Background/Aims: The efficacy and safety of mepolizumab in patients with severe eosinophilic asthma has been evaluated in a global clinical trial programme. This post hoc analysis assesses the efficacy and safety of mepolizumab in Korean patients. Methods: Data from Korean patients in the Phase III, placebo-controlled, randomised DREAM (MEA112997/NCT01000506) and MENSA (MEA115588/ NCT01691521) studies were included. Patients ≥ 12 years old with severe eosinophilic asthma received mepolizumab (DREAM: 75, 250 or 750 mg intravenously [IV]; MENSA: 75 mg IV or 100 mg subcutaneously [SC]), or placebo every 4 weeks for 52 weeks (DREAM) or 32 weeks (MENSA). The primary outcome was the rate of clinically significant asthma exacerbations. Secondary outcomes included forced expiratory volume in 1 second (FEV1), Asthma Control Questionnaire (ACQ) and St George’s Respiratory Questionnaire (SGRQ) scores (MENSA only). Blood eosinophil counts (BEC) and safety were assessed throughout. Results: Reductions in the rate of clinically significant asthma exacerbations were observed with the approved (100 mg SC) and bioequivalent (75 mg IV) doses of mepolizumab in Korean patients who participated in DREAM and MENSA. In MENSA, trends for improvements from baseline at week 32 in pre-bronchodilator FEV1 (75 mg IV group), ACQ-5 and SGRQ scores (in both treatment groups) were seen versus placebo in Korean patients. Incidence of on-treatment adverse events was similar in Korean patients versus non-Korean patients as were observed reductions from baseline in BEC. Conclusions Mepolizumab treatment provided clinical benefits for Korean patients with severe eosinophilic asthma; the safety profile is consistent with the overall population.

PURPOSE: To evaluate airway changes in ovalbumin-induced asthmatic mice in terms of postmortem micro-CT images and pathological findings. METHODS: Asthma was induced in mice by intraperitoneal injection and nasal instillation of ovalbumin aluminium hydroxide into mice (experimental group, n=6), and another group of mice received intraperitoneal injection and nasal instillation of distilled phosphate-buffered saline (control group, n=6). Bronchial lumen area was measured in the main bronchial lumen of the distal third bronchial branch level (6 parts per each mouse) on axial scans of Micro-CT, using a Lucion's smart pen (semi-automated) and a curve pen (manual). Bronchial wall thickness was obtained in 4 sections (2 levels on either side) after the third bronchial branch by measuring the diameter which was perpendicular to the longitudinal axis of the main bronchus on curved Multi-planar reconstruction (MPR) images. Histologic slides were obtained from the lesion that was matched with its CT images, and bronchial wall thicknesses were determined. RESULTS: The mean bronchial lumen area was 0.196+/-0.072 mm2 in the experimental group and 0.243+/-0.116 mm2 in the control group; the difference was significant. Bronchial wall thickness on micro-CT images (mean, 0.119+/-0.01 vs. 0.108+/-0.013 mm) and in pathological specimens (mean, 0.066+/-0.011 vs. 0.041+/-0.009 mm) were thicker in the experimental group than in the control group; bronchial wall thickness on micro-CT images correlated well with pathological thickness (for the experimental group, r=0.712; for the control group, r=0.46). The thick bronchial wall in the experimental group demonstrated submucosal hypertrophy along with goblet cell hyperplasia and smooth muscle hyperplasia. CONCLUSIONS: The results of this study suggest that asthma may induce thickening of bronchial wall and narrowing of the lumen area on micro-CT images and that these results may significantly correlate with pathological findings.
Airway Remodeling ; Animals ; Asthma* ; Axis, Cervical Vertebra ; Bronchi ; Case-Control Studies ; Evaluation Studies as Topic ; Goblet Cells ; Hyperplasia ; Hypertrophy ; Injections, Intraperitoneal ; Mice* ; Muscle, Smooth ; Ovalbumin ; X-Ray Microtomography

Capillary hemangioma of the tracheobronchial tree is an extremely rare benign tumor in adults, especially those located in the bronchus. Characteristics and treatment of capillary hemangiomas of adult tracheobronchial trees have not been well known. We present a 61-year-old man with hemoptysis, which was caused by a small tiny nodule in the left lingular segmental bronchus. The nodule was removed by a forcep biopsy, via flexible bronchoscopy, and it was revealed to be capillary hemangioma. A small isolated endobronchial capillary hemangioma can be treated with excisional forcep biopsy, but a risk of massive bleeding should not be overlooked.
Adult ; Biopsy ; Bronchi ; Bronchoscopy ; Capillaries ; Hemangioma, Capillary ; Hemoptysis ; Hemorrhage ; Humans ; Surgical Instruments

BACKGROUND/AIMS: When combined with pegylated interferon alpha-2b (Peg-IFN alpha-2b) for the treatment of genotype 1 chronic hepatitis C (CHC) in Korea, the current guideline for the initial ribavirin (RBV) dose is based on body weight. However, since the mean body weight is lower for Korean patients than for patients in Western countries, current guidelines might result in Korean patients being overdosed with RBV. METHODS: We retrospectively reviewed the medical records of patients with genotype 1 CHC who were treated with Peg-IFN alpha-2b and RBV combination therapy. We divided the patients into groups A (> or =15 mg/kg/day, n=23) and B (<15 mg/kg/day, n=26), given that the standard dose is 15 mg/kg/day. The clinical course in terms of the virologic response, adverse events, and dose modification rate was compared between the two groups after therapy completion. RESULTS: The early response rates (92.0% vs. 83.3%, P=0.634) and sustained virologic response rates (82.6% vs. 73.1%, P=0.506) did not differ significantly between the two groups. During the treatment period, the RBV dose reduction rate was significantly higher in group A than in group B (60.9% vs. 23.1%, P=0.01). CONCLUSIONS: RBV dose reduction is performed frequently when patients are treated according to the current Korean guidelines. Given that lowering the RBV dose did not appear to decrease the virologic response during therapy, reducing RBV doses below the current Korean guideline may be effective for treatment, especially in low-weight patients.
Antiviral Agents/pharmacology/*therapeutic use ; Body Mass Index ; Body Weight ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus/drug effects ; Hepatitis C, Chronic/*drug therapy/virology ; Humans ; Interferon-alpha/pharmacology/*therapeutic use ; Male ; Polyethylene Glycols/pharmacology/*therapeutic use ; RNA, Viral/analysis ; Recombinant Proteins/pharmacology/therapeutic use ; Retrospective Studies ; Ribavirin/pharmacology/*therapeutic use ; Sex Factors ; Treatment Outcome

Crohn's disease can cause intestinal strictures, perforations, fistulas, or abscesses. Although fistulas and abscesses are common complications of Crohn's disease, a presacral abscess with neuromuscular complications is very unusual. A delayed diagnosis and treatment may increase morbidity. The diagnosis is frequently delayed, because the clinical features of presacral abscess are variable and nonspecific. We experienced a case of a presacral abscess with bilateral sciatica in a 25-year-old male patient. He was diagnosed with Crohn's disease of the terminal ileum 2 months previously and has been managed with mesalazine. He visited our hospital due to pain in the buttocks and severe neuralgia in both thighs. We confirmed enteric fistulas, resulting in a presacral abscess, which extended symmetrically through both sciatic notches and the gluteus medius muscles. He was managed with antibiotics after a small bowel segmentectomy, right hemicolectomy, fistulectomy, and surgical drainage. The bilateral radicular pain resolved completely within 2 weeks of surgery. The patient has remained in remission and asymptomatic 1 year after surgery.
Abscess ; Adult ; Anti-Bacterial Agents ; Buttocks ; Constriction, Pathologic ; Crohn Disease ; Delayed Diagnosis ; Drainage ; Fistula ; Humans ; Ileum ; Male ; Mastectomy, Segmental ; Mesalamine ; Muscles ; Neuralgia ; Sciatica ; Thigh

BACKGROUND/AIMS: The incidence of treatment failure or recurrence of Clostridium difficile-associated diarrhea (CDAD) following metronidazole treatment has increased recently. We studied the treatment failure, recurrence rate, and risk factors predictive of treatment failure and recurrence after metronidazole treatment for CDAD. METHODS: We retrospectively identified consecutive patients who were admitted and treated for CDAD at a single tertiary institution in Korea over a recent 10-year period (i.e., 1998-2008). RESULTS: Metronidazole was administered as the initial treatment to 111 of 117 patients (94.9%) with CDAD. Fourteen patients (12.6%) had no clinical response to the metronidazole treatment, and in 13 patients (13.4%) CDAD recurred after successful metronidazole treatment. Diabetes mellitus (p=0.014) and sepsis (p=0.002) were independent risk factors for metronidazole treatment failure. Patients who had received surgery within 1 month before CDAD developed were more likely to experience a recurrence after metronidazole treatment (p=0.032). Vancomycin exhibited a higher response rate after treatment failure, and metronidazole showed a reasonable response rate in the treatment of recurrence. Treatment failure and recurrence rates increased with time after metronidazole treatment for CDAD over the 10-year study period. CONCLUSIONS: Our data suggest that diabetes mellitus and sepsis are independent risk factors for metronidazole treatment failure, and that operation history within 1 month of development of CDAD is a predictor of a recurrence after metronidazole treatment.
Clostridium ; Diabetes Mellitus ; Diarrhea ; Humans ; Incidence ; Korea ; Metronidazole ; Recurrence ; Retrospective Studies ; Risk Factors ; Sepsis ; Treatment Failure ; Vancomycin

Idiopathic interstitial pneumonia (IIP) is characterized by varying degrees of interstitial fibrosis. IL-13 and IL-4 are strong inducers of tissue fibrosis, whereas IFN-gamma has antifibrotic potential. However, the roles of these substances in IIP remain unknown. IL-13, IL-4, and IFN-gamma were measured in the BAL fluid of 16 idiopathic pulmonary fibrosis (IPF) patients, 10 nonspecific interstitial pneumonia (NSIP) patients, and 8 normal controls. The expression of IL-13 and IL-13Ralpha1/alpha2 in lung tissues was analyzed using ELISA and immunohistochemistry. IL-13 levels were significantly higher in IPF patients than the others (P<0.05). IL-4 levels were higher in both IPF and NSIP patients than in normal controls (P<0.05), and IFN-gamma levels were lower in NSIP patients than in normal controls (P=0.047). IL-13 levels correlated inversely with FVC% (r=-0.47, P=0.043) and DLCO% (r=-0.58, P=0.014) in IPF and NSIP patients. IL-13 was strongly expressed in the smooth muscle, bronchial epithelium, alveolar macrophages and endothelium of IPF patients. IL-13Ralpha1, rather than IL-13Ralpha2, was strongly expressed in the smooth muscle, bronchial epithelium, and endothelium of IPF patients. IL-13 and its receptors may contribute to the pathogenesis of fibrosis in IIP and appear to be related to the severity of the disease.
Adult ; Female ; Humans ; Idiopathic Interstitial Pneumonias/diagnosis/*metabolism ; Idiopathic Pulmonary Fibrosis/diagnosis/*metabolism ; Interferon-gamma/analysis ; Interleukin-13/*analysis ; Interleukin-13 Receptor alpha1 Subunit/*metabolism ; Interleukin-13 Receptor alpha2 Subunit/*metabolism ; Interleukin-4/analysis ; Lung/physiopathology ; Male ; Middle Aged

PURPOSE: Percutaneous aspiration with sclerotherapy has been widely used for the treatment of symptomatic or large simple renal cysts. Ethanol has been most commonly used as a sclerosing agent; however, a temporary percutaneous nephrostomy for multiple ethanol injections is necessary to achieve a low recurrence rate. Thus, we used OK-432 as a new sclerosing agent without a temporary percutaneous nephrostomy for multiple injections, and also compared our results with the results of previous studies. MATERIALS AND METHDOS: Between October 2005 and April 2006, 50 patients (63 simple renal cysts) who underwent percutaneous OK-432 sclerotherapy for simple renal cysts were evaluated. The simple renal cysts were aspirated under ultrasonography and fluoroscopy, after which OK-432 was injected into the cyst. Follow-up was performed with ultrasonography or CT scan after 3 months. Regression of the renal cyst or a >70% reduction in size with no symptoms was considered a treatment success. RESULTS: Among 63 renal cysts in 50 patients, complete regression occurred in 17(27.0%). Greater than a 90% reduction in size occurred in 8(12.7%), a 80-90% reduction in size occurred in 21(33.3%), and a 70-80% reduction in size occurred in 15(23.8%); a <70% reduction in size occurred in 2 (3%). The overall efficacies of success were 96.8%. After the procedure, there were only some minor complications, such as mild fever, local pain, and liver function test elevation that subsided with symptomatic treatment. CONCLUSIONS: Percutaneous OK-432 sclerotherapy is simple, safe, and effective and can be an alternative first-line therapy of simple renal cysts.
Cysts

Palatoplasty using Furlow's double-opposing Z-plasty has been performed from June, 1995 to September, 1999 at Seoul National University Children's Hospital. The goal of this study is to determine the optimal timing of repair and cleft severity affecting velopharyngeal function. This is the retrospective study of patients operated by the second author. The mean age of patients was 10.53 months. The patients could be divided into three groups-isolated cleft palate(n=70), unilateral cleft lip and palate(n=88), and bilateral cleft lip and palate(n=42). To evaluate the velopharyngeal function, we used two parameters, speech evaluation and cineofluorography using DSR(digital subtraction radiography). Also, to determine the relevance between cleft severity and speech development, we measured the distance between maxillary tuberosities and cleft margins. Among 200 patients, about 96% had no or minimal hypernasality and 87% had no or mild nasal emission. The cleft width and length of soft palate seemed not to be related with the speech development. Palatoplasty at the age under 12 months resulted in less 'nasal emission' and better 'articulation' of the parameters that were assessed at the age of 7 years. It can be concluded Furlow palatoplasty shows satisfactory results and also it seems that it is better to perform the operation before the age of 12 months.
Cleft Lip ; Cleft Palate* ; Humans ; Palate, Soft ; Retrospective Studies ; Seoul

Pulmonary bronchogenic cyst in adults is rare and the typical appearance is a sharply circumscribed, round or oval nodule or mass, usually in the medial third of the lungs. Bronchial polyps are rare histopathologically distinct nonneoplastic endobronchial lesions and are classified as multiple papillomas, solitary papillomas, and inflammatory polyps. We herein report a patient with polypoid endobronchial lung cyst. A 68-yr-old woman presented with a discomfort and pain in the right upper chest of four weeks' duration. Chest radiography revealed a cystic lesion in the right upper lung. Computed tomography revealed a 4x5 cm sized large cyst. Neither enlarged mediastinal lymph nodes nor extrabronchial involvements were observed. Flexible bronchoscopy revealed a peduncular polyp about 2 cm in length originating from the anterior segment of right upper lung. After bronchoscopic removal of polyp, cystic lesion of the right upper lung disappeared.
Aged ; Bronchogenic Cyst/*diagnosis/*surgery ; Bronchoscopy/*methods ; Female ; Humans ; Lung Diseases/*diagnosis/*surgery ; Research Support, Non-U.S. Gov't ; Treatment Outcome