• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1318-1325
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• 1997

Background : Since the late 1960s, mechanical ventilation has been accomplished primarily using volume controlled ventilation(VCV). While VCV allows a set tidal volume to be guaranteed, VCV could bring about excessive airway pressures that may be lead to barotrauma in the patients with acute lung injury. With the increment of knowledge related to ventilator-induced lung injury, pressure controlled ventilation(PCV) has been frequently applied to these patients. But, PCV has a disadvantage of variable tidal volume delivery as pulmonary impedance changes. Since the concept of combining the positive attributes of VCV and PCV(dual control ventilation, DCV) was described firstly in 1992, a few DCV modes were introduced. Pressure-regulated volume control(PRVC) mode, a kind of DCV, is pressure-limited, time-cycled ventilation that uses tidal volume as a feedback control for continuously adjusting the pressure limit However, no clinical studies were published on the efficacy of PRVC until now. 'This investigation studied the efficacy of PRVC in the patients with unstable respiratory mechanics. Methods : The subjects were 8 mechanically ventilated patients(M : F=6 : 2, $56{\pm}26$ years) who showed unstable respiratory mechanics, which was defined by the coefficients of variation of peak inspiratory pressure for 15 minutes greater than 10% under VCV, or the coefficients of variation of tidal volume greater than 10% under PCV. The study was consisited of 3 modes application with VCV, PCV and PRVC for 15 minutes by random order. To obtain same tidal volume, inspiratory pressure setting was adjusted in PCV. Respiratory parameters were measured by pulmonary monitor(CP-100 pulmonary monitor, Bicore, Irvine, CA, USA). Results : 1) Mean tidal volumes($V_T$) in each mode were not different(VCV, $431{\pm}102ml$ ; PCV, $417{\pm}99ml$ ; PRVC, $414{\pm}97ml$) 2) The coefficient of variation(CV) of $V_T$ were $5.2{\pm}3.9%$ in VCV, $15.2{\pm}7.5%$ in PCV and $19.3{\pm}10.0%$ in PRVC. The CV of $V_T$ in PCV and PRVC were significantly greater than that in VCV(p<0.01). 3) Mean peak inspiratory pressure(PIP) in VCV($31.0{\pm}6.9cm$ $H_2O$) was higher than PIP in PCV($26.0{\pm}6.5cm$ $H_2O$) or PRVC($27.0{\pm}6.4cm$ $H_2O$)(p<0.05). 4) The CV of PIP were $13.9{\pm}3.7%$ in VCV, $4.9{\pm}2.6%$ in PVC and $12.2{\pm}7.0%$ in PRVC. The CV of PIP in VCV and PRVC were greater than that in PCV(p<0.01). Conclusions : Because of wide fluctuations of VT and PIP, PRVC mode did not seem to have advantages compared to VCV or PCV in the patients with unstable respiratory mechanics.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1343-1352
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• 1997

Background : Heat-treated cells are known to be protected from lysis by TNF, which is considered to play a central role in the pathogenesis of sepsis-induced acute lung injury. The objective of the study was to investigate the effect of heat shock response by heat-pretreatment on the acute lung injury of the rats induced by intratracheally administered TNF-$\alpha$, Methods : We intratracheally instilled either saline or TNF (R&D, 500ng) with and without heat pretreatment in Sprague-Dawley rats weighing 250~350 g. The heated rats were raised their rectal temperature to $41^{\circ}C$ and was maintained thereafter for 13 minutes at 18 h before intratracheal administration of saline or TNF. After 5 h of intratracheal treatment, lung leak, lung myeloperoxidase activity (MPO) and heat shock proteins were measured in rats. Lung leak index was defined as counts per minute of $I^{25}$ in the right lung divided by counts per minutes of $I^{25}$ in 1.0 ml of blood. All data are expressed as means ${\pm}$SE. Results : There is no difference in acute lung leak index ($0.099{\pm}0.024$ vs $0.123{\pm}0.005$) among the rats given saline intratracheally with and without heat pretreatment, but MPO activity showed a decreased tendency in heat-pretreated rats ($4.58{\pm}0.79\;U/g$) compared with heat-unpretreated rats ($7.32{\pm}0.97\;U/g$) (P=0.064). Rats administered TNF intratracheally with heat-pretreatment had decreased lung leak index ($0.137{\pm}0.012$) and lung MPO activity ($5.51{\pm}1.04\;U/g$) compared with those of heat-unpretreated and TNF-administered rats ($0.186{\pm}0.016$, $14.34{\pm}1.22\;U/g$) (P<0.05 in each). There were no significant difference of lung leak index and MPO activity between TNF-treated rats with heat-pretreatment and saline-treated rats with and without heat-pretreatment. Conclusion : The heat shock response attenuated neutrophil recruitment and acute lung leak induced by intratracheal instillation of TNF-in rats.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.380-387
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• 1998

Background: Minimal pressure support(PSmin) is a level of pressure support which offset the imposed work of breathing(WOBimp) developed by endotracheal tube and ventilator circuits in pressure support ventilation While the lower applied level of pressure support compared to PSmin could induce respiratory muscle fatigue, the higher level than PSmin could keep respiratory muscle rest resulting in prolongation of weaning period during weaning from mechanical ventilation PSmin has been usually applied in the level of 5~10 cm$H_2O$, but the accurate level of PSmin is difficult to be determinated in individual cases. PSmin is known to be calculated by using the equation of "PSmin = peak inspiratory flow rate during spontaneus ventilation$\times$total ventilatory system resistance", but correlation of calculated PSmin and measured PSmin has not been known. The objects of this study were firstly to assess whether customarily applied pressure support level of 5~10 cm$H_2O$ would be appropriate to offset the imposed work of breathing among the patients under weaning process, and secondly to estimate the correlation between the measured PSmin and calculated PSmin. Method : 1) Measurement of PSmin : Intratracheal pressure changes were measured through Hi-Lo jet tracheal tube (8mm in diameter, Mallinckroft, USA) by using pulmonary monitor(CP-100 pulmonary monitor, Bicore, USA), and then pressure support level of mechanical ventilator were increased until WOBimp was reached to 0.01 J/L or less. Measured PSmin was defined as the lowest pressure to make WOBimp 0.01 J/L or less. 2) Calculation of PSmin : Peak airway pressure(Ppeak), plateau airway pressure(Pplat) and mean inspiratory flow rate of the subjects were measured on volume control mode of mechanical ventilation after sedation. Spontaneous peak inspiratory flow rates were measured on CPAP mode(O cm$H_2O$). Thereafter PSmin was calculated by using the equation "PSmin = peak inspiratory flow rate$\times$R, R = (Ppeak-Pplat)/mean inspiratory flow rate during volume control mode on mechanical ventilation". Results: Sixteen patients who were considered as the candidate for weaning from mechanical ventilation were included in the study. Mean age was 64(${\pm}14$) years, and the mean of total ventilation times was 9(${\pm}4$) days. All patients except one were males. The measured PSmin of the subjects ranged 4.0~12.5cm$H_2O$ in 14 patients. The mean level of PSmin was 7.6(${\pm}2.5\;cmH_2O$) in measured PSmin, 8.6 (${\pm}3.25\;cmH_2O$) in calculated PSmin Correlation between the measured PSmin and the calculated PSmin is significantly high(n=9, r=0.88, p=0.002). The calculated PSmin show a tendancy to be higher than the corresponding measured PSmin in 8 out of 9 subjects(p=0.09). The ratio of measured PSmin/calculated PSmin was 0.81(${\pm}0.05$). Conclusion: Minimal pressure support levels were different in individual cases in the range from 4 to 12.5 cm$H_2O$. Because the equation-driven calculated PSmin showed a good correlation with measured PSmin, the application of equation-driven PSmin would be then appropriate compared with conventional application of 5~10 cm$H_2O$ in patients under difficult weaning process with pressure support ventilation.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.1058-1066
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• 1998

Background: Actinomycotic infection is uncommon and primary actinomycosis of the lung and chest wall has been less frequently reported. This disease may present as chronic debilitating illness with radiologic manifestation simulating lung tumor, pulmonary infiltrating lesion, or chronic suppuration. Diagnosis of choice was not definded yet and role of bronchoscopy on diagnosis was not described yet. Methods: From 1989 to 1998, we experienced 17 cases of thoracic actinomycosis. We have reviewed the case notes of 17 patients with thoracic actinomycosis. The mean age at presentation was $53{\pm}13$ years, 11 were male. Results: Cough, hemoptysis, sputum production, chest pain and weight loss were the commonest symptoms. The mean delay between presentation and diagnosis was $6.6{\pm}7.8$ months. There were six patients who presented with a clinical picture of a suppurative lesion and eleven patients were suspected of having primary lung tumor initially. In no cases was made an accurate diagnosis at the time of hospital admission. Associated diseases were emphysema (1 case), bronchiectasis (2 cases) and tuberculosis (2 cases). Bronchoscopic findings were mucosal swelling and stenosis(n=4), mucosal swelling, stenosis and necrotic covering (n=2), mass (n=3), mass and necrotic covering (n=1) and normal(n=6). Radiologic findings were mass lesion(n=8), pneumonitis(n=3), atelectasis(n=3), pleural effusion(n=2), and normal(n=3). Final diagnosis was based on percutaneous needle aspiration and biopsy (n=3), bronchoscopic biopsy specimens (n=9), mediastinoscopic biopsy (n=1) and histologic examination of resected tissue in the remaining patients(n=4) who received surgical excision. Among 17 patients, 13 were treated medically and the other 4 received surgical intervention followed by antibiotic treatment. Regarding the surgically treated patients, suspected malignancy is the most common indication for operation. However. both medically and surgically treated patients achieved good clinical results. Conclusion: Thoracic actinomycosis is rare. but should still be considered in the differential diagnosis of a chrinic, localized pulmonary lesion. Thoracic actinomycosis may co-exist with pulmonary tuberculosis or lung cancer. If the lesion is located in the central of the lung. the bronchoscopy is recommanded for the diagnosis.

• Korean Journal of Poultry Science
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• v.16 no.2
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• pp.105-127
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• 1989

Although poultry industry in Japan has been much developed in recent years, it still needs to be developed , compared with developed countries. Since the poultry market in Korea is expected to be opened in the near future it is necessary to maximize the Productivity to reduce the production costs and to develop the scientific, technologies and management organization systems for the improvement of the quality in poultry production. Followings ale the summary of poultry industry in Japan. 1. Poultry industry in Japan is almost specized and commercialized and its management system is ： integrated, cooperative and developed to industrialized intensive style. Therefore, they have competitive power in the international poultry markets. 2. Average egg weight is 48-50g per day (Max. 54g) and feed requirement is 2. 1-2. 3. 3. The management organization system is specialized and farmers in small scale form complex and farmers in large scale are integrated.

• Tuberculosis and Respiratory Diseases
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• v.42 no.3
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• pp.351-360
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• 1995

Background: Pressure support(PS) is becomimg a widely accepted method of mechanical ventilation either for total unloading or for partial unloading of respiratory muscle. The aim of the study was to find out if PS exert different effects on respiratory mechanics in synchronized intermittent mandatory ventilation(SIMV) and continuous positive airway pressure (CPAP) modes. Methods: 5, 10 and 15 cm $H_2O$ of PS were sequentially applied in 14 patients($69{\pm}12$ yrs, M:F=9:5) and respiratory rate (RR), tidal volume($V_T$), work of breathing(WOB), pressure time product(PTP), $P_{0.1}$, and $T_1/T_{TOT}$ were measured using the CP-100 pulmonary monitor(Bicore, USA) in SIMV and CPAP modes respectively. Results: 1) Common effects of PS on respiratory mechanics in both CPAP and SIMV modes As the level of PS was increased(0, 5, 10, 15 cm $H_2O$), $V_T$ was increased in CPAP mode($0.28{\pm}0.09$, $0.29{\pm}0.09$, $0.31{\pm}0.11$, $0.34{\pm}0.12\;L$, respectively, p=0.001), and also in SIMV mode($0.31{\pm}0.15$, $0.32{\pm}0.09$, $0.34{\pm}0.16$, $0.36{\pm}0.15\;L$, respectively, p=0.0215). WOB was decreased in CPAP mode($1.40{\pm}1.02$, $1.01{\pm}0.80$, $0.80{\pm}0.85$, $0.68{\pm}0.76$ joule/L, respectively, p=0.0001), and in SIMV mode($0.97{\pm}0.77$, $0.76{\pm}0.64$, $0.57{\pm}0.55$, $0.49{\pm}0.49$ joule/L, respectively, p=0.0001). PTP was also decreased in CPAP mode($300{\pm}216$, $217{\pm}165$, $179{\pm}187$, $122{\pm}114cm$ $H_2O{\cdot}sec/min$, respectively, p=0.0001), and in SIMV mode($218{\pm}181$, $178{\pm}157$, $130{\pm}147$, $108{\pm}129cm$ $H_2O{\cdot}sec/min$, respectively, p=0.0017). 2) Different effects of PS on respiratory mechanics in CP AP and SIMV modes By application of PS (0, 5, 10, 15 cm $H_2O$), RR was not changed in CPAP mode($27.9{\pm}6.7$, $30.0{\pm}6.6$, $26.1{\pm}9.1$, $27.5{\pm}5.7/min$, respectively, p=0.505), but it was decreased in SIMV mode ($27.4{\pm}5.1$, $27.8{\pm}6.5$, $27.6{\pm}6.2$, $25.1{\pm}5.4/min$, respectively, p=0.0001). $P_{0.1}$ was reduced in CPAP mode($6.2{\pm}3.5$, $4.8{\pm}2.8$, $4.8{\pm}3.8$, $3.9{\pm}2.5\;cm$ $H_2O$, respectively, p=0.0061), but not in SIMV mode($4.3{\pm}2.1$, $4.0{\pm}1.8$, $3.5{\pm}1.6$, $3.5{\pm}1.9\;cm$ $H_2O$, respectively, p=0.054). $T_1/T_{TOT}$ was decreased in CPAP mode($0.40{\pm}0.05$, $0.39{\pm}0.04$, $0.37{\pm}0.04$, $0.35{\pm}0.04$, respectively, p=0.0004), but not in SIMV mode($0.40{\pm}0.08$, $0.35{\pm}0.07$, $0.38{\pm}0.10$, $0.37{\pm}0.10$, respectively, p=0.287). 3) Comparison of respiratory mechanics between CPAP+PS and SIMV alone at same tidal volume. The tidal volume in CPAP+PS 10 cm $H_2O$ was comparable to that of SIMV alone. Under this condition, the RR($26.1{\pm}9.1$, $27.4{\pm}5.1/min$, respectively, p=0.516), WOB($0.80{\pm}0.85$, 0.97+0.77 joule/L, respectively, p=0.485), $P_{0.1}$($3.9{\pm}2.5$, $4.3{\pm}2.1\;cm$ $H_2O$, respectively, p=0.481) were not different between the two methods, but PTP($179{\pm}187$, $218{\pm}181 cmH_2O{\cdot}sec/min$, respectively, p=0.042) and $T_1/T_{TOT}$($0.37{\pm}0.04$, $0.40{\pm}0.08$, respectively, p=0.026) were significantly lower in CPAP+PS than in SIMV alone. Conclusion: PS up to 15 cm $H_2O$ increased tidal volume, decreased work of breathing and pressure time product in both SIMV and CPAP modes. PS decreased respiration rate in SIMV mode but not in CPAP mode, while it reduced central respiratory drive($P_{0.1}$) and shortened duty cycle ($T_1/T_{TOT}$) in CPAP mode but not in SIMV mode. By 10 em $H_2O$ of PS in CPAP mode, same tidal volume was obtained as in SIMV mode, and both methods were comparable in respect to RR, WOB, $P_{0.1}$, but CPAP+PS was superior in respect to the efficiency of the respiratory muscle work (PTP) and duty cycle($T_1/T_{TOT}$).

• 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.46 no.5
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• pp.674-684
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• 1999

Background : It has been generally known that the incidence of lung cancer is higher in the patients with idopathic pumonary fibrosis (IPF) than those in general population. The reported incidence was variable from 4.8 to 43.2%. There were controversies on the most frequent cell type (squamous cell carcinoma vs. adenocarcinoma) and no study was done about the real concordance of cancer and the fibrotic lesion. And the pulmonary fibrosis may influence not only the development of cancer but also the treatment and prognosis of the cancer, but there was no report on that point. Method : Total 63 patients ($66.8{\pm}7.8$ year, M : F=61 : 2) were diagnosed as IPF combined with lung cancer (IFF-CA) at Asan Medical Center. A retrospective analysis was done about the risk factors of the lung cancer, pulmonary function test, the site of cancer(especially the relationship of the cancer with the fibrotic lesion), the histologic types, and the stage of cancer. The histologic types were compared with those of 2,660 patients with lung cancer who were diagnosed at the same institute for the same period. The effect of IPF on the treatment of the cancer was evaluated with the survival time after the detection of lung cancer. Results : The lung cancer was found in 63(22.9%) out of 281 patients with IPF. But in most of them(45 patients), lung cancer was detected at the same time with IPF and only in 18 patients, the cancer was diagnosed during the follow-up($25.2{\pm}17.7$ months) of IPF. So in our study, 6.7% of patients with IPF developed lung cancer during the course of the disease. The age ($66.8{\pm}7.84$ vs. $63.4{\pm}11.1$ years), percentage of smoker (88.9 vs. 67.2%), and the male gender (96.8 vs. 67.6%) were significantly higher in IPF-CA compared with lone IPF (p<0.05). The odds ratio of smoking was 4.7 compared with non smoking IPF controls. The lung cancer was located more frequently in the upper lobe and 55.5% was in the periphery of lung. The cancer was developed in the fibrotic lesion in 23 patients (35.9%), and in the majority of the patients, the cancer was separated from the fibrosis. The cell type of the lung cancer in IPF-CA was squamous cell carcinoma 34.9%, adenocarcinoma 30.2%, small cell carcinoma 19.0%, large cell undifferenciated carcinoma 6.3%, and others 9.5%. No significant difference in the distribution of histologic type of the lung cancer was found between IPF-CA and lone lung cancer. There was no significant difference in demographic features, cell types, location and the stage of the cancer between the group with concurrent IPF-CA and the group with cancer diagnosed during the follow up of IPF. There was a tendency (but statistically not significant : p=0.081) of higher incidence of adenocarcinoma among the cancers developed in the fibrotic area(43.5%) (F-CA) than in the cancers in non-fibrotic area (22.5%) (NF-CA). The prognosis of the patients with F-CA was poor (median survival : 4 months) compared with the patients with NF-CA (7 months, p=0.013), partly because the prevalence of severe IPF (the extent of fibrosis in HRCT 50%) was higher in F-CA group. Conclusion : These data suggest that the lung cancer in the patients with IPF has similar features to the ordinary lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.51 no.4
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• pp.303-314
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• 2001

Background : Matrix metalioproteinase(MMP)-2 and MMP-9 have been known to play an important role in cell migration and the tissue remodeling process by type IV collagen lysis, a major component of the basement membrane. Intra-alveolar fibrosis, secondary to an injury to the basement membrane of the alveolar epithelial lining, is a major process in the pathogenesis of idiopathic pulmonary fibrosis(IPF). Therefore, MMP-2 and MMP-9 was hypothesized to play an important role in IPF pathogenesis. As a result, their level may reflect the activity or prognosis. Method : Forty one progressive IPF patients(age $59.82{\pm}1.73$ years, M:F=23:18), 16 patients with stable IPF for more than one year without therapy(age : $63.6{\pm}2.8$ years, M:F=13:3), and 7 normal controls were enrolled in this study. The MMP-2 and MMP-9 levels in the BAL fluid and alveolar macrophage conditioned media(AM-CM) were measured by zymography and the TIMP-1 level was measured by ELISA. Results : 1) The MMP-2 level in BALF was highest in the progressive IPF group ($1.36{\pm}0.28$) followed by the stable group ($0.46{\pm}0.13$) and the controls ($0.08{\pm}0.09$), which was statistically significant. The MMP-9 level of the IPF ($0.31{\pm}0.058$) and the stable group ($0.22{\pm}0.078$) were higher than that of the control group ($0.002{\pm}0.004$). In the AM-CM, only MMP-9 was detected, which was significantly higher in IPF group ($0.80{\pm}0.1O$) than in the control group($0.23{\pm}0.081$). The TIMP-1 level was also higher in both the IPF ($36.34{\pm}8.62\;{\mu}g/ml$) and stable group ($20.83{\pm}8.53\;{\mu}g/ml$) compared to the control group ($2.80{\pm}1.05\;{\mu}g/ml$) (p<0.05). 3) There was a correlation between the MMP-2 level in the BALF with the total cell number(r=0.298) and neutrophils(r=0.357) (p<0.05), and the MMP-9 level with the number of neutrophils (r=0.407) and lymphocytes (r=0.574)(p<0.05). The TIMP-1 level correlated with the total number of cell (r=0.338, p<0.05) and neutrophils(r=0.449, p=0.059). Conclusion : Both MMP and TIMP appear to play an important role in IPF pathogenesis, and their level may reflect the disease activity.

• 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.