Searching for the Culprit Drugs for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis from a Nationwide Claim Database in Korea.

BACKGROUND: Ethnic differences exist in relation to culprit drugs for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We wanted to determine culprit drugs for SJS and TEN in Korean population. OBJECTIVE: To evaluate culprit drugs for SJS and TEN by applying an algorithm for assessment of drug causality for epidermal necrolysis (ALDEN) in a nationwide administrative database. METHODS: We used the claims database, which included claims data for the entire South Korean population. A retrospective cohort study was conducted by collecting subjects who were first diagnosed with SJS and TEN in 2011. All drugs prescribed to the subjects were reviewed and scored according to the ALDEN score. Drugs with an ALDEN score ≥2 were considered culprit drugs. RESULTS: A total of 187 subjects were included in the culprit drug analysis; 33 very probable, 101 probable, and 57 possible culprit drugs were identified for SJS and TEN according to the ALDEN score. The most frequently suspected culprit drug was allopurinol (19 cases), followed by carbamazepine (17 cases), lamotrigine (13 cases), amoxicillin (9 cases), and dorzolamide (9 cases). Most cases (78.8%, 52 of 66) associated with the use of allopurinol, carbamazepine, lamotrigine, dorzolamide, and methazolamide occurred between 13 and 44 days after initiating the drug. CONCLUSION: We applied the ALDEN score to the claims database to identify possible culprit drugs for SJS and TEN in South Korea. This approach could shed light on research and policymaking for drug adverse reactions.

Direct costs of severe cutaneous adverse reactions in a tertiary hospital in Korea.

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). CONCLUSION: 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.

The Fas Signaling Pathway Is a Common Genetic Risk Factor for Severe Cutaneous Drug Adverse Reactions Across Diverse Drugs.

PURPOSE: Human leukocyte antigen (HLA) has been recognized as the most important genetic risk factor for severe cutaneous adverse drug reactions (SCARs) caused by certain drugs. However, cumulated observations suggest the presence of genetic risk factors for SCARs other than drug-specific HLA. We aimed to identify a common genetic risk factor of SCARs across multiple drugs. METHODS: We performed 2 independent genome-wide association studies (GWASs). A total of 68 and 38 subjects with a diagnosis of SCAR were enrolled in each GWAS. Their allele frequencies were compared to those of healthy subjects in Korea. RESULTS: No single nucleotide polymorphism (SNP) with genome-wide significance was found in either GWAS. We next selected and annotated the 200 top-ranked SNPs from each GWAS. These 2 sets of annotated genes were then entered into the web interface of ConsensusPathDB for a pathway-level analysis. The Fas signaling pathway was significantly over-represented in each gene set from the 2 GWASs. CONCLUSIONS: Our observations suggest that the Fas signaling pathway may be a common genetic risk factor for SCARs across multiple drugs.

Clinical Features of Hereditary Angioedema in Korean Patients: A Nationwide Multicenter Study.

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.

Electronic Consultation Support System for Radiocontrast Media Hypersensitivity Changes Clinicians' Behavior.

PURPOSE: Patients with a history of radiocontrast media (RCM) hypersensitivity can be overlooked, resulting in repeated reactions. Therefore, a consultation support system for RCM hypersensitivity has been in operation at Seoul National University Bundang Hospital since December 2011. We analyzed the effect of this system on physicians' practice. METHODS: A retrospective study was conducted on patients with previous RCM reactions (December 1, 2010 to November 30, 2012). The control period was December 2010 to November 2011, and the intervention period was December 2011 to November 2012. The primary outcome was the composite outcome of premedication and consultation. Premedication was defined as preventive medication prescribed by the physician who ordered RCM-enhanced computed tomography (CT) at the same time. The secondary outcome was the recurrence rate after using the consultation support system. RESULTS: A total of 189 clinicians prescribed 913 CT scans during the control period and 225 clinicians performed 1,153 examinations during the intervention period. The odds ratio (OR) of achieving the composite outcome increased significantly after use of the consultation support system (OR, 1.54; 95% confidence interval [CI], 1.15-2.05). Clinicians in both medical (OR, 1.48; 95% CI, 1.06-2.07) and surgical (OR, 2.07; 95% CI, 1.24-3.46) departments showed significant changes in their behavior, whereas those in the emergency department did not (OR, 1.07; 95% CI, 0.41-2.78). Professors (OR, 1.47; 95% CI, 1.06-2.04) and trainees (OR, 1.97, 95% CI, 1.22-3.18) showed significant changes in their behavior toward patients with previous RCM reactions. The behavior of 86 clinicians who ordered CT scans during both the control and intervention periods was unchanged. CONCLUSIONS: The consultation support system for those with previous RCM hypersensitivity reactions changed physicians' practice patterns and decreased recurrent RCM hypersensitivity reactions as well.

Clinical course of asthma patients with H1N1 influenza infection and oseltamivir.

BACKGROUND: H1N1 influenza virus prevailed throughout the world in 2009. However, there are few reports on the clinical features of H1N1 influenza infection in adult asthma patients. We evaluated the clinical features in asthma patients with H1N1 influenza infection who took oseltamivir and compared them to those with other upper respiratory infections. METHODS: We reviewed asthma patients over 15 years of age who had visited Seoul National University Hospital and Seoul National University Bundang Hospital for suspected H1N1 influenza infection from August 2009 to March 2010. Various clinical features such as hospital admission days, respiratory symptoms, basal lung function, and past history was compared between H1N1 influenza PCR positive and negative groups. RESULTS: A total of 111 asthmatics were enrolled. All patients took oseltamivir. H1N1 RT-PCR was positive in 62 patients (55.9%), negative in 49 patients (44.1%). Wheezing developed more frequently in the H1N1 positive group. (43.5 vs. 16.7%, P=0.044). The rate of acute asthma exacerbations and pneumonia development were higher in the H1N1 positive group (59.7 vs. 51%, P=0.015, 25.0% vs. 0%, P<0.001). The rates for emergency room visit, hospital admissions, intensive care unit admissions, hospital days were not different between the groups. Underlying medical conditions were accompanied more frequently in the H1N1 negative patients (21.6% vs. 30.6%, P=0.002), especially cardiac disease (7.2% vs. 15.3%, P=0.011). CONCLUSIONS: H1N1 influenza infection may affect the clinical course of asthma combined with more severe manifestations; however, Oseltamivir could have affected the clinical course of H1N1 infected patients and made it milder than expected.

The virtual asthma guideline e-learning program: learning effectiveness and user satisfaction.

BACKGROUND/AIMS: Effective educational tools are important for increasing adherence to asthma guidelines and clinical improvement of asthma patients. We developed a computer-based interactive education program for asthma guideline named the Virtual Learning Center for Asthma Management (VLCAM). We evaluated the usefulness of program in terms of its effects on user awareness of asthma guideline and level of satisfaction. METHODS: Physicians-in-training at tertiary hospitals in Korea were enrolled in a cross-sectional questionnaire survey. The e-learning program on asthma guideline was conducted over a 2-week period. We investigated changes in the awareness of asthma guideline using 35-item self-administered questionnaire aiming at assessing physicians' knowledge, attitude, and practice. Satisfaction with the program was scored on 4-point Likert scales. RESULTS: A total of 158 physicians-in-training at six tertiary hospitals completed the survey. Compared with baseline, the overall awareness obtained from the scores of knowledge, attitude, and practice was improved significantly. Participants were satisfied with the VLCAM program in the following aspects: helpfulness, convenience, motivation, effectiveness, physicians' confidence, improvement of asthma management, and willingness to recommend. All items in user satisfaction questionnaires received high scores over 3 points. Moreover, the problem-based learning with a virtual patient received the highest user satisfaction among all parts of the program. CONCLUSIONS: Our computer-based e-learning program is useful for improving awareness of asthma management. It could improve adherence to asthma guidelines and enhance the quality of asthma care.

Characteristics of asthmatics with detectable IL-32γ in induced sputum.

BACKGROUND: Interleukin-32(IL-32)γ is a pro-inflammatory cytokine involved in the development and severity of chronic inflammatory diseases, but its role in asthma is unclear. OBJECTIVE: This study was conducted to evaluate the relationship of IL-32γ levels in sputum with the severity of asthma. METHODS: IL-32γ levels in the supernatant of induced sputum obtained from 89 patients with stable asthma were measured using a sandwich enzyme-linked immunosorbent assay (ELISA). The relationships between sputum IL-32γ levels and baseline forced expiratory volume in 1 s (FEV1% pred.), inflammatory cell profiles in sputum, and annual frequency of asthma exacerbation were determined. RESULTS: IL-32γ was detected in the sputum of 25 of 89 (28.1%) asthma patients, and the levels of sputum were negatively correlated with FEV1% pred. (ρ = -0.312, p = 0.003). The annual exacerbation rate was significantly higher in this group than in the IL-32-negative group (n = 64) (p = 0.03). Sputum IL-32γ levels correlated well with the annual exacerbation rate (ρ = 0.261, p = 0.014), but there were no differences in the inflammatory cell profiles in the induced sputum of IL-32-positive and IL-32-negative patients. CONCLUSION: The level of IL-32γ in induced sputum may be associated with asthma severity and related with higher risk of asthma exacerbation.

True rise in anaphylaxis incidence: Epidemiologic study based on a national health insurance database.

The incidence trend of anaphylaxis in Asia is not well investigated. The aim of this study is to estimate the entire population-based incidence of anaphylaxis in Korea using a nationwide administrative database.Data over a 7-year period (2008-2014) was obtained from the Korean National Health Insurance (NHI) claims database which covers 97.9% of the entire Korean population. Using diagnosis codes from the International Classification of Diseases-10 for anaphylaxis (T78.0, T78.2, T80.5, and T88.6), we identified the annual number of patients who had visited any hospital with a primary diagnosis of anaphylaxis. Incidence rates were calculated using the population distribution data of all NHI beneficiaries.The incidence of anaphylaxis in Korea was 32.19 episodes per 100,000 person-years in 2014, which nearly doubled from 2008 (16.02 episodes per 100,000 person-years). The incidence of anaphylaxis increased continuously throughout these years regardless of gender and age groups (P for trend < 0.001). Female was significantly less predisposed than male (adjusted odds ratio [OR], 0.69; 95% confident interval [CI], 0.66-0.72; P < 0.001). The incidence was the lowest in 0 to 19 age group and the highest in 40 to 69 age group (adjusted OR, 2.41; 95% CI, 2.29-2.54; P < 0.001).In conclusion, we report the increasing time trend of anaphylaxis incidence rates using nationwide claims database for the first time in Asia.

Fixed Food Eruption Caused by Actinidia arguta (Hardy Kiwi): A Case Report and Literature Review.

Fixed drug eruption (FDE) is a common hypersensitivity reaction characterized by recurrent, well-circumscribed, erythematous patches that arise at the same site as a result of systemic drug exposure. However, fixed food eruption (FFE), a lesion triggered by food ingestion, is a rare allergy that was first defined in 1996. Based on their anti-inflammatory and anti-oxidant properties, the fruit and leaves of Actinidia arguta, the hardy kiwi, are widely consumed across Korea, Japan, and China. This report describes the first case of FFE caused by hardy kiwi leaves, known as Daraesun in Korean, confirmed by oral provocation tests and skin biopsy.

Incidence of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Nationwide Population-Based Study Using National Health Insurance Database in Korea.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Overall, our data suggest that SJS, and TEN are infrequent but constantly arise throughout the years.

Feasibility of a smartphone application based action plan and monitoring in asthma.

BACKGROUND: Asthma patients may experience acute episodic exacerbation. The guidelines recommend that written action plan should be given to asthma patients. However, no one can predict when and where acute exacerbation will happen. As people carry smart phone almost anytime and anywhere, smartphone application could be a useful tool in asthma care. We evaluated the feasibility of the ubiquitous healthcare system of asthma care using a smartphone application (snuCare) based on the self-management guideline or action plan. METHODS: Forty-four patients including fragile asthmatics were enrolled from Seoul National University Bundang Hospital between December 2011 and February 2012. They were randomly assigned into application user (n = 22) or application nonuser group (n = 22). We evaluated user-satisfaction, and clinical parameters such as asthma control, Quality of Life Questionnaire for Adult Korean Asthmatics, and the adherence of patients. RESULTS: The characteristics were similar at baseline between the 2 groups except those who treated with short-term systemic steroid or increased dose of systemic steroid during previous 8 weeks (user vs. nonuser: 31.8% vs. 4.5%, p = 0.020). Total of 2,226 signals was generated during 8 weeks including 5 risky states. After eight weeks, the users answered that it was very easy to use the application, which was shown in highest scores in terms of satisfaction (mean ± standard deviation, 4.3 ± 0.56). Seventy-three percent of patients answered that the application was very useful for asthma care. User group showed improved the adherence scores (p = 0.017). One patient in application user group could avoid Emergency Department visit owing to the application while a patient in nonuser group visited Emergency Department. CONCLUSION: The ubiquitous healthcare system using a smartphone application (snuCare) based on the self-management guideline or action plan could be helpful in the monitoring and the management of asthma.

TNF-α enhance Th2 and Th17 immune responses regulating by IL23 during sensitization in asthma model.

BACKGROUND: TNF-α has been postulated to be a critical mediator contributing to airway inflammation. The purpose of this study was to evaluate the role of TNF-α in the induction of Th17 and Th2 cells related to asthma pathogenesis. OBJECTIVE: To evaluate detailed mechanisms for the modulation of IL-23 by TNF-α in sensitization period. METHODS: During sensitization period, 10µg of rat anti-mouse TNF-α mAb was intravenously administrated one hour before the application of OVA and 0.1µg of LPS. To see the relation between TNF-α and associated effectors cytokine, we replenished TNF-α KO mice with IL-23 during sensitization period. To assess cellular resources, CD11c+ cells isolated from lung tissue after sensitization were treated with anti-TNF-α Ab. RESULTS: Treatment of anti-TNF-α mAb during sensitization period significantly reduced airway eosinophilia, serum OVA-specific IgE levels and methacholine AHR compared to isotype Ab. Anti-TNF-α mAb treated mice showed significant reduction in the levels of IL-23 after sensitization in bronchoalveolar lavage fluid (BALF) as well as IL-17A, IL-4 levels in BALF after challenge compared with isotype Ab treated mice. Supplementation of IL-23 in TNF-α KO mice resulted in complete restoration of eosinophilic airway inflammation, AHR, and IL-17A and IL-4 expression in CD4+ T cells. Anti-TNF-α mAb treatment after sensitization significantly diminished the population of IL-23p19-secreting CD11c+ cells in lung. CONCLUSION: TNF-α plays an important role in the development of airway inflammation by enhancing IL-23/Th17 and Th2 immune responses.

Allergies are still on the rise? A 6-year nationwide population-based study in Korea.

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.

Family-Based Association Study of Pulmonary Function in a Population in Northeast Asia.

The spirometric measurement of pulmonary function by measuring the forced expiratory volume in one second (FEV1) is a heritable trait that reflects the physiological condition of the lung and airways. Genome-wide linkage and association studies have identified a number of genes and genetic loci associated with pulmonary function. However, limited numbers of studies have been reported for Asian populations. In this study, we aimed to investigate genetic evidence of pulmonary function in a population in northeast Asia. We conducted a family-based association test with 706 GENDISCAN study participants from 72 Mongolian families to determine candidate genetic determinants of pulmonary function. For the replication, we chose seven candidate single nucleotide polymorphisms (SNPs) from the 5 loci, and tested 1062 SNPs for association with FEV1 from 2,729 subjects of the Korea Healthy Twin study. We identified TMEM132C as a potential candidate gene at 12q24.3, which is a previously reported locus of asthma and spirometric indices. We also found two adjacent candidate genes (UNC93A and TTLL2) in the 6q27 region, which has been previously identified as a pulmonary function locus in the Framingham cohort study. Our findings suggest that novel candidate genes (TMEM132C, UNC93A and TTLL2) in two different regions are associated with pulmonary function in a population in northeast Asia.

Thalidomide inhibits alternative activation of macrophages in vivo and in vitro: a potential mechanism of anti-asthmatic effect of thalidomide.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Urban-rural differences in the prevalence of allergen sensitization and self-reported rhinitis in the elderly population.

BACKGROUND: Urbanization is frequently associated with allergic conditions during childhood; however, the literature lacks studies on the association between allergies and degree of urbanization in the elderly population. OBJECTIVE: To determine how the degree of urbanization affects the prevalence of allergic sensitization and self-reported rhinitis symptoms in elderly community populations. METHODS: The study population consisted of 1,311 elderly subjects identified from 2 community population cohort datasets who were divided into 3 groups according to the degree of urbanization (urban, semirural, and rural) where they resided. Current rhinitis symptoms were assessed using a questionnaire. Sensitization to inhalant allergen was measured using skin prick tests for 9 common allergens. RESULTS: Sensitization to inhalant allergen showed a positive correlation with degree of urbanization (urban 17.2%, semirural 9.8%, rural 6.0%; P for trend <.001), with a significant correlation observed between house dust mite allergens and degree of urbanization. Self-reported rhinitis symptoms were mostly nonallergic, but showed a positive correlation with degree of urbanization (urban 26.8%, semirural 18.2%, rural 11.5%; P for trend <.001). Self-reported rhinoconjunctivitis also correlated with urbanization. Correlations between self-reported allergic conditions and urbanization remained statistically significant in multivariate logistic regression tests. CONCLUSION: The present analyses found significant correlations between degree of urbanization with self-reported rhinitis symptoms and sensitization to inhalant allergen in the elderly population. These findings warrant further investigation of the roles that urban factors play in the development of elderly rhinitis and allergen sensitization.

Eosinophils Modulate CD4(+) T Cell Responses via High Mobility Group Box-1 in the Pathogenesis of Asthma.

Eosinophils have been reported to modulate T cell responses. Previously, we reported that high-mobility group box 1 protein (HMGB1) played a key role in the pathogenesis of asthma. This study was conducted to test our hypothesis that eosinophils could modulate T cell responses via HMGB1 in the pathogenesis of asthma characterized by eosinophilic airway inflammation. We performed in vitro experiments using eosinophils, dendritic cells (DCs), and CD4(+) T cells obtained from a murine model of asthma. The supernatant of the eosinophil culture was found to significantly increase the levels of interleukin (IL)-4 and IL-5 in the supernatant of CD4(+) T cells co-cultured with DCs. HMGB1 levels increased in the supernatant of the eosinophil culture stimulated with IL-5. Anti-HMGB1 antibodies significantly attenuated increases of IL-4 and IL-5 levels in the supernatant of CD4(+) T cells co-cultured with DCs that were induced by the supernatant of the eosinophil culture. In addition, anti-HMGB1 antibodies significantly attenuated the expressions of activation markers (CD44 and CD69) on CD4(+) T cells. Our data suggest that eosinophils modulate CD4(+) T cell responses via HMGB1 in the pathogenesis of asthma.

Impact of an electronic consultant system on hypersensitivity reactions to iodinated radiocontrast media: an observational study.

OBJECTIVE: To evaluate the impact of an electronic consultation support system on the incidence of hypersensitivity reactions to iodinated radiocontrast media (RCM). MATERIALS AND METHODS: A retrospective observational study was conducted before and after the introduction of the consultation support system. The 1-year study period was divided into two 6-month periods: before and after 1 December 2012 (baseline and intervention periods, respectively), which was when our consultation support system was introduced. Data from examinations were collected retrospectively from the hospital information centre and problem reporting sheets in the radiology department. The primary outcome was the incidence of RCM reactions before and after the introduction of the consultation support system. Generalised estimating equations were used to account for the correlation between the same patients measured on multiple occasions. RESULTS: There were 317/20,179 (1.6%) and 186/19,873 (0.9%) hypersensitivity reactions during the baseline and intervention periods, respectively. The consultation support system significantly decreased the odds of the occurrence of a RCM reaction (OR=0.59, 95% CI 0.49 to 0.71, p<0.001) compared with baseline. There was also a twofold increase in the premedication rate after initiation of the consultation support system (OR=2.05, 95% CI 1.16 to 3.65 p=0.01). However, there was no significant difference in the recurrence rate between the periods (OR=0.97, 95% CI 0.58 to 1.65, p<0.93). CONCLUSIONS: The introduction of the consultation support system reduced the incidence of hypersensitivity reactions to RCM and increased the use of premedication in patients with known hypersensitivity to RCM.