Epigenetic Regulation of Exercise Induced Asthma

Not Applicable

• Conditions: House Dust Mite Allergy; Exercise Induced Asthma

• Registration Number: NCT05174689
• Lead Sponsor: Johann Wolfgang Goethe University Hospital

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2021-08-01
• Study First Submitted: 2021-08-30
• Status Verified: 2021-12
• Study First Submitted QC: 2021-12-14
• Last Update Submitted: 2021-12-14
• Study First Posted: 2022-01-03
• Last Update Posted: 2022-01-03
• Primary Completion: 2022-08
• Study Completion: 2022-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 68

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%

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Dysregulation of miRNA-146	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.

Secondary Outcome Measures

Name	Time	Method
Comparison of ACT with significant dysregulated miRNA	1 Year	Comparison of the score in ACT with significant dysregulated miRNA in the EIA subgroups compared to the healthy controls
Comparison of DI with significant dysregulated miRNA	1 Year	Comparison of the scoresin DI with significant dysregulated miRNA in the EIA subgroups compared to the healthy controls
Dysregulation miRNAs affecting Th2 mediated bronchial inflammation (miRNA-126, miRNA-21, miRNA-145, let7-mimic)	1 Year	Dysregulation of other miRNAs affecting the Th2 mediated bronchial inflammation (miRNA-126, miRNA-21, miRNA-145, let7-mimic) and compare to the control group.; MiRNA preparation and measurement processes are described in Outcome 1.
Cange of eNO	1 Year	Change of eNO after ECC in the EIA subgroups compared to the healthy controls
Comparison eNO with significant dysregulated miRNA	1 Year	Comparison of the initial value of exhaled NO with significant dysregulated miRNA in the EIA subgroups compared to the healthy controls
Comparison of change of leucocytes and neutrophile granulocytes with significant dysregulated miRNA	1 Year	Comparison of the increase of leucocytes and neutrophile granulocytes after ECC significant dysregulated miRNA in the EIA subgroups compared to the healthy controls
Change of leucocytes and neutrophile granulocytes	1 Year	Change of leucocytes and neutrophile granulocytes after ECC in the EIA subgroups compared to the healthy controls
FEV1-decrease in ECC	1 Year	Comparison of the FEV1-decrease in ECC with significant dysregulated miRNA in the EIA subgroups compared to the healthy controls

Trial Locations

Locations (1)

Universitätsklinikum Frankfurt; 🇩🇪 Frankfurt, Hessen, Germany