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Immunoglobulin E (IgE) is one of the central players in asthma and allergic diseases. Although the serum IgE level, a useful endophenotype, is generally increased in patients with asthma, genetic factors influencing IgE regulation in asthma are still not fully understood. To identify the genetic variations associated with total serum and mite-specific IgEs in asthmatics, a genome-wide association study (GWAS) of 657,366 single nucleotide polymorphisms (SNPs) was performed in 877 Korean asthmatics. This study found that several new genes might be associated with total IgE in asthmatics, such as CRIM1 (rs848512, P = 1.18×10(-6); rs711254, P = 6.73×10(-6)), ZNF71 (rs10404342, P = 7.60×10(-6)), TLN1 (rs4879926, P = 7.74×10(-6)), and SYNPO2 (rs1472066, P = 8.36×10(-6); rs1038770, P = 8.66×10(-6)). Regarding the association of specific IgE to house dust mites, it was observed that intergenic SNPs nearby to OPRK1 and LOC730217 might be associated with Dermatophagoides pteronyssinus (D.p.) and Dermatophagoides farinae (D.f.) in asthmatics, respectively. In further pathway analysis, the phosphatidylinositol signaling system and adherens junction pathways were estimated to play a role in the regulation of total IgE levels in asthma. Although functional evaluations and replications of these results in other populations are needed, this GWAS of serum IgE in asthmatics could facilitate improved understanding of the role of the newly identified genetic variants in asthma and its related phenotypes.

Aspirin-intolerant asthma (AIA) is a rare condition that is characterized by the development of bronchoconstriction in asthmatic patients after ingestion of non-steroidal anti-inflammatory drugs including aspirin. However, the underlying mechanisms of AIA occurrence are still not fully understood. To identify the genetic variations associated with aspirin intolerance in asthmatics, the first stage of genome-wide association study with 109,365 single nucleotide polymorphisms (SNPs) was undertaken in a Korean AIA (n = 80) cohort and aspirin-tolerant asthma (ATA, n = 100) subjects as controls. For the second stage of follow-up study, 150 common SNPs from 11 candidate genes were genotyped in 163 AIA patients including intermediate AIA (AIA-I) subjects and 429 ATA controls. Among 11 candidate genes, multivariate logistic analyses showed that SNPs of CEP68 gene showed the most significant association with aspirin intolerance (P values of co-dominant for CEP68, 6.0×10(-5) to 4.0×10(-5)). All seven SNPs of the CEP68 gene showed linkage disequilibrium (LD), and the haplotype of CEP68_ht4 (T-G-A-A-A-C-G) showed a highly significant association with aspirin intolerance (OR= 2.63; 95% CI= 1.64-4.21; P = 6.0×10(-5)). Moreover, the nonsynonymous CEP68 rs7572857G>A variant that replaces glycine with serine showed a higher decline of forced expiratory volume in 1s (FEV(1)) by aspirin provocation than other variants (P = 3.0×10(-5)). Our findings imply that CEP68 could be a susceptible gene for aspirin intolerance in asthmatics, suggesting that the nonsynonymous Gly74Ser could affect the polarity of the protein structure.

Background: There is very limited evidence regarding long-term prognosis of chronic cough. We examined longitudinal outcomes among patients with chronic cough, and explored predictors of cough persistence. Methods: A retrospective cohort was constructed of adults who had newly visited a specialist cough clinic in 2012–2013. All had undergone systematic investigation for chronic cough. The Hull Airway Reflux Questionnaire (HARQ) was administered to assess reflux cough symptoms. A follow-up survey was conducted in 2016–2017 to assess cough persistence. Results: From 418 candidates, 323 participated in the follow-up study; main analyses focused on patients with chronic persistent cough (n = 64; 19.8%) and remitted cough (n = 193; 59.8%). Compared with remitted cough group, chronic persistent cough group had more family history of chronic cough (17.2% vs. 4.7%, p = 0.001) and cold air-sensitive cough (62.5% vs. 44.6%, p = 0.013). The total HARQ score did not differ; however, two items (cough with eating and cough with certain foods) scored significantly higher in chronic persistent cough. In multivariate analyses, a family history of chronic cough (adjusted odds ratio 4.27 [95% confidence interval 1.35–9.89]), cold air-sensitive cough (2.01 [1.09–3.73]), and cough with eating (1.22 [1.02–1.45]) were associated with chronic persistent cough at 4 years. Conclusions: Cough persists in about 20% of patients after 4 years following systematic assessment and treatments. Several cough characteristics, such as family history, cold air-sensitivity, or reflux cough, may be associated with cough persistence. Larger cohort studies are warranted to further understand long-term prognosis and confirm predictors of persistence in patients with chronic cough.

Non-allergic asthma: Possible therapeutic target identified Targeting levels of a pro-inflammatory protein may help quell responses to airway irritants in patients with non-allergic asthma. Asthma often occurs when allergen exposure triggers an increase in white blood cells called eosinophils and the subsequent release of pro-inflammatory proteins such as interleukin-23 (IL-23) in the airways. However, research suggests up to one-third of sufferers have non-allergic eosinophilic asthma (NAEA), wherein airway inflammation is triggered by no specific allergen. Heung-Woo Park at the Seoul National University Medical Research Center, South Korea, and co-workers created a mouse model with excess IL-23 to examine the protein’s role in NAEA inflammation. They monitored airway responses to low doses of an acid irritant or diesel exhaust particles. The combination of high IL-23 plus an irritant triggered the release of other pro-inflammatory proteins in the airways, aggravating asthma symptoms.

Background: Delayed hypersensitivity reactions (DHRs) to radiocontrast media (RCM) occur in approximately 0.5–23.0% of patients and are thought to be caused by T cell-mediated mechanisms. However, an optimal pharmacological preventive strategy is not yet established in patients with histories of delayed reactions to RCM. Objective: We aimed to evaluate the efficacy of pharmacological prevention in patients with histories of delayed reactions to non-ionic low-osmolar RCM when re-exposed to RCM. Methods: A retrospective review of electronic medical records of 117 patients with previous histories of DHRs to RCM who visited an allergy clinic for the prevention of reactions after the re-exposure to RCM was conducted. The effects of pharmacological prevention were compared according to the symptom scores of previous reactions based on their intensities and durations with electronic medical records (EMRs). Results: Of the 117 patients who experienced DHRs after RCM injection, we confirmed the outcomes of RCM re-exposure in 101 patients. For pharmacological prevention, 92 patients (91.1%) received steroids before RCM injection and among them, 50 patients (49.5%) received additional steroids after RCM injection. With this pharmacological prevention, patients of symptoms improved or no recurrence, recurrence of similar previous symptoms, and recurrence of worse symptoms were 98 (97.0%), 2 (2.0%), and 1 (1.0%), respectively. The proportions of no recurrence after pharmacological prevention were lower in patients with severe reactions and higher symptom scores. Conclusion: Pharmacological prevention showed a beneficial effect in most patients with delayed hypersensitivity to RCM. Further investigations are needed to establish an effective protocol for the prevention of delayed reactions to RCM.

Background/Aims There are only a few reports on the direct costs of severe cutaneous adverse reactions (SCARs), including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), despite the tremendous negative impact these reactions can have on patients. We estimated the direct costs of treating SCARs. Methods Patients admitted to a tertiary teaching hospital for the treatment of SCARs from January 1, 2005 to December 31, 2010 were included. Patients who had experienced SCARs during their admission for other medical conditions were excluded. The direct costs of hospitalization and outpatient department visits were collected. Inpatient and outpatient care costs were calculated, and factors affecting inpatient care costs were analyzed. Results The total healthcare cost for the management of 73 SCAR patients (36 with DRESS, 21 with SJS, and 16 with TEN) was 752,067 US dollars (USD). Most of the costs were spent on inpatient care (703,832 USD). The median inpatient care cost per person was 3,720 (range, 1,133 to 107,490) USD for DRESS, 4,457 (range, 1,224 to 21,428) USD for SJS, and 8,061 (range, 1,127 to 52,220) USD for TEN. Longer hospitalization significantly increased the inpatient care costs of the patients with DRESS (by 428 USD [range, 395 to 461] per day). Longer hospitalization and death significantly increased the inpatient care costs of the patients with SJS/TEN (179 USD [range, 148 to 210] per day and an additional 14,425 USD [range, 9,513 to 19,337] for the deceased). Conclusions The management of SCARs required considerable direct medical costs. SCARs are not only a health problem but also a significant financial burden for the affected individuals.

Asthma: How genetic factors and depression affect symptom severity A novel mutation affects how depression influences the severity of asthma symptoms, with opposite effects in children and the elderly. Depression is known to affect the severity of symptoms experienced by patients with chronic disorders, such as asthma. Heung-Woo Park at Seoul National University College of Medicine in South Korea and coworkers investigated how genetic factors might influence the interaction between depression and asthma. Using previously collected genetic data, the researchers identified a mutation linked with both asthma and depression. In children with the mutation, depression was linked to severe asthma symptoms; children with depression but without the mutation experienced milder symptoms. The researchers observed the opposite relationship in a group of elderly patients with asthma. They conclude that further study of this mutation could illuminate ways to improve asthma management strategies.

Allergic diseases such as asthma, allergic rhinitis, and atopicdermatitis are heterogeneous diseases characterized by multiplesymptoms and phenotypes. Recent advancements in geneticstudy enabled us to identify disease associated genetic factors.Numerous genome-wide association studies (GWAS) have revealedmultiple associated loci for allergic diseases. However,the majority of previous studies have been conducted in populationsof European ancestry. Moreover, the associations of singlenucleotide polymorphisms (SNPs) with allergic diseaseshave not been studied amongst the large-scale general Koreanpopulation. Herein, we performed the replication study to validatethe previous variants, known to be associated with allergicdiseases, in the Korean population. In this study, we categorizedthree allergic related phenotypes, one allergy and two asthmarelated phenotypes, based on self-reports of physician diagnosisand their symptoms from 8,842 samples. As a result, we foundnominally significant associations of 6 SNPs with at least one allergicrelated phenotype in the Korean population. [BMB reports2012; 45(5): 305-310]

Thalidomide is known to have anti-inflammatory and immunomodulatory actions. However, the effect and the anti-asthmatic mechanism of thalidomide in the pathogenesis of asthmatic airways are not fully understood.This study is designed to determine the effect and the potential mechanism of thalidomide in the pathogenesis of asthmatic airways using animal model of allergic asthma.Six-week-old female BALB/C mice were sensitized with alum plus ovalbumin (OVA) and were exposed to OVA via intranasal route for 3 days for challenge. Thalidomide 200 mg/kg was given via gavage twice a day from a day before the challenge and airway hyperresponsivenss (AHR), airway inflammatory cells, and cytokines in bronchoalveolar lavage fluids (BALF) were evaluated. The expression levels of pro-inflammatory cytokines and other mediators were evaluated using ELISA, real time (RT)-qPCR, and flow cytometry. CRL-2456, alveolar macrophage cell line, was used to test the direct effect of thalidomide on the activation of macrophages in vitro.The mice with thalidomide treatment showed significantly reduced levels of allergen-induced BALF and lung inflammation, AHR, and the expression of a number of pro-inflammatory cytokines and mediators including Th2 related, IL-17 cytokines, and altered levels of allergen-specific IgG1/IgG2a. Of interesting note, thalidomide treatment significantly reduced expression levels of allergen- or Th2 cytokine-stimulated alternative activation of macrophages in vivo and in vitro.These studies highlight a potential use of thalidomide in the treatment of allergic diseases including asthma. This study further identified a novel inhibitory effect of thalidomide on alternative activation of macrophages as a potential mechanism of anti-asthmatic effect of thalidomide.

BACKGROUND: Exercise-induced bronchoconstriction (EIB) was recently classified into EIB alone and EIB with asthma, based on the presence of concurrent asthma. OBJECTIVE: Differences between EIB alone and EIB with asthma have not been fully described. METHODS: We retrospectively reviewed who visited an allergy clinic for respiratory symptoms after exercise and underwent exercise bronchial provocation testing. More than a 15% decrease of forced expiratory volume in 1 second (FEV1) from baseline to the end of a 6 min free-running challenge test was interpreted as positive EIB. RESULTS: EIB was observed in 66.9% of the study subjects (89/133). EIB-positive subjects showed higher positivity to methacholine provocation testing (61.4% vs. 18.9%, p

Anaphylaxis is the most severe form of radiocontrast media (RCM) induced hypersensitivity and can be life-threatening if profound hypotension is combined. With increased use of iodine based RCM, related hypersensitivity is rapidly growing. However, the clinical characteristics and risk factors of RCM induced anaphylaxis accompanied by hypotension (anaphylactic shock) are not clearly defined. This study was performed to investigate the risk factors of RCM induced anaphylactic shock and the clinical value of RCM skin testing to identify causative agents in affected patients.We analyzed the data of RCM induced anaphylaxis monitored by an inhospital pharmacovigilance center at a tertiary teaching hospital from January 2005 to December 2012 and compared the clinical features and skin test results according to the accompanying hypotension.Among total of 104 cases of RCM induced anaphylaxis, 34.6% of patients, developed anaphylaxis on their first exposure to RCM. Anaphylactic patients presenting with shock were older (57.4 vs. 50.1 years, p = 0.026) and had a history of more frequently exposure to RCM (5.1±7.8 vs. 1.9±3.3, p = 0.004) compared to those without hypotension. Among RCMs, hypotension was more frequent in anaphylaxis related to iopromide compared to other agents (85.0% vs. 61.4%, p = 0.011). Skin tests were performed in 51 patients after development of RCM induced anaphylaxis. Overall skin test positivity to RCM was 64.7% and 81.8% in patients with anaphylactic shock.RCM induced anaphylactic shock is related to multiple exposures to RCM and most patients showed skin test positivity to RCM.

BACKGROUND: We have previously identified four distinct groups of asthma patients in KOREAN cohorts using cluster analysis: (A) smoking asthma, (B) severe obstructive asthma, (C) early-onset atopic asthma, and (D) late-onset mild asthma. METHODS AND RESULTS: A longitudinal analysis of each cluster in a Korean adult asthma cohort was performed to investigate the clinical significance of asthma clusters over 12 months. Cluster A showed relatively high asthma control test (ACT) scores but relatively low FEV1 scores, despite a high percentage of systemic corticosteroid use. Cluster B had the lowest mean FEV1, ACT, and the quality of life questionnaire for adult Korean asthmatics (QLQAKA) scores throughout the year, even though the percentage of systemic corticosteroid use was the highest among the four clusters. Cluster C was ranked second in terms of FEV1, with the second lowest percentage of systemic corticosteroid use, and showed a marked improvement in subjective symptoms over time. Cluster D consistently showed the highest FEV1, the lowest systemic corticosteroid use, and had high ACT and QLQAKA scores. CONCLUSION: Our asthma clusters had clinical significance with consistency among clusters over 12 months. These distinctive phenotypes may be useful in classifying asthma in real practice.

Abstract Background Transcriptomic analysis has been used to elucidate the complex pathogenesis of heterogeneous disease and may also contribute to identify potential therapeutic targets by delineating the hub genes. This study aimed to investigate whether blood transcriptomic clustering can distinguish clinical and immune phenotypes of asthmatics, and microbiome in asthmatics. Methods Transcriptomic expression of peripheral blood mononuclear cells (PBMCs) from 47 asthmatics and 21 non-asthmatics was measured using RNA sequencing. A hierarchical clustering algorithm was used to classify asthmatics. Differentially expressed genes, clinical phenotypes, immune phenotypes, and microbiome of each transcriptomic cluster were assessed. Results In asthmatics, three distinct transcriptomic clusters with numerously different transcriptomic expressions were identified. The proportion of severe asthmatics was highest in cluster 3 as 73.3%, followed by cluster 2 (45.5%) and cluster 1 (28.6%). While cluster 1 represented clinically non-severe T2 asthma, cluster 3 tended to include severe non-T2 asthma. Cluster 2 had features of both T2 and non-T2 asthmatics characterized by the highest serum IgE level and neutrophil-dominant sputum cell population. Compared to non-asthmatics, cluster 1 showed higher CCL23 and IL1RL1 expression while the expression of TREML4 was suppressed in cluster 3. CTSD and ALDH2 showed a significant positive linear relationship across three clusters in the order of cluster 1 to 3. No significant differences in the diversities of lung and gut microbiomes were observed among transcriptomic clusters of asthmatics and non-asthmatics. However, our study has limitations in that small sample size data were analyzed with unmeasured confounding factors and causal relationships or function pathways were not verified. Conclusions Genetic clustering based on the blood transcriptome may provide novel immunological insight, which can be biomarkers of asthma immune phenotypes. Trial registration Retrospectively registered

Abstract Mesenchymal stem cells (MSCs) possess immunomodulatory properties that have therapeutic potential for the treatment of inflammatory diseases. This study investigates the effects of direct MSC administration on asthmatic airways. Umbilical cord MSCs (ucMSCs) were intratracheally administered to six-week-old female BALB/c mice sensitized and challenged with ovalbumin; airway hyperresponsiveness (AHR), analyses of airway inflammatory cells, lung histology, flow cytometry, and quantitative real-time PCR were performed. Furthermore, ex vivo and in vitro experiments were performed to assess the effects of ucMSC on M2 activation. Intratracheally administered ucMSCs decreased degree of airway resistance and the number of inflammatory cells such as T helper 2 (Th2) cells, type 2 innate lymphoid cells (ILC2), and macrophages in the murine asthma model. Particularly, MHCII and CD86 expression diminished in dendritic cells and alveolar macrophages (AMs) following ucMSC treatment. SiglecF+CD11c+CD11b- AMs show a negative correlation with type II inflammatory cells including Th2 cells, ILC2, and eosinophils in asthmatic mice and were restored following intratracheal ucMSCs treatment. In addition, ucMSCs decreased the macrophage polarization to M2, particularly M2a. The expression levels of markers associated with M2 polarization and Th2 inflammation were also decreased. ucMSC reduced Il-12 and Tnfa expression as well as that of M2 markers such as Cd206 and Retnla ex vivo. Furthermore, the in vitro study using IL-4 treated macrophages confirmed that both direct and indirect MSC treatment significantly reduced the expression of Il-5 and Il-13. In conclusion, ucMSCs appear to suppress type II inflammation by regulating lung macrophages via soluble mediators.

Cigarette smoking may exacerbate asthma, but the underlying mechanisms have not been studied extensively in human patients. Here authors show that type 3 innate lymphoid cells with activated phenotypes are found in the sputum and blood of smokers in higher frequencies, which might result in the aggravation of asthma.

Background: Tiotropium, a long-acting muscarinic antagonist, is recommended for add-on therapy to inhaled corticosteroids (ICS)-long-acting beta 2 agonists (LABA) for severe asthma. However, real-world studies on the predictors of response to tiotropium are limited. We investigated the real-world use of tiotropium in asthmatic adult patients in Korea and we identified predictors of positive response to tiotropium add-on. Methods: We performed a multicenter, retrospective, cohort study using data from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA). We enrolled asthmatic participants who took ICS-LABA with at least 2 consecutive lung function tests at 3-month intervals. We compared tiotropium users and non-users, as well as tiotropium responders and non-responders to predict positive responses to tiotropium, defined as 1) increase in forced expiratory volume in 1 s (FEV1) ≥ 10% or 100 mL; and 2) increase in asthma control test (ACT) score ≥3 after 3 months of treatment. Results: The study included 413 tiotropium users and 1756 tiotropium non-users. Tiotropium users had low baseline lung function and high exacerbation rate, suggesting more severe asthma. Clinical predictors for positive response to tiotropium add-on were 1) positive bronchodilator response (BDR) [odds ratio (OR) = 6.8, 95% confidence interval (CI): 1.6–47.4, P = 0.021] for FEV1 responders; 2) doctor-diagnosed asthma-chronic obstructive pulmonary disease overlap (ACO) [OR = 12.6, 95% CI: 1.8–161.5, P = 0.024], and 3) initial ACT score

Abstract Background Transglutaminase 2 (TG2), a multifunctional calcium‐dependent acyltransferase, is upregulated in asthmatic airways and reported to play a role in the pathogenesis of allergic asthma. However, the underlying mechanism is not fully understood. Objective To investigate the role of TG2 in alternative activation of alveolar macrophages by using murine asthma model. Methods TG2 expression was assessed in induced sputum of 21 asthma patients and 19 healthy controls, and lung tissue of ovalbumin (OVA)‐induced murine asthma model. To evaluate the role of TG2 in asthma, we developed an OVA asthma model in both TG2 null and wild‐type mice. The expression of M2 macrophage markers was measured by fluorescence‐activated cell sorting (FACS) after OVA sensitization and challenge. To evaluate the effect of TG2 inhibition in vitro, interleukin 4 (IL‐4) or IL‐13‐stimulated expression of M2 macrophage markers was measured in CRL‐2456 cells in the presence and absence of a TG2 inhibitor. Results The expression of both TG2 and M2 markers was increased in the sputum of asthmatics compared with that of healthy controls. The expression of TG2 was increased in macrophages of OVA mice. Airway hyperresponsiveness, and the number of inflammatory cells, including eosinophils, was significantly reduced in TG2 null mice compared with wild‐type mice. Enhanced expression of M2 markers in OVA mice was normalized by TG2 knockout. IL‐4 or IL‐13‐stimulated expression of M2 markers in alveolar macrophages was also attenuated by TG2 inhibitor treatment in vitro. Conclusion Our results suggest that TG2‐mediated modulation of alveolar macrophage polarization plays important roles in the pathogenesis of asthma.

Background/Aims Omalizumab is the first biologic known to be effective in patients with severe allergic asthma. Methods This study was conducted as a multicenter, single-group, open trial to evaluate the improvement in the quality of life with the additional administration of omalizumab for 24 weeks in Korean patients with severe persistent allergic asthma. Results Of the 44 patients, 31.8% were men and the mean age was 49.8 ± 11.8 years. A score improvement of 0.5 points or more in the Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) was noted in 50.0% (22/44) of the patinets. In the improved group, the baseline total immunoglobulin E (IgE) level and the amount of omalizumab used were higher, and the day and night asthma symptoms were more severe, compared to those in the non-improved group. According to the Global Evaluation of Treatment Effectiveness, favorable outcomes were found in 78.6% of patients. The Korean asthma control test (p < 0.005) and forced expiratory volume in 1 second % predicted (FEV1%; p < 0.01) improved significantly in patients who received omalizumab treatment, compared to that at week 0, and the total dose of rescue systemic corticosteroids significantly decreased (p < 0.05). The improved group on KAQLQ showed a significant improvement in FEV1% (p < 0.001). Conclusions Omalizumab can be considered a biological treatment for Korean patients with severe allergic asthma. It is recommended to consider omalizumab as add-on therapy in patients with high baseline total IgE levels and severe asthma symptoms.

Background: Asthma is a heterogeneous inflammatory airway disorder with various phenotypes. Quantitative computed tomography (QCT) methods can differentiate among lung diseases through accurate assessment of the location, extent, and severity of the disease. The purpose of this study was to identify asthma clusters using QCT metrics of airway and parenchymal structure, and to identify associations with visual analyses conducted by radiologists. Methods: This prospective study used input from QCT-based metrics including hydraulic diameter (Dh), luminal wall thickness (WT), functional small airway disease (fSAD), and emphysematous lung (Emph) to perform a cluster analysis and made comparisons with the visual grouping analysis conducted by radiologists based on site of airway involvement and remodeling evaluated. Results: A total of 61 asthmatics of varying severities were grouped into 4 clusters. From C1 to C4, more severe lung function deterioration, higher fixed obstruction rate, and more frequent asthma exacerbations were observed in the 5-year follow-up period. C1 presented non-severe asthma with increased WT, Dh of proximal airways, and fSAD. C2 was mixed with non-severe and severe asthmatics, and showed bronchodilator responses limited to the proximal airways. C3 and C4 included severe asthmatics that showed a reduced Dh of the proximal airway and diminished bronchodilator responses. While C3 was characterized by severe allergic asthma without fSAD, C4 included ex-smokers with high fSAD% and Emph%. These clusters correlated well with the grouping done by radiologists and clinical outcomes. Conclusions: Four QCT imaging-based clusters with distinct structural and functional changes in proximal and small airways can stratify heterogeneous asthmatics and can be a complementary tool to predict clinical outcomes.

Background/Aims Skin (STs) and drug provocation (DPTs) tests are essential for identifying the culprit drugs causing drug hypersensitivity reactions (DHRs). Several protocols have been developed for the identification of some culprit drugs, but they are neither thoroughly validated nor standardized. Furthermore, language barriers may impede the exchange of information necessary for test standardization. Methods We searched the Korean literature for articles on drug hypersensitivity published from 1933 to 2016 using the KoreaMed search engine and archives of Korean journals. We reviewed and rated all articles according to the description of STs and DPTs. Results Of the 632 articles obtained in our initial search, 34 had adequate descriptions of 15 STs and 22 DPTs. Up to 27 healthy control subjects in STs were enrolled to determine non-irritating concentrations. The concentrations used for intradermal tests were commonly a 1/10 dilution of those used for skin prick tests. The interpretations of the STs were mostly similar among researchers. For DPTs, most procedures were single-arm open-label tests of various drugs. The initial dose ranged from a quarter dose to a single therapeutic dose, depending on the severity of the original hypersensitivity reaction. The interval between doses was usually 30 to 60 minutes, and a positive reaction usually occurred within twice the time of the original reaction. Conclusions Efforts to distribute information are necessary to standardize protocols and better understand DHRs.

Background: Epidemiology and risk factors of drug-induced anaphylaxis are difficult to estimate due to lack of confirmative diagnosis and under reporting. Here we report the current state of drug-induced anaphylaxis in Korea based on an in-hospital pharmacovigilance database in a tertiary hospital. Methods: This study is a retrospective analysis of drug-induced anaphylaxis, reported to an in-hospital pharmacovigilance center in Seoul National University Hospital from June 2009 to May 2013. Anaphylaxis occurred in patients under 18 years of age or developed by medications administered from outside pharmacies or hospitals were excluded. We assessed causative drug, incidence per use of each drug and risk factors of fatal anaphylactic shock. Results: A total of 152 in-hospital drug-induced anaphylaxis cases were reported during the study period. The single most frequently reported drug was platinum compound and the incidence of anaphylaxis and anaphylactic shock in platinum compounds users was 2.84 and 1.39 per 1000 patients use. Risk factors of anaphylactic shock among total anaphylaxis cases were identified as older age ≥70 years [Odd's ratio (OR), 5.86; 95% confidence interval (CI), 1.70–20.14]. The use of iodinated contrast media (OR, 6.19; 95% CI, 1.87–20.53) and aminosteroid neuromuscular blocking agent (NMBA) (OR, 12.82; 95% CI, 1.50–109.92) were also a risk factor for the development of anaphylactic shock. Conclusions: Platinum compounds are the most commonly reported causative agents of in-hospital drug-induced anaphylaxis. Older age ≥70 years and drugs such as iodinated contrast media and aminosteroid NMBA are related with high risk of anaphylactic shock.

Background: Some western countries recently have shown a slowdown in the incidence of allergic diseases after worldwide increasing trends, but there are few data from Asian populations concerning changing trend of allergic diseases. We evaluated the recent trends in the prevalence of asthma and other allergic diseases in Korea. Methods: From the database of Korean National Health Insurance, a nationwide diagnostic data from 2009 to 2014 were extracted and the national prevalence was analyzed. Results: The prevalence per 1000 people of atopic dermatitis, allergic rhinitis, and asthma in 2014 was 19.0, 133.1, and 36.3, respectively. The prevalence of three diseases was highest in the age group under 10 as, 95.0, 384.1, and 132.1 per 1000 people, while the prevalence in the over-10-year-group was only 11.6, 109.5, and 27.3, respectively. The prevalence of atopic dermatitis and allergic rhinitis gradually decreased with older age, but the prevalence of asthma showed a re-increasing pattern from the age group 30–39 and reached another peak for the age group 70–79. During the study period, the prevalence of asthma and atopic dermatitis showed decreasing tendency. In contrast, the prevalence of allergic rhinitis steadily increased until 2013, especially in the age group under 10. Conclusions: The national prevalence of atopic dermatitis, and asthma did not show noticeable increase any more in Korea. However, the prevalence of allergic rhinitis still on the rise until recently, especially in the age group under 10. This is the first report in Asia suggesting a slowdown of the incidence of allergic diseases.

BackgroundSome recent studies suggested that reflux esophagitis is positively correlated with asthma. However, there are debates on this issue. The aim of this study is to clarify the true association between reflux esophagitis and asthma in a large population.MethodsMedical records of subjects who received health surveillance checkup between January 2005 and December 2011 were reviewed. Their endoscopic findings, medical history, body mass index, and smoking history were analyzed. Erosive esophagitis was defined as endoscopically detected mucosal break at the Z-line, irrespective of reflux symptom. Information about asthma history was obtained from their questionnaires and medical records.ResultsOut of the total 15,999 patients, 986 had erosive esophagitis and 376 had asthma. In this population, erosive esophagitis was inversely related with asthma in univariable analysis (OR, 0.586; 95% CI, 0.342-1.003, p = 0.049). In multivariable analysis, asthma was demonstrated as an independent negative risk factor for erosive esophagitis (OR, 0.472; 95% CI, 0.257-0.869, p = 0.016), under adjustment with age (OR, 1.000; 95% CI, 0.994-1.006, p = 0.977), male sex (OR, 2.092; 95% CI, 1.683-2.601, p < 0.001), body mass index (OR, 1.115; 95% CI, 1.090-1.141, p < 0.001), smoking (OR, 1.584; 95% CI, 1.318-1.902, p < 0.001), and urban residence (OR, 1.363; 95% CI, 1.149-1.616, p < 0.001). Likewise, erosive esophagitis was shown to be an independent negative risk factor for asthma (OR, 0.558; 95% CI, 0.324-0.960, p = 0.035) under adjustment with age (OR, 1.025; 95% CI, 1.015-1.034, p ConclusionsContrary to previous studies, this large scale data showed inverse association between erosive esophagitis and asthma. Further studies investigating the clear mechanism of this phenomenon are warranted.

Background: Chronic respiratory diseases such as asthma, allergic rhinitis (AR), chronic obstructive pulmonary disease (COPD), and rhinosinusitis are becoming increasingly prevalent in the Asia-Pacific region. The Asia-Pacific Burden of Respiratory Diseases study examined the disease and economic burden of AR, asthma, COPD, and rhinosinusitis across the Asia-Pacific and more specifically India. Objectives: To estimate the proportion of adults receiving care for asthma, AR, COPD, and rhinosinusitis and assess the economic burden, both direct and indirect of these chronic respiratory disease. Subjects and Methods: Consecutive participants aged ≥18 years with a primary diagnosis of asthma, AR, COPD, or rhinosinusitis were enrolled. Surveys comprising questions about respiratory disease symptoms, healthcare resource utilization, work productivity, and activity impairment were completed by treating physicians and participants during one study visit. Costs, indirect and direct, that contributed to treatment for each of the four respiratory diseases were calculated. Results: A total of 1000 patients were enrolled. Asthma was the most frequent primary diagnosis followed by AR, COPD, and rhinosinusitis. A total of 335 (33.5%) patients were diagnosed with combinations of the four respiratory diseases; the most frequently diagnosed combinations were asthma/AR and rhinosinusitis/AR. Cough or coughing up sputum was the primary reason for the current visit by patients diagnosed with asthma and COPD while AR patients reported a watery, runny nose, and sneezing; patients with rhinosinusitis primarily reported a colored nasal discharge. The mean annual cost per patient was US$637 (SD 806). The most significant driver of direct costs was medications. The biggest cost component was productivity loss. Conclusions: Given the ongoing rapid urbanization of India, the frequency of respiratory diseases and their economic burden will continue to rise. Efforts are required to better understand the impact and devise strategies to appropriately allocate resources.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening diseases; however, it is hard to estimate their incidence due to the rarity of these diseases. We evaluated the incidence of SJS and TEN using a nationwide administrative database.We used a national medical insurance review system (Health Insurance Review and Assessment) database which contained the claim data of the entire nation from 2009 to 2013 to estimate the accurate incidence of SJS and TEN in Korea. The diagnostic codes of L511 (SJS) or L512 (TEN) from the International Classification of Diseases-10th revision were used to define the target study population. We also retrospectively followed up a 2011 SJS and TEN cohort for 24 months in order to assess the in-hospital mortality, related complications and total claims cost due to SJS and TEN.A total of 1,167 (938 SJS and 229 TEN) cases were newly diagnosed from 2010 to 2013. The age- and sex-standardized annual incidences estimated in this study were 3.96 to 5.03 in SJS and 0.94 to 1.45 in TEN per million. There was no significant change in annual incidence throughout the study periods. When analyzed by 10-year age groups, the annual incidence was the lowest in group 20-29 years and the highest in group 70 for both SJS and TEN. Based on the 2011 cohort analysis, the in-hospital mortality were 5.7 and 15.1% for SJS and TEN, respectively. The mortality increased with age, particularly, after 40 years of age. Among the complications related with SJS or TEN, ocular sequelae was the most common (43.1 and 43.4% of SJS and TEN patients, respectively) followed by urethral sequelae (5.7 and 9.4% of SJS and TEN patients, respectively).Overall, our data suggest that SJS, and TEN are infrequent but constantly arise throughout the years.

BACKGROUND: Epidemiologic clinical studies suggested that chronic exposure to chlorine products is associated with development of asthma and aggravation of asthmatic symptoms. However, its underlying mechanism was not clearly understood. Studies were undertaken to define the effects and mechanisms of chronic low-dose chlorine exposure in the pathogenesis of airway inflammation and airway hyperresponsiveness (AHR). METHODS: Six week-old female BALB/c mice were sensitized and challenged with OVA in the presence and absence of chronic low dose chlorine exposure of naturally vaporized gas of 5% sodium hypochlorite solution. Airway inflammation and AHR were evaluated by bronchoalveolar lavage (BAL) cell recovery and non-invasive phlethysmography, respectively. Real-time qPCR, Western blot assay, and ELISA were used to evaluate the mRNA and protein expressions of cytokines and other inflammatory mediators. Human A549 and murine epithelial (A549 and MLE12) and macrophage (AMJ2-C11) cells were used to define the responses to low dose chlorine exposure in vitro. RESULTS: Chronic low dose chlorine exposure significantly augmented airway inflammation and AHR in OVA-sensitized and challenged mice. The expression of Th2 cytokines IL-4 and IL-5 and proinflammatory cytokine IL-1β and IL-33 were significantly increased in OVA/Cl group compared with OVA group. The chlorine exposure also activates the major molecules associated with inflammasome pathway in the macrophages with increased expression of epithelial alarmins IL-33 and TSLP in vitro. CONCLUSION: Chronic low dose exposure of chlorine aggravates allergic Th2 inflammation and AHR potentially through activation of inflammasome danger signaling pathways.

Though insurance claims data are useful for researching asthma, they have important limitations, such as a diagnostic inaccuracy and a lack of clinical information. To overcome these drawbacks, we used the novel method by merging the clinical data from our asthma cohort with the National Health Insurance (NHI) claims data.Longitudinal analysis of asthma-related healthcare use from the NHI claims database, merged with data of 736 patients registered in a Korean asthma cohort, was conducted for three consecutive years from registration of the cohort. Asthma-related asthma healthcare referred to outpatient and emergency department visits, hospitalizations, and the use of systemic corticosteroids. Univariate and multivariate logistic regression analysis was used to evaluate risk factors for asthma-related healthcare. Over three years after enrollment, many patients changed from tertiary to primary/secondary hospitals with a lack of maintenance of inhaled corticosteroid-based controllers. An independent risk factor for emergency visits was a previous history of asthma exacerbation. In hospitalizations, old age and Asthma Control Test (ACT) score variability were independent risk factors. An independent risk factor for per person cumulative duration of systemic corticosteroids was the FEV1 (Forced expiratory volume in one second)%. The use of systemic corticosteroids was independently associated with being female, the FEV1%, and ACT score variability.We found that old age, being female, long-standing asthma, a low FEV1%, asthma brittleness, asthma drug compliance, and a history of asthma exacerbation were independent risk factors for increased asthma-related healthcare use in Korea.

BACKGROUND:The epidemiology of cough in the elderly population has not been studied comprehensively. The present study aimed to investigate the epidemiology of cough in a community elderly population, particularly in relation with their comorbidity. METHODS:A cross-sectional analysis was performed using a baseline dataset from the Korean Longitudinal Study on Health and Aging, a community-based elderly population cohort study. Three types of cough (frequent cough, chronic persistent cough, and nocturnal cough) were defined using questionnaires. Comorbidity was examined using a structured questionnaire. Health-related quality of life was assessed using the Short Form 36 questionnaire. RESULTS:The prevalence was 9.3% for frequent cough, 4.6% for chronic persistent cough, and 7.3% for nocturnal cough. In multivariate logistic regression analyses, smoking, asthma and allergic rhinitis were found to be risk factors for cough in the elderly. Interestingly, among comorbidities, constipation and uncontrolled diabetes mellitus (HbA1c ≥ 8%) were also found to have positive associations with elderly cough. In the Short Form 36 scores, chronic persistent cough was independently related to impairment of quality of life, predominantly in the mental component. CONCLUSIONS:Cough has a high prevalence and is detrimental to quality of life in the elderly. Associations with smoking, asthma and rhinitis confirmed previous findings in younger populations. Previously unrecognised relationships with constipation and uncontrolled diabetes mellitus suggested the multi-faceted nature of cough in the elderly.