Stratification of clinical and inflammatory phenotypes according to the urinary leukotriene E4 level in adult asthmatics

Purpose@#Cysteinyl leukotrienes (CysLTs) have been recognized as key mediators associated with type 2 inflammation in the airways of asthmatic patients. CysLTs are associated with airway constriction, eosinophil recruitment/activation, and airway remodeling. The study aimed to understand the role of CysLTs in adult asthmatics in a real-world clinical setting. @*Methods@#One hundred five adult asthmatics who had maintained antiasthmatic medications were enrolled. Asthmatic subjects were classified into 2 groups according to urinary leukotriene E4 (uLTE4) levels, and their clinical parameters and inflammatory mediators, including forced expiratory volume in 1 second (FEV1) %, fractional exhaled nitric oxide (FeNO), blood eosinophil count, serum periostin (sPON), and urinary eosinophil derived neurotoxin (uEDN) were compared between the high-uLTE4 and low-uLTE4 groups. @*Results@#The prevalence of chronic rhinosinusitis (CRS), severe asthma, and aspirin-exacerbated respiratory disease (AERD) were significantly higher in the high-uLTE4 group than in the low-uLTE4 group. The high-uLTE4 group had lower FEV1% and maximal midexpiratory flow %, but higher FeNO levels than the low-uLTE4 group. In addition, blood eosinophil count, sPON, and uEDN levels were significantly higher in the high-uLTE4 group than in the low-uLTE4 group. The presence of AERD and levels of FeNO, sPON, and uEDN were significantly associated with higher uLTE4 levels in asthmatics. @*Conclusion@#CysLTs are associated with type 2 inflammation in the airways of asthmatic patients, contributing to the development of AERD, CRS, and asthma severity. The stratification of clinical phenotypes according to the uLTE4 level could support optimizing anti-inflammatory therapy for better control of asthma.

Association between primary immunodeficiency and asthma exacerbation in adult asthmatics

Background/Aims@#Primary immunodef iciency (PID) is a serious comorbid condition in adult asthmatics that have frequent exacerbations, which requires monthly replacement of intravenous immunoglobulin (IVIG). However, the prevalence and clinical significance of PID in adult asthmatics in Korea have not yet been reported. The aim of this study is to assess the prevalence of PID and its association with asthma exacerbation in Korean adult asthmatics. @*Methods@#A total of 2,866 adult asthmatics were enrolled in this study. The PID group was defined as subjects who had lower levels of immunoglobulin G (IgG)/ A/M and/or IgG subclass presenting with recurrent respiratory infections. Serum samples were assayed for total IgG/A/M by immunoturbidimetry, and IgG subclasses by nephelometry. @*Results@#Of the 2,866 asthmatic patients enrolled, 157 (5.49%) had PID (classified as the PID group), while those without PID was classified as the non-PID group. IgG subclass deficiency (58%) is most prevalent, among which IgG3 subclass deficiency was most common (58%). The relative risk of asthma exacerbation was 1.70 times higher in the PID group compared to the non-PID group (1.696; 95% confidence interval, 1.284 to 2.239; p < 0.001); the prevalence of severe asthma was significantly higher in the PID group than in the non-PID group (32.48% vs. 13.00%, p < 0.001). Thirty-five among 157 patients in the PID group d maintained IVIG to prevent asthma exacerbation. @*Conclusions@#It is suggested that PID, especially IgG3 subclass deficiency, is a significant risk factor for asthma exacerbation. Screening of IgG subclass levels and IVIG replacement should be considered in the management in adult asthmatics.

Non-episodic Angioedema With Eosinophilia Successfully Treated With Reslizumab

No abstract available.

Characteristics of Adult Severe Refractory Asthma in Korea Analyzed From the Severe Asthma Registry

PURPOSE: Although mild to moderate asthma is much more common, the morbidity and mortality of severe asthma are much higher. This study was performed to identify and analyze the clinical characteristics of severe asthma in Korea. METHODS: We registered patients with severe refractory asthma into the Severe Asthma Registry supported by the Severe Asthma Work Group of the Korean Academy of Asthma, Allergy and Clinical Immunology. Patients were enrolled since 2010 from the 15 university hospitals nationwide in Korea. Severe asthma was defined according to modified European Respiratory Society/American Thoracic Society criteria. Information on demographics, medical history, pulmonary function tests and skin prick tests was collected; the clinical characteristics of severe asthmatics were analyzed from the collected data. RESULTS: A total of 489 patients were enrolled with a mean age of 62.3; 45% are male. Sixty percent of patients received Global Initiative for Asthma step 4 treatment, and 30% received step 5 treatment. The most common comorbidities were allergic rhinitis (58.7%). Aspirin hypersensitivity was observed in 14.0%. Approximately half (53.9%) are non-smokers. Atopy was proven in 38.5% of the patients. Regarding asthma medications, inhaled corticosteroids and long-acting β-agonist combination inhalers were most commonly prescribed (96.5%), followed by leukotriene antagonists (71.0%). A recombinant anti-immunoglobulin E monoclonal antibody (omalizumab) has been used in 1.8% of the patients. The mean forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and FEV1/FVC were 78.7%, 67.5% and 67.9% of predicted values, respectively. The mean Asthma Control Test and quality of life questionnaire scores were 16.5 out of 25 and 59.5 out of 85, respectively. CONCLUSIONS: The baseline characteristics of severe asthma patients in the Korea Severe Asthma Registry were analyzed and reported for the first time. With this cohort, further prospective studies should be performed to search for ways to improve management of severe refractory asthma.

Adaptation and Validation of the Korean Version of the Urticaria Control Test and Its Correlation With Salivary Cortisone

PURPOSE: Frequent changes in chronic urticaria (CU) activity over time can cause psychological stress, which also serves as a trigger of CU. To measure the control status of CU, the Urticaria Control Test (UCT) was developed in Germany. This study aimed to investigate the validity, reliability and responsiveness to changes in CU for the Korean version of the UCT (K-UCT) and its relation with salivary cortisol and cortisone levels. METHODS: Linguistic adaptation of the UCT into Korean was conducted. A total of 96 CU patients were enrolled, and 80 of them completed the study. The K-UCT and other outcome scores for CU were measured and repeated after 4 weeks of treatment. Control status was classified by physicians into well-controlled, partly-controlled, and uncontrolled CU. Salivary cortisol and cortisone were measured by liquid chromatography-tandem mass spectrometry. RESULTS: Excellent internal consistency and intra-class reliability were obtained. Strong correlations between the K-UCT and disease severity, reflected in the Urticaria Activity Score (UAS)/global assessment of urticaria control by physicians/patient assessment of symptom severity/CU-specific quality of life were noted. K-UCT scores ≥12 were found to be optimal for determining well-controlled CU (sensitivity, 75.0%; specificity, 758%; area under the curve, 0.824). Perceived stress scale scores were significantly correlated with the UAS and the K-UCT. Salivary cortisone levels were significantly correlated with K-UCT (r = 0.308, P = 0.009) and differed significantly according to control status determined by a K-UCT ≥12. CONCLUSIONS: This study demonstrated that the K-UCT can be a valid instrument with which to gauge CU control status in Korean patients. Further studies are needed to validate salivary cortisone as a biomarker for CU control.

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.

Serum Periostin Levels: A Potential Serologic Marker for Toluene Diisocyanate-Induced Occupational Asthma

PURPOSE: Toluene diisocyanate (TDI) is a leading cause of occupational asthma (OA). Periostin is a matricellular protein implicated in type 2 immunity-driven asthma. Its pathogenic role in TDI-OA has not been completely elucidated. The present study was performed to investigate the role of periostin in TDI-OA. MATERIALS AND METHODS: Serum periostin levels were measured in subjects with TDI-OA, asymptomatic TDI-exposure controls (AECs), non-occupational asthmatics (NAs), and unexposed normal controls (NCs). To understand the mechanism by which TDI induces periostin production, primary small airway epithelial cells (SAECs) were cultured under stimulation of TDI and neutrophils from asthmatic patients. RESULTS: Fifty-three subjects with TDI-OA, 71 AECs, 67 NAs, and 83 NCs were enrolled. Serum periostin levels were significantly higher in TDI-OA subjects than in AECs (p=0.001), NAs (p < 0.001), and NCs (p < 0.001). In TDI-exposed subjects (TDI-OA and AEC), the PC20 methacholine levels were significantly lower in subjects with a higher periostin level than in those with a lower periostin level. TDI exposure did not increase periostin production directly by SAECs; however, periostin production increased significantly after co-culture with TDI and neutrophils, which was suppressed by an antioxidant. In addition, increased release of TGF-β1 was noted from SAECs when exposed to TDI and neutrophils, which was also suppressed by an antioxidant. CONCLUSION: These results suggest that an increased periostin level may contribute to the progression of airway inflammation to remodeling in TDI-exposed workers. A high serum periostin level is a potential serologic marker of the phenotype of TDI-OA.

Perceptions of Severe Asthma and Asthma-COPD Overlap Syndrome Among Specialists: A Questionnaire Survey

PURPOSE: Severe asthma and asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) are difficult to control and are often associated with poor clinical outcomes. However, much is not understood regarding the diagnosis and treatment of severe asthma and ACOS. To evaluate the current perceptions of severe asthma and COPD among asthma and COPD specialists, we designed an e-mail and internet-based questionnaire survey. METHODS: Subjects were selected based on clinical specialty from among the members of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Academy of Tuberculosis and Respiratory Diseases. Of 432 subjects who received an e-mail invitation to the survey, 95 subjects, including 58 allergists and 37 pulmonologists, responded and submitted their answers online. RESULTS: The specialists estimated that the percentage of severe cases among total asthma patients in their practice was 13.9%±11.0%. Asthma aggravation by stepping down treatment was the most common subtype, followed by frequent exacerbation, uncontrolled asthma despite higher treatment steps, and serious exacerbation. ACOS was estimated to account for 20.7% of asthma, 38.0% of severe asthma, and 30.1% of COPD cases. A history of smoking, persistently low forced expiratory volume in 1 second (FEV1), and low FEV1 variation were most frequently classified as the major criteria for the diagnosis of ACOS among asthma patients. Among COPD patients, the highly selected major criteria for ACOS were high FEV1 variation, positive bronchodilator response, a personal history of allergies and positive airway hyperresponsiveness. Allergists and pulmonologists showed different assessments and opinions on asthma phenotyping, percentage, and diagnostic criteria for ACOS. CONCLUSIONS: Specialists had diverse perceptions and clinical practices regarding severe asthma and ACOS patients. This heterogeneity must be considered in future studies and strategy development for severe asthma and ACOS.

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.

Disease-specific impairment of the quality of life in adult patients with chronic spontaneous urticaria

BACKGROUND/AIMS@#Chronic urticaria (CU) is a common skin disorder characterized by wheals and pruritus lasting more than 6 weeks. Due to its long duration and changeable symptoms, the quality of life (QOL) of patients with CU can be impaired substantially. We evaluated the CU-QOL, a previously validated CU-specific QOL measure, and investigated factors influencing QOL in chronic spontaneous urticaria (CSU) patients.@*METHODS@#A hospital-based cross-sectional study was performed on 390 adult patients diagnosed with CSU from March 2009 to December 2012 at the Allergy and Clinical Immunology Clinic at Ajou University Hospital. The CU-QOL questionnaire, urticaria activity score (UAS), combined angioedema, and serum total immunoglobulin E (IgE) levels were investigated.@*RESULTS@#The average CU-QOL score obtained from the questionnaire was 70.6 (of 100 points). The CU-QOL scores correlated significantly with the UAS, particularly with the 15-point UAS (UAS-15; coefficient –0.532, p < 0.01) rather than the 6-point UAS (–0.502, p < 0.01). The patients presenting with angioedema and urticaria had poorer scores in the urticaria symptom domain than those with urticaria alone (37.4 vs. 46.9, p = 0.004). Log-transformed serum total IgE levels correlated significantly with CU-QOL (–0.131, p < 0.05). Multivariate regression models indicated that severe CU (UAS-15 score ≥ 13), log (total IgE), and the presence of angioedema were significant predictors of impaired CU-QOL (< 85 points).@*CONCLUSIONS@#CU has a substantial negative impact on QOL. The assessment of UAS-15, total IgE, and the presence of angioedema can be useful to predict QOL of the patients with CSU.

KAAACI Standardization Committee Report on the procedures and applications of the diagnostic tests for drug allergy

Diagnostic methods for drug allergy include the patient's history, in vivo skin test, in vitro laboratory test, and provocation test. However, the history is often not reliable, procedures for in vivo and in vitro tests are not standardized, and provocation tests are sometimes harmful to patients. Generally, skin prick and intradermal tests are useful for immediate reactions; in contrast, patch test and delayed reading of both skin prick and intradermal tests are helpful for delayed reactions. A drug provocation test is the gold standard for both responses, and it is necessary to be aware of exact indications and contraindications with appropriate drugs, doses, and intervals. To date, several methods have been developed to detect culprit agents for drug hypersensitivity reactions, but they are neither completely well validated nor standardized. Based on this awareness and necessity, the Korean Academy of Asthma, Allergy and Clinical Immunology launched the Standardization Committee to review the international guidelines and the literature, and then developed the consensus report on the procedures and applications of diagnostic tests for drug allergy.

An Ofloxacin-Induced Anaphylaxis through an IgG4-Mediated but Not IgE-Mediated Basophil Activation Mechanism / 대한구급학회지

No abstract available.

Linguistic adaptation of the rhinitis control assessment test in Korean

PURPOSE: Allergic rhinitis is one of the most common chronic diseases that affect in sleep, fatigue, headache, impaired cognition, and performances at work or school. Monitoring rhinitis control is important, because rhinitis is a life-long disease and affects patients' health-related quality of life. The rhinitis control assessment test (RCAT) completed its development and initial validation, following confirmation of its reliability, validity, and responsiveness in the United States. To apply the RCAT in Korean clinical practice, we conducted linguistic adaptation of the RCAT in Korean language. METHODS: The process of linguistic adaptation was composed of 10 steps: preparation, forward translation, reconciliation, back translation, back translation review, harmonization, cognitive debriefing, review of cognitive debriefing results and finalization, proofreading, and the final report. RESULTS: We completed a Korean version of the RCAT according to 10 steps. The Korean version of the RCAT was composed of 6 items, including nasal and ocular symptoms, sleep disturbances, limitation of casual activity, and symptom control. The score ranged from 5 to 30. Higher score indicated the well-controlled status of rhinitis. CONCLUSION: We conducted linguistic adaptation of the RCAT in Korean, which would be helpful in clinical practice to assess the status of rhinitis control and to adjust rhinitis medications.

Plasma LTE₄/PGF₂α Ratio and Blood Eosinophil Count Are Increased in Elderly Asthmatics With Previous Asthma Exacerbation

The tools for asthma control assessment recommended by the current guideline are cognitive function- and effort-dependent, which is substantially impaired in the elderly. The aim of this study is to investigate objective assessment tools of asthma control status and previous asthma exacerbation (AE) in elderly subjects. Asthmatics aged >60 years who were treated with step 2 or 3 by the Global Initiative for Asthma (GINA) guideline were enrolled. During the 12-week study period, the subjects used either 400 µg of budesonide plus 10 mg of montelukast or 800 µg of inhaled budesonide. The occurrence of AE during the 4-week run-in and 12-week treatment period was monitored. After 12-week of treatment, sputum eosinophil count, peripheral eosinophil count, the plasma leukotriene E₄ (LTE₄), and prostaglandin F₂α (PGF₂α) metabolite levels were measured using the UHPLC/Q-ToF MS system. The study subjects were divided into group 1 (asthmatics who experienced AE during the study period) and group 2 (those who did not). A total of 101 patients aged 60-85 years were enrolled. Twenty-three patients (22.8%) had experienced AE. The plasma LTE₄ level, LTE₄/PGF₂α ratio, and peripheral eosinophil count were significantly higher in group 1 than in group 2 (P=0.023, P=0.010, P=0.033, respectively). The plasma LTE₄/PGF₂α ratio and peripheral eosinophil count at week 12 were significantly associated with previous AE (odds ratio [OR]=1.748, P=0.013; OR=1.256, P=0.027). Receiver operating characteristic (ROC) curves to discriminate the subjects with previous AE, including these 2 parameters, showed that the area under the curve was 0.700 (P=0.004), with 73.9% sensitivity and 47.9% specificity. In conclusion, a combination of plasma LTE₄/PGF₂α ratio and peripheral eosinophil count can be an objective assessment tool which is significantly associated with asthma control status in elderly asthmatics.

An Ofloxacin-Induced Anaphylaxis through an IgG4-Mediated but Not IgE-Mediated Basophil Activation Mechanism / 대한중환자의학회지

No abstract available.

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.

Epithelial folliculin is involved in airway inflammation in workers exposed to toluene diisocyanate

Toluene diisocyanate (TDI) exposure can directly activate and damage airway epithelium. Folliculin (FLCN) is a protein expressed by human airway epithelial cells (HAECs) to maintain airway epithelial integrity and survival. This study investigated the involvement of FLCN in the pathogenesis of TDI-induced occupational asthma (OA). Enzyme-linked immunosorbent assay was used to measure serum levels of FLCN in TDI-exposed subjects (93 TDI-OA patients and 119 asymptomatic exposed controls (AEC)), 200 non-occupational asthma (NOA) patients and 71 unexposed healthy normal controls (NCs). Significantly more subjects in the TDI-OA and AEC groups had high serum levels of FLCN compared to those in the NOA group (P=0.002 and P=0.001, respectively), all of which were higher than the NC group (all P<0.001). The serum level of FLCN was positively correlated with TDI exposure duration (r=0.251, P=0.027), but was negatively correlated with asthma duration of TDI-OA patients (r=−0.329, P=0.029). TDI-exposed subjects with high FLCN levels had higher serum levels of total IgE than those with lower levels. The effects of TDI exposure on FLCN production was investigated by treating HAECs (A549 cells) with TDI-human serum albumin conjugate, which showed increased expression and release of FLCN and interleukin-8 from HAECs. Co-culture with peripheral blood neutrophils also induced FLCN expression and release from HAECs. In conclusion, TDI exposure and TDI-induced neutrophil recruitment into the airways can activate and stimulate HAECs to produce FLCN, which could be involved in airway inflammation in workers exposed to TDI.

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.

Effects of Immunoglobulin Replacement on Asthma Exacerbation in Adult Asthmatics with IgG Subclass Deficiency

PURPOSE: Recurrent respiratory tract infection is a common manifestation of primary immunodeficiency disease, and respiratory viruses or bacteria are important triggers of asthma exacerbations. Asthma often coexists with humoral immunodeficiency in adults, and some asthmatics with immunoglobulin (Ig) G subclass deficiency (IgGSCD) suffer from recurrent exacerbations. Although some studies suggest a benefit from Ig replacement, others have failed to support its use. This study aimed to assess the effect of Ig replacement on asthma exacerbation caused by respiratory infection as well as the asthma control status of adult asthmatics with IgGSCD. METHODS: This is a multi-center, open-label study of adult asthmatics with IgGSCD. All patients received monthly intravenous immunoglobulin (IVIG) for 6 months and were evaluated regarding asthma exacerbation related to infection, asthma control status, quality of life, and lung function before and after IVIG infusion. RESULTS: A total of 30 patients were enrolled, and 24 completed the study. Most of the patients had a moderate degree of asthma severity with partly (52%) or uncontrolled (41%) status at baseline. IVIG significantly reduced the proportion of patients with asthma exacerbations, lowered the number of respiratory infections, and improved asthma control status, compared to the baseline values (P<0.001). The mean asthma-specific quality of life and asthma control test scores were improved significantly (P=0.009 and P=0.053, respectively); however, there were no significant changes in lung function. CONCLUSIONS: IVIG reduced the frequency of asthma exacerbations and improved asthma control status in adult asthmatics with IgGSCD, suggesting that IVIG could be an effective treatment option in this population.