Establishment of a murine model based on chronic exposure to domestic house dust mites in Korea

Purpose@#Asthma is a chronic disorder characterized by bronchial hyperresponsiveness and reversible airflow obstruction. Repeated exposure to allergens of the respiratory tract causes chronic inflammation, followed by structural changes in the lung called airway remodeling. House dust mites (HDM) are known as the predominant inhalant allergens, and several studies have reported that the allergenic property of HDM extracts varied with the geographic regions where they were produced. This study aimed to establish a murine experimental model by long-term intranasal exposure to HDM allergen indigenous to Korea. @*Methods@#HDM extracts from cultured Dermatophagoides pteronissunus in Korea were used in our model. We administered the extracts intranasally to BALB/c mice 3 times a week for 8 or 10 consecutive weeks, followed by measuring airway allergic inflammation and airway remodeling. @*Results@#The number of neutrophils in the lungs was higher in the group with long-term exposure to HDM than in the normal control group. The levels of total IgE and a wide range of cytokines, including Th1/Th2/Th17 and proinflammatory cytokines, were significantly higher in the long-term HDM-exposed group than in the normal control group. The development of airway remodeling by chronic exposure to HDM was observed by measuring diverse factors, including collagens and transforming growth factor (TGF)-β. These significant results were more clearly shown in the group exposed to HDM for 8 weeks than 10 weeks. @*Conclusion@#A murine model of chronic exposure to domestic HDM in Korea was successfully established. We suggest that our model may be helpful in the research into asthma with airway remodeling.

Risk Factors and Comorbidities Associated With the Allergic Rhinitis Phenotype in Children According to the ARIA Classification

PURPOSE: Data are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study. METHODS: We enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed. RESULTS: The prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77–15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40–40.74). CONCLUSIONS: Moderate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.

Prevalence of Self-reported Allergic Diseases and IgE Levels: A 2010 KNHANES Analysis

PURPOSE: The prevalence of allergic diseases is known to be associated with both demographic and environmental factors. Herein, we aimed to determine significant factors associated with the prevalence of allergic diseases and with total immunoglobulin E (tIgE) and specific immunoglobulin E (sIgE) levels in Korea. METHODS: We analyzed unweighted data collected by the 2010 Korea National Health and Nutrition Examination Survey for 2,342 subjects who underwent serum tests for tIgE and sIgE to Dermatophagoides farinae, dog, and Blattella germanica, representing a sample of 16,003,645 citizens, by considering the sample weight and stratification. RESULTS: The overall prevalence of self-reported allergic diseases was 37.6%. The prevalence rates of allergic rhinitis and atopic dermatitis decreased with age, whereas the asthma prevalence was not affected by the age of the subjects. When analyzed according to the type of allergic diseases, the prevalence of self-reported allergic disease was significantly associated with various factors (e.g. age, occupation, living in urban areas, and depression). The tIgE level decreased with age, but later increased. Elevation of tIgE was significantly associated with male sex, type of occupation, obesity, and smoking status. However, the risk factors for the increased sIgE levels to each allergen were quite different. Sensitization to D. farinae was more likely in young subjects, whereas the prevalence of sensitization to B. germanica was significantly higher in subjects with male sex, residing in a house (houses), and with glucose intolerance. Finally, young age and the smoking status were significantly associated with sensitization to dog. CONCLUSIONS: Various demographic and environmental factors were significantly associated with the prevalence of self-reported allergic diseases and the levels of tIgE and sIgE to D. farinae, B. germanica, and dog in Korea.

The change in food allergy prevalence of elementary school children in Seoul since the last 20 years and the risk factor analysis

PURPOSE: There are many reports that the prevalence of food allergy (FA) is globally increasing. We investigated the change in FA prevalence since the last 20 years in elementary school children, in Seoul, Korea. METHODS: A modified International Study of Asthma and Allergies in Childhood questionnaire survey was done to elementary school children in Seoul, Korea in 1995, 2000, 2005, 2008, and 2012. The numbers of subjects included in the analysis were 7,963, 7,971, 7,131, 3,975, and 3,307, respectively. Blood and skin prick tests were done in 2008 and 2012. RESULTS: The prevalence rates of FA diagnosis ever were 4.6% (95% confidence interval [CI], 4.1-5.1), 5.2% (95% CI, 4.7-5.7), 6.4% (95% CI, 5.9-7.0), 5.5% (95% CI, 4.8-6.3), and 6.6% (95% CI, 5.8-7.6) in 1995, 2000, 2005, 2008, and 2012, respectively (P-value for trend <0.001). Asthma (adjusted odds ratio [aOR], 2.209; 95% CI, 1.589-3.072), allergic rhinitis (aOR, 1.874; 95% CI, 1.473-2.384), and atopic dermatitis (aOR, 4.288; 95% CI, 3.340-5.506) were associated with FA diagnosis. Parental allergic disease history (aOR, 2.191; 95% CI, 1.666-2.881), antibiotics use in infancy (aOR, 1.484; 95% CI, 1.170-1.883), and house mold exposure in infancy (aOR, 1.540; 95% CI, 1.172-2.024) were risk factors for FA diagnosis. Sensitization to inhalant allergens (aOR, 1.867; 95% CI, 1.091-3.194) and increased serum total IgE (aOR, 2.014; 95% CI, 1.081-3.752) were associated with FA diagnosis. CONCLUSION: The prevalence of FA diagnosis is likely to be increasing since the last 20 years in Seoul. Antibiotics use in infancy and house mold exposure in infancy were risk factors for FA diagnosis.

Antimicrobial Resistance among Clinical Isolates of Pseudomonas aeruginosa from Non-tertiary Care Hospitals in Korea, 2002-2004

BACKGROUND: Increasing numbers of resistant and multidrug resistant (MDR) isolates of Pseudomonas aeruginosa have become a worldwide problem. This report provides the trend of antimicrobial resistance, the proportions of MDR and metallo-beta-lactamase-producing isolates among clinical isolates of P. aeruginosa in Korea. MATERIALS AND METHODS: Clinical isolates of P. aeruginosa were collected from two representative reference laboratories during 2002-2004. Clinical information regarding specimens and type of hospital for isolates was investigated. Antimicrobial susceptibility against 11 antibiotics was tested by disk diffusion according to NCCLS criteria. MDR was assessed as resistance to > or =3 of the core drugs (ceftazidime, ciprofloxacin, gentamicin, imipenem and piperacillin). PCR assays and sequencing for detection of blaVIM-2 and blaIMP-1 gene were carried out. RESULTS: Of 1,748 P. aeruginosa isolates, 179 isolates were collected from primary care hospitals and 1,569 isolates were recovered from outpatients and inpatients in secondary care hospitals. From 2002 to 2004, rates of resistance to ceftazidime and imipenem increased from 10% to 12.3% and from 14.8% to 15.9%, respectively. Rates of resistance to amikacin (from 26.2% to 31.0%) and ciprofloxacin (from 35.6% to 46.2%) increased annually. In the period 2002-2004, decreasing of susceptibility to meropenem (from 83.4% to 76.8%) was observed, but meropenem was the most potent agent against P. aeruginosa isolates studied. During the 3-year period, MDR P. aeruginosa accounted for 26.4-33.5% of clinical isolates and the most common MDR phenotype was concurrent resistance to piperacillin, gentamicin and ciprofloxacin. The prevalence of VIM-2-producing isolates obviously increased from 1.7% in 2002 to 6.3% in 2004. CONCLUSIONS: These results suggested that MDR P. aeruginosa was already prevalent in one third of clinical isolates and VIM-2-producing P. aeruginosa isolates disseminated in non-tertiary care hospitals in Korea.

Prevalence and Genetic Relatedness of Vancomycin-resistant Enterococci Isolated from Livestock and Humans after Ban of Avoparcin in Korea

BACKGROUND: Avoparcin, cross-resistance with vancomycin, was added as feed-additive since 1970s and was prohibited in 1997 in Korea. After avoparcin was banned we examined prevalence and genetic relatedness of VRE in enterococci isolated from livestock and humans. MATERIALS AND METHODS: Using enrichment broth and 6 microgram/mL vancomycin-containing enterococcosel selective agar, vancomycin-resistant enterococci (VRE) were isolated from fecal sample of 255 pigs of 8 farms, 431 chickens of 9 farms, and 328 humans (Food industry employee and Institution cafeteria employee) of 5 public health centers, and 100 raw chicken meats from April to June 2003. Antimicrobial susceptibility was examined by disk diffusion and minimum inhibitory concentrations (MICs), and E-test. Species identification and genotyping were done by multiplex PCR method. Pulsed-field gel electrophoresis (PFGE) of vanA-type VRE isolates was performed by CHEF-Mapper system. RESULTS: 19 isolates from 255 pigs, 122 isolates from 431 chickens, 19 isolates from 100 raw chicken meat, and 7 isolates from 328 humans were resistant to vancomycin. Of the 167 VRE isolates, vanA gene was detected in 141 isolates; 1 isolate (0.4%) in pigs, 121 isolates (28.1%) in chickens, 18 isolates (18.0%) in raw chicken meat, and 1 isolate (0.3%) in humans. Resistant rates of streptomycin, tetracycline, and erythromycin were over 60% in vanA-type E. faecium isolated from poultry. PFGE analysis resulted in two major patterns, F and P types. Also PFGE pattern of 1 VRE from human was identical to that of 1 VRE from poultry. CONCLUSION: Despite the high prevalence of vanA-type VRE in poultry farms, VRE isolation rate in human was relatively low. This result suggests that the possibility of VRE transmission from poultry to human is low but that possibility may be not ruled out. In PFGE analysis showing 51.5% identical in 2 PFGE patterns, the dissemination of VRE isolates in poultry may be transmitted vertically and horizontally.

Antimicrobial Resistance among Clinical Isolates of Pseudomonas aeruginosa from Non-tertiary Care Hospitals in Korea, 2002-2004

BACKGROUND: Increasing numbers of resistant and multidrug resistant (MDR) isolates of Pseudomonas aeruginosa have become a worldwide problem. This report provides the trend of antimicrobial resistance, the proportions of MDR and metallo-beta-lactamase-producing isolates among clinical isolates of P. aeruginosa in Korea. MATERIALS AND METHODS: Clinical isolates of P. aeruginosa were collected from two representative reference laboratories during 2002-2004. Clinical information regarding specimens and type of hospital for isolates was investigated. Antimicrobial susceptibility against 11 antibiotics was tested by disk diffusion according to NCCLS criteria. MDR was assessed as resistance to > or =3 of the core drugs (ceftazidime, ciprofloxacin, gentamicin, imipenem and piperacillin). PCR assays and sequencing for detection of blaVIM-2 and blaIMP-1 gene were carried out. RESULTS: Of 1,748 P. aeruginosa isolates, 179 isolates were collected from primary care hospitals and 1,569 isolates were recovered from outpatients and inpatients in secondary care hospitals. From 2002 to 2004, rates of resistance to ceftazidime and imipenem increased from 10% to 12.3% and from 14.8% to 15.9%, respectively. Rates of resistance to amikacin (from 26.2% to 31.0%) and ciprofloxacin (from 35.6% to 46.2%) increased annually. In the period 2002-2004, decreasing of susceptibility to meropenem (from 83.4% to 76.8%) was observed, but meropenem was the most potent agent against P. aeruginosa isolates studied. During the 3-year period, MDR P. aeruginosa accounted for 26.4-33.5% of clinical isolates and the most common MDR phenotype was concurrent resistance to piperacillin, gentamicin and ciprofloxacin. The prevalence of VIM-2-producing isolates obviously increased from 1.7% in 2002 to 6.3% in 2004. CONCLUSIONS: These results suggested that MDR P. aeruginosa was already prevalent in one third of clinical isolates and VIM-2-producing P. aeruginosa isolates disseminated in non-tertiary care hospitals in Korea.

Prevalence and Genetic Relatedness of Vancomycin-resistant Enterococci Isolated from Livestock and Humans after Ban of Avoparcin in Korea

BACKGROUND: Avoparcin, cross-resistance with vancomycin, was added as feed-additive since 1970s and was prohibited in 1997 in Korea. After avoparcin was banned we examined prevalence and genetic relatedness of VRE in enterococci isolated from livestock and humans. MATERIALS AND METHODS: Using enrichment broth and 6 microgram/mL vancomycin-containing enterococcosel selective agar, vancomycin-resistant enterococci (VRE) were isolated from fecal sample of 255 pigs of 8 farms, 431 chickens of 9 farms, and 328 humans (Food industry employee and Institution cafeteria employee) of 5 public health centers, and 100 raw chicken meats from April to June 2003. Antimicrobial susceptibility was examined by disk diffusion and minimum inhibitory concentrations (MICs), and E-test. Species identification and genotyping were done by multiplex PCR method. Pulsed-field gel electrophoresis (PFGE) of vanA-type VRE isolates was performed by CHEF-Mapper system. RESULTS: 19 isolates from 255 pigs, 122 isolates from 431 chickens, 19 isolates from 100 raw chicken meat, and 7 isolates from 328 humans were resistant to vancomycin. Of the 167 VRE isolates, vanA gene was detected in 141 isolates; 1 isolate (0.4%) in pigs, 121 isolates (28.1%) in chickens, 18 isolates (18.0%) in raw chicken meat, and 1 isolate (0.3%) in humans. Resistant rates of streptomycin, tetracycline, and erythromycin were over 60% in vanA-type E. faecium isolated from poultry. PFGE analysis resulted in two major patterns, F and P types. Also PFGE pattern of 1 VRE from human was identical to that of 1 VRE from poultry. CONCLUSION: Despite the high prevalence of vanA-type VRE in poultry farms, VRE isolation rate in human was relatively low. This result suggests that the possibility of VRE transmission from poultry to human is low but that possibility may be not ruled out. In PFGE analysis showing 51.5% identical in 2 PFGE patterns, the dissemination of VRE isolates in poultry may be transmitted vertically and horizontally.

Antimicrobial Resistance of Clinical Isolates of Acinetobacter spp. Collected from Non-Tertiary Hospitals and Detection of a Metallo-beta-Lactamase-Producing Strain

BACKGROUND: The aim of this study was to investigate the antimicrobial resistance of clinical isolates of Acinetobacter spp. collected from non-tertiary hospitals and to characterize the phenotype and the genotype of imipenem-non-susceptible isolates. MATERIALS AND METHODS: Clinical isolates of Acinetobacter spp. were identified using recA-restriction fragment length polymorphism (RFLP) analysis with Tsp5091. Susceptibility to antimicrobial agents was determined using disk diffusion test and agar dilution test according to the criteria of the National Committee for Clinical Laboratory Standards. PCR and sequence analyses were used to detect the blaIMP-1 and blaVIM-2 genes, and to determine the content and order of the resistance genes inserted in integron. RESULTS: Of 71 Acinetobacter spp. isolates collected from non-tertiary hospitals during 2002 and 2003, 60 isolates were A. baumannii, and 2, 4, and 5 isolates were Acinetobacter genomic species 3, 13TU, and A. lwoffii, respectively. The resistance rate of Acinetobacter spp. isolates to beta-lactams, aminoglycosides, and fluoroquinolones was high except for imipenem and meropenem. The presence of blaVIM-2 gene was found in one isolate, Acinetobacter genomic species 13TU, for which the MIC of imipenem was 8 mg/L; the blaVIM-2 gene of this strain was located on 3 kb class 1 integron with aacA7 and aadA1 genes. CONCLUSIONS: Among the tested agents, imipenem and meropenem retained greatest activity against Acinetobacter spp. isolates collected from non-tertiary hospitals. This is the first report of VIM-2-producing Acinetobacter genomic species 13TU strains with class 1 integron containing blaVIM-2 gene.

Antimicrobial Resistance of Clinical Isolates of Acinetobacter spp. Collected from Non-Tertiary Hospitals and Detection of a Metallo-beta-Lactamase-Producing Strain

BACKGROUND: The aim of this study was to investigate the antimicrobial resistance of clinical isolates of Acinetobacter spp. collected from non-tertiary hospitals and to characterize the phenotype and the genotype of imipenem-non-susceptible isolates. MATERIALS AND METHODS: Clinical isolates of Acinetobacter spp. were identified using recA-restriction fragment length polymorphism (RFLP) analysis with Tsp5091. Susceptibility to antimicrobial agents was determined using disk diffusion test and agar dilution test according to the criteria of the National Committee for Clinical Laboratory Standards. PCR and sequence analyses were used to detect the blaIMP-1 and blaVIM-2 genes, and to determine the content and order of the resistance genes inserted in integron. RESULTS: Of 71 Acinetobacter spp. isolates collected from non-tertiary hospitals during 2002 and 2003, 60 isolates were A. baumannii, and 2, 4, and 5 isolates were Acinetobacter genomic species 3, 13TU, and A. lwoffii, respectively. The resistance rate of Acinetobacter spp. isolates to beta-lactams, aminoglycosides, and fluoroquinolones was high except for imipenem and meropenem. The presence of blaVIM-2 gene was found in one isolate, Acinetobacter genomic species 13TU, for which the MIC of imipenem was 8 mg/L; the blaVIM-2 gene of this strain was located on 3 kb class 1 integron with aacA7 and aadA1 genes. CONCLUSIONS: Among the tested agents, imipenem and meropenem retained greatest activity against Acinetobacter spp. isolates collected from non-tertiary hospitals. This is the first report of VIM-2-producing Acinetobacter genomic species 13TU strains with class 1 integron containing blaVIM-2 gene.

Molecular Relationship of vanA Glycopeptide Resistance Gene in Enterococci from Hospitalized Patients and Poultry in Korea / 감염

BACKGROUND: Vancomycin-resistant enterococci (VRE) with vanA gene have been reported as a significant nosocomial pathogen. The vanA gene cluster (Tn1546) located on mobile DNA elements is known to be transferable from VRE to other enterococci. The purpose of this study was to investigate the genetic relationship between the vanA VRE strains isolated from hospitalizd patients and poultry. METHODS: Total 145 isolates, including 58 E. faecium, 12 E. faecalis, 3 E. casseliflavus, and 4 E. gallinarum from humans and 68 E. faecium from poultry, were studied. Antimicrobial susceptibility tests were done by disk diffusion or agar dilution methods and molecular epidemiological analysis was performed by pulsed-field gel electrophoresis (PFGE). The internal and structural regions of vanA gene cluster were analyzed by PCR fragment length polymorphism, restriction enzyme, and sequencing of Orf2D region and vanXY intergenic region. The point mutation at Tn1546 nucleotide position 8234 (G->T) within the vanX gene was screened with DdeI restriction enzyme. RESULTS: The antibiotic resistance patterns of human isolates were different from those of poultry. PFGE patterns revealed high heterogeneity. Three PCR fragment length patterns in the vanA gene cluster were found : (I) PCR amplicon of the same size as prototype (E. faecium BM4147) in 17% of human isolates and 100% of poultry ones; (II) PCR amplicon for vanXY intergenic region due to an insertion between vanX and vanY genes in 2.5% of human isolates; (III) the insertions in vanX-vanY intergenic and Orf2 regions in 81% of human isolates. The T type in vanX gene of human and poultry isolates was not found. CONCLUSION: Despite the diverse PFGE patterns, 81% of human and all of poultry isolates belonged to vanA gene cluster type III and I, respectively. These results indicate that the horizontal spread of vanA gene is occurring among genetically diverse strains of VRE in Korea.

National Surveillance of Vibrio vulnificus Infections in 1998 / 감염

Surveillance for Vibrio vulnificus infections was performed by Korea National Institute of Health to investigate the epidemiological characteristics of recent occurence and to provide basic information for V. vulificus infection control. In 1998, a total of 44 cases of V. vulnificus infections were confirmed bacteriologically. The age groups of the patients ranged from thirties to seventies and 13 (29.5%) patients were in their fifties. Thirty-six (81.8%) patients had chronic liver diseases. Twenty-five (56.8%) had drinking habits. Eating uncooked seafood (fish, shrimp, and small octopus) produced in tideland was the main suspected source of infections and 32 (72.8%) cases were associated with raw seafood consumption. Two cases were associated with contaminated chopping board and 5 were infected through the wound. The incubation period ranged from less than 1 day to 7 days (median 2 days). The case fatality rate was 48%. In conclusion, V. vulnificus infection, a highly fatal disease, is not rare in Korea. Therefore, attention should be given to prevent V. vulnificus infections.

Plasmid Profile and B - Lactamase Type of Multidrug - Resistant Salmonella typhi Isolated from Korea, 1997

Eight strains of multidrug-resistant (MDR) Salmonella typhi were isolated from Kyonggi area during January-February,1997. They were resistant to ampiciUin, amoxicillin, carbeniciillin, tetracycline, chloramphenicol, trimethoprim/sulfamethoxazole, trimethoprim. Eight strains had one plasmid respectively which size was approximately M.W 220 kb and showed same restriction pattern by endonuclease HindIII. The plasmid was similar to the plasmid in size that was related to multidrug resistant S. typhi isolated from southeast Asia. It were transferred by conjugation to recipient E, coli K-12 in frequency of 2.43 x10-4 - 1.73 x 10-2 and transconjugant showed same drug-resistant pattem with donor cells. All of 8 strains produced B-lactamase that was assummed to TEM-1 type by isoelectric focusing and PCR.