• Tuberculosis and Respiratory Diseases
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• v.50 no.3
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• pp.343-352
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• 2001

Background : Advanced chronic obstructive pulmonary disease is characterized by progressive pulmonary hypertension leading to right heart dysfunction, which plays a Important role in clinical evaluation but remains difficult and challenging to quantify. The noninvasive doppler echocardiographic value referred to as the Tei index has been suggested as a simple, reproducible and reliable parameter of the right ventricular function. The purpose of this was to assess the right ventricular function in patients with chronic obstructive pulmonary disease using the Tei index and to evaluate its relationship with the pulmonary functional status. Methods : The study population comprised of 26 patients with chronic obstructive pulmonary disease and 10 normal control subjects. The Tei index was obtained by dividing the sum of the isovolumetric contraction and the relaxation times by the ejection time using a pulsed-wave doppler. It was compared with the other available Doppler echocardiographic parameters of systolic or diastolic function and with the pulmonary function of the patients. Results : The Tei indices of the patients with COPD were significantly higher than those of normal subjects($0.45{\pm}0.17$ vs. $0.27{\pm}0.03$, p<0.01). The isovolumetric contraction time/ejection time($0.32{\pm}0.08$ vs. $0.25{\pm}0.05$, p<0.05), the isovolumetric relaxation time/ejection time($0.29{\pm}0.16$ vs. $0.15{\pm}0.08$, p<0.05)and the preejection period/ejection time ($0.46{\pm}0.10$ vs. $0.38{\pm}0.06$, p<0.05) were prolonged and the ejection time ($255.2{\pm}32.6$ vs. $314.2{\pm}16.5$ msec, p<0.05) was significantly shortened in patients with COPD compared to normal subjects. The tei indices were inversely correlated with the $FEV_1$ (r=-0.46, p<0.05) and were prolonged significantly in patients with a severe obstructive ventilatory dysfunction(less than 35% of predicted $FEV_1$) compared to those with a mild and moderate ventilatory dysfunction. The tei indices showed an inverse correlation to with the ejection time (r=-0.469), the isovolumetric contraction time/ejection time(r=0.453), the isovolumetric relaxation time/ejection time(r=0.896) and the preejection period/ejection time(r=0.480). Conclusion : The tei index appeared to be a useful noninvasive means of evaluating the right ventricular function. It revealed a significant correlation with the pulmonary function in patients with COPD.

• Tuberculosis and Respiratory Diseases
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• v.57 no.6
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• pp.535-542
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• 2004

Background : Despite the clinical clues of bronchial asthma, some chronic coughers fail to be diagnosed due to negative test results. This study was aimed at evaluating the diagnostic performance of routine objective tests and identifying a cost-effective approach for asthmatics with a chronic cough. Methods : Patients with a chronic cough of more than 3 weeks duration, and showing normal chest radiograph and spirometry were enrolled. On the first visit, objective tests, composed of serum total IgE, peripheral blood eosinophil count, spontaneous sputum eosinophil count, methacholine bronchial provocation test (MBPT) and paranasal sinus radiograph, were performed, with the simultaneous administration of oral prednisolone (0.5mg/kg) for one week. The final diagnoses were made on the basis of the test results, and the patients grouped according to their steroid responsiveness. The role of the etiologic diagnosis tests was evaluated, and the medical costs of the final management plan simulated with respect to three assumed models. Results : Sixty chronic coughers were finally analyzed. The final diagnoses were as follows: bronchial asthma 21.7%, eosinophilic bronchitis 6.7%, paranasal sinusitis 18.3%, presumptive allergy 8.3% and non-diagnostic case 45.0%. Ninety percent were steroid responder. With the bronchial asthma cases, the positive rate of MBPT was 38.5%, with sputum eosinophil count in 84.6%, serum total IgE in 38.5%, and a peripheral blood eosinophil count rate of 30.8%. When the test results and steroid responsiveness data were applied to the 3 models, the chest radiograph, spirometry, sputum eosinophil count and paranasal sinus radiograph test results, and simultaneous short term steroid treatment seemed to have acceptable diagnostic performances, which could be used as a further guide to cost-effective planning. Conclusion : Objective tests, composed of chest radiograph, spirometry, paranasal sinus radiograph and sputum eosinophil count, with simultaneous short term steroid treatment, are suggested as cost-effective approaches for asthmatics with a chronic cough.

• Tuberculosis and Respiratory Diseases
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• v.66 no.4
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• pp.280-287
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• 2009

Background: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), became an attractive therapeutic option for advanced non-small-cell lung cancer (NSCLC). Several studies suggested that there might be some different efficacy or response predictors between gefitinib and erlotinib. We compared the efficacy and toxicity of gefitinib and erlotinib in Korean patients with advanced NSCLC and evaluated specific predictors of response for both gefitinib and erlotinib. Methods: We collected the clinical information on patients with advanced NSCLC, who were treated with gefitinib or erlotinib at the Ewha Womans University Hospital, between July 2003 and February 2009. Median survival times were calculated using the Kaplan-Meier method. Results: Eighty-six patients (52 gefitinib vs. 34 erlotinib) were enrolled. Patient median age was 64 years; 53 (62%) subjects were male. Out of the 86 patients treated, 83 received response evaluation. Of the 83 patients, 35 achieved a response and 12 experienced stable disease while 36 experienced progressive disease, resulting in a response rate of 42% and a disease control rate of 57%. After a median follow-up of 502 days, the median progression-free and overall survival time was 129 and 259 days, respectively. Comparing patients by treatment (gefitinib vs erlotinib), there were no significant differences in the overall response rate (44% vs. 39%, p=0.678), median survival time (301 days vs. 202 days, p=0.151), or time to progression (136 days vs. 92 days, p=0.672). Both EGFR-TKIs showed similar toxicity. In a multivariate analysis using Cox regression model, adenocarcinoma was an independent predictor of survival (p=0.006; hazard ratio [HR], 0.487; 95% confidence interval [CI], 0.292-0.811). Analyses of subgroups did not show any difference in response predictors between gefitinib and erlotinib. Conclusion: Comparing gefitinib to erlotinib, there were no differences in the response rate, overall survival, progression-free survival, or toxicity. No specific predictor of response to each EGFR-TKI was identified.

• Tuberculosis and Respiratory Diseases
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• v.65 no.6
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• pp.495-503
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• 2008

Background: Epigenetic alterations in certain genes are now known as at least important as genetic mutation in pathogenesis of cancer. Especially abnormal hypermethylation in or near promoter region of tumor suppressor genes (TSGs) are known to result in gene silencing and loss of gene function eventually. The authors tried to search for new lung cancer-specific TSGs which have CpG islands and HpaII sites, and are thought to be involved in carcinogenesis by epigenetic mechanism. Methods: Tumor tissue and corresponding adjacent normal tissue were obtained from 10 patients who diagnosed with non small cell lung cancer (NSCLC) and underwent surgery in Konyang university hospital in 2005. Methylation profiles of promoter region of 21 genes in tumor tissue & non-tumor tissue were examined with HpaII-MspI methylation microarray (Methyl-Scan DNA chip$^{(R)}$, Genomic tree, Inc, South Korea). The rates of hypermethylation were compared in tumor and non-tumor group, and as a normal control, we obtained lung tissue from two young patients with pneumothorax during bullectomies, methylation profiles were examined in the same way. Results: Among the 21 genes, 10 genes were commonly methylated in tumor, non-tumor, and control group. The 6 genes of APC, AR, RAR-b, HTR1B, EPHA3, and CFTR, among the rest of 11 genes were not methylated in control, and more frequently hypermethylated in tumor tissue than non-tumor tissue. Conclusion: In the present study, HTR1B, EPHA3, and CFTR are suggested as possible novel TSGs of NSCLC by epigenetic mechanism.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.309-318
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• 2002

Background : Usual interstitial pneumonia (UIP) is a fatal progressive fibrotic disorder of the lung with unknown etiology and characterized by a poor response to conventional immunosuppressive therapy. The histologic hallmark of UIP is parchy distribution of subpleural fibrosis and fibroblastic foci(FBF) with interposed normal appearing lung. Because FBF is a collection of actively proliferating myofibroblasts, it can be a marker of activity and prognosis of UIP. However, there were contradictory reports about the correlation between the degree of FBF and survival. Therefore we performed this study to investigate the value of FBF as prognostic marker of UIP. Methods : This was a retrospective study on the 46 patients(M:F=33:13, mean age:$59{\pm}12$ years) with UIP diagnosed by the surgical lung biopsy at the Asan Medical Center, Seoul, Korea between 1990 and 2000 and had follow-up of more than a year. All the biopsy specimens were reevaluated and diagnosed as UIP according to the ATS/ERS classification. Semiquantitative grading of FBF(absent, 0; mild 1; moderate 2; marked 3) by the experienced pathologists who did not know the clinical findings were compared to the clinical data and the follow up course. Results : Thirteen patients(28.2%) died of UIP progression during the study period. The median survival time of all the subjects was 26 months after the biopsy. At the univariate analysis, FVC, $D_Lco$, smoking history and the grade of FBF were significantly related to the survial. The survival was longer in subjects with lesser degrees of FBF, higher DLco, higher FVC and history of smoking. However the multivariate analysis with Cox regression test showed the extent of FBF was the only independent prognostic marker of UIP. Conclusion : These data suggested that the extent of FBF on the surgical lung biopsy can be used as a prognostic marker of UIP.

• Tuberculosis and Respiratory Diseases
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• v.46 no.4
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• pp.564-573
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• 1999

Background: With variable symptoms and nonspecific radiographic appearances, pulmonary embolism (PE) is a frequent and often undiagnosed cause of mortality and morbidity. The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study suggested that the majority of patients undergoing ventilation-perfusion (V-Q) scan would require additional studies to establish or to exclude the diagnosis of PE. Pulmonary angiography has been regarded as gold standard for diagnosis of PE. However, it is an invasive procedure that may be associated with significant notable morbidity and mortality. Thus, availability of an accurate, noninvasive screening examination is highly desirable. Method: From October 1994 to February 1997, twenty patients (male 13, female 7, range 23-91 years, median 58 years) who were suspected as pulmonary embolism on the basis of clinical evidence and underwent the spiral volumetric computed tomography (spiral CT), were studied retrospectively to evaluate the effectiveness of spiral CT as a diagnostic tool in PE. Results: PE could be excluded with spiral CT in 4 patients ; diagnoses of these patients were lung cancer, pneumonia with lung abscess, bilateral pleural effusion due to congestive heart failure, nonspecific pulmonary abnormality retrospectively. One patient who disclosed high probability in V/Q scan, could be diagnosed as pneumonia with lung abscess and underlying emphysema with spiral CT. Among 4 patients who showed intermediate and low probability in V/Q scan, 3 patients could be confirmed as PE with spiral CT. Spiral CT was helpful in 3 patients, in whom V/Q scan could not be performed due to other reasons (e.g. night time, mechanical ventilation) to confirm the diagnosis of PE. Spiral CT could demonstrate embolus above lobar artery level in 11 patients, and up to segmental artery level in 5 patients. Conclusion: This study demonstrated that spiral CT could allow accurate demonstration of thrombotic clots in centrally localized embolism. Spiral CT could be effective, specific, noninvasive and useful diagnostic screening modality for the diagnosis of pulmonary embolism.

• Tuberculosis and Respiratory Diseases
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• v.50 no.2
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• pp.158-170
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• 2001

Background : Although an oxidants and antioxidants imbalance has been considered in the pathogenesis of chronic obstructive pulmonary disease (COPD), there is a paucity of reports focussing on the smoking-induced changes of oxidants and antioxidants in COPD. Method : The concentration of antioxidants (ascorbic acid, uric acid, retinol, and $\alpha$- & $\gamma$-tocopherol) was measured in the serum and induced sputum of 30 healthy controls and 34 stable COPD patients using high performance liquid chromatography (HPLC). The inhibition of lipid peroxidation as an index of antioxidant capacity was measured in the serum by a TBA assay. Results : The serum concentration of ascorbic acid, $\alpha$-tocopherol, and retinol were significantly lower in the patients with COPD than in healthy controls ($484.8{\pm}473.3$ vs $1497.8{\pm}819.2\;pmol/L$, $48.38{\pm}17.34$ vs $73.96{\pm}26.29\;pmol/L$, p<0.001, and $9.51{\pm}8.33$ vs $15.01{\pm}5.88\;pmol/L$, p<0.05, respectively, mean$\pm$SD). However, there were little differences in the ascorbic acid and uric acid concentrations in the induced sputum between the COPD patients and the controls. The induced sputum to serum ratio of ascorbic acid was significantly higher in COPD patients compared with healthy control (0.375 vs 0.085, p<0.05). In the normal controls, the serum ascorbic acid concentration was lower in smokers than in nonsmokers ($1073{\pm}536$ vs $1757{\pm}845\;pmol/L$, p<0.05), but the level was still higher than that of the COPD patients (p<0.05). The serum retinol levels were correlated with $FEV_1$ in COPD patients (r=0.58, p<0.05). The products of lipid peroxidation were increased in normal smokers and COPD compared with norma1 nonsmokers ($115.56{\pm}19.93$ vs $120.02{\pm}24.56$ vs $91.87{\pm}20.71\;{\mu}mol/{\mu}mol$ Pi of liposome, p<0.05). Conclusion : Cigarette smoking may induce the dep1etion of serum antioxidants and this depletion of antioxidants is suggested to play a role in the pathogenesis of COPD.

• Tuberculosis and Respiratory Diseases
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• v.50 no.4
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• pp.415-425
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• 2001

Background : The correlation between the high resolution computed tomography(HRCT) emphysema score and the physiologic parameters including resting and exercise pulmonary function test was investigated in 14 patients($60.6{\pm}10.3$ years) with pulmonary emphysema. Methods : The patients underwent a HRCT, a resting pulmonary function test, and incremental exercise testing(cycle ergometer, 10 W/min). Computed tomography scans were obtained on a GE highlight at 10 mm intervals using 10 mm collimation, from the apex to the base after a full inspiration. The emphysema scores were determined by a CT program 'Density mask' outlining the areas with attenuation values less than -900 HU, indicating the emphysema areas, and providing an overall percentage of lung involvement by emphysema. Results : Among the resting PFT parameters, only the diffusing capacity(r=-0.75) and $PaO_2$ (r=-0.66) correlated with the emphysema score(p<0.05). Among the exercise test parameters, the emphysema score correlated significantly with the maximum power(r=-0.74), maximum oxygen consumption(r=-0.68), anaerobic threshold(V-slope method: r=-0.69), maximal $O_2$-pulse(r=-0.73), and the physiologic dead space ratio at the maximum workload(r=-0.80)(p<0.01). Conclusion: We could find that exercise testing parameters showed a much better correlation with the HRCT emphysema score, which is known to have a good correlation with the pathologic severity than the resting PIT parameters. Therefore it is suggested that exercise testing is superior to resting PIT for estimating in the estimation of the physiologic disturbance in emphysema patients.

• Tuberculosis and Respiratory Diseases
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• v.53 no.2
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• pp.127-135
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• 2002

Background : Idiopathic interstitial pneumonia is characterized by chronic inflammation and pulmonary fibrosis. The clara cell 10 kD protein (CC10, also designated CC16) is synthesized by the bronchial epithelium and has been suggested to have a potent anti-inflammatory effect. Therefore, CC-10 might be a candidate for controlling the inflammatory events in patients with idiopathic interstitial pneumonia. The aim of this study was to determine if the degrees of pulmonary fibrosis in idiopathic interstitial pneumonia is associated with CC-10 in the BAL fluid. Materials and Methods : The BAL fluid was collected from 29 patients and 10 controls. Densitometric analysis of the western blot assay for the CC-10 was subsequently performed. The RI (relative intensity) of each band was compared according to the diagnosis, the radiological degrees of pulmonary fibrosis and the relative proportion of inflammatory cells in the BAL fluid. Results : There were no differences in the CC-10 expression levels in the BAL fluid between the patients (RI $77.5{\pm}75.8%$) and the controls ($70.7{\pm}39.8%$) (p>0.05). In addition, the degrees of pulmonary fibrosis and airway inflammation in patients with usual interstitial pneumonia were not associated with CC-10 expression in the BAL fluid (p>0.05). Conclusion : This study suggests that CC-10 expression is not associated with the degrees of pulmonary fibrosis in patients with usual interstitial pneumonia.

• Tuberculosis and Respiratory Diseases
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• v.50 no.2
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• pp.236-244
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• 2001

Background : Most current research using prognostic scoring systems in critically ill patients have focused on prediction using the first intensive care unit (ICU) day data or daily updated data. Usually the mean ICU length of stay in Korea is longer than in the western world. Consequently, a more cost-effective and practical prognostic parameter is required. The principal aim of this study was to assess the prognostic value of the seventh day(7th day : the average mean ICU length of stay) APACHE III score in a medical intensive care unit. Methods : 241 medical ICU patients from July 1997 to April 1998 were enrolled. The 1st and 7th scores were measured by using the APACHE III scoring system and compared between survivors and non-survivors. Logistic regression analysis was performed to determine the relationship between the $1^{st}$ and $7^{th}$ APACHE III scores and the mortality risk. Results : 1 )The mean length of stay in the ICU was $10.3{\pm}13.8$ days. 2)The mean $1^{st}$ and $7^{th}$ day APACHE III scores were $59.7{\pm}30.9$ and $37.9{\pm}27.7$. 3) The mean $1^{st}$ day APACHE III score was significantly lower in survivors than in non- survivors($49.9{\pm}23.8$ vs $86.3{\pm}32.3$, P<0.0001). 4)The mean $7^{th}$ day APACHE III score was significantly lower in survivors than in non- survivors($30.1{\pm}18.5$ vs $80.1{\pm}30.4$, P<0.0001). 5)The odds ratios among the $1^{st}$ and $7^{th}$ day APACHE III scores and the mortality rate were 1.0507 and 1.0779 respectively. Conclusion : These results suggest that the seventh day APACHE III score is as useful in predicting the outcome as is such like the first day APACHE III score. Therefore, in comparison to the daily APACHE III score, measuring the $1^{st}$ and $7^{th}$ day APACHE III scores are also useful for predicting the prognosis of critically ill patients in terms of cost-effectiveness. It is suggested that the $7^{th}$ day APACHE III score is useful for predicting the clinical outcome.