Interaction between antibiotic use and MS4A2 gene polymorphism on childhood eczema: a prospective birth cohort study.

BACKGROUND: Eczema is usually the first allergic manifestation to appear in life attributed to gene-environment interactions. IL13, IL4, MS4A2 and ILR4A are four key inflammatory genes associated with atopy. This study aimed to explore gene-environment interactions on eczema in early life among the above four genes and environmental factors in Chinese Han children. METHODS: Five hundred ninety-seven children from a birth cohort who completed two-year follow-up were enrolled and their cord blood was collected. Subjects were genotyped for six polymorphisms in the aforementioned four genes. The children were followed at 6, 12 and 24 months, with epidemiologic information and medical history of eczema collected by questionnaire and eczema assessed by dermatologists. RESULTS: Among the 597 children, 168 were diagnosed with eczema and the others were not after 2 years of follow-up. MS4A2 rs569108 GG genotype (P = 1.68E-02, odds ratio (OR) = 4.66) and antibiotic use (P = 3.75E-4, OR = 2.02) were found independently associated with development of childhood eczema. Children with both antibiotic use and MS4A2 rs569108 GG genotype were more likely to develop eczema than those with only antibiotic use or GG homozygote (OR = 6.24 VS. 2.04 or 4.68). CONCLUSIONS: MS4A2 rs569108 polymorphism and antibiotic use were solely associated with eczema, and they interacted with each other to increase the risk of developing the disease in Chinese Han toddlers. Long-term follow-up along with functional and replication studies are still needed.

Four-locus gene interaction between IL13, IL4, FCER1B, and ADRB2 for asthma in Chinese Han children.

RATIONALE: IL13, IL4, IL4RA, FCER1B, and ADRB2 are important inflammatory genes associated with immunoglobulin E levels. This study attempts to determine whether there are gene-gene interactions in the five genes among asthmatic children of Chinese Han nationality. METHODS: Nine single-nucleotide polymorphisms (SNPs) in the five genes were genotyped in 1,000 asthmatic children and 1,000 healthy controls using TaqMan real-time quantitative polymerase chain reaction. Multifactor-dimensionality reduction method was applied for the analysis. RESULTS: A four-way gene-gene interaction model consisting of IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108 was chosen as the optimal one for determining asthma susceptibility (testing balanced accuracy = 0.6089, cross-validation consistency = 10/10, P = 6.98E-05). Each of the four SNPs was identified to have an independent association with childhood asthma (G allele of rs20541, odds ratio (OR) = 1.24, P = 1.23E-03; T allele of rs2243250, OR = 1.25, P = 3.81E-03; A allele of rs1042713, OR = 1.29, P = 6.75E-05; G allele of rs569108, OR = 1.27, P = 3.86E-03). Individuals homozygous for the risk alleles at all the four loci (rs20541 GG, rs2243250 TT, rs1042713 AA, and rs569108 GG) had a significantly higher risk of asthma compared with those without any risk homozygotes (OR = 13.55, P = 4.28E-03), and also greater than those with less than four risk homozygotes (OR = 10.09, P = 6.51E-03). CONCLUSIONS: Our results suggest that IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108, four SNPs with significant sole effect on asthma, interact to confer a higher risk for the disease in Chinese Han children.

Identification of IL13 C1923T as a Single Nucleotide Polymorphism for Asthma in Children from Mauritius.

Background: Research increasingly suggests that asthma is a familial and hereditary disorder and that genetic and environmental factors play a key role in its pathogenesis. Objective: The aim of this study was to investigate the associations between 10 single nucleotide polymorphism (SNP) loci in the development of asthma in children from the Mauritian population. Methods: The study population consisted of 193 children with asthma and 189 healthy controls from the Mauritian population. Asthma was diagnosed in accordance with the American Thoracic Society criteria. TaqMan real-time quantitative polymerase chain reaction was used to detect the genotypes of the SNP loci. Results: No statistically significant differences (p>0.05) were found between the experimental and control group in genotype distribution among nine of the loci (MS4A2 E237G, MS4A2 C-109T, ADRB2 R16G, IL4RA Q551R, IL4RA I75V, IL4 C-590T, IL13 A2044G, IL13 C-1112T, and CHI3L1 C-131G). However, the frequency of IL13 C1923T TT in the asthma group was significantly higher than in the control group (odds ratio=2.119, p=0.033) suggesting that carriers of IL13 C1923T TT in the Mauritian population may have a more significant risk of developing asthma. Conclusion: The nine loci have little contribution to the development of childhood asthma in the Mauritian population. IL13 C1923T TT has been detected to be the susceptible genotype and may have a significant effect on the pathogenesis of childhood asthma in the Mauritian population.

[Correlation analysis between the PM2.5, PM10 which were taken in the hazy day and the number of outpatient about breathing sections, breathing sections of pediatrics in Shanghai].

In order to explore the correlation between the concentration of PM10, PM2.5 which were taken during the day of haze pollution and the average number of outpatient service, pediatrics. Based on the date with the number of pediatric outpatient and the concentration of PM2.5, PM10 which were taken form the haze days on 1 January 2009 - December 31 in 6 hospital in shanghai such as xinhuan hospital, we analyzed the data and executed the risk evaluation. The results showed that: in the haze day, when the average concentration of PM10 increase 50 microg/m3, the average number of the outpatient service and pediatric clinic increased 3% and 0.5%, when the average concentration of PM2.5 increase 34 microg/m3, the average number of the outpatient service and pediatric clinic increased 1.9% and 3.2%, Also, the pollution of PM10 and PM2.5 has a larger cumulative effects on the number of outpatient service. And the accumulation effect will be To maximize after 6 days behind the haze pollution. Thus, PM2.5, PM10 which were taken during the haze of pollution in shanghai, has certain influence on the average number of outpatient service, pediatric clinic.

[Pathological change of partial liquid ventilation in a rabbit meconium aspiration lung injury model].

OBJECTIVE: To observe the pathological change of partial liquid ventilation (PLV) through establishing the rabbit model of acute lung injury (ALI) induced by meconium aspiration. METHODS: Adult, healthy male or female New Zealand white rabbits were randomly allocated into six groups as follows: (1) control group, (2) conventional mechanical ventilation (CMV) group, (3) high-frequency oscillatory ventilation (HFOV) group, (4) CMV combined with PLV group, (5) HFOV combined with PLV group and (6) normal group. The animals were anesthetized with 1% pentobarbital and tracheotomy was performed and endotracheal tube was placed, 20% meconium fluid (3 ml/kg) was quickly injected into the lung through the endotracheal tube and arterial blood gas was analyzed 30 minutes later. ALI was indicated when P/F ratio (PaO2)/FiO(2)) was < or = 300 mm Hg (1 mm Hg = 0.133 kPa) and Cdyn Dynamic Compliance declined by more than 30% of the baseline. The animals were then randomly allocated into one of the 6 groups. In PLV groups (including CMV + PLV and HFOV + PLV) warmed (37 degrees C) and oxygenated perfluorocarbon was slowly instilled into the lungs of the rabbits through the endotracheal tube at a low-dose 3 ml/kg, then set 15-min positive pressure by sacculus proprius to guarantee perfluorocarbon to steadily diffuse in to the lungs. Six hours after ventilation the animals were sacrificed by using overdose of room air instillation via vein. The lungs were taken and fixed in 4% paraformaldehyde (PFA) and were stained with hematoxylin-eosin (HE). Pathological evaluations included inflammatory manifestation, edema and hemorrhage in both alveolar and interstitial area, damages of small airway (alveolar tube and alveolar bursa) and hyaline membrane formation. One way analysis of variance, Student Newman-Keuls (SNK) method and Kruskal-Wallis (K-W) test were used for comparisons. RESULTS: With the exception of normal group 30 minutes after meconium injections blood gas analysis in different groups showed significant changes and PaO(2)/FiO(2) (< 300 mm Hg), Cdyn declined by more than 60% compared with baseline (P < 0.05). The pathological analysis showed that alveolar and interstitial inflammation, edema, alveolar and interstitial hemorrhage, and small airway damage existed in each group. The hyaline membrane formation was found in one of CMV + PLV group rabbits. The perfluorocarbon-treated animals (CMV + PLV and HFOV + PLV) showed significantly less injury in dependent lung and less damage of small airway (CMV + PLV or HFOV + PLV vs. CMV = 1.1 +/- 0.4 or 0.9 +/- 0.3 vs 2.6 +/- 0.5) compared with the animals of CMV group (P < 0.01). HFOV group (2.1 +/- 0.3) also had less alveolar and interstitial inflammation compared with CMV group (3.0 +/- 0) (P < 0.05), and there was less evidence of alveolar and interstitial edema in the animals treated with HFOV + PLV (1.0 +/- 0.7) compared with CMV (2.0 +/- 0.8) (P < 0.01). Treatment with perfluorocarbon did not result in significant difference in alveolar and interstitial hemorrhage. Compared with CMV and HFOV groups, the groups treated with PLV showed lower mortality of animals (21.4% and 14.3%). CONCLUSIONS: PLV can alleviate the histological damage of acute lung injury induced by meconium aspiration and increased survival chance and therefore PLV would be a useful treatment for MAS. The effectiveness and safety of application of PLV should be evaluated in clinical studies.

[Non-myeloperoxidase-mediated system activity of neutrophil in newborn infants].

OBJECTIVE: To evaluate the variety of non-myeloperoxidase-mediated system activity of neutrophils in newborns during bacterial infection and the effect of cord plasma on the activation of non-myeloperoxidase-mediated system. METHODS: An infection model with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) and a non-infection model with phorbol-12-myristate-13-acetate (PMA) were established to investigate the activation of non-myeloperoxidase-mediated system in neutrophils. According to the intensity of fluorescence, the activation of non-myeloperoxidase-mediated system of neutrophils was detected by flow cytometry (FCM). The blood cells and plasma were separated from cord blood and adult blood and cross-mixed in order to investigate the opsonic activity. RESULTS: In the non-infection model, the activation of non-myeloperoxidase-mediated system with PMA stimulation in cord blood was lower compared with that in adult blood, the statistical difference was significant (t = 3.378, P < 0.01). In the infection model, the activations of non-myeloperoxidase-mediated system in cord blood were also lower compared with those in adult blood, while the statistical difference could only be found in the model with E. coli stimulation (t = 12.150, P < 0.001). Furthermore the experiments demonstrated that cord plasma could deeply depress the non-myeloperoxidase-mediated system activity with E. coli stimulation. On the contrary, adult plasma could successfully recruit the potential of non-myeloperoxidase-mediated system activity of neutrophils in newborns. CONCLUSION: The function of neonatal neutrophils might not developed very well. As a stimulant, E. coli failed to induce the non-myeloperoxidase-mediated system activity in neonates, which might be related to the lower level of immunoglobulins in cord blood. This result indicated that immunoglobulins played a more important modulating role in bacterial killing during gram-negative bacterial infections.