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- Correction: Association between RANTES Gene Polymorphisms and Asthma: A Meta-Analysis. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e111818.
[This corrects the article DOI: 10.1371/journal.pone.0090460.].
- Identification of hot spots of DNA methylation in the adult male adrenal in response to in utero exposure to the ubiquitous endocrine disruptor plasticizer di-(2-ethylhexyl) phthalate. [JOURNAL ARTICLE]
- Endocrinology 2014 Oct 20.:en20141436.
Exposure to environmental toxicants during fetal development alters gene expression and promotes disease later in life. Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer widely used for the manufacturing of consumer products. Exposure to DEHP has been associated with obesity, asthma, and low testosterone levels. In utero exposure of pregnant dams to DEHP from gestational day 14 until birth resulted in reduced levels of serum testosterone and aldosterone in the adult male offspring. Since DEHP is rapidly cleared from the body, the effects observed in the adult are likely epigenetic in origin. Under the same experimental conditions, we used reduced-representation bisulfite sequencing to assess changes in DNA methylation. We identified hot spots of DNA methylation changes primarily within CpG islands followed by shelf regions of the genome known to control regional gene expression. We also identified epigenomic areas responsive to exposure to environmental levels of DEHP and found the chromosomal region that houses genes controlling immune responsiveness to be a primary target of DEHP. These data suggest that DEHP phthalate exposure early in life induces epigenetic changes that may be linked to altered gene expression and function in the adult.
- Parents in Fragile Families: The Influence of Parental Engagement on Emergency Care Use in Children With Asthma. [JOURNAL ARTICLE]
- Fam Syst Health 2014 Oct 20.
Current research focused on stress responsive illnesses such as asthma has identified a crucial role for families in the progression and maintenance of stress responsive illnesses. What is currently not clear is the differential effect of maternal versus paternal engagement in the management of pediatric asthma. This study explores whether or not mother, father, or the combined engagement has an effect on the management of pediatric asthma. A subsample of the Fragile Families Child and Wellbeing Study (FFCW Study) was used to examine the role of parental engagement (n = 475; 41.9% female, 58.1% male). Path analysis and actor partner interdependence modeling processes were used to examine the differential effect of mother and father engagement. A final nested model with only direct effects from the father's level of engagement proved to be the best fitting model, χ2(9) = 16.738, p = .05298, CFI = 0.995, GFI = 0.989, RMSEA = 0.043. Within this model father engagement had a moderating effect for child's emergency room (ER) use (β = -.124, p < .05). The mother's effect was best modeled as an indirect effect as this increased the father's level of engagement, but did not have a direct effect on the outcome of ER usage. This study is consistent with other studies that found that the predictability of a father's role and routine had positive health outcomes for the asthmatic child. Implications for future research and practice are identified and discussed. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
- Characteristics of eosinophilic and non-eosinophilic asthma during treatment with inhaled corticosteroids. [JOURNAL ARTICLE]
- J Asthma 2014 Oct 20.:1-23.
Abstract Objective: Eosinophilic inflammation in the respiratory tract is a hallmark of bronchial asthma. In naïve cases, the inflammatory profile is associated with disease severity and reactivity to inhaled corticosteroids (ICS). Sustained airway eosinophilia has been reported during ICS treatment. However, how this contributes to asthma control is unclear, nor are the immunologic characteristics of these cases known. This study was performed to determine the answer these questions. Methods: To compare phenotypes of eosinophilic and non-eosinophilic asthma (EA and NEA, respectively) under ICS treatment, clinical data were obtained from asthmatic subjects (n = 22) and healthy controls (n = 10), and the leukocyte compositions of induced sputum and peripheral blood were determined. T lymphocyte profiles in systemic blood were assessed by flow cytometry. Results: A higher frequency of emergency room visits was observed in the NEA group, which had a higher neutrophil count relative to the total inflammatory cell population in induced sputum than the EA group (59.5% vs. 36.6%; P < 0.01). The fraction of helper T (Th)17 lymphocytes as well as the ratio of Th17 to regulatory T cells (Treg) in the peripheral blood was higher in the NEA than in the EA group (0.24 vs. 0.13; P < 0.05). Conclusions: Th17 were more prevalent than Treg cells in the peripheral blood of NEA patients under ICS treatment, corresponding to neutrophil-dominant airway inflammation and a severe asthmatic phenotype. Thus, an imbalance in Th17/Treg may be associated with the pathogenesis of NEA in patients undergoing ICS treatment.
- Effects of Regular Treatment with Combination of Salmeterol / Fluticasone Propionate and Salmeterol Alone in Cough Variant Asthma. [JOURNAL ARTICLE]
- J Asthma 2014 Oct 20.:1-21.
Abstract Objective: Cough variant asthma (CVA) is an important cause of chronic cough, and pathophysiological features of the disease appear to be similar to typical asthma. Because CVA is recognized as a precursor of asthma, early intervention with long-term anti-inflammatory agents may be recommended. However, the role of combination therapy with inhaled corticosteroid and b2-agonist in the treatment of CVA has not been elucidated. To evaluate the effectiveness of the combination therapy, we investigated the clinical impact of regular treatment with salmeterol/fliticasone propionate combination (SFC) and inhaled salmeterol (SAL) alone in patients with CVA. Methods: The study was a randomized, controlled, parallel-group multi-center trial. Forty-three CVA patients were assigned to SFC (50/100mg once daily) or SAL (50mg twice daily) for 12 weeks. Then, these medications were stopped for the next 24 weeks. Main outcome measures were cough symptoms, pulmonary function and airway inflammation. Results: Treatment with each of SFC and SAL significantly decreased cough scores and increased FEV1 and PEF, where the efficacy was more pronounced with SFC than SAL. SFC also decreased sputum eosinophil counts and eosinophil cationic protein contents, whereas SAL had no effect. After discontinuation of the treatment, cough scores increased, pulmonary function and eosinophilic airway inflammation were aggravated and returned to the baseline levels. Conclusions: Maintenance therapy with SFC provides further improvements in cough symptoms, pulmonary function and airway inflammation, and discontinuation of the therapy causes worsening of the disease, indicating that stopping or interrupting anti-inflammatory therapy may not be advisable in patients with CVA.
- The FACT Score in Predicting Pneumococcal Antibody Levels in Asthmatics. [JOURNAL ARTICLE]
- J Asthma 2014 Oct 20.:1-23.
Abstract Background: There is no measure currently available to identify asthmatics with potential immune incompetence. Objective: We propose use of a novel scoring system called the FACT score, which is formulated based on 4 parameters: 1) Family history of asthma, 2) Atopic conditions, 3) Bacterial colonization, and 4) Th1 vs. Th2 immune profile. Methods: This was a cross-sectional study involving 16 asthmatics and 14 non-asthmatics. The first two parameters of the FACT score were obtained via a chart review and interview. For the third parameter, nasopharyngeal swab samples were cultured. The ratio of interleukin-5 to interferon--gamma for each patient was measured by peripheral blood mononuclear cells cultured with house dust mite. Antibodies to 23 pneumococcal antigens were used for humoral immunity. Results: The FACT scores for asthmatics (mean±SD: 5.2±1.87) were higher than those for non-asthmatics (mean±SD: 3.3±1.5)(p=0.008). Of the 16 asthmatics, 7 (44%) had 12 or more positive serotype-specific polysaccharide antibodies whereas 12 of 14 (86%) of non-asthmatics subjects had 12 or more positive serotype-specific polysaccharide antibodies (p = 0.014). Overall, the FACT score was inversely correlated with the number of positive serotype-specific antibody levels (rho (ρ) = -0.38, p = 0.04). The proportions of subjects with 12 or more positive serotype-specific antibodies among non-asthmatics and asthmatics below and above the median of the FACT scores were 86%, 50% and 38%, respectively (p = 0.052). Conclusions: The FACT score may help us identify a subset of asthmatics with immune incompetence. Study findings need to be replicated in a larger study.
- Differential Gene Expression Profiles of Peripheral Blood Mononuclear Cells in Childhood Asthma. [JOURNAL ARTICLE]
- J Asthma 2014 Oct 20.:1-29.
Abstract Objective: Asthma is a common childhood disease with strong genetic components. This study compared whole-genome expression differences between asthmatic young children and healthy controls to identify gene signatures of childhood asthma. Methods: Total RNA extracted from peripheral blood mononuclear cells (PBMC) was subjected to microarray analysis. QRT-PCR was performed to verify the microarray results. Classification and functional characterization of differential genes were illustrated by hierarchical clustering and gene ontology analysis. Multiple logistic regression (MLR) analysis, receiver operating characteristic (ROC) curve analysis and discriminate power were used to scan asthma-specific diagnostic markers. Results: For fold-change>2 and p<0.05, there were 758 named differential genes. The results of QRT-PCR confirmed successfully the array data. Hierarchical clustering divided 29 highly possible genes into 7 categories and the genes in the same cluster were likely to possess similar expression patterns or functions. Gene ontology analysis presented that differential genes primarily enriched in immune response, response to stress or stimulus and regulation of apoptosis in biological process. MLR and ROC curve analysis revealed the combination of ADAM33, Smad7 and LIGHT possessed excellent discriminating power. Conclusions: The combination of ADAM33, Smad7 and LIGHT would be a reliable and useful childhood asthma model for prediction and diagnosis.
- Oral hygiene and dental status as factors related to asthma in high school and college students. [JOURNAL ARTICLE]
- J Asthma 2014 Oct 20.:1-21.
Abstract Objective: Considering that oral microbiota might modulate immune responses, we explored if customary oral care procedures might influence immune-driven diseases such as asthma. Methods: This was a retrospective, cross-sectional analysis of responses to a self-completion medical questionnaire applied to subjects entering into college and high school programs during 2006-2011. Results: Responses from 329,780 students aged 14-24 years (97.6% of the original population) were analyzed. The prevalence of lifetime asthma was 4.01%. Subjects with asthma were slightly older, taller, and heavier than subjects without asthma, and these differences were equally present in males and females. Subjects currently having two or more decayed teeth had asthma less frequently than those with one or none decayed tooth, with an odds ratio (OR)=0.86 and 95% confidence interval (95% CI) 0.83-0.89. In contrast, asthma was reported more frequently among students having two or more missing or filled teeth [OR=1.1 (95% CI, 1.04-1.17) and OR=1.05 (95% CI, 1.01-1.09), respectively]. From 2008 on, subjects also responded questions about oral hygiene incorporated into the core questionnaire. In these subjects, the use of toothpaste, as well as the frequency and duration of toothbrushing were unrelated to asthma; regular use of mouthwash was associated with asthma in women [OR=1.16 (95% CI, 1.07-1.25)], but not in men [OR=1.04 (95% CI, 0.96-1.13)]. Results of multiple logistic regressions were in line with these findings. Conclusions: Our results suggested that oral hygiene and dental status could be novel factors influencing asthma development, and thus further studies to confirm and clarify this association are warranted.
- Microbial Communities in the Upper Respiratory Tract of Patients with Asthma and Chronic Obstructive Pulmonary Disease. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e109710.
Respiratory infections are well-known triggers of chronic respiratory diseases. Recently, culture-independent tools have indicated that lower airway microbiota may contribute to pathophysiologic processes associated with asthma and chronic obstructive pulmonary disease (COPD). However, the relationship between upper airway microbiota and chronic respiratory diseases remains unclear. This study was undertaken to define differences of microbiota in the oropharynx of asthma and COPD patients relative to those in healthy individuals. To account for the qualitative and quantitative diversity of the 16S rRNA gene in the oropharynx, the microbiomes of 18 asthma patients, 17 COPD patients, and 12 normal individuals were assessed using a high-throughput next-generation sequencing analysis. In the 259,572 total sequence reads, α and β diversity measurements and a generalized linear model revealed that the oropharynx microbiota are diverse, but no significant differences were observed between asthma and COPD patients. Pseudomonas spp. of Proteobacteria and Lactobacillus spp. of Firmicutes were highly abundant in asthma and COPD. By contrast, Streptococcus, Veillonella, Prevotella, and Neisseria of Bacteroidetes dominated in the healthy oropharynx. These findings are consistent with previous studies conducted in the lower airways and suggest that oropharyngeal airway microbiota are important for understanding the relationships between the various parts of the respiratory tract with regard to bacterial colonization and comprehensive assessment of asthma and COPD.
- Prostaglandin E2 Prevents Hyperosmolar-Induced Human Mast Cell Activation through Prostanoid Receptors EP2 and EP4. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e110870.
Mast cells play a critical role in allergic and inflammatory diseases, including exercise-induced bronchoconstriction (EIB) in asthma. The mechanism underlying EIB is probably related to increased airway fluid osmolarity that activates mast cells to the release inflammatory mediators. These mediators then act on bronchial smooth muscle to cause bronchoconstriction. In parallel, protective substances such as prostaglandin E2 (PGE2) are probably also released and could explain the refractory period observed in patients with EIB.This study aimed to evaluate the protective effect of PGE2 on osmotically activated mast cells, as a model of exercise-induced bronchoconstriction.We used LAD2, HMC-1, CD34-positive, and human lung mast cell lines. Cells underwent a mannitol challenge, and the effects of PGE2 and prostanoid receptor (EP) antagonists for EP1-4 were assayed on the activated mast cells. Beta-hexosaminidase release, protein phosphorylation, and calcium mobilization were assessed.Mannitol both induced mast cell degranulation and activated phosphatidyl inositide 3-kinase and mitogen-activated protein kinase (MAPK) pathways, thereby causing de novo eicosanoid and cytokine synthesis. The addition of PGE2 significantly reduced mannitol-induced degranulation through EP2 and EP4 receptors, as measured by beta-hexosaminidase release, and consequently calcium influx. Extracellular-signal-regulated kinase 1/2, c-Jun N-terminal kinase, and p38 phosphorylation were diminished when compared with mannitol activation alone.Our data show a protective role for the PGE2 receptors EP2 and EP4 following osmotic changes, through the reduction of human mast cell activity caused by calcium influx impairment and MAP kinase inhibition.