• Tuberculosis and Respiratory Diseases
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• v.42 no.1
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• pp.58-66
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• 1995

Background: Acute interstitial pneumonia is a relatively rare form of interstitial pneumonia, since the vast majority of interstitial pneumonia have a more chronic course. It corresponds to the lesion described by Hamman and Rich, as Hamman-Rich disease in 1944. Another name in the clinical literature is accelerated interstitial pneumonia, idiopathic acute respiratory distress syndrome (idiopathic ARDS), and the organizing stage of diffuse alveolar damage. Acute interstitial pneumonia differs from chronic interstitial pneumonia by clinical and pathologic features. Clinically, this disease is characterized by a sudden onset and a rapid course, and reversible disease. Method and Purpose: Five cases of pathologically proven acute interstitial pneumonia were retrospectively studied to define the clinical, radiologic, and pathologic features. Results: 1) The five cases ranged in age from 31 to 77 years old. The onset of illness was acute in all patients, it began with viral-like prodrome 6~40 days prior to shortness of breath, and respiratory failure eventually developed in all patients. In 2 cases, generalized skin rash was accompanied with flu-like symptoms. Etiologic agent could not be identified in any case. 2) All patients had leukocytosis and severe hypoxemia. Pulmonary function test of 3 available cases shows restrictive ventilatory defect, and one survived patient(case 5) has a complete improvement of pulmonary function after dismissal. 3) Diffuse bilateral chest infiltrates were present radiologically. Theses were the ground-glass, consolidation, and reticular densities without honeycomb fibrosis in all patients. The pathologic abnormalities were the presence of increased numbers of macrophages and the formation of hyaline membranes within alveolar spaces. There was also interstitial thickening with edema, proliferation of immature fibroblast, and hyperplasia of type II pneumocyte. In the survived patient(case5), pathologic findings were relatively early stage of acute interstitial pneumonia, such as hyaline membrane with mild interstitial fibrosis. 4) Of the 5 patients, four patients died of respiratory failure 14~90 days after onset of first symptom, and one survived and recovered in symptoms, chest X ray, and pulmonary function test Conclusion: These results emphasize that acute interstitial pneumonia is clinically, radiologically, and pathologically distinct form of interstitial pneumonia and should be separated from the group of chronic interstitial pneumonia. Further studies will be needed to evaluate the pathogenesis and the treatment of acute interstitial pneumonia.

• Tuberculosis and Respiratory Diseases
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• v.43 no.1
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• pp.75-87
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• 1996

Background: Lung cancer is the second most frequent malignancy in man in Korea. Surgery is the best treatment modality for non-small cell lung cancer, but most patients were presented in far advanced stage. So radiation therapy(RT) with or without chemotherapy is the next choice and radiation-induced pneumonitis and pulmonary fibrosis is the major limiting factor for the curative RT. Radiation pneumonitis is manifested with fever, cough and dyspnea, 2~3 months after the termination of radiotherpy. Chest X ray shows infiltration, typically limited to the radiation field, but occasionally bilateral infiltration was reported. Also Gibson et al reported that BAL lymphocytosis was found in both lungs, even though the radiation was confined to one lung. The aim of this study is to investigate the change of adhesion molecules expression on BAL cells and serum soluble ICAM-1(sICAM-1) level after the RT and its relationship to the development of radiation pneumonitis. The second aim is to confirm the bilaterality of change of BAL cell pattern and adhesion molecule expression. Subjects: BAL and the measurement of sICAM level in serum and BALF were done on 29 patients with lung cancer who received RT with curative intention. The BAL was done before the RT in 16 patients and 1~2 month after RT in 18 patients. 5 patients performed BAL before and after RT. Result: Clinically significant radiation pneumonitis developed in 7 patients. After RT, total cell count in BAL was significantly increased from $(20.2{\pm}10.2){\times}10^6\;cells/ml$ to $(35.3{\pm}21.6){\times}10^6\;cells/ml$ (p=0.0344) and %lymphocyte was also increased from $5.3{\pm}4.2%$ to $39.6{\pm}23.4%$ (p=0.0001) in all patient group. There was no difference between ipsilateral and contraleteral side to RT, and between the patients with and without radiation-pneumonitis. In whole patient group, the level of sICAM-1 showed no significant change after RT(in serum: $378{\pm}148$, $411{\pm}150\;ng/ml$, BALF: $20.2{\pm}12.2$, $45.1{\pm}34.8\;ng/ml$, respectively), but there was a significant difference between the patients with pneumonitis and without pneumonitis (serum: $505{\pm}164$ vs $345{\pm}102\;ng/ml$, p=0.0253, BALF: $67.9{\pm}36.3$ vs $25.2{\pm}17.9\;ng/ml$, p=0.0112). The expression of ICAM-1 on alveolar macrophages (AM) tends to increase after RT (RMFI: from $1.28{\pm}0.479$ to $1.63{\pm}0.539$, p=0.0605), but it was significantly high in patients with pneumonitis ($2.10{\pm}0.390$) compared to the patients without pneumonitis ($1.28{\pm}0.31$, p=0.0002). ICAM-1 expression on lymphocytes and CD 18 (${\beta}2$-integrin) expression tended to be high in the patients with pneumonitis but the difference was statiastically not significant. Conclusion: Subclinical alveolitis on the basis of BAL finding developed bilaterally in all patients after RT. But clinically significant pneumonitis occurred in much smaller fraction and the ICAM-1 expression on AM and the sICAM-1 level in serum were good indicator of it.

• Tuberculosis and Respiratory Diseases
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• v.40 no.1
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• pp.6-15
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• 1993

Background: Positive end, expiratory pressure (PEEP) has become one of the standard therapies for adult respiratory distress syndrome (ARDS). Total static compliance has been proposed as a guide to determine the size of PEEP ('best PEEP') which is of unproven clinical benefit and remains controversial. Besides increasing functional residual capacity and thus improving oxygenation, PEEP stimulate prostacyclin secretion and was proposed for the treatment of acute pulmonary embolism. But little is known about the effect of PEEP on hemodynamic and gas exchange disturbances in acute pulmonary embolism. Methods: To study the validity of total static compliance as a predictor of 'best PEEP' in ARDS and acute pulmonary embolism, experimental ARDS was induced in mongrel dog with oleic acid and acute pulmonary embolism with autologous blood clot. Then hemodynamic and gas exchange parameters were measured with serial increment of PEEP. Results:In ARDS group, total static compliance and oxygen transport were maximal at 5 cm$H_2O$, and decreased thereafter (p<0.05). With increment of PEEP, arterial oxygen tension ($PaO_2$) and arterial carbon dioxide tension ($PaCO_2$) increased and cardiac output and physiological shunt decreased. In pulmonary embolism group, total static compliance, oxygen transport, physiological shunt and cardiac output decreased and $PaO_2$ and $PaCO_2$ increased with increment of PEEP (p<0.05). Comparing the change induced by increment of PEEP by 1 cm$H_2O$ in ARDS group with that in pulmonary embolism group, there was no significant difference between two groups except cardiac output which decreased more in pulmonary embolism group (p<0.05). In ARDS group, oxygen transport and total static compliance increased after PEEP application, and total static compliance was maximal at the PEEP level where oxygen transport was maximal. However in pulmonary embolism group, oxygen transport and total static compliance decreased after application of PEEP. There was significant correlation between change of total static compliance and change of oxygen transport in both groups. Conclusion: In both ARDS and acute pulmonary embolism, it can be concluded that total static compliance is useful as a predictor of 'best PEEP'.

• Tuberculosis and Respiratory Diseases
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• v.53 no.4
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• pp.409-419
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• 2002

Background : The therapeutic effects of surfactant on acute lung injury derive not only from its recruiting action on collapsed alveoli but also from its anti-inflammatory effects. Pro-apoptotic action on alveolar neutrophils represents one of the important anti-inflammatory mechanisms of surfactant. In the present study, we evaluated the effects of sufactant on the apoptosis of human peripheral and rat alveolar neutrophils. Methods : In the (Ed- the article is not definitely needed but it helps to separate the two prepositions 'in') in vitro study, human neutrophils were collected from healthy volunteers. An equal number of neutrophils ($1{\times}10^6$) (Ed-confirm) was treated with LPS (10, 100, 1000ng/ml), surfactant (10, 100, $1000{\mu}g/ml$), or a combination of LPS (1000ng/ml) and surfactant (10, 100, $1000{\mu}g/ml$). After incubation for 24 hours, the apoptosis of neutrophils was evaluated by Annexin V method. In the in vivo study, induction of acute lung injury in SD rats by intra-tracheal instillation of LPS (5mg/kg) was followed by intra-tracheal administration of either surfactant (30mg/kg) or normal saline (5ml/kg). Tenty-four hours after LPS instillation, alveolar neutrophils were collected and the apoptotic rate was evaluated by Annexin V method. In addition, changes of the respiratory mechanics of rats (respiratory rate, tidal volume, and airway resistance) were evaluated with one chamber body plethysmography before, and 23 hours after, LPS instillation. Results : in the in vitro study, LPS treatment decreased the apoptosis of human peripheral blood neutrophils (control: $47.4{\pm}5.0%$, LPS 10ng/ml; $30.6{\pm}10.8%$, LPS 100ng/ml; $27.5{\pm}9.5%$, LPS 1000ng/ml; $24.4{\pm}7.7%$). The combination of low to moderate doses of surfactant with LPS promoted apoptosis (LPS 1000ng/ml + Surf $10{\mu}g/ml$; $36.6{\pm}11.3%$, LPS 1000ng/ml +Surf $100{\mu}g/ml$; $41.3{\pm}11.2%$). The high dose of surfactant ($1000{\mu}g/ml$) decreased apoptosis ($24.4{\pm}7.7%$) and augmented the anti-apoptotic effect of LPS (LPS 1000ng/ml + Surf $1000P{\mu}g/ml$; $19.8{\pm}5.4%$). In the in vivo study, the apoptotic rate of alveolar neutrophils of surfactant-treated rats was higher than that of normal saline-treated rats ($6.03{\pm}3.36%$ vs. $2.95{\pm}0.58%$). The airway resistance (represented by Penh) of surfactant-treated rats was lower than that of normal saline-treated rats at 23 hours after LPS injury ($2.64{\pm}0.69$ vs. $4.51{\pm}2.24$, p<0.05). Conclusion : Surfactant promotes the apoptosis of human peripheral blood and rat alveolar neutrophils. Pro-apoptotic action on neutrophils represents one of the important anti-inflammatory mechanisms of surfactant.

• Tuberculosis and Respiratory Diseases
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• v.52 no.4
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• pp.317-329
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• 2002

Background : Immunotherapy is another treatment modality for various cancers. There is little information on the antitumor effects of immunotherapy on implanted lung cancer mouse models. Toxoplasma gondii is able to potently induce a nonspecific stimulation of the host immune system. Therefore, this study evaluated the antitumor and antimetastatic effect of nonspecific immune stimulation by T. gondii in a Lewis lung cancer mouse model. Methods : Female C57BL/6 mice were injected with either Lewis lung cancer cells ($1{\times}10^6$ per mouse) or 5 cysts from the T. gondii Me49 strain with various schedules. The number of survival days, the tumor size of the implanted muscle and the histopathological findings of each group were noted. In addition to these mice, the Toxoplasma antigen($50{\mu}g$ per mouse) or a lymphokine (0.5 ml per mouse) was added to boost the immunotherapy. Results : No mouse in the Toxoplasma-infected group had died, whereas the mice receiving only the cancer cells (cancer control) survived for $29.1{\pm}4.4$ days. Cancer cells were revealed from 1 week after cancer cell inceulation in the muscle and from 3 weeks in the lung of the cancer control, whereas cancer cells were found in both the preinfection control and coinfection control groups from 2 weeks and 4 weeks in the lung respectively. The in the number of survival days were $32.4{\pm}3.3$ in the mice receiving T. gondii 2 weeks prior to the cancer cells inoculation (preinfection control), $30.9{\pm}5.1$ in mice received both simultaneously (coinfection control), and $34.9{\pm}2.9$ in mice received T. gondii 2 weeks after cancer cells implantation (postinfection control). These 3 infection groups had significantly longer survival days and suppressed tumor growth than those of the cancer control. In addition to these mice, and injection with the Toxoplasma antigen alone or in combination with lymphokine resulted in a significant increase in the number of survival days. Conclusion : These findings suggest that an injection with T. gondii can induce the antitumor and antimetastatic effects in Lewis lung cancer mouse models. Moreover, these effects were increased with an injection of the Toxoplasma antigen alone or in combination with lymphokine. However, this therapy can not prevent the development of cancer.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.323-331
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• 2000

Purpose: Brain metastases are present in approximately 10-16% of small cell lung cancer patients at diagnosis. Brain metastasis is an important clinical problem associated with increasing the survival rate, with a cumulative incidence of up to 80% in patients surviving 2 years. Prophylactic cranial irradiation(PCI) reduces the incidence of brain matastasis and may prolong survival in patients with limited small-cell lung cancer who achieved complete remission. This study was performed to analyze the incidence of brain metastasis, survival and clinical aspects after PCI in patients with limited small-cell lung cancer who achieved complete remission. Methods : Between 1989 and 1999, forty-two patients with limited small-cell lung cancer who achived achieved complete remission after therapy were enrolled into this study retrospectively. All patients received etoposide and cisplatin(VPP) alternating with cytoxan, adriamycin, and vincristine(CAV) every 3 weeks for at least 6 cycles initially. All patients received thoracic radiotherapy: concurrent(38.1%) and sequential(61.9%). All patients received late PCI. Results : Most patients(88.1%) were men, and the median age was 58 years. The median follow-up duration was 18.1 months. During the follow-up period, 57.1% of the patients developed relapse. The most frequent site of relapse was chest(35.7%), followed by brain(14.3%), liver(11.9%), adrenal gland(44%), and bone(2.2%). With the Kaplan-Meier method, the average disease-free interval was 1,090 days(median 305 days). The average time to development of brain relapse after PCI and other sites relapse(except brain) were 2,548 days and 1,395 days(median 460 days), respectively. The average overall survival was 1,233 days(median 634 days, 21.1 months), and 2-year survival rates was 41.7%. The average overall survival in the relapse group was 642 days(median 489 days) and in the no relapse group was 2,622 days(p<0.001). The average overall survival in the brain relapse group was 928 days(median 822 days) and in the no brain relapse group was 1,308 days(median 634 days)(p=0.772). In most patients(85.7%), relapse(except brain) or systemic disease was the usual cause of death. Brain matastasis was the cause of death in 14.3% of the cases. Conclusions : We may conclude that PCI reduces and delays brain metastasis in patients with limited small cell lung cancer who achieved complete remission. We found decreased survival in relapse group but, no significant survival difference was noted according to brain matastasis. And relapse(except brain) or systemic disease was the usual cause of death. In order to increase survival, new treatment strategies for control methods for relapse and systemic disease are required.

• Tuberculosis and Respiratory Diseases
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• v.46 no.6
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• pp.795-802
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• 1999

Objective : Cardiopulmonary exercise test is a useful tool to evaluate the operative risk and to plan exercise treatment for the patients with chronic obstructive pulmonary disease(COPD). In cardiopulmonary exercise test, most of the measured parameters are recorded at the time of peak exercise, which are hard to attain in COPD patients. So we evaluated the usefulness of the parameter, breathing reserve index(BRI=minute ventilation [$V_E$]/maximal voluntary ventilation[MVV]) at the time of anaerobic threshold($BRI_{AT}$) for the differentiation of COPD patients with normal controls. Methods : Thirty-six COPD patients and forty-two healthy subjects underwent progressive, incremental exercise test with bicycle ergometer upto possible maximal exercise. All the parameters was measured by breath by breath method. Results : The maximal oxygen uptake in COPD patients (mean$\pm$SE) was $1061.2{\pm}65.6ml/min$ which was significantly lower than $2137.6{\pm}91.4ml/min$ of normal subjects(p<0.01). Percent predicted maximal oxygen uptake was 54.3% in COPD patients and 86.0% in normal subjects(p<0.01). Maximal exercise(respiratory quotient; $VCO_2/VO_2{\geq}1.09$) was accomplished in 7 of 36 COPD patients(19.4%) and in 18 of 42 normal subjects(42.9%). The $BRI_{AT}$ of COPD patients was higher($0.50{\pm}0.03$) than that of control subject($028{\pm}0.02$, p<0.01), reflecting early hyperventilation in COPD patient during exercise. The correlation between $BRI_{AT}$ and BRI at maximal exercise in COPD patients was good(r=0.9687, p<0.01). Conclusion : The $BRI_{AT}$ could be a useful parameter for the differentiation of COPD patients with normal controls in the submaximal cardiopulmonary exercise test.

• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.415-428
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• 2003

Background : This study assessed the efficacy and toxicity of etoposide and carboplatin(EC) combination regimen as a first line therapy for small cell lung cancer(SCLC), and determined the efficacy and toxicity of topotecan for relapsed SCLC. Methods : One hundred and ten patients with previously untreated SCLC received etoposide($100mg/m^2$ i.v., day 1 to 3) and carboplatin($300mg/m^2$ i.v., day 1) combination chemotherapy every 3 weeks. For patients with relapsed SCLC after EC therapy, topotecan($1.5mg/m^2$) was administered for 5 consecutive days every 3 weeks. Response rate, survival and toxicity profiles were assessed. Response was recorded as CR(complete remission), PR(partial remission), SD(stable disease) and PD(progressive disease). Results : One hundred and one patients were assessed for response to EC. Overall response rate to EC was 57.4%(CR 15.8%, PR 41.6%) with a time to progression of 10.3 months(median). The toxicity was tolerable and there was no treatment-related death. Twenty one relapsed SCLC patients were treated with topotecan. Of those who relapsed within 3 months of EC(refractory relapse, RR), 15.4%(2/13) showed PR, while of those who relapsed after 3 months(sensitive relapse, SR), 25%(2/8) exhibited PR. Grade 4 neutropenia was noted in 9.5% and 14.3% showed thrombocytopenia(G4). Conclusion : The EC regimen showed a moderate response rate for SCLC with minimal toxicity. The use of topotecan for relapsed SCLC warrants further investigation.

• Tuberculosis and Respiratory Diseases
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• v.64 no.6
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• pp.433-438
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• 2008

Background: Measurement of the maximum oxygen uptake in patients with chronic obstructive pulmonary disease (COPD) has been used to determine the intensity of exercise and to estimate the patient's response to treatment during pulmonary rehabilitation. However, cardiopulmonary exercise testing is not widely available in Korea. The 6-minute walk test (6MWT) is a simple method of measuring the exercise capacity of a patient. It also provides high reliability data and it reflects the fluctuation in one' s exercise capacity relatively well with using the standardized protocol. The prime objective of the present study is to develop a regression equation for estimating the peak oxygen uptake ($VO_2$) for men with moderate to very severe COPD from the results of a 6MWT. Methods: A total of 33 male patients with moderate to very severe COPD agreed to participate in this study. Pulmonary function testing, cardiopulmonary exercise testing and a 6MWT were performed on their first visits. The index of work ($6M_{work}$, 6-minute walk distance [6MWD]${\times}$body weight) was calculated for each patient. Those variables that were closely related to the peak $VO_2$ were identified through correlation analysis. With including such variables, the equation to predict the peak $VO_2$ was generated by the multiple linear regression method. Results: The peak $VO_2$ averaged $1,015{\pm}392ml/min$, and the mean 6MWD was $516{\pm}195$ meters. The $6M_{work}$ (r=.597) was better correlated to the peak $VO_2$ than the 6MWD (r=.415). The other variables highly correlated with the peak $VO_2$ were the $FEV_1$ (r=.742), DLco (r=.734) and FVC (r=.679). The derived prediction equation was $VO_2$ (ml/min)=($274.306{\times}FEV_1$)+($36.242{\times}DLco$)+($0.007{\times}6M_{work}$)-84.867. Conclusion: Under the circumstances when measurement of the peak $VO_2$ is not possible, we consider the 6MWT to be a simple alternative to measuring the peak $VO_2$. Of course, it is necessary to perform a trial on much larger scale to validate our prediction equation.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.932-943
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• 2000

Background : Nonspecific interstitial pneumonitis (NSIP) is most likely to be confused with usual interstitial pneumonitis (UIP). Unlike patients witþ UIP, the majority of patients with NSIP have a good prognosis, with most patients improving after treatment with corticosteroids. Therefore it is clinically important to differentiate NSIP from UIP. Up to now, the only means of differentiating these two diseases was by means of surgical lung biopsy. American Thoracic Society (ATS) proposed a clinical diagnostic criteria for UIP to provide assistance to clinicians in its diagnosis without surgical lung biopsy. This study is aimed to investigate whether there were clinical and radiological differences between NSIP and UIP, and the usefulness of ATS clinical diagnostic criteria for UIP in Korea. Methods : We studied 60 patients with UIP and NSIP confirmed by surgical lung biopsy. Clinical manifestations, pulmonary function test, arterial blood gas analysis, bronchoalveolar lavage (BAL), and high resolution computed tomography (HRCT) were evaluated and analyzed by Chi-square test or t-test. The clinical criteria for UIP proposed by ATS were applied to all patients with idiopathic interstitial pneumonia. Results : Forty-two patients with UIP and 18 with NSIP were pathologically identified. Among the 18 patients with NSIP (M : F=1 : 17), the mean age was 55.2$\pm$8.4 (44~73) yr. Among the 42 patients with UIP (M : F=33 : 9), the mean age was 59.5$\pm$7.1 (45~74) yr (p=0.046). Fever was more frequent in NSIP (39%) (p=0.034), but clubbing was frequently observed in UIP (33%) (p=0.023). BAL lymphocytosis was more frequent (23%) (p=0.0001) and CD4/CD8 ratio was lower in NSIP (p=0.045). On HRCT, UIP frequently showed honeycomb appearance (36 of 42 patients) though not in NSIP (p=0.0001). Six of 42 UIP patients (14.3%) met the ATS clinical criteria for IPF, and 3 of 16 NSIP patients (18.8%) met the diagnostic criteria. Conclusion : Being a relatively young female and having short duration of illness, fever, BAL lymphocytosis, low CD4/CD8 ratio with the absence of clubbing and honeycomb appearance in HRCT increase the likelihood of the illness being NSIP. The usefulness of ATS clinical diagnostic criteria for UIP may be low in Korea.