Serum Levels of Eosinophil-Derived Neurotoxin: A Biomarker for Asthma Severity in Adult Asthmatics

PURPOSE: Eosinophilic inflammation is a key component of severe asthma (SA). However, there has been no reliable serum biomarker for the eosinophilic inflammation of SA. We hypothesized that serum eosinophil-derived neurotoxin (EDN) could predict the eosinophilic inflammation of SA in adult asthmatics. METHODS: Severe asthmatics (n = 235), nonsevere asthmatics (n = 898), and healthy controls (n = 125) were enrolled from Ajou University Hospital, South Korea. The serum levels of EDN and periostin were measured by enzyme-linked immunosorbent assay and compared between severe and nonsevere asthmatics. Their associations with total eosinophil count (TEC) and clinical parameters were evaluated; clinical validation of the K-EDN kit for the measurement of serum EDN was evaluated. RESULTS: Severe asthmatics were older and had longer disease duration with significantly lower levels of forced expiratory volume in 1 second and methacholine PC20 than nonsevere asthmatics. Significant differences were found in TEC or sputum eosinophil count (%) between the groups. The serum levels of EDN and periostin were significantly higher in severe asthmatics than in nonsevere asthmatics and in healthy controls (all P < 0.05). Although significant correlations were found between serum EDN levels measured by the 2 kits (ρ = 0.545, P < 0.0001), higher correlation coefficients between serum EDN levels measured by the K-EDN kit and TEC were higher (ρ = 0.358, P < 0.0001) than those between serum EDN levels measured by the MBL kit and TEC (ρ = 0.319, P < 0.0001) or serum periostin level (ρ = 0.222, P < 0.0001). Multivariate regression analysis demonstrated that serum EDN levels measured by the K-EDN kit predicted the phenotype of SA (P = 0.003), while 2 other biomarkers did not. CONCLUSIONS: The serum EDN level may be a useful biomarker for assessing asthma severity in adult asthmatics.

Familial IgG3 subclass deficiency: A report of two cases

Primary immunodeficiency in adults is thought to be underestimated in Korea. IgG subclass deficiency, defined as a deficiency at least among the 4 subtypes of IgG subclass, IgG1, IgG2, IgG3, and IgG4, results in recurrent infections, in which IgG3 subclass deficiency (IgGSD) is the most commonly found in adult asthmatic patients. Herein, we report 2 cases of familial IgG3SD. In family 1, a female patient aged 17 years with allergic rhinitis (AR) had recurrent upper respiratory infections (URIs), and gastroenteritis. Her mother aged 50 with AR had recurrent URI, otitis media, urinary tract infection, gastroenteritis, and oral ulcer. A younger sister aged 9 years with AR and asthma had recurrent URI almost all the year round. The serum IgA level was found to be lower than the normal level in her mother and the patient, and IgG3 was decreased in the patient and her sister. The IgG3 level of mother showed within the lower normal limit. In family 2, the mother aged 39 years with nonallergic rhinitis had recurrent URI and oral ulcer. Her son aged 16 years and daughter aged 13 years with AR and asthma had recurrent URI, resulting in uncontrolled asthma. Family 2 was found to be IgG3 deficiency in mother and son, and IgA deficiency in son. The IgG3 level of daughter was within the lower normal level. Mother and the first daughter in family 1 as well as mother and son in family 2 was treated with intravenous immunoglobulin, and their recurrent URI reduced. We reported 2 cases of familial IgG3SD.

A Retrospective Study of Clinical Response Predictors in Subcutaneous Allergen Immunotherapy With House Dust Mites for Allergic Rhinitis

PURPOSE: House dust mites (HDM) are major allergens that cause allergic rhinitis (AR). Allergen-specific subcutaneous immunotherapy (SCIT) has been shown to be clinically beneficial in many clinical trials. Such trials, however, are not reflective of all patient populations. The aim of this study was to describe the efficacy and safety of SCIT in routine clinical practice in Korean adults with AR sensitized to HDM. METHODS: We reviewed medical records of 304 patients with AR treated at an allergy clinic of a tertiary hospital using SCIT with aluminum hydroxide-adsorbed allergen extract targeting HDM alone or with pollens for at least 1 year from 2000 to 2012. Patients with asthma were excluded. Rates of remission, defined as no further requirement of maintenance medication, over time were determined by means of life tables and extension of survival analysis. Specific immunoglobulin E (IgE) levels to HDM were categorized into 6 classes. RESULTS: The mean time until achieving remission was 4.9±0.1 years, and the cumulative incidence of remission from AR was 76.6%. Severe AR (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.23-0.69; P=0.001), specific IgE levels to HDM ≥17.5 kU/L (OR, 1.85; 95% CI, 1.01-3.37; P=0.045), and duration of immunotherapy ≥3 years (OR, 7.37; 95% CI, 3.50-15.51; P<0.001) were identified as significant predictors of clinical remission during SCIT for patients with AR sensitized to HDM. Overall, 73 patients (24.0%) experienced adverse reactions to SCIT, and only 1 case of anaphylaxis (0.3%) developed. CONCLUSIONS: SCIT with HDM was found to be effective and safe for patients with AR. Specific IgE levels to HDM and a duration of SCIT ≥3 years may be predictors of clinical responses to SCIT in AR patients.

Therapeutic Effect of Omalizumab in Severe Asthma: A Real-World Study in Korea

PURPOSE: Omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody, has proved to be effective for the treatment of severe asthma. However, there is no direct evidence of effectiveness of omalizumab in Korean patients with severe asthma. We sought to evaluate the real-world effectiveness of omalizumab in Korean adult patients suffering from severe asthma and to identify predictors of favorable response. METHODS: A retrospective analysis of electrical medical records was performed on severe allergic asthmatic patients with omalizumab treatment group (OT group) for more than 6 months between March 2008 and February 2016. Propensity score matching was applied to define the standardized treatment control group (STC group) treated without omalizumab. Asthma-related outcomes were compared between the 2 groups, and analyzed before and after omalizumab use in the OT group. Responders to treatment were defined as patients showing >50% reduction in asthma exacerbations and/or systemic steroid requirement during the outcome period. RESULTS: One hundred twenty-four patients with severe asthma (62 in the OT group; 62 in the STC group) were enrolled in the study. Proportion of patients having the reduction of asthma exacerbation (53.2% vs 35.5%, P=0.015) and the rate of responders (67.7% vs 41.9%, P=0.007) were significantly higher in the OT group than in the STC group. Significant reductions were noted in asthma exacerbation (P=0.006), hospitalization (P=0.009), hospitalization days (P=0.006), systemic corticosteroid requirements (P=0.027), and sputum eosinophil count (P=0.031) in OT group compared with STC group. There were no significant differences in changes of forced expiratory volume in the 1 second (FEV1) levels between the 2 groups. No predictors of responders were found for omalizumab treatment. CONCLUSIONS: Omalizumab can reduce exacerbations/hospitalization/systemic steroid burst in Korean adult patients with severe asthma.

Evaluation of the allergenic relationship between Humulus japonicus and Humulus lupulus pollen allergens

PURPOSE: Humulus japonicus pollen (Hop J) is a major cause of inhalant allergy in autumn of the Far East countries, and its allergenic potency has been increasing with climate changes. Allergen immunotherapy has been considered in Hop J-sensitized allergic patients; however, Hop J allergen extracts for immunotherapy are not commercially available. We speculate that Humulus lupulus pollen (Hop L) belonged to the same genus may share cross-reacting allergens with Hop J and evaluated allergenic relationships between these 2 pollens. METHODS: Thirteen patients with allergic rhinitis and/or asthma sensitive to Hop J pollens were enrolled in Ajou University Hospital, Suwon, Korea. Hop J pollens were collected locally and lyophilized extracts were prepared, while lyophilized Hop L extracts were provided by Lofarma S.p.A. IgE-ELISA/enzyme-linked immunosorbent assay (ELISA) inhibition tests, sodium dodecyl sulphate-polyacrylamide gel electrophoresis and IgE-immunoblot/immunoblot inhibition analysis using sera from the enrolled subjects were performed. RESULTS: All patients had high serum specific IgE to both Hop J and Hop L extracts by ELISA, but no significant correlation was found between these 2 extracts. ELISA inhibition tests showed significant dose-dependent inhibitions on IgE-bindings to Hop L with serial additions of Hop J extracts in a dose-dependent manner, while minimal inhibitions of IgE binding to Hop J were noted with additions of Hop L. IgE-immunoblot analysis demonstrated that the major allergenic component of Hop J at 12 kDa was inhibited by Hop J, while no inhibitions were noted by Hop L extracts on IgE-immunoblot inhibition analysis. CONCLUSION: These findings suggest that there may not be a significant cross-allergenicity between Hop J and Hop L.

Prevalence and Clinical Characteristics of Local Allergic Rhinitis to House Dust Mites

Local allergic rhinitis (LAR) is a localized nasal allergic response in the absence of systemic atopy. The aim of this study was to evaluate the prevalence and clinical characteristics of LAR in Korean rhinitis patients compared to allergic rhinitis (AR) and non-allergic rhinitis (NAR). A total of 304 rhinitis patients were enrolled from November 2014 to March 2016. A skin prick test, serum total and specific immunoglobulin E, and a nasal provocation test (NPT) with house dust mite (HDM) were performed on all patients. Subjects also documented changes in rhinitis symptoms before and after NPT. Seventy-four patients with nasal hyper-reactivity and 80 patients with subclinical allergy were excluded. AR was diagnosed in 69 (46.0%) patients, NAR in 75 (50.0%) patients, and LAR to HDM in 6 (4.0%) patients. The average medication score and disease duration of each group were 14.5 points and 77.6 months in AR, 12.1 point and 51.1 months in NAR, and 17.7 point and 106.0 months in LAR, respectively. There were no significant differences in the baseline nasal symptom score of the three groups. However, after NPT with HDM, the score of rhinitis, itching, and obstructive were 4.83±1.47 vs. 1.95±2.53, 3.00±2.10 vs. 1.45±2.06, and 5.50±1.38 vs. 2.57±2.84 in LAR and NAR, respectively (p<0.05). LAR patients had longer duration of disease and tended to be older and have higher medication score than other rhinitis patients.

Subcutaneous Immunotherapy for Allergic Asthma in a Single Center of Korea: Efficacy, Safety, and Clinical Response Predictors

Allergen-specific immunotherapy is the only causal treatment for allergic diseases. However, the efficacy of immunotherapy may vary around the world due to differences in climate, the nature of aero-allergens and their distribution. The aim of this study was to describe the effects of subcutaneous immunotherapy (SCIT) in Korean adults with allergic asthma (AA). As a retrospective cohort study, we reviewed medical records for 627 patients with AA in Korea who were sensitized to house dust mite (HDM) and/or pollens and who underwent SCIT with aluminum hydroxide adsorbed allergen extract from 2000 to 2012. Rates of remission, defined as no further requirement of maintenance medication, over time were determined by means of life tables and extension of survival analysis. Herein, 627 asthmatic patients achieved remission within a mean of 4.7 ± 0.2 years. The cumulative incidence rates of remission from AA were 86.9% upon treatment with SCIT. Baseline forced expiratory volume in the first second (FEV1) ≥ 80% (hazard ratio [HR], 3.10; 95% confidence interval [CI], 1.79–5.39; P < 0.001), and maintenance of immunotherapy for more than 3 years (HR, 1.82; 95% CI, 1.21–2.72; P = 0.004) were significant predictors of asthma remission during SCIT. In 284 patients on SCIT with HDM alone, initial specific immunoglobulin E (IgE) levels to Dermatophagoides pteronyssinus and Dermatophagoides farinae did not show significant difference between remission and non-remission group after adjusting demographic variables. In conclusion, SCIT was effective and safe treatment modality for patients with AA. Initial FEV1 ≥ 80% and immunotherapy more than 3 years were found to be associated with favorable clinical responses to SCIT.

Photosensitivity caused by dronedarone: A case report

Dronedarone is a new antiarrhythmic drug for the treatment of nonpermanent atrial fibrillation. Compared with amiodarone, it is regarded as a safe medication due to its structural differences. In this report, we describe a 56-year-old man who developed photosensitivity due to dronedarone. He presented with itchy skin rashes for 1 week. Maculopapular exanthema was localized on the neck, both arms, and both hands, with sparing of the other parts of the body. Dronedarone was prescribed 4 weeks ago when atrial fibrillation occurred. After development of skin rashes, dronedarone was discontinued, and systemic steroid, antihistamine, and topical corticosteroid were administered for 1 week, with improvement in skin rashes. The photopatch test was performed with antiarrhythmic drugs, including dronedarone, amiodarone, and flecainide, 4 weeks after withdrawal of dronedarone. Positive reactions were recorded only to dronedarone at the site exposed to ultraviolet A. He was diagnosed with dronedarone-induced photosensitivity and advised to change the antiarrhythmic medication to others. There have been a few case reports on photosensitivity reactions due to dronedarone, which were diagnosed only by clinical suspicion. However, we suspected photosensitivity and proved it by the photopatch test. Photosensitivity should be considered in patients having skin rashes on the exposed area and taking antiarrhythmic medication, including dronedarone.

Factors Predicting Recovery From Asthma Exacerbations

No abstract available.

Sleep quality in rheumatoid arthritis, and its association with disease activity in a Korean population

BACKGROUND/AIMS: The aim of this study was to compare the sleep quality between rheumatoid arthritis (RA) patients and healthy controls; and to evaluate the relationship between RA disease activity and sleep quality in Korea. METHODS: A total of 130 RA patients and 67 age- and sex-matched healthy controls were enrolled in a comparative study of sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Age, gender, concomitant medication, erythrocyte sedimentation rate, serum C-reactive protein, Beck Depression Inventory second edition (BDI-II), 28 joints disease activity score (DAS28), pain visual analog scale (VAS), and PSQI were analyzed as covariates. We also analyzed the sleep quality of RA patients according to the disease activity (DAS28 or = 5.1, respectively). RESULTS: The total PSQI score and the frequency of poor sleep quality, were higher in the RA patients (5.62 +/- 4.19, 38.5%) than in the control subjects (3.57 +/- 2.17, 13.4%). The patients with poor sleep quality (PSQI > 5) were older and had a higher BDI-II and VAS score than the patients without sleep disturbance (PSQI < or = 5). The score in subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, daytime dysfunction, total PSQI, and frequency of poor sleep quality were increased when RA activity was high. CONCLUSIONS: Sleep disturbance was observed in RA patients (38.5%), and high RA disease activity was associated with poor sleep quality in Korea.

Transverse Myelitis in Patient with Behcet's Disease

Behcet's disease (BD) is a multisystem disorder presenting recurrent oral and genital ulcerations as well as ocular lesions, involving the nervous system in a subgroup of patients. BD develops at a young age and is frequently presented with an acute or subacute brainstem syndrome or hemiparesis, as well as with other various neurological manifestations, the syndrome is often included in the differential diagnosis of multiple sclerosis, stroke of the young adult, and other neurological disorders. Transverse myelitis (TM) is a clinical syndrome in which an immune-mediated process causes neural injury to the spinal cord, resulting in varying degrees of weakness, sensory alterations and autonomic dysfunction. Spinal Neuro-behcet's disease is rare case. We reported a 33-year old man who had been treated for BD for 3 years.