Epigenetic Regulation of Excercise Induced Asthma
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 68
- 试验地点
- 2
- 主要终点
- Dysregulation of miRNA-146
研究概览
简要总结
The purpose of this study is to investigate the micro ribonucleic acid (mRNA) profiles of patients with EIA without allergic sensitization and EIA with house dust mite sensitization compared to that of healthy controls.
详细描述
Patients with known EIA are periodically reexamined by medical history, clinical examination, bodyplethysmography, spirometry, exhaled nitric oxide (eNO), skin prick test, methacholin challenge test and exercise-challenge in a cold-chamber at 2-4°C (ECC). Additionally the investigators gathers the questionnaires: Asthma Control Test (ACT) and Dyspnoe Index (DI).
Besides these standard procedures the investigators want to investigate the micro-RNA profiles in two EIA subgroups: EIA with house-dust allergy (n = 24) and EIA without house-dust allergy (n = 24).
Both groups are characterized by different eNO levels. The patients with EIA and house-dust allergy should have an eNO > 30 ppb, the patients with EIA without house-dust allergy an eNO < 20 ppb.
The micro-RNA profiles of the both EIA subgroups will be compared the micro RNA profiles of 20 healthy controls .
Therefore blood will be taken (for a complete blood count and micro RNA analysis) at three points of time: before ECC, directly after ECC and after 24 hours ± 4 hours after ECC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 24 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For EIA patients
- •Inclusion Criteria:
- •written agreement
- •age >=12 and <= 24
- •known exercise induced asthma
- •Group 1: skin prick test positiv house-dust allergy, eNO > 30 ppb, MCT PD20 < 0,1 mg
- •Group 2: skin prick test negative house-dust allergy, eNO < 20 ppb, MCT PD20 < 1 mg
- •lung function before ECC forced vital capacity (FVC) ≥ 75% and forced exspiratory pressure in one second (FEV1) ≥ 70%
排除标准
- •age < 12 und > 24 years
- •lung function FVC < 75% und FEV1< 70%
- •inability to understand the range of the study
- •chronic asthma with systemic cortisone therapy
- •regular therapy with inhalative corticosteroids or leukotriene-antagonists <14 days before visit 1
- •intake of long acting beta-agonists (LABA) 48 h before examination
- •intake of short acting beta-agonists (SABA) 8 h before examination
- •acute severe infection (pneumonia) within the last 4 weeks
- •other chronic diseases or infections (HIV, Tbc)
- •pregnancy
- •For healthy controls
- •Inclusion Criteria:
- •written agreement
- •age >=18 and <= 24
- •Exclusion Criteria:
- •age < 18 and > 24 years
- •known asthma bronchiale or other chronic lung diseases
- •lung function FVC < 90% and FEV1 < 80%
- •allergic sensitization in skin prick test
- •eNO > 30 ppb
- •inability to understand the range of the study
- •acute severe infection (pneumonia) within the last 4 weeks
- •other chronic diseases or infections (HIV, Tbc)
- •pregnancy
结局指标
主要结局
Dysregulation of miRNA-146
时间窗: 1 Year
The primary endpoint is the dysregulation of miRNA-146 in comparison to the control group and within the subgroups which play an determined role in the bronchial inflammation. Therefore the total RNA, including miRNA, will be isolated using the PAXgene Blood miRNA Kit (Qiagen, Hilden, Germany). Concentration of RNA will be assessed using Nanodrop Lite spectrometry (Thermo Scientific, Dreieich, Germany). MiRNA libraries are generated with the QIAseq miRNA Library Kit (Qiagen, Hilden, Germany). Next generation sequencing (NGS) will be performed with the MiSeq Reagent Kit v3, the PhiX Sequencing Control v3 and the MiSeq™ Desktop Sequencer (all Illumina Inc., San Diego, CA, USA). Differential expression analysis will be performed in RStudio 1.2.1335 (https://cran.r-project.org/). False discovery rate correction will be applied and miRNAs are considered to be differentially expressed with p \< 0.05.
次要结局
- Comparison of ACT with significant dysregulated miRNA(1 Year)
- Comparison of DI with significant dysregulated miRNA(1 Year)
- Dysregulation miRNAs affecting Th2 mediated bronchial inflammation (miRNA-126, miRNA-21, miRNA-145, let7-mimic)(1 Year)
- Cange of eNO(1 Year)
- Comparison eNO with significant dysregulated miRNA(1 Year)
- Comparison of change of leucocytes and neutrophile granulocytes with significant dysregulated miRNA(1 Year)
- Change of leucocytes and neutrophile granulocytes(1 Year)
- FEV1-decrease in ECC(1 Year)
研究者
Stefan Zielen
Prof. Dr. med.
Johann Wolfgang Goethe University Hospital