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Asthma is a chronic eosinophilic inflammatory disease with an increasing prevalence worldwide. Endocannabinoids are known to have immunomodulatory biological effects. However, the contribution of oleoylethanolamide (OEA) to airway inflammation remains to be elucidated. To investigate the effect of OEA, the expression of proinflammatory cytokines was measured by RT-qPCR and ELISA in airway epithelial (A549) cells. The numbers of airway inflammatory cells and cytokine levels in bronchoalveolar lavage fluid, airway hyperresponsiveness, and type 2 innate lymphoid cells (ILC2s) were examined in BALB/c mice after 4 days of OEA treatment. Furthermore, eosinophil activation after OEA treatment was evaluated by measuring cellular CD69 levels in eosinophils from human peripheral eosinophils using flow cytometry. OEA induced type 2 inflammatory responses in vitro and in vivo. OEA increased the levels of proinflammatory cytokines, such as IL-6, IL-8, and IL-33, in A549 cells. In addition, it also induced eosinophilic inflammation, the production of IL-4, IL-5, IL-13, and IL-33 in bronchoalveolar lavage fluid, and airway hyperresponsiveness. OEA increased the numbers of IL-5- or IL-13-producing ILC2s in a mouse model. Finally, we confirmed that OEA increased CD69 expression (an eosinophil activation marker) on purified eosinophils from patients with asthma compared to those from healthy controls. OEA may play a role in the pathogenesis of asthma by activating ILC2s and eosinophils., Asthma: A physiological cannabinoid promotes inflammation Oleoylethanolamide (OEA), an endocannabinoid similar to those found in cannabis, occurs naturally in the body, and has now been implicated in promoting symptoms of asthma. OEA activates white blood cells called eosinophils and ILC2 cells, which are both parts of our immune response. Researchers in South Korea, led by Ga-Young Ban at Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, studied the effect of OEA on respiratory system cells from people with asthma and in mice used to model the condition in humans. OEA-induced inflammatory responses associated with asthma by stimulating the release of signaling molecules called cytokines. However, some other endocannabinoids have anti-inflammatory effects. Studying the effects of all endocannabinoids could yield new insights into asthma, with this study opening new possibilities for treating asthma by interfering with OEA-induced signaling responses.

Introduction: Chronic spontaneous urticaria (CSU) is a common cutaneous disease caused by mast-cell degranulation. Human β-defensin 2 (HBD2) is a well-known antimicrobial peptide that is also a pruritogen inducing vascular permeability via non-IgE-mediated mast-cell degranulation. Objective: We investigated the associations between serum HBD2 levels and the clinical characteristics of CSU patients. Methods: Serum samples from 124 CSU patients and 56 healthy controls were screened for the levels of HBD2 and translationally controlled tumor protein (TCTP)_ by using ELISA. The urticaria activity score over 7 days (UAS7) was used to measure disease activity in CSU patients. Accompanying angioedema was self-reported. Results: Serum HBD2 levels were higher in the CSU group than in healthy subjects (median [interquartile range], 84.1 [43.5, 142.5] vs. 59.5 [26.7, 121.5], p = 0.034). In CSU patients, serum HBD2 level was negatively correlated with the peripheral basophil percentages (Spearman’s rho = −0.229, p = 0.01) and vitamin D levels (−0.262, p = 0.02), but positively correlated with TCTP levels (0.252, p = 0.006). In CSU patients, HBD2 level was higher in those with than without angioedema (101.7 [50.9, 184.2] vs. 66.7 [37.9, 132.0], p = 0.019). It did not differ by aspirin hypersensitivity or atopy status, or autologous serum skin test positivity. Conclusion: A known mast-cell degranulator, HBD2 was elevated in the sera from CSU patients compared to healthy controls and may be involved in the pathogenesis of accompanying angioedema.

Although younger patients with allergic rhinitis (AR) have been successfully treated with pharmacotherapy, there are no definitive data on treatment outcomes in older patients with AR. We performed a prospective study of 51 older adults with AR (aged over 65 years) and 101 younger AR patients (aged from 19 to 40 years) to compare clinical outcomes between the 2 groups and to evaluate the impact of depressed mood on treatment outcomes in older AR patients. Changes in total symptom scores (TSS), rhinitis-specific quality of life questionnaire (RQLQ) results, rhinitis control assessment test (RCAT) results and visual analog scale (VAS) scores were evaluated after 4-week treatment according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline, and the severity of depressed mood was assessed by using the geriatric depression scale. After 4-week treatment, younger AR patients had greater improvements in clinical scores compared with older adults; differences in least squares mean changes from baseline in older patients vs. younger patients were 1.71 (P = 0.004) for TSS, 10.84 (P < 0.001) for RQLQ, 0.80 (P = 0.275) for RCAT, and 8.60 for VAS score (P = 0.061). Multiple logistic regression analysis showed that the severity of depressed mood was independently associated with severe chronic upper airway disease (adjusted odds ratio, 1.385; P = 0.004). Our results suggest that older AR patients are less responsive to standard treatment compared with younger AR patients and that depressed mood is strongly associated with the increased risk of uncontrolled AR in older AR patients.

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.

PURPOSE A need for useful measures reflective of the socio-economic burden of chronic urticaria (CU) has arisen. To obtain utility estimates for CU, we investigated EuroQol-5-Dimension (EQ-5D) indices according to urticaria control status and urticaria severity. METHODS In this prospective observational study, we administered patient-oriented questionnaires on EQ-5D and urticaria outcomes, including Urticaria Activity Score over 7 days (UAS7), Urticaria Control Test (UCT), and CU-specific quality of life (CU-QOL). EQ-5D utility index scores were compared according to urticaria control status and disease severity. Conditional process analysis (CPA) was used to map EQ-5D utility scores from UAS7 and UCT. RESULTS Greater EQ-5D utility values were obtained in patients with better urticaria control (0.91 ± 0.10 for well controlled CU, 0.84 ± 0.12 for partly controlled, 0.77 ± 0.14 for uncontrolled, P < 0.001). According to CU severity, mean utility values were ranged from 0.746 (severe, UAS7 ≥ 28) to 0.860 (moderate), 0.878 (mild), and 0.953 (urticaria free). CPA suggested that UAS7 was directly correlated with UCT (regression coefficient, -0.251; 95% confidence interval [CI], -0.278, -0.223; P < 0.001) and EQ-5D utility (-0.002; 95% CI, -0.003, -0.001; P = 0.007) after controlling for age, sex, urticaria duration, and combined allergic diseases. CONCLUSIONS EQ-5D values increased with improvement in urticaria control and decreased with urticaria severity. A predictive model mapping EQ-5D utility from UAS7 and UCT scores suggested that EQ-5D can be useful for the pharmacoeconomic evaluation of individualized treatments for CU patients.

Backgrounds: Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by itchy wheals of at least 6 weeks in duration, wherein the autoimmune mechanism is involved to activate IgE receptors (FcεRIα) on mast cells. We aimed to assess levels of IgG autoantibody against FcεRIα in sera from CSU patients using dot-blot immunoassay. Methods: We performed a hospital-based cross-sectional study of 125 CSU patients (64 ASST-positive, 61 ASST-negative) and 64 age-and sex-matched healthy controls. The cut-off value of IgG FcεRIα autoantibody was determined as the mean intensity plus two standard deviations of values in controls. Positivity for IgG autoantibody to FcεRIα was analyzed according to clinical parameters of disease duration, urticaria activity score (UAS), ASST, response to antihistamine treatment, complement levels, and the presence of other autoantibodies. Nonparametric tests were applied for statistical analyses. Results: IgG positivity to FcεRIα was noted in 24.8% of CSU patients and was significantly more frequent in ASST-positive patients than in ASST-negative patients (32.8% vs 16.4%, P = 0.040). Only 3.1% of healthy controls had this autoantibody. Complement 3 levels were significantly lower in anti-FcεRIα antibody-positive patients than antibody-negative patients (109.8 ± 19.9 vs 123.1 ± 30.9, P = 0.035). No significant associations were found between IgG positivity to FcεRIα and UAS, serum total IgE levels, atopic status, clinical responses to antihistamines, or the presence of anti-thyroid and anti-nuclear antibodies. Conclusion: These findings suggest that circulating IgG autoantibody to FcεRIα in a subset of patients may be involved in the autoimmune mechanism of CSU. Further studies are needed to clarify its clinical significance. Keywords: Urticaria, Chronic, IgE receptor, Autoimmunity

PURPOSE Asthma control in older asthmatics is often less effective, which may be attributed to small airway dysfunction and poor inhalation technique. We compared the efficacy of 2 inhalers (fluticasone propionate/formoterol treatment using a pressurized metered-dose inhaler [p-MDI group] vs. fluticasone propionate/salmeterol treatment using a dry powder inhaler [DPI group]) in older asthmatics. METHODS We conducted a 12-week, randomized, open-label, parallel-designed trial in older patients (over 55 years old) with moderate-to-severe asthma, and compared the efficacy and safety for asthma control between the 2 groups. Subgroup analyses on disease duration and air trapping were performed. Clinical parameters, including changes in lung function parameters, inhaler technique and adherence, were compared with monitoring adverse reactions between the 2 groups. RESULTS A total of 68 patients underwent randomization, and 63 (30 in the p-MDI group and 33 in the DPI group) completed this study. The p-MDI group was non-inferior to the DPI group with regard to the rate of well-controlled asthma (53.3% vs. 45.5%, p < 0.001; a predefined non-inferiority limit of 17%). In subgroup analyses, the proportion of patients who did not reach well-controlled asthma in the p-MDI group was non-inferior to that in the DPI group; the difference was 12.7% among those with a longer disease duration (≥ 15 years) and 17.5% among those with higher air-trapping (RV/TLC ≥ 45%), respectively (a predefined non-inferiority limit of 17%, p < 0.001). No significant differences were observed in lung function parameters, inhalation techniques, adherence and adverse reactions between the 2 groups. CONCLUSION These results suggest that the p-MDI group may be comparable to the DPI group in the management of older asthmatics in aspects of efficacy and safety.

Background/aims Asthma is not a single disease but, rather, a heterogeneous inf lammatory disorder with various pathogenic mechanisms. We analyzed the associations between the cellular profile of sputum and the serum levels of inflammatory mediators/cytokines in a cohort of adult asthmatics. Methods We recruited 421 adult asthmatic patients. All subjects were classified into four groups according to their sputum cellular profiles: G1, eosinophilic; G2, mixed granulocytic; G3, neutrophilic; and G4, paucigranulocytic. Serum levels of cytokines and mediators including periostin, eosinophil-derived neurotoxin (EDN), S100A9, and folliculin were quantified. Results Among 421 patients, G1 accounted for 149 (35.4%), G2 for 71 (16.9%), G3 for 155 (36.8%), and G4 for 46 (10.9%). Serum periostin and EDN levels were significantly higher in G1 (p = 0.004, and p = 0.031) than in the others. Serum S100A9 levels were elevated in G2 and G3 (p = 0.008). Serum folliculin levels differed significantly among the four groups, with the highest level in G4 (p = 0.042). To identify G1 from G1 plus G2 groups, the optimal serum cut-off levels were 1.71 ng/mL for periostin, and 1.61 ng/mL for EDN. When these two parameters were combined, the sensitivity was 76.0% and the specificity was 64.3% (area under the curve, 0.701; p = 0.004). Conclusion The serum periostin and EDN levels may be used as predictors to discriminate the eosinophilic asthma group from patients having eosinophilic or mixed granulocytic asthma, and the serum folliculin level is significantly elevated in patients with paucigranulocytic asthma compared to those with different inflammatory cell profile.

This document summarizes the aims of GA2 LEN/HAEi Angioedema Centers of Reference and Excellence (ACAREs) and elaborates the requirements that ACAREs must fulfill to become certified. It also provides (see Appendix S1) background information on GA2LEN and HAEi, including HAEi member organizations and regional patient advocates, on why we need an Angioedema Center of Reference and Excellence (ACARE) program and network, and on the accreditation and certification process, governance and funding, and on the interaction with other GA2LEN networks of centers of reference and excellence. The protocols, aims, requirements, and provisions related to becoming a certified CARE are based on (a) the experience of the GA2LEN UCARE network and (b) input from angioedema patients, general practitioners, and angioedema specialists.

Purpose Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. Methods A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. Results A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. Conclusions The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.

Background: IgE bound on the surface of mast cells contributes to the pathogenesis of chronic spontaneous urticaria (CSU). Atopy is a predisposing factor for CSU, where omalizumab is a widely used monoclonal antibody to control urticaria symptoms via capturing serum free IgE. However, the role of serum free IgE is not clarified in CSU. The present study evaluated the clinical relevance of serum free IgE in patients with CSU. Methods: Eighty-eight patients with CSU and 76 healthy controls (HCs) were enrolled in this study. Serum total and Dermatophagoides pteronyssinus (Der p)-specific IgE levels were measured by ImmunoCAPs. The serum free IgE levels were measured by ELISA using a novel IgETRAP, and their associations with clinical parameters, including urticaria activity score (UAS), were evaluated. Changes in serum free and total IgE levels after omalizumab treatment were observed in 23 CSU patients in comparison between responders (≥50% reduction in UAS) and non-responders (

Quite a few patients with chronic spontaneous urticaria (CSU) are refractory to H₁-antihistamines, even though the dose of H₁-antihistamines is increased up to 4-fold. CSU that is not controlled with H₁-antihistamines results in increased disease burden. Several immunomodulators have been used to manage these patients. The guidelines reported herein are connected to Part 1 of the KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children, and aimed to provide evidence-based recommendations for the management of H₁-antihistamine-refractory CSU. Part 2 focuses on the more commonly used additional treatment options for refractory CSU, including omalizumab, cyclosporine, leukotriene receptor antagonist, dapsone, methotrexate, and phototherapy. The evidence to support their efficacy, dosing, safety, and selection of these agents is systematically reviewed. To date, for patients with refractory CSU, the methodologically sound data to evaluate the use of omalizumab has been growing; however, the evidence of other immunomodulators and phototherapy is still insufficient. Therefore, an individualized stepwise approach with a goal of achieving complete symptom control and minimizing side effects can be recommended. Larger controlled studies are needed to elevate the level of evidence to select a rational therapeutic agent for patients with refractory CSU.

BackgroundPatients with aspirin-exacerbated respiratory disease (AERD) are known to have poor clinical outcomes. The pathogenic mechanisms have not yet been completely understood.ObjectiveWe aimed to assess the involvement of the de-novo synthetic pathway of sphingolipid metabolism in patients with AERD compared to those with aspirin tolerant asthma (ATA).MethodsA total of 63 patients with AERD and 79 patients with ATA were enrolled in this study. Analysis of mRNA expression of serine palmitoyl transferase, long-chain base subunit 2 (SPTLC2) and genotyping of ORMDL3 SNP (rs7216389) was performed.ResultsSignificantly higher levels of SPTLC2 mRNA expression were noted in patients with AERD, which showed significant positive correlations with peripheral/sputum eosinophil counts and urine LTE4 (all PConclusion & clinical relevanceThis is the first study that shows the dysregulated de novo synthetic pathway of sphingolipids may be involved in the eosinophilic inflammation and airflow limitation in AERD.

Purpose The prevalence of asthma is increasing globally as the world population increases; however, and the prevalence and mortality of asthma have not been extensively investigated. Also, the effects of severity and aging on asthma prevalence and mortality are unknown. We aimed to investigate trends of the prevalence and mortality of asthma as well as health care uses and costs over 14 years according to disease severity by using real-world data in Korea. Methods Using the National Health Insurance Sharing Service database, we extracted asthmatic patients having diagnosis codes of asthma and prescription records of antiasthmatic medications from 2002 to 2015 and categorized them according to asthma exacerbation and regular treatment. We defined asthma-associated death in terms of patients' prescription records within 3 months before all-cause death, then linked with the Cause of Death Statistics. The annual asthma-related health care uses and costs were analyzed. Results The prevalence rates of asthma (1.6% to 2.2%) and severe asthma (SA; 3.5% to 6.1% among total asthmatics) have increased steadily over the decade in Korea, where the proportion of elderly asthmatics having increased. The asthma-related health care uses and costs had increased during the study period with the highest uses/costs in SA. The asthma mortality had a steady rising trend from 16.2 to 28.0 deaths per 100,000 with the highest mortality in SA. Conclusions The prevalence and mortality of asthma as well as SA increases along with the burden of health care uses/costs. More active interventions, including changes in health care policies, are needed to reduce the prevalence and mortality of asthma, especially SA.

Cefaclor, a second-generation oral cephalosporin, is the most frequently prescribed cephalosporin in Korea. Studies, however, have yet to analyze the incidence of cefaclor-associated adverse drug reactions (ADRs), including hypersensitivity (HS), according to total national usage rates. This study aimed to investigate the incidence rates and clinical features of cefaclor ADRs reported to the Korean Adverse Event Reporting System (KAERS) and Health Insurance Review and Assessment Service (HIRA) database for the most recent 5 years. Reviewing the HIRA database, which contains information on all insurance claims, including prescribed medications and patient demographics, we identified the total number of individuals who had been prescribed cefaclor and other cephalosporins including 2nd generation without cefaclor and 3rd generation antibiotics from January 2014 to December 2018. Additionally, we retrospectively analyzed all ADRs reported to the KAERS for these drugs over the same study period. Incidence rates for ADRs, HS, and anaphylaxis to cefaclor were 1.92/10,000 persons, 1.17/10,000 persons, and 0.38/10,000 persons, respectively, lower than those to other 2nd and 3rd cephalosporins. Among all ADRs, HS (60.9% vs. 43.6% vs. 44.8%, P P nd and 3rd cephalosporins. Females, individuals under 65 years of age, concomitant use of drugs, and serious ADRs were more strongly associated with HS to cefaclor than with HS to other 2nd and 3rd cephalosporins. In a nationwide database for the Korean population, the incidence of cefaclor-induced ADRs, particularly HS and anaphylaxis, was high. Female sex, age younger than 65 years, and concomitant use of drugs may be associated with HS to cefaclor.

Background It has been known that a high serum total immunoglobulin E (IgE) level is a predisposing factor of allergic asthma; however, there are considerable limitations to apply it in clinical practice. Objective To determine the clinical significance of the serum-free IgE level in patients with adult asthma. Methods We measured free IgE levels using our homemade enzyme-linked immunosorbent assay by applying a novel IgE TRAP protein (GI innovation, Seoul, Republic of Korea) in sera of adults with asthma (n = 116) compared with healthy controls (n = 32); enzyme-linked immunosorbent assay inhibition test was performed to validate its binding specificity. Associations between asthma-related clinical and laboratory parameters were analyzed. The diagnostic value and cutoff point for detecting atopy and type 2 asthma were determined using receiver operating characteristic curve analysis. Results The serum-free IgE levels were significantly higher in adults with asthma than in healthy controls and were significantly associated with atopic status and type 2 asthma (all P Conclusion It is suggested that a higher serum-free IgE level may be a useful biomarker of atopy and type 2 asthma in adults with asthma.

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.

Background Autophagy and neutrophil extracellular DNA traps (NETs) are implicated in asthma; however, their roles in asthma pathogenesis have not been elucidated. Objectives We compared autophagy and NET production levels from peripheral blood neutrophils (PBNs) of patients with severe asthma (SA) and non-severe asthma (NSA). Additionally, we investigated the inflammatory effects of NETs on human airway epithelial cells (AECs) and peripheral blood eosinophils (PBEs). Methods PBNs from patients with SA (n=30) and NSA (n=38) were treated with interleukin (IL)-8 (100 ng/ml). Autophagy (light chain 3-II expression) and NET production levels were evaluated by western blot, immunofluorescence microscopy, and PicoGreen assay. The effects of NETs on AECs were assessed by investigating cell death, cell detachment, expression of occludin and claudin-1, and IL-8 production; the effects of NETs on PBEs were examined by investigating the activation and release of eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN). Results Untreated and IL-8-treated PBNs from the SA group produced higher autophagy and NET levels compared with those from the NSA group (P

SummaryBackground To date, there has been no reliable in vitro test to diagnose aspirin-exacerbated respiratory disease (AERD). Objective To investigate potential diagnostic biomarkers for AERD using metabolomic analysis. Methods An untargeted profile of serum from asthmatics in the first cohort (group 1) comprising 45 AERD, 44 patients with aspirin-tolerant asthma (ATA), and 28 normal controls was developed using the ultra-high-performance liquid chromatography (UHPLC)/Q-ToF MS system. Metabolites that discriminate AERD from ATA were quantified in both serum and urine, which were collected before (baseline) and after the lysine-aspirin bronchoprovocation test (Lys-ASA BPT). The serum metabolites were validated in the second cohort (group 2) comprising 50 patients with AERD and 50 patients with ATA. Results A clear discrimination of metabolomes was found between patients with AERD and ATA. In group 1, serum levels of LTE4 and LTE4/PGF2α ratio before and after the Lys-ASA BPT were significantly higher in patients with AERD than in patients with ATA (P < 0.05 for each), and urine baseline levels of these two metabolites were significantly higher in patients with AERD. Significant differences of serum metabolite levels between patients with AERD and ATA were replicated in group 2 (P < 0.05 for each). Moreover, serum baseline levels of LTE4 and LTE4/PGF2α ratio discriminated AERD from ATA with 70.5%/71.6% sensitivity and 41.5%/62.8% specificity, respectively (AUC = 0.649 and 0.732, respectively P < 0.001 for each). Urine baseline LTE4 levels were significantly correlated with the fall in FEV1% after the Lys-ASA BPT in patients with AERD (P = 0.008, r = 0.463). Conclusions and Clinical Relevance Serum metabolite level of LTE4 and LTE4/PGF2α ratio was identified as potential in vitro diagnostic biomarkers for AERD using the UHPLC/Q-ToF MS system, which were closely associated with major pathogenetic mechanisms underlying AERD.

An association between drug treatment for viral infections and severe cutaneous adverse reactions has been noted. We investigated six patients diagnosed with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) after being prescribed acetaminophen for suspected viral illnesses. Multiplex analysis was performed to measure cytokine levels in sera before and after treatment. IL-2Rα levels significantly decreased during the convalescence phase. Although acetaminophen is relatively safe, the drug can trigger SJS/TEN in patients with suspected viral infections. T-cells and monocytes may be key components of the link between viral infection and acetaminophen-induced SJS/TEN.

We are in the era of rapid aging of the global population. Elderly asthmatic patients have an increased frequency of hospitalization and a high mortality rate. In this review, we focus on comorbidities and treatment issues in terms of the predictors of asthma control in the elderly.Some frequent comorbidities, such as chronic obstructive pulmonary disease, chronic sinusitis, obesity, and depression, are associated with uncontrolled asthma in elderly asthmatic patients. Smoking status in elderly asthmatic patients was associated with more frequent exacerbations. Management of comorbidities should be taken into account when we treat elderly asthmatic patients. Low treatment adherence, which is common in elderly asthmatic patients, predicts poor asthma control status. A poor knowledge about asthma, cognitive function impairment, and inappropriate inhaler technique result in low treatment adherence. Polypharmacy is associated with low treatment adherence, adverse drug reactions, and drug-drug interactions, and it is supposed to be a predictor of asthma control.Multifactorial assessments, including comorbidities, treatment adherence, and polypharmacy, are important for better asthma control in elderly asthmatic patients. Further studies on the strategy for the management of elderly asthmatic patients in a real-world setting are warranted.

In the era of novel coronavirus epidemics, vaccines against coronavirus disease 2019 (COVID-19) have been recognized as the most effective public health interventions to control the pandemic. An adverse event following immunization (AEFI) is defined as any untoward occurrence following immunization, and the majority of AEFIs are caused by protective immune responses stimulated by vaccines. Most of the reported AEFIs are not serious, and many are not immunologically mediated or even reproducible on re-exposure. However, uncommon severe allergic adverse reactions, such as anaphylaxis or other allergic reactions, can occur after vaccinations. Confirmed allergic reactions to vaccines may be caused by residual non-human protein, preservatives, or stabilizers in the vaccine formulation (also known as excipients). There are 2 main potential allergenic/immunogenic excipients in COVID-19 vaccines, polyethylene glycol (PEG) and polysorbate 80. PEG, also known as macrogol, is an ingredient in various laxatives and injectable formulations, such as depot steroids. Polysorbate 80 is present in various medical products, creams, ointments, lotions, and medication tablets. Contraindications to the administration of COVID-19 vaccines include a previous history of severe allergic reactions to the first dose of COVID-19 vaccine or proven hypersensitivity to a vaccine component, such as PEG or polysorbate 80. Anaphylaxis or other allergic reactions following immunization can cause fear and loss of confidence in the safety of vaccines among the public. A better understanding of these events is thought to help alleviate concerns about the current COVID-19 vaccines and provide reassurance to the general population by analyzing the exact incidence of anaphylaxis and potential risk factors. COVID-19 vaccine-associated anaphylaxis could be prevented and managed by risk stratification based on our local and global experience.

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.

Patients with severe eosinophilic asthma (SEA) suffer from frequent asthma exacerbations, where eosinophils are major effector cells in airway inflammation, and anti-interleukin (IL)-5 becomes an effective treatment modality to control eosinophilic inflammation of SEA. Fifteen patients with SEA who had been treated with anti-IL5 (reslizumab, 100 mg monthly intravenously) for 6 months at Ajou University Hospital (Suwon, Korea) were enrolled in this study. Clinical parameters, including total blood eosinophil count (TEC), FEV1%, fractional exhaled nitric oxide (FeNO) levels, and serum biomarkers such as eosinophil-derived neurotoxin (EDN), periostin (PON), and transforming growth factor-β1 (TGF-β1), were analyzed. EDN levels and TEC decreased significantly after 1 month of treatment (P < 0.05 for both), while no changes were noted in FeNO/PON/TGF-β1 levels. FEV1% increased after 2 months of treatment (P < 0.05). A positive correlation was observed between TEC and EDN levels (r = 0.60, P = 0.02). Significant negative correlations were noted between age and TEC/EDN levels (r = −0.57, P = 0.02 and r = −0.56, P = 0.03, respectively). Baseline TEC was higher in the EDN-responder group (≥75% decrease) than in the non-responder group (P = 0.06) with a positive correlation between %reduction in EDN and TEC (r = 0.67, P = 0.01). The onset age was younger and asthma duration was longer in the FEV1%-non-responder group (

Purpose Minimizing the future risk of asthma exacerbation (AE) is one of the main goals of asthma management. We investigated prognostic factors for risk of severe AE (SAE) in a real-world clinical setting. Methods This is an observational study evaluating subjects who were diagnosed with asthma and treated with anti-asthmatic medications from January 1995 to June 2018. Risk factors for SAE were analyzed in 2 treatment periods (during the initial 2 years and the following 3–10 years of treatment) using the big data of electronic medical records. Results In this study, 5,058 adult asthmatics were enrolled; 1,335 (28.64%) experienced ≥ 1 SAE during the initial 2 years of treatment. Female sex, higher peripheral eosinophil/basophil counts, and lower levels of forced expiratory volume in 1 second (FEV1; %) were factors predicting the risk of SAEs (P < 0.001 for all). Higher serum total immunoglobulin E levels increased the risk of SAEs among the patients having ≤ 2 SAEs (P = 0.025). Patients with more frequent SAEs during the initial 2 years of treatment had significantly higher risks of SAEs during the following years of treatment (P < 0.001, for all) (patients with ≥ 4 SAEs, odds ratio [OR], 29.147; those with 3 SAEs, OR, 14.819; those with 2 SAEs, OR, 9.867; those with 1 SAE, OR, 5.116), had higher maintenance doses of systemic steroids, and showed more gradual decline in FEV1 (%) and FEV1/forced vital capacity levels maintained during the following years of treatment (P < 0.001 for all). Conclusions Asthmatics having risk factors for SAEs (female sex, higher peripheral eosinophil/basophil counts, and lower FEV1) should be strictly monitored to prevent future risk and improve clinical outcomes.

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.

Background: Although the prevalence of anaphylaxis is increasing worldwide, the large-scale studies in Asia evaluating anaphylaxis in all age groups are limited. We aimed to collect more precise and standardized data on anaphylaxis in Korea using the first multicenter web-based registry. Methods: Twenty-two departments from 16 hospitals participated from November 2016 to December 2018. A web-based case report form, designed by allergy specialists, was used to collect anaphylaxis data. Results: Within the 2-year period, 558 anaphylaxis cases were registered. The age of registered patients ranged from 2 months to 84 years, and 60% were aged

Translationally controlled tumor protein (TCTP) is also known as histamine releasing factor as it has the ability to activate mast cells. To investigate the role of TCTP in the pathogenesis of chronic spontaneous urticaria (CSU), we evaluated serum level of TCTP and effect of TCTP on basophil and mast cell degranulation. TCTP levels in the sera from 116 CSU patients and 70 normal healthy controls (NCs) were measured by ELISA. CD203c expression on basophils from CSU patients and β-hexosaminidase release from Laboratory of Allergic Disease 2 mast cells were measured upon stimulation monomeric and dimeric TCTP. Non-reducing Western blot analysis was used for detecting dimeric TCTP. No difference was observed in serum TCTP levels between CSU patients and NCs (p=0.676). However, dimeric TCTP intensity on Western blot was stronger in CSU patients than in NCs. TCTP levels were higher in patients with severe CSU (p=0.049) and with IgG positivity to FcɛRIα (p=0.038). A significant positive correlation was observed between TCTP and eosinophil cationic protein levels (Spearman's rho=0.341; p=0.001). Both basophil and mast cell degranulation were significantly increased after stimulation with dimeric TCTP, but not with monomic TCTP. The ability of TCTP to activate basophil and mast cells is dependent on dimerization, suggesting that the inhibition of TCTP dimerization can be a therapeutic option for CSU. Association between TCTP levels and the presence of IgG to high affinity Fc epsilon receptor I alpha subunit in CSU patients indicates that autoimmune mechanisms may be involved in the dimerization of TCTP.

PURPOSE In asthmatic patients, treatment with corticosteroids, in addition to conventional risk factors for osteoporosis, may lead to bone loss. Trabecular bone score (TBS) is an indirect new parameter of bone quality. This study aimed to evaluate TBS in asthmatics in comparison to propensity score-matched controls and to investigate correlations between TBS and cumulative systemic and inhaled corticosteroid doses 1 year prior to bone mineral density (BMD) measurement in patients with asthma. METHODS In total, 627 patients with asthma and the same number of non-asthmatic controls matched for sex and age were included in this retrospective cohort study. TBS was calculated in the lumbar region, based on 2 dimensional projections of dual-energy X-ray absorptiometry. RESULTS Patients with severe asthma exhibited lower vertebral TBS values (1.32 ± 0.1) than those with non-severe asthma (1.36 ± 0.1, P = 0.001), with non-active asthma (1.38 ± 0.1, P < 0.001), and without asthma (1.39 ± 0.1, P < 0.001). No significant differences in BMD were noted among the study groups. TBS was significantly correlated with cumulative systemic and inhaled corticosteroid doses as well as asthma duration, lung function and airway hyper-responsiveness. A generalized linear model revealed that age, severe asthma, and frequency of oral corticosteroid burst were significant predictors for TBS levels. CONCLUSIONS TBS can be used as an early indicator of altered bone quality stemming from glucocorticoid therapy or, possibly, more severe asthma.

PURPOSE Asthma in the elderly has different clinical features including more severe phenotypes with higher comorbidities. Epithelial cells are known to initiate innate/adaptive immune responses in asthmatic airways. We investigated clinical features and epithelial derived cytokine levels in elderly asthmatics compared to non-elderly asthmatics in a cross-sectional cohort of adult asthmatics in order to further understand its pathogenic mechanisms. METHODS A total of 1,452 adult asthmatics were enrolled from a single tertiary hospital and were classified into 2 groups: 234 elderly (≥ 60 years at initial diagnosis) and 1,218 non-elderly (< 60 years at initial diagnosis) asthmatics. Asthma-related clinical parameters were compared between the 2 groups. Serum levels of epithelial cell-derived cytokines including interleukin (IL)-31, IL-33, IL-8, eotaxin-2, transforming growth factor beta 1 (TGF-β1) and periostin were measured by enzyme-linked immunosorbent assay. RESULTS Significantly higher prevalence rates of late-onset asthma (onset age ≥ 40 years) and severe asthma, as well as the lower rate of atopy, blood/sputum eosinophil counts, total immunoglobulin E and eosinophil cationic protein levels were noted in elderly asthmatics compared to non-elderly asthmatics (P < 0.05, respectively). The forced expiratory volume in 1 second (FEV1, % predicted) level tended to be lower in elderly asthmatics (P = 0.07). In addition, serum IL-33 and IL-31 levels were significantly lower in elderly asthmatics, while no differences were found in the serum level of IL-8, eotaxin-2, TGF-β1 or periostin. Among elderly asthmatics, subjects with severe asthma had lower FEV1 (% predicted) value, but showed significantly higher serum levels of eotaxin-2 and TGF-β1, than those with non-severe asthma (P < 0.05 for each). CONCLUSIONS These findings suggest that age-related changes of epithelial cell-derived cytokines may affect clinical phenotypes and severity of elderly asthma: decreased levels of IL-33 and IL-31 may contribute to less Th2 phenotype, while increased levels of eotaxin-2 and TGF-β1 may contribute to severity.

Purpose Allergic rhinitis (AR) is a common and increasing disease in which Dermatophagoides (D.) farinae is one of the most common causative allergens. The aims of this study were to confirm the presence of locally produced antibodies to D. farinae in nasal secretions between nasal provocation test (NPT)-positive and -negative groups of AR patients, to evaluate their relationships with the levels of inflammatory mediators, and to determine adaptive and innate immune responses in nasal mucosa. Methods Sixty AR patients sensitive to house dust mites confirmed by skin prick test or serum specific IgE to D. farinae underwent NPT for D. farinae. Nasal packs were placed in both nasal cavities of the patients for 5 minutes to obtain nasal secretions after NPT. The levels of total IgE, specific IgE to D. farinae, eosinophil cationic protein (ECP), and tryptase in nasal secretions were detected by using ImmunoCAP. The levels of specific IgE, IgA, and secretory IgA antibodies to D. farinae in nasal secretions were measured by using ELISA. The levels of IL-8, VEGF, IL-25, and IL-33 were also measured by using ELISA. Results High levels of total IgE, specific IgE, specific IgA, and secretory IgA to D. farinae, as well as inflammatory mediators, such as ECP, IL-8, VEGF and tryptase, were detected in nasal secretions, although the differences were not statistically significant between the NPT-positive and NPT-negative groups. Levels of all immunoglobulins measured in this study significantly correlated with ECP, IL-8, and VEGF (P0.05). IL-33 and IL-25 were also detected, and IL-25 level significantly correlated with IL-8 (r=0.625, P

Thyroid antibodies are frequently observed in urticaria patients, but their roles in urticaria are not clearly elucidated. We investigated the role of serum specific IgE to thyroid peroxidase (TPO) in patients with aspirin intolerant acute urticaria (AIAU) and aspirin intolerant chronic urticaria (AICU). We recruited 59 AIAU and 96 AICU patients with 69 normal controls (NC). Serum specific IgE to TPO was measured by manual direct ELISA, and CD203c expressions on basophil with additions of TPO were measured to prove a direct role of TPO in effector cells. The prevalences of serum specific IgE to TPO were significantly higher in AIAU (15.2%) and AICU groups (7.5%) compared to NC (0%, P=0.018: P=0.013, respectively). Flow cytometry showed CD203c induction in a dose dependent manner with serial additions of TPO in some AIAU and AICU patients having high specific IgE to TPO. Our findings show that the prevalence of serum specific IgE to TPO was significantly higher in both AIAU and AICU patients than in NC. It is suggested that specific IgE to TPO play a pathogenic role in AIAU and AICU. Graphical Abstract

PURPOSE This study aims to determine the efficacy and safety of house dust mite (HDM)-sublingual immunotherapy (SLIT) in elderly patients with AR. METHODS A total of 45 patients aged ≥ 60 years with HDM-induced AR who had ≥ 3 A/H ratio on skin prick test and/or ≥ 0.35 IU/L to both Dermatophagoides farinae and Dermatophagoides pteronyssinus by ImmunoCAP were enrolled in 4 university hospitals. To evaluate additional effects of HDM-SLIT, they were randomized to the SLIT-treated group (n = 30) or control group (n = 15). Rhinoconjunctivitis total symptom score (RTSS), rhinoscopy score, Korean rhinoconjunctivitis quality of life questionnaire, rhinitis control assessment test, asthma control test scores, and adverse reactions, were assessed at the first visit (V1) and after 1 year of treatment (V5); for immunological evaluation, serum levels of HDM-specific immunoglobulin A/IgE/IgG1/IgG4 antibodies and basophil response to HDMs were compared between V1 and V5 in both groups. RESULTS There were no significant differences in demographics, RTSS, skin reactivity to HDMs, or serum total/specific IgE levels to HDMs (P < 0.05, respectively) between the 2 groups. Nasal symptom score and RTSS decreased significantly at year 1 in the 2 groups (P < 0.05). There were no significant differences in percent decrease in nasal symptom score and RTSS at year 1 between the 2 groups (P < 0.05); however, rhinoscopic nasal symptom score decreased significantly in the SLIT-treated group (P < 0.05). Immunological studies showed that serum specific IgA levels (not specific IgE/IgG) and CD203c expression on basophils decreased significantly at V5 in the SLIT-treated group (P = 0.011 and P = 0.001, respectively), not in the control group. The control group required more medications compared to the treatment group, but there were no differences in adverse reactions. CONCLUSIONS It is suggested that HDM-SLIT for 1 year could induce symptom improvement and may induce immunomodulation in elderly rhinitis patients.

Aspirin-exacerbated respiratory disease (AERD) is an endotype of severe and eosinophilic adult asthma characterized by chronic rhinosinusitis with nasal polyps and hypersensitivity to aspirin and/or nonsteroidal anti-inflammatory drugs. A genetic contribution of dipeptidyl-peptidase 10 (DPP10) to asthma susceptibility and lung function decline has been reported. However, little is known about the role of DPP10 in the pathogenesis of AERD.To identify genetic variants of DPP10 that confer susceptibility to AERD or severe asthma.A case-control association study of DPP10 gene polymorphisms was performed in 3 groups of patients: 274 with AERD, 272 with aspirin-tolerant asthma, and 99 normal healthy controls. The rs17048175 single-nucleotide polymorphism was targeted based on a preliminary genomewide association study using an Affymetrix genomewide human single-nucleotide polymorphism array in a Korean population. DPP10, 15-hydroxyeicosatetraenoic acid, and YKL-40/chitinase-3-like protein were measured by enzyme-linked immunosorbent assay in sera taken from the study subjects.There was a significant association between rs17048175 and the AERD phenotype, but not with aspirin-tolerant asthma. The DPP10 level was significantly higher in sera from patients with AERD compared with patients with aspirin-tolerant asthma and control subjects (P = .021 and P.001, respectively). In addition, there was a significant difference of serum DPP10 level according to the single-nucleotide polymorphism (P = .001). Serum DPP10 level showed a strong correlation with 15-hydroxyeicosatetraenoic acid (r = 0.226, P = .017) and YKL-40 (r = 0.364, P = .004).This study suggests a genetic contribution of rs17048175 to DPP10 in eosinophilic inflammation induction in the airways and to AERD susceptibility.

Background: S100A8 and S100A9 can be produced by lipopolysaccharide-stimulated granulocytes and provoke an innate immune-mediated airway inflammation. Involvement of S100A8 and S100A9 has been implicated in asthma. To further understand the role of S100A8 and S100A9 during innate immune responses in baker's asthma, we investigated the associations of serum S100A8 and S100A9 with exposure to bakery allergens and polymorphisms of the Toll-like receptor 4 (TLR4) gene. Methods: Totally, 381 bakery workers and 100 unexposed healthy controls were recruited. Skin prick tests for bakery allergens were performed. Serum levels of S100A8, S100A9, myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, and interleukin (IL)-8 were measured using ELISA. Predictive values of serum S100A8 and S100A9 in bakery workers were evaluated by receiver-operating characteristic (ROC) curves. Polymorphisms of TLR4 -2027A→G and -1608T→C were genotyped. Results: Higher serum levels of S100A8 and S100A9 were noted in bakery workers compared to the normal controls (p < 0.001); however, no significant differences were noted according to work-related symptoms. The area under the ROC curve of serum S100A8 was 0.886 for occupational exposure (p < 0.001). The TLR4 -1608CC genotype was significantly associated with a higher serum S100A8 level (p = 0.025). Serum S100A8 and S100A9 levels were correlated with serum levels of MPO (r = 0.396 and 0.189, respectively), TNF-α (r = 0.536 and 0.280, respectively), and IL-8 (r = 0.540 and 0.205, respectively; p < 0.001 for all). Conclusion: S100A8 and S100A9 are involved in innate immune responses under the regulation of TLR4 polymorphisms in baker's asthma pathogenesis. Serum S100A8 could be a potential biomarker for predicting occupational exposure to wheat flour in bakery workers.

Background: Hereditary angioedema (HAE) is a genetically heterogeneous autosomal dominant disorder characterized by recurrent episodes of nonpruritic, nonpitting edema increasing after puberty. It can be fatal due to laryngeal or gastrointestinal (GI) involvement with varied and changing frequency of mortality according to studies published from the Western countries. Epidemiological and clinical data of HAE in Asian countries are sparse. We sought to examine the clinical characteristics of HAE patients in Korea. Methods: Patients diagnosed with HAE at 15 tertiary hospitals across the country until 2016 were retrospectively reviewed. Results: A total of 65 patients diagnosed with HAE by 2016 were identified. The prevalence of HAE was estimated at 1.3/1,000,000 in Korea. Of the 65 patients, 21 (32.3%) were males. A total of 90.8% patients had type I HAE, while the remaining 9.2% patients had type II HAE. The first symptom developed after 20 years in 73.8% of patients, with a mean age 28.4 ± 14.1 years. The age at diagnosis was 36.5 ± 15.8 years, with a mean time delay of 7.8 ± 10.5 years. While the face (82.3%) and extremities (upper 71.0%, lower 62.9%) were the most frequently involved, the GI tract was affected in 40.5% of Korean HAE patients. Prophylaxis was maintained in 62.5% of patients. There was no reported case of death from HAE so far. Conclusions: The clinical manifestation and severity of HAE may vary according to ethnicity. HAE is more infrequent and GI involvement is less likely in Korea compared with Western countries.

PURPOSE Increasing in prevalence, food allergy (FA) is becoming an important public health concern. In Korean adults, however, clinical phenotypes and causes of FA have not been studied. We aimed to study common causative allergens and clinical manifestations of FA in Korean adults. METHODS This study was conducted as a retrospective review of medical records for 95 patients (≥19 years old) diagnosed with FA from September 2014 to August 2015 at a single university hospital. RESULTS In the 95 patients, 181 FA events were recorded. The mean age of first onset of FA symptoms was 34.7±15.8 years. The most frequent causative food was seafood (34.8%); shrimp and crab allergies ranked highest, regardless of age and sex. Among all FA events, there were 47 (26.0%) cases of anaphylaxis and 26 (14.4%) cases of oral allergy syndrome (OAS). Seafood (51.1%) was the most frequent cause of anaphylaxis, followed by grains (14.9%). Most OAS cases were associated with fruits (95.7%). The frequency of fruit-induced FA was significantly higher in males than in females (23.0% vs 8.4%, P=0.011). While no cases of vegetables-induced FA were noted in younger individuals (19 to 30 years), vegetables accounted for 20.5% of FA symptoms in older subjects (≥51 years, P

Purpose Anaphylaxis is an immediate allergic reaction characterized by potentially life-threatening, severe, systemic manifestations. While studies have evaluated links between serious illness and posttraumatic stress disorder (PTSD), few have investigated PTSD after anaphylaxis in adults. We sought to investigate the psychosocial burden of recent anaphylaxis in Korean adults. Methods A total of 203 (mean age of 44 years, 120 females) patients with anaphylaxis were recruited from 15 university hospitals in Korea. Questionnaires, including the Impact of Event Scale-Revised-Korean version (IES-R-K), the Korean version of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Beck Depression Inventory (K-BDI), were administered. Demographic characteristics, causes and clinical features of anaphylaxis, and serum inflammatory markers, including tryptase, platelet-activating factor, interleukin-6, tumor necrosis factor-α, and C-reactive protein, were evaluated. Results PTSD (IES-R-K ≥ 25) was noted in 84 (41.4%) patients with anaphylaxis. Of them, 56.0% had severe PTSD (IES-R-K ≥ 40). Additionally, 23.2% and 28.1% of the patients had anxiety (K-BAI ≥ 22) and depression (K-BDI ≥ 17), respectively. IES-R-K was significantly correlated with both K-BAI (r = 0.609, P < 0.0001) and K-BDI (r = 0.550, P < 0.0001). Among the inflammatory mediators, tryptase levels were lower in patients exhibiting PTSD; meanwhile, platelet-activating factor levels were lower in patients exhibiting anxiety and depression while recovering from anaphylaxis. In multivariate analysis, K-BAI and K-BDI were identified as major predictive variables of PTSD in patients with anaphylaxis. Conclusions In patients with anaphylaxis, we found a remarkably high prevalence of PTSD and associated psychological distresses, including anxiety and depression. Physicians ought to be aware of the potential for psychological distress in anaphylactic patients and to consider psychological evaluation.