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Background Cefaclor, a second-generation oral cephalosporin, is widely prescribed to treat infectious diseases. Immediate hypersensitivity (HS) reactions to cefaclor have continuously been reported and are expected to increase with its greater use. This study aimed to investigate the clinical characteristics and risk factors of immediate HS to cefaclor over the most recent 5 years. Methods This retrospective study investigated 521 adverse drug reactions (ADRs) to cefaclor at pharmacovigilance centers at two tertiary hospitals from January 2014 to December 2018. In total, 459 patients with immediate HS to cefaclor were reviewed. Results A total of 459 cases of cefaclor immediate HS were included among 521 cefaclor ADRs, and anaphylaxis was recorded in 61.2%. Female sex (odds ratio 2.917, 95% confidence interval 2.397–3.550, P P P P = 0.010), asthma (8.075, 5.301–12.302, P P Conclusions Cefaclor was found to elicit high proportions of immediate HS and anaphylaxis. Physicians ought to be cautious with prescribing cefaclor to females, individuals with hypertension, liver diseases, or asthma, and patients taking nonsteroidal anti-inflammatory drugs. Trial registration This study was retrospectively registered.

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.

Chronic urticaria (CU) defined as repeatedly occurred itchy wheals and/or angioedema for at least 6 weeks. Due to the unpredictability, recurrent and disabling symptoms, and a considerably impaired quality of life, effective and tolerable treatment for CU patients is crucial. Almost a half of patients with CU are refractory to H1-antihistamines, even though the dose of antihistamines is increased up to 4-fold. Recently treatment modulating IgE levels and activities provides an efficient therapeutic approach. Omalizumab, the only approved anti-IgE treatment for chronic spontaneous urticaria (CSU) patients until now, with a strong evidence of the efficacy and safety, opened a new horizon in the care of the patients whose urticaria is not controlled with antihistamines. Recent international guidelines recommend omalizumab as the first choice of treatment for antihistamine-refractory CSU. However, as it is not curative neither disease-modifying agent, there is a subpopulation of CSU patients responding partly or never to omalizumab. The other things to be solved in the treatment of CU is that clinical evidence is still limited on chronic inducible urticaria (CIndU) and special populations. Thus, a new anti-IgE treatment, ligelizumab is actively evaluated in the efficacy compared with both placebo and omalizumab. Further understandings on the pathogenesis of CU can lead to the development of new mechanism-based therapeutics for CU patients.

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.

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.

Urticaria is a common cutaneous disease characterized by recurrent and transient wheals and pruritus, sometimes accompanied angioedema. The classification of urticaria is based on the duration of the disease and whether extrinsic triggers are identified or not. Acute urticaria is usually occurred by specific causes, such as drug, food, and infection, etc. Therefore, acute urticaria can be remitted within 6 weeks just by avoiding the exposure to the causes. However, chronic urticaria defined as repeatedly occurred itchy wheals and/or angioedema for at least 6 weeks, has a significant effect on patients’ quality of life. Chronic inducible urticaria can be triggered by various physical stimuli including dermographism, delayed pressure, cold, heat, cholinergic stimuli, sunlight, and exercise. Chronic spontaneous urticaria (CSU) is diagnosed when no specific extrinsic cause is identified in the patients. CSU due to autoimmune mechanism accounts for 30-50%, autologous serum skin test and anti-thyroid autoantibody can be evaluated. However, various physical stimuli, emotional or physical stress, drugs, particularly aspirin and non-steroidal anti-inflammatory drugs can exacerbate urticaria in 30-75% of patients with CSU. Allergic diseases and autoimmune diseases are more common in CSU patients than in general populations. To assess the severity of urticaria and to adjust treatment step, urticaria activity score over 7 days, calculated by the number of wheals and the severity of pruritus, is recommended by recent international guidelines. (Korean J Med 2019;94:353-357)

Background Aging populations are often accompanied by comorbidity and polypharmacy, leading to increases in adverse drug reactions (ADRs). We sought to evaluate the causes and characteristics of ADRs in older Korean adults (≥65 years) in comparison to younger individuals ( Methods Of 37,523 cases reported at a Korean pharmacovigilance center from 2011 to 2018, we reviewed 18,842 ADRs of certain or probable causality on the basis of WHO-UMC criteria. We estimated the number of ADRs per 1000 patients exposed to the major culprit drugs, and incidence rate ratios were obtained to assess high- and low-risk medications in older adults. Results In total, 4152 (22.0%) ADRs were reported for 3437 older adults (mean age, 74.6 years and 57.3% female). Tramadol (rate ratio, 1.32; 95% confidence interval [CI], 1.21–1.44; P P = 0.002) posed higher risks of ADRs in the older adults, whereas nonsteroidal anti-inflammatory drugs (NSAIDs) (0.35, 0.30–0.40, P P P P = 0.001) were higher in the older adults than in the younger patients. Analgesics primarily elicited cutaneous ADRs in the younger patients and gastrointestinal reactions in the older adults. ICM more commonly led to anaphylaxis in the older adults than the younger patients (3.0% vs. 1.6%, P = 0.019). Conclusion For early detection of ADRs in older adults, better understanding of differences in the causes and characteristics thereof in comparison to the general population is needed.

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.

Background Delayed drug hypersensitivity to first-line anti-tuberculosis medication is a major challenge in tuberculosis treatment. Objective This study was performed to investigate the efficacy/tolerability of desensitization therapy in treatment of first-line anti-tuberculosis medication hypersensitivity and the usefulness of immunologic evaluation therein. Methods This study was conducted as a prospective, observational cohort study. Subjects who experienced hypersensitivity reactions, including maculopapular exanthema (MPE) and drug reaction with eosinophilia and systemic symptoms (DRESS), to first-line anti-tuberculosis medications (isoniazid [INH], ethambutol [EMB], rifampin [RFP], and pyrazinamide [PZA]) were enrolled. Patch, intradermal, lymphocyte transformation, and oral provocation tests were performed to determine culprit drugs, which were desensitized with rapid and graded challenge protocols. Breakthrough reactions (BTRs) during or after desensitization were assessed. Results In total, 31 desensitization treatments (INH, 8; EMB, 8; RFP, 11; PZA, 4) to 12 patients (8 with MPE and 4 with DRESS) were performed. The overall success rate of desensitization was 80.7%. All the study subjects except one completed the full course of anti-tuberculosis treatment. The overall BTR free rate was 64.5%. Sixteen (80%) treatments for MPE and four (36.4%) for DRESS were BTR free (P = 0.023). Drugs that were positive on any two of three immunologic studies showed significantly high BTR rates (P = 0.014), although this was not correlated with desensitization failure rate. Conclusion Rapid desensitization therapy to multiple anti-tuberculosis medications for delayed drug hypersensitivity was safe and successful. Combination of multiple immunologic evaluations may predict BTR although it needs validation in larger studies.

Exposure-response and clinical outcome (CO) model for inhaled budesonide/formoterol was developed to quantify the relationship among pharmacokinetics (PK), pharmacodynamics (PD) and CO of the drugs and evaluate the covariate effect on model parameters. Sputum eosinophils cationic proteins (ECP) and forced expiratory volume (FEV1) were selected as PD markers and asthma control score was used as a clinical outcome. One- and two-compartment models were used to describe the PK of budesonide and formoterol, respectively. The indirect response model (IDR) was used to describe the PD effect for ECP and FEV1. In addition, the symptomatic effect on the disease progression model for CO was connected with IDR on each PD response. The slope for the effect of ECP and FEV1 to disease progression were estimated as 0.00008 and 0.644, respectively. Total five covariates (ex. ADRB2 genotype etc.) were searched using a stepwise covariate modeling method, however, there was no significant covariate effect. The results from the simulation study were showed that a 1 puff b.i.d. had a comparable effect of asthma control with a 2 puff b.i.d. As a result, the 1 puff b.i.d. of combination drug could be suggested as a standardized dose to minimize the side effects and obtain desired control of disease compared to the 2 puff b.i.d.

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.

Toluene diisocyanate (TDI) exposure induces oxidative stress and epithelial cell-derived inflammation, which affect the pathogenesis of TDI-induced occupational asthma (TDI-OA). Recent studies suggested a role for clusterin (CLU) and progranulin (PGRN) in oxidative stress-mediated airway inflammation. To evaluate CLU and PGRN involvement in airway inflammation in TDI-OA, we measured their serum levels in patients with TDI-OA, asymptomatic exposed controls (AECs), and unexposed healthy normal controls (NCs). Serum CLU and PGRN levels were significantly lower in the TDI-OA group than in the AEC and NC groups (P, Occupational asthma: Protein-based biomarkers show diagnostic promise Tracking the levels of two key proteins in workers’ blood may help identify those at risk of occupational asthma (OA). Exposure to toxic chemicals such as toluene diisocyanate (TDI), used in industrial foams and paints, can trigger OA. The condition often has a poor prognosis yet remains difficult to diagnose. Hae-Sim Park at Ajou University in Suwon, South Korea, and co-workers have pinpointed two proteins, clusterin and progranulin, the levels of which could indicate if a person is suffering from OA. The team measured serum levels in patients with TDI-OA, controls exposed to TDI with no symptoms and healthy un-exposed controls. Both clusterin and progranulin levels were significantly lower in TDI-OA patients than in both control groups. These two serum markers may help diagnose workers with OA and also identify those most at risk.

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.

Background: Many patients with chronic spontaneous/idiopathic urticaria (CSU/CIU) do not respond adequately to treatment with non-sedating H1 antihistamines (H1AH). There are limited studies on use of omalizumab as add-on therapy for treatment of CSU in an Asian population. Objective: The POLARIS study (NCT02329223), representing the first randomized, double-blind, placebo controlled phase III trial of omalizumab for CSU in an Eastern Asian population, evaluated efficacy and safety of omalizumab as add-on therapy for treatment of CSU. Methods: This 26-week multicenter (41 Japanese/Korean sites) study enrolled patients (12-75 years) who were symptomatic despite H1AH treatment. Eligible participants (N = 218) were randomized 1:1:1 to receive three subcutaneous injections of omalizumab 300 mg, 150 mg, or placebo every 4 weeks, followed by 12 weeks of follow-up. Primary outcome was change from baseline to Week 12 (Wk12) in weekly itch severity score (ISS7). Safety was assessed through the summary of adverse events (AEs). Results: Baseline demographics and disease characteristics were generally well balanced across treatment groups. At Wk12, statistically significant decreases from baseline were observed in ISS7 with omalizumab vs placebo (mean changes -10.22, -8.80, and -6.51 for omalizumab 300 mg, 150 mg and placebo; p < 0.001 and p = 0.006 vs placebo, respectively). Overall AE incidence was similar across treatment groups (54.8%, 57.7%, and 55.4% in omalizumab 300 mg, 150 mg, and placebo groups, respectively); nasopharyngitis was the most frequently reported AE in all treatment arms. Conclusion: The POLARIS study demonstrates that omalizumab is an efficacious and well-tolerated add-on therapy in Japanese and Korean H1AH-refractory patients with CSU.

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.

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.

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.

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.

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.

Background Because severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) rarely occur, clinical data based on large-scale studies are still lacking. Objective To provide information on culprit drugs and clinical characteristics, including morbidity and mortality of SCARs based on a nationwide registry. Methods SCAR cases that occurred from 2010 to 2015 were recruited to the Korean SCAR registry from 34 tertiary referral hospitals. Demographics, causative drugs, causality, and clinical outcomes were collected by reviewing the medical record. Results A total of 745 SCAR cases (384 SJS/TEN cases and 361 DRESS cases) due to 149 drugs were registered. The main causative drugs were allopurinol (14.0%), carbamazepine (9.5%), vancomycin (4.7%), and antituberculous agents (6.3%). A strong preference for SJS/TEN was observed in carbonic anhydrase inhibitors (100%), nonsteroidal anti-inflammatory drugs (84%), and acetaminophen (83%), whereas dapsone (100%), antituberculous agents (81%), and glycopeptide antibacterials (78%) were more likely to cause DRESS. The mortality rate was 6.6% (SJS/TEN 8.9% and DRESS 4.2%). The median time to death was 19 days and 29 days in SJS/TEN and DRESS respectively, and 89.8% of deaths occurred within 60 days after the onset of the skin symptoms. Conclusion Allopurinol, carbamazepine, vancomycin, and antituberculous agents were the leading causes of SCARs in Korea. Some drugs preferentially caused a specific phenotype. The mortality rate of SCARs was 6.6%, and most of the deaths occurred within 2 months.

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

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.

Background: In asthmatic patients, treatment with corticosteroids, in addition to conventional risk factors for osteoporosis, may lead to bone loss. Trabecular bone score (TBS) is a new, indirect parameter of bone quality. Studies have yet to evaluate TBS in asthmatic patients in relation to disease severity and corticosteroid use. Objective: 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 gender and age were included in this retrospective cohort study. TBS was calculated in the lumbar region, based on two dimensional projections of dual-energy X-ray absorptiometry. Results: Patients with severe asthma exhibited lower vertebral TBS values (1.33±0.11) than those with non-severe asthma (1.37±0.10, P=0.004), with non-active asthma (1.38±0.10, P 0.05). A TBS of 1.42 was determined as a cut-off for osteoporosis. TBS was significantly associated with cumulative systemic and inhaled corticosteroid doses, as well as lung function and airway hyper-responsiveness. Conclusion: TBS can be used as an early indicator of altered bone quality stemming from glucocorticoid therapy or, possibly, more severe asthma.

PURPOSE Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but serious condition that systematically damages various internal organs through T-cell-mediated immunological drug reactions. We aimed to investigate whether clinical manifestations of DRESS syndrome differ according to culprit drugs. METHODS We retrospectively analyzed data from 123 patients with probable/definite DRESS syndrome based on the RegiSCAR criteria (January 2011 to July 2016). The data were obtained from the Korean Severe Cutaneous Adverse Reaction Registry. Causality was assessed using the World Health Organization-Uppsala Monitoring Centre criteria. The culprit drugs were categorized as allopurinol, carbamazepine, anti-tuberculosis drug, vancomycin, cephalosporins, dapsone, and nonsteroidal anti-inflammatory drugs. RESULTS Differences were observed among culprit drugs regarding the frequencies of hepatitis (P

PURPOSE Cefaclor, a second-generation oral cephalosporin, is known to cause IgE-mediated hypersensitivity. Assays of serum-specific IgE (sIgE) to cefaclor are commercially available via the ImmunoCAP system (Thermo Fisher Scientific). While serum levels of sIgE >0.35 kU/L are considered indicative of an allergy, some patients with cefaclor allergy show low serum IgE levels. This study aimed to evaluate the proper cut-off levels of sIgE in the diagnosis of immediate hypersensitivity to cefaclor. MATERIALS AND METHODS A total of 269 patients with drug allergy history, who underwent assays of sIgE to cefaclor at Ajou University hospital and Dong-A University Hospital, were reviewed retrospectively. Among them, 193 patients exhibited cefaclor-induced immediate hypersensitivity with certain or probable causality of an adverse drug reaction according to the WHO-UMC (the World Health Organization-the Uppsala Monitoring Centre) algorithm, and 76 controls showed delayed hypersensitivity reactions to non-antibiotics. RESULTS In total, 126 of the 193 patients (65.3%) experienced anaphylaxis; they had higher serum sIgE levels than patients with immediate hypersensitivity who did not experience anaphylaxis (6.36±12.39 kU/L vs. 4.28±13.61 kU/L, 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.

Both immediate and delayed hypersensitivity reactions to iodinated contrast media (ICM) are relatively common. However, there are few data to determine the clinical utility of immunologic evaluation of ICM. To evaluate the utility of ICM skin testing in patients with ICM hypersensitivity, 23 patients (17 immediate and 6 delayed reactions) were enrolled from 3 university hospitals in Korea. With 6 commonly used ICM including iopromide, iohexol, ioversol, iomeprol, iopamidol and iodixanol, skin prick (SPT), intradermal (IDT) and patch tests were performed. Of 10 patients with anaphylaxis, 3 (30.0%) and 6 (60.0%) were positive respectively on SPTs and IDTs with the culprit ICM. Three of 6 patients with urticaria showed positive IDTs. In total, 11 (64.7%) had positive on either SPT or IDT. Three of 6 patients with delayed rashes had positive response to patch test and/or delayed IDT. Among 5 patients (3 anaphylaxis, 1 urticaria and 1 delayed rash) taken subsequent radiological examinations, 3 patients administered safe alternatives according to the results of skin testing had no adverse reaction. However, anaphylaxis developed in the other 2 patients administered the culprit ICM again. With 64.7% (11/17) and 50% (3/6) of the sensitivities of corresponding allergic skin tests with culprit ICM for immediate and delayed hypersensitivity reactions, the present study suggests that skin tests is useful for the diagnosis of ICM hypersensitivity and for selecting safe ICM and preventing a recurrence of anaphylaxis caused by the same ICM. Graphical Abstract

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.

Background Drug hypersensitivity reactions (DHRs) constitute a large portion of adverse drug reactions (ADRs), but studies for DHR incidence based on national data are scarce. Objective This study aimed to estimate the incidence and patterns of DHRs in a Korean population and the associated utilization of medical resources using the national claims data. Setting The retrospective cohort study performed using the national insurance claim database of the Health Insurance Review and Assessment (HIRA) in Korea. Methods The International Classification of Disease 10th revision code was used to identify DHRs with 20 drug induced DHR codes. The claim data with a diagnosis of DHR in the 2009-2014 periods were analyzed. Main outcome and measure The annual incidence and the 6-year incidence rates were calculated. Incidence rate coefficients were analyzed by sex, age, and year. DHRs following with visits of emergency department (ED) or intensive care unit (ICU) were assessed for utilization of medical resources and risk of ER or ICU visits by sex and age Results A total of 535,049 patients with 1,083,507 claims were assessed in the HIRA database for 6 years. DHR incidence was high in the elderly. The risk of ED and ICU visit with DHR was also higher in the elderly than in the young [highest relative risk, RR of ED 2.59 (1.65–4.07), ICU 5.04 (2.50–10.18)]. DHRs related to blood were high in the young age. Conclusion Incidence of DHRs in the real-world clinical practice was higher in the elderly and female. Clinical consequence was more severe in the elderly.

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.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Purpose: Differences in definitions of the condition, relevant triggers, and the geographical locations of study centers, cause estimates of the prev alence of anaphylaxis to vary. Recent epidemiological data indicate that the incidence of anaphylaxis is rising. Methods: To investigate the causes and clinical features of anaphylaxis in Korean adults, factors associated with the severity of the condition, and serious outcomes, a retrospective medical record review was performed on adult patients diagnosed with anaphylaxis between 2007 and 2011 in 15 University Hospitals of South Korea. Results: A total of 1,806 cases (52% male, age 16-86 years) were reported. Cutaneous symptoms (84.0%), combined with respiratory (53.9%) and/or cardiovascular (55.4%) symptoms, were the most frequent presentations. Using a recognized grading system, 1,776 cases could be classified as either mild, 340; moderate, 690; or severe, 746. Although eliciting factors varied significantly by age, gender, and regional and seasonal factors, drugs (46.5%; including nonsteroidal anti-inflammatory drugs, antibiotics, and radiocontrast media) were the most common cause of anaphylaxis, followed by foods (24.2%), insect stings (16.4%), exercise (5.9%), and unknown etiology (7.0%). All of age, multi-organ involvement, a history of allergic disease, and drug-induced anaphylaxis, were significant predictors of serious outcomes requiring hospital admission or prolongation of hospi tal stay. Epinephrine auto-injectors were prescribed for 7.4% of reported cases. Conclusions: The principal causes of anaphylaxis in Korean adults were drugs, food, and insect stings. Drug-associated anaphylaxis, a history of allergic disease, multi-organ involvement, and older age, were identified as predictors of serious outcomes.

Background and objective Airway hyperresponsiveness is a common feature of asthma. Methacholine and mannitol are two representative agonists for bronchial challenge. They have theoretically different mechanisms of action, and may have different diagnostic properties. However, their difference has not been directly evaluated among Korean adults. In this study, we compare the diagnostic properties of methacholine and mannitol bronchial provocation tests. Methods Asthmatic patients and non-asthmatic controls were recruited prospectively from four referral hospitals in Korea. Participants were challenged with each of methacholine and mannitol inhalation on different days. Their diagnostic utility was evaluated by calculating their sensitivity and specificity for asthma diagnosis. Response-dose ratio was also compared. Results A total of 50 asthmatic adults and 54 controls were enrolled (mean age 43.8 years). The sensitivity and specificity of mannitol challenge (defined by a PD15 of Conclusions The present study demonstrated overall similar diagnostic properties of two diagnostic tests, but also suggested their intercomplementary roles for asthma. The clinical trial registration number at ClinicalTrial.gov is NCT02104284.

Aim: This study aimed to identify prognostic factors of aspirin-exacerbated respiratory disease by comparing clinical and genetic data with the clinical course. Patients & methods: Patients were classified into two groups according to their response to inhalation rechallenge with lysine-aspirin after at least 1 year of regular treatment with antiasthmatic medications. Results: Forty eight patients (39.3%, group I) had negative responses, whereas 74 patients (60.7%, group II) had positive responses (n = 23) or were not rechallenged owing to persistent symptoms (n = 51). FEV1 at diagnosis and follow-up were significantly lower in group II than in group I. The CCR3 polymorphism at -520T/G differed significantly between the two groups, whereas no difference was found in other SNPs. Conclusion: Baseline FEV1 and lower lung function after treatment were clinical factors indicating a poor prognosis of aspirin-exacerbated respiratory disease. The G allele of CCR3 -520T>G was associated with persistent bronchial hypersensitivity to aspirin. Original submitted 17 June 2013; Revision 3 January 2014

Increased filaggrin expression was found to be correlated with severity scores in chronic spontaneous urticaria (CSU); however, the role of filaggrin breakdown products (FBPs) in CSU has not been studied. We collected stratum corneum (SC) specimens from the volar forearms of 10 CSU patients, 10 AD patients, and 10 healthy normal controls (NCs) and measured contents of FBPs (pyrrolidone carboxylic acid [PCA] and urocanic acid [UCA]) using UPLC-MS/MS, transepidermal water loss (TEWL) and epidermal pH. Compared to NCs, cis-UCA level was increased in CSU lesions (P P cis-to-trans-UCA ratio in SC specimens from CSU patients was significantly greater than those from AD and NC subjects. AD lesions had lower FBP and PCA contents compared to NC skin (both P cis-UCA, but not trans-UCA, enhanced the IgE-mediated basophil activation, as well as IgE- and calcium-mediated degranulation of LAD-2 cells, in a dose-dependent manner. These findings suggest that increased cis-to-trans UCA ratio in the epidermis is a distinct feature of CSU, which could enhance mast cell degranulation. Modulation of cis-UCA may be a potential target for skin diseases associated with IgE-mediated mast cell degranulation.