Search

Background: Dysregulation of eicosanoids is associated with asthma and a composite of oxylipins, including exhaled leukotriene B4 (LTB4), characterizes childhood asthma. While fractional exhaled nitric oxide (FeNO) has been used as the standard for monitoring steroid responsiveness, the potential utility of eicosanoids in monitoring the therapeutic outcomes remains unclear. We aimed to examine the levels of major eicosanoids representing different metabolic pathways in exhaled breath condensates (EBCs) of children with asthma during exacerbation and after treatment. Methods: Levels of 6 exhaled eicosanoid species in asthmatic children and healthy subjects were evaluated using ELISA. Results: In addition to those previously reported, including LTB4, the levels of exhaled 15‐hydroxyeicosatetraenoic acid (15‐HETE), but not thromboxane B2 (TXB2), showed significant difference between asthmatics (N = 318) and healthy controls (N = 97), particularly the severe group showed the lowest levels of exhaled 15‐HETE. Receiver operating characteristic (ROC) curve analyses revealed similar distinguishing power for the levels of 15‐HETE, FEV1 (forced expiratory volume in the first second), and FeNO, while the 15‐HETE/LTB4 ratio was significantly lower in subjects with asthma as compared to that of healthy controls (p < 0.0001). Analysis of asthmatics (N = 75) during exacerbation and convalescence showed significant improvement in lung function (FEV1, p <.001), but not FeNO, concomitant with significantly increased levels of 15‐HETE (p <.001) and reduced levels of TXB2 (p <.05) at convalescence, particularly for those who at the top 30% level during exacerbation. Further, decreased LTB4 and lipoxin A4 (LXA4) at convalescence were noted only in those at the top 30 percentile during exacerbation. Conclusion: The exhaled 15‐HETE was found to discriminate childhood asthma while decreased levels of exhaled TXB2 and increased levels of 15‐HETE were prominent at convalescence. [ABSTRACT FROM AUTHOR]

Abstract Background Mannose receptor (MR) is a member of the C-type lectin receptor family involved in pathogen molecular-pattern recognition and thought to be critical in shaping host immune response. The aim of this study was to investigate potential associations of genetic variants in the MRC1 gene with sarcoidosis. Methods Nine single nucleotide polymorphisms (SNPs), encompassing the MRC1 gene, were genotyped in a total of 605 Japanese consisting of 181 sarcoidosis patients and 424 healthy controls. Results Suggestive evidence of association between rs691005 SNP and risk of sarcoidosis was observed independent of sex and age in a recessive model (P = 0.001). Conclusions These results suggest that MRC1 is an important candidate gene for sarcoidosis. This is the first study to imply that genetic variants in MRC1, a major member of the C-type lectin, contribute to the development of sarcoidosis.

Abstract Background Past work on asthmatic African American families revealed a strong linkage peak with modest evidence of association on chromosome 11q. Here, we perform tests of association for asthma and a panel of 609 SNPs in African American subjects using a sliding window approach. While efficient in screening a region of dense genotyping, this approach does create some problems: high numbers of tests, assimilating thousands of results, and questions about setting priorities on regions with association signals. Results We present a newly developed tool, Graphical Assessment of Sliding P-values or GrASP, which uses color display to indicate the width of the sliding windows, significance of individual tests, density of SNP coverage and location of known genes that simplifies some of these issues, and use it to identify regions of interest in these data. Conclusion We demonstrate that GrASP makes it easier to visualize, summarize and prioritize regions of interest from sliding window haplotype analysis, based jointly on the p-value from all the tests from these windows and the building of haplotypes of significance in the region. Using this approach, five regions yielded strong evidence for linkage and association with asthma, including the prior peak linkage region.

Abstract Background Catecholamines, such as epinephrine, are elaborated in stress responses, and mediate vasoconstriction to cause elevation in systemic vascular resistance and blood pressure. Our previous study has shown that IL-1 can induce mast cells to produce proinflammatory cytokines which are involved in atherogenesis. The aim of this study was to determine the effects of epinephrine on IL-1-induced proatherogenic cytokine production from mast cells. Results Two ml of HMC-1 (0.75 × 106 cells/ml) were cultured with epinephrine (1 × 10-5 M) in the presence or absence of IL-1β (10 ng/ml) for 24 hrs. HMC-1 cultured alone produced none to trace amounts of IL-6, IL-8, and IL-13. IL-1β significantly induced production of these cytokines in HMC-1, while epinephrine alone did not. However, IL-6, IL-8, and IL-13 production induced by IL-1β were significantly enhanced by addition of epinephrine. The enhancing effect appears to involve NF-κB and p38 MAPK pathways. Flow cytometry showed the presence of β1 and β2 adrenoreceptors on resting mast cells. The enhancing effect of proatherogenic cytokine production by epinephrine was down regulated by the β1 and β2 adrenoceptor antagonist, propranolol, but not by the β1 adrenoceptor antagonist, atenolol, suggesting the effect involved β2 adrenoceptors. The enhancing effect of epinephrine on proatherogenic cytokine production was also down regulated by the immunosuppressive drug, dexamethasone. Conclusions These results not only confirm that an acute phase cytokine, IL-1β, regulates mast cell function, but also show that epinephrine up regulates the IL-1β induction of proatherogenic cytokines in mast cells. These data provide a novel role for epinephrine, a stress hormone, in inflammation and atherogenesis.

Epidemiological studies have suggested the effects of ambient fine particles (PM2.5) on asthma, but the effects of specific components of PM2.5 on asthma remain to be explored. Here, we studied the effect of PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) on asthma acute exacerbation. The data on daily counts of emergency room visits (ERVs) were obtained from Wan Fang Medical Center, Taipei, Taiwan, from 2012 to 2015. The daily concentrations of PM2.5 and pollutant gases were obtained from a local air quality monitoring station. The levels of PM2.5-bound PAH were estimated by an established grid-scale model. Relative risks for ERVs as the increase in the level of ambient pollutants were calculated by using a generalized additive model of Poisson regression. In the present study, we observed statistically significant positive associations between PM2.5 and asthma ERVs for all age groups. PM2.5-bound PAH was also associated with asthma ERVs for all age groups. In the adult subgroup analysis, there was a significant association between PM2.5-bound PAH and asthma ERVs at lags 1 and 2 (RR 1.289, 95% CI 1.050–1.582 and RR 1.242, 95% CI 1.039–1.485). The impacts of air pollution on the risk of pediatric asthma ERV were found to be significant for PM2.5 at lag day 0 (RR 1.310, 95% CI 1.069–1.606). Moreover, pediatric asthma ERVs were significantly associated with the levels of PM2.5-bound PAH at lag 1 and 2 days (RR 1.576, 95% CI 1.371–1.810 and RR 1.426, 95% CI 1.265–1.607). The study provides evidence that PM2.5-bound PAHs were associated with an increased risk of asthma attacks. Our data further suggested that traffic exhaust is a primary source of PM2.5-bound PAHs. [ABSTRACT FROM AUTHOR]