• Tuberculosis and Respiratory Diseases
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• v.70 no.1
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• pp.69-73
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• 2011

The combination therapy of pegylated interferon and ribavirin is the mainstay of treatment for chronic hepatitis C patients. Anti-viral therapy is commonly associated with side effects such as headache, fever, myalgia, and arthralgia. However, anti-viral therapy can continue because these side effects are mostly mild and can be improved with supportive management. Anti-viral therapy should be stopped promptly if serious side effects, such as interstitial pneumonitis or hemolytic anemia occur, although those serious side effects are rare. There were a few case reports of interferon-related interstitial pneumonitis worldwide. In Korea, one atypical case report of interstitial pneumonitis has been reported, which followed the combination therapy of interferon-alpha and ribavirin in a patient with chronic hepatitis C. We present a case of interstitial pneumonitis and pancytopenia following the combination therapy of pegylated interferon and ribavirin in a patient with chronic hepatitis C.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.637-644
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• 1996

Interstitial pneumonitis associated with interferon alpha therapy for chronic hepatitis C was first describe6 in 1994 by Kazoo et al In Japan. The mechanism of interstitial pneumonitis developed by interferon alpha was still unknown but immunologic, allergic of direct lung toxicity were suggested. We experienced a case of interstitial pneumonitis developed during interferon alpha therapy for chronic hepatitis C in a 52-year-old male patient. He was treated with 6 million units of interferon alpha intramuscularly 3 times per week for 4 weeks and noted progressive dyspnea and cough. These symptoms were subsided after 6 weeks' discontinuation of interferon alpha therapy. And so, he was retreated with 3 million units of interferon alpha 3 times per week for 8 weeks and felt dyspnea again. He was admitted to our hospital for further evaluation of progressive dyspnea. Arterial blood gas(ABG) values were $PaO_2$ 90.7 mmHg and $PaCO_2$ 31.9 mmHg, and antinuclear antibody(ANA) was negative. A chest X-ray film revealed diffuse reticulo-nodular shadows in bilateral lung fields, suggesting a diagnosis of interstitial pneumonitis. A marked increase in lymphocyte count and suppressor T cell were observed in bronchoalveolar lavage(BAL) fluid. Lymphocyte stimulation test with interferon alpha was positive. Interstitial pneumonitis was confirmed by transbronchial lung biopsy. After discontinuation of interferon alpha, we gave oral steroid in the condition that clinical symptoms were being improved gradually.

• The Journal of Korean Medicine
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• v.25 no.2
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• pp.41-50
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• 2004

Backgrounds & Objectives: Many acute and chronic lung disorders with variable degrees of pulmonary inflammation and fibrosis are collectively referred to as interstitial lung diseases. Idiopathic pulmonary fibrosis (IPF) is one of several idiopathic interstitial pneumonias with the pathogenesis unclear. Astragali Radix is known to inhibit the Th2 immune response. The effects of Astragali Radix on bleomycin-induced lung fibrosis were evaluated. Materials and Methods: Astragali Radix extract was daily given to the normal rats, control (bleomycin) and treated (bleomycin and Astragali Radix extract, 24.0 mg/10g body weight) rats for 14 days. After 14 days, we observed the change of total leukocyte count and percentage, IFN-gamma and IL-4 in BALF (Bronchoalveolar lavage fluid), and of semiquantitative histological index (SHI). Results: Compared to the control group, Astragali Radix decreased total leukocyte count (p<0.05), lymphocyte (p<0.05), neutrophil (no significance) percentage, SHI (p<0.05), IFN-gamma and IL-4 (p<0.05). Otherwise, macrophage percentage was increased (p<0.01). Conclusion: This study showed that Astragali Radix reduced the incidence of inflammatory cells and cytokines and prevented the fibrosis of tissue in bleomycin-induced lung fibrosis rats.

• Journal of Yeungnam Medical Science
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• v.39 no.2
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• pp.153-160
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• 2022

Multicentric Castleman disease (MCD) is an uncommon systemic lymphoproliferative disorder that may cause multiple organ damage. Castleman disease-associated diffuse parenchymal lung disease (DPLD) has not been well studied. A 32-year-old man was referred to our hospital for progressive generalized weakness, light-headedness, and dyspnea on exertion for more than one year. Laboratory evaluations showed profound anemia, an elevated erythrocyte sedimentation rate, and an increased C-reactive protein level with polyclonal hypergammaglobulinemia. Chest radiography, computed tomography (CT), and positron emission tomography-CT scan demonstrated diffuse lung infiltration with multiple cystic lesions and multiple lymphadenopathy. In addition to these clinical laboratory findings, bone marrow, lung, and lymph node biopsies confirmed the diagnosis of idiopathic MCD (iMCD). Siltuximab, an interleukin-6 inhibitor, and glucocorticoid therapy were initiated. The patient has been tolerating the treatment well and had no disease progression or any complications in 4 years. Herein, we report this case of human herpesvirus-8-negative iMCD-associated DPLD accompanied by multiple cystic lesions, multiple lymphadenopathy, and polyclonal hypergammaglobulinemia with elevated immunoglobulin G (IgG) and IgG4 levels. We recommend a close evaluation of MCD in cases of DPLD with hypergammaglobulinemia.

• Tuberculosis and Respiratory Diseases
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• v.40 no.4
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• pp.357-366
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• 1993

Background: Lung clearance of inhaled $^{99m}Tc$-DTPA reflects alveolar epithelial permeability and it had been reported as more sensitive than conventional pulmonary function tests in detecting lung epithelial damage. However, measuring lung clearance of inhaled $^{99m}Tc$-DTPA by gamma camera may not always reflect alveolar epithelial permeability exactly because it is influenced by mucociliary clearance depending on the site of particle deposition. Moreover, this method takes much time and patient's effort because he has to sit or lie still in front of the camera for a prolonged period. Most of the absorbed DTPA is excreted in urine within 24 hours and the amount of excreted DTPA in urine during the first few hours after inhalation is influenced by absorption rate which is correlated with the alveolar-epithelial permeability suggesting that the urinary excretion, especially in first few hours, may be an alternate index for lung clearance. The purpose of this study was to evaluate the usefulness of ratio of excreted $^{99m}Tc$-DTPA in 2 hour and 24 hour urine as an index of alveolar-epithelial damage. Methods: Pulmonary function tests including diffusing capacity and lung clearance of $^{99m}Tc$-DTPA measured by gama camera ($T_{1/2}$) and 2hr/24hr urine excretion ratio (Ratio) of inhaled $^{99m}Tc$-DTPA in 8 normal subjects and 14 patients with diffuse interstitial lung disease were compared. Results: 1) In the normal control, there was significant negative correlation between the $T_{1/2}$ and the Ratio (r=-0.77, p<0.05). In patients with diffuse interstitial lung disease, there also was significant negative correlation between $T_{1/2}$ and Ratio(r=-0.63, p<0.05). 2) In diffuse interstitial lung disease patients, the $T_{1/2}$ was $38.65{\pm}11.63$ min which was significantly lower than that of normal control, $55.53{\pm}11.15$ min and the Ratio was $52.15{\pm}10.07%$ also signifantly higher than that of the normal control, $40.43{\pm}5.53%$ (p<0.05). 3) There was no significant correlations between $T_{1/2}$ or Ratio and diffusing capactiy of lung in both patients and controls (p>0.05). Conclusion: These results suggests that 2hr/24hr urine excretion ratio of inhaled $^{99m}Tc$-DTPA is a useful simple bedside test in assessing alveolar epithelial permeability and that it may be used as an additive follow-up test in patients with diffuse interstitial lung disease complementing conventional pulmonary function tests.

• The Journal of Pediatrics of Korean Medicine
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• v.22 no.2
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• pp.37-49
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• 2008

Objectives : Idiopathic pulmonary fibrosis (IPF) is chronic fibrotic interstitial pneumonia and the pathogenesis is unknown. Peucedani Radix is well-known for the treatment of respiratory diseases and pulmonary hypertension. This study was to evaluate the effectiveness of Peucedani Radix on the bleomycin-induced lung fibrosis model (BLFM) in mouse. Methods : We induced lung fibrosis by intratracheal instillation of bleomycin in C57BL/6J. We compared two groups BLFM without Peucedani Radix (group I) and BLFM with Peucedani Radix (group II). We performed bronchoalveolar lavages (BAL) and obtained lung specimens from both group I and II on the 7th (A) and 21st (B) day, and also for the normal group. We compared with group I and II to find BAL by using ANOVA test and to find pathologic symptoms by using semiquantitative histological index (SHI). Results : In BAL, total cell counts, lymphocytes, and neutrophils was increased in both group I and II comparing with normal group. However, lymphocyte level was decreased more in group IIB than group IB. It was statistically significant. In microscopic findings, scores of SHI in normal group, group IB and IIB were 0.33, 4.47, and 1.96 each. Conclusions : Peucedani Radix might have inhibitory effect on lung fibrosis by reducing inflammatory cells in bleomycin-induced lung fibrosis model in mouse.

• Tuberculosis and Respiratory Diseases
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• v.49 no.5
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• pp.601-613
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• 2000

Background : Idiopathic pulmonary fibrosis (IPF) is a fatal progressive fibrous disease of the lung of unknown etiology. Recently it has been classified into several distinct entities on the basis of pathologic and clinical characteristics, ie : usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), acute interstitial pneumonia (AIP), bronchiolitis obliterans with organizing pneumonia (BOOP), and nonspecific interstitial pneumonia (NSIP). IPF is now applied only for UIP, which has the worst prognosis. The previous reports of 3-5 year median survival appears to be overoptimistic because other types with better prognosis like NSIP or BOOP might have been included. Therefore, this study was performed to determine the clinical course and the prognostic factors of UIP as diagnosed by surgical lung biopsy. Methods : The subjects were 72 UIP patients (age $58.2{\pm}11.6$ years, M : F=45 : 27, median follow up period : 18.1 months (0.7-103.6) diagnosed by surgical lung biopsy at the Asan Medical Center (68 patients) and the Paik Hospital in Seoul (4 patients). Clinical scores (level of dyspnea : 1-20 points), radiologic score (honeycombing : HC score 0-5 points, ground glass : GG score 0-5 points), and physiologic scores (FVC : 1-12 points, $FEV_1$ : 0-3 points, TLC : 0-10 points, $D_{LCO)$ : 0-5 points, $AaDO_2$ : 0-10 points) were summed into a total CRP score. Results : 1) The one year survival rate was 78.3%, while the rate for three year survival was 58.1%, and the median survival period was 42.5months. 2) Short term (1 year) prognosis : The patients who died within one year of diagnosis (14 patients) had the higher initial total CRP score ($28.6{\pm}8.3$ vs. $16.6{\pm}9.7$) than those who lived longer than one year (46 patients). The difference in the total CRP score was attributed to the symptom score ($8.4{\pm}2.1$ vs. $5.7{\pm}3.9$) and the physiologic score ($15.7{\pm}7.1$ vs. $6.7{\pm}5.7$) including FVC, $D_{LCO)$ and $AaDO_2$. 3) Long-term (3year) prognosis : The total CRP score ($12.2{\pm}6.7$ vs. $28.7{\pm}7.9$ : including symptom score, FVC, $D_{LCO)$ and $AaDO_2$) at the time of diagnosis were also different for the long-term survivors and those who lived less than 3 years. 4) Cox regression analysis showed $D_{LCO)$ (${\geq}$60%) (Hazard ratio : 4.56, 95% CI : 2.30-16.04) was the independent prognostic factors of UIP (P<0.05). Conclusion : These results suggest that $D_{LCO)$ at the time of diagnosis seem to be a prognostic markers of biopsy-proven UIP.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.954-964
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• 1996

Background : The type of the infiltrating cells in al veolitis may be determined by the chemokines in the lesion. MIP-1 ${\alpha}$, a C-C type chemokine, stimulates proliferation and cytokine secretion from macrophages and induces early neutrophilic and later monocytic inflammation in vi vo. IL-8, a C-X-C type chemokine is known to attract neutrophils and T-lymphocytes. This study is performed to find out the relative role of two different chemokines in diffuse interstitial lung disease. Subject and Method : We measured the secretion of MIP- 1 ${\alpha}$ and IL-8 from alveolar macrophages(AM), and their level in BAL fluid of 26 patients with DILD (10 IPF, 4 collagen disease, 10 sarcoidosis, and 2 hypersensitivity pneumonitis) and 7 normal control. Result: IL-8 secretion was significantly increased in patients with DILD ($8.15{\pm}4.58$ ng/ml) than in normal ($1.10{\pm}0.93$ ng/ml, p=0.0003). Significant correlation was found between IL-8 secretion and total cell number in BAL fluid (r=0.484, p=0.0068), %(r=0.592, p=0.0004) and No. (r=0.516, p=0.0042) of lymphocyte, and % of AM (r=-0.505, 0.0032). MIP- 1 ${\alpha}$ secretion was also increased in DILD ($2.41{\pm}1.45$ ng/ml) compared to control ($0.63{\pm}0.30$ ng/ml, p=0.0031), and showed a tendency of correlation with total cell number (r=0.368, p=0.0456) and No. of alveolar macrophages (r=0.356, p=0.0579) in BAL fluid. The concentration of IL-8 in BAL fluid was significantly increased in the patients with DILD ($40.4{\pm}34.5$ pg/ml) compared to control ($3.90{\pm}2.47$ pg/ml, p=0.0094) and it showed a significant correlation with the total cell number (r=0.484, p=0.0068), %(r=-0.505, p=0.0032) of AM, and % (r=0.592, p=0.0004) and No. (r=0.516, p=0.0042) of lymphocyte in BAL fluid. But there was a no significant difference in MIP- 1 ${\alpha}$ concentration in BAL fluid between normal control group and the patients with DILD. Conclusion : From the above results, we concluded that AM of DILD releases increased amount of both IL-8 and MIP- 1 ${\alpha}$ but IL-8 has better correlation with the type of alveolitis.

• Tuberculosis and Respiratory Diseases
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• v.38 no.1
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• pp.1-7
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• 1991

To study the frequency of the underlying disease of the diffuse pulmonary infiltrates in korea, we ansalyzed retrospectively 982 patients who were seen at nine university hospitals and one general hospital in Seoul area. The results are folloing: 1) Among the total 982 patients, 490 patients were male and 492 patients were female. The mean age was 44.3 years. 2) The most common etiology was milliary tuberculosis (38%), which was followed by, idopathic pulmonary fibrosis (27%), pulmonary fibrosis associated with collagen-vascular disease (15%), and diffuse pulmonary infiltrates by malignancy (10%). 3) Amon the connective tissue disease which was accompanied by the interstitial lung disease, rheumatoid arthritis was the most common disease (43%), systemic lupus erythematosus was the 2nd (28%), and progressive systemic sclerosis was the 3re (16%). 4) Among 101 cases of malignant disease, lung was the most frequent primary site (31%), which was followed by stomach (28%), thyroid (16%), and breast (6%). 5) For the diagnosis of the underlying disease of pulmonary infiltrates, the transbronchial lung biopsy was performed in 21% of the patients and open lung biopsy was done in 7%.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.835-845
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• 1998

Background: Silica-induced lung diseases is characterized by the accumulation of inflammatory cells at early stage and fibrosis in pulmonary parenchyma and interstitium at late stage. As a consequence of inflammation, silicosis is accompanied with the expansion of interstitial collagen and the formation of fibrotic nodule. In this process, several kinds of lung cells produce cytokines which can amplify and modulate pulmonary fibrosis. The alveolar macrophage is a potent source of proflammatory cytokines and growth factor. But in the process of silicotic inflammation and fibrosis, there are many changes of the kinetics in cytokine network. And the sources of cytokines in each phase are not well known. Method: 2.5 mg of silica was instillated into the lung of C57BL/6J mice. After intratracheal instillation of silica, the lungs were removed for imunohistochemical stain at 1, 2, 7 day, 2, 4, 8, 12 week, respectively. We investigated the expression of IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ in lung tissue. Results: 1) The expression of IL-6 increased from 1 day after exposure to 8 weeks in vascular endothelium. Also peribronchial area were stained for IL-6 from 7 days and reached the peak level for 4 weeks. 2) The IL-1 $\beta$ was expressed weakly at the alveolar and peribronchial area through 12 weeks. 3) The TNF-$\alpha$ expressed strongly at alveolar and bronchial epithelia during early stage and maintained for 12 weeks. 4) TGF-$\beta$ was expressed strongly at bronchial epithelia and peribronchial area after 1 week and the strongest at 8 weeks. Conclusion: The results above suggests IL-6, TNF-$\alpha$ appear to be a early inflammatory response in silica induced lung fibrosis and TGF-$\beta$ play a major role in the maintenance and modulation of fibrosis in lung tissue. And the regulation of TNF-$\alpha$ production will be a key role in modultion of silica-induced fibrosis.