The serotype-specific prevalence of pneumococci in hospitalized pneumonia patients with COPD: a prospective, multi-center, cohort study

Background/Aims@#The overall incidence of pneumococcal pneumonia is declining. However, the change in the pathogenic distribution of community-acquired pneumonia (CAP) in chronic obstructive pulmonary disease (COPD) patients and the serotype specificity of Streptococcus pneumoniae have not been evaluated in the post-era of pneumococcal vaccination in Korea. @*Methods@#We conducted a prospective, multi-center, cohort study from seven University-affiliated hospitals. The primary objective was the identification of serotype-specific prevalence of pneumococcal pneumonia in COPD patients hospitalized for CAP. For the purpose, we conducted serotype-specific urine antigen detection (SS-UAD) assays for S. pneumoniae. The secondary objectives were other clinical characteristics of pneumonia including vaccination status. @*Results@#The total number of participants was 349. Most of them were male (95.1%) with old ages (75.55 ± 8.59 y). The positive rate for S. pneumoniae was 9.2% with SS-UAD assay and the common serotypes were 22F, 6A, and 6B. In the sputum, Pseudomonas aeruginosa (5.0%) and Haemophilus influenzae (4.0%) were common pathogens. The vaccination rate was 78.8%, 53.0%, and 25.8% for influenza, pneumococcal polysaccharide vaccine 23 (PPV 23), and pneumococcal protein- conjugated vaccine 13 (PCV 13), respectively. Thirteen patients died during hospitalization (mortality rate; 3.7%). There was no difference in the respective rate of influenza vaccination (79.2% vs. 69.2%, p = 0.288) and PCV 13 vaccination (25.6% vs. 30.8%, p = 0.443) between survivors and the deceased. @*Conclusions@#Serotypes 22F, 6A, and 6B, which are covered either by PPV 23 or by PCV 13, are still common pneumococcal serotypes in COPD pneumonia in the post-vaccination era in Korea.

Therapeutic effect of atorvastatin on interleukin-13-induced lung pathology

Purpose@#Asthma is a common chronic lung disease, in which interleukin (IL)-13 is implicated as a central regulator of IgE synthesis, mucus hypersecretion, airway hyperresponsiveness (AHR), and fibrosis. This study was designed to determine the anti-inflammatory effect of atorvastatin, a widely used lipid-lowering agent, on the IL-13-induced lung pathology through the modulation of macrophages. @*Methods@#Atorvastatin (40 mg/kg) was given to transgenic mice overexpressing IL-13 (IL-13 TG mice) and their wild type littermates by oral gavage for 2 weeks. AHR, numbers of inflammatory cells in the airway, and cytokine levels in IL-13 TG mice were measured.Using the alveolar macrophage cell line CRL-2456, the direct effect of atorvastatin on macrophages activated by recombinant IL-13 was assessed. @*Results@#Significant reduction in total leukocytes and alleviation of AHR were observed with administration of atorvastatin in IL-13 TG mice compared to those without atorvastatin treatment (P< 0.05). Atorvastatin administration resulted in upregulation of IL-10 in the lungs of IL-13 TG mice (P< 0.05). In addition, mRNA expression of connective tissue growth factor, fibronectin, and type III collagen as well as chord length enhanced by IL-13 overexpression were reduced by atorvastatin administration (P< 0.05). M2 macrophage markers, such as Ym-1 and CD206, were decreased, while M1 macrophage marker, inducible nitric oxide synthase, was increased upon atorvastatin treatment (P< 0.05). Administration of atorvastatin resulted in improved removal of apoptotic cells (P< 0.05). @*Conclusion@#The results of this study reveal a potential of atorvastatin as an effective antiasthmatic agent by reducing IL-13-induced lung inflammation via the modulation of macrophage polarization.

Recent Advances in Molecular Basis of Lung Aging and Its Associated Diseases / 결핵및호흡기질환

Aging is often viewed as a progressive decline in fitness due to cumulative deleterious alterations of biological functions in the living system. Recently, our understanding of the molecular mechanisms underlying aging biology has significantly advanced. Interestingly, many of the pivotal molecular features of aging biology are also found to contribute to the pathogenesis of chronic lung disorders such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis, for which advanced age is the most crucial risk factor. Thus, an enhanced understanding of how molecular features of aging biology are intertwined with the pathobiology of these aging-related lung disorders has paramount significance and may provide an opportunity for the development of novel therapeutics for these major unmet medical needs. To serve the purpose of integrating molecular understanding of aging biology with pulmonary medicine, in this review, recent findings obtained from the studies of aging-associated lung disorders are summarized and interpreted through the perspective of molecular biology of aging.

Recent Advances in Molecular Basis of Lung Aging and Its Associated Diseases / 결핵

Aging is often viewed as a progressive decline in fitness due to cumulative deleterious alterations of biological functions in the living system. Recently, our understanding of the molecular mechanisms underlying aging biology has significantly advanced. Interestingly, many of the pivotal molecular features of aging biology are also found to contribute to the pathogenesis of chronic lung disorders such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis, for which advanced age is the most crucial risk factor. Thus, an enhanced understanding of how molecular features of aging biology are intertwined with the pathobiology of these aging-related lung disorders has paramount significance and may provide an opportunity for the development of novel therapeutics for these major unmet medical needs. To serve the purpose of integrating molecular understanding of aging biology with pulmonary medicine, in this review, recent findings obtained from the studies of aging-associated lung disorders are summarized and interpreted through the perspective of molecular biology of aging.

A Mitochondrial Perspective of Chronic Obstructive Pulmonary Disease Pathogenesis / 결핵및호흡기질환

Chronic obstructive pulmonary disease (COPD) encompasses several clinical syndromes, most notably emphysema and chronic bronchitis. Most of the current treatments fail to attenuate severity and progression of the disease, thereby requiring better mechanistic understandings of pathogenesis to develop disease-modifying therapeutics. A number of theories on COPD pathogenesis have been promulgated wherein an increase in protease burden from chronic inflammation, exaggerated production of reactive oxygen species and the resulting oxidant injury, or superfluous cell death responses caused by enhanced cellular injury/damage were proposed as the culprit. These hypotheses are not mutually exclusive and together likely represent the multifaceted biological processes involved in COPD pathogenesis. Recent studies demonstrate that mitochondria are involved in innate immune signaling that plays important roles in cigarette smoke-induced inflammasome activation, pulmonary inflammation and tissue remodeling responses. These responses are reviewed herein and synthesized into a view of COPD pathogenesis whereby mitochondria play a central role.

Symptom Questionnaire and Laboratory Findings in Subjects with Airflow Limitation: a Nation-wide Survey / 결핵및호흡기질환

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation that is not fully reversible. COPD has systemic effects, such as skeletal muscle dysfunction and abnormal weight loss. It also has been suggested that COPD is related to other chronic disease, such as cardiovascular disease, osteoporosis, and anemia. The aim of this study was to evaluate a symptom questionnaire and laboratory findings in subjects with air flow limitation. METHODS: We evaluated a symptom questionnaire and laboratory findings in subjects with airflow limitation detected by spirometry in conjunction with the Second Korean National Health and Nutrition Examination Survey. A total of 9,243 adults over the age of 18 were recruited. Among the adults, we finally analyzed 2,217 subjects who met the acceptability and repeatability criteria of spirometry, showed normal findings on chest radiography, and were older than 40 years of age. RESULTS: There were 288 subjects with airflow limitation as determined by spirometry. The frequency of respiratory symptoms such as cough, sputum and wheezing were significantly higher in subjects with airflow limitation (p<0.01). Hemoglobin and hematocrit levels were higher in subjects with airflow limitation (hemoglobin level 13.98 mg/dL vs. 13.62 mg/dL, hematocrit 42.10% vs. 40.89%; p<0.01). The HDL cholesterol level was lower in subjects with airflow limitation (44.95 mg/dL vs. 45.60 mg/dL; p<0.01). There was no significant difference in the total cholesterol, triglyceride, blood urea nitrogen, creatinine, and fasting glucose levels. CONCLUSION: In subjects with airflow limitation, prevalence of respiratory symptoms was higher than in normal spirometry subjects and the levels of hemoglobin and the hematocrit were higher. The HDL cholesterol level was lower in subjects with airflow limitation.

An Evaluation of the Use of Statistical Methods in the Journal of Tuberculosis and Respiratory Diseases / 결핵및호흡기질환

BACKGROUND: The statistical analysis is an essential procedure ensuring that the results of researches are based on evidences rather than opinion. The purpose of this study is to evaluate which statistical techniques are used and whether these statistical methods are used appropriately or not in the journal of Tuberculosis and Respiratory Diseases. MATERIALS AND METHODS: We reviewed 185 articles reported in the journal of Tuberculosis and Respiratory Diseases in 1999. We evaluated the validity of used statistical methods based upon the checklist that was developed on the basis of the guideline for statistical reporting in articles for medical journals by International Committee of Medical Journal Editors. RESULTS: Among 185 articles, original articles and case reports were 110 (59.5%) and 61 (33.0%) respectively. In 112 articles excluding case reports and reviews, statistical techniques were used in 107 articles (95.5%). In 94 articles (83.9%) descriptive and inferential methods were used, while in 13 (11.6%) articles only descriptive methods were used. With the types of inferential statistical techniques, comparison of means was most commonly used (64/94, 68.1%), followed by contingency table (43/94, 45.7%) and correlation or regression (18/94, 19.1%). Among the articles in which descriptive methods were used, 83.2% (89/107) showed inappropriate central tendency and dispersion. In the articles in which inferential methods were used, improper methods were applied in 88.8% (79/89) and the most frequent misuse of statistical methods was inappropriate use of parametric methods (35/89, 39.3%). Only 14 articles (13.1%) were satisfactory in utilization of statistical methodology. CONCLUSION: Most of the statistical errors found in the journal were misuses of statistical methods related to basic statistics. This study suggests that researchers should be more careful when they describe and apply statistical methods and more extensive statistical refereeing system would be needed.

Lung Matrix Metalloproteinase-9 Correlates with Cigarette Smoking and Obstruction of Airflow

Cigarette smoking is the most important risk factor for obstruction of airflow in chronic obstructive pulmonary disease (COPD). Matrix metalloproteinases (MMPs) or an imbalance between MMPs and their inhibitors, the tissue inhibitors of MMP (TIMPs), is considered to play a role in the pathogenesis of COPD. We investigated whether the MMPs expression or the imbalance between MMPs and TIMP-1 is associated with the amount of cigarette smoking and the FEV1 value, in the lung parenchyma of 26 subjects (6 non-smokers and 20 cigarette smokers). First, we performed zymographic analysis to identify the profile of the MMPs, which revealed gelatinolytic bands mainly equivalent to MMP-9 in the smokers. We then measured, using enzyme immunoassay, the concentrations of MMP-9 and its inhibitor, TIMP-1. Correlation analysis revealed that both the MMP-9 concentrations and the molar ratios of MMP-9 to TIMP-1 (MMP-9/TIMP-1) were correlated with the amount of cigarette smoking. Furthermore, MMP-9 concentrations were inversely correlated with FEV1. In conclusion, this study shows that MMP-9 expression in human lung parenchyma is associated with cigarette smoking and also with the obstruction of airflow, suggesting that MMP-9 may play a role in the pathogenesis of the cigarette smoke-induced obstruction of airflow known as the characteristic of COPD.

A Case of Giant Cell Interstitial Pneumonia without History of Exposure to Hard Metal / 결핵

A 44 year old man was admitted complaining of exertional dyspnea. The patient denied denied any occupational history of hard metal exposure. Chest radiography showed an increased interstitial marking at the peripheral po rtion of both lower lung fields. The spirometric values were within the normal ranges. However, the diffusion capacity of the lungs was lower. In the bronchial lavage fluid, the characteristic multinucleated giant cells were noticed, and the macrophage compartment was 96% and the neutrophils were 4%. Highresolution CT scan revealed ground glass opacities with emphysematous lung changes at the peripheral portion of the whole lung. An open lung biopsy confirmed the presence of numerous multinucleated giant cells (Define GIF) with an associated interstitial fibrosis throughout the lung. The radiographic abnormalities and symptoms subsequently improved following treatment with oral corticosteroids.

A Case of Giant Cell Interstitial Pneumonia without History of Exposure to Hard Metal / 결핵

A 44 year old man was admitted complaining of exertional dyspnea. The patient denied denied any occupational history of hard metal exposure. Chest radiography showed an increased interstitial marking at the peripheral po rtion of both lower lung fields. The spirometric values were within the normal ranges. However, the diffusion capacity of the lungs was lower. In the bronchial lavage fluid, the characteristic multinucleated giant cells were noticed, and the macrophage compartment was 96% and the neutrophils were 4%. Highresolution CT scan revealed ground glass opacities with emphysematous lung changes at the peripheral portion of the whole lung. An open lung biopsy confirmed the presence of numerous multinucleated giant cells (Define GIF) with an associated interstitial fibrosis throughout the lung. The radiographic abnormalities and symptoms subsequently improved following treatment with oral corticosteroids.

Usefulness of Tuberculin Skin Test by Tuberculin PPD RT23 2 TU / 결핵

BACKGROUND: Tuberculin skin test is a method to examine M. tuberculosis infection and has been used all over the world. But various factors make it difficult to understand testing results. In 2000, the American Thoracic Society recommended that skin test results should be decided by considering risk factors of the tested. In Korea, high tuberculosis infection rate and BCG vaccination rate make it difficult to differentiate current infection, past infection, and no infection by the skin test. This study was attempted to examine a negative predictive value of the skin test to understand how the skin test acts on deciding administration of anti-tuberculosis drug. METHOD: From Mar. 1 to Jul. 31 in 2001, the test was performed for patients hospitalized in Department of Internal Medicine, Hallym University College of Medicine, Chunchon, Korea by administering Tuberculin PPD RT23 2 TU (0.1 ml)to them that has been currently used in Korea based on Mantoux method. They were decided to be infected with tuberculosis bacilli by following diagnostic standard: 1) tuberculosis bacilli was cultured in sputum by microbiological diagnostic standard or Acid-fast bacilli was proven on a microscopic examination or 2) tuberculosis bacilli was not proven in the aforesaid microbiological test by clinical diagnostic standard, while there was opinion or symptom suitable for tuberculosis by radiographic or histological standard so the doctor decided to apply the tuberculosis treatment. RESULTS: In this study, total 210 patients except 20 patients (8.7%) among 230 hospitalized patients were evaluated. Their average age was 60 16.8 years, and male-female rate was 1.28 : 1 (male: 118, female: 92). Number of patient, who was diagnosed and decided as tuberculosis, was 53(25.2%). Pulmonary tuberculosis was found in 45 patients (84.9%); 22 patients were decided to be positive in the Acid-fast bacilli smear test by microbiological examination (culture positive: 13, culture negative: 9), and 23 patients were decided to be tuberculosis patients by clinical diagnosis standard. Tuberculosis pleuritis was found in 8 patients (15.1%); 4 patients were diagnosed and decided by histological standard, and 4 patients were decided and treated by clinical standard. In differentiating patients into 'Negative' and 'Positive' by the skin test standard of the American Thoracic Society, negative predictive value 92.3%, positive predictive value 47.3%, sensitivity and specificity were 83%, 68.8%, respectively. CONCLUSION: In hospitalized respiratory patients, there was high negative predictive vlaue 92.3% by tuberculin skin test, therefore skin test would be a important factor for deciding administration of anti-tuberculosis drug on negative skin test patient.

A Case of Bronchus-Associated Lymphoid Tissue(BALT) Lymphoma in the Lung of the Patient with Primary Sjogren's Syndrome / 결핵

A bronchus-associated lymphoid tissue(BALT) lymphoma of the lung is a rare disorder of patients with Sjogren's syndrome. A 49-year-old woman was admitted for an evaluation of exertional dyspnea and general weakness which had persisted for two years. The patient had suffered from dry mouth and dry eyes for five years. The physical examinations showed a coarse breath sound with inspiratory crackles on the whole lung field, particularly on the both basal lungs. The laboratory data disclosed high titers of anti-nuclear antibodies, and anti-SSA (Ro), and anti-SSB(La) antibodies. Chest radiographs demonstrated the presence of bilateral, diffuse, reticulonodular densities in both lungs. Thin-section CT scans showed diffusely distributed mosaic pattern of an inhomogeneous attenuation extending over the entire lung zone. The histological findings from an open-lung biopsy specimen revealed an accumulation of lymphoid cells around the bronchioles and an extension of malignant lymphoma cells from the bronchiolar epithelium toward the alveolar space. Immunohistochemically, the neoplastic cells reacted positively to the CD 20 antigen and were focally positive for the UCHL 1 antigen. The histological diagnosis was consistent with a low grade marginal zone B-cell lymphoma originating in the BALT. Here, we present a case of a histologically proven BALT lymphoma of the lung in a patient with primary Sjogren's Syndrome.

How Reliable is Sputum PCR Test in the Diagnosis of Pulmonary Tuberculosis When Sputum Smear is Negative? / 결핵

BACKGROUND: Recent technological developments have introduced a new method to identifying M. tuberculosis complex DNA in clinical samples directly. The direct amplification test (DAT) is approved for identifying M. tuberculosis complex in respiratory specimens that are smear-positive for acid-fast bacilli (AFB). When there is a discrepancy between the AFB smear and DAT, no information on their clinical utility is currently available. In this study, the diagnostic reliability of DAT was investigated in suspected pulmonary tuberculosis patients whose sputum AFB smear was negative. METHODS: From June 1, 1998 through May 30, 1999, 909 patients with presumed active pulmonary tuberculosis were enrolled. A sputum AFB stain, culture, DAT and /or biopsy were performed. using the criteria of clinical tuberculosis or confirmed tuberculosis, the positive predictive value of DAT in diagnosing pulmonary tuberculosis was investigated. RESULTS: The positive predictive value of DAT was 82.1% by the clinically active tuberculosis criteria. However, it decreased to 61.5% when diagnosis was restricted to only to culture positive or biopsy proven cases. The false positive rate of DAT was 18.0%. CONCLUSION: The DAT is a valuable diagnostic method in suspected patients whose sputum AFB is was negative.

The Etiological Role of Legionella Pneumophila in Patients with Community-Acquired Pneumonia in Korea / 결핵

BACKGROUND: Legionella pneumophila has been recognized as an important cause of community-acquired pneumonia(CAP) requiring hospitalization. However, epidemiological data on the occurrence of legionella-related pneumonia is unavailable in Korea. The purpose of this study was to evaluated the etiological imprtance of legionella pneumophila serogroup 1 in patients hospitalized with CAP. METHOD: The CAP patient over 16 year-old were recruited from July 1999 to June 2000 at the Chunchon Sacred Heart Hospital. Fifty four patients (male 29, female 25, average age 63.8±15.3) were included in this study. A diagnosis of a legionella pneumophila infection was based on a urinary antigen test using the Binax Company enzyme immunoassay. The severity of pneumonia was assessed using the Fine's PORT scoring system. RESULT: The average Fine's PORT score was 99.7(±44.9). According to the risk classification proposed by the Infectious Disease Society of America, the number of patients in each class(from class I to class V) were 6(11.1%), 13(24.1%), 9(16.7%), 14(25.8%), and 12(22.2%), respectively. Thirty two patients(59.3%) were initially admitted to the intensive care unit. The mortality rate was 16.7%(9 in 54). In all patients, urinary antigens to Legionella pneumophila serogroup 1 were not detected. CONCLUSION: Legionella pneumophila may play little role in causing adult CAP in Korea. Therefore, the routine use of macrolide in the empirical treatment of the CAP patients based upon the ATS guidelines(1993) in Korea should be reevaluated.

The Increased Expression of Gelatinolytic Proteases Due to Gigarette Smoking Exposure in the Lung of Guinea Pig / 결핵

BACKGROUND: Chronic obstructive pulmonary disease(COPD) is one of the major contributors to morbidity and mortality amont the adult population. Cigarette smoking(CS) is undoubtedly the single most important factor in the pathogenesis of COPD. However, its mechanism is unclear. The current hyopthesis regarding the pathogenesis of COPD postulates that an imbalance between proteases and antiproteases leads to the destructive changes in the lung parenchyma. This study had two aims. First, to evaluate the effect of CS exposure on histologic changes of the lung parenchyme, and second, to evaluate the effect of CS exposure on the expression of the gelatinolytic enzymes in BAL fluid cells in guinea pigs. METHODS: Two groups of five guinea pigs were exposed to the whole smoke of 20 commerical cigarettes per day, 5 hours/day, 5 days/week, for 6 weeks, and 12 weeks, respectively, using a smoking apparatus. Five agematched guinea pigs exposed to room air were used as controls. Five or more sections were microscopically examined(×400) and the number of cellular infiltration of the alveolar wall was measured in order to evaluate the effect of CS exposure on the histologic changes of lung parenchyme. The statistical significance was analyzed by a linear regression method. To evaluate the expression of the gelatinolytic enzymes in intraalveolar cells, BAL fluid was obtained and the intraalveolar cells were separated by centrifugation (500 g for 10 min at 4℃). Two sets of culture plates were loaded with 1×106 intraalveolar cells. One plate, contained 0.1mM EDTA, a inhibitor of matrix metalloproteases(MMPs), and the other plate had no EDTA. Both plates were incubated for 48 hours at 37℃. After incubation, gelatinolytic protease expression in the supernatants was analyzed by gelatin zymography. RESULTS: At the end of CS exposure, the level of blood carboxy Hb had increased significantly(4.1g/dl in control group, 24g/dl immediately after CS exposure, 18g/dl 30 min after CS exposure). Alveolar inflammatory cells were identified in the CS exposed guinea pigs. The number of alveolar cellular cells observed in a microscopic field (400×) was 121.4±7.2, 158.0±20.2, 196.8±32.8, in the control, the 6 weeks, and the 12 weeks group, respectively. The increased extent of inflammatory cellular infiltration of the lung parenchema showed a statistically significant linear relationship with the duration of CS exposure(p=0.001, r2=0.675). Several types of gelatinolytic enzymes in the intraalveolar cells of CS exposed guinea pigs were expressed, of which some were inhibited by EDTA. However, the gelatinolytic enzymes were not expressed in the control groups. CONCLUSION: CS exposure increases inflammatory cellular infiltration of the alveolar wall and the expression of gelatinolytic preoteases in guinea pigs. EDTA inhibits some of the gelatinolytic proteases. These findings suggest a possibility that CS exposure may increase MMP expression in the lungs of gunea pigs.

Clinical Significance of PCR-Based Rapid Detection of Mycobacterium tuberculosis DNA in Peripheral Blood / 결핵

BACKGROUND: Since the advent of AIDS, tuberculosis has become a major public health problem in the western society. Therefore, it is essential that pulmonary tuberculosis be rapidly diagnosed. Light microscopic detection of acid-fast organisms in sputum has traditionally been used for rapidly diagnosing tuberculosis. However positive smears are only observed in about one-half to three-quarters of cases. Studies using PCR for diagnosing pulmonary tuberculosis disclosed several shortcomings suggesting an inability to distinguish between active and treated or in active tuberculosis. In this study, the clinkcal significance of a PCR-bases rapid technique for detecting Mycobacterium tuberculosis DNA in peripheral blood investigated. MATERIALS AND METHODS: From July 1, 1998 through to August 30, 1999, 59 patients with presumed tuberculosis, who had no previous history of anti-tuberculosis medication use whithin one year prior to this study were recruite and followed up for more than 3 months. AFB stain and culture in the sputum and/or pleural fluids and biopsies when needed were performed. Blood samples from each of the 59 patients were obtained in order to identify Mycobacterium Tuberculosis DNA by a PCR test. RESULTS: 1) Forty five out of 59 patients had a final diagnosis of tugerculosis; Twenty eight were confirmed as having active pulmonary tuberculosis by culture or biopsy. Four were clinkcally diagnosed with pulmonary tuberculosis. The othe 13 patients were diagnosed as having tuberculous pleurisy (9) and extrapulmonary tuberculosis (4). 2) Fourteen patients showed a positive blood PCR test. The PCR assay correctly identified active tuberculosis in 13 out of 14 patients. The overall sensitivity and specificity of this blood PCR assay for diagnosing tuberculosis were 29% and 93%, respectively. The positive predictive value was 93%, the negative predictive value was 29% and diagnostic accuracy was 44%. 3) Six out of 14(43%) patients with blood PCR positive tuberculosis were immunologically compromised hosts. 4) A simple chest radiograph in blood PCR positive tuberculosis patients showed variable and inconsistent findings. CONCLUSION: A peripheral blood PCR assay for Mycobacterium tuberculosis is not recommended as screening method for diagnosing active tuberculosis. However, it was suggested that the blood PCR assay could contribute to an early diagnostic rate due to its high positive predictive value.

The Influence of Aging on Pulmonary Function Tests in Elderly Korean Population / 결핵

BACKGROUND: Many studies have shown that pulmonary function differs widely among race, age and geographical residency. By virtue of the improvement of nutrition and environment, the elderly population in Korea is markedly increasing and so are the ages of patients complaining respiratory symptoms. However, we do not have our own data on the pulmonary functional reserve of elderly persons in Korea. We evaluate the deterioration of pulmonary functional reserve and standardize the predictive values of pulmonary function in the elderly population. METHOD: Pulmonary function tests were conducted in 100 men and 100 women over the age of 65. We analyzed changes of FVC and FEV1 according to age and height by linear regression. We compared our new multiple linear regression equation with other equations currently used in Korea. RESULTS: In men, the mean age was 71.5±5.2(mean±SD) years and the mean height was 163.6±6.2cm. The mean FVC was 3.42±0.49ℓ and the mean FEV1, 2.72±0.40ℓ. In women, the mean age was 72.0±5.1 years and the mean height was 149.1±5.9cm. The mean FVC was 2.22±0.42ℓ and the mean FEV1, 1.83±0.34ℓ. Multiple linear regression equation using age and height as an independent factors was as follows : FVC(ℓ)=1.857-0.0356×age(year)+0.02157×height(cm) (p<0.01, R2=0.279), FEV1(ℓ)=1.340-0.02698×age(year)+0.02021×height(cm) (p<0.01, R20.255) in men, FVC(ℓ)=-0.09765-0.03332×age(year)+0.03164×height(cm) (p<0.01, R2=0.435), FEV1(ℓ)=-0.169-0.02469×age(year)+0.02539×height(cm) (p<0.01, R2=0.41) in women. CONCLUSION: We established prediction regressions for pulmonary functional tests in the elderly Korean population. We also confirmed that currently adopted equations do not exactly anticipate the expected pulmonary functional reserve in the aged person over 65 years old. We suggest that our new equations from this study should be applied to interpret the pulmonary function tests in the elderly population in Korea.

Endothelium-Dependent Relaxation Is Impaired by Environmental Tobacco Smoke Exposure in Guinea Pig Aorta

BACKGROUND & OBJECTIVES: Smoking is a risk factor for the development of atherosclerosis. However, the exact mechanism of smoking-related damage to the arterial wall and its relation to the atherosclerotic process are not known. The endothelium plays an important role for the regulation of vascular tone and its function is impaired in the presence of risk factors early in the process of atherosclerosis. To assess the effect of smoking on endothelium-dependent relaxation, we examined vascular reactivity in vitro in an animal model of environmental tobacco smoke exposure. MATERIALS & METHODS: Guinea pigs were randomized to control group or environmental tobacco smoke exposure group. The source of environmental tobacco smoke exposure was sidestream smoke during 6 hours per day and 5 days per week over 6 weeks or 12 weeks in a smoking chamber. Fresh aortic rings were suspended in organ baths(37degrees C, 95%O2-5%CO2). Rings were precontracted with phenylephrine(10(-7)M) and exposed to acetylcholine(10(-7)-10(-4)M) and sodium nitroprusside(10(-7)-10(-5)M) in increasing doses and isometric tension was recorded to evaluate the endothelium-dependent and -independent relaxation. RESULTS: Acetylcholine-induced maximal relaxation(mean+/-SD) was 18+/-9% in the rings from the 6-week smoked guinea pigs and 4+/-3% in the rings from the 12-week smoked guinea pigs in comparison with 49+/-6% of the controls(p<0.05). The endothelium-dependent relaxation of the rings from 12 week-exposure was significantly less than that of 6 week-exposure. In contrast endothelium-independent relaxation to SNP was not different among three groups. CONCLUSION: Environmental tobacco smoke exposure impairs endothelial function in guinea pig aorta.

Prognosis of Patients with Non-Small Cell Lung Cancer after Surgery / 결핵

BACKGROUND: Lung cancer continues to be the leading cause of cancer death in the United States and it's incidence has been rapidly increasing in Korea, too. The overall cure rate for non-small cell lung cancer(NSCLC) is approximately 10%, and the cure is generally achieved by surgery. Unfortunately, however, less than 15% of all patients and less than 25% of those who present with localized disease are candidates for curative surgical resection. So preoperative staging evaluation followed by curative resection has a major role in determining the long term prognosis of NSCLC patients. Therefore, we have conducted this study to compare pre-operative and post-operative staging and the long-term relapse-free survival rates in NSCLC patients according to its stage. METHODS: We analyzed the medical records of 217 NSCLC patients who were operated on for curative resection in Seoul National University Hospital, retrospectively. Among them, 170 patients who were completely resected were selected to determine the long term relapse-free survival rates. RESULTS: Among 217 NSCLC patients, men were 157 and women were 30. The median age was 58 and the difference between men and women was not found. The discrepancy rate between preoperative and postoperative staging was 40.1%. Its major cause was due to the difference of nodal staging. The 3-year relapse-free survival rates were 73%, 53% and 48% in stage I, II and IIIa, respectively. There was no difference of relapse-free duration in recurred patients according to the stage or histologic types. CONCLUSION: The postoperative pathologic staging determines the long term prognosis of patients with NSCLC after surgery, but current preoperative clinical staging can not predict the postoperative pathologic staging correctly. So the improved modality of staging system is required to predict the pathologic staging more correctly.

Role of Oxygen Free Radical in the Expression of Interleukin-8 andInterleukin-1beta Gene in Mononuclear Phagocytic Cells / 결핵

BACKGROUND: Oxygen free radicals have generally been considered as cytotoxic agents. On the other hand, recent results suggest that small nontoxic amounts of these radicals may act a role in intracellular signal transduction pathway and many efforts to reveal the role of these radicals as secondary messengers have been made. It is evident that the oxygen radicals are released by various cell types in response to extracellular stimuli including LPS, TNF, IL-1 and phorbol esters, all of which translocate the transcription factor NFkappaB from cytoplasm to nucleus by releasing an inhibitory protein subunit, MB. Activation of NFkappaB is mimicked by exposure to mild oxidant stress, and inhibited by agents that remove oxygen radicals. It means the cytoplasmic form of the inducible tanscription factor NFkappaB might provide a physiologically important target for oxygen radicals. At the same time, it is well known that LPS induces the release of oxygen radicals in neutrophil with the activation of NFkappaB. From above facts, we can assume the expression of IL-8 and IL-1beta gene by LPS stimulation may occur through the activation of NFkappaB, which is mediated through the release of MB by increasing amounts of oxygen radicals. But definitive evidence is lacking about the role of oxygen free radicals in the expression of IL-8 and IL-1beta gene in mononuclear phagocytic cells. We conducted a study to determine whether oxygen radicals act a role in the expression of IL-8 and IL-1beta gene in mononuclear phagocytic cells. METHOD: Human peripheral blood monocytes were isolated from healthy volunteers. Time and dose relationship of H2O2-induced IL-8 and IL-1beta mRNA expression was observed by Northern blot analysis. To evaluate the role of oxygen radicals in the expression of IL-8 and IL-1beta mRNA by LPS stimulation, pretreatment of various antioxiants including PDTC, TMTU, NAC, ME, Desferrioxamine were done and Northern blot analysis for IL-8 and IL-1beta mRNA was performed. RESULTS: In PBMC, dose and time dependent expression of IL-8 and IL-1beta mRNA by exogenous H2O2 was not observed. But various antioxidants suppressed the expression of LPS-induced IL-8 and IL-1beta mRNA expression of PBMC and the suppressive activity was most prominant when the pretreatment was done with TMTU. CONCLUSION: Oxygen free radical may have some role in the expression of IL-8 and IL-1beta mRNA of PBMC but that radical might not be H2O2.