Use of Delta Neutrophil Index for Differentiating Low-Grade Community-Acquired Pneumonia From Upper Respiratory Infection

No abstract available.

Clinical Experience of Rigid Bronchoscopy in Single Center / 결핵및호흡기질환

BACKGROUND: The aim of this study was to analyze clinical situations requiring rigid bronchoscopy and evaluate usefulness of rigid bronchoscopic intervention in benign or malignant airway disorders. METHODS: We retrospectively reviewed 29 patients who underwent rigid bronchoscopy from November 2007 to February 2011 at St. Paul's Hospital, The Catholic University of Korea School of Medicine. RESULTS: Of the 29 patients, the most frequent underlying etiology was benign stenosis of trachea (n=20). Of those 20 patients, 16 had post-intubation tracheal stenosis (PITS), 2 had tracheal stenosis due to inhalation burn (IBTS) and other 2 had obstructive fibrinous tracheal pseudomembrane (OFTP). Other etiologies were airway malignancy (n=6), endobronchial stenosis due to tuberculosis (n=2), and foreign body (n=1). For treatment, silicone stent insertion was done in 16 cases of PITS and IBTS and mechanical removal was performed in 2 cases of OFTP. In 6 cases of malignant airway obstruction mechanical debulking was performed and silicone stents were inserted additionally in 2 cases. Balloon dilatation and electrocautery were used in 2 cases of endobronchial stenosis due to tuberculosis. In all cases of stent, airway obstructive symptom improved immediately. Granulation tissue formation was the most common complication. CONCLUSION: Tracheal stenosis was most common indication and silicone stenting was most common procedure of rigid bronchoscopy in our center. Rigid bronchoscopic procedures, at least tracheal silicone stenting, should be included in pulmonary medicine fellowship programs because it is a very effective and indispensable method to relieve critical airway obstruction which needs training to learn.

Vitamin D Receptor Gene TaqI, BsmI and FokI Polymorphisms in Korean Patients with Tuberculosis

BACKGROUND: The active metabolite (1, 25-dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to activation of macrophages and deficiency of vitamin D seems to be involved in the risk of tuberculosis. The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and may be influenced by polymorphism in the VDR gene. In this study, variation in the VDR gene was investigated in Korean population with tuberculosis. METHODS: We typed three VDR polymorphisms of restriction endonuclease sites for TaqI, BsmI and FokI in 155 patients with tuberculosis and 105 healthy volunteers. RESULTS: The frequencies of FokI genotypes determined from TB patients were 29.13% for FF, 56.31% for Ff, and 14.56% for ff. We observed 1.4-fold increased prevalence of the Ff genotype in TB patients compared with normal healthy groups (p=0.0857). However, there was no significant association between the genotype groups, TB patient and normal control, for FokI polymorphism. There was also no significant association between VDR gene and tuberculosis in another polymorphism (BsmI and TaqI). CONCLUSION: Three polymorphisms (TaqI, BsmI and FokI) in the VDR gene do not appear to be responsible for host susceptibility to human tuberculosis in Korean population.

Vitamin D Receptor Gene TaqI, BsmI and FokI Polymorphisms in Korean Patients with Tuberculosis

BACKGROUND: The active metabolite (1, 25-dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to activation of macrophages and deficiency of vitamin D seems to be involved in the risk of tuberculosis. The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and may be influenced by polymorphism in the VDR gene. In this study, variation in the VDR gene was investigated in Korean population with tuberculosis. METHODS: We typed three VDR polymorphisms of restriction endonuclease sites for TaqI, BsmI and FokI in 155 patients with tuberculosis and 105 healthy volunteers. RESULTS: The frequencies of FokI genotypes determined from TB patients were 29.13% for FF, 56.31% for Ff, and 14.56% for ff. We observed 1.4-fold increased prevalence of the Ff genotype in TB patients compared with normal healthy groups (p=0.0857). However, there was no significant association between the genotype groups, TB patient and normal control, for FokI polymorphism. There was also no significant association between VDR gene and tuberculosis in another polymorphism (BsmI and TaqI). CONCLUSION: Three polymorphisms (TaqI, BsmI and FokI) in the VDR gene do not appear to be responsible for host susceptibility to human tuberculosis in Korean population.

Relationship between Arousal Indices and Clinical Manifestations in Patients Who Performed Polysomnography / 결핵및호흡기질환

BACKGROUND: Repeated arousals during sleep have been known to be associated with excessive daytime sleepiness and cardiovascular complications. We investigated the relationship between arousal indices and clinical parameters. METHODS: We retrospectively reviewed medical records of 41 patients who performed polysomnography for a diagnosis of obstructive sleep apnea syndrome. We defined total arousal index (TAI) as the number of arousals per hour and respiratory arousal index (RAI) as the number of arousals associated with apnea or hypopnea per hour. RESULTS: There were significant positive correlations between arousal indices and apnea-hypopnea index (AHI) (RAI vs. AHI, r=0.958, p<0.001; TAI vs. AHI, r=0.840, p<0.001). RAI and mean oxygen saturation showed a significant negative correlation with each other (r=-0.460, p=0.002). TAI revealed a significant positive correlation with mean systolic blood pressure (MSBP) and mean diastolic blood pressure (MDBP) (TAI vs. MSBP, r=0.389, p=0.014; TAI vs. MDBP, r=0.373, p=0.019). There was no significant correlation between arousal indices and parameters of sleepiness. RAI had a significant positive correlation with body mass index (BMI) and neck circumference (NC) (RAI vs. BMI, r=0.371, p=0.017; RAI vs. NC, r=0.444, p=0.004). When partial correlation analysis was performed to adjust for other variables, there was significant correlation between RAI and AHI (r=0.935, p<0.001). CONCLUSION: This study shows that respiratory arousal index could be a useful index reflecting of severity of obstructive sleep apnea syndrome. Arousal during sleep would be concerned in the development of cardiovascular complication of obstructive sleep apnea. And some anthropometric factors would contribute to the development of arousals during sleep. Further studies are needed to clarify any cause-effect relationship.

IP-10 Decreases TNF-alpha Induced MUC5AC Expression in Human Airway Epithelial Cells: a Possible Relation with Little Sputum Production in Idiopathic Pulmonary Fibrosis / 결핵및호흡기질환

BACKGROUND: IPF is characterized by chronic, fibrosing inflammatory lung disease of unknown etiology. Typical symptoms of IPF are exertional dyspnea with nonproductive cough. Why patients with typical IPF have dry cough rather than productive cough, is unknown. IP-10 plays an important regulatory role in leukocyte trafficking into the lung. The present study investigated the effect of IP-10 in the pathogenesis of dry cough rather than productive cough in IPF patients. METHODS: IP-10 concentration was measured by ELISA from BALF of IPF patients. To evaluate the role of IP-10 in mucin expression, the expression of the MUC5AC mucin gene was measured in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, after stimulation by TNF-alpha with or without IP-10 pretreatment. EGFR-MAPK expression was also examined as a possible mechanism. RESULTS: IP-10 levels were significantly higher in the BALF of IPF patients compared to healthy controls. IP-10 pretreatment reduced TNF-alpha induced MUC5AC mucin expression by inhibiting the EGFR-MAPK signal transduction pathway in NCI-H292 cells. CONCLUSION: These findings suggest that little mucus production in IPF patients might be attributable to IP-10 overproduction, which inhibits the EGFR-MAPK signal transduction pathway required for MUC5AC mucin gene expression.

Prognostic Value of Vascular Endothelial Growth Factor (VEGF) and Basic Fibroblast Growth Factor (bFGF) Expression in Resected Non-small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: Tumor angiogenesis plays an important role in tumor growth, maintenance and metastatic potential. Tumor tissue produces many types of angiogenic growth factors. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumor angiogenesis. In this study, the expression of tissue VEGF and bFGF from non-small cell lung cancer (NSCLC) patients were analyzed. METHODS: We retrospectively investigated 35 patients with a histologically confirmed adenocarcinoma or squamous cell carcinoma of the lung, where the primary curative approach was surgery. An ELISA was employed to determine the expression of VEGF and bFGF in extracts prepared from 35 frozen tissue samples taken from the cancer patients. RESULTS: VEGF and bFGF concentrations were significantly increased in lung cancer tissue as compared with control (non-cancerous) tissue. The VEGF concentration was significantly increased in T2 and T3 cancers as compared with T1 cancer. Expression of VEGF was increased in node-positive lung cancer tissue as compared with node-negative lung cancer tissue (p=0.06). VEGF and bFGF expression were not directly related to the stage of lung cancer and patient survival. CONCLUSION: Expression of VEGF and bFGF were increased in lung cancer tissue, and the expression of VEGF concentration in lung cancer tissue was more likely related with tumor size and the presence of a lymph node metastasis than the expression of bFGF. However, in this study, expression of both VEGF and bFGF in tissue were not associated with patient prognosis.

Time Sequence of Airway Remodeling in a Mouse Model of Chronic Asthma: the Relation with Airway Hyperresponsiveness

During the course of establishing an animal model of chronic asthma, we tried to elucidate the time sequence of airway hyperresponsiveness (AHR), airway inflammation, airway remodeling, and associated cytokines. Seven-week-old female BALB/c mice were studied as a chronic asthma model using ovalbumin (OVA). After sensitization, mice were exposed twice weekly to aerosolized OVA, and were divided into three groups depending on the duration of 4 weeks, 8 weeks, and 12 weeks. At each time point, airway responsiveness, inflammatory cells, cytokines in bronchoalveolar lavage fluids (BALF), serum OVA-specific IgE, IgG1, IgG2a, and histological examination were carried out. AHR to methacholine, increased levels of OVA-specific IgG1 and IgG2a, and goblet cell hyperplasia were continuously sustained at each time point of weeks. In contrast, we observed a time-dependent decrease in serum OVA-specific IgE, BALF eosinophils, BALF cytokines such as IL-13, transforming growth factor-beta1, and a time-dependent increase in BALF promatrix metalloproteinase-9 and peribronchial fibrosis. In this OVA-induced chronic asthma model, we observed airway remodelings as well as various cytokines and inflammatory cells being involved in different time-dependent manners. However, increased airway fibrosis did not directly correlate with a further increase in airway hyperresponsiveness.

Inflammatory and Remodeling Events in Asthma with Chronic Exposure to House Dust Mites: A Murine Model

Although animal models with ovalbumin have been used to study chronic asthma, there are difficulties in inducing recurrence as well as in maintaining chronic inflammation in this system. Using a murine model of house dust mite (HDM)-induced bronchial asthma, we examined the airway remodeling process in response to the chronic exposure to HDM. During the seventh and twelfth weeks of study, HDM were inhaled through the nose for three consecutive days and airway responsiveness was measured. Twenty-four hours later, bronchoalveolar lavage and histological examination were performed. The degree of overproduction of mucus, subepithelial fibrosis, and the thickness of the peribronchial smooth muscle in the experimental group was clearly increased compared to the control group. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. In the bronchoalveolar lavage fluid, the number of total cells and eosinophils was increased; during the twelfth week, the number of neutrophils increased in the experimental group. With regard to changes in cytokines, the concentrations of IL-4, IL- 13, and transforming growth factor-beta (TGF-beta) were increased in the experimental group. The data suggest that eosinophils, IL-4, IL-13, and TGF-beta might play an important role in the airway remodeling process and that neutrophils may be involved with increased exposure time.

A Case of Tracheal Diverticula in a Hemoptysis Patient with Tuberculosis Sequela and Fungus Ball / 결핵및호흡기질환

We experienced a rare case of trachea diverticula combined with the sequela of tuberculosis and a fungus ball. The patient had complained of coughing and hemoptysis for a long time after experiencing tuberculosis. He was admitted due to hemoptysis and the aggravation of coughing. The CT scan showed a variable sized trachea diverticula combined with tuberculosis sequela and a fungus ball in the right lung fields. The diagnosis was made by bronchoscopy and a CT scan. After bronchial artery embolization and conservative treatment, the patient's symptoms improved and the patient was discharged.

Airway Remodeling / 결핵및호흡기질환

No Abstract available.

p16(INK4a) Promoter Hypermethylation in Sputum, Blood, and Tissue from Non-Small Cell Lung Cancer and Pulmonary Inflammation / 결핵및호흡기질환

BACKGROUND: The aberrant promoter hypermethylation of p16(INK4a), as a tumor suppressor gene, is contributory factor to non-small cell lung cancer(NSCLC). However, its potential diagnostic impact of lung cancer is unclear. This study measured the level of p16(INK4a) promoter hypermethylation in the sputum and blood, and compared this with the level measured in the tissue obtained from NSCLC and pulmonary inflammation. METHODS: Of the patients who visited the Our Lady of Mercy Hospital in Incheon, Korea for an evaluation of a lung mass and underwent blood, sputum, and tissue tests, 23patients (18 NSCLC, 5 pulmonary inflammation) were enrolled in this study. DNA was extracted from each sample and the level of p16(INK4a) methylation was determined using methylation-specific polymerase chain reaction. RESULTS: p16(INK4a) methylation of the blood was observed in 88.9% (16 of 18) and 20.0% (1 of 5) of NSCLC and from pulmonary inflammation samples, respectively (P=0.008). Methylation of the sputum was observed in 83.3% (10 of 12) 80.0% (4 of 5) of NSCLC and pulmonary inflammation samples, respectively (P=1.00). Among the 8 NSCLC tissue samples, methylation changes were detected in 75.0% of samples (6 cases). Four out of seven tissue samples (57.1%) showed concordance, being methylated in both the blood and sputum. CONCLUSIONS: There was a higher level of p16(INK4a) methylation of the blood from NSCLC patients than from pulmonary inflammation. The tissue showed a high concordance with the blood in the NSCLC samples. These findings suggest that p16(INK4a) promoter hypermethylation of the blood can used to discriminate between NSCLC and pulmonary inflammation.

Pharmacology in Airway Diseases / 결핵및호흡기질환

No abstract available.

Pharmacology in Airway Diseases / 결핵및호흡기질환

No abstract available.

Analysis of Sleep Questionnaires of Patients who Performed Overnight Polysomnography at the University Hospital / 결핵및호흡기질환

BACKGROUND: The objective of this study was to understand sleep-related problems, and to determine whether the sleep questionnaires is a clinically useful method in patients who need polysomnography. METHODS: Subjects were patients who performed polysomnography and who asked to answer a sleep questionnaires at the Sleep Disorders Clinic of St. Paul's Hospital, Catholic University of Korea. Baseline characteristics, past medical illness, behaviors during sleep-wake cycle, snoring, sleep-disordered breathing and symptoms of daytime sleepiness were analyzed to compare with data of polysomnography. RESULTS: The study population included 1081 patients(849 men, 232 female), and their mean age was 44.2+/-12.8 years. Among these patients, 38.9% had an apnea-hypopnea index(AHI) < 5, 27.9% had 5 < or = AHI < 20, 13.2% had 20 < or = AHI < 40, and 20.0% had 40 < or = AHI. The main problems for visiting our clinic were snoring(91.7%), sleep apnea(74.5%), excessive daytime sleepiness(8.0%), insomnia(4.3%), bruxism(1.1%) and attention deficit(0.5%). The mean value of frequency of interruptions of sleep was 1.6 and the most common reason was urination(46.3%). Epworth Sleepiness Scale(ESS) had a weak correlation with AHI(r=0.209, p<0.01). When we performed analysis of sleep questionnaires, there were significant differences in the mean values of AHI according to the severity of symptoms including snoring, daytime sleepiness, taking a nap and arousal state after wake(p<0.05). CONCLUSION: On the basis of statistical analysis of sleep questionnaires, the severity of subjective symptoms such as ESS, snoring, daytime sleepiness and arousal state after wake correlated with the AHI significantly. Therefore the sleep questionnaires can be useful instruments for prediction of the severity of sleep disorder, especially sleep-disordered breathing.

Analysis of Sleep Questionnaires of Patients who Performed Overnight Polysomnography at the University Hospital / 결핵및호흡기질환

BACKGROUND: The objective of this study was to understand sleep-related problems, and to determine whether the sleep questionnaires is a clinically useful method in patients who need polysomnography. METHODS: Subjects were patients who performed polysomnography and who asked to answer a sleep questionnaires at the Sleep Disorders Clinic of St. Paul's Hospital, Catholic University of Korea. Baseline characteristics, past medical illness, behaviors during sleep-wake cycle, snoring, sleep-disordered breathing and symptoms of daytime sleepiness were analyzed to compare with data of polysomnography. RESULTS: The study population included 1081 patients(849 men, 232 female), and their mean age was 44.2+/-12.8 years. Among these patients, 38.9% had an apnea-hypopnea index(AHI) < 5, 27.9% had 5 < or = AHI < 20, 13.2% had 20 < or = AHI < 40, and 20.0% had 40 < or = AHI. The main problems for visiting our clinic were snoring(91.7%), sleep apnea(74.5%), excessive daytime sleepiness(8.0%), insomnia(4.3%), bruxism(1.1%) and attention deficit(0.5%). The mean value of frequency of interruptions of sleep was 1.6 and the most common reason was urination(46.3%). Epworth Sleepiness Scale(ESS) had a weak correlation with AHI(r=0.209, p<0.01). When we performed analysis of sleep questionnaires, there were significant differences in the mean values of AHI according to the severity of symptoms including snoring, daytime sleepiness, taking a nap and arousal state after wake(p<0.05). CONCLUSION: On the basis of statistical analysis of sleep questionnaires, the severity of subjective symptoms such as ESS, snoring, daytime sleepiness and arousal state after wake correlated with the AHI significantly. Therefore the sleep questionnaires can be useful instruments for prediction of the severity of sleep disorder, especially sleep-disordered breathing.

Antibacterial Effect of Lidocaine, Thrombin, and Epinephrine

BACKGROUND: We performed this stody to find out about antimicrobial effect of lidocaine which is commonly used local anesthetic, and thrombin and epinephrine used for hemostasis during bronchoscopic procedures. MATERIALS AND METHODS: The microorganisms that were cultured from specimens obtained during bronchoscopy were Staphylococcus aureus (n=42), Streptococcus pneumoniae (n=42), Klebsiella pneumoniae (n=42), and Pseudomonas aeruginosa (n=43) collected from St. Mary's Hospital, from March to Sep 2004 were used for susceptibity testing. Susceptibility to lidocaine, thrombin, and epinephrine were tested according to the National Committee for Clinical Laboratory Standards. RESULT: MIC50 and MIC90 of lidocaine for S. aureus, S. pneumoniae, P. aeruginosa were all 20,000 microgram/mL and that for K. pneumoniae were 10,000 microgram/mL. MIC50 and MIC90 of thrombin for both S. aureus and P. aeruginosa was 500 IU/mL and above 500 IU/mL, respectively; that for K. pneumoniae were all above 500 IU/mL and for S. pneumoniae they were 125 IU/mL, MIC50 and MIC90 of epinephrine for K. pneumoniae and S. pneumoniae were above 500 microgram/mL; that for S. aureus and P. aeruginosa were 500 microgram/mL. CONCLUSION: We observed possible antimicrobial effect of lidocaine, thrombin, and epinephrine in vitro against pathogens such as S. aureus, S. pneumoniae, K. pneumoniae, P. aeruginosa, which are common respiratory microorganisms. The use of these agants could affect the result of bacterial culture.

Antibacterial Effect of Lidocaine, Thrombin, and Epinephrine

BACKGROUND: We performed this stody to find out about antimicrobial effect of lidocaine which is commonly used local anesthetic, and thrombin and epinephrine used for hemostasis during bronchoscopic procedures. MATERIALS AND METHODS: The microorganisms that were cultured from specimens obtained during bronchoscopy were Staphylococcus aureus (n=42), Streptococcus pneumoniae (n=42), Klebsiella pneumoniae (n=42), and Pseudomonas aeruginosa (n=43) collected from St. Mary's Hospital, from March to Sep 2004 were used for susceptibity testing. Susceptibility to lidocaine, thrombin, and epinephrine were tested according to the National Committee for Clinical Laboratory Standards. RESULT: MIC50 and MIC90 of lidocaine for S. aureus, S. pneumoniae, P. aeruginosa were all 20,000 microgram/mL and that for K. pneumoniae were 10,000 microgram/mL. MIC50 and MIC90 of thrombin for both S. aureus and P. aeruginosa was 500 IU/mL and above 500 IU/mL, respectively; that for K. pneumoniae were all above 500 IU/mL and for S. pneumoniae they were 125 IU/mL, MIC50 and MIC90 of epinephrine for K. pneumoniae and S. pneumoniae were above 500 microgram/mL; that for S. aureus and P. aeruginosa were 500 microgram/mL. CONCLUSION: We observed possible antimicrobial effect of lidocaine, thrombin, and epinephrine in vitro against pathogens such as S. aureus, S. pneumoniae, K. pneumoniae, P. aeruginosa, which are common respiratory microorganisms. The use of these agants could affect the result of bacterial culture.

An Endobronchial Fibroepithelial Polyp Treated by Bronchoscopic Excision / 결핵및호흡기질환

An 81-year-old man underwent bronchoscopy to investigate the cause of his dyspnea symptoms. A benign natured mass was observed in the bronchus and was excised. The pathology examination revealed a fibroepithelial polyp. He has been asymptomatic since the simple bronchoscopic excision. A fibroepithelial polyp is a benign tumor with a mesodermal origin. It is commonly found in the skin, urogenital area and chest, but is extremely rare in the respiratory system. We report a case of a fibroepithelial polyp in the bronchus, which was treated with a bronchoscopic excision, with a brief review of the relevant literature.

Muc5ac Gene Expression Induced by Cigarette Smoke is Mediated Via a Pathway Involving ERK1/2 and p38 MAPK / 결핵및호흡기질환

OBJECT: Cigarette smoking is a major cause of mucus hypersecretion, which is a pathophysiological feature of many inflammatory airway diseases. Mucins, which are an important part of the airway mucus, are synthesized from the Muc gene in airway epithelial cells. However, the signaling pathways for cigarette smoke-induced mucin synthesis are unknown. The aim of this study was to determine the signal pathway for smoking induced Muc5ac gene expression. METHODS: A549 cells were cultured and transiently transfected with the Muc5ac promoter fragment. These cells were stimulated with 5% cigarette smoke extract (CSE) alone or with CSE after a pretreatment with various signal transduction pathway inhibitors (AG1478, PD98059 and SB203580). The Muc5ac promoter activity was examined using the luciferase reporter system, and the level of phosphorylated EGFR, ERK1/2, p38 MAPK and JNK were all examined using Western blot analysis. Muc5ac mRNA expression was also examined using reverse transcriptase polymerase chain reactions (RT-PCR). RESULTS: 1. The peak level of luciferase activity of the Muc5ac promoter was observed at 5% concentration and after 3 hours of incubation with the CSE. The level of EGFR phosphorylation and the luciferase activity of the transfected cells caused by the CSE were significantly suppressed by AG1478 or PD98059 (P<0.01). 2. CSE phosphorylated ERK1/2 or p38 MAPK but not JNK. The Muc5ac mRNA expression level was increased by the CSE but that was suppressed by PD98059 or AG1478. 3. The CSE-induced phosphorylation of ERK1/2 was blocked by PD98059 and that of p38 MAPK was blocked by either PD98059 or SB203580. Either PD98059 or SB203580 suppressed the luciferase activity of the transfected cells (P<0.0001). CONCLUSION: The Muc5ac mRNA expression level was increased by the CSE. The increased CSE-induced transcriptional activity was mediated via EGF receptor activation, which led to ERK1/2 and p38 MAPK phosphorylation.