Efficacy and safety of mepolizumab in Korean patients with severe eosinophilic asthma from the DREAM and MENSA studies

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.

A Case of Sterile Abscess Induced by Hyaluronic Acid Filler Injection

No abstract available.

Efficacy and Safety of Benralizumab for Korean Patients With Severe, Uncontrolled Eosinophilic Asthma

PURPOSE: In the Phase III SIROCCO trial (NCT01928771), benralizumab significantly reduced asthma exacerbations and improved lung function and symptoms for patients with severe, uncontrolled eosinophilic asthma. The aim of this subgroup analysis was to evaluate efficacy and safety of benralizumab for Korean patients in SIROCCO. METHODS: SIROCCO was a randomized, double-blind, parallel-group, placebo-controlled trial of 1,204 patients aged 12–75 years with severe asthma uncontrolled by high-dosage inhaled corticosteroids/long-acting β2-agonists (ICS/LABA). Patients received benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W; first 3 doses Q4W) or placebo Q4W for 48 weeks. The primary analysis population comprised patients with blood eosinophil counts ≥ 300 cells/µL. This subgroup analysis evaluated Korean patients from this group. RESULTS: Of 122 Korean patients randomized, 86 had blood eosinophil counts ≥ 300 cells/µL. Benralizumab reduced the annual asthma exacerbation rate by 70% (Q4W: rate estimate 0.79, rate ratio 0.30 [95% confidence interval {CI}, 0.13–0.65], nominal P = 0.003; n = 28) and 85% (Q8W: rate estimate 0.40, rate ratio 0.15 [95% CI, 0.06–0.36], nominal P < 0.001; n = 30) vs. placebo (rate estimate 2.67, n = 28). Prebronchodilator forced expiratory volume in 1 second was increased with benralizumab treatment by 0.270 L (Q4W: 95% CI, 0.039–0.500, nominal P = 0.023; n = 28) and 0.362 L (Q8W: 95% CI, 0.143–0.582, nominal P = 0.002; n = 30) vs. placebo (n = 27). Total asthma symptom score was similar for patients receiving either benralizumab Q4W (−0.27 [95% CI, −0.83 to 0.30], nominal P = 0.356; n = 27) or benralizumab Q8W (0.10 [95% CI, −0.44 to 0.65], nominal P = 0.708; n = 30) vs. placebo (n = 28). Drug-related adverse events were experienced by 2%, 8%, and 5% of patients in the placebo, benralizumab Q4W, and benralizumab Q8W arms. CONCLUSIONS: Benralizumab reduced annual asthma exacerbation rates, increased lung function, and was well-tolerated by Korean patients with severe, uncontrolled eosinophilic asthma.

A Case of Type IV Hyperlipoproteinemia with Palmar Xanthoma, Tuberous Xanthoma, and Eruptive Xanthoma / 대한피부과학회지

No abstract available.

An Unusual Clinical Presentation of Elastosis Perforans Serpiginosa / 대한피부과학회지

No abstract available.

A Case of Nevus Lipomatosus Superficialis without External Manifestations / 대한피부과학회지

Nevus lipomatosus superficialis is a rare type of benign hamartomatous skin lesion characterized by the presence of mature adipose tissues in the dermis; it usually manifests as a protruding papule or groups of papules or nodules that have smooth or wrinkled surfaces. We report a case of nevus lipomatosus superficialis without external manifestations in a 49-year-old woman.

Arytenoid cartilage dislocation after reversed total shoulder replacement surgery in the beach chair position: a case report / 대한마취과학회지

Arytenoid cartilage dislocation is not a common complication, but its delayed diagnosis reduces the therapeutic effect of treatment. A male patient underwent reversed total shoulder replacement surgery in the beach chair position under general anesthesia. The patient experienced postoperative hoarseness, and it was revealed that he had right arytenoid dislocation. Voice restoration was accomplished with closed reduction. We discussed changes in patient position during the operation and how they may contribute to the arytenoid dislocation. Flexion and a slight rotation of the neck during the operation can lead to an increase in intracuff pressure of the endotracheal tube. It is necessary to check neck position and monitor intracuff pressure in patients undergoing operations in the beach chair position. Also, the anesthesiologist should suspect arytenoid dislocation in the case of persistent hoarseness after surgery in the beach chair position.

Influence of Self Esteem, Family Function and Social Support on Wellness of Mothers of Children with Disabilities

PURPOSE: Purpose of this study was to investigate factors influencing wellness, and provide basic data for development of intervention programs to improve wellness in mothers of children with disabilities. METHODS: Participants were 147 mothers of children with disabilities from an elementary school and kindergarten for children with disabilities located in J and C cities in G province. Data were collected from February 24 to April 24, 2015 using questionnaires. RESULTS: Mean scores were 3.24+/-0.38 of 5 for wellness, 2.40+/-0.41 of 4 for self-esteem, and 2.87+/-0.36 of 4 for family function. There were significant differences in wellness according to religion, education, and type of education program for the children. There were positive correlations between self-esteem, family function, social support, and wellness. Factors influencing wellness were selfesteem (beta =.450), family function (beta =.313), type of education program for the children (beta =.140), and religion (beta =.127). These factors explained 42.7% of the variance in wellness. CONCLUSION: Findings show that levels of wellness in these mothers are not sufficient to allow them to care for their children and to maintain their own overall health. Therefore to increase wellness of mothers of children with disabilities, intervention strategies that focus on improving self-esteem and family functioning need to be developed.

A Study on Dietary Habits and Lifestyle of Girls with Precocious Puberty / 대한소아소화기영양학회지

PURPOSE: This study was conducted to analyze the change in the obesity index in girls receiving a gonadotropin-releasing hormone agonist (GnRHa), based on treatment duration, and to aid in nutritional counseling by investigating dietary habits and lifestyle. METHODS: Anthropometric examinations were conducted on 62 girls treated with GnRHa from January 2010 through July 2014. Parents were asked to fill out questionnaires on patient dietary habits and lifestyle. RESULTS: The group taking GnRHa for over 1 year had a higher rate of obesity increase than the group taking GnRHa for less than 1 year, but they had common habits related to obesity, which should be corrected. In addition, 69.2% of the normal weight group taking GnRHa for over 1 year gained weight, and needed more intensive programs, which include physical exercise and nutritional education. Although girls with precocious puberty showed a decrease in the intake of high-calorie foods with nutritional intervention regardless of treatment duration, they still had problems that needed improvement, such as shorter meals and lack of exercise. CONCLUSION: Girls with precocious puberty and their parents should emphasize maintenance of proper body weight, especially when treatment for over 1 year is anticipated. Consistent education in nutrition, ways to increase intensity and duration of physical activity, and the need to slow down mealtimes are important in managing obesity; doctors need to perform regular checkups and provide nutritional counseling.

Usefulness of COPD Assessment Test as valuable predictor of depression in chronic obstructive pulmonary disease / 동물의과학연구지

Chronic obstructive pulmonary disease (COPD) is associated with multiple comorbidities, including depression, which carries a higher risk of exacerbation and hospitalization in patients with stable COPD. A newly developed questionnaire, the COPD Assessment Test (CAT), was developed as an alternative to other complex, time-consuming tools for quantifying the symptom burden of COPD in routine practice. It is possible that the correlation between the CAT and depression scales could be useful for early evaluation and management of depression in COPD patients. Thus, we investigated the relationship between the CAT and depression as measured by the Patient Health Questionnaires-9 (PHQ- 9). We performed a retrospective observational COPD cohort study. A total of 97 patients were enrolled. The Korean versions of the CAT and PHQ-9 were completed for stable patients. A correlation analysis was performed between the PHQ-9 and CAT scores. Significant depression among the groups based on the 2011 GOLD guidelines occurred only in class Gold B and D patients (40% and 60%, respectively). The frequency of depression was significantly higher in the group with higher CAT scores (20~29 versus > or =30; odds ratio: 5.67 versus 22.66). Significant association was observed between the PHQ-9 and CAT scores (r=0.545 and P<0.001). As a result, the PHQ-9 score was significantly higher in COPD patients with a higher CAT score. The CAT is a simple and valuable predictor of depression in COPD patients, and it should be frequently used to detect COPD patients with depression in clinical practice.

Seasonal and regional variations in the causes of anaphylaxis in Korean adults

PURPOSE: To investigate whether causes of anaphylaxis vary according to regions and seasons in Korean adults. METHODS: Based on previous retrospective studies of anaphylaxis between 2007 and 2011 at the 15 university hospitals. Regions were classified into 4 groups: region I, Seoul; region II, Gyeonggi; region III, Chungcheong; and region IV, Chonnam and Busan. The cases induced by 5 major allergens including drugs, food, bee sting, radiocontrast media, and exercise, were analyzed in the present study. RESULTS: Among a total of 1,661 cases reported (53% male, 45.9+/-16.0 years), 367 (22.2%), 706 (42.5%), 319 (19.2%), and 269 cases (16.2%) were enrolled in regions I, II, III, and IV, respectively. Of the 5 major allergens, drugs (37.3%) were the most frequently reported, followed by food (25.7%), bee sting (17.9%), radiocontrast media (12.9%), and exercise (6.2%). There was no significant difference in the total occurrence of anaphylaxis in 4 seasons (374 in spring, 460 in summer, 460 in autumn, and 367 in winter). Multiple logistic regression analysis revealed that drug-induced anaphylaxis was significantly associated with the winter season (odds ratio [OR] 1.0 vs. OR 0.597, P<0.05 for spring; OR 1.0 vs. OR 0.481, P<0.01 for summer; OR 1.0 vs. OR 0.653, P<0.05 for autumn). Food-associated anaphylaxis was mainly reported in region I, whereas the frequency of insect sting was relatively higher in regions II, III, and IV than in region I. Older age and female gender were significantly associated with drug-induced anaphylaxis. CONCLUSION: Specific causative allergens of anaphylaxis in adults may vary according to age, gender, region, and season in Korea.

Predictors of the Severity and Serious Outcomes of Anaphylaxis in Korean Adults: A Multicenter Retrospective Case Study

PURPOSE: Differences in definitions of the condition, relevant triggers, and the geographical locations of study centers, cause estimates of the prevalence of anaphylaxis to vary. Recent epidemiological data indicate that the incidence of anaphylaxis is rising. METHODS: To investigate the causes and clinical features of anaphylaxis in Korean adults, factors associated with the severity of the condition, and serious outcomes, a retrospective medical record review was performed on adult patients diagnosed with anaphylaxis between 2007 and 2011 in 15 University Hospitals of South Korea. RESULTS: A total of 1,806 cases (52% male, age 16-86 years) were reported. Cutaneous symptoms (84.0%), combined with respiratory (53.9%) and/or cardiovascular (55.4%) symptoms, were the most frequent presentations. Using a recognized grading system, 1,776 cases could be classified as either mild, 340; moderate, 690; or severe, 746. Although eliciting factors varied significantly by age, gender, and regional and seasonal factors, drugs (46.5%; including nonsteroidal anti-inflammatory drugs, antibiotics, and radiocontrast media) were the most common cause of anaphylaxis, followed by foods (24.2%), insect stings (16.4%), exercise (5.9%), and unknown etiology (7.0%). All of age, multi-organ involvement, a history of allergic disease, and drug-induced anaphylaxis, were significant predictors of serious outcomes requiring hospital admission or prolongation of hospital stay. Epinephrine auto-injectors were prescribed for 7.4% of reported cases. CONCLUSIONS: The principal causes of anaphylaxis in Korean adults were drugs, food, and insect stings. Drug-associated anaphylaxis, a history of allergic disease, multi-organ involvement, and older age, were identified as predictors of serious outcomes.

A Case of Epithelioid Blue Nevus without Carney Complex / 대한피부과학회지

Epithelioid blue nevus is a rare variant of blue nevus that was first described in patients with Carney complex, a familial lentiginosis and multiorgan neoplasm (spotty cutaneous pigmentation, cutaneous/cardiac/mammary myxomas, endocrine overactivity, and psammomatous melanotic schwannomas). Epithelioid blue nevus is an intradermal melanocytic nevus composed of heavily pigmented globular and polygonal cells and lightly pigmented spindle and dendritic cells. Recently, cases of epithelioid blue nevi have been reported in patients without Carney complex. Herein, we describe a child who developed epithelioid blue nevus on her right foot without Carney complex symptoms and review the relevant literature.

Eosinophilic Pleuritis due to Sparganum: A Case Report

Sparganosis is a rare parasitic disease caused by migrating plerocercoid tapeworm larva of the genus Spirometra. Infection in humans is mainly caused by the ingestion of raw or inadequately cooked flesh of infected frogs, snakes, and chickens. Here, we report a rare case of a 45-year-old man who was admitted to our hospital with left lower chest pain. The chest radiograph and computed tomography (CT) scan revealed localized pleural effusion in the left lower lobe; further, peripheral blood eosinophilia and eosinophilic pleural effusion were present. Percutaneous catheter drainage was performed, which revealed long worm-shaped material that was identified as a sparganum by DNA sequencing. The patient showed clinical improvement after drainage of the sparganum. This study demonstrates the importance of considering parasitic diseases in the differential diagnosis of eosinophilic pleural effusion.

Occupational asthma induced by beat-galactosidase

Galactosidase is generated from Aspergillus oryzae, which is widely used for antidiarrhea medicine to infants. Antibiotics and digestives were reported as a causative allergen inducing occupational asthma. Galatosidase-induced occupational asthma has not been reported yet. A forty-year-old female has suffered from rhinorrhea, sneezing, and nasal obstruction 1 year after handling galactosidase at obstetric and pediatric hospital, and then dyspnea appeared later. Skin prick test with inhalent allergens, beta-galactosidase, and Aspergillus oryzae showed strong positive reaction to beta-galactosidase only. Immunoinhibition test with beta-galactosidase and A. oryzae revealed inhibition to beta-galactosidase only. Bronchial provocation test with beta-galactosidase showed the dual asthmatic response. With these results, we confirmed that the patient has beta-galactosidase-induced occupational asthma and rhinitis.

Anaphylaxis induced by lysozyme in Green cough

Lysozyme is a small protein composed of 129 amino acids with a molecular weight of 14.3 kD. In human, it is in the eye drop, saliva, nasal secretion, and gastric juice. Because of its bactericidal properties, this protein is used as an additive in various food and drug products. A 34-year-old female patient had visited at emergency room for generalized urticaria, angioedema, and dyspnea a few minutes after taking Green cough capsule which contains lysozyme. Her serum tryptase level measured by florescence enzyme immunoassay was 11 mg/mL. Skin prick tests with Green cough itself, and then with its 10 ingredients including lysozyme chloride showed strong positive reaction to Green cough and lysozyme chloride. Base on her symptoms and the results obtained from high level of serum trypase and skin prick tests, we have concluded her conditions to be an anaphylaxis induced by lysozyme.

Polymorphisms of ATF6B Are Potentially Associated With FEV1 Decline by Aspirin Provocation in Asthmatics

PURPOSE: Endoplasmic reticulum (ER) stress has recently been observed to activate NF-kappaB and induce inflammatory responses such as asthma. Activating transcription factor 6beta (ATF6B) is known to regulate ATFalpha-mediated ER stress response. The aim of this study is to investigate the associations of ATF6B genetic variants with aspirin-exacerbated respiratory disease (AERD) and its major phenotype, % decline of FEV1 by aspirin provocation. METHODS: Four common single nucleotide polymorphisms (SNPs) of ATF6B were genotyped and statistically analyzed in 93 AERD patients and 96 aspirin-tolerant asthma (ATA) as controls. RESULTS: Logistic analysis revealed that 2 SNPs (rs2228628 and rs8111, P=0.008; corrected P=0.03) and 1 haplotype (ATF6B-ht4, P=0.005; corrected P=0.02) were significantly associated with % decline of FEV1 by aspirin provocation, whereas ATF6B polymorphisms and haplotypes were not associated with the risk of AERD. CONCLUSIONS: Although further functional and replication studies are needed, our preliminary findings suggest that ATF6B may be related to obstructive phenotypes in response to aspirin exposure in adult asthmatics.

A Study of a Patient with Hypereosinophilic Syndrome Presenting with Generalized Cutaneous Blisters / 대한피부과학회지

Hypereosinophilic syndrome is a multisystem disorder with unexplained persistent eosinophilia and marked preference for systemic organ involvement. More than half of all patients have cutaneous involvement, usually presenting as angioedema, urticarial lesions, and eczematous, pruriginous papules. Hypereosinophilic syndrome presenting with generalized cutaneous blisters is rare, and we report the findings of a patient who was successfully treated with interferon-alpha.

A Case of Lichen Amyloidosis on the Auricular Concha and a Review of the Literature / 대한피부과학회지

Lichen amyloidosis is composed of firm, yellowish to brownish papules, usually found on the pretibial area. Amyloidosis of the auricular concha is a rare variant of primary cutaneous amyloidosis, presenting papules or plaques localized to the ear. Histopathologically, it is characterized by hyperkeratosis, acanthosis and deposition of eosinophilic materials in the papillary dermis similar to the presentation of lichen amyloidosis. Herein, We report a case of lichen amyloidosis occurring on the auricular concha of a 48-year-old Korean woman, presented with a 3-years history of asymptomatic monomorphous papules on her both ears.

Association Analysis Between FILIP1 Polymorphisms and Aspirin Hypersensitivity in Korean Asthmatics

PURPOSE: Aspirin exacerbated respiratory disease (AERD) results in a severe asthma attack after aspirin ingestion in asthmatics. The filamin A interacting protein 1 (FILIP1) may play a crucial role in AERD pathogenesis by mediating T cell activation and membrane rearrangement. We investigated the association of FILIP1 variations with AERD and the fall rate of forced expiratory volume in one second (FEV1). METHODS: A total of 34 common FILIP1 single nucleotide polymorphisms (SNPs) were genotyped in 592 Korean asthmatic subjects that included 163 AERD patients and 429 aspirin-tolerant asthma (ATA) controls. RESULTS: This study found that 5 SNPs (P=0.006-0.01) and 2 haplotypes (P=0.01-0.03) of FILIP1 showed nominal signals; however, corrections for the multiple testing revealed no significant associations with the development of AERD (P corr>0.05). In addition, association analysis of the genetic variants with the fall rate of FEV1, an important diagnostic marker of AERD, revealed no significant evidence (P corr>0.05). CONCLUSIONS: Although further replications and functional evaluations are needed, our preliminary findings suggest that genetic variants of FILIP1 might be not associated with the onset of AERD.