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.
Acetylcholine ; Asthma ; Autoreceptors ; Humans ; Inhalation ; Korea ; Methacholine Chloride ; Models, Animal ; Muscle, Smooth ; Neurons* ; Pilocarpine ; Pulmonary Medicine ; Receptors, Muscarinic* ; Respiratory Tract Infections ; Vagus Nerve

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.
Animals ; Collagen ; Coloring Agents ; Cytokines ; Endothelial Cells ; Endothelin-1* ; Endothelium, Vascular ; Epithelial Cells ; Exudates and Transudates ; Fibrosis ; Lung ; Macrophages ; Microscopy ; Models, Animal ; Necrosis ; Paraquat* ; Pneumocytes ; Pulmonary Fibrosis* ; Rats* ; Rats, Sprague-Dawley ; Receptor, Endothelin A*

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.
Diagnosis, Differential ; Eosinophilic Granuloma ; Fungi ; Humans ; Lung ; Neck ; Neoplasm Metastasis ; Physical Examination ; Radiography ; Silicosis ; Thorax ; Thyroid Gland ; Thyroid Neoplasms ; Thyroidectomy ; Tuberculosis

BACKGROUND: Lung cancer is the leading cause of cancer deaths in Korea and the number of lung cancer deaths is increasing. The higher response rates, decreased toxicity and improved performance status of the first-line treatments have resulted in an increased number of patients becoming candidates for second-line therapy. Several new anti??neoplastic agents, including gemcitabine, docetaxel and paclitaxel, have recently demonstrated second-line activity. This phase II study evaluated the efficacy and toxicity of gemcitabine and vinorelbine as combination chemotherapy for Korean patients with NSCLC as a second-line treatment. METHODS: Sixty response-evaluable patients were enrolled from December 2000 to July 2003. We conducted a phase II study of a combination gemcitabine and vinorelbine chemotherapy for patients with histologically confirmed NSCLC that was stage IIIB and IV disease at the time of diagnosis, and the disease had progressed onward or the patients had relapsed after first-line platinum-based chemotherapy. They were treated with intravenous gemcitabine 1000mg/m2 and intravenous vinorelbine 25mg/m2 on days 1 and 8. This chemotherapy regimen was repeated every 3 weeks. RESULTS: A total of 215 cycles of treatment were given and the mean number of cycles was 3.6 cycles. All the patients were evaluable for the toxicity profile. The response rate was 10% according to the WHO criteria.?The median progression free survival was 3.8 months and the median survival time was 10.1 months. The 1-year survival rate was 32.9%. Grade III and IV neutropenia were seen in 20 (33.3%) and 7 (11.7%) patients, respectively. CONCLUSION: The combination of gemcitabine and vinorelbine is active and well tolerated as a second-line therapy for patients with advanced nonsmall cell lung carcinoma.
Carcinoma, Non-Small-Cell Lung ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Drug Therapy, Combination* ; Humans ; Korea ; Lung Neoplasms ; Lung* ; Neutropenia ; Paclitaxel ; Survival Rate

BACKGROUND/AIMS: Obstructive sleep apnea (OSA) is associated with an increased risk of obesity and non-alcoholic fatty liver disease (NAFLD), but it remains unclear whether the risk of NAFLD is independently related to OSA regardless of visceral obesity. Thus, the aim of the present study was to examine whether OSA alone or in combination with excessive daytime sleepiness (EDS) or short sleep duration was associated with NAFLD independent of visceral fat in Korean adults. METHODS: A total of 621 participants were selected from the Korean Genome and Epidemiology Study (KoGES). The abdominal visceral fat area (VFA) and hepatic fat components of the participants were assessed using computed tomography scans and they were then categorized into four groups depending on the presence of OSA and EDS. RESULTS: The proportions of NAFLD were 21.1%, 18.5%, 32.4%, and 46.7% in participants without OSA/EDS, with only EDS, with only OSA, and with both OSA and EDS, respectively. A combination of OSA and EDS increased the odds ratio (OR) for developing NAFLD (OR, 2.75; 95% confidence interval [CI], 1.21 to 6.28) compared to those without OSA/EDS, and this association remained significant (OR, 2.38; 95% CI, 1.01 to 5.59) even after adjusting for VFA. In short sleepers (< 5 hours) with OSA, the adjusted OR for NAFLD was 2.50 (95% CI, 1.08 to 5.75) compared to those sleeping longer than 5 hours without OSA. CONCLUSIONS: In the present study, OSA was closely associated with NAFLD in Korean adults. This association was particularly strong in those with EDS or short sleep duration regardless of VFA.
*Adiposity ; Aged ; Asian Continental Ancestry Group ; Chi-Square Distribution ; Disorders of Excessive Somnolence/diagnosis/*epidemiology/physiopathology ; Female ; Humans ; Intra-Abdominal Fat/*physiopathology ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Non-alcoholic Fatty Liver Disease/diagnosis/*epidemiology/physiopathology ; Obesity, Abdominal/diagnosis/*epidemiology/physiopathology ; Odds Ratio ; Republic of Korea/epidemiology ; Risk Factors ; *Sleep ; Sleep Apnea, Obstructive/diagnosis/*epidemiology/physiopathology

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.
Biopsy ; Cough ; Developed Countries ; Diagnosis ; Diagnosis, Differential ; Dyspnea ; Follow-Up Studies ; Humans ; Korea ; Lung ; Lung Diseases ; Lung Diseases, Interstitial* ; Lymphocytes ; Middle Aged ; Prevalence ; Respiratory Sounds ; Sputum ; Thorax

Background: We aimed to investigate the moderating effects of obesity, age, and sex on the association between sleep duration and the development of diabetes in Asians. Methods: We analyzed data from a cohort of the Korean Genome and Epidemiology Study conducted from 2001 to 2020. After excluding shift workers and those with diabetes at baseline, 7,407 participants were stratified into three groups according to sleep duration: ≤5 hoursight, >5 to 7 hoursight (reference), and >7 hoursight. The Cox proportional hazards analyses were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes mellitus (T2DM). Subgroup analyses were performed according to obesity, age, and sex. Results: During 16 years of follow-up, 2,024 cases of T2DM were identified. Individuals who slept ≤5 hight had a higher risk of incident diabetes than the reference group (HR, 1.17; 95% CI, 1.02 to 1.33). The subgroup analysis observed a valid interaction with sleep duration only for obesity. A higher risk of T2DM was observed in the ≤5 hoursight group in non-obese individuals, men, and those aged <60 years, and in the >7 hoursight group in obese individuals (HRs were 1.34 [95% CI, 1.11 to 1.61], 1.22 [95% CI, 1 to 1.49], and 1.18 [95% CI, 1.01 to 1.39], respectively). Conclusion This study confirmed the effect of sleep deprivation on the risk of T2DM throughout the 16-year follow-up period. This impact was confined to non-obese or young individuals and men. We observed a significant interaction between sleep duration and obesity.