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Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous adverse reaction involving various internal organs. Flare-ups after recovery from the initial presentation of DRESS are caused by relapse of drug-induced T-cell-mediated reactions. However, the specific underlying mechanism is unclear. Here, we report a case of a 60-year-old man with allopurinol-induced DRESS who suffered recurrent episodes of generalized rash with eosinophilia, which mimicked immune reconstitution inflammatory syndrome. Analysis of immunological profiles revealed that the percentages of T lymphocytes and regulatory T cells in the patient with DRESS were higher than those in healthy controls. In addition, there was a notable change in the subtype of monocytes in the patient with DRESS; the percentage of nonclassical monocytes increased, whereas that of classical monocytes decreased. Upon viral infection, nonclassical monocytes exhibited strong pro-inflammatory properties that skewed the immune response toward a Th2 profile, which was associated with persistent flare-ups of DRESS. Taken together, the results increase our understanding of the pathogenesis of DRESS as they suggest that expansion of nonclassical monocytes and Th2 cells drives disease pathogenesis.

As an essential part of patient safety, pharmacovigilance is of worldwide interest and should expand its scope and focus on new emerging issues. South Korea has been making continuous efforts in the field of pharmacovigilance for the last 3 decades since voluntary adverse drug reaction (ADR) reporting system was first launched in 1988. Korea joined the World Health Organization Program for International Drug Monitoring in 1992, and the activities of Pharmacovigilance Research Network, Korean Society for Pharmacoepidemiology and Risk Management, and Regional Pharmacovigilance Center (RPVC) have contributed to the remarkable progress in the pharmacovigilance area and global status. RPVCs have played pivotal roles in establishment of pharmacovigilance system in Korea by monitoring voluntary ADR reports. RPVCs started with 3 hospitals in 2006 and have now expanded to 27 hospitals nationwide. The Korea Institute of Drug Safety & Risk Management was established in 2012 and in charge of operating the decentralized national pharmacovigilance system. The voluntary report of ADR, which is the basis of current pharmacovigilance system, has various limitations and an active surveillance system can be the overarching alternative. This change in pharmacovigilance paradigm is a global trend and Korea has excellent infrastructure such as broad distribution of electronic medical recording systems and a nationwide single healthcare insurance. As a result, the pharmacovigilance in Korea is now expected to progress to a new active surveillance system from traditional spontaneous reporting system.

Chronic cough is a significant medical condition with high prevalence and a strong negative impact on the quality of life. Cough hypersensitivity is thought to underlie chronic cough, with several environmental and host factors interacting to cause neuronal sensitization and chronicity. Comorbid conditions affecting cough reflex pathways, such as upper airway diseases, asthma, and gastroesophageal reflux, play important roles in chronic cough. However, their prevalence may vary in patients living in different geographical regions or with different ethnicities. We conducted a literature review to examine common comorbidities in Korean adult patients with chronic cough, their clinical implications, and the issues that still need to be addressed in the development of clinical evidence of chronic cough in Korean adult patients.

Background Single premedication with antihistamines for radiocontrast media (RCM) hypersensitivity is frequently used in real world at the emergent situation although its efficacy is not proven. Objective To evaluate the effect of intravenous antihistamines as a premedication in general population who had experience of mild adverse reactions to iodinated RCM. Methods A retrospective observational study on 14,785 subjects who had RCM-enhanced computed tomography scans between January 2014 and December 2015 in Seoul National University Hospital Gangnam Healthcare Center, Seoul, South Korea. Results Among 453 subjects who had a history of mild RCM-induced hypersensitivity reactions, 273 subjects had a single premedication of intravenous antihistamine. When comparing antihistamine-premedication group and nonpremedication group, there is no protective effect of antihistamines on the incidence rate and severity of hypersensitivity (10.6% vs. 11.7%, p = 0.729). Conclusion The clinical efficacy of a single premedication of antihistamines for mild RCM-induced hypersensitivity was not confirmed.

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.

The prevalence of allergic diseases has increased dramatically in recent decades, and are now considered major chronic diseases at the global level. The increasing burden of allergic diseases has led to numerous worldwide and local researchers to investigate the time trends in its prevalence and identify its driving factors. Environmental changes such as urbanization and industrialization have been suggested to explain the increasing prevalence, but recent reports from Western countries suggest that this prevalence has reached a plateau or even possibly, started to decrease. However, such environmental changes are still occurring in many Asia-Pacific countries, including Korea, and it is speculated that the peak in allergy epidemics has yet to come. The present systematic literature review aimed to explore the time trends in the prevalence of allergic diseases in Korea and to identify the unmet needs for facilitating further studies.

Tacrolimus and cyclosporine have been used in various formulations, but their hypersensitivity reactions are rare in practice. Castor oil derivatives are nonionic surfactants used in aqueous preparations of hydrophobic active pharmaceutical ingredients. Castor oil derivatives that can be used as additives to tacrolimus and cyclosporine may play a role in the development of hypersensitivity reactions, especially anaphylaxis. Various immunologic and nonimmunologic mechanisms have been implicated in hypersensitivity reactions induced by castor oil derivatives. Physicians should be aware that not only the drug itself, but also its additives or metabolites could induce hypersensitivity reactions. We report a case of anaphylaxis caused by vitamin K (phytonadine), serotonin antagonist (granisetron), intravenous tacrolimus, and cyclosporine. Interestingly, the patient tolerated oral cyclosporine, which did not contain Cremophor EL or polysorbate 80.

Chlorpheniramine is a widely prescribed H1-antihistamine for relieving urticaria or histamine-mediated allergic reactions. However, although rare, it may cause immediate hypersensitivity reactions. The diagnosis is usually made by provocation test, but its application is often limited due to comorbidities or potential risk of severe reactions. In those cases, skin tests and basophil activation tests can be considered as additional diagnostic tests for the drug allergy. Here, we report a 33-year-old female with underlying chronic urticaria, who recurrently developed anaphylaxis after chlorpheniramine administration. Intradermal test showed positive responses in the patient at 0.02 mg/mL of chlorpheniramine, but not in healthy controls. Basophil activation test showed significant up-regulation of CD63 and CD203c by chlorpheniramine. The present case reminds the rare but potential allergic risk of chlorpheniramine, and also suggests the potential utility of basophil activation test in making the diagnosis.

Eosinophilic myocarditis is a condition resulting from various eosinophilic diseases, including helminth infection, drug hypersensitivity, systemic vasculitis or idiopathic hypereosinophilic syndromes. Clinical manifestations of eosinophilic myocarditis may vary from early necrosis to endomyocardial fibrosis. Eosinophilic myocarditis is one of the most fatal complications of hypereosinophilia. However, eosinophilic myocarditis has been rarely reported in the literature, particularly in Asia Pacific regions, reflecting the under-recognition of the disease among clinicians. Early recognition is crucial for improving clinical outcomes of eosinophilic myocarditis. Early administration of systemic corticosteroid is necessary in eosinophilic myocarditis regardless of underlying causes, as delayed treatment may result in fatal outcomes. In addition, differential diagnoses of underlying causes for eosinophilia are necessary to improve long-term outcomes.

Background Human rhinoviruses are the major cause of asthma exacerbation in both children and adults. Recently, impaired antiviral interferon (IFN) response in asthmatics has been indicated as a primary reason of the susceptibility to respiratory virus, but the mechanism of defective IFN production is little understood to date. The expression of IFN regulatory factor 7 (IRF7), a transcriptional factor for virus-induced type I IFN production is known to be regulated epigenetically by DNA methylation. Objective We aimed to investigate the expression of IFN-α, IFN-β, and IRF7 in response to rhinovirus infection in the adult asthmatics and evaluate DNA methylation status of IRF7 gene promotor. Methods Twenty symptomatic adult asthmatics and 10 healthy subjects were enrolled and peripheral blood was collected from each subject. Peripheral blood mononuclear cells (PBMCs) were isolated, cultured, and ex vivo stimulated with rhinovirus-16. The mRNA expressions of IFN-α, IFN-β, and IRF7 were analyzed using real time quantitative polymerase chain reaction. Genomic DNA was isolated from untreated PBMCs and the methylation status of IRF7 gene promotor was investigated using bisulfite pyrosequencing. Results The mean age of asthmatics was 45.4 ± 15.7 years and 40% was male, which were not different with those of control group. Asthmatics showed significantly decreased mRNA expressions (relative expression to beta-actin) of IFN-α and IFN-β compared with normal control. The mRNA expression of IRF7 in the asthmatics was also significantly lower than those in the normal control. No significant difference of DNA methylation was observed between asthmatics and controls in all analyzed positions of IRF7 promotor CpG loci. Conclusion The mRNA expression of type I IFN in response to rhinovirus was impaired in the PBMCs of adult asthmatics. The mRNA expression of IRF7, transcriptional factor inducing type I IFN was also reduced, but not caused by altered DNA methylation in the IRF7 gene promotor.

BACKGROUND: Standardized questionnaire is one of key instruments for general population surveys. OBJECTIVE: The present study aimed to develop and validate the Korean version of the European Community Respiratory Health Survey (ECRHS) screening questionnaire for adult asthma surveys. METHODS: The ECRHS screening questionnaire was translated into Korean language according to the international criteria. Study participants were prospectively recruited from six referral hospitals and one health check-up center. Comprehensibility of the translation was tested in a pilot study of 10 patients. The reliability was evaluated by internal consistency and test-retest repeatability. Validity was assess with regard to physician-diagnosed asthma. RESULTS: A total of 100 adult asthma patients and 134 volunteers were recruited. Reliability was examined for 10 items in 100 asthmatics; Cronbach α coefficients were 0.84, and test-retest repeatability was good (Cohen κ coefficient, 0.71-1.00). Validity was assessed for 8 items in 234 participants; in particular, 'recent wheeze' showed a high sensitivity (0.89) for physician-diagnosed asthma. 'Recent asthma attack' and 'current asthma medication' showed high specificity (0.96-0.98). CONCLUSION: The present study demonstrated that the Korean version of the ECRHS screening questionnaire was comprehensible, reliable and valid. We suggest the questionnaire to be utilized in further epidemiological studies for asthma in Korean adult populations.

Lamotrigine is a recent medication which is prescribed for various neuropsychiatric conditions. It is generally well-tolerated, but recent pharmacoepidemiological evidence suggests that lamotrigine is associated with risks of developing severe cutaneous drug reactions like toxic epidermal necrolysis (TEN). However, there still remains the diagnostic challenge regarding how to confirm the drug causality in suspected cases. In most cases so far, lamotrigine causality has not been objectively demonstrated, which was possibly due to high risk of oral challenge tests or the lack of useful in vitro drug assays. Here we report a case of lamotrigine-induced TEN, of which the drug causality was confirmed by in vitro granulysin and cytokine assays.

BACKGROUND Upper respiratory diseases have been linked with lower respiratory diseases. However, the long-term effect of sinusitis on the clinical outcomes of asthma has not been fully evaluated. OBJECTIVE The aim of this study was to investigate the impact of sinusitis on the disease progression of asthma. METHODS Seventy-five asthmatic patients confirmed with the methacholine bronchial provocation test or bronchodilator response were included. The study patients underwent paranasal sinus x-ray upon their asthma evaluation and they visited the hospital at least 3 years or longer. We retrospectively reviewed their medical records and compared data according to the presence of comorbid sinusitis. RESULTS Among the 75 asthmatic subjects, 38 subjects (50.7%) had radiologic evidence of sinusitis. Asthmatics with sinusitis had significantly lower forced expiratory volume in 1 second (FEV1; 79.2% vs. 88.2%) and PC20 values (5.2 mg/mL vs. 8.9 mg/mL) compared to asthmatics without sinusitis at the time of diagnosis. This difference in FEV1 disappeared (82.6% vs. 87.2%) in the 3-year follow-up, although FEV1 was more variable (31.7% vs. 23.5%) and worst FEV1 was also significantly lower in patients with sinusitis compared to those without (70.9% vs. 79.0%). There were no significant differences in the number of hospital visits, acute exacerbations, and scores for the asthma control test. CONCLUSION Although sinusitis was associated with lower baseline lung function and higher hyperreactivity, sinusitis was not related with significant deterioration in lung function over 3 years of follow-up. Asthmatics with sinusitis showed more variability in lung function during the follow-up period. Healthcare utilization was not different except antibiotics use.

BACKGROUND Induced sputum analyses are widely utilized to evaluate airway inflammation in asthmatics. However, the values have not been examined in Korean adults. OBJECTIVE The purpose of this study is to determine reference ranges for induced sputum eosinophils and their influencing factors in Korean adults. METHODS A total of 208 healthy nonasthmatic adults were recruited. Sputum induction and processing followed the international standard protocols. RESULTS Adequate sputum samples were successfully collected from 81 subjects (38.9%). The upper 90 percentile for sputum eosinophil was calculated as 3.5%. The median value of eosinophil count percentage was significantly higher in subjects with atopy than those without atopy (median, 1.6%; range, 0-11.0% vs. median, 0%; range 0-3.6%, p=0.030). However, no significant correlations were found with age, gender, body mass index, smoking status, blood eosinophil, or fractional exhaled nitric oxide levels. CONCLUSION Current study was the first attempt to determine the reference ranges of induced sputum eosinophils in Korean adults. The cutoff value for sputum eosinophilia was 3.5%, and was significantly associated with atopy.

Background Several epidemiologic studies showed the significant association of insulin resistance with asthma. Objective The aim of this study was to evaluate the association of insulin resistance with airway hyperresponsiveness (AHR) in adult population. Methods 1,058 subjects who visited to the Seoul National University Hospital Gangnam Center from October 2007 to January 2009 for a routine health check-up were enrolled. All subjects completed a questionnaire, anthropometric measurements such as body mass index (BMI) and waist circumference, blood tests, pulmonary function test, and methacholine bronchial provocation test (MBPT). Insulin resistance was estimated from the homeostasis model of assessment of insulin resistance (HOMA-IR). Results Thirty-three subjects (3.1%) had AHR based on MBPT. The subjects with AHR had higher BMI, waist circumference, and HOMA-IR than those without AHR (p < 0.001, p = 0.003, and p = 0.002, respectively). In case of men, fasting insulin level and HOMA-IR had significant correlation with forced expiratory volume in 1 second (%) (r = -0.1440, p = 0.011, and r = -0.1156, p = 0.042, respectively). Fasting insulin level and HOMA-IR were higher in men with AHR than in those without (p = 0.046 and p = 0.040, respectively). In binary logistic regression analysis after adjustment for age, HOMA-IR was the significant risk factor for AHR in men (HOMA-IR: odds ratio [OR], 3.21; 95% confidence interval [CI], 1.00-10.30). In case of women, fasting insulin, glucose level, or insulin resistance had no significant correlation with lung function. BMI, waist circumference, and HOMA-IR were significantly higher in women with AHR than in those without (p = 0.001, p = 0.011, and p = 0.010, respectively). In binary logistic regression analysis after adjustment for age, BMI and HOMA-IR were the significant risk factors for AHR in women (BMI: OR, 2.20; 95% CI, 1.23-3.82; insulin resistance: OR, 1.05; 95% CI, 1.00-1.09). Conclusion Insulin resistance was significantly associated with bronchial hyperreactivity, which is the most characteristic feature of asthma.

Asia is the world's most dynamic area. Asthma is a major chronic disease in Asia, like other continents. However, unlike childhood asthma, the epidemiological burden of asthma in Asian adults has been unclear. Here we reviewed the currently available literatures on the epidemiology of adult asthma in the Asian community populations. Adult asthma prevalence was generally lower in Asian than in Europe, but the increasing trends suggested the disease burden to rise in the near future. However, for better understanding, it may be essential to prepare for the Asian multinational network for the standardization and collaboration of research.

Background Theophylline is mainly metabolized by cytochrome P450 (CYP) 1A2 and CYP2E1 which show inter-individual variations. However, the underlying mechanism remains unknown in humans. We investigated the relationship between differences in theophylline clearance and genetic polymorphisms in the CYP1A2 and CYP2E1 gene in 89 Korean asthmatic patients. Methods Polymerase chain reaction (PCR) was performed on the 5'-flanking region of those genes. PCR products were directly sequenced and confirmed using the SNaP shot method. We determined whether the detected SNPs affected gene transcription using electrophoretic mobility shift assay (EMSA). Theophylline clearance (mL/kg/h) was assessed by using a Bayesian approach. Results Genetic polymorphisms were identified at 7 sites in the CYP1A2 gene and at 10 sites in the CYP2E1. Among them, subjects with genotypes (GA+AA) of the -3860G>A polymorphism were found to show higher theophylline clearance than those with genotypes GG (29.11 ± 0.91 mL/kg/h vs. 26.12 ± 0.80 mL/kg/h, p = 0.014). This polymorphic site was revealed to be a protein binding site by conducting EMSA on nuclear hepatocyte extracts. Conclusion In conclusion, increased theophylline clearance was significantly related to the -3860G>A polymorphism, which could be associated with increased CYP1A2 inducibility in Korean non-smoking asthmatics.

Fixed drug eruption is an uncommon adverse drug reaction caused by delayed cell-mediated hypersensitivity. Levocetirizine is an active (R)-enatiomer of cetirizine and there have been a few reports of fixed drug eruption related to these antihistamines. We experienced a case of levocetirizine-induced fixed drug eruption and cross-reaction with other piperazine derivatives confirmed by patch test. A 73-year-old female patient presented with recurrent generalized itching, cutaneous bullae formation, rash and multiple pigmentation at fixed sites after taking drugs for common cold. She took bepotastine besilate (Talion®) and levocetirizine (Xyzal®) as antihistamine. She took acetaminophen, pseudoephedrine 60 mg / triprolidine 2.5 mg (Actifed®), dihydrocodeinebitartrate 5 mg / di-methylephedrine hydrochloride 17.5 mg / chlorpheniramine maleate 1.5 mg / guaifenesin 50 mg (Codening®) and aluminium hydroxide 200 mg / magnesium carbonate 120 mg (Antad®) at the same time. Patch test was done with suspected drugs and the result was positive with levocetirizine. We additionally performed patch test for other antihistamines such as cetirizine, hydroxyzine, fexofenadine and loratadine. Piperazine derivatives (cetirizine and hydroxyzine) were positive, but piperidine derivatives (fexofenadine and loratadine) were negative to patch test. There was no adverse drug reaction when she was challenged with fexofenadine. We report a case of levocetirizine-induced fixed drug eruption confirmed by patch test. Cross-reactions were only observed in the piperazine derivatives and piperidine antihistamine was tolerant to the patient.

Background We reported that level of lipopolysaccharide (LPS) exposure determined the type of airway inflammation in a murine model of asthma. Objective The purpose of this study is to evaluated the role of IL-13 in low dose LPS induced murine model of asthma using IL-13 and signal transducer and activator of transcription 6 (STAT6) deficient mice. Methods Mice were sensitized with an intranasal application of LPS-depleted ovalbumin (OA) and different doses of LPS (0.1 and 10 µg), and then challenged intranasally with OA alone. The phenotype changes between wild type (WT) and IL-13-/- mice and between WT and STAT6-/- mice were evaluated. Results We confirmed again that low and high dose LPS resulted in different phenotypes of murine asthma. In the present study, we observed that phenotypes of murine asthma induced by low dose LPS were abolished in the homozygous null mutation of the IL-13 and STAT6 gene. However, those changes were not shown in mice sensitized OA plus high dose LPS. Conclusion IL-13 plays an important role in low dose LPS induced murine model of asthma. Our results provided a new insight in understanding of the potential role of IL-13 in innate immunity in human allergic asthma.

Background Recent literature suggests that Staphylococcal enterotoxin specific IgE may be a risk factor for asthma. Objective To investigate the associations between Staphylococcal enterotoxin sensitization and asthma. Methods A systematic review and meta-analysis was performed for relevant case-control or population-based studies, published in the peer-reviewed journals until February 2013. Data were extracted on study designs, subjects, definitions and the prevalence of Staphylococcal enterotoxin sensitization. Results A total of 683 studies were initially identified, of which 7 studies finally met the inclusion criteria (5 case-control and 2 population-based studies). All the included studies reported higher prevalence of the sensitization in asthmatics than in controls, despite clinical and methodological heterogeneity. In a meta-analysis, the pooled odds ratio of the sensitization for asthma was 2.95 (95% confidence intervals 2.28-3.82). Conclusion Staphylococcal enterotoxin sensitization was significantly associated with asthma. The mechanisms of associations warrant further elucidation.

Background Immunotherapy was introduced 100 years ago and has a unique role in the treatment of allergic diseases in that only immunotherapy can induce long-term immunological tolerance. However, only a few mouse models of immunotherapy have been developed so far. Objective We tried to establish murine immunotherapy models that have similar findings in human using subcutaneous rush immunotherapy-like schedule. Methods To determine the maximal safe or maximal tolerable dose, injection dose was doubled twice a day from the dose of sensitization. Mice with established asthma using ovalbumin (OVA) were repeatedly injected with OVA from the dose of sensitization subcutaneously twice a day: after reaching to the maximal safe or maximal tolerable dose, mice were injected with each dose either 10 times or 24 times. Results Short term immunotherapy (10 times) with the maximal safe and tolerable dose of OVA showed decreased IL-5 production, decreased IL-5/INF-γ ratio, and increased IgG2a/IgG1 but there was no significant difference in airway hyperresponsiveness (AHR) or airway inflammation. Prolonged immunotherapy (24 times) with the maximal tolerable dose not only decreased cytokine productions of IL-5 and even INF-γ, but also decreased IgE, IgG1 and even IgG2a production. Remarkably, the prolonged immunotherapy provided a protective effect on AHR. Conclusion This study suggested immunotherapy models with some beneficial immunological and physiological effects in murine asthma.

Background Chronic rhinitis is a heterogeneous group of diseases that cause nasal inflammation. And the nose may be a window into the lung in the concept of "one airway one disease." Objective This study was conducted to evaluate differences between the different forms of chronic rhinitis in terms of lower airway inflammation. Methods Patients that attended the allergy clinic and presented with moderate/severe persistent rhinitis symptoms for more than 1 year were enrolled. The patients with chronic rhinitis were classified into two groups (house dust mites [HDM]-sensitive allergic rhinitis [AR] or non-allergic rhinitis [NAR]) according to the presence of atopy, and additionally according to nasal polyposis and airway hyperresponsiveness, respectively. Medical records were reviewed and the mRNA expression levels of IL-5, IFN-γ, TGF-β1, IL-17A, and IL-25 were evaluated in induced sputum samples in each group. Results Induced sputum samples of 53 patients were evaluated. Patients with NAR were significantly older than patients with HDM-sensitive AR (p < 0.05). Nasal polyposis was more prevalent in NAR patients than in HDM-sensitive AR patients (10.2% vs. 62.5%, p < 0.001). The expression levels of IL-17A mRNA were higher in NAR patients, regardless of the presence of airway hyperresponsiveness (p = 0.005). Conclusion These results suggest that patients with different forms of chronic rhinitis could have different inflammatory environments in their lower airway and NAR patients might have bronchial inflammation related to the elevated levels of IL-17A compared to HDM-sensitive AR patients.

Food-dependent exercise-induced anaphylaxis (FDEIA) is a type of exercise-induced anaphylaxis associated with postprandial exercise. We describe a 19-year-old man with FDEIA. Our patient complained of urticaria, angioedema, dizziness and hypotension associated with exercise after ingestion of walnut-containing foods in a warm environment. Skin prick test and prick to prick test were positive for walnut antigen. The attack didn't occur by free running outside for 10 min 2 h after taking walnuts, and the temperature was about -2℃. Food-exercise test was done again in a warm environment based on prior history. Anaphylaxis was developed after exercise for 10 min in a warm environment after taking walnuts. Some environmental factors such as high temperature and high humidity or cold temperature may influence exercise-induced anaphylaxis. In our case, the cofactor was a warm environment: the challenge test done in a cold environment was negative, but positive in a warm environment. Physicians should be aware that the challenge test of FDEIA can show different results depending on temperature.

Many international and national asthma guidelines are now available in large parts of the world, but they are not yet implemented appropriately. There is a gap between scientific evidence-based medicine and real clinical practice. Implementation of guidelines is highly complex. Special strategies are needed to encourage guideline-based, high-quality care. It is important to understand the contents, the format, and the learning strategies which physicians prefer for the dissemination of guidelines. Physicians prefer more concise and immediately available guidelines that are practical to use. Thus, asthma guidelines should be disseminated as convenient and easily accessible tools. Various education programs and decision-support tools have been designed and applied to the clinical management of asthma to solve these challenging problems. Many of them have been shown to be effective at increasing physicians' knowledge and adherence to asthma guidelines and improving patients' clinical outcomes. These educational and decision-support tools are expected to contribute to a narrowing of the gap between asthma guidelines and practice/implementation of the guidelines.

Human seminal plasma allergy is a rare phenomenon. Its clinical manifestations are diverse, and range from mild local pruritus to fatal anaphylaxis. Treatment varies with severity of the reactions: abstinence, condom usage or immunotherapy (subcutaneous or intravaginal) with seminal fluid. Local allergic reactions can be managed by prophylactic use of antihistamines or local cromolyn cream. A 33-year-old female visited the Asthma and Allergy Clinic in Seoul National University Bundang Hospital for the recurrent generalized urticarial reactions after sexual intercourse. She had been suffering from asthma, allergic rhinoconjunctivitis and atopic dermatitis for 10 years. She gave birth to a baby 6 months ago and no problem before. However, recently she began to recognize unexpected generalized urticaria that occurred after the sexual intercourse with husband. She wanted to have the second baby but hesitated because of the recurrent symptoms after the intercourse. She showed positive response to skin prick test with her husband's seminal fluid. The IgE-binding components were 15, 22, 28, and 35 kDa. Considering her moderate cutaneous reactions, we decided to try prophylactic treatments with oral anti-histamine one hour before sexual intercourse. She did not experience urticarial reactions with intercourse while oral anti-histamine was administered in advance. Finally, treatment outcome was successful, and the couple successfully gave birth to their second baby. We suppose that prophylactic antihistamine may be also applied in seminal plasma allergy patients if systemic reactions are limited to mild to moderate generalized urticaria.

Background Bronchial asthma is usually associated with high sputum eosinophil levels. However, recent reports have suggested the importance of noneosinophilic asthma (NEA) as a distinct phenotype of asthma. Objective The aim of this study was to evaluate clinical significance of sputum eosinophilia and long-term treatment outcomes related to sputum eosinophilia in Korean asthmatics. Methods A total of 201 steroid-naive asthmatics who had undergone induced sputum analysis at baseline were selected from the Cohort for Reality and Evolution of Adult Asthma study population. Clinical evaluation, spirometry, a skin-prick test, a methacholine bronchial provocation test, and sputum eosinophil analysis were performed initially, and patients received the treatment recommended by the Global Initiative for Asthma. Lung function was evaluated every 6 months, and 53 patients completed 24 months of regular follow-up visits. Sputum eosinophilia was defined as a sputum eosinophil count of >3%. Results Of the 201 steroid-naive asthmatics, 97 patients had NEA and 104 had eosinophilic asthma (EA). Only 52% of steroid-naive asthmatic subjects had elevated baseline sputum eosinophil levels. A higher percentage of sputum eosinophils was associated with a lower PC20 (r = -0.193; p = 0.009, Spearman correlation), but not with forced expiratory volume in one second (FEV1) (r = 0.045; p = 0.525). During the 24-month study period, the percentage change of FEV1 was significantly lower in the NEA group than in the EA group at 6, 12, 18, and 24 months (p < 0.05). The NEA group, unlike the EA group, showed no significant improvement in FEV1 at 6, 12, 18, or 24 months (p > 0.05). Conclusion A higher sputum eosinophil percentage was correlated with a higher airway hyperresponsiveness. Compared with EA patients, NEA patients had poor treatment outcomes in the 2-year follow-up of a Korean asthma cohort population.

Asthma in the elderly is a disease with emerging concern. Despite some recent advances in our understanding of epidemiology and pathophysiology, there is a considerable lack of clinical evidence specific to elderly patients. Currently available high quality clinical evidence has been mostly obtained from younger adults, but rarely from elderly patients. Under-representation of elderly patients in previous randomized trials may have been due to being, old age, or having comorbidities. Thus, a question may be raised whether current clinical evidence could be well generalized into elderly patients. Further clinical trials should address clinical issues raised in elderly population. In this review, we aimed to overview the efficacy and safety of pharmacological management, and also to summarize the literature relevant to elderly asthma.

The prevalence of allergic diseases has been increasing rapidly, especially in developing countries. Various adverse health outcomes such as allergic disease can be attributed to rapidly increasing air pollution levels. Rapid urbanization and increased energy consumption worldwide have exposed the human body to not only increased quantities of ambient air pollution, but also a greater variety of pollutants. Many studies clearly demonstrate that air pollutants potently trigger asthma exacerbation. Evidence that transportation-related pollutants contribute to the development of allergies is also emerging. Moreover, exposure to particulate matter, ozone, and nitrogen dioxide contributes to the increased susceptibility to respiratory infections. This article focuses on the current understanding of the detrimental effects of air pollutants on allergic disease including exacerbation to the development of asthma, allergic rhinitis, and eczema as well as epigenetic regulation.

We've just celebrated the first anniversary of Asia Pacific Allergy (AP Allergy), the official journal of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI) in the last issue of April. AP Allergy is recently indexed by EMBase and is now indexed/ tracked/ covered by PubMed, PubMed Central, EMBase, CAB Abstracts, Global Health, CrossRef and Google Scholar databases. This issue of AP Allergy features important issues on healthcare utilization and medical costs for childhood asthma in Taiwan [1], occupational asthma in Japan [2], recent progress of elucidating the mechanisms of drug hypersensitivity [3], and an aerobiological perspective in allergy and asthma [4] in review articles. As the prevalence of asthma is increasing, the socioeconomic burden like healthcare utilization and medical cost is increasing worldwide. In Korea, recently, a nationwide survey and a survey from tertiary hospitals have reported the financial burden of asthma [5, 6]. The survey from the tertiary hospitals analyzed the financial burden according to the severity and control status [6]. In this issue, Wang et al. [1] have updated us with this topic in childhood asthma from Taiwan. He used the data from Taiwan National Health Insurance Research Database and addressed the importance of a government-sponsored disease management program. In the same issue, Dobashi [2] has reviewed on occupational asthma in Japan. Occupational asthma is one of the major occupational diseases in developing countries. This review provides an opportunity to review article the history and the current status of occupational asthma in Japan. Drug hypersensitivity is increasing worldwide as the consumption of drug is increasing. Drug hypersensitivity became a hot topic in the field of allergy and clinical immunology. In the same issue, Hashizume has updated the mechanisms of drug hypersensitivity such as hapten hypothesis and the pi concept and provided his recent data [3]. Pollens are important allergens. Singh and Mathur [4] have updated this subject in the same issue. They provided an in-depth educational review article on various aerobiological parameters of environmental pollen from different parts of the world with a special emphasis on India. Readers of this journal will also find original articles on the sensitization by house dust mite and the prediction of persistent wheeze in children between 8 to 14 years old from Singapore [7], lack of efficacy of a herbal preparation (RCM-102) for seasonal allergic rhinitis: a double blind, randomised, placebo-controlled trial from Australia [8], and the measurement of Hymenoptera venom specific IgE by the IMMULITE 3gAllergy in subjects with negative or positive results by ImmunoCAP [9] from Japan. Readers may have a new idea how to set up a clinical trial of herbal preparation like RCM-102 although it was found to be not an effective preparation for seasonal allergic rhinitis [8]. This issue includes an educational case report of Gianotti-Crosti syndrome: a case report of a pruritic acral exanthema in a child, which was initially misdiagnosed as atopic dermatitis [10]. Readers can learn about the difference between two diseases.