• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.823-834
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• 1998

Background: Chronic inhalation of silica induces the lung fiborsis. The alveolar macrophages ingest the inhaled silica; they liberate the pro-inflammatory cytokines such as IL-1$\beta$, IL-6, TNF-$\alpha$ and fibrogenic cytokines, TGF-$\beta$ and PDGF. Cytokines liberated from macrophage have pivotal role in pulmonary fibrosis. There is a complex cytokine network toward fibrosis. However, the exact roles and the interaction among the proinflammatory cytokines and TGF-$\beta$, a fibrogenic cytokine, have not been defined, yet. In this study, we investigated silica induced IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ production and the effect of IL-1$\beta$, IL-6, TNF-$\alpha$ on the production of TGF-$\beta$ from lung macrophages of Balb/C mice. Method: We extracted the lung of Balb/C mice and purified monocytes by Percoll gradient method. Macrphages were stimulated by silica ($SiO_2$) in the various concentration for 2, 4, 8, 12, and 24 hours. The supernatants were used for the measurement of protein levels by bioassay, and cells for the levels of mRNA by in situ hybridization. Results: The production of IL-6 was not observed till 4 hours, and reached the peak levels at 8 hours after stimulation of silica. The production of TNF-$\alpha$ increased from 2 hours and reached the peak levels at 4 hours after stimulation of silica. The spontaneous TGF-$\beta$ production reached the peak levels at 24 hours. TNF-$\alpha$ upregulated the silica induced TGF-$\beta$ production. Silica induced TGF-$\beta$ production was blocked by pretreated anti-TNF-$\alpha$ antibody. In situ hybridization revealed the increased positive signals at 4 hours in IL-6, at 4 hours TNF-$\alpha$ and 12 hours in TGF-$\beta$. Conclusion: The results above suggest that silica induced the sequential production of IL-6, 1NF-$\alpha$ and TGF-$\beta$ from macrophages and TNF-$\alpha$ upregultaes the production of TGF-$\beta$ from silica-induced macrophages.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1252-1264
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• 1998

Background : Patients with established ARDS have a mortality rate that exceeds 50 percent despite of intensive care including artificial ventilation modality, Mortality has been associated with sepsis and organ failure preceding or following ARDS ; APACHE II score ; old age and predisposing factors. Revised ventilator strategy over last 10 years especially at ARDS appeared to improve the mortality of it. We retrospectively investigated 40 ARDS patients of respiratory-care unit to examine how these factors influence outcome. Methods : A retrospective investigation of 40 ARDS patients in respiratory-care unit with ventilator management over 46 months was performed. We investigated the clinical characteristics such as a risk factor, cause of death and mortality, and also parameters such as APACHE II score, number of organ dysfunction, and hypoxia score (HS, $PaO_2/FIO_2$) at day 1, 3, 7 of severe acute lung injury, and simultaneously the PEEP level and tidal volume. Results : Clinical conditions associated with ARDS were sepsis 50%, pneumonia 30%, aspiration pneumonia 20%, and mortality rate based on the etiology of ARDS was sepsis 50%, pneumonia 67%(p<0.01 vs sepsis), aspiration pneumonia 38%. Overall mortality rate was 60%. In 28 day-nonsurvivors, leading cause of death was severe sepsis(42.9%) followed by MOF(28.6%), respiratory failure(19.1 %), and others(9.5%). There were no differences in variables of age, sex, APACHE II score, HS, and numbers of organ dysfunction at day 1 of ARDS between 28-days survivor and nonsurvivors. In view of categorized variables of age(>70), APACHE II score(>26), HS(<150) at day 1 of ARDS, there were significant differences between 28-days survivor and nonsurvivors(p<0.05). After day 1 of ARDS, the survivors have improved their APACHE II score, HS, numbers of organ dysfunction over the first 3d to 7d, but nonsurvivors did not improve over a seven-day course. There were significant differences in APACHE II score and numbers of organ dysfunction of day 3, 7 of ARDS, and HS of day 7 of ARDS between survivors and nonsurvivors(p<0.05). Fatality rate of ARDS has been declined from 68% to less than 40% between 1995 and 1998. There were no differences in APACHE II score, HS, numbers of organ dysfunction, old age at presentation of ARDS. In last years, mean PEEP level was significantly higher and mean tidal volume was significantly lower than previous years during seven days of ARDS(p<0.01). Conclusions : Improvement of HS, APACHE II score, organ dysfunction over the first 3d to 7d is associated with increased survival Decline in ARDS fatality rates between 1995 and 1998 seems that this trend must be attributed to improved supportive therapy including at least high PEEP instead of conventional-least PEEP approach in ventilator management of acute respiratory distress syndrome.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.232-240
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• 1997

Background : Postprimary pulmonary tuberculosis is located mainly in upper lobes. The tuberculous lesion involving the lower lobes usually arises from the upper lobe cavity through endobronchial spread. When tuberculosis is confined to the lower lung field, it often masquerades as pneumonia, lung cancer, bronchiectasis, or lung abscess. Thus the correct diagnosis may be sometimes delayed for a long time. Methods : We carried out, retrospectively, a clinical study on 50 patients confirmed with lower lung field tuberculosis who visited the Department of Pulmonary Medicine at Hanyang University Hospital from January 1992 to December 1994. The following results were obtained. Results : Lower lung field tuberculosis without concomitant upper lobe disease occurred in fifty patients representing 6.9% of the total admission with active pulmonary tuberculosis over a period of 3 years. It occurred most frequently in the third decade but age distribution was relatively even. The mean age was 43 years old. Female was more frequently affected than male (male to female ratio 1 : 1.9). The most common symptom was cough(68%), followed by sputum(52%), fever(38%), and chest discomfort(30%). On chest X-ray of the 50patients, consolidation was the most common finding in 52%, followed by solitary nodule(22%) collapse(16%), cavitary lesion(10%), in decreasing order. The disease confined to the right side in 25 cases, left side 20 cases, and both sides 5 cases. Endobronchial tuberculosis (1) Endobronchial involvement was proved by bronchoscopic examination in 20 of 50patients. (2) Mean age was 44years old and female was more affected than man (male to female ratio 1 : 3). Sputum AFB stain and Mycobacterium tuberculosis culture were positive only in 50% of cases unlikely upper lobe tuberculosis, additional diagnostic methods were needed. In our study, bronchoscopic examination and percutaneous fine needle aspiration biopsy increased diagnostic yield by 18% and 32%, respectively. The most common associated condition was diabetes mellitus(18%) and others were anemia, anorexia nervosa, stomach cancer, and systemic steroid usage. Conclusion : When we find a lower lung field lesion, we should suspect tuberculosis if the patient has diabetes mellitus, anemia, systemic steroid usage, malignancy or other immune suppressed states. Because diagnostic yield of sputum AFB smear & Mycobacterium tuberculosis culture was low, additional diagnostic methods such as bronchoscopy and fine needle aspiration biopsy were needed.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.153-168
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• 1998

Background: The existing data indicate that obstructive sleep apnea syndrome contributes to the development of cardiovascular dysfunction such as systemic hypertension and cardiac arrhythmias, and the cardiovascular dysfunction has a major effect on high long-term mortality rate in obstructive sleep apnea syndrome patients. To a large extent the various studies have helped to clarify the pathophysiology of obstructive sleep apnea, but many basic questions still remain unanswered. Methods: In this study, the influence of obstructive sleep apnea on systemic blood pressure, cardiac rhythm and urinary catecholamines concentration was evaluated. Over-night polysomnography, 24-hour ambulatory blood pressure and ECG monitoring, and measurement of urinary catecholamines, norepinephrine (UNE) and epinephrine (UEP), during waking and sleep were undertaken in obstructive sleep apnea syndrome patients group (OSAS, n=29) and control group (Control, n=25). Results: 1) In OSAS and Control, UNE and UEP concentrations during sleep were significantly lower than during waking (P<0.01). In UNE concentrations during sleep, OSAS showed higher levels compare to Control (P<0.05). 2) In OSAS, there was a increasing tendency of the number of non-dipper of nocturnal blood pressure compare to Control (P=0.089). 3) In both group (n=54), mean systolic blood pressure during waking and sleep showed significant correlation with polysomnographic data including apnea index (AI), apnea-hypopnea index (AHI), arterial oxygen saturation nadir ($SaO_2$ nadir) and degree of oxygen desaturation (DOD). And UNE concentrations during sleep were correlated with AI, AHI, $SaO_2$ nadir, DOD and mean diastolic blood pressure during sleep. 4) In OSAS with AI>20 (n==14), there was a significant difference of heart rates before, during and after apneic events (P<0.01), and these changes of heart rates were correlated with the duration of apnea (P<0.01). The difference of heart rates between apneic and postapneic period (${\Delta}HR$) was significantly correlated with the difference of arterial oxygen saturation between before and after apneic event (${\Delta}SaO_2$) (r=0.223, P<0.001). 5) There was no significant difference in the incidence of cardiac arrhythmias between OSAS and Control In Control, the incidence of ventricular ectopy during sleep was significantly lower than during waking. But in OSAS, there was no difference between during waking and sleep. Conclusion : These results suggested that recurrent hypoxia and arousals from sleep in patients with obstructive sleep apnea syndrome may increase sympathetic nervous system activity, and recurrent hypoxia and increased sympathetic nervous system activity could contribute to the development of cardiovascular dysfunction including the changes of systemic blood pressure and cardiac function.

• Tuberculosis and Respiratory Diseases
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• v.46 no.3
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• pp.372-385
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• 1999

Background: The purpose of this study was to examine the causes and pathologic process of chronic non-productive cough as an isolated symptom with a normal spirometry and chest radiograph by investigating clinicopathologic findings. Method: We studied 25 adults with chronic non-productive cough over a 3-week period with a normal chest radiograph and pulmonary function tests without any other symptoms. Clinical assessment, cough score, chest and sinus radiograph, pulmonary function tests, methacholine challenge, allergic skin prick test, and bronchoscopy for bronchial biopsies were performed. Subjects were then treated with prednesolone 20 to 30 mg/day for 1 to 2 weeks. Results: The experimental group was divided into two subgroups-those infiltrated with eosinophils, and those infiltrated with lymphocytes depending on eosinophil and lymphocyte counts, both of which were respectively higher than those of the control group. Eosinophils infiltrated group had mean numbers of eosinophil of 89.8 $cells/mm^3$ while control group's mean was 0.4 $cells/mm^2$(p=0.005). Lymphocyte infiltrated group was 4 patients whose mean was 84.3 $cells/mm^2$ with 28.4 $cells/mm^2$ of control group(P=0.026). In addition, the mean thickness of the basement membrane of experimental group was $14.20{\pm}5.20{\mu}m$ in contrast of control group whose mean was $3.50{\pm}1.37{\mu}m$(P=0.001). With the methacholine challenge test, 7 of the 21 eosinophil infiltrated subjects were diagnosed with cough variant asthma ; the other 14 with eosinophilic bronchitis. Three subjects with eosinophilic bronchitis were atopic positive (21.4%) with the skin prick test In the lymphocyte dominant group, all four subjects were diagnosed with lymphocytic bronchitis. Cough score was improved after steroid treatment in 22 of 25 subjects in the experimental group (88.0%). Conclusion: These results suggest chronic non-productive cough as an isolated symptom with a normal spirometry and chest radiograph was associated with airway inflammation by eosinophil and lymphocyte infiltration. The causes for chronic non-productive cough were eosinophilic bronchitis, cough variant asthma, and lymphocytic bronchitis(written in frequency). They further suggest that therapeutic treatment with steroids can provide effective symptomatic relief.

• Tuberculosis and Respiratory Diseases
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• v.47 no.6
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• pp.775-785
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• 1999

Background : Though surgery plays an important role in the management of patients with Mycobacterium tuberculosis infection, there is little information regarding the timing of resection. We tried to find out the ideal timing of operation. Method: A retrospective review was performed in 69 patients underwent pulmonary resection for pulmonary tuberculosis between January 1993 and December 1997. They were categorized into various groups according to the length of preoperative specific drug therapy. The rates of treatment failure, realpse and complication in each group were compared statistically by $x^2$-test. Results: Eighty one point two percent were men and 18.8 % women with a median age of 33 years(range, 16 to 63 years). The mean number of resistant drugs was 3.l(range, 0 to 9). Patients were treated preoperatively with multidrug regimens, which mean number of preoperative specific drugs was 4.6, in an effort to reduce the mycobacterial burden with the mean length of preoperative drug therapy, 5.0 months. Postoperative treatment was conducted for a mean period of 13.0 months with a mean number of postoperative specific drugs, 4.4. Postoperative treatment failures were confirmed in 8 among 69 patients(11.6%). 2 of these 8 patients were showed up in the preoperative 3 to 4 months medication group and each of the rest was occurred in the preoperative 2 to 3, 5 to 6, 6 to 7, 12 to 13, 17 to 18 months, less than one month medication group, respectively. 59 of 69 patients were available for evaluation of the relapse rate with the mean duration of the postoperative follow-up, 19.8 months. In 4 patients bacterial relapse was confirmed(6.8%). Each of these 4 was in the preoperative 1 to 2, 2 to 3, 3 to 4, 5 to 6 months medication group. Categorized into various groups according to the length of preoperative specific therapy, there were no statistical significances of the treatment failure rate, relapse rate and complication rate in the groups. There were seven treatment failures of 28 who were AFB culture positive until the time of operation(25%, p<0.01). Categorized the preoperative AFB culture positive group into various groups according to the length of preoperative drug therapy, there were no statistical significances, either. Conclusion: We believe that operation plays an important ancillary role in the treatment of pulmonary tuberculosis. Our results indicate that the timing of resection according to the length of preoperative drug therapy may not cause trouble.

• Tuberculosis and Respiratory Diseases
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• v.47 no.6
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• pp.824-835
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• 1999

Background: Sleep-related breathing disorders are commonly found in patients with chronic renal failure and particularly, sleep apnea may have an influence on the long-term mortality rates in these patients. Maintenance hemodialysis is the mainstay of medical measures for correcting the metabolic derangements of chronic renal failure but it is uncertain whether it may alleviate sleep disorders including sleep apnea. Methods: Forty seven patients on maintenance hemodialysis were surveyed with the sleep questionnaire about their clinical symptoms related to sleep disorders. Among them, 15 patients underwent the polysomnography and their blood levels of urea nitrogen, creatinine, electrolytes and the arterial blood gases in the nights before and following hemodialysis were measured. Results: Forty(85.1%) of the 47 patients complained of the symptoms associated with sleep-wake cycle disturbances, 55.3% experienced snoring and 27.7% reported witnessed apneas. The duration of REM sleep increased significantly in the nights after hemodialysis compared to the nights without hemodialysis(p<0.05) and the percentage of total sleep time comprising NREM sleep decreased significantly in the nights following hemodialysis compared to the nights before hemodialysis(p<0.05). The percentage of total sleep time consisting of the stage 1 and 2 NREM sleep showed the trend for a decrease in the nights after hemodialysis(p=0.051), while the percentage of total sleep time comprising the stage 3 and 4 NREM sleep did not change between nights. The obstructive sleep apnea was more predominant type than the central one in both nights and there were no differences in the apnea index and the apnea-hypopnea index between the nights. The decrease in the blood level of urea nitrogen, creatinine, potassium and phosphorus was observed after hemodialysis(p<0.05), but the differences of parameters measured during polysomnography between the nights did not correlate with the changes of biochemical factors obtained on the two nights. Arterial blood gas analysis showed that pH was significantly greater in the nights after hemodialysis than in the nights before hemodialysis(p<0.05), but there were no correlations between the parameters examined during polysomnography and the parameters of arterial blood gas analysis(p<0.05). Conclusion: These results suggest that chronic renal failure is an important systemic disorder which is strongly associated with sleep disorders. Maintenance hemodialysis, although it is a widely accepted measure to treat chronic renal failure, did not significantly modulate the sleep architecture and the severity of sleep apnea. Thus, taking the patients with chronic renal failure into account, it is advisable to try not only to find a substantial way for correcting metabolic derangements but also to consider the institution of more effective treatments for sleep disorders.

• Tuberculosis and Respiratory Diseases
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• v.51 no.6
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• pp.559-569
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• 2001

Background : Pleural effusion is one of the most common clinical manifestations associated with a variety of pulmonary diseases such as malignancy, tuberculosis, and pneumonia. However, there are no useful laboratory tests to determine the specific cause of pleural effusion. Therefore, an attempt was made to analyze the various types of pleural effusion and search for useful laboratory tests for pleural effusion in order to differentiate between the diseases, especially between a malignant pleural effusion and a non-malignant pleural effusion. Methods : 93 patients with a pleural effusion, who visited the Severance hospital from January 1998 to August 1999, were enrolled in this study. Ultrasound-guided thoracentesis was done and a confirmational diagnosis was made by a gram stain, bacterial culture, Ziehl-Neelsen stain, a mycobacterial culture, a pleural biopsy and cytology. Results : The male to female ratio was 56 : 37 and the average age was $47.1{\pm}21.8$ years. There were 16 cases with a malignant effusion, 12 cases with a para-malignant effusion, 36 cases with tuberculosis, 22 cases with a para-pneumonic effusion, and 7 cases with transudate. The LDH2 fraction was significantly higher in the para-malignant effusion group compared to the para-pneumonic effusion group [$30.6{\pm}6.4%$ and $20.2{\pm}7.5%$, respectively (p<0.05)] and both the LDH1 and LDH2 fraction was significantly in the para-malignant effusion group compared to those with tuberculosis [$16.4{\pm}7.2%$ vs. $7.6{\pm}4.7%$, and $30.6{\pm}6.4%$ vs.$17.6{\pm}6.3%$, respectively (p<0.05)]. The pleural effusion/serum LDH4 fraction ratio was significantly lower in the malignant effusion group compared to those with tuberculosis [$1.5{\pm}0.8$ vs. $2.1{\pm}0.6$, respectively (p<0.05)]. The LDH4 fraction and the pleural effusion/serum LDH4 fraction ratio was significantly lower in the para-malignant effusion group compared to those with tuberculosis [$17.0{\pm}5.8%$ vs. $23.5{\pm}4.6%$ and $1.3{\pm}0.4$ vs. $2.1{\pm}0.6$, respectively (p<0.05)]. Conclusion : These results suggest that the LDH isoenzyme was the only useful biochemical test for a differential diagnosis of the various diseases. In particular, the most useful test was the pleural effusion/serum LDH4 fraction ratio to distinguish between a para-malignant effusion and a tuberculous effusion.

• Tuberculosis and Respiratory Diseases
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• v.46 no.3
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• pp.350-362
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• 1999

Background: Acute Respiratory failure which is developed after extubation in the weaning process from mechanical ventilation is an important cause of weaning failure. Once it was developed, endotracheal reintubation has been done for respiratory support. Noninvasive Positive Pressure Ventilation (NIPPV) has been used in the management of acute or chronic respiratory failure, as an alternative to endotracheal intubation, using via nasal or facial mask. In this study, we evaluated the usefulness of NIPPV as an alternative method of reintubation in patients who developed acute respiratory failure after extubation. Method: We retrospectively analyzed thirty one patients(eighteen males and thirteen females, mean ages $63\pm13.2$ years) who were developed acute respiratory failure within forty eight hours after extubation, or were extubated unintentionally at medical intensive care unit(MICU) of Asan Medical Center. NIPPV was applied to the patients. Ventilatory mode of NIPPV, level of ventilatory support and inspiratory oxygen concentration were adjusted according to the patient condition and results of blood gas analysis by the attending doctors at MICU. NIPPV was completely weaned when the patients maintained stable clinical condition under 8 $cmH_2O$ of pressure support level. Weaning success was defined as maintenance of stable spontaneous breathing more than forty eight hours after discontinuation of NIPPV. Respiratory rate, heart rate, arterial blood gas analysis, level of pressure support, and level of PEEP were monitored just before extubation, at thirty minutes, six hours, twenty four hours after initiation of NIPPV. They were also measured at just before weaning from NIPPV in success group, and just before reintubation in failure group. Results: NIPPV was successfully applied to thirty-one patients of thirty-two trials and one patient could not tolerated NIPPV longer than thirty minutes. Endotracheal reintubation was successfully obviated in fourteen patients (45%) among them. There was no difference in age, sex, APACHE III score on admission at MICU, duration of intubation, interval from extubation to initiation of NIPPV, baseline heart rate, respiratory rate, arterial blood gas, and $PaO_2/FiO_2$ between the success and the failure group. Heart rate and respiration rate were significantly decreased with increase $SaO_2$ after thirty minutes of NIPPV in both groups(p<0.05). However, in the patients of failure group, heart rate and respiratory rate were increased again with decrease in $SaO_2$ leading to endotracheal reintubation. The success rate of NIPPV treatment was significantly higher in the patients with COPD compared to other diseases(62% vs 39%) (p=0.007). The causes of failure were deterioration of arterial blood gas without aggravation of underlying disease(n=9), aggravation of undelying disease(n=5), mask intolerance(n=2), and retained airway secretion(n=l). Conclusion: NIPPV would be a useful therapeutic alternative which can avoid reintubation in patient who developed acute respiratory failure after extubation.

• 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.