 87.9% (bilaterally in 78.8% and unilaterally in 9.1%). 18) According to Siltzbach's classification, stage 0 was 5%, stage 158.3%, stage 228.3%, and stage 38.3%. 19) Hilart enlargement on chest CT was present in 92.6% (bilaterally 76.4% and unilaterally in 16.2%). 20) HRCT was done in 16 cases. The most common findings were nodules, interlobular thickening, focal patchy infiltrations in order. Two cases was normal finding. 21) Other radiologic examinations showed bone change in one case and splenomegaly in two cases. 22) Gallium scan was done in 12 cases. Radioactivity was increased in hilar and mediastinal lymph nodes in 8 cases and in parenchyme in 2 cases. 23) The pathologic diagnosis was commonly performed by transbrochial lung biopsy (TBLB, 47.3%), skin and mediastinal lymph nodes biopsy (34.5%), peripheral lymph nodes biopsy (23.6%), open lung biopsy (18.2%) and bronchial biopsy in order. 24) The most common findings in pathology were non·caseating granuloma (100%), multi-nucleated giant cell (47.3%), hyalinized acellular scar (34.5%), reticulin fibrin network (20%), inclusion body (10.9%), necrosis (9.1%), and lymphangitic distribution of granuloma (1.8%) in order. Conclusion: Clinical, laboratory, radiologic and pathologic findings were summarized. This collected data will assist in finding a test for detection and staging of sarcoidosis in Korea in near future.