Project description:BackgroundMicroRNAs are small non-coding RNAs that regulate gene expression at the post-transcriptional level. While they have been implicated in various diseases, the profile changes in allergen inhalation challenge are not clarified in human. We aimed to evaluate changes in the microRNA profiles in the peripheral blood of asthmatic subjects undergoing allergen inhalation challenge.ResultsSeven mild asthmatic subjects participated in the allergen inhalation challenge. In addition, four healthy control subjects (HCs) were recruited. MicroRNA profiles in peripheral blood samples (pre-challenge and 2 hours post-challenge) were measured by the NanoString nCounter assay to determine changes in miRNA levels as these asthmatic subjects underwent an allergen inhalation challenge. One common miRNA, miR-192, was significantly expressed in both comparisons; HCs vs. pre-challenge and pre- vs. post-challenge, showing that miR-192 was significantly under-expressed in asthmatics compared to HCs and decreased in post-challenge at an FDR of 1%. Cell-specific statistical deconvolution attributed miR-192 expression in whole blood to PBMCs. MiR-192 was technically validated using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) showing that the level in asthmatics (pre-challenge) was significantly lower than HCs and that post-challenge was significantly lower than pre-challenge. The normalized relative miR-192 expression quantified using RT-qPCR specific to PBMCs was also validated. Ontology enrichment and canonical pathway analyses for target genes suggested several functions and pathways involved in immune response and cell cycle.ConclusionsThe miRNA profile in peripheral blood was altered after allergen inhalation challenge. Change in miR-192 levels may be implicated in asthma mechanisms. These results suggest that allergen inhalation challenge is a suitable method to characterize peripheral miRNA profiles and potentially elucidate the mechanism of human asthma.

Project description:Background: Allergen inhalation challenge in mild asthmatics induces airflow obstruction, airway hyperresponsiveness and inflammation, providing a model for hypothesis-generating experiments to understand regulation of these responses. We have sought to evaluate the peripheral whole blood transcriptome, post-challenge compared to pre-challenge, and to determine the effect of globin mRNA reduction methodology. Methods: Asthmatic subjects (20-60 years of age, with stable, mild allergic asthma, n=17) underwent allergen inhalation challenges. All subjects had an early asthmatic response of ≥ 20% fall in FEV1; most had a late phase response of ≥ 15% fall in FEV1. Blood was collected immediately prior to, and two hours after allergen challenge. Transcriptome analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST arrays, with and without globin mRNA reduction (PAX-GR and PAX-NGR, respectively) in 4 subjects. Replication studies for expression of nine genes contributing to the top canonical pathway, Nrf2-mediated oxidative stress response pathway, were performed with 5 independent subjects with microarray data, also with the same 4 subjects had microarray results and 8 other independent subjects with QPCR. Data were analyzed using paired t-test and Partek® Genomics Suite™. Results: The number of differentially expressed probe sets from PAX-NGR samples was twice that of PAX-GR samples. Paired analysis of each subjects' pre- and post-sample additionally demonstrated twice the power to detect differentially expressed probe sets. The Nrf2-mediated oxidative stress response pathway was identified as the top canonical pathway in the PAX-NGR samples. ATP-binding cassette sub-family C member 1 (ABCC1) gene was significantly reduced two hours after allergen challenge in the 5 subjects’ microarray dataset and the 2 QPCR replication datasets with P < 0.05. Conclusions: Globin mRNA reduction does not provide benefits to detect differentially expressed genes during allergen inhalation challenge. Allergen inhalation challenge is associated with decreased peripheral blood cell transcript level of ABCC1 gene.

Project description:Background: Allergen inhalation challenge in mild asthmatics induces airflow obstruction, airway hyperresponsiveness and inflammation, providing a model for hypothesis-generating experiments to understand regulation of these responses. We have sought to evaluate the peripheral whole blood transcriptome, post-challenge compared to pre-challenge, and to determine the effect of globin mRNA reduction methodology. Methods: Asthmatic subjects (20-60 years of age, with stable, mild allergic asthma, n=17) underwent allergen inhalation challenges. All subjects had an early asthmatic response of ≥ 20% fall in FEV1; most had a late phase response of ≥ 15% fall in FEV1. Blood was collected immediately prior to, and two hours after allergen challenge. Transcriptome analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST arrays, with and without globin mRNA reduction (PAX-GR and PAX-NGR, respectively) in 4 subjects. Replication studies for expression of nine genes contributing to the top canonical pathway, Nrf2-mediated oxidative stress response pathway, were performed with 5 independent subjects with microarray data, also with the same 4 subjects had microarray results and 8 other independent subjects with QPCR. Data were analyzed using paired t-test and Partek® Genomics Suite™. Results: The number of differentially expressed probe sets from PAX-NGR samples was twice that of PAX-GR samples. Paired analysis of each subjects' pre- and post-sample additionally demonstrated twice the power to detect differentially expressed probe sets. The Nrf2-mediated oxidative stress response pathway was identified as the top canonical pathway in the PAX-NGR samples. ATP-binding cassette sub-family C member 1 (ABCC1) gene was significantly reduced two hours after allergen challenge in the 5 subjects’ microarray dataset and the 2 QPCR replication datasets with P < 0.05. Conclusions: Globin mRNA reduction does not provide benefits to detect differentially expressed genes during allergen inhalation challenge. Allergen inhalation challenge is associated with decreased peripheral blood cell transcript level of ABCC1 gene. 26 array were analyzed. We first identified differentially expreed genes between post- and pre-challenge samples from 4 asthmatic subjects by using globin reduction samples and non-globin reduction samples (16 arrays). Then we replicated our findings using 10 arrays from 5 asthmatic subjects challenged with allergen. Includes 4 normal blood samples.

Project description:BackgroundAtrial fibrillation (AF) is associated with increased risks of stroke and heart failure. Electronic health record (EHR)-based AF risk prediction may facilitate efficient deployment of interventions to diagnose or prevent AF altogether.MethodsWe externally validated an electronic health record AF (EHR-AF) score in IBM Explorys Life Sciences, a multi-institutional dataset containing statistically deidentified EHR data for over 21 million individuals (Explorys Dataset). We included individuals with complete AF risk data, ≥2 office visits within 2 years, and no prevalent AF. We compared EHR-AF to existing scores including CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology Atrial Fibrillation), C2HEST (coronary artery disease or chronic obstructive pulmonary disease, hypertension, elderly, systolic heart failure, thyroid disease), and CHA2DS2-VASc. We assessed association between AF risk scores and 5-year incident AF, stroke, and heart failure using Cox proportional hazards modeling, 5-year AF discrimination using C indices, and calibration of predicted AF risk to observed AF incidence.ResultsOf 21 825 853 individuals in the Explorys Dataset, 4 508 180 comprised the analysis (age 62.5, 56.3% female). AF risk scores were strongly associated with 5-year incident AF (hazard ratio per SD increase 1.85 using CHA2DS2-VASc to 2.88 using EHR-AF), stroke (1.61 using C2HEST to 1.92 using CHARGE-AF), and heart failure (1.91 using CHA2DS2-VASc to 2.58 using EHR-AF). EHR-AF (C index, 0.808 [95% CI, 0.807-0.809]) demonstrated favorable AF discrimination compared to CHARGE-AF (0.806 [95% CI, 0.805-0.807]), C2HEST (0.683 [95% CI, 0.682-0.684]), and CHA2DS2-VASc (0.720 [95% CI, 0.719-0.722]). Of the scores, EHR-AF demonstrated the best calibration to incident AF (calibration slope, 1.002 [95% CI, 0.997-1.007]). In subgroup analyses, AF discrimination using EHR-AF was lower in individuals with stroke (C index, 0.696 [95% CI, 0.692-0.700]) and heart failure (0.621 [95% CI, 0.617-0.625]).ConclusionsEHR-AF demonstrates predictive accuracy for incident AF using readily ascertained EHR data. AF risk is associated with incident stroke and heart failure. Use of such risk scores may facilitate decision support and population health management efforts focused on minimizing AF-related morbidity.

Project description:The use of oxygen-driven aerosol inhalation therapy with budesonide (suspension) and terbutaline sulfate for the treatment of pediatric asthmatic bronchitis was studied. Sixty pediatric patients diagnosed with asthmatic bronchitis in Xuzhou Children's Hospital during the period comprising April 2013 to December 2015 were enrolled in the study. After randomly dividing the patients into a control (conventional dexamethasone drip) and a treatment group (inhalation of budesonide with terbutaline sulfate) of 30 patients each, the symptoms were treated using antibiotics when necessary. The results of our evaluation showed the overall effective rate of treatment in the control group was 73.33% (40% with marked improvement, 33.33% with some improvement and 26.67% with no improvement) and that in the treatment group was 96.67% (73.73% with marked improvement, 23.33% with some improvement and only 3.33% with no improvement) with a statistically significant difference (p<0.05). The pulmonary functions of all pediatric patients showed no statistically significant differences in the pulmonary function indexes between the two groups before treatment (p>0.05). However, the differences in FEV1, FVC, FEV1/FVC and PEF between control and treatment groups before and after treatment were statistically significant (p<0.05), with overall improvement being higher in the treatment group. Finally, the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level in patients of the two groups improved significantly after treatment (p<0.05). The ESR and CRP level in the treatment group were improved to a higher degree than those in the control group (p<0.05). There were only minor adverse reactions in two patients in the treatment group, and the overall rate of adverse reactions was not significantly different between the two groups (p>0.05). Based on our evaluation the aerosol inhalation therapy of budesonide (suspension) with terbutaline sulfate has definite curative effects and is safe to use on pediatric asthmatic bronchitis patients. The approach is superior to the conventional dexamethasone treatment and is worth studying in larger populations for recommending it widely.

Dataset Information

Exercise performance after salbutamol inhalation in non-asthmatic, non-athlete individuals: a randomised, controlled, cross-over trial.

Publications

Exercise performance after salbutamol inhalation in non-asthmatic, non-athlete individuals: a randomised, controlled, cross-over trial.

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