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.

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.

An effective strategy to prevent allopurinol-induced hypersensitivity by HLA typing.

PURPOSE: This study was conducted to evaluate the usefulness of human leukocyte antigen (HLA) typing in preventing allopurinol-induced severe cutaneous adverse reactions (SCARs) through the application of an allopurinol tolerance induction protocol or prescription of other alternative medications in high-risk patients. METHODS: HLA typing was performed in patients with chronic renal insufficiency who needed allopurinol. HLA-B*58:01-negative patients were prescribed the usual dose of allopurinol. For HLA-B*58:01-positive patients, administration of either allopurinol based on a 28-day tolerance induction protocol or alternative medications was initiated. Hypersensitivity reactions were surveyed for 90 days and compared with the result of a previous retrospective cohort study. RESULTS: Among a total of 401 study subjects, no SCARs were noted in HLA-B*58:01-positive patients with application of the tolerance induction protocol (n = 30) or alternative medications (n = 16), nor were any SCARs observed in HLA-B*58:01-negative patients who started allopurinol at the usual dose (n = 355). Compared with the previous retrospective cohort study, a significant reduction in SCARs was observed in HLA-B*58:01-positive patients (0 vs. 18%; P = 0.002). CONCLUSION: This study shows the usefulness of HLA-B*58:01 screening in identifying patients at high risk for the development of allopurinol-induced SCARs and suggests that application of a tolerance induction protocol or alternative medications could be an effective strategy to prevent allopurinol-induced SCARs in HLA-B*58:01-positive patients.

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.

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.

Xenon ventilation computed tomography and the management of asthma in the elderly.

BACKGROUND AND OBJECTIVE: Xenon ventilation computed tomography (CT) has shown potential in assessing the regional ventilation status in subjects with asthma. The purpose of this study was to evaluate the usefulness of xenon ventilation CT in the management of asthma in the elderly. METHODS: Treatment-naïve asthmatics aged 65 years or older were recruited. Before initiation of medication, spirometry with bronchodilator (BD) reversibility, questionnaires to assess the severity of symptoms including a visual analogue scale (VAS), tests to evaluate cognitive function and mood, and xenon ventilation CT were performed. Xenon gas trapping (XT) on xenon ventilation CT represents an area where inhaled xenon gas was not expired and was trapped. Symptoms and lung functions were measured again after the 12-week treatment. RESULTS: A total of 30 elderly asthmatics were enrolled. The severity of dyspnoea measured by the VAS showed a significant correlation with the total number of areas of XT on the xenon ventilation CT taken in the pre-BD wash-out phase (r = -0.723, P < 0.001). The total number of areas of XT significantly decreased after BD inhalation, and differences in the total number of areas of XT (between the pre- and post-BD wash-out phases) at baseline showed significant correlations with the per cent increases in forced expiratory volume in 1 s after subsequent anti-asthma treatment (r = -0.775, P < 0.001). CONCLUSIONS: Xenon ventilation CT may be an objective and promising tool in the measurement of dyspnoea and prediction of the treatment response in elderly asthmatics.

Diagnostic properties of the methacholine and mannitol bronchial challenge tests: a comparison study.

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 <635 mg) were 48.0% and 92.6%, respectively, whereas those of methacholine (defined by a PC20 of <16 mg/mL) were 42.0% and 98.1%, respectively. Twenty asthmatic participants (24%) showed positive response to a single agonist only. In the receiver operating curve analyses using response-dose ratio values, area under the curve was 0.77 (95% confidence interval (CI): 0.68-0.86) for mannitol, and 0.89 (95% CI: 0.83-0.95) for methacholine. The correlations between log- transformed mannitol and methacholine response-dose ratios were significant but moderate (r = 0.683, P < 0.001). 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.

Expression levels of eosinophil granule protein mRNAs in induced sputum reflect airway hyperresponsiveness and airflow limitation.

Eosinophils are regarded as the major effector cells that produce symptoms in allergic diseases. Activation of eosinophils induces extracellular release of a number of eosinophil granule proteins, including major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin. The objective of this study was to evaluate the differences and significance of the sputum eosinophil% and expression levels of eosinophilic granule protein mRNAs in allergic airway disease. Induced sputum samples were obtained from non-smokers with 25 asthma, 54 eosinophilic bronchitis, 16 allergic rhinitis, and 19 healthy control subjects. The eosinophil granule protein mRNAs were measured with real time RT-PCR. There was no correlation between the sputum eosinophil% and the mRNA level of any of eosinophil granule proteins. However, the expression levels of MBP and ECP mRNAs were higher in subjects with each of the specified allergic diseases than those in control subjects (P < 0.05). Moreover, in the subjects with allergic sensitization, the expression levels of MBP and EPO mRNAs were significantly higher in those with airway hyperresponsiveness (13 subjects) than in those without airway hyperresponsiveness (32 subjects) (P = 0.004 and 0.010, respectively). In asthma patients, the FEV1% was negatively correlated with ECP mRNA levels (r = -0.510, P = 0.022), but showed no correlation with sputum eosinophil%. In conclusion, mRNA levels of eosinophil granule proteins, rather than sputum eosinophil%, may reflect airway hyperresponsiveness and airflow limitation. In practice, consideration for the eosinophil% as well as the eosinophil granule proteins levels in induced sputum is needed.

Clinical features and prognostic factors in severe cutaneous drug reactions.

BACKGROUND: Severe cutaneous adverse reactions (SCARs) include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). SJS and TEN (SJS/TEN) and DRESS are thought to be different diseases; however, they share some clinical and laboratory features. Although SCORTEN serves as an excellent prognostic marker for SJS/TEN, there is still a need for development of other prognostic markers for SCARs. METHODS: The study population consisted of 88 SCAR patients. Clinical characteristics and clinical manifestations were compared between SJS/TEN and DRESS. Risk factor analyses for prolonged hospitalization were performed. RESULTS: Of the 88 patients, 41 were SJS/TEN and 47 were DRESS. Mortality rates of TEN and DRESS were 9.8 and 2.1%, respectively. Allopurinol and carbamazepine were the most common causes of both SJS/TEN and DRESS (34.7 and 62.9%, respectively). Some of the systemic presentations, such as fever and laboratory abnormalities were common in both phenotypes. Thrombocytopenia tended to be related to prolonged hospitalization (longer than 3 weeks) in SJS/TEN (odds ratio, OR = 5.1, 95% confidence interval, CI 0.8-31.8, p = 0.076). In DRESS patients, leukocytosis at presentation (OR 4.8, 95% CI 1.1-20.3, p = 0.03) was related to prolonged hospitalization. CONCLUSIONS: Clinical features of SCARs in a tertiary hospital in Korea were similar to those reported previously. SJS/TEN and DRESS shared some clinical and laboratory features. Thrombocytopenia for SJS/TEN and leukocytosis at presentation for DRESS may be useful prognostic markers for prolonged hospitalization.

Allergic rhinitis and serum 25-hydroxyvitamin D level in Korean adults.

BACKGROUND: Recently, it has been suggested that airway hyper-responsiveness, asthma, and atopic dermatitis are associated with a low vitamin D level. OBJECTIVE: To evaluate whether the occurrence of allergic rhinitis (AR) is related to serum vitamin D levels in the general Korean adult population. METHODS: Data obtained as part of the fourth annual Korean National Health and Nutrition Examination Survey (2009) of 8,012 adults older than 18 years were analyzed. The correlation between serum 25-hydroxyvitamin D (25[OH]D) level and presence of AR using questionnaires on symptoms, history of diagnosis of AR, and rhinoscopic findings were analyzed. All estimates were calculated based on sampling weight. RESULTS: Mean age was 44.41 years and men constituted 49.8% of the sample. Participants with diagnosed AR constituted 11.1%. The mean 25(OH)D level of the AR group was lower than that of the non-AR group (16.71 ± 0.30 vs 17.75 ± 0.25 ng/mL, P < .001). A comparison of the prevalence of AR in the 3 groups showed that AR steadily decreased in the higher 25(OH)D groups (13.0% in group I [<15 ng/mL], 11.5% in group II [≥15-<25 ng/mL], and 7.2% in group III [≥25 ng/mL], P < .001). After adjusting for body mass index, smoking status, age, sex, sun exposure, income quartile, exercise, and body fat percentage, lower serum 25(OH)D levels remained significantly associated with the presence of AR compared with group III (hazard ratio 1.559 in group I and 1.430 in group II). CONCLUSION: This study suggested a potential association between low vitamin D levels and AR prevalence in Korean adults.

Obstructive sleep apnea is associated with reduced quality of life in adult patients with asthma.

BACKGROUND: Recent data suggest that obstructive sleep apnea (OSA) is an important contributor to severe uncontrolled asthma. OBJECTIVE: To investigate the clinical characteristics, asthma control, and asthma-related quality of life in adult patients with asthma at a high risk for OSA. METHODS: A total of 217 patients with asthma who visited our tertiary-care clinic were randomly recruited. They completed the Berlin questionnaire, which screens for OSA risk, a quality-of-life questionnaire for adult Korean patients with asthma (QLQAKA), and underwent an asthma control test (ACT). Fraction of exhaled nitric oxide (FeNO), lung function, blood lipid profiles, and body composition were evaluated. RESULTS: The mean age was 58.4 ± 15.4, and 91 (41.9%) were male. Eighty-nine subjects (41.0%) were classified as high risk for OSA from the Berlin questionnaire. Patients with a high OSA risk were significantly older, had a higher prevalence of hypertension, higher BMI, non-atopic predisposition, and longer asthma treatment duration in the baseline clinical characteristics. The high OSA risk group had a lower ACT score than the low OSA risk group, but it was not statistically significant (20.9 ± 3.6 vs 21.5 ± 3.3, P = .091). The QLQAKA score was significantly lower in the high OSA risk group compared with the low OSA risk group (64.4 ± 10.9 vs 68.1 ± 11.1, P = .026), especially in the activity-domain (P = .005). The FeNO was not significantly different between the 2 groups. CONCLUSION: Quality of life is significantly decreased in adult patients with asthma with a high risk of OSA. Special consideration is needed for the care and treatment of patients with asthma who have a high risk of OSA.

Rhinitis in a community elderly population: relationships with age, atopy, and asthma.

BACKGROUND: Rhinitis is one of the most frequent medical conditions. However, there is sparse epidemiologic evidence for rhinitis in the elderly population. OBJECTIVE: To investigate the prevalence of rhinitis in elderly adults and its relations to asthma and other comorbidities. METHODS: A cross-sectional analysis was performed using the baseline dataset of the Korean Longitudinal Study on Health and Aging, a community-based elderly population cohort in Korea (≥65 years old). Structured questionnaires were used to define rhinitis, asthma, and comorbidity, and allergen skin prick tests were used to define atopy. Health-related quality of life was assessed by short-form 36 questionnaires. RESULTS: In total, 982 elderly adults (98.2%) were included in the present study. The prevalence of rhinitis was 25.6% and did not decrease until 90 years of age. The prevalence of atopy was 17.2% (18.8% in participants with rhinitis), and atopy did not show a significant association with rhinitis. In multivariate logistic regression analyses, relations between asthma and rhinitis were significant. Among comorbid conditions, none were significantly associated with rhinitis. In the short-form 36 questionnaire analyses, rhinitis was independently related to a decrease in the physical aspects of quality of life. CONCLUSION: The present study found a high prevalence of nonallergic rhinitis in elderly participants, which was significantly related to asthma and quality of life.

New insight into the assessment of asthma using xenon ventilation computed tomography.

BACKGROUND: Image analyses include computed tomography (CT), magnetic resonance imaging, and xenon ventilation CT, which is new modality to evaluate pulmonary functional imaging. OBJECTIVE: To examine the usefulness of dual-energy xenon ventilation CT in asthmatic patients. METHODS: A total of 43 patients 18 years or older who were nonsmokers were included in the study. Xenon CT images in wash-in and wash-out phases were obtained at baseline and after inhalation of methacholine and salbutamol. The degrees of ventilation defects and xenon trappings were evaluated through visual analysis. RESULTS: Ventilation defects and xenon trapping were significantly increased and decreased after methacholine challenge and salbutamol inhalation, respectively (P < .005). The ventilation abnormalities were not significantly related to the percentage of forced expiratory volume in 1 second (FEV1) or the ratio of FEV1 to forced vital capacity. Xenon trappings after salbutamol inhalation were negatively related to the scores of the asthma control test, wheezing, or night symptoms, with statistical significance (P < .05), whereas, FEV1 showed no significant correlation with symptom scores. Baseline FEV1 was significantly lower and dyspnea and wheezing were more severe in the non-full reversal group than in the full reversal group after salbutamol inhalation in xenon CT (P < .05). The degree of ventilation defects were positively correlated with FEV1 improvement after 3 months of treatment (P = .02). CONCLUSION: The results of this study suggest that xenon ventilation CT can be used as a new method to assess ventilation abnormalities in asthma, and these ventilation abnormalities can be used as novel parameters that reflect the status of asthma control and symptom severity.

Expression pattern of GSTP1 and GSTA1 in the pathogenesis of asthma.

Reactive oxygen species (ROS) are known aggravating factors for airway inflammation in asthma. Glutathione S-transferases (GSTs) detoxify ROS and toxic compounds in environmental exposures. However, little is known about the regulation of GST and expression of GST subtypes in asthma. The aim of this study was to evaluate how GSTs are regulated in asthma. We observed total GST activity and expression of GST subtypes in murine asthma models and GST expressions in induced sputum cells of asthmatics. Total GST activity was increased in BAL fluids of OVA-treated murine asthma model. GSTP and GSTA are highly expressed in peribronchiolar mononuclear inflammatory cells and epithelial cells in OVA-treated mice. GSTM are expressed in epithelial cells in both OVA and PBS-treated groups. GSTP1 mRNA expression was increased in the lung of OVA-treated mice compared with PBS-treated mice. GSTA1, GSTM1, and GSTT1 mRNA expressions were not different between both groups. GSTA1 mRNA expression was increased in induced sputum cells of asthmatics compared with healthy controls. GSTP1, GSTM1, and GSTT1 mRNA expressions were not different between asthmatics and healthy controls. In asthmatics, GSTP1 and GSTA1 mRNA expressions were higher in induced sputum cells of asthmatics with PC20 ≤ 4 mg/ml than those with PC20 > 4 mg/ml. GSTM1 and GSTT1 mRNA expressions were not different between two groups. These findings suggest that GSTs are upregulated in the airways of asthmatics in response to increased oxidative stress. GSTP and GSTA are thought to play an important role in protecting the airways of asthmatics compared with GSTM and GSTT.

Expression of semaphorin 3A and neuropilin 1 in asthma.

Neuropilin 1 (NP1) is a part of essential receptor complexes mediating both semaphorin3A (SEMA3A) and vascular endothelial growth factor (VEGF) which is one of important mediators involved in the pathogenesis of asthma. Therefore, it is possible that SEMA3A plays a role in the pathogenesis of asthma through attenuation of VEGF-mediated effects. In the present study, we aimed to evaluate expression levels of SEMA3A and NP1 using induced sputum of asthmatics and a murine model of asthma. Firstly, SEMA3A and NP1 expressions in induced sputum of asthmatics and SEMA3A and NP1 expression on bronchoalveolar lavage (BAL) cells and lung homogenates of asthmatic mice were determined. Then we evaluated the immunolocalization of VEGF receptor 1 (VEGFR1), VEGF receptor 2 (VEGFR2), and NP1 expressions on asthmatic mice lung tissue and their subcellular distributions using fibroblast and BEAS2B cell lines. Sputum SEMA3A and NP1 expressions were significantly higher in asthmatics than controls. Similarly, SEMA3A and NP1 expressions on BAL cells and lung homogenates were significantly elevated in asthmatic mice compared to control mice. Immunohistochemical analysis showed that VEGFR1, VEGFR2, and NP1 expressions were also uniformly increased in asthmatic mice. Our observations suggest that SEMA3A and NP1 may play important roles in the pathogenesis of asthma.

Immediate hypersensitivity reaction to gadolinium-based MR contrast media.

PURPOSE: To determine the incidence and risk factors of immediate hypersensitivity reactions to gadolinium-based magnetic resonance (MR) contrast agents. MATERIALS AND METHODS: Institutional review board approval and a waiver of informed consent were obtained. A retrospective study of patients who had been given gadolinium-based MR contrast media between August 2004 and July 2010 was performed by reviewing their electronic medical records. In addition to data on immediate hypersensitivity reaction, the kinds of MR contrast media and demographic data including age, sex, and comorbidity were collected. To compare the groups, the χ(2) test, Fisher exact test, χ(2) test for trend, Student t test, analysis of variance test, and multiple logistic regression test were performed. RESULTS: A total of 112 immediate hypersensitivity reactions (0.079% of 141 623 total doses) were identified in 102 patients (0.121% of 84 367 total patients). Among the six evaluated MR contrast media, gadodiamide had the lowest rate (0.013%) of immediate hypersensitivity reactions, while gadobenate dimeglumine had the highest rate (0.22%). The rate for immediate hypersensitivity reactions was significantly higher in female patients (odds ratio = 1.687; 95% confidence interval: 1.143, 2.491) and in patients with allergies and asthma (odds ratio = 2.829; 95% confidence interval: 1.427, 5.610). Patients with a previous history of immediate hypersensitivity reactions had a higher rate of recurrence after reexposure to MR contrast media (30%) compared with the incidence rate in total patients (P < .0001). The incidence of immediate hypersensitivity reactions increased depending on the number of times patients were exposed to MR contrast media (P for trend = .036). The most common symptom was urticaria (91.1%), and anaphylaxis occurred in 11 cases (9.8%). The mortality rate was 0.0007% because of one fatality. CONCLUSION: The incidence of immediate hypersensitivity reactions to MR contrast media was 0.079%, and the recurrence rate of hypersensitivity reactions was 30% in patients with previous reactions.

Association between obesity and asthma in the elderly population: potential roles of abdominal subcutaneous adiposity and sarcopenia.

BACKGROUND: Obesity is a significant risk factor for asthma; however, the association of asthma with obesity has rarely been studied in the elderly population. The role of central obesity has been suggested as a link between the 2 entities but has not been comprehensively studied in elderly populations. OBJECTIVE: To investigate the mechanisms of association between obesity and asthma in the elderly population. METHODS: This cross-sectional analysis included 994 participants (aged ≥65 years) in the Korean Longitudinal Study on Health and Aging. Asthma was defined by using questionnaires. Spirometry and chest radiography were performed to exclude asthma-mimicking conditions. Measurements of abdominal subcutaneous and visceral fat were calculated by computed tomography of the abdomen, and regional body compositions were measured by dual energy X-ray absorptiometry. Biochemical parameters were also measured. RESULTS: The prevalence of asthma was 5.4%. The study population had a mean body mass index (BMI) of 24.0. Multivariate logistic regression tests revealed that the risk of asthma increased in proportion to an increase in BMI or abdominal subcutaneous adiposity. However, no association was found with visceral adiposity, serum adiponectin levels, or serum vitamin D levels. The dual energy X-ray absorptiometry-measured appendicular fat-free mass index was inversely related to asthma among patients with a BMI of 25.0 or greater. CONCLUSION: Our findings suggest that the relationships between obesity and asthma in the elderly population may be mediated by factors such as abdominal subcutaneous adiposity and sarcopenia. These associations warrant further investigations to identify their potential roles.

Surveillance of contrast-media-induced hypersensitivity reactions using signals from an electronic medical recording system.

BACKGROUND: Contrast-media (CM) hypersensitivity is a well-known adverse drug reaction. Surveillance of adverse drug reactions usually depends on spontaneous reports. However, the rate of spontaneous reports is low. Recent progress in information technology enables the electronic search on signals of adverse drug reactions from electronic medical recording (EMR) systems. OBJECTIVES: To analyze the incidence and clinical characteristics of CM hypersensitivity using an EMR-based surveillance system. METHODS: The surveillance system used signals from standardized terms within the international classification of nursing practice terms that can indicate symptoms of CM hypersensitivity and from the order codes for procedures that used contrast media, antihistamine, and epinephrine. The search strategy was validated by allergists comparing the electronic search strategy versus manually reviewing medical charts over one month. The main study covered for one year period. RESULTS: Detection rate of the electronic search method was 0.9% (7/759), while that of the manual search method was 0.8% (6/759). EMR-based electronic search method was highly efficient: reduced the charts that needed to be reviewed by 96% (28/759). The sensitivity of electronic screening was 66.7%, specificity was 99.6%, and the negative predictive value was 99.7%. CM hypersensitivity reactions were noted in 266 among 12,483 cases (2.1%). Urticaria was the most frequent symptom (74.4%). CT was the most frequent procedure (3.6%) that induced CM hypersensitivity. CONCLUSION: A surveillance system using EMR may be a useful tool in the study of drug hypersensitivity epidemiology and may be used in an adverse drug reaction alarm system and as a clinical, decision making support system.

Economic costs for adult asthmatics according to severity and control status in Korean tertiary hospitals.

OBJECTIVE: The prevalence of asthma is increasing, and asthma causes considerable socioeconomic burden worldwide. Few studies have been conducted to evaluate the risk factors associated with economic cost of asthma in Korea. This study evaluated asthma cost according to severity, control, and patient factors in Korean tertiary hospitals. METHODS: Direct and indirect costs were assessed in physician-diagnosed adult asthmatics recruited from eight tertiary hospitals in Korea. Official direct medical costs were derived from the analysis of 1-year expenditures related to hospital care utilization and asthma medication. Nonofficial medical costs, nonmedical direct costs, and indirect costs were investigated using a questionnaire designed specifically for the study. RESULTS: A total of 314 patients with persistent asthma were recruited. Both direct and indirect costs were significantly higher for patients with severe persistent asthma than for those with mild and moderate persistent asthma ($2214 vs. $871 and $978, p < .001; $2927 vs. $490 and $443, p < .001, respectively). Costs of asthma increased significantly in poorly controlled compared with somewhat controlled and well-controlled asthma ($7009.8 vs. $2725.3 vs. $1517.3, respectively; p < .001). After stratification for severity, a significant cost increase in the poorly controlled asthma group was observed only for indirect costs and not for direct costs. A multivariate analysis showed that female gender was a risk factor for increased indirect costs. CONCLUSION: The burden of asthma was higher both for patients with severe persistent asthma and for patients with poorly controlled asthma. More effective strategies are needed to improve control status, particularly targeting patients with severe asthma.