Summary Background There has been no large-scale and comprehensive study of the differences between asthma in elderly asthmatics (EA) and non-elderly (i.e. young) asthmatics (NEA). Methods We ...performed principal component analysis (PCA) using 2067 asthmatics (434 EA and 1633 NEA) from the Korean Cohort for Reality and Evolution of adult Asthma (COREA). EA was defined as asthmatics with the chronological age of 65 or more and eleven clinical variables measured at enrollment were used for PCA; symptom score, symptom duration, number of exacerbation during previous one year, smoking pack year, number of controller medications, body mass index, predicted % of FEV1 , predicted % FVC, post-bronchodilator FEV1 /FVC ratio, atopy index and number of eosinophils in peripheral blood. Results PCA of all asthmatics showed that EA and NEA were distinctly separated by the first and second principal component on the plot of individual asthmatics according to their scores. For further analysis, we divided all asthmatics into the EA and the NEA group and performed PCA again in each group. The first four principal components with eigenvalues ≥ 1.0 were identified in both groups and they explained 55.5% of the variance in the EA group and 52.4% in the NEA group respectively. Clinical variables showed distinctly different patterns of loading on the first four principal components between the EA and the NEA group. Conclusion EA and NEA have different compositional patterns underlying their clinical variables. These observations helped in understanding the differences between EA and NEA from the integrated view covering various clinical aspects.
The management of recalcitrant atopic dermatitis (AD) is a challenging issue for both clinicians and patients. In this study, we evaluate the clinical efficacy and safety of double‐filtration ...plasmapheresis (DFPP) in patients with recalcitrant AD. Eighteen patients with recalcitrant AD whose clinical condition had not been effectively controlled by current standard medical therapies were treated by either a single course of DFPP (N = 9) or with standard medical therapies only (N = 9). Clinical severity of AD was measured at baseline and at 1 and 4 weeks after treatment in patients in the DFPP group and at the corresponding time points in the control group using the standardized clinical severity scoring system for atopic dermatitis (SCORAD). In the nine patients who underwent DFPP, SCORAD values significantly decreased from 80.6 ± 16.7 (mean ± SD) at baseline to 65.9 ± 20.1 at 1 week and 69.8 ± 20.4 at 4 weeks after DFPP treatment (Wilcoxon signed‐rank test, P < 0.05). No significant side‐effects were observed during DFPP treatment. In the nine patients with recalcitrant AD who were treated with standard medical therapies, there were no significant differences between the SCORAD values at baseline (70.6 ± 13.9), 1 week (68.0 ± 14.4), and 4 weeks (69.8 ± 17.7) (P > 0.05). DFPP resulted in significant clinical improvements in patients with recalcitrant AD. Further studies are needed to evaluate the long‐term clinical usefulness of DFPP in the treatment of patients with recalcitrant AD.
Allergen immunotherapy is regarded as the only disease-modifying treatment option for various allergic conditions, including allergic rhinitis and asthma. Among the routes of administration of ...allergens, sublingual immunotherapy (SLIT) has gained clinical interest recently, and the prescription of SLIT is increasing among patients with allergies. After 30 years of SLIT use, numerous pieces of evidence supporting its efficacy, safety, and mechanism allows SLIT to be considered as an alternative option to subcutaneous immunotherapy. Based on the progressive development of SLIT, the current guideline from the Korean Academy of Asthma, Allergy, and Clinical Immunology aims to provide an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. This guideline addresses the use of SLIT, including 1) mechanisms of action, 2) appropriate patient selection for SLIT, 3) the currently available SLIT products in Korea, and 4) updated information on its efficacy and safety. This guideline will facilitate a better understanding of practical considerations for SLIT.
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.
This report evaluated long-term changes in clinical severity and laboratory parameters in 3 adult patients with severe recalcitrant atopic dermatitis (AD) who were treated with intramuscular ...injections of 50 mg of autologous immunoglobulin G (IgG) twice a week for 4 weeks (autologous immunoglobulin therapy, AIGT) and followed up for more than 2 years after the treatment. We observed the following 4 major findings in these 3 patients during the long-term follow-up after AIGT. (1) Two of the 3 patients showed a long-term clinical improvement for more than 36 weeks after AIGT with a maximum decrease in clinical severity score greater than 80% from baseline. (2) These 2 patients also showed long-term decreases in serum total IgE concentrations and peripheral blood eosinophil count for more than 36 weeks after AIGT with a maximum decrease in the two laboratory parameters of allergic inflammatory greater than 70% from baseline. (3) No significant side effect was observed during the 2 years of follow-up period after the AIGT in all 3 patients. (4) Serum levels of IgG anti-idiotype antibodies to the F(ab')₂ fragment of autologous IgG administered for the treatment were not significantly changed after AIGT in all 3 patients. These findings suggest that AIGT has long-term favorable effects on both clinical severity and laboratory parameters in selected patients with severe recalcitrant AD. Further studies are required to evaluate the clinical usefulness and therapeutic mechanism of AIGT for AD.
Aggregation of high-affinity receptors for immunoglobulin E (FcϵRI) on the surface of mast cells results in degranulation, a response that is potentiated by binding of stem cell factor (SCF) to its ...receptor Kit. We observed that one of the major initial signaling events associated with FcϵRI-mediated activation of human mast cells (HuMCs) is the rapid tyrosine phosphorylation of a protein of 25 to 30 kDa. The phosphorylation of this protein was also observed in response to SCF. This protein was identified as non–T-cell activation linker (NTAL), an adaptor molecule similar to linker for activated T cells (LAT). Unlike the FcϵRI response, SCF induced NTAL phosphorylation in the absence of detectable LAT phosphorylation. When SCF and antigen were added concurrently, there was a marked synergistic effect on NTAL phosphorylation, however, SCF did not enhance the phosphorylation of LAT induced by FcϵRI aggregation. FcϵRI- and SCF-mediated NTAL phosphorylation appear to be differentially regulated by Src kinases and/or Kit kinase, respectively. Diminution of NTAL expression by silencing RNA oligonucleotides in HuMCs resulted in a reduction of both Kit- and FcϵRI-mediated degranulation. NTAL, thus, appears to be an important link between the signaling pathways that are initiated by these receptors, culminating in mast cell degranulation.
The clinical efficacy of subcutaneous allergen immunotherapy (SCIT) for the treatment of patients with severe atopic dermatitis (AD) using house dust mite (HDM) extract has been reported. Cyclosporin ...has been regarded as an effective medication for treatment of severe AD. In this study, we investigated a clinical usefulness of combined treatment with SCIT and cyclosporin in patients with severe AD.
Nine patients with severe AD and hypersensitivity to HDM were treated with a combination of SCIT using HDM extract and cyclosporin for 12 months. The primary efficacy outcome was the change in the standardized clinical severity scoring system for AD (SCORAD) values, measured at 6 and 12 months, in comparison with the values at baseline. Daily dose of cyclosporin was decreased or discontinued according to the degrees of clinical improvements in individual patients.
In 8 patients who completed 12 months of treatment, the SCORAD values significantly decreased from 71.5 ± 15.5 (mean ± SD) at baseline to 20.4 ± 14.6 at 6 months and 26.3 ± 13.6 at 12 months (Wilcoxon signed-rank test, p=0.01), and no significant systemic side effects were observed. Cyclosporin was discontinued in 4 of 8 patients within 8 months after starting the combined treatment.
In this study, combined treatment with SCIT and cyclosporin resulted in significant clinical improvements in patients with severe AD. Further studies are needed to test the clinical usefulness of this combined treatment for patients with severe AD.
Abstract Autoantibodies against double-stranded DNA (dsDNA) are found in the serum of systemic lupus erythematosus (SLE) patients. However, the mechanism by which anti-dsDNA antibodies (Abs) ...contribute to the pathogenesis of SLE is not yet fully understood. In this study, we investigated four anti-dsDNA mouse monoclonal autoantibodies that share positively charged amino acids (including arginines) in their complementarity determining regions for their ability to penetrate RAW264.7 macrophage cells, activate NF-κB and stimulate TNF-α production. All four antibodies penetrated into macrophage cells and increased the level of extracellular TNF-α; two also activated NF-κB. The fact that two of four cell-penetrating anti-dsDNA mAbs induced both NF-κB activation and TNF-α production in macrophages suggests that at least some autoantibodies against dsDNA may play a role in the pathogenesis of SLE by penetrating into macrophage cells and nuclei, and subsequently inducing the pro-inflammatory cytokine, TNF-α, by binding to the NF-κB gene and stimulating its transcriptional activity.
Allergen immunotherapy (AIT) has been used as a curative and specific treatment of allergic diseases. However, no data on the prescription patterns of AIT in Korea is available. Therefore, we ...surveyed the prescription patterns of AIT by allergy specialists in Korea.
We emailed a questionnaire on AIT prescription patterns to the 690 members of the Korean Academy of Asthma, Allergy and Clinical Immunology with clinical practice experience. All returned answers were evaluated.
The response rate was 21.0%. Only 69.0% of the respondents performed AIT in practice. Hindrance factors for performing AIT in the practice included a lack of facilities (21%), lack of practical experience during their subspecialty or postgraduate educational training programs (15.8%), no need for AIT because of sufficient pharmacotherapy (14.5%), insufficient economic profits (14.5%), and risks for adverse reactions (13.2%). Ninety-two allergy specialists (82%) performed AIT subcutaneously subcutaneous immunotherapy (SCIT) and 20 allergy specialists (18%) performed it sublingually sublingual immunotherapy (SLIT). Only 8 specialists performed both SCIT and SLIT. The allergens used for SCIT were house dust mites (98.9%), pollens (72.8%), and animal dander (23.9%). SLIT was prescribed only for house dust mites. Twenty-eight physicians (30.4%) observed anaphylactic reactions during SCIT. Eight physicians (40.0%) who prescribed SLIT observed adverse reactions, including local reactions, but none of them observed anaphylactic reactions.
In this survey, 69.0% of the respondents performed AIT in clinical practice. SCIT prescription is more popular than SLIT. The Lack of facilities and clinical education is a critical barrier to performing AIT. Therefore, proper clinical education of AIT is necessary for Korean allergists.
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