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Glycogen storage disease type Ia (GSD-Ia) is an inherited metabolic disease caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC) which plays a critical role in blood glucose homeostasis by catalyzing the hydrolysis of glucose-6-phosphate (G6P) to glucose and phosphate in the terminal step of glycogenolysis and gluconeogenesis. Patients with GSD-Ia manifest life-threatening fasting hypoglycemia along with the excessive accumulation of hepatic glycogen and triglycerides which results in hepatomegaly and a risk of long-term complications such as hepatocellular adenoma and carcinoma (HCA/HCC). The etiology of HCA/HCC development in GSD-Ia, however, is unknown. Recent studies have shown that the livers in model animals of GSD-Ia display impairment of autophagy, a cellular recycling process which is critical for energy metabolism and cellular homeostasis. However, molecular mechanisms of autophagy impairment and its involvement in pathogenesis in GSD-Ia are still under investigation. Here, we summarize the latest advances for signaling pathways implicated in hepatic autophagy impairment and the roles of autophagy in hepatic tumorigenesis in GSD-Ia. In addition, recent evidence has illustrated that autophagy plays an important role in hepatic metabolism and liver-directed gene therapy mediated by recombinant adeno-associated virus (rAAV). Therefore, we highlight the possible role of hepatic autophagy in metabolic control and rAAV-mediated gene therapy for GSD-Ia. In this review, we also provide potential therapeutic strategies for GSD-Ia on the basis of molecular mechanisms underlying hepatic autophagy impairment in GSD-Ia.

Viral mediated gene therapy has progressed after overcoming early failures, and gene therapy has now been approved for several conditions in Europe and the USA. Glycogen storage disease (GSD) type Ia, caused by a deficiency of glucose-6-phosphatase-α, has been viewed as an outstanding candidate for gene therapy. This follow-up report describes the long-term outcome for the naturally occurring GSD-Ia dogs treated with rAAV-GPE-hG6PC-mediated gene therapy. A total of seven dogs were treated with rAAV-GPE-hG6PC-mediated gene therapy. The first four dogs were treated at birth, and three dogs were treated between 2 and 6 months of age to assess the efficacy and safety in animals with mature livers. Blood and urine samples, radiographic studies, histological evaluation, and biodistribution were assessed. Gene therapy improved survival in the GSD-Ia dogs. With treatment, the biochemical studies normalized for the duration of the study (up to 7 years). None of the rAAV-GPE-hG6PC-treated dogs had focal hepatic lesions or renal abnormalities. Dogs treated at birth required a second dose of rAAV after 2–4 months; gene therapy after hepatic maturation resulted in improved efficacy after a single dose. rAAV-GPE-hG6PC treatment in GSD-Ia dogs was found to be safe and efficacious. GSD-Ia is an attractive target for human gene therapy since it is a monogenic disorder with limited tissue involvement. Blood glucose and lactate monitoring can be used to assess effectiveness and as a biomarker of success. GSD-Ia can also serve as a model for other hepatic monogenic disorders.

Hepatocellular adenoma/carcinoma (HCA/HCC) is a long-term complication of glycogen storage disease type-Ia (GSD-Ia) which is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC), a key enzyme in gluconeogenesis. Currently, there is no therapy to address HCA/HCC in GSD-Ia. We have previously shown that a recombinant adeno-associated virus (rAAV) vector-mediated G6PC gene transfer to 2-week-old G6pc−/− mice prevents HCA development. However, it remains unclear whether G6PC gene transfer at the tumor developing stage of GSD-Ia can prevent tumor initiation or abrogate the pre-existing tumors. Using liver-specific G6pc-knockout (L-G6pc−/−) mice that develop HCA/HCC, we now show that treating the mice at the tumor-developing stage with rAAV-G6PC restores hepatic G6Pase-α expression, normalizes glucose homeostasis, and prevents de novo HCA/HCC development. The rAAV-G6PC treatment also normalizes defective hepatic autophagy and corrects metabolic abnormalities in the non-tumor liver tissues of both tumor-free and tumor-bearing mice. However, gene therapy cannot restore G6Pase-α expression in the HCA/HCC lesions and fails to abrogate any pre-existing tumors. We show that the expression of 11 β-hydroxysteroid dehydrogenase type-1 that mediates local glucocorticoid activation is down-regulated in HCA/HCC lesions, leading to impairment in glucocorticoid signaling critical for gluconeogenesis activation. This suggests that local glucocorticoid action downregulation in the HCA/HCC lesions may suppress gene therapy mediated G6Pase-α restoration. Collectively, our data show that rAAV-mediated gene therapy can prevent de novo HCA/HCC development in L-G6pc−/− mice at the tumor developing stage, but it cannot reduce any pre-existing tumor burden.

Background This study evaluated the impact of lymph node-related factors on the risk of and site of recurrence in patients who had papillary thyroid carcinoma with lymph node metastasis in the lateral compartment (classified as pN1b). Methods Patients underwent total thyroidectomy with unilateral modified radical neck dissection for classical papillary thyroid carcinoma. Risk factors for recurrence were evaluated according to the pattern of recurrence. Results A total of 324 patients were included in the study. The median follow-up was 63 (range 14–181) months. Recurrence was detected in 47 patients (14·5 per cent). In the multivariable analysis, a maximum diameter of metastatic lymph nodes larger than 2·0 cm (hazard ratio (HR) 1·15, 95 per cent c.i. 1·06 to 1·25; P = 0·033) and a central compartment metastatic lymph node ratio of more than 0·42 (HR 3·35, 1·65 to 6·79; P < 0·001) were identified as independent risk factors for locoregional recurrence. Age 45 years or older (HR 5·69, 1·24 to 26·12; P = 0·025) and extranodal extension of metastasis (HR 12·71, 1·64 to 98·25; P = 0·015) were risk factors for distant metastasis. In subgroup analysis of locoregional recurrence, several lymph node-related factors affected the risk of recurrence according to the specific site of metastasis. Conclusion Lymph node-related factors are of importance for the risk of recurrence in patients with classical papillary thyroid carcinoma classified as pN1b.

Background: Understanding the burden of disease is important to establish cost-effective treatment strategies and to allocate healthcare resources appropriately. However, little reliable information is available regarding the overall economic burden imposed by chronic obstructive pulmonary disease (COPD) in Korea. Methods: This study is a multicenter observational research on the COPD burden in Korea. Total COPD costs were comprised of three categories: direct medical, direct non-medical, and indirect costs. For direct medical costs, institutional investigation was performed at 13 medical facilities mainly based on the claims data. For direct non-medical and indirect costs, site-based surveys were administered to the COPD patients during routine visits. Total costs were estimated using the COPD population defined in the recent report. Results: The estimated total costs were approximately 1,245 million US dollar (1,408 billion Korean won). Direct medical costs comprised approximately 20% of the total estimated costs. Of these, formal medical costs held more than 80%. As direct non-medical costs, nursing costs made up the largest percentage (39%) of the total estimated costs. Costs for COPD-related loss of productivity formed four fifths of indirect costs, and accounted for up to 33% of the total costs. Conclusion: This study shows for the first time the direct and indirect costs of COPD in Korea. The total costs were enormous, and the costs of nursing and lost productivity comprised approximately 70% of total costs. The results provide insight for an effective allocation of healthcare resources and to inform establishment of strategies to reduce national burden of COPD.

Chronic cough is common in the community and causes significant morbidity. Several factors may underlie this problem, but comorbid conditions located at sensory nerve endings that regulate the cough reflex, including rhinitis, rhinosinusitis, asthma, eosinophilic bronchitis, and gastroesophageal reflux disease, are considered important. However, chronic cough is frequently non-specific and accompanied by not easily identifiable causes during the initial evaluation. Therefore, there are unmet needs for developing empirical treatment and practical diagnostic approaches that can be applied in primary clinics. Meanwhile, in referral clinics, a considerable proportion of adult patients with chronic cough are unexplained or refractory to conventional treatment. The present clinical practice guidelines aim to address major clinical questions regarding empirical treatment, practical diagnostic tools for non-specific chronic cough, and available therapeutic options for chronic wet cough in children and unexplained chronic cough in adults in Korea.

Rationale: Severe respiratory syncytial virus (RSV) bronchiolitis has been associated with deficient IFN-γ production in humans, but the role of this cytokine in determining the outcome of reinfection is unknown. Objectives: To define the role of IFN-γ in the development of RSV-mediated airway hyperresponsiveness (AHR) and lung histopathology in mice. Methods: Wild-type (WT) and IFN-γ knockout mice were infected with RSV in the newborn or weaning stages and reinfected 5 weeks later. Airway responses were assessed on Day 6 after the primary or secondary infection. Measurements and Main Results: Both WT and IFN-γ knockout mice developed similar levels of AHR and airway inflammation after primary infection. After reinfection, IFN-γ knockout mice, but not WT mice, developed AHR, airway eosinophilia, and mucus hyperproduction. Intranasal administration of IFN-γ during primary infection but not during reinfection prevented the development of these altered airway responses on reinfection in IFN-γ knockout mice. Adoptive transfer of WT T cells into IFN-γ knockout mice before primary infection restored IFN-γ production in the lungs and prevented the development of altered airway responses on reinfection. Treatment of mice with IFN-γ during primary neonatal infection prevented the enhancement of AHR and the development of airway eosinophilia and mucus hyperproduction on reinfection. Conclusions: IFN-γ production during primary RSV infection is critical to the development of protection against AHR and lung histopathology on reinfection. Provision of IFN-γ during primary infection in infancy may be a potential therapeutic approach to alter the course of RSV-mediated long-term sequelae.

Landau-Kleffner syndrome is characterized by epileptic aphasia associated with electrical status epilepticus of slow wave sleep. A 5-year-old female, who had manifested normal developmental progress, was referred with principal complaints of fluctuating sensory aphasia and bizarre behavior during the preceding 4 months. Landau-Kleffner syndrome was confirmed by clinical and electroencephalographic features; in addition, the patient's mitochondrial respiratory chain-complex I deficiency was confirmed by fibroblast culture with the evidence of energy metabolism disorder. This patient's seizures were intractable to many antiepileptic drugs, adrenocorticotrophic hormone, and intravenous immunoglobulin, with catastrophic cognitive and behavioral decline, but the seizures were successfully controlled by ketogenic diet with supplementary mitochondrial cocktail including coenzyme Q10, riboflavin, L-carnitine, and high-dose multivitamins. The patient finally regained fully normal cognitive functioning. Landau-Kleffner syndrome with mitochondrial respiratory chain-complex I deficiency was controlled in this case by ketogenic diet and supplementary mitochondrial cocktail therapy.

Study objectives: Extensive airway inflammation and excessive mucus production are implicated in deaths from asthma. High-resolution CT (HRCT) can be used to image both large and small airway abnormalities in asthmatics. The aims of this study were to clarify the distinction of HRCT features between near-fatal asthma (NFA) and non-NFA, and to evaluate serial follow-up HRCT scans of patients with NFA. Patients and design: Abnormalities of the large airway (bronchial wall thickness) and small airways (prominence of centrilobular structures and air trapping) were measured semiquantitatively on HRCT scans of 24 non-NFA, 16 NFA, and 16 control subjects. In addition, these abnormalities were reevaluated after intensive and relatively long-term (> 6 months) treatment with inhaled corticosteroids. Results: Prominence of centrilobular structures was observed in 36% of mild asthma cases, in 70% of moderate-to-severe asthma cases, and in 100% of NFA cases. Prominence of centrilobular structures, but neither bronchial wall thickness nor the area of air trapping, was significantly increased in NFA, as compared with mild or moderate-to-severe asthma (p < 0.05). In the seven non-NFA and five NFA patients who underwent follow-up HRCT scans, only bronchial wall thickness was decreased significantly in the NFA cases (p < 0.05), while bronchial wall thickness and the prominence of centrilobular structures were significantly decreased in the non-NFA cases. These small airway abnormalities were partially reversible in the both groups. Residual prominence of centrilobular structures after long-term inhaled corticosteroid treatment was significantly higher in NFA than non-NFA patients. Conclusions: The results of our study indicate that extensive small airway abnormalities may be associated with NFA, and that these abnormalities are partially reversible after the successful control of asthma symptoms. (CHEST 2004; 126:1840–1848)

Study objectives Eosinophilic bronchitis (EB) presents as a chronic cough and sputum eosinophilia without airflow limitation or bronchial hyperreactivity. Its long-term clinical course remains unknown. This study evaluated how frequently EB recurs and whether it develops chronic airway obstruction. Design This study was a prospective analysis. Methods Cough severity, FEV 1 , provocative concentration of methacholine causing a 20% fall in FEV 1 , and sputum eosinophil percentages were serially measured in 36 subjects for up to 48 months. All subjects inhaled corticosteroids until cough subsided. Results Five of the twenty four follow-up subjects (21%) had a recurrent episode of EB 4 to 6 months after disappearance of the first episode of EB (recurrent eosinophilic bronchitis). Progressive FEV 1 reduction > 20% was observed in three of the subjects, including a subject with asthma developing at the ninth month. Nineteen subjects had no recurrence of cough (nonrecurrent eosinophilic bronchitis) and no progressive FEV 1 reduction > 20%. However, sputum eosinophilia recurred between 4 months and 24 months in 10 subjects. Mean values of FEV 1 at the ninth and 12th months of the study were significantly lower in the recurrent eosinophilic bronchitis group than in the nonrecurrent eosinophilic bronchitis group (p Conclusion These results suggest that repeated episode of EB is associated with the development of chronic airflow obstruction, including asthma.

Recently, immediate allergic reactions, including anaphylaxis, after Pachycondyla chinensis ant stings have been frequently reported in Korea. To estimate the prevalence of these reactions and the sensitization rate to P chinensis , we undertook a visit-questionnaire survey of the 327 adult residents living in a town in an ant-infested area in Korea. Skin prick tests with 6 common inhalant allergens, 3 bee venom allergens, and P chinensis whole body extract were performed on all ant-allergic subjects, on 86 asymptomatic residents, and on 37 controls outside the area. The serum-specific IgE to P chinensis extract was determined by ELISA. Seven subjects (2.1%) reported that they had experienced systemic allergic reactions to P chinensis stings; 4 of them had anaphylactic reactions. Large local reactions occurred in an additional 5 subjects (1.6%). All subjects with systemic allergic reactions had positive skin prick test results to P chinensis extract, whereas 23.3% of asymptomatic residents and 2.7% of the controls showed positive skin prick test results. The serum-specific IgE level was significantly higher in the subjects with systemic reactions than in the subjects with local reactions, the asymptomatic sensitizers, and the nonatopic controls. Sensitization to bee venom was found in 25% of the P chinensis -allergic subjects; this was significantly higher than the 3% rate seen in nonsensitized subjects. In conclusion, we report a 2.1% prevalence of systemic allergic reactions after P chinensis stings, based on self-reported symptoms, in an ant-infested area in Korea. (J Allergy Clin Immunol 2002;110:54-7.)

Allergic rhinitis (AR) is one of the most common chronic allergic respiratory diseases worldwide. Various practical guidelines for AR have been developed and updated to improve the care of AR patients; however, up to 40% patients remain symptomatic. The unmet need for AR care is one of the greatest public health problems in the world. The gaps between guideline and real-world practice, and differences according to the region, culture, and medical environments may be the causes of unmet needs for AR care. Because there is no evidence-based AR practical guideline reflecting the Korean particularity, various needs are increasing. The purpose of the study was to evaluate whether existing guidelines are sufficient for AR patient management in real practice and whether development of regional guidelines to reflect regional differences is needed in Korea. A total of 99 primary physicians comprising internists, pediatricians, and otolaryngologists (n=33 for each) were surveyed by a questionnaire relating to unmet needs for AR care between June 2 and June 16 of 2014. Among 39 question items, participants strongly agreed on 15 items that existing guidelines were highly insufficient and needed new guidelines. However, there was some disagreement according to specialties for another 24 items. In conclusion, the survey results demonstrated that many physicians did not agree with the current AR guideline, and a new guideline reflecting Korean particularity was needed.

Depression is an important comorbidity of asthma. However, little information is available about depression and its potential impact on asthma control in Korean adult asthma patients. We aimed to estimate the prevalence and risk factors for depression in Korean adults with persistent asthma. The 127 non-elderly (20-64 yr) and 75 elderly (≥65 yr) patients with asthma were recruited. Demographic and clinical data were extracted, and the patients completed the Asthma Specific Quality of Life (AQOL) questionnaire and asthma control test (ACT). Depression status was defined using the Korean version of the Patient Health Questionnaire-9 (PHQ-9). Depression was more prevalent in non-elderly (18.9%) than in elderly patients with asthma (13.3%). Patients with depression were significantly younger, had lower economic status, shorter disease duration, poorer asthma control, and worse AQOL scores (P

Summary Xylitol has many uses, such as in dentistry and as a sweetening agent, and is synthesized from fungus by fermentation. According to some publications, xylitol has no adverse effects on the lungs in either healthy people or patients with cystic fibrosis, but no studies have examined the effects of long-term exposure. Here, we report a patient who developed occupational asthma due to xylitol as confirmed with provocation tests.

Summary We report a case of bulla formation in usual interstitial pneumonia (UIP) after a 5-year follow-up, proven by open lung biopsy, in a 35-year-old Korean man with dermatomyositis. Chest computed tomography showed marked bulla formation and bilateral hydrothorax. To our knowledge, the end result of UIP is honeycombing, respiratory failure, and infection. We postulate that if patients show good compliance in dealing with their UIP, the next form of honeycombing is bulla formation. This is the first report of bulla formation in UIP with dermatomyositis after long-term follow-up.

Background : An appreciable number of patients with toluene diisocyanate (TDI)-induced asthma have high serum levels of specific IgE (sIgE) antibody to TDI-human serum albumin conjugate (HSA). A recent investigation suggested a role of specific IgG (sIgG) in the development of TDI asthma. Methods : We observed the changes in the levels of specific IgE and IgG antibodies to TDIHSA conjugate in TDI-induced asthmatic patients during seven years avoidance. Results : Six subjects with high sIgE and five with high sIgG were enrolled. All of them had taken anti-asthmatic medications with complete avoidance. Serum levels of sIgE and sIgG to TDI-HSA conjugate were detected by ELISA. The level of sIgE continued to decline up to 7 years and the mean half-life was 3.9 years. The mean half-life of sIgG was 4.5 yrs. Conclusion : These findings suggest that both sIgE and sIgG to TDI-HSA conjugate may persist for several years after the last exposure to TDI.

Object The authors propose that anterior callosotomy—thought to have some advantages over total callosotomy—is not superior to total callosotomy for prevention of seizure propagation or other complications. Methods The study comprised 34 patients in whom generalized epilepsy syndrome or frontal lobe seizures with a secondary generalization were diagnosed. Preoperatively, all patients suffered from disabling drop attacks or intense head-drop seizures, and some patients also experienced other types of seizures. The male/female ratio was 22:12, and patients ranged in age between 1 to 19 years (mean 8.7 years). The follow-up period ranged from 1.08 to 5.0 years (mean 2.58 years). Seizure outcome, parental assessment of daily function, and parental satisfaction with the outcome was assessed postoperatively. Results After undergoing 1-stage total callosotomy, drop attacks disappeared completely in 25 patients during the follow-up period, and in 6 patients the frequency of drop attacks decreased to < 10% of baseline. With regard to other types of seizures, seizures resolved completely in 12 patients, and in another 18 seizure frequency decreased. Two patients experienced a transient disconnection syndrome for 2 and 4 weeks. One patient experienced ataxic hemiparesis for 3 weeks before it completely abated. The overall daily function of the patients improved, and all parents were satisfied with the surgical outcome. Conclusions For pediatric generalized epilepsy syndrome, 1-stage total callosotomy will be the first choice in treatment for controlling generalized seizures.

Boda Nam, MD, Jung Hwa Hwang, MD*, Young Mok Lee, MD, Jai Soung Park, MD, Sung Shick Jou, MD, Youngbae Kim, MD 1Department of Radiology, Soonchunhyang University Hospital, Seoul, Korea 2Bangbae GF Allergy Clinic, Seoul, Korea 3Department of Radiology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea 4Department of Radiology, Soonchunhyang University Cheonan Hospital, Cheonan, Korea 5Department of Preventive Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea

We report a case of hypersensitivity pneumonitis in a 30-yr-old female housewife caused by Penicillium species found in her home environment. The patient was diagnosed according to history, chest radiograph, spirometry, high-resolution chest CT, and transbronchial lung biopsy. To identify the causative agent, cultured aeromolds were collected by the open-plate method. From the main fungi cultured, fungal antigens were prepared, and immunoblot analysis with the patient's serum and each fungal antigen was performed. A fungal colonies were isolated from the patient's home. Immunoblotting analysis with the patient's sera demonstrated a IgG-binding fractions to Penicillium species extract, while binding was not noted with control subject. This study indicates that the patient had hypersensitivity pneumonitis on exposure to Penicillium species in her home environment.

Background: Airway hyperresponsiveness in asthmatics is considered to be one of the major consequences of airway inflammation and remodelling. Airway responsiveness is normal in patients with eosinophilic bronchitis (EB), despite eosinophilic inflammation of the airways comparable to that which occurs in asthmatics. Comparisons between asthma and EB should clarify the changes in airway morphology that are related specifically to AHR in asthmatics. Methods: Eighteen asthmatic patients, 15 patients with EB, and 11 healthy subjects were recruited. Airway wall area percentage (WA%), centrilobular prominence, and air trapping were compared using thin slice section computed tomography. Results: WA% was significantly greater in asthmatics than in patients with EB (72 (3.1)% v 54 (2.1)%, p = 0.032) and was similar in EB patients and controls (54 (2.1)% v 57 (1.8)%, p>0.05). Centrilobular prominence and air trapping were similar in EB patients and asthmatics and were significantly greater than in controls. Conclusion: WA% rather than air trapping or centrilobular prominence may be associated with the airway hyperresponsiveness that occurs in asthmatics but not in patients with EB.

Inhaled glucocorticoids (GCs) are the most effective control therapy for asthma. Although the clinical effects of inhaled GCs vary, there are few data on the differences in the responsiveness of individuals to inhaled GCs. The purpose of this study was to identify those factors that are associated with responsiveness to high-dose inhaled GCs in patients with moderate-to-severe asthma.This study was a prospective analysis.Outpatient clinics of tertiary hospitals.Eighty-six adult outpatients with moderate-to-severe asthma.Eighty-six patients with asthma who had initial FEV1 values of80% predicted after they had received inhaled GCs (fluticasone propionate, 1,000 microg/d) for 4 weeks. The primary end points were FEV1, FEV1/FVC ratio, forced expiratory flow (midexpiratory phase), and the score at presentation in the asthma-related quality-of-life questionnaire (AQLQ).The inhalation of GCs for 4 weeks had significant improvements in the FEV1% predicted and in the AQLQ score compared with the baseline values. Asthmatic patients with responses of12% (n = 46, 53.4%) in the change in FEV1 (deltaFEV1 = [FEV1 at 4 weeks--baseline FEV1]/baseline FEV1 x 100) also had significantly higher proportions of blood eosinophils and lower FEV1 values (in liters) prior to treatment. The change in FEV1 values correlated with the number of sputum eosinophils prior to GC inhalation (r = 0.242; p0.05) and correlated inversely with the FEV1 percent predicted values prior to GC inhalation (r = -0.462; p0.001).The FEV1 percent predicted and the blood and sputum eosinophil levels prior to GC inhalation are associated with the responsiveness to inhaled GCs in patients with moderate-to-severe asthma.

To investigate the pathogenic mechanism of late asthmatic response in comparison to early asthmatic response, changes of serum neutrophil chemotactic activity (NCA) using the Boyden chamber method and histamine level using the automated fluorometric analyzer were observed in 13 aspirin (ASA)-sensitive asthma subjects (group I: 7 early responders and group II: 6 dual responders) during lysine aspirin bronchoprovocation test (L-ASA BPT). Sera were collected before, and 30 min and 240 min after L-ASA BPT. Serum NCA increased significantly after 30 min (p=0.02) and decreased significantly at 240 min (p=0.02) in group I, while serum NCA of group II increased significantly at 30 min (p=0.04), tending to increase further up to 240 min with no statistical significance. NCA at 240 min in group II subjects was significantly higher than baseline NCA (p=0.02). The serum NCAs collected before and 240 min were significantly higher in group II than in group I (p

Background: Airway eosinophilia is frequently observed during acute exacerbation of asthma. Interleukin-5 (IL-5) and eotaxin are directly involved in the airway eosinophilia found in persistent asthma. Interrelation between these cytokines is expected to occur in acute exacerbation of asthma. Thus, we evaluated the relevance of interaction between eotaxin and IL-5 in the airway inflammation of acute exacerbation. Methods: We measured the number of inflammatory cells and the amount of eotaxin and IL-5 in sputum from 22 healthy subjects, 21 asthmatics with acute exacerbation and 16 patients with mild persistent asthma, and reassessed these values in 7 subjects with acute exacerbation after 7 days’ treatment with systemic steroid (2 mg/kg/day). Sources of IL-5 and eotaxin were investigated by immunohistochemical staining of sputum cells of 4 cases from each group. Results: Both IL-5 and eotaxin levels were higher in patients with acute exacerbation of asthma than in patients with persistent asthma and normal subjects. IL-5 and eotaxin levels were significantly correlated with eosinophil percentages in mild persistent asthma. Eotaxin staining was found mainly on macrophages and occasionally on eosinophils. Steroid treatment markedly decreased eosinophil percentages and IL-5 levels within 7 days but did not alter eotaxin levels. Conclusions: Both IL-5 and eotaxin are associated with acute exacerbation of asthma. IL-5 rather than eotaxin is effectively decreased by the inhibitory effect of steroid in acute exacerbation.

1 , Jong Won Park, M.D. Background: The rising prevalence of asthma worldwide may be associated with the rising prevalence of obesity in developed nations. Although several studies have suggested a relationship between asthma and obesity, controversy still remains. The aim of this study was to examine the relationship between obesity and asthmatic factors such as atopy, eosinophilia, serum total Ig E and bronchial hyperresponsiveness in chronic cough patients. Methods: This study was a retrospective, observational study in two centers done between January 2007 and June 2008. The subjects included individuals who had a chronic cough. We examined body mass index (BMI) to measure obesity and pulmonary function. We did a metacholine provocation test for airway hyperresponsiveness (AHR), a skin prick test for atopy, and tests for blood eosinophils and serum IgE. Results: A total of 1022 subjects were included. Airway hyperresponsiveness was not related with obesity (p=0.06), and atopy incidence was significant higher in non obese patients (p=0.00). There was no significant difference in serum IgE and blood eosinophil counts between obese and non obese patients. Forced expiratory volue in one second (FEV 1)/forced vital capacity (FVC) was significantly reduced in obese patients (p=0.03), but FEV1 and FVC were no significant difference between obese and non obese patients. Conclusion: There is no relationship between obesity and bronchial hyperresponsiveness. The nonobese group appears to have more atopy. The relationship between obesity and bronchial hyperresponsiveness and atopy need further investigation.

Purpose Leukotriene receptor antagonists (LTRAs) are used to treat aspirin-intolerant asthma (AIA); however, the protective effects of long-term LTRA administration against aspirin-induced bronchospasm have not been evaluated. Objectives We investigated the efficacy of a 12-week treatment with a LTRA in protecting against aspirin-induced asthma in AIA patients. Methods Fifty-two adult patients with AIA underwent an aspirin challenge test just before administration of montelukast (10 mg/day) and just after 12 weeks of treatment. The protective effect was assessed as the disappearance of aspirin-induced bronchospasm after 12 weeks of treatment. The results were compared according to the patients' clinical and physiological parameters. Results The decline in FEV1 following aspirin challenge was significantly reduced from 28.6±1.9% to 10.2±1.7% (P=0.0001) after 12 weeks of montelukast treatment. However, 14 subjects (30%) still showed a positive response (>15% decline in FEV1) to aspirin challenge. Grouping the subjects into good and poor responders according to post-treatment responses revealed that the pretreatment aspirin-induced FEV1 decline was significantly greater in the poor responders and that the triggering dose of aspirin and the induction time for a positive response were lower and shorter, respectively, in the poor responders. Histories of aspirin hypersensitivity and sinusitis were more prevalent among the poor responders than among the good responders. Conclusions Twelve weeks of treatment with montelukast protected against aspirin-induced bronchospasm in 70% of the AIA cases. A poor response was associated with more severe aspirin-induced bronchospasms before treatment and a history of aspirin hypersensitivity or sinusitis. Clinical implications A severe response to aspirin challenge may be a predictor of poor responsiveness to leukotriene antagonist treatment.

Methods: Fifty patients with COPD were enrolled in this study. Their subjective dyspnea score (modified Borg scale dyspnea index), spirometry, and lung volume were measured. Simultaneous hyperinflations of chest x-ray score ("chest score") and degree of emphysema of HRCT ("HRCT score") were measured. The "chest score" were composed of lung length, retrosternal space width, and height of the arc of the diaphragm and "HRCT score" were composed of severity and extent of emphysema. Results: The mean age of patients was 69 years old and their mean FEV1 was 51.7%. The Borg score significantly correlated with parameters of spirometry and lung volume, including FVC, FEV1, FEV1/FVC, RV, RV/TLC, and DLCO. The Borg score correlated well with "HRCT score", but did not correlate with "chest score". Also, the Borg scale correlates inversely with body mass index. Conclusion: The quantity of emphysema on chest HRCT may serve as an objective marker of dyspnea in patients with COPD.

Background Respiratory syncytial virus (RSV)–specific IgE is a component of the host response to RSV infection, but its role in the subsequent enhancement of altered airway responsiveness is unknown. Objective To define the role of RSV-specific IgE in the enhancement of airway responsiveness on reinfection of newborn mice. Methods Mice were infected as newborns with RSV and were reinfected 5 weeks later. The role of IgE was determined by documenting RSV-specific IgE response after neonatal infection, and by assessing airway responsiveness on reinfection. Results After neonatal infection, wild-type (WT) mice developed an RSV-specific IgE response. On reinfection, these mice developed enhanced airway hyperresponsiveness (AHR), airway eosinophilia, and mucus hyperproduction, and their T-cell cytokine response was skewed toward a T H 2 phenotype. None of these altered responses developed on reinfection of IL-4 −/− /IL-13 −/− mice, and no RSV-specific IgE could be detected after neonatal infection of these mice. FcɛRI −/− mice did not develop the enhanced AHR on reinfection, and airway eosinophilia and mucus production were significantly attenuated. These responses could be restored in deficient mice reconstituted with WT mast cells. In RSV-infected newborn WT mice, administration of anti-IgE prevented the enhancement of AHR and attenuated eosinophilia and mucus hyperproduction on reinfection, an effect that was associated with diminished T H 2 cytokine production and increased IFN-γ production. Conclusion Respiratory syncytial virus–specific IgE enhances the development of T H 2-biased airway responsiveness on reinfection of mice initially infected as newborns.

Churg-Strauss syndrome (CSS) or allergic granulomatous angiitis is a rare syndrome that is characterized by hypereosinophilic systemic necrotizing vasculitis affecting small- to medium-sized arteries and veins. In gen-eral, it occurs in individuals with pre-existing allergic asthm a. When CSS appears in patients, it has the follow-ing characteristics: eosinophilia of more than 10% in peripheral blood, paranasal sinusitis, pulmonary in-filtrates, histological proof of vasculitis with extravascular eosinophils, and mononeuritis multiplex or polyneuropathy. Therapeutic trials dedicated to Churg-Strauss syndrome have been limited due to the rarity of this disorder and the difficulty in making a histological diagnosis. Proper treatment of patients with CSS is not widely known. In this case study, we report on our experience with an unusual patient case, charac-terized by purpura and a perforation of the small intestine after inadequate steroid therapy.Key Words: Churg-Strauss syndrome, Asthma, Intestinal perforation, Eosinophilic infiltration

Bronchogenic cyst arises from anomalous budding of the primitive foregut during embryonic development and it represents a part of the spectrum of bronchopulmonary foregut malformations. Approximately two-thirds of the malformations are found within the mediastinum, and one-third are found in the lung parenchyma. The prevalence of bronchogenic cyst is unknown, presumably because most patients are asymptomatic. Incidentally detected bronchogenic cysts are usually removed at the time of diagnosis. We do not know how and why bronchogenic cysts grow. We recently experienced a case of rapidly growing mediastinal mass in a young adult, and this presented as a huge mass that had newly developed within one year. This mass was pathologically confirmed to be a bronchogenic cyst. We report on this case of a rapidly growing bronchogenic cyst, which is a rare characteristic of this type of cyst.

Reexpansion pulmonary edema is not a common phenomenon after chest tube insertion but some reports from 0% to 14%. There are various resulting complications, including acute respiratory distress syndrome. We report a case of focal reexpansion pulmonary edema after chest tube insertion. A 49-year-old male came to the hospital due to ongoing dyspnea and left chest pain for 3 days. On chest X-ray, the patient had a left pneumothrax. We planned to insert a chest tube for symptom relief. To determine whether or not the chest had expanded as a result of the chest tube insertion, the patient underwent repeated chest X-rays the following day. The patient experienced brief respiratory symptoms upon initial suction; a chest PA showed patchy consolidated infiltration at the inserted site. After 5 days of conservative management, the recovered completely.

The mechanism and cause of acute eosinophilic pneumonia are largely unknown. Many factors including the smoking of cigarettes have been suggested, but none have been proven to directly cause acute eosinophilic pneumonia. The authors report a case of acute eosinophilic pneumonia in a young Asian male who recently started smoking. The diagnosis was made based on his clinical course and results of chest radiography, lung spirometry, bronchoalveolar lavage, and transbronchial lung biopsies. After administration of methylprednisolone, his clinical course rapidly improved. A provocation test was designed to establish a connection between cigarette smoking and the development of acute eosinophilic pneumonia. After the provocation test, the patient showed identical symptoms, increase in sputum eosinophils, and worsening of pulmonary function. The results of the provocation test suggest that smoking may directly cause acute eosinophilic pneumonia, and support previous reports of cigarette smoking-induced acute eosinophilic pneumonia.

Neurilemmomas are benign nerve sheath tumors derived from Schwann cells that rarely occur in the chest wall. Neurilemmomas of the chest wall are usually solitary lesions th at bulge toward the pleural cavity. Neurilemmomas are confirmed histologically based on the presence of Verocay bodies, Antoni A and Antoni B tissue patterns and S-100 protein. Bilateral neurilemmomas in the chest wall are extremely rare, as are those that grow in the subcutaneous tissue but not the pleural area. We report here a case of bilateral chest wall neurilemmomas in which the tumors bulged out to the skin and were palpable. (Tuberc Respir Dis 2008;65:318-322)Key Words: Bilateral neurilemmomas, Chest wall

결핵균은 공기를 매개로 전파되고 결핵균에 노출된 시간과 최초의 노출 정도가 전파의 위험을 증가 시키는 중요한 인자로 알려져 있다. 활동성 폐결핵 환자와 함께 생활하는 가족 내에서 감염이 현저히 증가하는데 이는 결핵균에 노출되는 기회 및 시간이 증가하기 때문이다. 하지만 고식적인 접촉자 조사만으로는 흔히 결핵 발생률을 과소평가할 수 있기 때문에 접촉자 조사와 결핵균의 유전형 조사를 병행하는 것이 감염의 위험이 높은 집단을 선별해내고 발생빈도 및 전염경로를 밝히는 데 보다 효과적인 것으로 보고되고 있다. 이에 접촉자 조사와 결핵균의 유전형 조사를 통해 가족 내 결핵균 전파를 증명한 1예를 보고하는 바이다. (Tuberc Respir Dis 2008;65:512-516)

Tracheomegaly is a distinctive condition that presents with marked dilation of the trachea. Spontaneous pneumomediastinum is the result of alveolar rupture with dissection of the airway along the bronchus and into the mediastinum. Tracheomegaly and recurrent spontaneous pneumomediastinum are rare complications of pulmonary fibrosis when combined with rheumatoid arthritis. We present a case of tracheomegaly and recurrent spontaneous pneumomediastinum that was precipitated by repeated respiratory infection and chronic cough in a patient with pulmonary fibrosis that was associated with rheumatoid arthritis.

A bronchial artery aneurysm is a rare condition, which needs optimal treatment due to the possibility of a life-threatening hemorrhage by rupture. The surgical removal of the aneurysm is the standard treatment. However, there are a few reports of coil embolization with a transcatheter. A 69 year-old man was referred for a further evaluation of a mass in the right hilum on chest radiography. He denied any respiratory symptoms. A chest CT scan showed a 3 × 3 × 4.5 cm sized vascular mass with strong contrast enhancement on the right hilar area that originated from the bronchial artery. On the angiogram, the bronchial artery originated from the descending thoracic aorta at the T8 level. A bronchial artery aneurysm was catheterized selectively. and embolized successfully with a coil. After coil embolization, the selective bronchial arteriography confirmed complete occlusion. We report this case of bronchial aneurysm that was treated successfully with coil embolization. (Tuberc Respir Dis 2007; 62: 62-66)

A 29-year-old female patient presented with exertional dyspnea that she had suffered with for 2 months. The chest X-ray displayed right pleural effusion that was diagnosed as chyle, according to the level of cholesterol and triglyceride in the pleural fluid. VATS (video assisted thoracic surgery) of the right lung was performed on the 7th day of hospitalization for obtaining a lung biopsy and to control the of pneumochylothorax. On the 11th hospitalization day, VATS of left lung was also performed to control the recurrent pneumothorax via pleurodesis. The lung biopsy showed moderate amounts of spindle-shaped and rounded cells (so-called LAM cells), which were reactive to actin and HMB45 (on immunohistochemical stains). We report here on a rare case of lymphangioleiomyomatosis combined with chylothorax and bilateral pneumothroraces.

A 29-year-old male patient was admitted due to his general weak ness and poor oral intake for several months. He was diagnosed as having Crohn disease 16 years ago and total colect omy was performed 10 years ago. On the 3rd day after admission, gross hematuria and sudden hemoptysis combined with diffuse infiltration were noted on chest X-ray. His symptoms and the diffusely increased lung opacities improved wi th administering high-dose steroid therapy. Later, anti-GBM antibody was found to be positive on the laboratory fi ndings. We report here on a rare case of Goodpsture syndrome combined with prolonged Crohn disease along with a review of literature. (Tuberc Respir Dis 2006; 61: 384-388)Key word: Goodpsture syndrome, Crohn disease, anti-GBM antibody Address for correspondence : Soo-taek Uh, M.D. Department of Internal Medicine, Soonchunhyang University, School of Medicine, 657, Hannam-Dong, Yougsan-Ku, Seoul 140-743, KoreaPhone: +82-2-709-9482, Fax: +82-2-709-9554E-mail: uhs@hosp.sch.ac.krReceived : May. 18. 2006Accepted : Aug. 14. 2006

Background : Glutathion S-transferase P1 (GSTP1), the abundant isoform of glutathione S-transferase in lung epithelium, plays an important role in cellular protection against oxidative stress and toxic foreign chemicals. GSTP1 (Ile105Val) polymorphism has been reported to be associated with asthma related phenotypes such as atopy and bronchial hyperresponsiveness. Therefore we investigated whether this polymorphism may be associated with the development of aspirin-intolerant asthma (AIA). Methods : GSTP1 Ile105Val polymorphism was determined using a single based extension method in 88 AIA subjects and compared to 154 aspirin-tolerant asthma (ATA) subjects and 119 normal healthy controls (NC) recruited from the Korean population. Results : No significant differences in allele and genotype frequencies of the GSTP1 Ilel105Val polymorphism were observed in the three groups (p>0.05). However, minor G allele frequency of the GSTP1 Ilel105Val polymorphism in AIA group (16.5%) tended to be lower than in the NC group (20.6%). Conclusion : These results suggest a lack of association of the GSTPI Ilel105Val gene polymorphism with AIA phenotype in the Korean population [word count: 159].

Background : A pulmonary embolism often presents with nonspecific symptoms and signs. However, a delayed diagnosis can result in catastrophic outcome. The majority of preventable deaths associated with a pulmonary embolism can be ascribed to a missed diagnosis rather than to the failure of existing treatments. Therefore, accurate and rapid diagnostic methods are essential for the management of a pulmonary embolism. The recent generation of multidetector-row spiral CT scanners appears to outperform other imaging modalities in detecting a central and peripheral pulmonary embolism. However, there are some variations in the interpretations of the findings between observers. This study examined the inter-observer differences of the diagnoses in patients with a pulmonary embolism. Method : 64 patients who were diagnosed with a pulmonary embolism either clinically or with spiral chest CT from 2002 to 2004, were included. Two thoracic radiologists interpreted the multidetector-row spiral CT in terms of the diagnosis of a pulmonary embolism and the location of the thrombus independently. Among 64 patients, 14 patients were excluded because there was no evidence of a pulmonary embolism or there was different interpretation of the pulmonary embolism between radiologists. A clinical diagnosis was based on "Rules for predicting the probability of embolism". Results : The mean score of the patients according to the Wells method was (0-9). The accordance of the radiologists was 95% in the main, 85% in the lobar, 91.2% in the segmental, and 96% in the sub-segmental pulmonary arteries. After excluding the negative interpretation from both radiologists, their agreement was 76.2%( 0.83) in the main, 57.6%( 0.63) in the lobar, 51.5%( 0.63) in the segmental, and 34.6%( 0.49) in the sub-segmental pulmonary arteries. Conclusion : Chest CT has been recently applied to patients suspected of having a pulmonary embolism. It was found that spiral CT is a rapid test for diagnosing a thrombus, and there was reliable accordance between the observers from the area of the large pulmonary arteries. However, there was a lack of agreement between the observers in diagnosing thrombi located distal to the sub-segmental arteries.

Background : Diagnosing a pulmonary embolism is difficult because its presenting symptoms are nonspecific and there are limitations with all of the objective tests. The D-dimer is known to be a marker of the lysis of intravascular cross-linked fibrin as a result of the activation of the endogenous fibrinolytic pathways, and the D-dimer assay is these an objective method for diagnosing a pulmonary embolism. This study assessed the benefits of the D-dimer test for diagnosing a pulmonary embolism using semiquantitative latex agglutination. Methods : The latex agglutination results of 185 patients were retrospectively reviewed. The D-dimer test was performed at the time a pulmonary embolism was suspected. Ninety patients(group I) were diagnosis with PE through spiral chest CT or a chest CT angiogram, perfusion/ventilation scans, and/or pulmonary angiogram. Ninety-five patients (group II) were found not to have a pulmonary embolism through the above tests. Results : The male to female ratio and mean age in groups I and II was 37:55, and 57 years old to 50:45 and 52 years old, respectively. When the cut off value for a positive D-dimer assay was set to , the sensitivity, positive predictive value, negative predictive value and specificity was 86.7%, 61.4%, 79.3%, and 48.4%, respectively. Conclusion : The semiquantitative latex agglutination method in the D-dimer test has a lower sensitivity and negative predictive value than the well known ELISA test particularly for small emboli. Therefore, this test is not a suitable screening test for excluding a pulmonary embolism.

Aspergillus fumigatus causes a variety clinical syndrome in lung including aspergilloma, chronic necrotizing aspergillosis, invasive pulmonary aspergillosis, and allergic bronchopulmonary aspergillosis. Aspergilloma develops by a colonization and growing of Aspergillus inside lung cavities with underlying lung disease. There is a few report of endobronchial aspergilloma without lung parenchymal lesion. We experienced a case of endobronchial aspergilloma did not fit any category of Aspergillus-induced lesion, who show minimal fibrostreaky denstities on chest PA and chest CT. Massive hemoptysis was improved by a removal of the aspergilloma in this patient. Here, we report a rare case of endobronchial aspergilloma showing massive hemoptysis with review of literatures. (Tuberc Respir Dis 2004; 57:589-593)