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ABSTRACT: Antituberculosis drug (ATD)-induced hypersensitivity syndrome (HSS) is a serious adverse reaction to ATDs, but much remains to be determined regarding its characteristics and genetic risk factors. In this study, we have collected cases of ATD-induced HSS and their clinical features, and investigated the associations of ATD-induced HSS with human leukocyte antigen (HLA). Subjects with ATD-induced HSS and ATD-tolerant controls were recruited through analysis of a multicenter adverse drug reaction registry in Korea. HLA allele frequencies were compared between subjects with ATD-induced HSS (n = 14) and two control groups: ATD-tolerant controls (n = 166) and the general population (n = 485). The number of enrolled subjects with ATD-induced HSS (n = 14) was comparable to those of patients with HSS induced by other common drugs such as allopurinol during the recruitment period. The frequency of Cw*0401 was much higher in the cases (50.0%) compared with ATD-tolerant controls (12.7%, Pc = 0.0204, OR = 6.90) and the general population (12.8%, Pc = 0.0132, OR = 6.82). Our results suggest that ATD is an important causative agent inducing HSS with distinct clinical features. The strong association of Cw*0401 with the risk for ATD-induced HSS suggests immunological involvement in the development of this syndrome.
Tuberculosis (Edinburgh, Scotland) 11/2012; · 2.54 Impact Factor
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ABSTRACT: Genetic variants in ATP-binding cassette (ABC) transporter genes are associated with increased susceptibility to adverse drug reactions. We hypothesized that genetic variant ABC transporters (ABCB1 and ABCC2) may be candidate markers for predicting maculopapular eruption (MPE) induced by antituberculosis therapy. We compared the genotype distributions of single nucleotide polymorphisms and haplotypes in the ABCB1 and ABCC2 genes between 62 antituberculosis drug (ATD)-induced MPE cases and 159 ATD-tolerant controls using multivariate logistic regression analysis. There was no significant association between genetic polymorphisms in ABCB1 and ATD-induced MPE (P>0.05). Among seven selected SNPs of ABCC2, IVS3-49C>T in intron and I1324I were associated with ATD-induced MPE (P=0.029 and 0.036, respectively). In an analysis of the ABCC2 haplotypes (ht; -1549G>A_-24C>T_IVS3-49C>T_V417I), ht1[G-C-C-G] was significantly associated with ATD-induced MPE (P=0.032, OR=0.35, 95% CI: 0.16-0.95). No significant association between the other haplotypes and ATD-induced MPE was observed. An ABCC2 haplotype is associated with the presence of ATD-induced MPE in patients with tuberculosis and may be a genetic risk factor for the development of MPE induced by ATD.
Allergy, asthma & immunology research 11/2012; 4(6):362-6. · 1.91 Impact Factor
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ABSTRACT: Drug-induced liver injury (DILI) is the most common adverse drug reaction; however, it is not easily predicted. We hypothesize that DILI has a common genetic basis. Based on the findings of previous animal studies on toxic hepatitis, we selected the thioredoxin reductase 1 gene (TXNRD1) as a candidate marker of DILI for this genetic association study.
Records from 118 patients with DILI were extracted from the database of the Adverse Drug Reaction Research Group in South Korea. Causative drugs included antituberculosis drugs (n=68, 57.6%), antibiotics (n=22, 18.6%), antiepileptic drugs (n=7, 5.9%), non-steroidal anti-inflammatory drugs (n=5, 4.2%), and others (n=16, 13.7%). Seven single nucleotide polymorphisms (SNPs) in TXNRD1 (rs10735393, rs4964287, rs4595619, rs10861201, rs11111997, rs4246270, and rs4246271) were scored in 118 DILI patients and in 120 drug-matched controls without liver injury.
No differences were found between the frequencies of any of the 7 SNPs in the cases and controls; however, a significant association was found between a TTA haplotype composed of rs10735393, rs4964287, and rs4595619 and DILI using an allele model (odds ratio, 1.79; 95% confidence interval, 1.18-2.73; P=0.008; Bonferroni corrected P=0.024).
These results suggest that genetic variations in TXNRD1 favor the development of DILI, although a larger confirmative study is needed.
Allergy, asthma & immunology research 05/2012; 4(3):132-6. · 1.91 Impact Factor
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ABSTRACT: Unusual drug accumulation is a common mechanism underlying serious drug-induced liver injury. Polymorphisms in three drug transporter genes (ABCB1, SLCO1B1 and ABCC2) may be risk markers for hepatitis induced by the unusual accumulation of anti-tuberculosis drugs (ATDs). We therefore investigated whether polymorphisms and haplotypes of these genes are associated with ATD-induced hepatitis by comparing the frequencies and distributions of single nucleotide polymorphisms and haplotypes of these three drug transporter genes among 67 patients with ATD-induced hepatitis and 159 patients tolerant to ATDs using a multivariate logistic regression analysis. We found that the frequencies of polymorphisms and haplotypes of ABCB1, SLCO1B1 and ABCC2 were similar in patients with ATD-induced hepatitis and ATD-tolerant controls. The present results suggest that these drug transporters do not play important roles in the pathogenesis of ATD-induced hepatitis in Korean patients.
Tuberculosis (Edinburgh, Scotland) 12/2011; 92(1):100-4. · 2.54 Impact Factor
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ABSTRACT: While the mechanisms underlying the development of drug-induced liver injury are not clear, there is evidence to suggest that tumor necrosis factor-α (TNF-α) plays an important role in drug- or drug metabolite-induced immune responses. We hypothesized that polymorphisms in the TNF-α gene are associated with anti-tuberculosis drug (ATD)-induced hepatitis.
Patients who suffered from ATD-induced hepatitis were enrolled in the study. ATD-induced hepatitis was defined as an increase in liver transaminase levels that were more than three times the upper limit of normal. ATD-tolerant patients were used as a control. Patients were treated with first line ATD therapies including isoniazid, rifampicin, ethambutol, and pyrazinamide. We compared the genotype frequencies of the TNF-α polymorphism -308G/A in 77 patients with ATD-induced hepatitis and 229 ATD-tolerant patients.
The frequency of carrying the variant allele (AG or AA) was significantly higher in patients with ATD-induced hepatitis compared with ATD-tolerant patients [26.0% vs. 15.3%, P = 0.034, OR (95% CI) = 1.94 (1.043.64)] and the frequency of the A allele was significantly different between the two groups [0.143 vs. 0.079, P = 0.018, OR (95% CI) = 1.95 (1.113.44)].
These results reveal that the TNF-α genetic polymorphism -308G/A is significantly associated with ATD-induced hepatitis. This genetic variant may be a risk factor for ATD-induced hepatitis in individuals from Korea.
Liver international: official journal of the International Association for the Study of the Liver 12/2011; 32(5):809-14. · 3.82 Impact Factor
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Sae-Hoon Kim,
Kyung Wha Lee,
Woo-Jung Song,
Sang-Heon Kim, Young-Koo Jee,
Sang-Min Lee,
Hye-Ryun Kang,
Heung-Woo Park,
Sang-Heon Cho,
Seong-Ho Park,
Kyung-Up Min,
Yoon-Seok Chang
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ABSTRACT: 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.
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.
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.
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.
Epilepsy research 09/2011; 97(1-2):190-7. · 2.48 Impact Factor
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Hye-Ryun Kang, Young Koo Jee,
Yon-Soo Kim,
Chang Hwa Lee,
Jae-Woo Jung,
Sae Hoon Kim,
Heung-Woo Park,
Yoon-Seok Chang,
In-Jin Jang,
Sang-Heon Cho,
Kyung-Up Min,
Sang-Heon Kim,
Kyung Wha Lee
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ABSTRACT: Recent investigations suggest genetic susceptibility of allopurinol-induced severe cutaneous adverse reactions (SCARs). However, the strength of association was variable according to phenotypes and ethnic backgrounds. To explore genetic markers for allopurinol-induced SCARs in Koreans, we genotyped human leukocyte antigen (HLA) class I alleles of 25 cases of allopurinol-induced SCARs (20 cases of drug-induced hypersensitivity syndrome and five cases of Stevens-Johnson syndrome/toxic epidermal necrolysis) and 57 patients tolerant to allopurinol. Frequencies of B*5801 [92.0 vs. 10.5%, P(c)=2.45×10(-11), odds ratio (OR)=97.8], Cw*0302 (92.0 vs. 12.3%, P(c)=9.39×10(-11), OR=82.1), and A*3303 (88.0 vs. 26.3%, P(c)=3.31×10(-6), OR=20.5) were significantly higher in SCARs compared with tolerant controls. In contrast, A*0201 was not found in SCARs patients despite relatively high frequency in tolerant controls (29.8%). We found strong positive association of HLA-B*5801 and negative association of HLA-A*0201 with the development of allopurinol-induced SCARs in the Korean population.
Pharmacogenetics and Genomics 02/2011; 21(5):303-7. · 3.48 Impact Factor
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Sang Min Lee,
Yoon-Seok Chang,
Cheol-Woo Kim,
Tae-Bum Kim,
Sang-Heon Kim,
Yong-Eun Kwon,
Jong-Myung Lee,
Soo-Keol Lee,
Jae-Won Jeong,
Jung-Won Park,
Sang-Heon Cho,
Hee-Bom Moon, Young-Koo Jee
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ABSTRACT: The objective of this study was to evaluate skills in handling inhalers and factors associated with these skills among patients with asthma who had undergone treatment at special asthma and allergy clinics in Korea.
We enrolled 78 subjects who used Turbuhaler and 145 who used Diskus for asthma control at special clinics in 10 university hospitals and visually assessed their skills in handling these inhalers. We also evaluated skills in 137 subjects who had used pressurized metered-dose inhalers (pMDIs) for symptom relief. Age, sex, duration of asthma and inhaler use, smoking status, monthly income, highest grade completed in school and previous instruction for handling inhalers were also measured to evaluate their association with overall inhaler skills.
Performance grade was inadequate for 12.8% of participants using Turbuhaler, 6.2% for Diskus, and 23.4% for pMDIs. The success rates for each step in handling the inhalers were relatively high except for the "exhale slowly to residual volume" step, in which success rates ranged from 24.2% to 28.5%. Older age, male sex, lower educational grade, and absence of previous instruction for handling inhalers were associated with inadequate inhaler technique in univariate analysis; however, only older age and absence of previous instruction remained significant independent risk factors in multivariate analysis.
Among Korean asthmatic patients in special asthma and allergy clinics, skills in handling their inhalers were mostly excellent; meanwhile, older age and absence of previous instruction for handling inhalers were associated with inadequate techniques.
Allergy, asthma & immunology research 01/2011; 3(1):46-52. · 1.91 Impact Factor
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ABSTRACT: It has been suggested that drug-metabolizing enzymes might play important roles in the development of anti-tuberculosis drug (ATD)-induced maculopapular eruption (MPE), as in ATD-induced hepatitis. We investigated the associations between the genetic polymorphisms of drug-metabolizing enzymes and ATD-induced MPE.
We enrolled 62 patients with ATD-induced MPE (mean age 47.2 ± 19.0, male 59.7%) and 159 patients without any adverse reactions to ATD (mean age 42.8 ± 17.6, male 65.4%), among patients with pulmonary tuberculosis (TB) and/or TB pleuritis and treated with first-line anti-TB medications, including isoniazid, rifampin, ethambutol, and pyrazinamide. We compared the genotype distributions of single nucleotide polymorphisms and haplotypes in four drug-metabolizing enzymes (N-acetyltransferase 2 (NAT2), cytochrome P450 (CYP) 2 C9, CYP2C19, and CYP2E1) among patients with ATD-induced MPE and patients tolerant to ATD using a multivariate logistic regression analysis. These analyses were made without identification of the responsible ATD.
-1565 C > T of CYP2C9 showed a significant association with ATD-induced MPE (P = 0.022, OR = 0.23, 95% CI 0.07-0.78), with a lower frequency of genotypes carrying minor alleles (CT or TT) in the case group than in the controls. Additionally, W212X of CYP2C19 was significantly associated with the risk of ATD-induced MPE (P = 0.042, OR = 0.27, 95% CI 0.09-0.82). In an analysis of the CYP2C19-CYP2C9 haplotypes (-1418 C > T_W212X_-1565 C > T_-1188 C > T), ht3[T-A-T-C] showed a significant association with the development of ATD-induced MPE (P = 0.012, OR = 0.13, 95% CI 0.03-0.57). No significant associations between the other genetic polymorphisms and ATD-induced MPE were observed.
CYP2C19 and CYP2C9 genetic polymorphisms are significantly associated with the risk of developing ATD-induced MPE, and the genetic variants in NAT2 and CYP2E1 are not closely related to the development of this adverse reaction.
European Journal of Clinical Pharmacology 10/2010; 67(2):121-7. · 2.85 Impact Factor
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ABSTRACT: 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.
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.
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).
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.
Pharmacogenomics 06/2010; 11(6):879-84. · 3.97 Impact Factor
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ABSTRACT: Hypersensitivity to mosquito bites (HMB) is a disorder characterized by a necrotic skin reaction and generalized symptoms subsequent to mosquito bites. It has been suggested that HMB is associated with chronic Epstein-Barr virus (EBV) infection and natural killer cell leukemia/lymphoma. We describe here a Korean child who had HMB associated with chronic EBV infection and natural killer cell lymphocytosis. A 5-yr-old boy was suffered from necrotic skin lesions on the right ear lobe. Type A EB virus was detected from hlood cells and bone marrow biospy recognized hemophagocyrosis.
Journal of Korean medical science 02/2010; 25(2):321-3. · 0.84 Impact Factor
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ABSTRACT: Adverse reactions induced by antituberculosis drugs (ATD) often result in serious morbidities, impeding scheduled treatment and cure. In the development of ATD-induced adverse reactions, glutathione S-transferase has been suggested to play a protective role as an intracellular scavenger by conjugating toxic reactive metabolites of ATD. This study examined the association of null mutations in GST enzyme genes (GSTT1 and GSTM1) with the development of ATD-induced hepatitis and cutaneous reactions. We compared the frequencies of GSTT1 and GSTM1 null mutations in 57 patients with hepatitis, 94 patients with cutaneous adverse reactions, and 190 ATD-tolerant controls. The frequency of null mutations in GSTT1 and GSTM1 in patients with ATD-induced hepatitis was not significantly different from that of controls (59.6% vs. 54.2% and 45.6% vs. 54.7%, respectively). Additionally, no significant difference was observed in the frequency of either null mutation in patients with ATD-induced cutaneous reactions, including maculopapular eruption, compared with controls (58.5% vs. 54.1% for GSTT1 and 59.6% vs. 54.6% for GSTM1). These findings indicate that GSTT1 and GSTM1 null mutations are not associated with the development of ATD-induced hepatitis or cutaneous reactions in this Korean population, and suggest that glutathione S-transferase enzymes do not play important roles in the pathogenesis of these conditions.
Tuberculosis (Edinburgh, Scotland) 01/2010; 90(1):39-43. · 2.54 Impact Factor
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Sang-Heon Kim,
Sang-Hoon Kim,
Joon-Woo Bahn,
Yoon-Keun Kim,
Yoon-Seok Chang,
Eun-Soon Shin,
Youn-Seup Kim,
Jae-Seuk Park,
Bo-Hyung Kim,
In-Jin Jang,
Junghan Song,
Seung-Hyun Kim,
Hae-Sim Park,
Kyung-Up Min, Young-Koo Jee
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ABSTRACT: Although some genetic risk factors have been reported for the development of hepatitis due to anti-TB drugs, an extensive candidate gene approach evaluating drug-metabolizing enzymes has not been attempted. This study aimed to investigate the association of genetic polymorphisms in drug-metabolizing enzymes with anti-TB drug-induced hepatitis.
We compared genotype distributions of tagging SNPs in promoter, exons and haplotypes in seven drug-metabolizing enzyme genes (CYP2C9, CYP2C19, CYP2D6, CYP2E1, NAT2, UGT1A1 and UGT1A3) between 67 cases and 159 controls.
Among four tagging SNPs of N-acetyltransferase 2 (NAT2), -9796T>A in promoter and R197Q were significantly associated (p = 0.0016 and p = 0.0007, respectively). NAT2 haplotype 2 [A-A-A-G] carrying A allele of -9796T>A and A allele of R197Q showed significant association (p = 0.0004). However, there was no significant association between genotypes of other enzyme-metabolizing genes and anti-TB drug-induced hepatitis. The constructs containing -9796A of NAT2 showed significantly lower luciferase activity (p < 0.01), suggesting decreased expression of NAT2. The variant alleles and haplotype 2 showed significantly higher peak serum levels of isoniazid, lower acetyl isoniazid:isoniazid ratio and lower isoniazid clearance compared with wild-types.
These findings suggest that genetic variants in the promoter and exons of NAT2 increase the risk of anti-TB drug-induced hepatitis by modifying acetylation phenotypes and/or gene expression of NAT2, and there is no essential role for genetic mutation of the other metabolizing enzymes in the development of this adverse reaction.
Pharmacogenomics 11/2009; 10(11):1767-79. · 3.97 Impact Factor
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ABSTRACT: While initial education and regular evaluation of inhaler technique in patients are emphasized in the management of asthma and chronic obstructive pulmonary disease, health care professionals are not experienced in using inhalers. This study assessed whether internal medicine residents used common inhalers correctly and whether a single teaching session successfully improved their performance.
We evaluated 142 internal medicine residents from six university hospitals in Korea for their techniques with three different inhaler devices: a metered dose inhaler (MDI), Diskus, and Turbuhaler. We assessed whether participants completed each step in using the three inhalers and classified overall performance as good, adequate, or inadequate for each inhaler type. To estimate the effect of a single teaching session, reassessment was performed 2 months after education.
Performance grade was inadequate for 50.7% of participants with a MDI, 43.0% for Diskus, and 51.4% for Turbuhaler. An early year of residency was associated significantly with inappropriate technique for Diskus (p = 0.003), but not for MDI and Turbuhaler. After a single teaching session, overall skills improved significantly for all three inhalers. The proportion of subjects with good or adequate skill changed notably from 39.7% to 83.8% for MDI (p = 0.001), from 50.0% to 86.8% for Diskus (p = 0.001), and from 44.1% to 88.2% for Turbuhaler (p = 0.001).
These findings demonstrate that a high proportion of internal medicine residents cannot use inhalers correctly and just a single teaching can effectively enhance their inhaler technique.
Journal of Asthma 11/2009; 46(9):944-50. · 1.52 Impact Factor
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ABSTRACT: Few health-related quality of life (HRQOL) studies of asthma patients have been conducted in Korea, mainly due to the lack of a psychometrically validated asthma-specific instrument.
The aims of the present study were to develop and evaluate an instrument for assessing HRQOL in Korean asthma patients (asthma-specific quality of life, [A-QOL]).
Items were generated using in-depth interviews and a review of the literature and were subsequently reviewed by a panel of experts. Content-validated items were evaluated psychometrically with the aid of 422 asthma patients who were recruited from university hospitals in South Korea. The participants were asked to complete a preliminary A-QOL questionnaire (comprising the content-validated items), the Asthma Control Test, the Center for Epidemiologic Studies-Depression Survey (CES-D), and the Short Form-36 Health Survey. The Global Initiative for Asthma Guideline classification was also used to classify the severity of asthma. The psychometric properties of the data were analyzed.
Thirty-six preliminary items were generated, from which factor analysis extracted a six-factor solution. Six of the items were not loaded significantly on any of the factors, such that they were not heterogeneous items. Multi-trait scaling analysis supported item convergence and discriminant validity. The A-QOL was associated significantly with the CES-D. Patients with controlled asthma had higher A-QOL scores than those whose asthma was not controlled. The quality of life measured by the A-QOL was more sensitive than that measured by the generic Short Form-36 Health Survey. The values of Cronbach's alpha for the subscales of the A-QOL were all greater than 0.70. The responsiveness of all subscales, excluding the "environmental distress" subscale, was established.
The A-QOL is an easily applied tool that exhibits good psychometric properties for asthma patients. The A-QOL questionnaire is valid for and can be used reliably in both practice and clinical trials.
Journal of Asthma 10/2009; 46(7):716-21. · 1.52 Impact Factor
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ABSTRACT: Patterns of prescriptions are markedly influenced by regional disease entities, medical education, culture, economic status, and available pharmaceutical companies. Features of adverse drug reactions (ADRs) may vary in different countries. In this study, we analyzed the causative drugs and clinical manifestations of spontaneously reported ADRs in Korea.
Six Korean Regional Pharmacovigilance Centers collected 1418 cases of spontaneously reported adverse drug events (ADEs) by doctors, pharmacists, and nurses, and the clinical features and causative drugs were evaluated. The data were collected from general hospitals (76.5%), primary clinics, and pharmacies (23.5%).
Based upon the World Health Organization (WHO)-Uppsala Monitoring Center criteria (certain-13.7%, probable-46.1%, possible-32.1%), 91.9% of the collected events were suspected to be ADRs and 15.8% of patients experienced serious ADRs. The most prevalent causative drugs were antibiotics (31.6%), followed by contrast dyes (14.0%), non-steroidal anti-inflammatory drugs (NSAIDs) (11.1%), anti-psychotics (5.4%), anti-convulsants (5.2%), cardiovascular agents (4.8%), anti-neoplastics (4.6%), and opiates and non-opiate pain killers (3.5%). Among the antibiotics, cephalosporins (8.1%) were the most common, followed by anti-tuberculosis agents (5.7%), quinolones (4.0%), vancomycin (3.1%), and penicillin (2.8%). The most common side effect was skin manifestations, which were seen in 42% of the patients, followed by neurologic manifestations (14%), gastrointestinal involvements (12.9%), generalized reactions (9.4%), and respiratory involvements (4.5%).
Antibiotics, contrast dyes, and NSAIDs were the most common causative drugs for ADRs, which reflects the prescription pattern and the prevalence of diseases in Korea. These data may be useful in establishing a Korean pharmacovigilance system.
Pharmacoepidemiology and Drug Safety 08/2009; 18(10):910-5. · 2.53 Impact Factor
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ABSTRACT: Good adherence to inhaled corticosteroid (ICS) therapy is essential for effective asthma control. The factors affecting ICS therapy adherence vary among individuals and countries. As few data on adherence have been reported in Korea, the factors influencing such adherence, and the clinical implications thereof, were evaluated in Korean asthma patients. A total of 185 asthma patients who had taken ICS regularly for over 1 year were randomly selected from the recently established domestic adult asthma cohort, COREA (Cohort for Reality and Evolution of Adult Asthma Korea). To obtain adherence to ICS, both prescription refill adherence and self-reported adherence over 1 year (these are objective and subjective measurements respectively) were assessed without any interventions that might affect patients' adherence to ICS. Patients' information such as age, sex, smoking history and number of medication taken, was collected. Assessment of asthma severity, pulmonary function tests, and asthma symptom score were performed to evaluate the possible clinical implication of adherence to ICS. Approximately half of the patients (50.9%) showed less than 80% of prescription refill adherence. There was a considerable discrepancy between prescription refill adherence and self-reported adherence especially in the patients whose refill adherence was under than 50%. Younger asthma patients showed lower adherence to ICS than did older (> or = 60 years old) patients. Higher asthma severity was significantly associated with lower refill adherence to ICS. However, asthma symptom scores and forced expiratory volume in 1 second (FEV(1)) values were not directly related with refill adherence. To improve asthma control in Korea, enhancement of adherence to ICS is critical: our findings emphasize the need to use objective measurements when adherence to asthma medication is to be assessed in clinical practice.
Journal of Asthma 08/2009; 46(6):591-5. · 1.52 Impact Factor
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ABSTRACT: Combination treatment of inhaled corticosteroid (ICS) plus long-acting beta2-agonist (LABA) is widely used as a maintenance regimen for the management of asthma. This study evaluated the effect of the beta2-adrenergic receptor (ADRB2) polymorphism on lung function and asthma control with regular use of combination treatment of an inhaled ICS plus LABA.
43 Korean asthmatics who were symptomatic despite regular ICS use for at least 3 months were enrolled. For a 2-week run-in period, they received ICS (budesonide 800 microg/day) plus terbutaline (5 microg prn). as needed. During the 24-week active treatment period, they received budesonide 160 microg and formoterol 4.5 microg b.i.d. as maintenance and rescue medication. Pulmonary function and quality of life scores were monitored every 8 weeks; morning/evening peak expiratory flow meter (PEFR) was recorded daily. Patients were genotyped for ADRB2 Arg16Gly using single base extension methodology.
During the run-in period, there were no significant between-group differences in lung function; after 8 weeks of active treatment, Arg/Arg patients had significantly higher forced expiratory volume in 1 secord (FEV(1)) and maximal mid-expiratory flow (MMEF) (p = 0.023 and p = 0.021, respectively), and better asthma control and quality of life after 24 weeks (p = 0.016 and p = 0.028, respectively). During treatment, there was a greater improvement in morning/evening PEFR in Arg/Arg patients.
Asthmatic patients with the Arg/Arg genotype at codon 16 of ADRB2 achieve better asthma control with long-term regular use of combined budesonide and formoterol treatment, suggesting that the ADRB2 genotype may dictate choice of treatment strategy.
Yonsei medical journal 05/2009; 50(2):182-8. · 0.77 Impact Factor
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Mina Ha,
Ho-Jang Kwon,
Myung-Ho Lim, Young-Koo Jee,
Yun-Chul Hong,
Jong-Han Leem,
June Sakong,
Jong-Myun Bae,
Soo-Jong Hong,
Young-Man Roh,
Seong-Joon Jo
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ABSTRACT: The goal of this study was to examine the association between low levels of lead and mercury in blood and symptoms of attention-deficit hyperactivity disorder (ADHD) among Korean children.
One thousand seven hundred and seventy eight children at 10 elementary schools in six South Korea cities participated in this study. Parents and guardians administered a questionnaire including Conners' parents rating ADHD scale to determine the presence of ADHD symptoms. In addition, clinical examinations of the children and determination of blood lead and mercury levels were included in the first Children's Health and Environment Research (CHEER) survey, which is now conducted annually in Korea.
The risk for the appearance of ADHD symptoms was found to increase with the blood lead concentration. The mean blood lead concentration was low with a geometric mean of 1.8 microg/dl. The odds ratios (95% confidence intervals) for the presence of ADHD symptoms were 1.28 (0.57, 2.86), 1.32 (0.63, 2.74), 1.65 (0.77, 3.56), and 1.98 (0.76, 5.13) in children with blood lead levels of 1-<1.5, -<2.5, -<3.5, and >3.5 microg/dl, compared to those with blood lead levels of <1.0 microg/dl; these results statistically represented a borderline trend (p for trend: 0.07). The blood lead level showed a significant positive association with the Conners' ADHD score (beta=0.50, p<0.0001). However, the blood mercury levels were not found to be significantly associated with ADHD symptoms in children. The geometric mean mercury concentration in the blood was 2.4 microg/l.
The observed association between blood lead concentration and the appearance of ADHD symptoms in Korean children suggests that lead, even at low concentrations, is a risk factor for ADHD.
NeuroToxicology 11/2008; 30(1):31-6. · 3.10 Impact Factor
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ABSTRACT: The glucocorticoid receptor (GR) is able to participate in regulation of transcription by a variety of mechanisms, one of which involves DNA binding and recruitment of regulatory cofactors. The best-studied forms of the receptor are the 777-amino-acid alpha and the 742-amino-acid beta variants. The beta isoform, which does not bind cortisol in human subjects, has been proposed to be a dominant-negative inhibitor of the transcriptional activation-competent GRalpha isoform.
GRalpha has roles in both transcriptional activation and repression. We wished to determine the influence of GRbeta on genes that are normally transcriptionally repressed by glucocorticoids. We studied IL5 and IL13, which both contribute to the asthmatic phenotype.
We used transient transfection systems and coimmunoprecipitation experiments to determine whether GRbeta has repressive activity on the promoters of the human IL5 and IL13 genes.
GRbeta is able to act as a transcriptional repressor of cytokine genes and mediates its function through the recruitment of histone deacetylase complexes.
GRalpha and GRbeta act in a similar manner on IL5 and IL13 promoters, serving to repress transcription. In this circumstance GRbeta does not act as a dominant-negative inhibitor of GRalpha.
The Journal of allergy and clinical immunology 02/2008; 121(1):203-208.e1. · 9.17 Impact Factor
