Predicting responses to omalizumab in antihistamine-refractory chronic urticaria: A real-world longitudinal study.

Background: Treating chronic urticaria (CU) that is unresponsive to H1-antihistamines (H1AHs) is challenging, and the real-world effectiveness of omalizumab remains unclear. Objective: Our aim was to evaluate the real-world effectiveness of omalizumab, optimal response assessment timing, and predictive factors. Methods: Initially, 5535 patients with CU who were receiving at least 20 mg of loratadine daily for at least 6 months (January 2007-August 2021) were screened. Ultimately, 386 patients who had been receiving omalizumab add-on treatment for >6 months were followed-up for more than 2 years. Predictors of treatment response to omalizumab add-on therapy for patients with antihistamine-refractory CU were identified by using a generalized linear model. Results: In our retrospective cohort, omalizumab treatment showed cumulative response rates of 55.2% at 3 months, 71.0% at 6 months, and 81.4% at 9 months for patients with H1AH-refractory CU. Analysis of longitudinal responses to omalizumab treatment revealed 3 distinct clusters: favorable (cluster 1 [n = 158]), intermediate (cluster 2 [n =1 43]), and poor responses (cluster 3 [n = 85]). Subjects were categorized on the basis of whether they had achieved a complete response within 3 months; 213 early responders, 117 late responders, and 56 nonresponders were identified. The initial dose of omalizumab differed significantly among the 3 clusters. Low total IgE level (<40 kU/L) predicted nonresponse (odds ratio [OR] = 3.10 [P = .018]). Early responders were associated with a higher initial omalizumab dose (≥300 mg) (OR = 2.07 [P = .016]), higher basophil counts (OR = 2.0 [P = .014]), total IgE levels exceeding 798 kU/L (OR = 0.37 [P = .047]), and lower platelet-to-lymphocyte ratio (OR = 0.50 [P = .050]). Conclusion: Real-world data reveal 3 distinct clusters for response to omalizumab treatment; confirm low serum total IgE level (<40 kU/L) as a predictor of nonresponse; and identify potential biomarkers, including IgE level, basophil count, and PLR, for early responders.

The KAAACI Guidelines for Sublingual Immunotherapy.

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.

Mechanism underlying polyvalent IgG-induced regulatory T cell activation and its clinical application: Anti-idiotypic regulatory T cell theory for immune tolerance.

The regulatory T (Treg) cells constitute a functionally defined subpopulation of T cells that modulate the immune system and maintain immune tolerance through suppression of the development of autoimmune responses to self-antigens and allergic reactions to external antigens. Reduction in the number or function of Treg cells has been suggested as a key immune abnormality underlying the development of autoimmune and allergic diseases. In vitro studies have demonstrated that purified polyvalent immunoglobulin G (IgG) from multiple healthy blood donors can exert immunomodulatory effects on Treg cells. Incubation of polyvalent human IgG with purified CD4+CD25high T cells increased the intracellular expression of interleukin (IL)-10. Intravenous administration of polyvalent human IgG induced significant expansions of CD4+ Foxp3+ Treg cells and clinical improvements in patients with autoimmune diseases. In human clinical trials, intramuscular administration of autologous total IgG significantly increased the percentage of IL-10-producing CD4+ Treg cells in the peripheral blood of healthy subjects and provided significant clinical improvements in patients with atopic dermatitis. These results suggest a clinical usefulness of polyvalent IgG-induced activation of Treg cells in human subjects. This review proposes a new hypothesis for immune tolerance mechanism by integrating the pre-existing "idiotypic network theory" and "Treg cell theory" into an "anti-idiotypic Treg cell theory." Based on this hypothesis, an "active anti-idiotypic therapy" for allergic and autoimmune diseases using autologous polyvalent IgG (as immunizing antigens) is suggested as follows: (1) Intramuscular or subcutaneous administration of autologous polyvalent IgG produces numerous immunogenic peptides derived from idiotypes of autologous IgG through processing of dendritic cells, and these peptides activate anti-idiotypic Treg cells in the same subject. (2) Activated anti-idiotypic Treg cells secrete IL-10 and suppress Th2 cell response to allergens and autoimmune T cell response to self-antigens. (3) These events can induce a long-term clinical improvements in patients with allergic and autoimmune diseases. Further studies are needed to evaluate the detailed molecular mechanism underlying polyvalent IgG-induced Treg cell activation and the clinical usefulness of this immunomodulatory therapy for autoimmune and allergic diseases.

KAAACI Guidelines for Allergen Immunotherapy.

Allergen immunotherapy (AIT) is a causative treatment for various allergic diseases such as allergic rhinitis, allergic asthma, and bee venom allergy that induces tolerance to offending allergens. The need for uniform practice guidelines in AIT is continuously growing because of the increasing discovery of potential candidates for AIT and evolving interest in new therapeutic approaches. This guideline is an updated version of the Korean Academy of Asthma Allergy and Clinical Immunology recommendations for AIT published in 2010. This updated guideline proposes an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. The guideline deals with basic knowledge and methodological aspects of AIT, including mechanisms, clinical efficacy, patient selection, allergens extract selection, schedule and doses, management of adverse reactions, efficacy measurements, and special consideration in pediatrics. The guidelines for sublingual immunotherapy will be covered in detail in a separate article.

Regulatory T Cell-Targeted Immunomodulatory Therapy for Long-Term Clinical Improvement of Atopic Dermatitis: Hypotheses and Perspectives.

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disorder characterized by itching and eczematous lesions. It is often associated with a personal or familial history of allergic diseases. Allergic inflammation induced by immunoglobulin E and T-helper type 2 (Th2) cell responses to common environmental agents has been suggested to play an essential role in AD pathogenesis. The standard therapies for AD, including topical or systemic agents, focus on controlling skin inflammation. Recently developed monoclonal antibody to interleukin-4 receptor alpha or Janus kinase inhibitors can provide significant clinical improvements in patients with AD by inhibiting Th2 cell-mediated skin inflammation. However, the clinical efficacy of the Th2 cell-targeted therapy is transient and incomplete in patients with AD. Patients with AD are seeking a permanent cure. Therefore, the development of novel immunomodulatory strategies that can improve a long-term clinical outcome and provide a long-term treatment-free clinical remission of AD (disease-modifying therapy) is needed. Regulatory T (Treg) cells play a critical role in the maintenance of immune tolerance and suppress the development of autoimmune and allergic diseases. This review provides three working hypotheses and perspectives for the treatment of AD by Treg cell activation. (1) A decreased number or function of Treg cells is a critical event that causes the activation of Th2 cells, leading to the development and maintenance of AD. (2) Activation of Treg cells is an effective therapeutic approach for AD. (3) Many different immunomodulatory strategies activating Treg cells can provide a long-term clinical improvement of AD by induction of immune tolerance. The Treg cell-targeted immunomodulatory therapies for AD include allergen immunotherapy, microbiota, vitamin D, polyvalent human immunoglobulin G, monoclonal antibodies to the surface antigens of T cell or antigen-presenting cell, and adoptive transfer of autologous Treg cells or genetically engineered Treg cells expanded in vitro.

Intramuscular Injection of Autologous Serum in Adolescent and Adult Patients with Atopic Dermatitis: A Preliminary Randomized Clinical Trial.

PURPOSE: The favorable clinical efficacies of intramuscular injection of autologous blood in patients with atopic dermatitis (AD) and intramuscular injection of autologous serum in patients with chronic urticaria have been demonstrated by randomized clinical trials. In this study, we assessed the clinical effectiveness and safety of the intramuscular injection of autologous serum in patients with AD. MATERIALS AND METHODS: In this randomized, placebo-controlled, and double-blind trial, 23 adolescent and adult patients with moderate-to-severe AD were enrolled. The patients were randomized to receive eight intramuscular injections of 5 mL of autologous serum (n=11) or saline (n=12) over 4 weeks, and were followed up until week 8. Changes in the clinical severity scores of AD assessed by SCORing Atopic Dermatitis (SCORAD), patient-reported Dermatology Life Quality Index (DLQI) score, and incidence of adverse events were assessed from baseline to week 8. RESULTS: One patient in the treatment group and two patients in the placebo group were lost to follow-up before week 8. The intramuscular administration of autologous serum, compared with saline, decreased the SCORAD clinical severity score (-14.8% vs. 10.7%, p=0.006) and improved the DLQI score (-32.6% vs. 19.5%, p=0.01) from baseline to week 8. Serious adverse events were not observed. CONCLUSION: Intramuscular injection of autologous serum may be effective in treating AD. Further studies are needed to evaluate the clinical usefulness of this intervention for AD (KCT0001969).

Intramuscular administration of autologous total immunoglobulin G induces immunomodulatory effects on T cells in healthy human subjects: An open-labeled prospective single-arm trial.

BACKGROUND: We hypothesized that intramuscular administration of autologous total immunoglobulin G (IgG) could induce an immunomodulatory effect in human subjects. In our previous studies, we showed that intramuscular administration of autologous total IgG could induce significant clinical improvements and increases of the serum levels of interleukin-10 (IL-10) and interferon-gamma (IFN-γ) in patients with atopic dermatitis. OBJECTIVE: To investigate the mechanism of immunomodulation induced by intramuscular administration of autologous total IgG, we evaluated changes in T cells before and after intramuscular administrations of autologous total IgG in this study. METHODS: Thirteen healthy adults received 8 intramuscular injections of 50 mg autologous total IgG for 4 weeks (from week 0 to week 4). The percentages of IL-10- or IFN-γ-producing peripheral blood T cells, as well as serum levels of IL-10, IFN-γ, and immunoglobulins, were measured at baseline (week 0) and at weeks 4, 8, and 12. RESULTS: The percentage of IL-10-producing CD4+ T cells was significantly increased at weeks 8 and 12 compared to baseline (P < .05), while the percentage of IFN-γ-producing CD3+ T cells was significantly increased at week 12 compared to baseline (P < .05). There were no significant differences in the serum levels of IL-10, IFN-γ, and immunoglobulins before and after intramuscular administration of autologous total IgG (P > .05). No serious adverse events were observed. CONCLUSION: Intramuscular administration of autologous total IgG induced immunomodulatory effects on T cells in healthy human subjects. This simple intervention could be a safe, effective, and economical T cell immunomodulation method for human subjects (NCT03695757).

Clusters of Severe Eosinophilic Asthma in a Korean Asthma Cohort.

BACKGROUND: Targeted therapies have broadened the available treatment options for patients with severe eosinophilic asthma (SEA). However, differences in the magnitude of treatment responses among patients indicate the presence of various underlying pathophysiological processes and patient subgroups. OBJECTIVES: We aimed to describe the characteristics of SEA and identify its patient subgroups. METHODS: Clinical data from the Cohort for Reality and Evolution of Adult Asthma in Korea were analyzed. Cluster analysis was performed among those with SEA using 5 variables, namely, prebronchodilator forced expiratory volume in 1 s, body mass index, age at symptom onset, smoking amount, and blood eosinophil counts. RESULTS: Patients with SEA showed prevalent sensitization to aeroallergens, decreased lung function, and poor asthma control status. Cluster analysis revealed 3 distinctive subgroups among patients with SEA. Cluster 1 (n = 177) consisted of patients reporting the lowest blood eosinophils (median, 346.8 cells/µL) and modest severe asthma with preserved lung function during the 12-month treatment period. Cluster 2 (n = 42) predominantly included smoking males with severe persistent airway obstruction and moderate eosinophilia (median, 451.8 cells/µL). Lastly, cluster 3 (n = 95) included patients with the most severe asthma, the highest eosinophil levels (median, 817.5 cells/µL), and good treatment response in terms of improved lung function and control status. CONCLUSIONS: Three subgroups were identified in SEA through the cluster analysis. The distinctive features of each cluster may help physicians predict patients who will respond to biologics with greater magnitude of clinical improvement. Further research regarding the underlying pathophysiology and clinical importance of each subgroup is warranted.

Real Clinical Practice Data of Monthly Dupilumab Therapy in Adult Patients With Moderate-to-Severe Atopic Dermatitis: Clinical Efficacy and Predictive Markers for a Favorable Clinical Response.

PURPOSE: Dupilumab is recommended to be administered biweekly to treat adult patients with moderate-to-severe atopic dermatitis (AD). Real clinical practice data on the clinical efficacy of monthly dupilumab therapy are limited. We analyzed real clinical practice data on the clinical efficacy of monthly dupilumab therapy and predictive markers for favorable clinical responses to the therapy. METHODS: Medical records of 57 adult patients with moderate-to-severe AD who received dupilumab therapy every 4 weeks for 16 weeks were analyzed retrospectively. Eczema Area and Severity Index (EASI) were recorded at baseline and week 16. Clinical responses to monthly dupilumab therapy were defined as the proportion of patients with decreased EASI scores of at least 50% or 75% from baseline at week 16 (EASI-50 or EASI-75). Blood eosinophil counts and serum lactate dehydrogenase (LDH) levels were measured at baseline and week 16. RESULTS: Monthly dupilumab therapy showed EASI-50 and EASI-75 clinical responses in 48 (84.2%) and 27 (47.4%) of 57 patients at week 16, respectively. The percentage decrease in EASI scores from baseline at week 16 was significantly inversely correlated with baseline blood eosinophil count (correlation coefficient [r] = -0.405, P = 0.002) and baseline serum LDH level (r = -0.466, P < 0.001). The EASI-75 response rate was higher in patients with low (< 500/µL, 73.3%) than in those with high (≥ 500/µL, 37.5%) baseline blood eosinophil counts (P = 0.032), and was higher in patients with low (< 400 U/L, 55.6%) than those with high (≥ 400 U/L, 10.0%) baseline serum LDH levels (P = 0.013). CONCLUSIONS: Monthly dupilumab therapy was clinically effective in adult patients with moderate-to-severe AD in real clinical practice. Baseline blood eosinophil count and serum LDH level could be predictive markers for clinical response to dupilumab therapy.

Erratum: Clustering the Clinical Course of Chronic Urticaria Using a Longitudinal Database: Effects on Urticaria Remission.

This corrects the article on p. 390 in vol. 13, PMID: 33733635.

Clustering the Clinical Course of Chronic Urticaria Using a Longitudinal Database: Effects on Urticaria Remission.

PURPOSE: Little is known about the clinical course of chronic urticaria (CU) and predictors of its prognosis. We evaluated CU patient clusters based on medication scores during the initial 3 months of treatment in an attempt to investigate time to remission and relapse rates for CU and to identify predictors for CU remission. METHODS: In total, 4,552 patients (57.9% female; mean age of 38.6 years) with CU were included in this retrospective cohort study. The K-medoids algorithm was used for clustering CU patients. Kaplan-Meier survival analysis with Cox regression was applied to identify predictors of CU remission. RESULTS: Four distinct clusters were identified: patients with consistently low disease activity (cluster 1, n = 1,786), with medium-to-low disease activity (cluster 2, n = 1,031), with consistently medium disease activity (cluster 3, n = 1,332), or with consistently high disease activity (cluster 4, n = 403). Mean age, treatment duration, peripheral neutrophil counts, total immunoglobulin E, and complements levels were significantly higher for cluster 4 than the other 3 clusters. Median times to remission were also different among the 4 clusters (2.1 vs. 3.3 vs. 6.4 vs. 9.4 years, respectively, P < 0.001). Sensitization to house dust mites (HDMs; at least class 3) and female sex were identified as significant predictors of CU remission. Around 20% of patients who achieved CU remission experienced relapse. CONCLUSIONS: In this study, we identified 4 CU patient clusters by analyzing medication scores during the first 3 months of treatment and found that sensitization to HDMs and female sex can affect CU prognosis. The use of immunomodulators was implicated in the risk for CU relapse.

Efficacy, Safety, and Immunomodulatory Effect of the Intramuscular Administration of Autologous Total Immunoglobulin G for Atopic Dermatitis: A Randomized Clinical Trial.

PURPOSE: The management of patients with atopic dermatitis (AD) is often difficult. We hypothesized that repeated intramuscular administration of autologous total immunoglobulin G (IgG) could induce clinical improvement in patients with AD through immune modulation. This clinical trial was conducted to evaluate the efficacy, safety, and immunomodulatory effect of the intramuscular administration of autologous total IgG in patients with AD. METHODS: In this randomized, double-blind, placebo-controlled trial, 51 adolescent and adult patients with moderate-to-severe AD were randomized to receive 8 weekly intramuscular administrations of autologous total IgG 50 mg (n = 26) or saline (n = 25) over a 7-week period and were followed up to week 16. Changes in the clinical severity score (Eczema Area and Severity Index), affected body surface area, patient-reported Dermatology Life Quality Index (DLQI) score, laboratory biomarkers, and incidence of adverse events from baseline to week 16 were assessed. RESULTS: The intramuscular administration of autologous total IgG, compared with saline, decreased the clinical severity score (-64.8% vs. -20.3%, P < 0.001), reduced the affected body surface area (-53.9% vs. -19.1%, P < 0.001), improved the DLQI score (-35.4% vs. -14.4%, P = 0.015), increased serum interleukin-10 and interferon-γ levels (P = 0.011 and P = 0.003, respectively), and reduced the incidence of AD exacerbation (11.5% vs. 48.0%, P = 0.004) from baseline to week 16. No serious adverse events were observed. CONCLUSIONS: The intramuscular administration of autologous total IgG provided clinical improvements and a systemic immunomodulatory effect in adolescent and adult patients with moderate-to-severe AD without significant side effects. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0001597.

Safety of Ultra-rush Schedule of Subcutaneous Allergen Immunotherapy With House Dust Mite Extract Conducted in an Outpatient Clinic in Patients With Atopic Dermatitis and Allergic Rhinitis.

PURPOSE: Ultra-rush schedule of subcutaneous allergen immunotherapy (UR-SCIT) administering maximum maintenance dose of allergen extract within one day can save time and effort for allergen immunotherapy in patients with allergic disease. However, UR-SCIT is associated with an increased risk of systemic reaction (SR) and typically has been conducted in a hospital admission setting. To overcome disadvantages of UR-SCIT, we evaluated the safety of UR-SCIT conducted in an outpatient clinic in patients with atopic dermatitis (AD) and allergic rhinitis (AR). METHODS: UR-SCIT was performed in 538 patients with AD and/or AR sensitized to house dust mite (HDM). A maximum maintenance dose of tyrosine-adsorbed HDM extract (1 mL of maintenance concentration) was divided into 4 increasing doses (0.1, 0.2, 0.3, and 0.4 mL) and administered to the patients by subcutaneous injection at 2-hour intervals for 8 hours in an outpatient clinic. SRs associated with UR-SCIT were classified according to the World Allergy Organization grading system. RESULTS: SR was observed in 12 of 538 patients (2.2%) with AD and/or AR during UR-SCIT. The severity grades of the observed SRs were mild-to-moderate (grade 1 in 7 patients, grade 2 in 4 patients, and grade 3 in 1 patient). The scheduled 4 increasing doses of HDM extract could be administered in 535 of 538 patients (99.4%) except 3 patients who experienced SR before administration of the last scheduled dose. SR was observed within 2 hours in 11 patients after administration of the scheduled doses of HDM extract except one patient who experienced a grade 2 SR at 5.5 hours after administration of the last scheduled dose. CONCLUSIONS: UR-SCIT with tyrosine-adsorbed HDM extract conducted in an outpatient clinic was tolerable in patients with AD and AR. UR-SCIT can be a useful method to start a SCIT in patients with AD and AR.

Factors Associated with Adherence to Allergen Specific Subcutaneous Immunotherapy.

PURPOSE: Allergen-specific immunotherapy (AIT) is known to be the only therapeutic modality to alter the natural course of allergic diseases. However, at least 3 years of treatment is recommended for achieving long-term disease modifying effect. This study aimed to investigate factors associated with immunotherapy non-adherence in real practice. MATERIALS AND METHODS: We retrospectively reviewed medical records of patients who were diagnosed with allergic rhinitis, asthma, or atopic dermatitis, and received AIT to common allergens such as house dust mite and/or pollens from January 2007 to August 2014. In this study, non-adherence was defined as not completing 3 years of AIT. RESULTS: Among 1162 patients enrolled, 228 (19.6%) failed to complete 3 years of AIT. In multivariate analysis, age less than 20 years [odds ratio (OR) 3.11, 95% confidence interval (CI) 1.70-5.69] and 20 to 40 years (OR 2.01, 95% CI 1.17-3.43), cluster build-up (OR 1.78, 95% CI 1.05-3.02) and ultra-rush build-up schedules (OR 5.46, 95% CI 2.40-12.43), and absence of visit to other departments in the same hospital (OR 1.87, 95% CI 1.05-3.32) were independently associated with immunotherapy non-adherence. Disease duration of 5-10 years was negatively associated with non-adherence compared to shorter disease duration of less than 5 years (OR 0.61, 95% CI 0.40-0.94). Although male sex and commercial product of AIT, Tyrosine S®, compared to Novo-Helisen® were non-adherent factors in univariate analysis, no statistical significances were identified in multivariate analysis. CONCLUSION: Various factors are associated with immunotherapy adherence affecting the utility of immunotherapy. Clinicians should be aware of factors associated with adherence to maximize the utility of allergen-specific subcutaneous immunotherapy.

High ACT score is not sufficient to reduce the risk of asthma exacerbations in asthma with low lung function.

BACKGROUND: Low forced expiratory volume in 1 s (FEV1) is a risk factor for asthma exacerbations (AEs). We aimed to determine if asthma control could reduce the future risk of AEs in patients with low FEV1. This study was conducted to evaluate the future risks of AEs within six months according to Asthma Control Test™ (ACT) score and FEV1. METHODS: A total of 565 patients with asthma were enrolled from the COREA cohort. The ACT score, lung function test, and number of AEs were assessed at baseline, three-month follow-up, and six-month follow-up with conventional asthma treatments by asthma specialists in real clinical settings. RESULTS: Female sex, low ACT score, low FEV1, low FVC, and AE history in the previous three months were related with increased AEs within six months. AEs during six-month follow-up occurred in 24% of patients with ACT <20 and FEV1 < 60% at baseline. Among patients with an ACT score ≥20, 3.4% of patients with an FEV1 < 2.16 L and 9.8% of patients with FEV1 ≥ 2.16 L had experienced AEs (P = 0.01), although no differences were observed in the presence of AEs within six months according to the predicted FEV1 (FEV1 ≥ 60% vs. FEV1 < 60%, 5.66% vs. 8.51%, P = 0.65). CONCLUSION: Patient with low FEV1 seemed to show higher risk of AEs than those with near-normal FEV1 despite ACT score ≥20 and asthma treatments. Therefore, treatment strategies that prevent AEs are needed in high-risk asthmatic patients.

Video education versus face-to-face education on inhaler technique for patients with well-controlled or partly-controlled asthma: A phase IV, open-label, non-inferiority, multicenter, randomized, controlled trial.

BACKGROUND: Education on inhaler technique is critical for effective asthma treatment. However, traditionally used face-to-face education is time-consuming, costly, and often laborious. The current study evaluated the efficacy of a newly developed video-based inhaler technique education method. METHODS: A total of 184 subjects with well-controlled or partly-controlled asthma were enrolled from 12 hospitals in South Korea from 30 November 2015 to 01 June 2016. Subjects were randomly divided into two groups in a 1:1 ratio; a control group that received face-to-face education, and a study group that received video education. All subjects received fluticasone propionate plus salmeterol xinafoate (Fluterol® 250/50 inhalation capsules) for 12 weeks. The primary outcome measure was forced expiratory volume in the 1st second (FEV1) at 12 weeks. The secondary outcome measures were change in FEV1 at 4 weeks, change in asthma control test (ACT) score, and changes in various inhaler technique parameters. These measures were assessed with a non-inferiority margin of 10% between the control group and the study group. RESULTS: FEV1 was significantly improved at 12 weeks in the control group and the study group. After adjustment, FEV1 improvement was not significantly inferior in the study group compared to the control group. The secondary outcome measures, including change in FEV1 at 4 weeks, ACT score, and various parameters pertaining to inhaler technique and satisfaction at 4 and 12 weeks did not differ significantly in the two groups. In subgroup analysis of elderly subjects and subjects with well-controlled asthma, FEV1 was significantly improved at 12 weeks in the study group but not the control group. CONCLUSION: The newly developed video education technique investigated functioned as a suitable substitute for face-to-face education on inhaler technique (dry powder inhalation capsule) in patients with stable asthma, particularly in elderly patients and patients with well-controlled asthma.

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.

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.

Immunomodulatory effects induced by intramuscular administration of autologous total immunoglobulin G in patients with atopic dermatitis.

BACKGROUND: Polyvalent human immunoglobulin G (IgG) preparations produced from the plasma pools of healthy blood donors have been used for the treatment of various autoimmune diseases and allergic diseases because of their anti-inflammatory and immunomodulatory effects. We hypothesized that intramuscular administration of autologous total IgG would induce immunomodulatory effects in patients with allergic diseases, based on the clinical efficacy of autologous blood therapy in patients with atopic dermatitis (AD). METHODS: Sixteen adult AD patients with IgE-mediated sensitization to the house dust mite (Dermatophagoides farinae) received intramuscular injections of 50 mg autologous total IgG twice a week for 4 weeks. The serum levels of IgE, IgG, and IgG4 antibodies to the recombinant group 2 major allergen of Dermatophagoides farinae (Der f 2) and serum levels of interleukin (IL)-10, IL-4, IL-12, and interferon gamma (IFN-γ) were measured by enzyme-linked immunosorbent assay at baseline and at weeks 4, 8, and 12. RESULTS: The serum level of IgE antibodies to Der f 2 was significantly decreased at 12 weeks compared with baseline (p<0.005). The serum levels of IgG and IgG4 antibodies to Der f 2 were significantly increased at 4, 8, and 12 weeks compared with baseline (p<0.05). The serum levels of IL-10 and IFN-γ were significantly increased at 4, 8, and 12 weeks compared with baseline (p<0.05). There were no significant differences in the serum levels of IL-4 or IL-12 before and after intramuscular administrations of autologous total IgG (p>0.05). CONCLUSION: Intramuscular administration of autologous total IgG induced anti-allergic immunomodulatory effects in AD patients. Further studies are required to evaluate the detailed immunological mechanism underlying these effects.

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.