The Bronchial Biopsies and Steroid Response in Unexplained Chronic Non-Productive Cough / 결핵

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(2) 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 thickeness of the basement membrane of experimental group was 14.20+/-5.20microM in contrast of control group whose mean was 3.50+/-1.37microM(P=0.001). With the methacholine challenge test, 7 of the 21 eosinophil infiltrated subjects were diagnosed with cough 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.

Clinical Investigation of Women with Asthma Worsened during Pregnancy / 결핵

BACKGROUND: Asthma is the most common respiratory crisis encountered in clinical practice, occurring in up to 4% of all pregnancies. Pregnancy often appears to alter the course of asthma. But the mechanisms responsible for variable changes in the asthma course during pregnancy remain unknown. Poor control and exacerbations of asthma during pregnancy may result in serious maternal and fetal complications. To investigate the course of asthma during pregnancy in korean women, we did a retrograde study of 27 pregnant women who had been admitted to Korea University Hospital for asthma worsened. METHOD: Twenty seven pregnant women who had been visited to Korea University Hospital for asthma worsened were enrolled in our retrospective study. We reviewed medical recordings and interviewed patients with asthma. RESULTS: Twenty seven pregnant women with asthma were evaluated, and 25 patients were enrolled to our study. Two patients experienced abortions at 6 weeks and 25 weeks gestation, respectively. The period of asthma worsened was commonly during weeks 20 to 28 of gestation. And all patients wosened were improved during the last 4 weeks of pregnancy. Twenty(80%) of 25 women whose asthma worsened during pregnancy reverted toward their prepregnancy status after delivery(p<0.002). The causes of asthma worsened during pregnancy are reduction or even complete cessaton of medication due to fears about its safety(40%), worsening after upper respiratory infection(28%), and unknown(32%). There were no adverse perinatal outcomes in 25 pregnant asthma subjects. CONCLUSIONS: A major problem of therapy for asthma during pregnancy is reduction or even complete cessation of medication due to fears of fetal effects. Therefore, maternal education and optimal clinical and pharmacologic management is necessary to mitigate maternal and fetal complications.

Clinical Investigation of Women with Asthma Worsened during Pregnancy / 결핵

BACKGROUND: Asthma is the most common respiratory crisis encountered in clinical practice, occurring in up to 4% of all pregnancies. Pregnancy often appears to alter the course of asthma. But the mechanisms responsible for variable changes in the asthma course during pregnancy remain unknown. Poor control and exacerbations of asthma during pregnancy may result in serious maternal and fetal complications. To investigate the course of asthma during pregnancy in korean women, we did a retrograde study of 27 pregnant women who had been admitted to Korea University Hospital for asthma worsened. METHOD: Twenty seven pregnant women who had been visited to Korea University Hospital for asthma worsened were enrolled in our retrospective study. We reviewed medical recordings and interviewed patients with asthma. RESULTS: Twenty seven pregnant women with asthma were evaluated, and 25 patients were enrolled to our study. Two patients experienced abortions at 6 weeks and 25 weeks gestation, respectively. The period of asthma worsened was commonly during weeks 20 to 28 of gestation. And all patients wosened were improved during the last 4 weeks of pregnancy. Twenty(80%) of 25 women whose asthma worsened during pregnancy reverted toward their prepregnancy status after delivery(p<0.002). The causes of asthma worsened during pregnancy are reduction or even complete cessaton of medication due to fears about its safety(40%), worsening after upper respiratory infection(28%), and unknown(32%). There were no adverse perinatal outcomes in 25 pregnant asthma subjects. CONCLUSIONS: A major problem of therapy for asthma during pregnancy is reduction or even complete cessation of medication due to fears of fetal effects. Therefore, maternal education and optimal clinical and pharmacologic management is necessary to mitigate maternal and fetal complications.

Eotaxin mRNA Expression in Bronchial Mucosa of Patients with Asthma / 결핵

BACKGROUND: Asthma is a chronic inflammatory disease of the airways characterized by a marked infiltration of ecsinophils in the bronchial mucosa. Asthmatic bronchial muosa produces many factors described as king chernotaetic for inflammatory cells. IL-5, RANTES, and MCP-1 alpha are the chemotactic factors for eosinophils, but their roles are controversiaL Recently eotaxin that is a potent eosinophil chernoattracttnt cytokine was detected in a guinea-pig model of allergic airway inflammation, and human eotaxin was cloned. Eotaxin is a specific chemoattractant for eosinophils, but its role in asthma is not confirmed. We examined the in vivo expression of a,taxin in bronchi of asthmatic patients. METHODS: 11 asthmatics and 2 normal controls were enrolled. All subjects were underwent brcnchcscopy with bronchial biopsies in 2nd or 3rd carina. RNA extraction from biopsy samples was done by acid-guanidium method. Semi-quantitaive RT-PCR was done for evaluation of eotaxin mRNA expression. The extent of eosinophil infiltrartion was evaluated by counting the eosinophils in submucosa in HPF of microscope. RESULTS: Eotaxin mRNA expressed in symptomatic, uncontrolled asthma. Steroid inhibited expression of eotaxin mRNA in asthma. Expression of eotaxin mRNA correlated with eosinohil infiltration in bronchial tissues. CONCLUISON: Expression of eotaxin mRNA increases in uncontrolled asthma and eotaxin is involved in the recruitment of eosinophils.

Investigation of the Relationship between Interleukin-4 Promoter Polymorphism and Severity of Patients with Bronchial Asthma / 결핵

BACKGROUND: Interleukin-4 plays an important role in pathogenesis of asthma, especially in developing atopy by means of switching B lymphocytes to produce IgE. It has been shown that there is polymorphism in the Interleukin-4 promoter region, transversion of cytosine to thymine at-598 from translation initiation site of IL-4 gene. There has also been quite a few works to reveal the role of the polymorphism of IL-4 gene in patients with asthma. We performed this investigation to determine the role of the polymorphism in the severity of symptoms of patients with asthma. We also examined the frequency and the type of the polymorphism in asthmatics compared with non-asthmatics as well. METHOD: The subjects enrolled in this study were 49 asthmatics and 33 non-asthmatics. All the asthmatics were classified as mild and moderate to severe by the NHLBI/WHO Workshop. DNA from both asthmatics and non-asthmatics was extracted, then performed ARMS(Amplification Refractory Mutation System) as well as RFLP using BsmF1 restriction enzyme in order to confirm the polymorphism of IL-4 gene. RESULTS: There was no significant difference in the occurrence of polymorphism of the IL-4 promoter sequence between asthm and non-asthma groups(P=0.7). Among those with polymorphisms, the number of C/C type was slightly more than C/T type in both asthmatics and non-asthmatics, 26 vs 21 in asthmatics and 18 vs 15 in non-asthmatics, which was, however, insignificant statistically. No significant relationship between the severity of asthma and the polymorphism was found(P=0.7). CONCLUSION: There was no significant difference between the severity of asthma and the IL-4 promoter polymorphism(P=0.709). Interestingly, the frequency of the polymorphism in both asthmatics as well as non-asthmatics was found to be even higher than that occurred in Caucasians. However, no significant difference in the frequency of the polymorphism was found in both groups.

Genetic Polymorphisms of the beta2-Adrenergic Receptor in the Severity of Bronchial Asthma / 결핵

BACKGROUND: Genetic and environmental factors are known to affect the incidence and severity of asthma. Stimulation of beta2-Adrenergic Receptor (beta 2AR) results in smooth muscle relaxation, leading to decrease in resistance of airflow. The gene encoding the beta 2AR has recently been seguenced. The beta 2AR genotype at the polymorphic lociof codons 16, 27, 34, and 164 was known to cause changes in the amino acids. The relationships between the structure of the beta 2AR and its functions are being elucidated. PURPOSE: The gene encoding the beta 2AR was carried out to assess the frequency of polymorphisms in bronchial asthma, to determine wheather these polymorphisms have any relation to the severity, or nocturnal symptoms in bronchial asthma. METHOD: The subjects studied were 103 patients with bronchial asthma, which consisted of 30 mild episodic, 32 mild persistent, 17 moderate, and 24 severe asthma patients. The polymorphisms of the beta 2AR gene were detected by mutated allele specific amplification (MASA) method at the codons 16, 27, 34, and 164. RESULTS: The most frequent polymorphism was arginine 16 to glycine. The other two polymorphisms, valine 34 to methionine and glutamine 27 to glutamic acid occured in 11 and 6 patients respectively. The polymorphism of threonine 164 to isoleucine was not found in our enrolled patients. The homozygous polymorphism of beta 2AR gene was found in only arginine 16 to glycine (12.6%). The heterozygous polymorphisms of beta 2AR gene were in arginine 16 to glycine, valine 34 to methionine, and glutamine 27 to glutamic acid, as 65.1%, 10.7%, and 5.8% respectively in asthma patients. The presence of agrginine 16 to glycine heterozygous or/and homozygous polymorphism was associated in severe asthma (p=0.015), but there was no association between the other three polymorphisms and the severity of asthma. The frequency of the 182AR gene polymorphisms was no relation in nocturnal asthma as compared with non-nocturnal asthma. CONCLUSION: The arginine 16 to glycine polymorphism of the beta 2AR gene is the most frequently found in asthma patients and association with severe asthma. But there was no association between the polymorphism of the beta 2AR gene and nocturnal asthma.

Castleman's Disease of the Lung / 결핵

Castleman's disease is uncommon lymphoproliferative disorder as giant lymph node hyperplasia and angiofollicular lymph node hyperplasia. Multicentric variant of Cagtleman's disease, plasma cell type has been, described that has mort generalized lymph node involvement as well as involvement of other organ systems than localized type. Multicentric plasma cell type is frequently accompanied by systemic manifestations, such as weight loss, lowgrade fever and weakness. But the reported cases of pulmonary parenchymal involvement are rare and have almost consisted of hyalinized ganuloma adjacent 13 a bronchus. We report a patient with Castleman's disease of the lung, pathologically proven interstitial pulmonary involvement.

Usefulness of LIFE in diagnosis of bronchogenic carcinoma / 결핵

BACKGROUND: Although the overall prognosis of patients with lung cancer is poor, highly effective treatment exists for the small subset of patients with early lung cancer(carcinoma in situ/micro- invasive cancer). But very few patients have benefit from them because these lesions are difficult to detect and localize with conventional white-light bronchoscopy. To overcome this problem, a Lung Imaging Fluorescence Endoscopic device(LIFE) was developed to detect and clearly delineate the exact location and extent of premalignant and early lung cancer lesions using differences in tissue autofluorescence. PURPOSE: The purpose of this study was to determine the difference of sensitivity and specificity in detecting dysplasia and carcinoma between fluorescence imaging and conventional white light bronchoscopy. MATERIAL AND METHODS: 35 patients (16 with abnormal chest X-ray, 2 with positive sputum study, 2 with undiagnosed pleural effusion, 15 with respiratory symptom) hale been examined by LIFE imaging system. After a white light bronchoscopy, the patients were submitted to fluorescence bronchoscopy and the findings of both examinations have been classified in 3 categories(class I, II, III). From of all class II and III sites, 79 biopsy specimens have been collected for histologic examination: a comparison between histologic results and white light or fluorescence bronchoscopy has been performed for assessing sensitivity and specificity of the two methods. RESULTS: 1) Total 79 sites in 35 patients were examined. Histology demonstrated 8 normal mucosa, 21 hyperplasia, 23 dysplasia, and 27 microinvasive and invasive carcinoma. 2) The sensitivity of white light or fluorescence bronchoscopy in detecting dysplasia was 60.9% and 82.6%, respectively. 3) The results of. this study showed 70.3 % sensitivity for microinvasive or invasive carcinoma with LIFE system, versus 100% sensitivity for white light in 27 cases of carcinoma. The false negative study of LIFE system was 8 cases(3 adenocarcinoma and 5 small cell carcinoma), which were infiltrated in submucosal area and had normal epithelium. CONCLUSION: To improve the ability to diagnose and stage more accurately, fluorescence imaging may become an important adjunct to conventional bronchoscopic examination because of its high detection rate of premalignant and malignant epithelial lesion. But, it has limitation to detect in submucosal infiltrating carcinoma.

The Usefulness of Nested Polymerase Chain Reaction(PCR) for M. tuberculosis in Differential Diagnosis of Solitary Pulmonary Nodule / 대한내과학회지

OBJECTIVES: The evaluation and management of a patient with solitary pulmonary nodule(SPN) are guided by principles that were derived from earlier surgical studies. SPN has a relatively good prognosis even if it is a malignant lesion. In Korea, where there is a high incidence of pulmonary tuberculosis, approximately 40% to 70% of clinically encountered solitary pulmonary nodules are tuberculous lesions. SPNs can be diagnosed by clinical findings and chest imaging techniques, but confirmed only by pathologic or cytologic studies. Transthoracic needle aspiration biopsy(TNAB) or cytology will be diagnostic in 80% to 95% of malignant nodules, but will identify the benign nature in 50% to 90% of benign nodules; such results imply lower accuracy of TNBA or cytology in diagnosing benign nodules. Differential diagnosis of SPNs can be difficult in tuberculosis endemic areas, such as in Korea, Nested polymerase chain reaction(PCB) is the widely used method to test very small amount of pathogene and to detect M, tuberculosis in fine needle aspirates. METHODS: 33 patients with SPN found on chest radiographs were evaluated by chest CT, mycobacteriologic and cytologic studies from sputum, bronchial washing fluids, and transthoracic fine needle aspirates, 17 cases were malignant SPNs(51.5%), consisting af 14 primary lung cancers and 3 metastatic SPNs, 18 cases were benign SPNs(48.5%), consisting of 8 tuberculous, 4 localized pneumonia, 1 pulmonary sequestration, and 3 radiologically suspected tuberculous lesions without response to anti-TB drugs. Nested PCR for detecting M. tuberculosis using TB-1, TB-2, TB-28, and TB-29C was carried out on fine needle aspirates from 33 patients with SPN. RESULTS: Among the pathologically proven 17 malignant SFNs, 15(88.5%) cases were detected as cancer on chest CT. 15(88.5%) cases were confirmed by transthoracic needle aspiration cytology, among which 3(17.7%) cases showed positive on sputum cytology, and other 3(17.7%) cases yielded positive on bronchial washing cytology as well. Two cases of malignant nodules were confirmed by open resection. In 8 tuberculous SPNs, Neither AFB stain of sputum, bronchial washings, nor transthoracic needle aspirates showed positive. However, mycobacterium was cultured in 1 (9.l%) case from sputum, in 3 (27.3%) cases from bronchial washing fluids, and in 2 (18.2%) cases from transthoracic needle aspirates. Thus, five cases were confirmed bacteriologically; one case had positive culture results on both bronchial washing and transthoracic needle aspirates. Three out of 8 tuberculous cases were radiologically suspected and showed response to anti-TB drugs, but were not bacteriologically confirmed. Chest CT could detect 72.7% of tuberculous nodules. Aspirates from malignancy, pneumonia, and sequestration were negative on nested PCR for tuberculosis, One of the 3 radiologically suspected tuberculous nadules without response to anti-TB drugs yielded positive results on nested PCR for M, tuberculosis. In contrast, 7 out of 8(87.5%) aspirates from proven tuberculous nodules showed positive results on nested PCR for M. tuberculous, which included 4 bacteriologically proven tuberculous nodules and 3 radiologically suspected tuberculous nodules with response to anti-TB drugs. CONCLUSION: Nested PCR could be used to detect M. tuberculosis in fine needle aspirates from tuberculous SPN with good sensitivity (87.5%) and specificity(96.0%). Therefore, nested PCR for detecting M. tuberculosis in fine needle aspirates may be useful in the differential diagnosis of solitary pulmonary nodules.

Effects of FK224, a NK1 and NK2 Receptor Antagonist, on Plasma Extravasation of Neurogenic Inflammation in Rat Airways / 결핵

BACKGROUND: Asthma is an inflammatory disease because there are many inflammatory changes in the asthmatic airways. Axon reflex mechanisms may be involved in the pathogenesis of asthma. Sensory neuropeptides are involved in this inflammation, which is defined as neurogenic inflammation. Substance p, neurokinin A, and neurokinin B may be main neuropeptides of neurogenic inflammation in airways. These tachykinins act on neurokinin recptors. Three types of neurokinin receptors, such as NK1, NK2, and NK3, are currently recognized, at which substance p,neurokinin A, and neurokinin B may be the most relvant natural agonist of neurogenic inflammation in airways. The receptor subtypes present in several tissues have been characterized on the basis of differential sensitivity to substance p, neurokinin A, and neurokinin B. Plasma extravasation and vasodilation are induced by substance p more potently than by neurokinin A, indicating NK1 receptors on endothelial cells mediate the response. But airway contraction is induced by neurokinin A more potently than by substance P, indicating the NK2 receptors in airway smooth muscles. These receptors are used to evaulate the pathogenesis of brochial asthma. FK224 was identified from the fermentation products of Streptomyces violaceoniger. FK224 is a dual antagonist of both NK1 and NK2 recptors. PURPOSE: For a study of pathogenesis of bronchial asthma, the effect of FK224 on plasma extravasation induced by vagal NANC electrical stimulation was evaluated in rat airway. METHOD: Male Sprague-Dawley rats weighing 180~450gm were anesthetized by i.p. injection of urethane. Plasma extravasation was induced by electrical stimulation of cervical vagus NANC nerves with 5Hz, 1mA, and 5V for 2 minutes(NANC2 group) and for sham operation without nerve stimulation(control group). To evaluate the effect of FK224 on plasma extravasation in neurogenic inflammation, FK224(lmg/kg, Fujisawa Pharmaceutical Co., dissolved in dimethylsul- phoxide; DMSO, Sigma Co.) was injected 1 min before nerve stimulation(FK224 group). To assess plasma exudation, Evans blue dye(20mg/kg,dissolved in saline) was used as a plasma marker and was injected before nerve stimulation. After removal of intravascular dye, the evans blue dye in the tissue was extracted in formamide(37degreesC, 24h) and quantified spectrophotometrically by measuring dye absorbance at 629nm wavelength. Tissue dye content was expressed as ng of dye per mg of wet weight tissue. The amount of plasma extravasation was measured on the part of airways in each groups. RESULTS: 1) Vagus nerve(NANC) stimulation significantly increased plasma leakage in trachea, main bronchus, and peripheral bronchus compared with control group, 14.1 +/-1.6 to 49.7+/-2.5, 17.5 +2.0 to 38.7 +/-2.8, and 12.7+/-2.2 to 19.1 +/-1.6ng of dye per mg of tissue(mean +/- SE), respectively(p0.05) 2) FK224 had significant inhibitory effect upon vagal nerve stimulation-induced airway plasma leakage in any airway tissues of rat,such as trachea, main bronchus, and peripheral bronchus compared with vagus nerve stimulation group, 49%, 58%, and 70%, respectively(p<0.05). Inhibitory effect of FK224 on airway plasma leakage in neurogenic inflammation was revealed the more significant in peripheral bronchus, but no significant in lung parenchyma. CONCLUSION: These results suggest that FK224 is a selective NK receptor antagonist which effectively inhibits airway plasma leakage induced by the endogenous neurotransmitters relased by neurogenic inflammation in rat airway. Tachykinin receptor antagonists may be useful in the treatment of brochial asthma.

Clinicopathologic features of Acute Interstitial Pneumonia / 결핵

BACKGROUND: Acute interstitial pneumonia is a relatively rare form of interstitial pneumonia, since the vast majority of interstitial pneumonia have a more chronic course. It corresponds to the lesion described by Hamman and Rich, as Hamman-Rich disease in 1944. Another name in the clinical literature is accelerated interstitial pneumonia, idiopathic acute respiratory distress syndrome (idiopathic ARDS), and the organizing stage of diffuse alveolar damage. Acute interstitial pneumonia differs from chronic interstitial pneumonia by clinical and pathologic features. Clinically, this disease is characterized by a sudden onset and a rapid course, and reversible disease. METHOD AND PURPOSE: Five cases of pathologically proven acute interstitial pneumonia were retrospectively studied to define the clinical, radiologic, and pathologic features. RESULTS: 1) The five cases ranged in age from 31 to 77 years old. The onset of illness was acute in all patients, it began with viral-like prodrome 6~40 days prior to shortness of breath, and respiratory failure eventually developed in all patients. In 2 cases, generalized skin rash was accompanied with flu-like symptoms. Etiologic agent could not be identified in any case. 2) All patients had leukocytosis and severe hypoxemia. Pulmonary function test of 3 available cases shows restrictive ventilatory defect, and one survived patient(case 5) has a complete improvement of pulmonary function after dismissal. 3) Diffuse bilateral chest infiltrates were present radiologically. Theses were the ground-glass, consolidation, and reticular densities without honeycomb fibrosis in all patients. The pathologic abnormalities were the presence of increased numbers of macrophages and the formation of hyaline membranes within alveolar spaces. There was also interstitial thickening with edema, proliferation of immature fibroblast, and hyperplasia of type II pneumocyte. In the survived patient(case5), pathologic findings were relatively early stage of acute interstitial pneumonia, such as hyaline membrane with mild interstitial fibrosis. 4) Of the 5 patients, four patients died of respiratory failure 14~90 days after onset of first symptom, and one survived and recovered in symptoms, chest X ray, and pulmonary function test CONCLUSION: These results emphasize that acute interstitial pneumonia is clinically, radiologically, and pathologically distinct form of interstitial pneumonia and should be separated from the group of chronic interstitial pneumonia. Further studies will be needed to evaluate the pathogenesis and the treatment of acute interstitial pneumonia.