Sae-Hoon Kim

Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans

BACKGROUND Although the US FDA recommends screening for HLA-B*1502 allele in most of Asian ancestry before initiating carbamazepine therapy, the HLA associations with carbamazepine hypersensitivity in non-Chinese Asian populations remain unclear. This study investigated the association between the HLA class I genotype and carbamazepine-induced severe cutaneous adverse reaction (SCAR) in Koreans. METHODS Twenty-four patients who had developed carbamazepine-induced SCAR (7 Stevens-Johnson syndrome (SJS), 17 drug hypersensitivity syndrome (HSS)), 50 carbamazepine-tolerant controls from the Korean Pharmacogenetic Adverse Drug Reaction Research Network and data of 485 Korean general population from a previously published study were recruited. HLA-A, -B, and -C genotyping was performed by direct DNA sequence analysis. RESULTS Only one of the seven SJS patients was positive for the B*1502 allele, but the frequency of B*1511 was much higher in the patients with CBZ-SJS than in the CBZ-tolerant control patients (P=0.011, P(c)=not significant; OR=18.0(2.3-141.2)). The frequencies of A*3101 in carbamazepine-induced HSS and SCAR were significantly higher than those in carbamazepine-tolerant controls (P(c)=0.011, OR=8.8(2.5-30.7) and P(c)=0.013, OR=7.3(2.3-22.5), respectively). The frequencies of B*1511 in carbamazepine-SJS and A*3101 in carbamazepine-HSS/SCAR were significantly higher than those in the general population. CONCLUSIONS HLA-B*1502 does not seem to be an effective predictive marker for carbamazepine-induced SCAR, while HLA-B*1511 and A*3101 was associated with carbamazepine-induced SJS and HSS/SCAR respectively in the Korean population.

Epidemiologic and clinical features of anaphylaxis in Korea

BACKGROUND Little is known about the characteristics of anaphylaxis in Korea or even in Asia. OBJECTIVE To evaluate the incidence of anaphylaxis and the clinical features of patients with anaphylaxis in a Korean tertiary care hospital. METHODS We performed a retrospective review from January 1, 2000, through July 31, 2006, of 138 patients with anaphylaxis, including inpatients, outpatients, and emergency department visitors, in the Seoul National University Hospital. RESULTS Among 978,146 patients, 138 (0.014%) had anaphylaxis. Two cardiopulmonary resuscitations were performed and 1 death occurred. The total mortality rate of anaphylactic patients was 0.0001%. The causes of anaphylaxes were drug (35.3%), food (21.3%), food-dependent exercise-induced (13.2%), idiopathic (13.2%), insect stings (11.8%), exercise induced (2.9%), blood products (1.5%), and latex (0.7%). Radiocontrast media and buckwheat were the leading causes of drug and food anaphylaxis, respectively. The organs most frequently involved in the anaphylaxis were cutaneous (95.7%), cardiovascular (76.8%), and respiratory (74.6%). The most common manifestations were dyspnea (71.3%), urticaria (81.9%), and angioedema (69.4%). Three of 138 patients (2.2%) had biphasic reactions. CONCLUSIONS The incidence, mortality rate, and clinical features of Korean patients with anaphylaxis were similar to rates for patients from other countries, despite some differences in causative agents.

HLA-B58 can help the clinical decision on starting allopurinol in patients with chronic renal insufficiency

BACKGROUND Although allopurinol is a very effective urate-lowering drug for complicated hyperuricemia, in some patients, it can induce severe cutaneous adverse reactions (SCARs). Recent investigations suggest that HLA-B*5801 is a very strong marker for allopurinol-induced SCARs, especially in the population with a high frequency of HLA-B*5801. Korea is one of the countries with a high frequency of HLA-B*5801 which is the only subtype of HLA-B58 in the Korean population. Objective. This study was conducted to find out the incidence of allopurinol-induced hypersensitivity on patients with chronic renal insufficiency (CRI) according to HLA-B58 and the clinical implications of HLA-B58 as a risk marker for the development of allopurinol-induced hypersensitivity. METHODS We retrospectively reviewed the medical records of patients with CRI who took allopurinol and carried out serologic human leukocyte antigen (HLA) typing for kidney transplantation between January 2003 and May 2010. RESULTS Among a total of 448 patients with CRI, 16 (3.6%) patients experienced allopurinol hypersensitivity. Nine of these patients (2.0%) were diagnosed with SCARs (two Stevens-Johnson syndrome and seven allopurinol hypersensitivity syndrome) and seven patients (1.6%) had simple maculopapular rashes. The HLA-B58 allele was present in all patients with allopurinol-induced SCARs, while the frequency of HLA-B58 was only 9.5% in allopurinol-tolerant patients (P < 0.05). The incidence of allopurinol-induced SCARs in CRI shows a wide disparity according to HLA-B58 [18% in HLA-B58 (+) versus 0% in HLA-B58 (-)]. Among patients without HLA-B58, most (98.2%) of the CRI patients were tolerant to allopurinol and only 1.8% experienced simple rashes after taking allopurinol. CONCLUSIONS In this study, the incidence of allopurinol-induced SCARs was considerably high in CRI patients with HLA-B58. This finding indicates that the presence of HLA-B58 may increase the risk of allopurinol-induced SCARs. Screening tests for HLA-B58 in CRI patients will be clinically helpful in preventing severe allopurinol hypersensitivity reactions.

HLA-B*5901 is strongly associated with methazolamide-induced Stevens-Johnson syndrome/toxic epidermal necrolysis

AIMS The carbonic anhydrase inhibitor methazolamide infrequently causes Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). An association between these diseases and the HLA-B59 serotype has been suggested in case reports. This study examined the disease-associated B*59 allele and investigated the association of these diseases with other HLA class I alleles. METHODS We performed high-resolution HLA-A, -B and -C genotyping in five patients with methazolamide-induced SJS/TEN using a PCR-sequencing-based typing method and analyzed the association between HLA-class I alleles and occurrence of methazolamide-induced SJS/TEN. RESULTS B*5901 and Cw*0102 alleles were observed in all patients and A*2402 was observed in four patients. The B*5901 allele showed the strongest association with methazolamide-induced SJS/TEN (p < 0.001; odds ratio: 249.8; 95% CI: 13.4-4813.5), followed by Cw*0102 (p = 0.004; odds ratio: 22.1; 95% CI: 1.2-414.3), when compared with the general population as a control. The frequency of the patients carrying B*5901, Cw*0102 and A*2402 simultaneously was significantly higher than that in the general population (p < 0.001; odds ratio: 110.1; 95% CI: 11.7-1038.6). CONCLUSION A strong association was observed between HLA-B*5901 and methazolamide-induced SJS/TEN in Korean patients. HLA-B*5901 may be a useful screening marker for predicting methazolamide-induced SJS/TEN in patients of Korean and Japanese ancestry.

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.

Risk of hepatitis B virus reactivation in patients with asthma or chronic obstructive pulmonary disease treated with corticosteroids

Background and objective:  Reactivation of hepatitis B virus (HBV) is thought to be associated with immunosuppressive treatments, but insufficient information is available on the effect of corticosteroids. The aim of this study was to evaluate the risk of HBV reactivation in hepatitis B surface antigen‐seropositive patients with asthma or COPD, who were treated with systemic corticosteroids (SCS) in addition to inhaled corticosteroids (ICS).

Outcomes of premedication for non-ionic radio-contrast media hypersensitivity reactions in Korea

BACKGROUND Radio-contrast media (CM)-related adverse reactions are important clinical problems that may cause fatal anaphylaxis. Accordingly, it has been common practice to premedicate patients who have had previous reactions to CM with corticosteroids, antihistamines, and H2 blockers to prevent hypersensitive reactions. However, the effectiveness of premedication has not been properly demonstrated, especially in cases related to non-ionic CM. In this study, we evaluated the effectiveness of premedication at preventing of non-ionic CM immediate-type hypersensitivity reactions. METHODS A total of 30 patients who had been pretreated with corticosteroid and H1 antihistamines and/or H2 blockers in a 3-year period were enrolled. The results of premedication were evaluated in terms of clinical characteristics and the features of breakthrough reactions. RESULTS Hypersensitivity reactions were not prevented in 5 of the 30 patients who had experienced prior CM reactions (overall recurrence rate after premedication 16.7%; 4/17 patients with mild previous reactions, and 1/13 patients with severe previous reactions). The recurrence rate after premedication was significantly higher in patients with mild previous reactions than in those with severe reactions (23.5% vs. 7.7%; p<0.001). The breakthrough reactions were similar to the prior reactions in terms of severity and clinical manifestations. CONCLUSION Premedication with corticosteroid and H1 antihistamines and/or H2 blockers effectively prevent non-ionic CM-related adverse events in most patients who have had severe previous reactions to CM. However, physicians should be aware of the possibility of premedication failing and of breakthrough reactions, even in cases in which the previous reactions were mild.

Cough in the Elderly Population: Relationships with Multiple Comorbidity

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

Airway Hyperresponsiveness Is Negatively Associated with Obesity or Overweight Status in Patients with Asthma

Background: Obesity is a risk factor for asthma in the general population, but the effect of obesity on airway hyperresponsiveness (AFHR) or airway inflammation in asthma is not clear. This study evaluated the relationship between obesity and asthma, assessing aspects of symptoms, AHR, and severity. Methods: In total, 852 patients with asthma diagnosed by asthma specialists based on AHR as confirmed by a methacholine bronchial provocation test, were enrolled from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA) adult asthma cohort. The intensity of AHR was assessed by the concentration of methacholine needed to cause a 20% decrease in FEV1 (PC20). Patients were classified into four categories based on body mass index (BMI): underweight (<18.5), normal weight (18.5–24.9), overweight (25.0–29.9), and obese (≥30). Results: BMI was negatively correlated with FEV1 (l), FVC (l), and FEV1/FVC (%) in lung function tests. The prevalence of wheezing increased with higher BMI after adjustment for age, sex, smoking, medication history, and PC20 (p < 0.0001). logPC20 was lower in the normal weight group compared with the overweight group (p = 0.003). The risk of moderate or severe AHR (PC20 ≤ 4 mg/ml) decreased with increased BMI after adjustment for age, sex, smoking, and medication history (p = 0.035). Conclusions: Obesity is a risk factor for asthma in the general population, but obesity in asthmatic patients is negatively correlated with the intensity of AHR and is not related to asthma severity. Obesity is positively related with the prevalence of wheezing but negatively related to AHR in asthmatic patients.

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.