• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.987-996
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• 1996

Background : We prospectively evaluated the applicability and effect of noninvasive ventilation (NIV) in acute respiratory failure and tried to find out the parameters that could predict successful application of NIV. Methods : Twenty-six out of 106 patients with either acute ventilatory failure (VF: $PaCO_2$ > 43 mm Hg with pH < 7.35) or oxygenation failure (OF: $PaO_2/AO_2$ < 300 mm Hg with $pH{\geq}7.35$) requiring mechanical ventilation were managed by NIV (CPAP + pressure suppon, or BiPAP) with face mask. Eleven out of 19 cases with VF (57.9%) (M : F=7 : $55.4{\pm}14.6$ yrs) and 15 out of 87 cases with OF (17.2%) (M : F=12 : 3, $50.6{\pm}15.6$ yrs) were s uilable for NIY. Respiratory rates, arterial blood gases and success rate of NIV were analyzed in each group. Results: 81.8% (9/11) of YF and 40% (6/15) of OF were successfully managed on NIV and were weruled from mechanical ventilator without resorting to endotracheal intubation. Complications were noted in 2 cases (nasal skin necrosis 1, gaseous gastric distension 1). In NIV for ventilatory failure, the respiration rate was significantly decreased at 12 hour of NIV ($34{\pm}9$ /min pre-NIV, $26{\pm}6$ /min at 12 hour of NIV, p=0.045), while $PaCO_2$ ($87.3{\pm}20.6$ mm Hg pre-NIV, $81.2{\pm}9.1$ mm Hg at 24 hour of NIV) and pH ($7.26{\pm}0.04$, $7.32{\pm}0.02$, respectively, p <0.05) were both significantly decreased at 24 hour of NIV In NIV for oxygenation failure, $PaCO_2$ were not different between the successful and the failed cases at pre-NIV and till 12 hours after NIV. The $PaO_2/FIO_2$ ratio, however, significantly improved at 0.5 hour of NIV in successful cases and were maintained at around 200 mm Hg (n=6 : at baseline, 0.5h, 6h, 12h : $120.0{\pm}19.6$, $218.9{\pm}98.3$, $191.3{\pm}55.2$, $232.8{\pm}17.6$ mm Hg, respectively, p=0.0211), but it did not rise in the failed cases (n=9 : $127.9{\pm}63.0$, $116.8{\pm}24.4$, $100.6{\pm}34.6$, $129.8{\pm}50.3$ mm Hg, respectively, p=0.5319). Conclusion : From the above results we conclude that NIV is effective for hypercapnic respiratory failure and its success was heralded by reduction of respiration rale before the reduction in $PaCO_2$ level. In hypoxic respiratory failure, NIV is much less effective, and the immediate improvement of $PaO_2/FIO_2$ ratio at 0.5h after application is thought to be a predictor of successful NIV.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.535-547
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• 1995

Background: Intensive care units(ICUs) probably represent the single largest identifiable source of infection within the hospital. Although there are several studies on ICU infections in respect to their bacteriology or mortality rate for individual types of ICU, few studies have compared ICU infections between different types of ICU. The aim of this study was to identify clinical differences in bacteremia between medical ICU(MICU) and surgical ICU(SICU) patients. Methods: 256 patients with bacteremia were retrospectively evaluated. Medical records were reviewed to obtain the clinical and bacteriologic informations. Results: 1) The mean age of the patients with bacteremia of MICU($58.6{\pm}17.2\;yr$) was greater than that of all MICU patients($54.3{\pm}17.1\;yr$)(p<0.01), but there was no significant difference in SICU patients(patients with bacteremia of SICU: $56.3{\pm}18.6\;yr$, all SICU patients: $62.0{\pm}16.8$)(p>0.05). ICU stay was longer(MICU patients: $23.4{\pm}40.8$ day, SICU patients: $30.3{\pm}26.8$ day) than the mean stay of all patients($6.8{\pm}15.5$ day)(p<0.05, respectively). Bacteremia of both ICU patients developed past the average day of ICU stay(all MICU patients: 7.9 day, all SICU patients: 6.0 day, MICU bacteremia: 19th day, SICU bacteremia: 17th day of ICU stay)(p<0.05, respectively). 2) There were no significant differences in mean age, sex, and length of stay of both ICU patients with bacteremia. 3) Use of antibiotics or steroid, use of percutaneous devices and invasive procedures before development of bacteremia were more frequent in SICU patients than in MICU patients(prior antibiotics use: MICU 45%, SICU 63%, p<0.05; steroid use: MICU 14%, SICU 36%, p<0.01; use of percutaneous devices: MICU 19%, SICU 39%, p<0.01; invasive procedures: MICU 19%, SICU 61 %, p<0.01). 4) The prevalence of community acquired infections was significantly higher in MICU patients than in SICU patients(MICU 42%, SICU 9%)(p<0.01), whereas SICU patients showed higher prevalence of ICU-acquired infection than MICU patients(MICU 48%, SICU 78%)(p<0.01). 5) There were no differences in causative organisms, primary sites of infection and time interval to bacteremia between both ICUs. 6) There were no significant differences in outcome according to pathogenic organisms or primary sites of infection. 7) The mortality rate was higher in patients with bacteremia than without bacteremia(MICU mortality rate: patients with bacteremia 72.5%, patients without bacteremia 36.0%, p<0.01; SICU mortality rate: patients with bacteremia 40.3%, patients without bacteremia 8.5%, p<0.05), and the mortality rate of MICU bacteremia was significantly higher compared with that of SICU bacteremia(MICU 72.5%, SICU 40.3%)(p<0.01). Conclusion: ICU patients with bacteremia stayed longer before the development of bacteremia, and showed higher mortality than the overall ICU population. The incidence of bacteremia was higher in MICU patients than SICU patients. MICU patients with bacteremia showed higher prevalence of liver diseases and acute respiratory failure, community-acquired bacteremia and greater mortality rate than SICU patients with bacteremia. SICU patients with bacteremia, on the other hand, showed higher prevalence of trauma, prior use of immunosuppressive agents, invasive procedures, and ICU-acquired bacteremia, and lower mortality rate than MICU patients with bacteremia.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.555-568
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• 1995

Background: It is most physiologic to measure the diffusing capacity of the lung by using oxygen, but it is so difficult to measure partial pressure of oxygen in the capillary blood of the lung that in clinical practice it is measured by using carbon monoxide, and single-breath diffusing capacity method is used most widely. However, since the process of withholding the breath for 10 seconds after inspiration to the total lung capacity is very hard to practice for patients who suffer from cough, dyspnea, etc, the intra-breath lung diffusing capacity method which requires a single exhalation of low-flow rate without such process was devised. In this study, we want to know whether or not there is any significant difference in the diffusing capacity of the lung measured by the single-breath and intra-breath methods, and if any, which factors have any influence. Methods: We chose randomly 73 persons without regarding specific disease, and after conducting 3 times the flow-volume curve test, we selected forced vital capacity(FVC), percent of predicted forced vital capacity, forced expiratory volume within 1 second($FEV_1$), percent of forced expiratory volume within 1 second, the ratio of forced expiratory volume within 1 second against forced vital capacity($FEV_1$/FVC) in test which the sum of FVC and $FEV_1$ is biggest. We measured the diffusing capacity of the lung 3 times in each of the single-breath and intra-breath methods at intervals of 5 minutes, and we evaluated which factors have any influence on the difference of the diffusing capacity of the lung between two methods[the mean values(ml/min/mmHg) of difference between two diffusing capacity measured by two methods] by means of the linear regression method, and obtained the following results: Results: 1) Intra-test reproducibility in the single-breath and intra-breath methods was excellent. 2) There was in general a good correlation between the diffusing capacity of the lung measured by a single-breath method and that measured by the intra-breath method, but there was a significant difference between values measured by both methods($1.01{\pm}0.35ml/min/mmHg$, p<0.01) 3) The difference between the diffusing capacity of the lung measured by both methods was not correlated to FVC, but was correlated to $FEV_1$, percent of $FEV_1$, $FEV_1$/FVC and the gradient of methane concentration which is an indicator of distribution of ventilation, and it was found as a result of the multiple regression test, that the effect of $FEV_1$/FVC was most strong(r=-0.4725, p<0.01) 4) In a graphic view of the difference of diffusing capacity measured by single-breath and intra-breath method and $FEV_1$/FVC, it was found that the former was divided into two groups in section where $FEV_1$/FVC is 50~60%, and that there was no significant difference between two methods in the section where $FEV_1$/FVC is equal or more than 60% ($0.05{\pm}0.24ml/min/mmHg$, p>0.1), but there was significant difference in the section, less than 60%($-4.5{\pm}0.34ml/min/mmHg$, p<0.01). 5. The diffusing capacity of the lung measured by the single-breath and intra-breath method was the same in value($24.3{\pm}0.68ml/min/mmHg$) within the normal range(2%/L) of the methane gas gradient, and there was no difference depending on the measuring method, but if the methane concentration gradients exceed 2%/L, the diffusing capacity of the lung measured by single-breath method became $15.0{\pm}0.44ml/min/mmHg$, and that measured by intra-breath method, $11.9{\pm}0.51ml/min/mmHg$, and there was a significant difference between them(p<0.01). Conclusion: Therefore, in case where $FEV_1$/FVC was less than 60%, the diffusing capacity of the lung measured by intra-breath method represented significantly lower value than that by single-breath method, and it was presumed to be caused largely by a defect of ventilation-distribution, but the possibility could not be excluded that the diffusing capacity of the lung might be overestimated in the single-breath method, or the actual reduction of the diffusing capacity of the lung appeared more sensitively in the intra-breath method.

• Tuberculosis and Respiratory Diseases
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• v.40 no.6
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• pp.631-637
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• 1993

Background: In normal adults, ventilation is uneven and greater in the base than the apex of the lung in tidal volume breathing. However infants have fragile chest wall and reduced elastic recoil, resulting in easy closure of peripheral airways especially in the dependent portion of the lung. So ventilation in infants is greater in the apex than the base of the lung. We assumed that in adults whose closing volume is increased, dependent portion could be easily collapsed during tidal breathing and ventilation could be greater in the uppear than than the lower portion of the lung. Methods: We measured spirometry and closing volume(CV) in normal controls and in patients with chronic lung disease. Also we measured fractional distribution of ventilation at supine, left lateral and right lateral decubitus with $^{133}Xe$ ventilation scan in normal controls, patients with normal closing volume and patients with increased closing volume. Results: The subjects consisted of 7 normal controls(mean $age{\pm}SD$, $62.9{\pm}6.1$ years). 6 patients with normal CV($62.8{\pm}8.2$ years) and 7 patients with increased CV($63.0{\pm}15.3$ years). 1) Normal controls have mean(${\pm}SD$) FVC $104{\pm}11%$ of predicted value, $FEV_1\;120{\pm}16%,\;FEV_1/FVC\;112{\pm}5%$ and CV $86.9{\pm}12.5%$. Patients with normal CV have FVC $62{\pm}11%,\;FEV_1\;54{\pm}17%,\;FEV_1/FVC\;84{\pm}23%$ and CV $92.6{\pm}15.5%$. Patients with increased CV, have FVC $53{\pm}9%,\;FEV_1\;38{\pm}13,\;FEV_1/FVC\;69{\pm}16%$ and CV $176.1{\pm}36.6%$, CV was significantly different between two patient groups(p<0.02) 2). In normal controls mean fractional ventilation to left lung was $48.1{\pm}5.3%$ at supine, $54.1{\pm}9.8%$ at dependent and $40.9{\pm}6.5%$ at left uppermost position. In patients with normal CV mean fractional ventilation to left lung was $44.6{\pm}2.1%$ at supine, $59.7{\pm}5.6%$ at left dependent and $31.7{\pm}8.3%$ at left uppermost position. In patients with increased CV mean fractional ventilation to left lung was $48.7{\pm}4.5%$ at supine, $41.7{\pm}6.6%$ at left dependent and $60.9{\pm}15.7%$ at left uppermost position. In normal controls and patients with normal CV, ventilation to left lung at left dependent position tends to be higher than that at supine position but without statisitical significance and it was significantly lower at left uppermost than at left lung dependent position. In patients with increased CV, ventilation to left at left dependent position tends to be higher than that at supine position but without significance and it was significantly higher at left uppermost than that at left dependent position. Conclusion: These data suggest that in patients with increased CV ventilation to one side of lung could be higher at uppermost than at dependent position on lateral decubitus during tidal breathing and this fact should be taken into account in positioning of patients with unilateral lung disease.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.516-524
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• 1997

Background : Cancer invasion and metastasis require the dissolution of the extracellular matrix in which several proteolytic enzymes are involved. One of these enzymes is the urokinase-type plasminogen activator(u-PA), and plasminogen activator inhibitors(PAI-1, PAI-2) also have a possible role in cancer invasion and metastasis by protection of cancer itself from proteolysis by u-PA. It has been reported that the levels of u-PA and plasminogen activator inhibitors in various cancer tissues are significantly higher than those in normal tissues and have significant correlations with tumor size and lymph node involvement. Here, we measured the concentration of plasma u-PA and PAI-1 antigens in the patients with lung cancer and compared the concentration of them with histologic types and staging parameters. Methods : We measured the concentration of plasma u-PA and PAI-1 antigens using commercial ELISA kit in 37 lung cancer patients, 21 benign lung disease patients and 24 age-matched healthy controls, and we compared the concentration of them with histologic types and staging parameters in lung cancer patients. Results : The concentration of u-PA was $1.0{\pm}0.3ng/mL$ in controls, $1.0{\pm}0.3ng/mL$ in benign lung disease patients and $0.9{\pm}0.3ng/mL$ in lung cancer patients. The concentration of PAI-1 was $14.2{\pm}6.7ng/mL$ in controls, $14.9{\pm}6.3ng/mL$ in benign lung disease patients, and $22.1{\pm}9.8ng/mL$ in lung cancer patients. The concentration of PAI-1 in lung cancer patients was higher than those of benign lung disease patients and controls. The concentration of u-PA was $0.7{\pm}0.4ng/mL$ in squamous cell carcinoma, $0.8{\pm}0.3ng/mL$ in adenocarcinoma, 0.9ng/mL in large cell carcinoma, and $1.1{\pm}0.7ng/mL$ in small cell carcinoma. The concentration of PAI-1 was $22.3{\pm}7.2ng/mL$ in squamous cell carcinoma, $22.6{\pm}9.9ng/mL$ in adenocarcinoma, 42 ng/mL in large cell carcinoma, and $16.0{\pm}14.2ng/mL$ in small cell carcinoma. The concentration of u-PA was 0.74ng/mL in stage I, $1.2{\pm}0.6ng/mL$ in stage II, $0.7{\pm}0.4ng/mL$ in stage IIIA, $0.7{\pm}0.4ng/mL$ in stage IIIB, and $0.7{\pm}0.3ng/mL$ in stage IV. The concentration of PAI-1 was 21.8ng/mL in stage I, $22.7{\pm}8.7ng/mL$ in stage II, $18.4{\pm}4.9ng/mL$ in stage IIIA, $25.3{\pm}9.0ng/mL$ in stage IIIB, and $21.5{\pm}10.8ng/mL$ in stage IV. When we divided T stage into T1-3 and T4, the concentration of u-PA was $0.8{\pm}0.4ng/mL$ in T1-3 and $0.7{\pm}0.4ng/mL$ in T4, and the concentration of PAI-1 was $17.9{\pm}5.6ng/mL$ in T1-3 and $26.1{\pm}9.1ng/mL$ in T4. The concentration of PAI-1 in T4 was significantly higher than that in T1-3. The concentration of u-PA was $0.8{\pm}0.4ng/mL$ in M0 and $0.7{\pm}0.3ng/mL$ in M1, and the concentration of PAI-1 was $23.6{\pm}8.3ng/mL$ in M0 and $21.5{\pm}10.8ng/mL$ in M1. Conclusions : The plasma levels of PAI-1 in lung cancer were higher than benign lung disease and controls, and the plasma levels of PAI-1 in T4 were significantly higher than T1-3. These findings suggest involvement of PAI-1 with local invasion of lung cancer, but it should be confirmed by the data on comparison with pathological staging and tissue level in lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.534-546
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• 1997

Background : The p53 and retinoblastoma(Rb) tumor suppressor genes are associated with the pathogenesis of several types of human cancer. Substantial proportion of the primary lung cancers or cell lines have been reported to have the p53 and/or the Rb gene mutations. But, so far there is no report on the analysis of the Rb gene polymorphism as one of the genetic susceptibility marker. This study was undertaken to establish the gene frequencies of the polymorphic genotypes of the p53 and Rb genes in Koreans to evaluate the possible involvement of these genotypes as a risk factor of lung cancer. Methods : In this study 145 controls without previous and present tumor history and 128 lung cancer patients were subjected to analysis. The two intragenic polymorphisms of the p53 gene(exon 4/ AccII, intron 6/MspI) and one intron 17/XbaI polymorphism of the Rb gene were analysed by the method of polymersae chain reaction- restriction fragment length polymorphisms(PCR-RFLPs). The genotype of the intron 3/16 bp repeat polymorphism of p53 was determined by PCR and direct gel electrophoresis. Results : There were no significant differences in the genotype distributions of the p53 gene between lung cancer patients and controls. But heterozygotes(Arg/Pro) of the exon 4/AccII polymorphisms were slightly over-represented than controls, especially in the Kreyberg type I cancer, which was known to be associated with smoking. The intron 3/16 bp duplication and the intron 6/MspI polymorphisms were in complete linkage disequilibrium. About 95% of the individuals were homozygotes of the common alleles both in the 16 duplication and MspI polymorphisms, and no differences were deteced in the genotype distributions between lung cancer patients and controls. Overall genotype distributions of the Rb gene polymorphisms between lung cancer patients and controls were not significantly different However, the genotype distributions in the Kreyberg type I cancer were significantly different from those of controls(p = 0.0297) or adenocarcinomas(p = 0.0008). It was noticeable that 73.4% of the patients with adenocarcinomas were heterozygotes(r1/r2) whereas 39.2% of the Kreyberg type I cancer were heterozygous at this polymorphisms. In the lung cancer patients, significant differences were also noted between the high dose smokers and low dose smokers including non-smokers(p = 0.0258). The relative risk to Kreyberg type I cancer was significantly reduced in the individuals with the genotype of r1/r2(odds ratio = 0.46, 95% C.I. = 0.25-0.86, p = 0.0124). The combined genotype distribution of the exon 4 AccII of the p53 and the intron 17 Rb gene polymorphisms in Kreyberg type I cancers were significantly different from dose of controls or adenocarcinomas. The highest odds ratio were observed in the individuals with the genotypes of Arg/Pro and r2/r2(odds ratio = 1.97,95% C.I. = 0.84-4.59) and lowest one was in the patients with Arg/Arg, r1/r2 genotype(odds ratio = 0.54, 95% C.I. = 0.25-1.14). Conclusion : The p53 and the Rb gene polymorphisms modulate the risk of smoking induced lung cancer development in Koeans. However, the exact mechanism of risk modulation by these polymorphism remains to be determined. For more discrete clarification of associations between specific genotypes and lung cancer risk, the evaluations of these polymorphisms in other ethnics and more number of patients will be needed.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1308-1317
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• 1997

Background : Pulmonary aspergillomas usually arise from colonization and proliferation of Aspergillus in preexisting cavitary lung disease of any cause. About 15% of patients with tuberculous pulmonary cavities were found to have aspergilloma. We analyzed the clinical features and course of 91 patients with pulmonary aspergilloma. Method : During the ten-year period from June 1986 to May 1996, 91 patients whose condition was diagnosed as pulmonary aspergilloma at 4 university hospitals in Taegu city were reviewed. All patients fulfilled one of the following criteria : 1) histologic evidence of aspergilloma within abnormal air space in tissue sections, or 2) a positive Aspergillus serum precipitin test with the radiologic finding of a fungus ball. The histological diagno-sis was established in 81 patients(89.0%) and clinical diagnosis in 10 patients(11.0%). Results : 1) The age range was 22 to 65 years, with an average of 45 years. A male and female ratio was 1.7 : 1 (57 men and 34 women). 2) Hemoptysis was far the most frequent symptom(89%), followed by cough, dyspnea, weakness, weight loss, fever, chest pain. 3) In all but 14 cases(15.4%) there had been associated conditions. Pulmonary tuberculosis was far the most frequent underlying condition found(74.7%), followed by bronchiectasis (6.6%), cavitary neoplasm(2.2%), pulmonary sequestration(1.1%). 4) The involved area was usually in the upper lobes; the right upper lobe was involved in 39(42.9%), the left upper lobe in 31(34.1%), the left lower lobe in 13(14.3%), the right lower lobe in 7(7.7%), and the right middle lobe in 1(1.1%). 5) On standard chest roent geno gram the classic "bell-like" image of a fungus ball was found in 62.6% of the subjects. On CT scan, 88.1% of the subjects in which they were done. 6) The surgical therapy was undertaken in 76 patients, and medical therapy in 15 patients, including 4 patients with intracavitary instillation of amphotericin B. 7) The surgical modality was lobectomy in 55 patients(72.4%), segmentectomy in 16 patients(21.1%), pneumonectomy in 4 patients(5.3%), wedge resection in 1 patient(1.3%). The mortality rate was 3.9% (3 patients) ; 2 patients died of sepsis and 1 died of hemoptysis. The postoperative complications were encountered in 6 patients (7.9%), including each one patient with respiratory failure, bleeding, bronchopleural fistula, empyema, and vocal cord paralysis. 8) In the follow-up cases, each 2 patients of 71 patients with surgical treatment and 10 patients with medical treatment had recurrent hemoptysis. Conclusion : During follow-up of the chronic pulmonary disease with abnormal air space, if the standard chest roentgenograms are insufficient to detect a fungus ball, computed tomographic scan and serum precipitin test are likely to aid the diagnosis of patients with suspected pulmonary aspergilloma. A reasonable recommendation for management of a patient with aspergilloma would be to reserve surgical resection for those patients who have had severe, recurrent hemoptysis. And a well controlled cooperative study to the medical treatment such as intracavitary antifungal therapy is further needed.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.900-912
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• 1995

Background: Although graded exercise stress tests are widely used for the evaluation of cardiorespiratory performance, normal standards on respiratory gas exchange and ventilatory functions at maximal exercise in Koreans have not been well established. The purpose of this study is to provide reference values on these by sex and age, along with derivation of some of their prediction equations. Method: Symptom-limited maximal exercise test was carried out by Bruce protocol in 1,000 healthy adults consisting of 603 males and 397 females, aged 20~66 years. Among them VC, $FEV_1$ and MVV were also determined in 885 cases. All the subjects were members of a health center, excluding athletes. During the exercise, subjects were allowed to hold on to front hand rail of the treadmill for safety purpose. Results: The $VO_2\;max/m^2$, $VCO_2\;max/m^2$ and $V_E\;max/m^2$ were greater in males than in females and decreased with age. The RR max in men and women was similar but decreased slightly with age. The $V_T$ max was markedly greater in men but showed no significant changes with age in either gender. The mean of $V_T$ max/VC, $V_E$ max/MVV and BR revealed that there were considerable ventilatory reserves at maximal exercise even in older females. The regression equations of the cardinal parameters obtained using exercise time(ET, min), age(A, yr), height(Ht, cm), weight(W, kg), sex(S, 0=male; 1=female), VC(L), $FEV_1$(L) and $V_E$ max(L) as variables are as follows: $VO_2\;max/m^2$(L/min)=1.449+0.073 ET-0.007A+0.010W-0.006Ht-0.209S, $VCO_2\;max/m^2$(L/min)=1.672+0.063ET-0.008A+0.010W-0.005Ht-0.319S, VE max/$m^2$(L/min)=58.161+1.503ET-0.315A-9.871S or VE max/$m^2$(L/min)=47.873+6.548 $FEV_1$-5.715 S, and VT max(L)=1.497+0.223VC-0.493S. Conclusion: Respiratory gas exchange and ventilatory variables at maximal exercise were studied in 1,000 non-athletes by Bruce protocol. During exercise, the subjects were allowed to hold on to hand rail of the treadmill for safety purpose. We feel that our results would provide ideal target values for patients and healthy individuals to be achieved, since our study subjects were members of a health center whose physical fitness levels were presumably higher than ordinary population.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.846-854
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• 1995

Background: Cytokeratin 19 is a subunit of cytokeratin intermediate filament expressed in simple epithelia such as respiratory epithelial cells and their malignant counterparts. An immunoradiometric assay is available to detect a fragment of the cytokeratin, referred to as Cyfra 21-1 in the serum. This study was conducted to evaluate the clinical utility of this new marker in the diagnosis of lung cancer compared with established markers of squamous cell carcinoma antigen (SCC Ag) and carcino-embryonic antigen(CEA). In addition, we compared the diagnostic sensitivity and specificity of Cyfra 21-1 with those of SCC Ag in squamous cell carcinoma of the lung. We also measured the level of Cyfra 21-1 in the different stages of squamous cell carcinoma of the lung. Method: We measured Cyfra 21-1(ELSA-CYFRA 21-1), SCC Ag(ABBOTT SCC RIABEAD) and CEA(ELSA2-CEA) in 79 patients with primary lung cancer and in 78 persons as a comparison group including 32 patients with pulmonary tuberculosis, 23 patients with benign lung disease and 23 cases with healthy individual. Cyfra 21-1 is measured by a solid-phase immunoradiometric assay(CIS Bio International, France) based on the two-site sandwich method. SCC Ag is measured by a radioimmunoassay(Abbott Laboratories, USA). CEA is measured by a immunoradiometric assay(CIS Bio International, France). All data were expressed as the mean$\pm$standard deviation. Results: 1) The mean value of Cyfra 21-1 was $18.38{\pm}3.65\;ng/mL$ in the lung cancer and $1.l6{\pm}0.53\;ng/mL$ in the comparison group(p<0.0001). SCC Ag was $3.53{\pm}6.06\;ng/mL$ in the lung cancer and $1.19{\pm}0.5\;ng/mL$ in the comparison group(p<0.01). CEA was $35.03{\pm}13.9\;ng/mL$ in the lung cancer and $2.89{\pm}1.01\;ng/mL$ in the comparison group(p<0.0001). 2) Cyfra 21-1 level in squamous cell carcinoma($31.52{\pm}40.13\;ng/mL$) was higher than that in adenocarcinoma($2.41{\pm}1.34\;ng/mL$)(p<0.0001) and small cell carcinoma($2.15{\pm}2.05\;ng/mL$)(p=0.007). SCC Ag level in squamous cell carcinoma($5.1{\pm}7.68\;ng/mL$) was higher than that in adenocarcinoma($1.36{\pm}0.69\;ng/mL$)(p=0.009) and small cell carcinoma($1.1{\pm}0.24\;ng/mL$) (p=0.024). 3) The level of Cyfra 21-1 was not correlated with the progression of stage in squamous cell carcinoma of the lung. 4) Using the cut-off value of 3.3ng/mL, the diagnostic sensitivity of Cyfra 21-1 was 83% in squamous cell carcinoma, 22% in adenocarcinoma and 17% in small cell carcinoma. The sensitivity of SCC Ag and CEA were 39% and 20%, respectively in squamous cell carcinoma, 11% and 39% in adenocarcinoma, and 0% and 33% in small cell carcinoma. 5) Comparison of the receiver operating characteristics curves(ROC curve) for Cyfra 21-1, SCC Ag and CEA revealed that Cyfra 21-1 showed highest diagnostic sensitivity among them in the diagnosis of lung cancer. Conclusion: Cyfra 21-1 is thought to be a better tumor marker for the diagnosis of lung cancer than SCC Ag and CEA, especially in squamous cell carcinoma of the lung.

• Tuberculosis and Respiratory Diseases
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• v.49 no.6
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• pp.691-702
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• 2000

Background : Acute lung injury (ALI) is a commonly encountered respiratory disease and its prognosis is poor when the treatment is not provided promptly and properly. However no specific pharmacologic treatment is currently available for ALI, although recently several supportive drugs have been under scrutiny. We studied anti-inflammatory effects of pentoxifylline (PF), a methylated xanthine, and ONO-5046, a synthetic neutrophil elastase inhibitor on lipopolysaccharide (LPS)-induced ALI in vitro. Methods : To establish an in vitro model of LPS-induced ALI, primary rat alveolar macrophages and peripheral neutrophils in various ratios (1:0, 5:1, 1:1, 1:5, 0:1) were co-cultured with transformed rat alveolar epithelial cells (L2 cell line) or vascular endothelial cells (IP2-E4 cell line) under LPS stimulation. Each experiment was divided into five groups-control, LPS, LPS+PF, LPS+ONO, and LPS+PF+ONO. We compared LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils in various ratios, and the resultant cytotoxicity on L2 cells or IP2-E4 cells between groups. In addition we also compared the productions of tumor necrosis factor (TNF)-$\alpha$ interleukin (IL)-$1{\beta}$, monocyte chemotactic protein(MCP)-1, IL-6, and IL-10 as well as mRNA expressions of TNF-$\alpha$ inducible nitric oxide synthetase(iNOS), and MCP-1 from LPS-stimulated primary rat alveolar macrophages between groups. Results : (1) PF and ONO-5046 in each or both showed a trend to suppress LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils regardless of their ratio, except for the LPS+PF+ONO group with the 1:5 ratio, although statistical significance was limited to a few selected experimental conditions. (2) PF and ONO-5046 in each or both showed a trend to prevent IP2-E4 cells from LPS-induced cytotoxicity by primary rat alveolar macrophages and peripheral neutrophils regardless their ratio, although statistical significance was limited to a few selected experimental conditions. the effects of PF and/or ONO-5046 on LPS-induced L2 cell cytotoxicity varied according to experimental conditions. (3) PF showed a trend to inhibit LPS-induced productions of INF-$\alpha$ MCP-1, and IL-10 from primary rat alveolar macrophages. ONO-5046 alone didnot affect the LPS-induced productions of proinflammatory cytokines from primary rat alveolar macrophages but the combination of PF and ONO-5046 showed a trend to suppress LPS-induced productions of INF-$\alpha$ and IL-10 PF and ONO-5046 in each or both showed a trend to increase LPS-induced IL-$\beta$ and IL-6 productions from primary rat alveolar macrophages. (4) PF and ONO-5046 in each or both showed a trend to attenuate LPS-induced mRNA expressions of TNF-$\alpha$ and MCP-1 from primary rat alveolar macrophages but at the same time showed a trend increase iNOS mRNA expression. Conclusion : These results suggest that PF and ONO-5046 may play a role in attenuating inflammation in LPS-induced ALI and that further study is needed to use these drugs as a new supportive therapeutic strategy for ALI.