• The Journal of Internal Korean Medicine
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• v.36 no.4
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• pp.547-561
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• 2015

Objectives In this study, we divided Korean asthma patients into excess syndrome or deficiency syndrome groups according to clinical phenotype. Genetic analysis was conducted to investigate the association of exonic SNPs in the CD46 gene polymorphism with the clinical phenotype based on the differentiation syndrome of the bronchial asthma patients.Methods There were 95 healthy patients (control group) and 53 asthma patients. (The deficiency syndrome group included 24 and the excess syndrome group 29). We searched the exonic areas of the CD46 gene in the NCBI website SNPs with <0.01 minor allele frequency (MAF) and <0.01 heterozygosity. We finally selected two SNPs: rs138843816, Ser13Phe and rs7144, 3’-UTR. Hardy-Weinberg equilibrium was calculated using SNPStats.Results There were significant differences in the codominant 1 model and the dominant model between the healthy group and the asthma group. There were significant differences between deficiency syndrome group and the excess syndrome group in the genotype frequencies and in the codominant 1 model, the dominant model, and the log-additive model. The allele frequency of rs7144C showed a significant difference between the deficiency syndrome group and the excess syndrome group. Two-SNP haplotype analysis showed a significant difference in frequency in the deficiency syndrome group and in the excess syndrome group. There were significant differences between the healthy group and the excess syndrome group in the codominant 1 model, the dominant model, and the log-additive model. The frequency of the rs7144 C allele exhibited a significant difference in the demonstration. SNP haplotype analysis between the healthy group and the excess syndrome group showed a significant difference in the frequency of the CT haplotype and the CC haplotype.Conclusions The results indicate that two CD46 SNPs (rs138843816, Ser13Phe and rs7144, 3′–UTR) might be associated with the symptomatic excess syndrome in Korean asthma patients.

• Tuberculosis and Respiratory Diseases
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• v.62 no.3
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• pp.192-196
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• 2007

Background: Right middle lobe syndrome (RMLS) is defined as transient or chronic and recurrent atelectasis of the right middle lobe. Although numerous conditions are associated with RMLS, there are very few recent reports in Korea. This study evaluated the causes of RMLS in a local tertiary hospitalover a period of 42 months. Method: Eighty-eight patients (M:F=64:22, mean age: $67.2{\pm}10.3years$), who had consistent chest radiography findings and underwent bronchoscopy in Gyeongsang University Hospital from January 2003 to July 2006, were enrolled in this study. The clinical characteristics and causes of RMLS in these patients were retrospectively reviewed. Results: The most common symptoms fo RMLS were cough, dyspnea and sputum. Tuberculosis was the most common cause (endobronchial tuberculosis in 22 and pulmonary tuberculosis in 1) The other causes were bronchial stenosis by benign fibrotic changes in 22 cases (25%), anthracofibrosis in 13 cases (14.8%), pneumonia in 11 cases (12.5%), lung cancer in 10 cases (11.4%), mucus impaction in 3 cases (3.4%), bronchiectasis in 2 cases (2.3%) and no demonstrable causes in 7 cases (8%). The bronchoscopy findings were mucosal edema with hyperemic changes in 38 cases (43.2%), mucosal edema with anthracotic pigmentation in 16 cases (18.2%), mucus impaction in 13 cases (14.8%), fibrotic stenosis in 13 cases (14.8%), a mass like lesion in 8 cases (9.1%), exudative necrotic material in 4 cases (4.5%), narrowing as a result of extrinsic compression in 2 cases (2.3%) and no demonstrable abnormalities in 12 cases (13.6%). Conclusion: Right middle lobe syndrome was observed more frequently in patients over the age of 65. The causes were mainly benign diseases with endobronchial tuberculosis being the most common.

• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.1072-1082
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• 1997

Background : To characterize the clinical features and determine the prognostic factors of severe community-acquired pneumonia. This study is the first of its kind in Korea. Methods : Recruited were 40 patients diagnosed as severe community-acquired pneumonia in Hallym University Hospital from January 1, 1989 through July 31, 1996. Patients were analysed retrospectively for age, sex, underlying disease, respiration rate, hypoxemia, requirement of mechanical ventilation, involvement on chest radiograph, shock, and the serum concentration of BUN and albumin. All parameters were compared between survived and dead group. Results : Male to female ratio was 2.07 : 1. The mean age was $63.1{\pm}17.5$years(range 25~90years) with 65% of patients aged equal to or more than 60. The major underlying diseases were old pulmonary tuberculosis(12.5%), chronic obstructive pulmonary disease(7.5%), bronchial asthma(5%), bronchiectasis(2.5%), and diabetes mellitus(22.5%). Microbiologic diagnosis was made in 26 out of 40 patients(65%). The most common causative organism was S. pneumoniae(17.5%, 7/40) followed by S. aureus(15.0%, 6/40), K. Pneumoniae(12.5%, 5/40), M. tuberculosis(7.5%, 3/40), H. influenzae(2.5%, 1/40), coagulase negative staphylococcus(2.5%, 1/40), P. aeruginosa(2.5%. 1/40), E. cloaceae(2.5%, 1/40), and E. coli(2.5%, 1/40). M. pneumoniae was detected in no patient. The most frequent drugs administered in single or combination therapy were aminoglycosides(75%, 30/40), second- and third-generation cephalosporin(40%, 16/40 and 27.5%, 11/40), macrolides(27.5%, 11/40), and amoxicillin/clavulanic acid(22.5%, 9/40). Of the 40 patients, 14 died of severe community-acquired pneumonia(37.5%). Among them, seven patients (50%) expired within 72h of hospital arrival. According to multivariate analysis, mortality was significantly associated with requirement of mechanical ventilation, bilateral pulmonary involvement, and serum albumins$\leq$3.0g/dl. Conclusion : An understanding of the clinical characteristics and prognostic factors in severe community-acquired pneumonia identified in this study will optimize therapeutic approach in this disease and help decreasing its notorious mortality rate.

• Tuberculosis and Respiratory Diseases
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• v.42 no.2
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• pp.149-155
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• 1995

Background: Cytokeratin 19 is 40KD acidic molecule whose distribution is restricted to simple or pseudo-stratified epithelia, such as the epithelial layer of the bronchial tree. Immunohistochemical study have shown that cytokeratin 19 is overexpressed in lung carcinoma tissue. An immunoradiometric assay, CYFRA 21-1 has been developed using two monoclonal antibody, BM 19-21 and KS 19-1, reactive to different epitopes on cytokeratin 19. We studied the diagnostic value of CYFRA 21-1 in lung cancer. Method: The serum CYFRA 21-1 level using immunoradiometric kit(ELSA-CYFRA 21-1) was measured in 54 patients who admit to Yeungnam University Hospital from April, 1993 to August, 1994. Lung cancer group was 39 primary lung cancer patients(19 patients with squamous cell carcinoma, 11 patients with adenocarcinoma and 9 patients with small cell carcinoma). Control group was 15 patients with non malignant lung diseases(8 patients with pulmonary tuberculosis, 3 patients with chronic obstructive pulmonary disease, 2 patients with pneumonia and 2 patients with chronic obstructive pulmonary disease combined with pulmonary tuberculosis). Results: The mean serum value of CYFRA 21-1 was $20.2{\pm}4.7ng/ml$ in squamous cell carcinoma, $7.2{\pm}1.6ng/ml$ in adenocarcinoma and $15.5{\pm}4.7ng/ml$ in non-small cell lung cancer. The serum value of CYFRA 21-1 in control group was $1.7{\pm}0.5ng/ml$. All of the serum values of 3 histologic types were significantly higher than that of control group(p<0.01). The serum value of CYFRA 21-1 of squamous cell carcinoma was significantly higher than that of adenocarcinoma(p <0.05). Serum value of CYFRA 21-1 in small cell lung cancer was $2.9{\pm}0.9ng/ml$ and not significantly different compared with control group. Using cut off value of 3.3ng/ml, sensitivity and specificity was 11.1%, 65.2% in small cell lung cancer, 70.0%, 62.5% in non-small cell lung cancer, 73.7%, 75% in squamous cell carcinoma and 63.6%, 78.9% in adenocarcinoma, respectively. Conclusion: The serum levels of CYFRA 21-1 may be useful in diagnosis of non-small cell lung carcinoma, especially in squamous cell carcinoma with its high specificity.

• Tuberculosis and Respiratory Diseases
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• v.55 no.5
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• pp.459-466
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• 2003

Background : Asthma and eosinophilic bronchitis(EB) are eosinophilic inflammatory diseases of the airway. However, EB differs from asthma in that there is no variable airway obstruction or airway hyper-responsiveness. Pathologically, asthma is characterized by the accumulation of eosinophils and CD4+ T lymphocytes in the submucosa. A recent study showed that there was no significant difference between asthma and EB in terms of the submucosal eosinophil and T lymphocyte count. However, it is not known whether or not an infiltration of CD4+ and CD8+ T lymphocytes occurs in the airways of EB patients. The aim of this study was to identify the difference between the two conditions by measuring the submucosal CD4+ and CD8+ T lymphocyte count. Methods : Immunohistochemical analysis of bronchial-biopsy specimens was performed in 17 subjects with asthma and 24 subjects with EB. Results : The CD4+ T lymphocytes count in the asthma subjects and the EB subjects was similar (median, 58.6 vs 50.0 $cells/mm^2$, respectively; P=0.341). In contrast, the number of CD8+ T lymphocytes in the EB subjects was higher than that in the asthma subjects (median, 46.7 vs 11.8 $cells/mm^2$, respectively; P=0.003). Conclusion : The infiltration of submucosal CD8+ T lymphocytes may be associated with the pathophysiology of EB.

• Tuberculosis and Respiratory Diseases
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• v.54 no.1
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• pp.80-90
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• 2003

Background : Goblet cell hyperplasia is a critical pathological feature in hypersecretory diseases of the airways. A bacterial infection of the lung is also known to induce inflammatory responses, which can lead to the overproduction of mucus. Recently, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression and activation. In addition, it was reported that migration of the activated neutrophils is dependent on the matrix metalloproteinases (MMPs), especially MMP-9. In this study, bacterial lipopolysaccharide (LPS)-induced goblet cell hyperplasia and mucus hypersecretion by EGFR cascade, resulting from the MMPs-dependent neutrophilic inflammation were investigated in the rat airways. Methods : Pathogen-free Sprague-Dawley rats were studied in vivo. Various concentrations of LPS were instilled into the trachea in $300{\mu}{\ell}$ PBS (LPS group). Sterile PBS ($300{\mu}{\ell}$) was instilled into the trachea of the control animals (control group). The airways were examined on different days after instilling LPS. For an examination of the relationship between the LPS-induced goblet cell hyperplasia and MMPs, the animals were pretreated 3 days prior to the LPS instillation and daily thereafter with the matrix metalloproteinase inhibitor (MMPI; 20 mg/Kg/day of CMT-3; Collagenex Pharmaceuticals, USA). The neutrophilic infiltration was quantified as a number in five high power fields (HPF). The alcian blue/periodic acid-Schiff (AB/PAS) stain were performed for the mucus glycoconjugates and the immunohistochemical stains were performed for MUC5AC, EGFR and MMP-9. Their expressions were quantified by an image analysis program and were expressed by the percentage of the total bronchial epithelial area. Results : The instillation of LPS induced AB/PAS and MUC5AC staining in the airway epithelium in a time- and dose-dependent manner. Treatment with the MMPI prevented the LPS-induced goblet cell hyperplasia significantly. The instillation of LPS into the trachea induced also EGFR expression in the airway epithelium. The control airway epithelium contained few leukocytes, but the intratracheal instillation of LPS resulted in a neutrophilic recruitment. A pretreatment with MMPI prevented neutrophilic recruitment, EGFR expression, and goblet cell hyperplasia in the LPS-instilled airway epithelium. Conclusion : Matrix metalloproteinase is involved in LPS-induced mucus hypersecretion, resulting from a neutrophilic inflammation and EGFR cascade. These results suggest a potential therapeutic role of MMPI in the treatment of mucus hypersecretion that were associated with a bacterial infection of the airways.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.1000-1011
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• 1998

Background: For the diagnosis or evaluation of airway obstruction in bronchial asthma and chronic obstructive lung disorders, various parameters derived from the forced expiratory volume curve and maximal expiratory flow volume curve have been used. Recently the peak expiratory flow(PEF) measured by the peak flow meter is widely used because of its simplicity and convenience. But there were still no data of the predicted normal values measured by the peak flow meter in Korea. This study was to obtain the predicted normal value of PEF and to know the accuracy of this value to predict $FEV_1$. Method: The measurements of PEF by the MiniWright peak flow meter and several parameters derived from the forced expiratory volume and maximal expiratory flow volume curves by the Microspiro HI 501(Chest Co.) were done in 129 men and 125 women without previous history of the respiratory diseases. The predicted normal values of parameters according to the age and the height were obtained, and the regression equation of $FEV_1$ by PEF was calculated. Results: The predicted normal values of PEF(L/min) were -2.45$\times$Age(year) +1.36 $\times$ Height(cm)+427 in men, and -0.96 $\times$ Age (year) + 2.01 $\times$ Height (cm) + 129 in women. FEFmax derived from the maximal expiratory flow volume curve was less than by 125 L/min in men and 118 L/min in women respectively compared to PEF. $FEV_1$(ml) predicted by PEF was 5.98 $\times$ PEF(L/min) + 303 in men, and 4.61 $\times$ PEF(L/min) + 291 in women respectively. Conclusion : The predicted normal value of PEF measured by the peak flow meter was calculated and it could be used as a standard value of PEF while taking care of patients with airway obstruction. $FEV_1$, the gold standard of ventilatory function, could be predicted by PEF to a certain extent.

• Tuberculosis and Respiratory Diseases
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• v.56 no.1
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• pp.77-84
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• 2004

Background : We hypothesized that there was a relationship between body weight change and bronchodilator response (BDR) in patients with chronic renal failure (CRF) on hemodialysis (HD). Several mechanisms such as pulmonary edema due to water retention or increased permeability of alveolar capillary may play a important role in pulmonary function impairment and bronchial hyperresponsiveness in patients with CRF on HD. But, no studies have been published concerning BDR in patients with CRF on HD. This study was aimed to know the immediate effect of hemodialysis on pulmonary function and BDR in patients with CRF on HD. Methods : This study included 30 patients with CRF on HD. We collected data including age, sex, height, pretibial and pedal pitting edema, interdialysis weight gain, postdialysis weight loss, underlying diseases, duration of HD, $FEV_1$, FVC, $FEV_1/FVC$, and BDR before and after HD. Results : Interdialysis weight gain of the patients was $3.4{\pm}1.0kg$, and postdialysis weight loss was $3.2{\pm}0.7kg$. Before HD,$FEV_1$, FVC, and $FEV_1/FVC$ of the patients were $89{\pm}22%$, $86{\pm}19%$ of predicted, and $87{\pm}10%$. After bronchodilator inhalation, these parameters were changed to $95{\pm}22%$, $90{\pm}19%$ of predicted, and $88{\pm}9%$ respectively. BDR was positive in 15 patients. After HD, $FEV_1$, FVC, and $FEV_1/FVC$ of the patients were $100{\pm}23%$, $94{\pm}18%$ of predicted, and $88{\pm}11%$. After bronchodilator inhalation, these parameters were changed to $102{\pm}23%$, $96{\pm}18%$ of predicted, and $89{\pm}8%$ respectively. BDR was positive in 9 patients. Conclusion : First, HD increases $FEV_1$, FVC, and $FEV_1/FVC$ but little affects BDR. Second, there is no correlation between postdialysis weight loss and increases in $FEV_1$, FVC, and $FEV_1/FVC$ after HD. Third, there is also no correlation not only between interdialysis weight gain and BDR before HD but between postdialysis weight loss and BDR after HD.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.558-570
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• 1996

Background : The detection of Collapsible airways has important therapeutic implications in chronic airway disease and bronchial asthma. The distinction of a purely collapsible airways disease from that of asthma is important because the treatment of the dormer may include the use of pursed lip breathing or nasal positive pressure ventilation whereas in the latter, pharmacologic approaches are used. One form of irreversible airflow limitation is collapsible airways, which has been shown to be a Component of asthma or to emphysema, it can be assessed by the volume difference between what exits the lung as determined by a spirometer and the volume compressed as measured by the plethysmography. Method : To investigate whether volume difference between slow and forced vital Capacity(SVC-FVC) by spirometry may be used as a surrogate index of airway collapse, we examined pulmonary function parameters before and after bronchodilator agent inhalation by spirometry and body plethysmography in 20 cases of patients with evidence of airflow limitation(chronic obstructive pulmonary disease 12 cases, stable bronchial asthma 7 cases, combined chronic obstructive pulmonary disease with asthma 1 case) and 20 cases of normal subjects without evidence of airflow limitation referred to the Pusan National University Hospital pulmonary function laboratory from January 1995 to July 1995 prospectively. Results : 1) Average and standard deviation of age, height, weight of patients with airflow limitation was $58.3{\pm}7.24$(yr), $166{\pm}8.0$(cm), $59.0{\pm}9.9$(kg) and those of normal subjects was $56.3{\pm}12.47$(yr), $165.9{\pm}6.9$(cm), $64.4{\pm}10.4$(kg), respectively. The differences of physical characteristics of both group were not significant statistically and male to female ratio was 14:6 in both groups. 2) The difference between slow vital capacity and forced vital capacity was $395{\pm}317ml$ in patients group and $154{\pm}176ml$ in normal group and there was statistically significance between two groups(p<0.05). Sensitivity and specificity were most higher when the cut-off value was 208ml. 3) After bronchodilator inhalation, reversible airway obstructions were shown in 16 cases of patients group, 7 cases of control group(p<0.05) by spirometry or body plethysmography d the differences of slow vital capacity and forced vital capacity in bronchodilator response group and nonresponse group were $300.4{\pm}306ml$, $144.7{\pm}180ml$ and this difference was statistically significant. 4) The difference between slow vital capacity and forced vital capacity before bronchodilator inhalation was correlated with airway resistance before bronchodilator(r=0.307 p=0.05), and the difference between slow vital capacity and forced vital capacity after bronchodilator was correlated with difference between slow vital capacity and forced vital capacity(r=0.559 p=0.0002), thoracic gas volume(r=0.488 p=0.002) before bronchodilator and airway resistance(r=0.583 p=0.0001), thoracic gas volume(r=0.375 p=0.0170) after bronchodilator, respectively. 5) The difference between slow vital capacity and forced vital capacity in smokers and nonsmokers was $257.5{\pm}303ml$, $277.5{\pm}276ml$, respectively and this difference did not reach statistical significance(p>0.05). Conclusion : The difference between slow vital capacity and forced vital capacity by spirometry may be useful for the detection of collapsible airway and may help decision making of therapeutic plans.

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

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