Combined IgE neutralization and Bifidobacterium longum supplementation reduces the allergic response in models of food allergy.

IgE is central to the development of allergic diseases, and its neutralization alleviates allergic symptoms. However, most of these antibodies are based on IgG1, which is associated with an increased risk of fragment crystallizable-mediated side effects. Moreover, omalizumab, an anti-IgE antibody approved for therapeutic use, has limited benefits for patients with high IgE levels. Here, we assess a fusion protein with extracellular domain of high affinity IgE receptor, FcεRIα, linked to a IgD/IgG4 hybrid Fc domain we term IgETRAP, to reduce the risk of IgG1 Fc-mediated side effects. IgETRAP shows enhanced IgE binding affinity compared to omalizumab. We also see an enhanced therapeutic effect of IgETRAP in food allergy models when combined with Bifidobacterium longum, which results in mast cell number and free IgE levels. The combination of IgETRAP and B. longum may therefore represent a potent treatment for allergic patients with high IgE levels.

Emerging Hop Japanese Pollinosis in Asia.

Hop Japanese (Hop J) pollen has been considered one of the major causative pollen allergens in Far East Asia in the autumn season. The sensitization rate, pollen count, and allergenicity of Hop J pollens are increasing in this region because of increased air pollution and global warming. However, commercial skin test agents for the diagnosis and allergen extracts for the allergen immunotherapy are not available. This review summarizes recent data on clinical impact of Hop J pollinosis in order to facilitate the development of diagnostic and therapeutic agents for this region.

Cancer development in patients with COPD: a retrospective analysis of the National Health Insurance Service-National Sample Cohort in Korea.

BACKGROUND: COPD is a well-known risk factor for lung cancer, independent of smoking behavior. By investigating the retrospective National Health Insurance Service-National Sample Cohort (NHIS-NSC) in Korea, this study attempted to prove the hypothesis that COPD is a risk factor for major cancers developing outside of the lungs. We also aimed to investigate the environmental factors associated with the development of lung cancer in COPD patients. METHODS: This study analyzed data from the NHIS-NSC over a 12-year period. Among the 514,795 subjects in the NHIS-NSC, 16,757 patients who were diagnosed with any cancer from 2002 to 2003 were excluded. This cohort enrolled six arms consisting of never-smokers without COPD (N = 313,553), former smokers without COPD (N = 41,359), smokers without COPD (N = 112,627), never-smokers with COPD (N = 7789), former smokers with COPD (N = 1085), and smokers with COPD (N = 2677). RESULTS: Incident rate of lung cancer per 100,000 person-year was higher according to smoking and COPD (216 in non-COPD and 757 in COPD among never-smokers, 271 in non-COPD and 1266 in COPD among former smokers, 394 in non-COPD and 1560 in COPD among smokers, p <  0.01). Old age, male sex, lower BMI, low exercise level, history of diabetes mellitus, smoking, and COPD were independent factors associated with the development of lung cancer (p <  0.01). Multi-variable analyses showed that COPD, regardless of smoking status, contributed to the development of lung cancer, and colorectal cancer and liver cancer among other major cancers (p <  0.01). CONCLUSION: Our data suggested that COPD was an independent risk factor for the development of lung cancer, and colorectal cancer and liver cancer among other major cancers in the Korean population, regardless of smoking status.

Clinical Manifestations and Risk Factors of Anaphylaxis in Pollen-Food Allergy Syndrome.

PURPOSE: Many studies have reported that pollen-food allergy syndrome (PFAS) can cause anaphylaxis. No comprehensive investigations into anaphylaxis in PFAS have been conducted, however. In this study, we investigated the clinical manifestations and risk factors for anaphylaxis in PFAS in Korean patients with pollinosis. MATERIALS AND METHODS: Data were obtained from a nationwide cross-sectional study that previously reported on PFAS in Korean patients with pollinosis. Data from 273 patients with PFAS were collected, including demographics, list of culprit fruits and vegetables, and clinical manifestations of food allergy. We analyzed 27 anaphylaxis patients and compared them with patients with PFAS with oropharyngeal symptoms only (n=130). RESULTS: The most common cause of anaphylaxis in PFAS was peanut (33.3%), apple (22.2%), walnut (22.2%), pine nut (18.5%), peach (14.8%), and ginseng (14.8%). Anaphylaxis was significantly associated with the strength of sensitization to alder, hazel, willow, poplar, timothy, and ragweed (p<0.05, respectively). Multivariable analysis revealed that the presence of atopic dermatitis [odds ratio (OR), 3.58; 95% confidence interval (CI), 1.25-10.23; p=0.017]; sensitization to hazel (OR, 5.27; 95% CI, 1.79-15.53; p=0.003), timothy (OR, 11.8; 95% CI, 2.70-51.64; p=0.001), or ragweed (OR, 3.18; 95% CI, 1.03-9.87; p=0.045); and the number of culprit foods (OR, 1.25; 95% CI, 1.15-1.37; p<0.001) were related to the development of anaphylaxis in PFAS. CONCLUSION: The most common culprit foods causing anaphylaxis in PFAS were peanut and apple. The presence of atopic dermatitis; sensitization to hazel, timothy, or ragweed; and a greater number of culprit foods were risk factors for anaphylaxis in PFAS.

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.

Predictors of Asthma Control by Stepwise Treatment in Elderly Asthmatic Patients.

The geriatric population is increasing, and asthma severity increases with age. We determined the predictors of asthma control, exacerbation, and the factors that affect asthma-specific quality of life (A-QOL) in elderly asthmatic patients. This was a prospective, multicenter, real-life study for 6 months with stepwise pharmacologic treatment based on the Global Initiative for Asthma (GINA) guideline. A total of 296 asthmatic patients aged ≥ 60 yr were recruited from 5 university centers in Korea. The improved-asthma control group was defined as the group of patients who maintained well-controlled or improved disease and the not-improved asthma control group was defined as the remaining patients. Fewer number of medications for comorbidities (2.8 ± 3.3 in the improved vs. 4.5 ± 4.4 in the control) and higher physical functioning (PF) scale (89.8 ± 14.2 in the improved vs. 82.0 ± 16.4 in the control) were significant predictors in the improved-asthma control group (OR = 0.863, P = 0.004 and OR = 1.028, P = 0.018, respectively). An asthma control test (ACT) score of ≤ 19 at baseline was a significant predictor of asthma exacerbation (OR = 3.938, P = 0.048). Asthma duration (F = 5.656, P = 0.018), ACT score (F = 12.237, P = 0.001) at baseline, and the presence of asthma exacerbation (F = 5.565, P = 0.019) were significant determinants of changes in A-QOL. The number of medications for comorbidities and performance status determined by the PF scale may be important parameters for assessing asthma control in elderly asthmatic patients.

Paradoxical increase of IgE binding components during allergen-specific immunotherapy in pollinosis patients.

Allergen-specific immunotherapy (SIT) reduces allergen specific IgE (sIgE) levels and achieves clinical and immunological tolerance by modulating innate and adaptive immunological responses. Increased temperature and CO2 concentrations caused by climate changes contribute to an increase of pollen count and allergenicity that influences clinical SIT outcomes. In this study, we investigated the changes of IgE binding components to tree and weed pollens in pollinosis patients who showed a paradoxical increase of serum sIgE level during pollen-SIT. We enrolled nine patients who showed an increasing pattern of serum sIgE level to alder, birch, ragweed and mugwort pollens by enzyme-linked immunosorbant assay. IgE immunoblot analysis confirmed the intensification or new generation of major IgE binding components that could be induced by climate change. The findings suggest that the regular monitoring of sIgE levels and symptom changes is required to improve the clinical outcomes of SIT in patients undergoing SIT for tree and weed pollens.

Impact of meteorological variation on hospital visits of patients with tree pollen allergy.

BACKGROUND: Climate change could affect allergic diseases, especially due to pollen. However, there has been no epidemiologic study to demonstrate the relationship between meteorological factors, pollen, and allergic patients. We aimed to investigate the association between meteorological variations and hospital visits of patients with tree pollen allergy. METHODS: The study subjects were adult patients who received skin prick tests between April and July from 1999 to 2008. We reviewed the medical records for the test results of 4,715 patients. Patients with tree pollen allergy were defined as those sensitized to more than 1 of 12 tree pollen allergens. We used monthly means of airborne tree pollen counts and meteorological factors: maximum/average/minimum temperature, relative humidity, and precipitation. We analyzed the correlations between meteorological variations, tree pollen counts, and the patient numbers. Multivariable logistic regression analyses were used to investigate the associations between meteorological factors and hospital visits of patients. RESULTS: The minimum temperature in March was significantly and positively correlated with tree pollen counts in March/April and patient numbers from April through July. Pollen counts in March/April were also correlated with patient numbers from April through July. After adjusting for confounders, including air pollutants, there was a positive association between the minimum temperature in March and hospital visits of patients with tree pollen allergy from April to July(odds ratio, 1.14; 95% CI 1.03 to 1.25). CONCLUSIONS: Higher temperatures could increase tree pollen counts, affecting the symptoms of patients with tree pollen allergy, thereby increasing the number of patients visiting hospitals.

Current status of Oriental medicine in treating Korean allergy patients.

PURPOSE: To evaluate the prevalence, compliance, pattern of use, and economic cost of OM in Korean allergy patients. METHODS: A total of 647 allergy patients were enrolled from 10 general hospitals, and were surveyed by the questionnaire. It consisted of 12 items and regarded the prescription rates, reasons for referring, their opinions for the efficacy of OM, and economic costs. RESULTS: A total of 259 (40.5%) patients had used OM, and 35.5% of these patients experienced two or more kinds of these practices. A patients' income or education level did not affect the prescription rates of OM. Of the patients that used OM, 34.6% of them were satisfied with the effect of OM treatment, and 40.9% of them were inclined to continue with their OM treatments. The most frequent reasons for choosing OM were the patient's belief that OM can predispose 'allergic constitution to normal' (30.2%), worries about the possible adverse reactions of the long-term administration of the proven drugs (20.2%), and the safety of OM (15.6%). However, 18.9% of these patients experienced perceived adverse events to their OM treatment such as skin rashes, gastrointestinal discomfort, and hepatitis. The patients that have used OM spent on average $915 US dollars annually for OM treatment. CONCLUSIONS: Many Korean allergy patients are cliental to OM. Some patients experienced a satisfactory treatment effect from OM, however, others had no treatment effect, even adverse event. Therefore, it is important to educate people to use OM appropriately to make harmony with modern medicine.

Identification of Dioscorea batatas (sanyak) allergen as an inhalant and oral allergen.

Dioscorea batatas is widely used in Asia as a herbal medicine or food product with potential health benefits. There have been several reports of occupational asthma caused by inhalation of D. batatas dust. However, there has been no report of systemic allergic reactions after oral administration of D. batatas. Two patients with D. batatas allergy were enrolled. One had experienced severe urticaria and angioedema after indigestion, and the other had been exposed to D. batatas dust and was diagnosed as having occupational asthma. Both patients had high serum-specific IgE and IgG4 antibodies to D. batatas. And IgE immunoblot demonstrated that both sera bound to a 27-kDa protein with an IgE-binding motif, which was revealed by 2-D-electrophoresis to have the sequence Asn-Val-Glu-Asp-Glu-Phe-Ser-X-Ile- Glu-Gly-Asn-Pro-X-X-Pro-Glu-Asn-X-Gly (pI 6.40, 6.04). In conclusion, discorin from D. batatas (DB3S) was identified as the major allergen of D. batatas in patients sensitized via an oral or inhalant route.

Changes of serum cytokines after the long term immunotherapy with Japanese hop pollen extracts.

Japanese hop (Hop J) pollen has been considered as one of the major causative pollen allergens in the autumn season. We developed a new Hop J immunotherapy extract in collaboration with Allergopharma (Reinbeck, Germany) and investigated immunologic mechanisms during 3 yr immunotherapy. Twenty patients (13 asthma with rhinitis and 7 hay fever) were enrolled from Ajou University Hospital. Sera were collected before, 1 yr, and 3 yr after the immunotherapy. Changes of serum specific IgE, IgG1, and IgG4 levels to Hop J pollen extracts and serum IL-10, IL-12, TGF-beta1 and soluble CD23 levels were monitored by ELISA. Skin reactivity and airway hyper-responsiveness to methacholine were improved during the study period. Specific IgG1 increased at 1 yr then decreased again at 3 yr, and specific IgG4 levels increased progressively (p<0.05, respectively), whereas total and specific IgE levels showed variable responses with no statistical significance. IL-10, TGF-beta1 and soluble CD23 level began to decrease during first year and then further decreased during next two years with statistical significances. (p<0.05, respectively). In conclusion, these findings suggested the favorable effect of long term immunotherapy with Hop J pollen extracts can be explained by lowered IgE affinity and generation of specific IgG4, which may be mediated by IL-10 and TGF-beta1.

Chestnut as a food allergen: identification of major allergens.

To evaluate the clinical significance of chestnut as a food allergen in Korea, skin prick test and ELISA were done in 1,738 patients with respiratory allergies. To identify the IgE binding components, IgE-immunoblotting, 2D IgE-immunoblotting and MALDITOF were performed. To observe the effects of digestive enzymes and a boiling treatment, simulated gastric fluid (SGF) and simulated intestinal fluids (SIF) were incubated with chestnut extracts, and IgE-immunoblotting were then repeated. Skin prick test revealed that 56 (3.2%) patients showed more than 2+ of allergen to histamine ratio to chestnut. Among the 21 IgE binding components, 9 bands were found in more than 50% of the sera tested and the 24 kDa protein had the highest binding intensity. The amino acid sequence of the 24 kDa protein (pI 6.3) had homology with legume protein of oak tree. SGF, SIF and boiling treatment were able to suppress the IgE binding components. In conclusion, chestnut ingestion was shown to induce IgE mediated responses with a 3.2% sensitization rate. Twenty one IgE binding components and one new allergen (the 24 kDa protein) were identified. Digestive enzymes and boiling treatment were able to decrease the allergenic potency.