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- Exposure to psychosocial job strain during pregnancy and odds of asthma and atopic dermatitis among 7-year old children - a prospective cohort study. [JOURNAL ARTICLE]
- Scand J Work Environ Health 2014 Aug 27.
Few epidemiological studies have studied maternal stress exposure during pregnancy and odds of asthma and atopic dermatitis (AD) among offspring, and none have extended the focus to psychosocial job strain. The aim of this study was to assess the association between maternal job strain during pregnancy and asthma as well as AD among 7-year-old children.The study is based on the Danish National Birth Cohort and includes prospective data from 32 104 pregnancies. Job strain was assessed early in pregnancy by use of two questions on demands and control. We categorized participants into four job strain categories: low strain (low demands, high control), active (high demands, high control), passive (low demands, low control), and high strain (high demands, low control). Information on asthma and AD until age seven was collected using maternal self-report. Multinomial logistic regression models were used to estimate odds ratios (OR) with 95% confidence intervals (95% CI) adjusted for several covariates.Maternal exposure to self-reported high strain during pregnancy was associated with 15% higher odds of atopic dermatitis among 7-year-old children (OR adj1.15, 95% CI 1.02-1.31). Furthermore, an association between the active jobs and asthma among 7-year-old children was found (OR adj1.13, 95% CI 1.03-1.24).Maternal exposure to high strain and active jobs during pregnancy was associated with asthma and atopic dermatitis among 7-year-old children.
- RSV - still more questions than answers. [JOURNAL ARTICLE]
- Pediatr Infect Dis J 2014 Aug 26.
- Lipoxin Generation is Related to Soluble Epoxide Hydrolase Activity in Severe Asthma. [JOURNAL ARTICLE]
- Am J Respir Crit Care Med 2014 Aug 27.
Rationale: Severe asthma is characterized by airway inflammatory responses associated with aberrant metabolism of arachidonic acid. Lipoxins (LX) are arachidonate-derived pro-resolving mediators that are decreased in severe asthma, yet mechanisms for defective LX biosynthesis and a means to increase LXs in severe asthma remain to be established. Objective: To determine if oxidative stress and soluble epoxide hydrolase (sEH) activity are linked to decreased LX biosynthesis in severe asthma. Methods: Aliquots of blood, sputum and bronchoalveolar lavage fluid (BALF) were obtained from asthma subjects for mediator determination. Select samples were exposed to t-butyl-hydroperoxide or sEH inhibitor (sEHI) prior to activation. Peripheral blood leukocyte-platelet aggregates were monitored by flow cytometry, and bronchial contraction was determined with cytokine-treated human lung sections. Measurements and Main Results: 8-isoprostane levels in sputum supernatants were inversely related to LXA4 in severe asthma (r=-0.55, p=0.03) and t-butyl-hydroperoxide decreased LXA4 and 15-epi-LXA4 biosynthesis by peripheral blood leukocytes. LXA4 and 15-epi-LXA4 levels were inversely related to sEH activity in sputum supernatants and sEHIs significantly increased 14,15-EET and 15-epi-LXA4 generation by severe asthma whole blood and BALF cells. The abundance of peripheral blood leukocyte-platelet aggregates was related to asthma severity. In a concentration-dependent manner, LXs significantly inhibited platelet-activating factor induced increases in leukocyte-platelet aggregates (70.8% inhibition (LXA4 100nM), 78.3% inhibition (15-epi-LXA4 100 nM)) and 15-epi-LXA4 markedly inhibited TNF-alpha-induced increases in bronchial contraction. Conclusions: Lipoxin levels were decreased by oxidative stress and sEH activity. Inhibitors of sEH increased LXs that mediated anti-phlogistic actions, suggesting a new therapeutic approach for severe asthma. Clinical trial registration available at www.clinicaltrials.gov, ID NCT00595114.
- IL-17 in Severe Asthma: Where Do We Stand? [JOURNAL ARTICLE]
- Am J Respir Crit Care Med 2014 Aug 27.
Asthma is a major chronic disease ranging from mild to severe refractory disease and is classified into various clinical phenotypes. Severe asthma is difficult to treat and frequently requires high doses of systemic steroids. In some cases, severe asthma even responds poorly to steroids. Several studies have suggested a central role of IL-17 (also called IL-17A) in severe asthma. Indeed, high levels of IL-17 are found in induced sputum and bronchial biopsies obtained from severe asthmatics. The recent identification of a steroid-insensitive pathogenic TH17 pathway is therefore of major interest. In addition, IL-17A has been described in multiple aspects of asthma pathogenesis, including structural alterations of epithelial cells and smooth muscle contraction. In this perspective article, we frame the topic of IL-17A effects in severe asthma by reviewing updated information from human studies. We summarize and discuss the implications of IL-17 in the induction of neutrophilic airway inflammation, steroid insensitivity, the epithelial cell profile, and airway remodeling.
- Results from a community-based trial testing a community health worker asthma intervention in Puerto Rican youth in Chicago. [JOURNAL ARTICLE]
- J Asthma 2014 Aug 27.:1-12.
Abstract Objective: Puerto Rican children suffer disproportionately from asthma. Project CURA tested the efficacy of a community health worker (CHW) intervention to improve use of inhaled corticosteroids (ICS) and reduce home asthma triggers in Puerto Rican youth in Chicago. Methods: This study employed a behavioral randomized controlled trial design with a community-based participatory research approach. Medications and technique were visually assessed; adherence was determined using dose counters. Home triggers were assessed via self-report, visual inspection and salivary cotinine. All participants received education on core asthma topics and self-management skills. Participants in the CHW arm were offered home education by the CHW in four visits over four months. The attention control arm received four newsletters covering the same topics. Results: While most of the participants had uncontrolled persistent asthma, < 50% had ICS at baseline. In the CHW arms, 67% of participants received the full four-visit intervention. In the Elementary school cohort (n = 51), the CHW arm had lower odds of having an ICS (OR = 0.2; p = 0.02) at 12-months; no differences were seen in other outcomes between arms at any time point. The only significant treatment arm difference in the high school cohort (n = 50) was in inhaler technique where the CHW arm performed 18.0% more steps correct at five months (p < 0.01) and 14.2% more steps correct at 12 months (p < 0.01). Conclusions: While this CHW intervention did not increase the number of participants with ICS or reduce home asthma triggers, important lessons were learned including challenges to CHW intervention fidelity and the need for CHWs to partner with clinical providers.
- Is elective cesarean section associated with a higher risk of asthma? A meta-analysis. [JOURNAL ARTICLE]
- J Asthma 2014 Aug 27.:1-10.
Abstract Background: Recent meta-analyses indicate that children delivered by cesarean section have increased risk for asthma. However, the studies included in these previous meta-analyses showed significant heterogeneity. Furthermore, no previous meta-analysis has distinguished the association of elective and emergency CS, spontaneous and instrumental vaginal deliveries (VD) with the odds of asthma. Objective: To examine the association between specific mode of delivery and the prevalence of asthma. Methods: PUBMED, Google Scholar, EMBASE, and MEDLINE were searched to identify relevant studies. Odds ratio (OR) and 95% confidence interval (CI) were calculated from the prevalence of asthma in children born by elective CS, emergent CS, instrumental VD and spontaneous VD. Meta-analysis was then used to derive a combined OR. Heterogeneity between studies was also tested in the findings. Results: A total of 26 studies were identified. The overall meta-analysis revealed an increase in the risk of asthma in children delivered by CS (OR = 1.16, 95% CI 1.14, 1.29), and no evidence of heterogeneity was found (I(2) = 24.6%). Elective and emergency CS moderately increased the risk of asthma (OR = 1.21, 95% CI 1.17, 1.25; I(2) = 39.9%; OR = 1.23, 95% CI 1.19-1.26). The risk of asthma was also higher in the children born by instrumental VD (OR = 1.07, 95% CI, 1.04-1.11) but with evidence of heterogeneity (I(2) = 54.9%). Conclusion: About 20% increase in the subsequent risk of asthma was both found in children delivered by elective and emergency CS. The increasing rates of CS worldwide might partly explain the concomitant rise in asthma during the same time period.
- Respiratory outcomes study (RESPOS) for preterm infants at primary school age. [JOURNAL ARTICLE]
- J Asthma 2014 Aug 27.:1-7.
Abstract Objective: Pulmonary function abnormalities and hospital re-admissions in survivors of neonatal lung disease remain highly prevalent. The respiratory outcomes study (RESPOS) aimed to investigate the respiratory and associated atopy outcomes in preterm infants <30 weeks gestational age (GA) and/or birth-weight (BWt) <1000 g at primary school age, and to compare these outcomes between infants with and without chronic lung disease (CLD). Methods: In the RESPOS 92 parents of preterm infants admitted to the Neonatal unit in Canberra Hospital between 1/1/2001 and 31/12/2003 were sent a questionnaire regarding their respiratory, atopy management and follow-up. Results: Fifty-three parents responded, including 28 preterm infants who had CLD and 25 who had no CLD. The gestational age was significantly lower in the CLD group compared to the non-CLD group [26.9 (26.3-27.5) CLD and 28.6 (28.3-29.0) non-CLD] [weeks [95% confidence interval (CI)]], as was the birth weight [973 (877.4-1068.8) CLD versus 1221 (1135.0-1307.0) non-CLD] [g (CI)]. CLD infants compared to non-CLD infants were significantly more likely to have been: given surfactant, ventilated and on oxygen at 28 days and 36 weeks. These neonates were also more likely to have: been discharged from the neonatal unit on oxygen, exhibit a history of PDA or sepsis and to have a current paediatrician. However, despite these differences, there was no significant difference in the proportion of asthma or atopic disease between the two groups. Conclusions: The RESPOS could not demonstrate respiratory and/or atopy differences between the CLD and the non-CLD groups at primary school age.
- DNA methylation dynamics during ex vivo differentiation and maturation of human dendritic cells. [Journal Article]
- Epigenetics Chromatin 2014.:21.
Dendritic cells (DCs) are important mediators of innate and adaptive immune responses, but the gene networks governing their lineage differentiation and maturation are poorly understood. To gain insight into the mechanisms that promote human DC differentiation and contribute to the acquisition of their functional phenotypes, we performed genome-wide base-resolution mapping of 5-methylcytosine in purified monocytes and in monocyte-derived immature and mature DCs.DC development and maturation were associated with a great loss of DNA methylation across many regions, most of which occurs at predicted enhancers and binding sites for known transcription factors affiliated with DC lineage specification and response to immune stimuli. In addition, we discovered novel genes that may contribute to DC differentiation and maturation. Interestingly, many genes close to demethylated CG sites were upregulated in expression. We observed dynamic changes in the expression of TET2, DNMT1, DNMT3A and DNMT3B coupled with temporal locus-specific demethylation, providing possible mechanisms accounting for the dramatic loss in DNA methylation.Our study is the first to map DNA methylation changes during human DC differentiation and maturation in purified cell populations and will greatly enhance the understanding of DC development and maturation and aid in the development of more efficacious DC-based therapeutic strategies.
- An Innovative Childhood Asthma Score Predicts the Need for Bronchodilator Nebulization in Children With Acute Asthma Independent of Auscultative Findings. [JOURNAL ARTICLE]
- Respir Care 2014 Aug 26.
We sought to compare the accuracy of a newly developed childhood asthma score (CAS) with routine clinical assessment of respiratory status in children with acute asthma in predicting requirements for bronchodilator nebulization.In this prospective observational study in children 2-18 y old with acute asthma, we evaluated the association between the CAS and routine clinical assessment as well as inter-rater agreement.The need for bronchodilator nebulization was assessed during 134 episodes of acute asthma in 47 children. Overall, bronchodilators were administered after routine clinical assessment in 74 episodes (55.2%). The median CAS was 2.5 (interquartile range of 2.0-3.0) for subjects who did not receive nebuli-zation and 6.0 (interquartile range of 4.0-7.0) for subjects who did receive nebulization (P < .001). A CAS cutoff score of 4 yielded a sensitivity of 0.91 (95% CI 0.84-0.97) and a specificity of 0.77 (95% CI 0.66-0.87), with a positive predictive value of 0.83 (95% CI 0.75-0.91) and a negative predictive value of 0.87 (95% CI 0.78-0.96). In 79 episodes, the CAS was assessed by 2 independent raters. With a weighted kappa of 0.77, a good inter-rater agreement was obtained.Using a cutoff value of 4, the newly developed CAS accurately predicts the requirement for bronchodilator nebulization in children with acute asthma without use of auscultative findings.
- Melatonin reduces airway inflammation in ovalbumin-induced asthma. [JOURNAL ARTICLE]
- Immunobiology 2014 Aug 10.
Asthma is a common chronic inflammatory airway disease that is recognized as a major public health problem. In this study, we evaluated the effects of melatonin on allergic asthma using a murine model of ovalbumin (OVA)-induced allergic asthma and BEAS-2B cells. To induce allergic asthma, the mice were sensitized and airway-challenged with OVA. Melatonin was administered by intraperitoneal injection once per day at doses of 10 and 15mg/kg from days 21 to 23 after the initial OVA sensitization. We investigated the effects of melatonin on proinflammatory cytokines and matrix metalloproteinase-9 (MMP-9) activity and expression in tumor necrosis factor (TNF)-α-stimulated BEAS-2B cells. The administration of melatonin significantly decreased the number of inflammatory cells, airway hyperresponsiveness, and immunoglobulin (Ig) E with reductions in interleukin (IL)-4, IL-5, and IL-13. Melatonin attenuated the airway inflammation and the mucus production in lung tissue and significantly suppressed elevated MMP-9 expression and activity induced by an OVA challenge. In TNF-α-stimulated BEAS-2B cells, treatment with melatonin significantly reduced the levels of proinflammatory cytokines and lowered the expression and activity of MMP-9. These results indicate that melatonin effectively suppressed allergic asthma induced by an OVA challenge. The results suggest a potential role for melatonin in treating asthma.