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.

Chronic pancreatitis (CP) is a debilitating disease that can result in chronic abdominal pain, malnutrition, and other related complications. The main aims of treatment are to control symptoms, prevent disease progression, and correct any complications. A multidisciplinary approach involving medical, endoscopic, and surgical therapy is important. Endoscopic therapy plays a specific role in carefully selected patients as primary interventional therapy when medical measures fail or in patients who are not suitable for surgery. Endoscopic therapy is also used as a bridge to surgery or as a means to assess the potential response to pancreatic surgery. This review addresses the role of endoscopic therapy in relief of obstruction of the pancreatic duct (PD) and bile du ct, closure of PD leaks, and drainage of pseudocysts in CP. The role of endoscopic ultrasound-guided celiac plexus block for pain in chronic pancreatitis is also discussed.

Background/Aims: The clinical efficacy and safety of a three-drug combination of melphalan, prednisone, and thalidomide were assessed in patients with multiple myeloma who were not candidates for high-dose therapy as a firstline treatment. Because the side effects of thalidomide at a dose of ${\geq}$ 100 mg daily can be a barrier to effective treatment for these patients, we evaluated the efficacy and safety of a reduced dose of thalidomide, 50 mg, for non-transplant candidates. Methods: Twenty-one patients were treated in 4-week cycles, receiving 4 mg/$m^{2}$ melphalan and 40 mg/$m^{2}$ prednisone on days 1-7 and 50 mg thalidomide daily. The primary efficacy outcome was the overall response rate. Aspirin (100 mg daily) was also provided as prophylactic treatment for thromboembolism. Results: The overall response rate was 57.1%; a complete response was seen in 23.8% of patients, a partial response in 33.3%, and stable disease in 9.5%. After a median follow-up time of 16.1 months, the median time to progression was 11.4 months (95% confidence interval, 2.1 to 20.6); the median overall survival was not reached. Grades 3 and 4 adverse events included infection (10%), peripheral neuropathy (5%), diarrhea (5%), thrombosis (10%), and loss of consciousness (10%). Two patients discontinued treatment due to loss of consciousness and neuropathy. Conclusions: Low-dose thalidomide (50 mg) plus melphalan and prednisone is an effective combination drug therapy option for newly diagnosed myeloma patients who are ineligible for high-dose chemotherapy.

Background/Aims: The aim of this study was to identify changes in left ventricular (LV) performance in patients with a myocardial bridge (MB) in the left anterior descending coronary artery during resting and in an inotropic state. Methods: Myocardial strain measurement by speckle-tracking echocardiography and conventional LV wall-motion scoring was performed in 18 patients with MB (mean age, 48.1 ${\pm}$ 1.7 years, eight female) during resting and intravenous dobutamine challenge (10 and 20 ${\mu}$g/kg/min). Results: Conventional LV wall-motion scoring was normal in all patients during resting and in an inotropic state. Peak regional circumferential strain increased dose dependently upon dobutamine challenge. Longitudinal strains of the anterior and anteroseptal segments were, however, reduced at 20 ${\mu}$g/kg/min and showed a dyssynchronous pattern at 20 ${\mu}$g/kg/min. Although there were no significant differences in radial strain and displacement of all segments at rest compared with under 10 ${\mu}$g/kg/min challenge, radial strain and displacement of anterior segments at 20 ${\mu}$g/kg/min were significantly reduced compared with posterior segments at the papillary muscle level (44.8 ${\pm}$ 14.9% vs. 78.4 ${\pm}$ 20.1% and 5.3 ${\pm}$ 2.3 mm vs. 8.5 ${\pm}$ 1.8 mm, respectively; all p < 0.001), and showed plateau (40%) or biphasic (62%) patterns. Conclusions: Reduced LV strain of patients with MB after inotropic stimulation was identified. Speckle-tracking strain echocardiography identified a LV myocardial dyssynchrony that was not demonstrated by conventional echocardiography in patients with MB.

Background/Aims: Complete endotracheal tube obstruction is a medical emergency, and partial occlusion causes increased breathing rates and failure to wean off mechanical ventilation. Partial occlusion may be underestimated due to the lack of proper detection methods. We tested whether the sound of an endotracheal tube could be used to detect an endotracheal tube obstruction using an in vitro model. Methods: An endotracheal tube was connected to a ventilator on one end and a test lung on the other. Sounds were recorded with a microphone located inside the endotracheal tube via a connector. During mechanical ventilation, we changed the endotracheal tube internal diameter from 5.0 to 8.0 mm and different grades of obstruction at different sites were used along the tube. Sound energy was compared among the different conditions. Results: The energy of endotracheal tube sounds was positively correlated with the internal diameter and negatively correlated with the degree of obstruction. The rate of decline in energy differed with obstruction location. When the obstruction was more distal, the rate of decline in endotracheal sound energy was more rapid. Conclusions: Changes in the sound of an endotracheal tube can be used to detect an obstruction. Further studies are needed for clinical application.

Background/Aims: To determine whether female smokers are more or less susceptible to the detrimental pulmonary-function effects of smoking when compared to male smokers among patients with lung cancer. Methods: Pack-years and pulmonary function indices were compared between 1,594 men and women with lung cancer who were smokers or had a history of smoking. Differences in individual susceptibility to smoking were estimated using a susceptibility index formula. Results: Of the patients, 959 (92.8%) men and 74 (7.2%) women were current smokers. Common histological types of lung cancer were squamous cell carcinoma, adenocarcinoma, and small cell carcinoma, among others. Women had a lower number of pack-years, forced expiratory volume in 1 second ($FEV_{1}$, liters), forced vital capacity (FVC, liters), and total lung capacity (TLC, liters) compared to those of men (25.0 ${\pm}$ 19.2 vs. 42.9 ${\pm}$ 21.7 for pack-years; 1.4 ${\pm}$ 0.5 vs. 2.0 ${\pm}$ 0.6 for $FEV_{1}$; 3.0 ${\pm}$ 0.7 vs. 2.0 ${\pm}$ 0.6 for FVC; 4.5 ${\pm}$ 0.8 vs. 5.7 ${\pm}$ 1.0 for TLC; all p < 0.001). The susceptibility index for women was significantly higher compared to that of men (1.1 ${\pm}$ 4.1 vs. 0.7 ${\pm}$ 1.1; p = 0.001). A significant inverse association was shown between the susceptibility index and TLC and FVC (r = -0.200 for TLC, -0.273 for FVC; all p < 0.001). Conclusions: The results suggest that the detrimental effects of smoking on pulmonary function are greater in women, as compared to those in men, among patients with lung cancer.

Background/Aims: The proper treatment of subclinical hypothyroidism and the normal range of serum thyroid stimulating hormone (TSH) concentration are intensely debated. However, few reports have investigated TSH concentrations in Asian ethnic groups. Therefore, the present study was designed to define the TSH reference range in a Korean population and to investigate the metabolic significance of TSH concentration. Methods: We enrolled patients who underwent medical examination at the CHA Bundang Medical Center. Anthropometric data were evaluated, and serum TSH, free T4, and lipid profiles were assayed. Results: A total of 7,270 subjects were included. Mean TSH concentration of the study population was 1.82 ${\pm}$ 0.95 mU/L, and we observed a sex-related difference in TSH concentration (male, 1.67 ${\pm}$ 0.87 mU/L; female, 2.02 ${\pm}$ 1.01 mU/L; p < 0.01). When the 2.5 and 97.5 percentiles were calculated, 95% TSH reference limits were 0.52-4.29 mU/L. TSH concentration was higher in elderly subjects, during winter, in postmenopausal women, and in obese males. Moreover, TSH showed significantly positive correlations with serum total cholesterol, triglyceride, and low density lipoprotein cholesterol regardless of sex, age, season, obesity, or menopausal status (all p < 0.01). Finally, TSH concentration was positively related to the prevalence of metabolic syndrome. Conclusions: We demonstrated the association between TSH concentration within the normal reference range and serum lipid levels. TSH concentration varies according to sex, age, season, and body mass index (only in males). Moreover, high normal TSH levels were significantly associated with an increased prevalence of metabolic syndrome, which may be of importance when evaluating subjects with high normal TSH concentration.

Background/Aims: Reports of the prevalence of and trends in metabolic syndrome in Korea have been inconsistent. Thus, we investigated the reasons underlying these inconsistencies. Methods: We estimated the prevalence of metabolic syndrome using different diagnostic criteria, exclusion criteria, and sampling weights among 5,509 respondents, aged 20-79, who participated in the 2001 Korean National Health and Nutrition Examination Surveys (KNHANES). Trends in metabolic syndrome were assessed by examining the 1998 (n = 6,747), 2001 (n = 4,337), and 2005 (n = 5,139) KNHANES. Results: The estimated prevalence of metabolic syndrome in 2001 ranged from 1.6 to 29.6% in males and from 10.1 to 32.8% in females, depending on the diagnostic criteria used. The exclusion criteria and sampling weights did not significantly affect the prevalence estimates. The prevalence of metabolic syndrome first significantly increased and then decreased between 1998, 2001, and 2005 in males (26.2, 29.6, and 27.2%, respectively) and females (29.2, 32.8, and 24.7%, respectively). Among the individual metabolic variables, triglyceride levels in 2001 were significantly higher than in 1998 and 2005, whereas other variables remained relatively constant during the same period. The exceptionally high triglyceride levels in 2001 might have contributed to the increased prevalence of metabolic syndrome between 1998 and 2001. Conclusions: Different diagnostic criteria for metabolic syndrome represent a major cause of the inconsistent estimates of prevalence, and the absence of standardized laboratory methods might have affected the trend estimates.

Background/Aims: Antiphospholipid antibodies (aPL) have been detected in various proportions of patients with primary immune thrombocytopenia (ITP), but the clinical significance of this is debatable. The present study aimed to determine the frequency and clinical implications of elevated aPL in adult patients with ITP. Methods: We prospectively studied newly diagnosed adult patients with ITP who were enrolled between January 2003 and December 2008 at Chungnam National University Hospital. They were evaluated for the presence of lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) at diagnosis and were followed for the development of thrombosis. Results: Seventy consecutive patients with ITP (median age, 48 years; range, 18 to 79) were enrolled. Twenty patients (28.5%) were positive for aPL at the time of diagnosis: aCL alone in 15 (75%), aCL and LA in two (10%), and LA alone in three (15%). Patients who had platelet counts < $50,000/{\mu}L$ were administered oral prednisolone with or without intravenous immune globulin. No difference was found between the aPL-positive and -negative groups regarding gender, initial platelet count, and response to the therapy. After a median follow-up of 20 months (range, 2 to 68), two of 20 patients who were aPL-positive (10%) developed thrombosis, whereas no thrombotic event was found among those who were aPL-negative. Conclusions: Our data suggest that aPL levels should be determined at the initial presentation of ITP and that patients found to be aPL-positive should receive closer follow-up for thrombotic events.

Takotsubo cardiomyopathy (TTC) is an infrequent cardiac syndrome characterized by acute onset chest pain with apical ballooning on echocardiography. It is often triggered by severe emotional or physical stress, and in contrast to acute myocardial infarction (AMI), the regional wall motion abnormality returns to normal within days. Here, we describe a 62-year-old female who presented with acute onset chest pain during treatment for a liver abscess. We presumed a diagnosis of AMI because of ST segment elevation on electrocardiography and elevated cardiac enzyme levels. However, the patient's coronary arteries were normal on angiography, and apical ballooning was seen on echocardiography. A diagnosis of TTC was made, and the patient was managed with intensive cardiopulmonary support using vasopressors in our hospital's medical intensive care unit. The patient's symptoms improved, but persistent severe left ventricular dysfunction was detected on follow-up echocardiography. After 5 weeks, a new apical mural thrombus appeared, and anticoagulation therapy was started. The apical ballooning persisted 3 months later, although the patient's overall ejection fraction was slightly improved. The apical thrombus was completely resolved without any embolic event. Non-adrenergic inotropics can be recommended in TTC with shock, and clinicians should keep in mind the potential risk of thrombus formation and cardioembolism.

We report a case of central venous stenosis due to a structural deformity caused by a tuberculosis-destroyed lung in a 65-year-old woman. The patient presented with left facial edema. She had a history of pulmonary tuberculosis, and the chest X-ray revealed a collapsed left lung. Angiography showed leftward deviation of the innominate vein leading to kinking and stenosis of the internal jugular vein. Stent insertion improved her facial edema.

Sodium bromate is a strong oxidant used as a neutralizing solution in hair permanents, as well as an auxiliary agent in printing and dyeing. Accidental or deliberate ingestion of bromate solution has rarely been reported in Korea. The clinical manifestations of bromate intoxication are vomiting, diarrhea, central nervous system symptoms, oliguric or non-oliguric acute kidney injury, hemolytic anemia, and deafness; most of these manifestations are reversible, with the exception of renal failure and deafness. Here, we report on two patients who demonstrated distinct clinical progressions. In the first case, a 16-year-old woman was successfully treated with hemodialysis and recovered renal function without hearing loss. However, in the second case, delayed hemodialysis resulted in persistent renal failure and hearing loss in a 77-year-old woman. This suggests that emergency therapeutic measures, including hemodialysis, should be taken as soon as possible, as the rapid removal of bromate may be essential to preventing severe intoxication and its sequelae.

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by persistent infectious mononucleosis-like symptoms, an unusual pattern of Epstein-Barr virus (EBV) antibodies, detection of the EBV genome in affected tissues or peripheral blood, and chronic illness that cannot be attributed to any other known disease. This is the first reported Korean case of an immunocompetent adult with CAEBV-associated interstitial pneumonitis. A 28-year-old female was admitted with a fever that persisted for 3 weeks. She had multiple lymphadenopathy, hepatosplenomegaly, pancytopenia, and elevated serum aminotransferase levels. Serology for antibodies was positive and chest computed tomography showed diffuse ground glass opacities in both lungs. Histopathology of the lung tissue showed lymphocyte infiltration, and EBV DNA was detected in those lymphocytes using in situ hybridization with an EBV-encoded RNA probe. After 1 month of hospitalization, she improved without specific treatment.

The World Health Organization classifies lupus nephritis as class I to V or VI. However, a few cases of minimal change glomerulopathy have been reported in association with systemic lupus erythematosus (SLE). Mycophenolate mofetil has been shown to be effective for treatment of minimal change disease and lupus nephritis. A 24-year-old woman diagnosed with SLE five years prior to presentation complained of a mild generalized edema. The urinalysis showed microscopic hematuria and proteinuria. The assessed amount of total proteinuria was 1,618 mg/24 hours. A renal biopsy demonstrated diffuse fusion of the foot processes of podocytes on electron microscopy. Mycophenolate mofetil was started in addition to the maintenance medications of prednisolone 10 mg/day and hydroxychloroquine 400 mg/day. After six months of treatment, the microscopic hematuria and proteinuria resolved, and the total urine protein decreased to 100 mg/24 hours.