Recent Advances in Mechanisms and Treatments of Airway Remodeling in Asthma: A Message from the Bench Side to the Clinic

Airway remodeling in asthma is a result of persistent inflammation and epithelial damage in response to repetitive injury. Recent studies have identified several important mediators associated with airway remodeling in asthma, including transforming growth factor-beta, interleukin (IL)-5, basic fibroblast growth factor, vascular endothelial growth factor, LIGHT, tumor necrosis factor (TNF)-alpha, thymic stromal lymphopoietin, IL-33, and IL-25. In addition, the epithelium mesenchymal transformation (EMT) induced by environmental factors may play an important role in initiating this process. Diagnostic methods using sputum and blood biomarkers as well as radiological interventions have been developed to distinguish between asthma sub-phenotypes. Human clinical trials have been conducted to evaluate biological therapies that target individual inflammatory cells or mediators including anti IgE, anti IL-5, and anti TNF-alpha. Furthermore, new drugs such as c-kit/platelet-derived growth factor receptor kinase inhibitors, endothelin-1 receptor antagonists, calcium channel inhibitors, and HMG-CoA reductase inhibitors have been developed to treat asthma-related symptoms. In addition to targeting specific inflammatory cells or mediators, preventing the initiation of EMT may be important for targeted treatment. Interestingly, bronchial thermoplasty reduces smooth muscle mass in patients with severe asthma and improves asthma-specific quality of life, particularly by reducing severe exacerbation and healthcare use. A wide range of different therapeutic approaches has been developed to address the immunological processes of asthma and to treat this complex chronic illness. An important future direction may be to investigate the role of mediators involved in the development of airway remodeling to enhance asthma therapy.

The Effect of Nonspecific Endothelin-1 Receptor Blocker (Bosentan®) on Paraquat Induced Pulmonary Fibrosis in Rat / 결핵

BACKGROUND: Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-β1(TGF-β1), tumor necrosis factor-α(TNF-α), endothelin-1(ET-1) and interferon-γ(IFN-γ). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF-β1 expression in lung lesions were examined using immunohistochemical staining. After Bosentan® administration, an orally active ET-1A and ET-1B receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF-β1 expression were analyzed. METHOD: Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis-Bosentan®-treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-β1. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. RESULTS: The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with Bosentan®(100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased imunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF-β1 expression was higher on the exudate, macrophages, some infalmmatory cells, pneumocytes(type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF-β1 expression. CONCLUSION: Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF-β1 expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker(Bosentan®) on antifibrosis.

Effects of Immunostimulatory CpG-Oligodeoxynucleotides of Bronchial Asthma in Rat / 결핵

BACKGROUND AND OBJECT: Immunostimulatory CpG-oligodeoxynucleotides (ISS CpG-ODN) up-regulate the TH1-type immune response and down-regulate the TH2-type response. This study was performed to investigate the immune response changes resulting from ISS CpG-ODN on bronchial hyperrestponsiveness, eosinophilic inflammation and mucus hypersecretion in rat asthma. MATERIALS AND METHODS: 10 normal controls(NC) and 26 asthmatic rats, which were generated by ovallbumin(OVA) sensitization and challenge, were studied. The asthmatic rats were randomized into 11 asthma controls(AC) and 15 in the asthma-CpG treatment group(CpG). The CpG group was administered ISS CpG-ODN intramuscularly and the AC group was administered a placebo(0.9% NaCl)on day 15 and 20. After CpG-ODN or placebo administration, we measured the IFN-(TH1-type cytokine) and IL-4(TH2-type cytokine) levels in the bronchoalveolar lavage fluid(BALF), the specific airway resistance(sRaw), eosinophilic fraction in BALF, eosinophilic infiltration, goblet cell dysplasia and MUC5AC gene expression in the lung tissue. RESULTS: In the BALF of the CpG group, the IFN-γ concentration was significantly high and the IL-4 concentration was significantly low when compared with the AC group. Both the sRaw and eosinophilic fraction, and infiltration into the BALF and lung tissue significantly lower in the CpG group when compared with the AC group. However, little difference in goblet cell dysplasia and MUC5Ac gene expression was observed between the CpG group and the Ac group. CONCLUSION: ISS CpG-ODN decreases bronchial hyperresponsiveness and eosinophilic inflammation in the rat asthma model through the up-regulation of the TH1-type immune response with the down-regulation of the TH2-type response. However, the effect of these immune response changes on mucus hypersecretion was is not remarkable in this study.

Clinical Study fo Pulmonary Thromboembolism / 결핵

BACKGROUND: Pulmonary thromboembolism is relatively frequent and potentially fatal. However, it is commonly misdiagnosed. The incidence of pulmonary thromboembolism is not decreasing despite advances in diagnosis and effective prophylatic measures. Its potential for significant sequela necessitates a prompt diagnosis and treatment. Unfortunately, there are many difficulties and problems regarding accurate diagnosis. There is a low prevalence of deep vein thrombosis and pulmonary thromboembolism in Korea and only few reports on this subject are available. METHOD: The clinical features of 36 patients, who were diagnosed with pulmonary thromboembolism at the Korea University medical center, were reviewed. RESULTS: 1) There was no significant difference in prevalence between men an women, and the mean age was 50.9 years in men 59.2 years in women. 2) The frequent causes of pulmonary thromboembolism were malignancies (22.2%), surgery (22.2%), and heart disease(8.2%). Specific causes were not identified in 33.3%. 3) The most common symptom was dyspnea(72.2%), and the most common sign was tachypnea(61.1%). 4) The EKG findings were normal in 28.6%, and S1Q3T3 pulmonale pattern in 25.7%, ST or QRS changes in others. 5) The chest X-ray findings indicated pulmonary infiltation in 37.5%, cardiomegaly in 15.6%, pleural effusion in 12.5%, and normal in 27.8%. The perfusion lung scan showed a high probability in 66.7%, and intermediate or low probability in 33.3%. 6) The pulmonary arterial pressure(PAP) in the high probability groups was 57.9mmHg with a higher mortality rate(35%). CONCLUSION: Pulmonary thromboembolism is not uncommon in Korea and its clinical features do not differ greatly from those reported in the literature. When pulmonary thromboemblism of unknown causes are diagnosed, a search for an occult malignancy is recommended. Rapid diagnosis and treatment are achieved when thromboemblism is suspected.

Protection Against Respiratory Syncytial Virus Infection Induced Airway Hyperresponsiveness by DNA Encoding RSV-G Protein Immunization / 소아알레르기및호흡기학회지

PURPOSE: Respiratory syncytial virus is the primary cause of pneumonia and bronchiloitis in young children and infants. RSV infection is also known to be very important to asthma patient, because previous RSV infection increases the frequency of the asthma development and RSV infection may cause airway hyperresponsiveness. Natural RSV infection does not provide complete immunity and reinfection occurs throughout life. Several strategies have recently been used in RSV vaccine development, including the generation of formalin inactivated RSV(FI-RSV), peptides, recombinant vaccine viruses (rVV), and DNA based vaccines. Previous studies in mice primed with RSV G protein enhanced lung pathology resulted from a Th2 host immune response against the viral G protein. We studied for the evaluation of protective immunity, effect on airway hyperesponsiveness, and influence on lung pathology after pND G immunization. METHODS: BALB/c mice were injected with pND G(50g in 1 g/l PBS), pND G-HA (50 g), pND(50 g) FI-RSV(10 6PFU) i.d.at 0, 2, 4 weeks. Four weeks later, mice were challenged with RSV(10 6PFU). Mice were sacrificed on postchallenge day 4 and their lungs were removed for RT-PCR and viral titration. The other mice were sacrificed on postchallenge day 6 for bronchoalveolar lavage, serum and histologic examination. Airway responsiveness was assessed by using a single chamber whole body plethysmography on post challenge day 5. RESULTS: 1) Vaccination with pND-G reduced the Mch(methacholine) induced airway hyperresponsiveness after RSV infection(P0.05). CONCLUSION: In this study, immunization with pND encoding G protein induced decrease in airway hyperresponsiveness, and protection against RSV infection of the lower respiratory tract infection and also induced virus neutralizing antibody and decrease in lymphocytic inflammation. pND G immunization elicited balanced pulmonary Th1/Th2 cytokine response without atypical pulmonary inflammatory responses.

Function of the neuronal M2 muscarinic receptor in asthmatic patients / 결핵

BACKGROUND: The dominant innervation of airway smooth muscle is parasympathetic fibers which are carried in the vagus nerve. Activation of these cholinergic nerves releases acetylcholine which binds to M3 muscarinic receptors on the smooth muscle causing bronchocontraction. Acetylcholine also feeds back onto neuronal M2 muscarinic receptors located on the postganglionic cholinergic nerves. Stimulation of these receptors further inhibits acetylcholine release, so these M2 muscarinic receptors act as autoreceptors. Loss of function of these M2 receptors, as it occres in animal models of hyperresponsiveness, leads to an increase in vagally mediated hyperresponsiveness. However, there are limited data pertaining to whether there are dysfunctions of these receptors in patients with asthma. The aim of this study is to determine whether there are dysfunction of M2 muscarinic receptors in asthmatic patients and difference of function of these receptors according to severity of asthma. METHODS: We studied twenty-seven patients with asthma who were registered at Pulmonology Division of Korea University Hospital. They all met asthma criteria of ATS. Of these patients, eleven patients were categorized as having mild asthma, eight patients moderate asthma and eight patients severe asthma according to severity by NAEPP Expert Panel Report 2(1997). All subjects were free of recent upper respiratory tract infection within 2 weeks and showed positive methacholine challenge test(PC 20<16mg/ml). Methacholine provocation tests performed twice on separate days allowing for an interval of one week. In the second test, pre-treatment with the M2 muscarinic receptor agonist pilocarpine(180µg) through inhalation was performed before the routine procedures. RESULTS: Eleven subjects with mild asthma and eight aubjects with moderate asthma showed significant increase of PC20 from 5.30±5.23mg/ml(mean±SD) to 20.82±22.56mg/ml(p=0.004) and from 2.79±1.5mg/ml to 4.67±3.53mg/ml(p=0.012) after pilocarpine inhalation, respectively. However, in the eight subjects with severe asthma significant increase of PC20 from 1.76±1.50mg/ml to 3.18±4.03mg/ml(p=0.161) after pilocarpine inhalation was not found. CONCLUSION: In subjects with mild and moderate asthma, function of M2 muscarinic receptors was normal, but there was a dysfunction of these receptors in subjects with severe asthma. These results suggest that function of M2 muscarinic receptors is different according to severity of asthma.

Diffuse pulmonary nodular lesions persisting for 5 years / 결핵

Diffuse pulmonary nodular lesions have many causes. When they are caused by infection, the likely organisms are M. tuberculosis and various fungi. Silicosis, eosinophilic granuloma and pulmonary metastasis should be considered for differential diagnosis. Differential diagnosis needs detailed clinical history, physical examination and various laboratory tests. A case of persistent diffuse pulmonary nodular lesions which had persisted 5 years is reported. The patient was a 25 years old man with minimal pulmonary symptoms. Detailed past history and physical examination suggested thyroid tumor. Chest radiography showed numerous evenly sized well-defined nodules scattered in entire lung fields. Previous chest X-rays showed similar nodular lesions, which had lasted for 5 years. The number of nodules was slightly increased. Neck CT showed heterogenous mass in left lobe of thyroid gland and multiple lymphadenopathies along both internal jugular chains. Total thyroidectomy was performed. A case of lung metastasis which progressed slowly in papillary thyroid cancer is reported.

Correlation Between Primary Tuberculous Pleurisy and NRAMP1 Genetic Polymorphism / 결핵

BACKGROUND: The phagolysosomal function of alveolar macrophage against M. tuberculosis infection is influenced by Nramp1, which is encoded by the NRAMP1 gene. There are several genetic polymorphisms in NRAMP1, and these polymorphisms affect the innate host resistance through the defect in production and function of Nramp1. To investigate this relationship, we determined the NRAMP1 genetic polymorphism in patients with primary tuberculous pleurisy was determined. METHODS : 56 Fifty-six primary tuberculous pleurisy patient (,) who were diagnosed by pleural biopsy(,) were designated to the pleurisy group and 45 healthy adults were designated to the healthy control group. 3 Three genetic polymorphisms of NRAMP1 (,) such as a single point mutation in intron 4(469+14G/C, INT4), a nonconservative single-base substitution at codon 543 that changes aspartic acid to asparagine(D543N) and a TGTG deletion in the 3' untranslated region(1729+55del4, 3'UTR)(,) were determined. Polymerase chain reaction(PCR) and polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) were used. RESULTS: The frequencies of mutanat mutant genotypes of INT4 and 3'UTR were significantly high in pleurisy group(p=0.001, p=0.023). But the frequencies of D543N were not significantly different between the both two groups(p=0.079). Odds The odds ratios(,) which are a comparison with wild genotype for determining mutant genotypes(,) were 8.022(95% confidence interval=2.422 ~26.572) for INT4 and 5.733(95% confidence interval=1.137 ~28.916) for 3'UTR which were ;these were statistically significant. But the odds ratio for D543N was not significant. In the combined analysis of the INT4 and 3'UTR polymorphisms, as compared with GG/++ homozygotes, (delete) the odds ratios were 6.000(95% confidence interval=1.461 ~ 24.640) for GC/++ genotype and 14.000(95% confidence interval=1.610 ~121.754) for GC/+del when compared with GG/++ homozygotes which ;these were statisticallysignificant. CONCLUSION: Among the NRAMP1 genetic polymorphisms, a single point mutation in intron 4(469+14G/C, INT4) and a TGTG deletion in the 3' untranslated region(1729+55del4, 3'UTR) were closely related to the primary tuberculous pleurisy.

The Effects of Cyclooxygenase-2 (COX-2) Inhibitor on COX-2 and Prostaglandin E2 Expression in Ovalbumin Induced Early Phase Bronchoconstriction of Rats / 결핵

BACKGROUND: Bronchial asthma is characterized by airway hyperresponsiveness (BHR) and airway (delete) inflammation. The cyclooxygenase(COX) seems (is believed ) to be one of the important enzyme (enzymes) in these inflammatory reaction (reactions). Recently, the COX was divided into two isoforms, COX1 and COX2. COX2 is induced by lipopolysaccharide and some cytokines at the site of inflammation (inflammation site). Prostaglandin E2 (PGE2), which is (delete) produced from COX2, may affect on (delete) airway inflammation. The purpose of this study was (is) to evaluate the effect of COX2 inhibitor on COX2 expression, plasma PGE2 and(,)airway resistance and histologic finding in (an) animal asthma model. METHODS : Sprague-Dawley rats were divided into 3 groups. Normal control didn't (The normal control group did not) receive any treatment. Asthma (,but the asthma) control group was sensitized by ovalbumin but not treated with (the) COX2 inhibitor(nimesulide, Mesulid ). Treatment (The treatment) group was sensitized and treated with nimesulide. We examined specific airway resistance (sRaw) before and after nimesulide ingestion (was investigated) . Also, we examined (The) PGE2 level in (the) plasma was examined and performed COX2 immunogold-silver stain on lung tissue (was performed). RESULTS: sRaw and eosionophilic infiltration on airway were,( which) increased in the asthma control group which was (, was) compared to normal control(p=0.014). But there However, there was no difference in eosinophilic infiltration between asthma control and treatment group (groups)(p=0.408). There was (and) no difference in COX2 expression on bronchiolar epithelium among (the) three groups. Plasma PGE2 levels were no statistically significant difference (were not statically different) among (the) three groups. CONCLUSION: We conclude that the role (The role )of COX2 in the allergen(-) induced BHR was not significant. The effect of nimesulide was not observed on BHR, COX2 expression, and plasma PGE2 level. Therefore, COX2 may not be a major substance on (of) allergic asthma.

Fat embolism syndrome with pulmonary hemorrhage of unknown origin / 결핵

Fat embolism syndrome is a rare but serious complication occurring most of the time in patients with long bone fractures. And it occasionally occurs when patient had underlying disease. For example, pancreatitis, diabetes mellitus, alcoholic liver disease and connective tissue disease can be risk factors. The 44-year old woman visited to the Korea university hospital because of sudden dry cough, blood tinged sputum, and exertional dyspnea. We found petechiae on her anterior chest wall. Chest X-ray and CT showed patchy opacities and multifocal ground-glass opacities in both lung fields. Open lung biopsy demonstrated diffuse pulmonary hemorrhage and intravascular macrovesicular fat bubbles. After conservative management, her symptoms and radiologic findings were significantly improved. We report a case of fat embolism syndrome without any known risk factors.

The effects of treatment with cyclophosphamide and methylprednisolone on expression of endothelin-1 in unilateral instillation of paraquat-induced pulmonary fibrosis in guinea pigs / 결핵

BACKGROUND: The herbicide paraquat can cause severe lung injury and fibrosis in experimental animals. In this study we have investigated the changes in lung endothelin-1 levels and immunohistochemical localization in relation to treatment with cyclophosphamide and methylprednisolone in paraquat induced pulmonary fibrosis in guinea pigs. MATERIAL AND METHODS: 29 male Hartley guinea pigs were divided into 4 groups. Group I was normal control. Paraquat was instilled into the lung of guinea pig of group II, III and IV unilaterally. Group II was treated with cyclophosphamide and methylprednisolone. Group III was treated with methlprednisolone. Group IV was not treated. The degree of fibrosis was evaluated by H-E stains and Masson's trichrome stains and cell activity was assessed by endothelin-1 immunohistochemical stains. Statistical evaluation was performed using the Kruskawallis oneway analysis. RESULTS: Paraquat induced an increase in numbers of fibroblasts and total amount of lung collagen in Group IV compared to the normal controls. There was no significant difference in total numbers of fibroblasts between any of paraquat instilled groups, but there was significant increase in total amount of collagen in Group IV compared to group II and III (p<0.05).The treatment of cyclophosphamide and methyprednisolone suppressed the growths of both fibroblasts and collagen, but this suppression was stastically significant only in the case of collagen. ET-1(endothelin 1) immunoreactivities of bronchial epithelium, type II pneumocytes, endothelial cells and fibroblast in group II and III were decreased compared to those in group IV. CONCLUSION: These results demonstrate that ET-1 is an important contributing factor in the pathogenesis of pulmonary fibrosis. ET-1 is synthesized and released by bronchial epithelium, Type II pneumocyte, endothelial cells, alveolar macrophages and fibroblasts.Especially they are associated with alveolar macrophage and fibroblasts. We conclude that combined therapy of cyclophosphamide and methylprednisolone are more effective in the control of ET-1 expression and collagen deposition.

Effects of pranlukast on ovalbumin induced early-phase bronchoconstriction in guinea pigs / 결핵

BACKGROUND: Leukotriene (LT) C4, D4, and E4, the main components of slow-reacting substance of anaphylaxis (SRS-A), have been suggested to play an important role in bronchial asthma such as antigen- induced bronchoconstriction, airway hyperreactivity, and pulmonary eosinophil accumulation. The purpose of this study was to evaluate the effects of treatment with the cysteinyl-LTs (cys-LTs) antagonist, pranlukast on allergen-induced guinea pig asthma model. METHODS: Guinea pigs of treatment and placebo groups were sensitized by subcutaneous injection of ovalbumin (OVA) and challenged by inhalation of aerosolized OVA (1% weight/volume OVA). Normal control group did not sensitize with OVA. Oral ingestion of pranlukast and normal saline to the treatment and placebo groups was performed. In the treatment and placebo groups, airway resistance was measured before and after oral ingestion. Serum LTC4 and eosinophilic infiltration of the bronchiolar and peribronchiolar tissues were measured after ingestion in the treatment and placebo groups. RESULTS: Allergen-induced airway constriction developed in 20 (8 in treatment group, 12 in placebo group) among 35 guinea pigs. Airway resistance was significantly decreased at 3 and 6 minutes after OVA challenge in the pranlukast treatment group. In the placebo group, there was no difference of airway resistance between before and after saline ingestion. Serum LTC4 levels showed 348.4 pg/ml in the treatment group, 373.9 pg/ml in the placebo group, and 364.4 pg/ml in the control group. There were no statistically significant difference between treatment and placebo group (p=0.232), and treatment and control group (p=0.501). Eosinophilic infiltrations in the peribronchiolar region per one-microscopic field (X400 high power fields) demonstrated 7.06 in the treatment group, 19.2 in the placebo group, and 4.50 in the control group. There was significant decrement of eosinophilic infiltration in the treatment group which was compared with placebo group (p=0.001). CONCLUSION: These results demonstrate that pranlukast, a cys-LTs receptor antagonist, can attenuate allergen induced early-phase bronchoconstriction and eosinophilic infiltration in the bronchiolar tissues.

A Lung Abscess Combined with Mediastinal Air Shadow / 결핵

No abstract available.

A case of Nonspecific Interstitial Pneumonitis Mimicking Pneumoncystis carinii Pneumoni in HIV-positive patient / 결핵

The prevalence of nonspecific interstitial pneumonitis(NSIP) in HIV-positive patients with pulmonary disease has varied from 11 to 38%. But NSIP in HIV-positive patients is indistinguishable from Pneu mocystis carinii pneumonia(PCP) clinically and radiologically. The number of HIV-positive patients is less in Korea than in western developed countries, so little attention has been paid to the differential diagnosis between NSIP and PCP. We report a case of NSIP in HIV-positive, 61-year-old man which mimicked PCP. He presented with cough, sputum and mild exertional dyspnea. Lung sound was clear. But, chest X-ray and HRCT demonstrated diffuse patch and bilateral ground-glass opacities in central and perihilar area of both lung. Microbial pathogens were not found on sputum, BAL flued and tissues taken by TBLB. In transbronchial lung biopsy specimen, interstitial infiltrates with lymphocytes were distributed on peribronchiolar regions. A pathlolgic diagnosis of NSIP was suggested, he received symptomatic treatment. The follow-up chest X-ray showed near complete resolution.

Association between beta2 adrenoceptor polymorphisms and atopy/serum IgE in asthmatic patients / 결핵

BACKGROUND: The beta2 adrenergic receptor (beta2 AR) polymorphisms occurring at amino acid position 16 (Arg to Gly), 27 (Gln to Glu), 34 (Val to Met), and 164 (Thr to Ile) are known to be functionally relevant and also disease-modifying in subjects with asthma. However the contribution of these polymorphisms to the development of the asthmatic phenotype or other markers for allergic disease remains to be established. METHODS: 109 patients with bronchial asthma and 42 healthy person were included. Serum total IgE, allergen specific IgE, and skin prick test were performed to all of the subjects. beta2 AR polymorphisms were checked by mutated allele specific amplification (MASA) method. RESULTS: The results were as follows. The frequencies of beta2 AR polymorphisms in asthmatic patients and healthy person were not statistically different(p>0.05). There was no association between beta2 AR polymorphisms of amino acid position 16, 27, 34 and the existence of atopy among asthmatic patients (p>0.05). Between asthmatic patients with or without elevated IgE level and beta2 AR polymorphisms of amino acid position 16, 27, 34, there was no statistically significant association(p>0.05). CONCLUSION: There was no difference in frequency of the beta2 AR polymorphism between asthmatic patients and healthy person. In the bronchial asthma, association of beta2 AR polymorphism and atopy/serum total IgE was not found.

Correlation Between Angiotensin-Converting Enzyme(ACE) Inhibitor Induced Dry Cough and ACE Gene Insertion/Deletion(I/D) Polymorphism / 결핵

BACKGROUND: Persistent nonproductive cough is a major adverse effect encountered with ACE inhibitor treatment and the most frequent reason for withdrawal of the drug. The mechanism of cough was postulated to be associated with accumulation of bronchial irritants which are substrates of ACE. It has been speculated that occurrence of this adverse effect is genetically predetermined; in particular, variants of the genes encoding ACE. To investigate this relationship, we determined ACE gene Insertion/Deletion polymorphism in subjects with and without a history of ACE inhibitor-induced cough. METHODS: Among the 339 patients with ACE inhibitor treatment, subjects who developed cough that resolved when not taking medication were designated to cough group and other subjects who did not complain cough were designated to non-cough group. Clinical characteristics of the patients were collected by review of medical records. ACE genotypes were determined by PCR amplification of DNA from peripheral blood RESULTS: 37 patients complained of dry cough(cough group) and 302 patients did not complained of cough(non-cough group). The incidence of ACE inhibitor induced dry cough was 10.9%. There was a preponderance of females in the cough group (M:F=24.3%:75.7%) compared to the non-cough group(M:F=49.7%:50.3%, p=0.004). There was no significant difference in mean age, underlying diseases, and kinds and frequencies of ACE inhibitors and their mean dosage between the both groups. ACE genotypic frequencies were I/I : I/D : D/D = 16.2%:18.9%:64.9% in the cough group and 18.9%:18.2%:62.9% in the non-cough group which showed no significant difference between the both groups(p=0.926). Allelic frequencies were I : D = 25.7%:74.3% and 28.0%:72.0% in the cough and non-cough group respectively and the difference was not significant(p=0.676). CONCLUSION: The incidence of ACE inhibitor-induced cough are 10.9%, and women are more susceptible to ACE inhibitor-induce cough. ACE inhibitor induce dry cough is not associated with ACE gene Insertion/Deletion polymorphism.

Leukotriene C4 synthase promoter polymorphism in aspirin - induced asthma / 천식및알레르기

BACKGROUND: Aspirin/NSAIDs can release cysteinyl-leukotriene (cys-LTs) into airways and precipitate asthmatic symptoms in aspirin - induced asthma(AIA). It has been reported that there is profound overexpression of LTC4 synthase in their bronchial mucosa, compared to aspirin-tolerant asthma. Objective : We observed whether genetic polymorphism of LTC4 synthase may be predisposed to LTC4 synthase overexpression in AIA. Subject and METHOD: Forty - four AIA patients having positive responses on lysin aspirin bron choprovocation tests and 47 non - aspirin induced asthma ( non - AIA ) patients having negative challenges and 32 healthy controls were enrolled. The genotypes of the promoter LTC4 synthase gene ( A,C transversion ) were determined by polymerase chain reaction and restriction fragment length polymorphism ( RFLP ) method. RESULTS: LTC4 synthase promoter polymorphism ( A444C btransversion) was not significantly different between non - AIA and AIA patients (p>0.05). Conclusion These findings suggest that genetic polymorphism of LTC4 synthase promoter may not be predisposed to LTC, synthase overexpression in AIA.

A polymerphism of the angiorensin-converting enzyme gene according to the asthma severity / 천식및알레르기

BACKGROUND: The angiotensin-converting enzyme (ACE) has a major role in the degradation of bradykinin, tachykinin, substance P which are associated with bronchial hyperresponsiveness and inflammation. The other role of ACE is the genesis of angiotensin II which causes bronchial smooth muscle contraction. The deletion polymorphism of ACE gene(DDtype) may be related to the high serum level of ACE. OBJECTIVE: We studied to evaluate an association between the insertion /deletion polymorphism of the ACE gene and asthma, and its severity. Materials and methods: Sixty asthmatic patients and 44 healthy controls were enrolled. Severity of asthma was classified by the guideline of NHLBI/WHO workshop. The ACE genotypes of all the subjects were determined by polymerase chain reaction. RESULTS: The distribution of ACE genotypes were not significantly different between healthy controls and asthma group (p)0.05). In asthmatic patients, the genetic polymorphism was similar between different severity groups (p) 0.05). Conchcsion: It is suggested that I/D polymorphism of the ACE gene may not be associated with development of asthma. The severity of asthma may not be influenced by I/D polymorphism of the ACE gene.

The Effects of High Dose Rate Brachytherapy in Recurrent Obstructive Bronchogenic Cancer after External Irradiation Therapy / 결핵

BACKGROUND: Patients with centrally recurred bronchogenic carcinoma make a complaint of many symptoms like hemoptysis, cough & dyspnea. At these conditions, the goal of treatment is only to relieve their symptoms. High dose rate brachytherapy(HDR-BT) is the palliative treatment modality of centrally located endobronchial tumor regardless of previous external irradiation(XRT) on the same site in symptomatic patients. METHOD: We studied the effects of HDR-BT in 26 patients with symptomatic recurrent lung cancer. Patients(male: 24, mean age: 54yrs)were treated with HDR-BT underwent bronchoscopic placement of 192Ir HDR after loading unit(Gammamed(R), Germany) to deliver 500cGY intraluminal irradiation at a depth of 1cm every 1wk on 3 occasions. Evaluation at base line and 4wks after HDR brachytherapy included chest X-ray, bronchscopy, symptoms (Standadized Scale for dyspnea, cough, hemoptysis), and Karnofsky performance scale. RESULTS: Endobronchial obstruction was improved in 11/26 patients(37%). Atelectasis in chest X-ray was improved in 5/15 patients(33%). Hemoptysis, dyspnea & cough were improved in 5/10 patients (50%), 5/8 patients (62%) & 10/18 patients (56%) respectively. Karnofsky performance status was changed from 76.4 scores in pretreatment to 77.6 scores after treatment. During HDR-BT, massive hemoptysis (2 patients) and pneumothorax(1 patient) were occurred as complications. CONCLUSION: We concluded that HDR-BT gave additional benefits for the control of symptoms and general performance and endobronchial obstruction & atelectasis. And HDR-BT will be an additional treatment for the recurrent and endobronchial obstructive lung cancer.

Early Bronchoconstriction After Allergen Challenge of Nonanesthetized Guinea Pigs / 결핵

BACKGROUND: Bronchial asthma is a complex disease, which is characterized by spontaneous exacerbations of airway obstruction and persistent bronchial hyperresponsiveness. Animal models have fallen short of reproducing the human disease, particularly in mimicking the spontaneous and persistent airflow obstruction that characterized in asthma. In animals, airflow obstruction is usually assessed by measuring airflow resistance during tidal breathing under such invasive technique as tracheostomy and anesthesia. A noninvasive technique for measuring pulmonary function in small animals is needed to evaluate long-term changes in lung function during the course of experimentally produced disease without sacrificing the animal. PURPOSE: The purpose of this study was to evaluate early bronchoconstrcition after allergen challenge and airway responsiveness (AR) to inhaled methacholine in nonanethetized, unrestrained guinea pigs. METHOD: Guinea pig model of asthma was sensitized by subcutaneous injection with ovalbumin and challenged by inhalation of aerosolized ovalbumin(1% wt/vol ovlabumin). Airflow obstruction of conscious guinea pig was measured as specific airway resistance (airway resistance x thoracic gas volume). Airway resistance and thoracic gas volume of conscious guinea pig were assessed by body plethysmography before challenge and at regular intervals for as long as 30 minutes after challenge. AR to aerosolized methacholine of asthma group was compared with that of control group in body plethysmography. RESULT: Asthma models developed in 13(65%) among 20 guinea pigs, in which early responses occurred in the airways after the exposure to inhalation with ovalbumin. Airway challenge with ovalbumin caused increase in specific airway resistance, which peaked at 6 minutes and amounted to a 231.5+/-30.4% increase from baseline. AR to aerosolized methacholine of asthma model increased significanfly compared with control group. CONCLUSION: These results have showed a useful animal model to evaluate early bronchoconstrcition after allergen challenge and airway responsiveness in nonanethetized, unrestrained guinea pigs.