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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EIA wih house dust mite | Other | Patients with EIA and house-dust mite allergy and an eNO > 30 ppb |
|
| EIA without sensitization | Other | Patients with EIA without allergic sensitization and an eNO < 20 ppb |
|
| Healthy controls | Other | Healthy controls without allergic sensitization or known asthma |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Exercise challenge in the cold chamber (ECC) | Diagnostic Test | Exercise challenge (defined as running on a treadmill for 6-8 minutes on submaximal work load in a cold chamber. Gradient: 10%, temperature 2-4°C. After the exercise challenge controlling bodyplethysmography and spirometry after 5, 10, 15 and 30 minutes. A positive reaction is a decrease of ≥ 10% of FEV1 in comparison to the initial value. |
| Measure | Description | Time Frame |
|---|---|---|
| Dysregulation of miRNA-146 | 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 MiSeqâ„¢ 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. | 1 Year |
| Measure | Description | Time Frame |
|---|---|---|
| Dysregulation miRNAs affecting Th2 mediated bronchial inflammation (miRNA-126, miRNA-21, miRNA-145, let7-mimic) | 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. | 1 Year |
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For EIA patients
Inclusion Criteria:
Exclusion Criteria:
For healthy controls
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Melanie Dreßler, MD | Contact | +49-69-6301-4588 | melanie.dressler@kgu.de | |
| Helena Donath, MD | Contact | +49-69-6301-4588 | helena.donath@kgu.de |
| Name | Affiliation | Role |
|---|---|---|
| Melanie Dreßler, MD | Johann Wolfgang Goethe University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Universitätsklinikum Frankfurt | Recruiting | Frankfurt am Main | Hesse | 60590 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23634861 | Background | Parsons JP, Hallstrand TS, Mastronarde JG, Kaminsky DA, Rundell KW, Hull JH, Storms WW, Weiler JM, Cheek FM, Wilson KC, Anderson SD; American Thoracic Society Subcommittee on Exercise-induced Bronchoconstriction. An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction. Am J Respir Crit Care Med. 2013 May 1;187(9):1016-27. doi: 10.1164/rccm.201303-0437ST. | |
| 31097027 |
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| ID | Term |
|---|---|
| D001250 | Asthma, Exercise-Induced |
| D000092542 | Dust Mite Allergy |
| ID | Term |
|---|---|
| D001249 | Asthma |
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D012130 | Respiratory Hypersensitivity |
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The micro RNA profile of patients with known EIA and house dust mite allergy and patients with EIA without allergic sensitization are compared to the micro RNA profile of healthy controls
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|
| mRNA profile | Diagnostic Test | Blood taking with full blood exam and PAXgene tube for investigation oft the micro RNA profiles. The PAXgene Blood RNA kit insulates total RNA inclusive miRNA and small RNA which are centrifugated, pelletised, washed and incubated to detach proteins. For mapping the particular miRNA there will be generated libraries with specifical codes to match the analysis to the original probe. Next generation sequencing will be performed by MISeq REagent Kit v3 and the analysis oft the different expressions in the R Version 3.2.3. The divergent expressions will be refurbished by computer and databased. |
|
| standard diagnostic | Diagnostic Test | bodyplethysmography, spirometry, exhaled NO, skin prick test, asthma control test (ACT) |
|
| Cange of eNO | Change of eNO after ECC in the EIA subgroups compared to the healthy controls | 1 Year |
| Change of leucocytes and neutrophile granulocytes | Change of leucocytes and neutrophile granulocytes after ECC in the EIA subgroups compared to the healthy controls | 1 Year |
| FEV1-decrease in ECC | Comparison of the FEV1-decrease in ECC with significant dysregulated miRNA in the EIA subgroups compared to the healthy controls | 1 Year |
| Comparison eNO with significant dysregulated miRNA | Comparison of the initial value of exhaled NO with significant dysregulated miRNA in the EIA subgroups compared to the healthy controls | 1 Year |
| Comparison of change of leucocytes and neutrophile granulocytes with significant dysregulated miRNA | Comparison of the increase of leucocytes and neutrophile granulocytes after ECC significant dysregulated miRNA in the EIA subgroups compared to the healthy controls | 1 Year |
| Comparison of ACT with significant dysregulated miRNA | Comparison of the score in ACT with significant dysregulated miRNA in the EIA subgroups compared to the healthy controls | 1 Year |
| Comparison of DI with significant dysregulated miRNA | Comparison of the scoresin DI with significant dysregulated miRNA in the EIA subgroups compared to the healthy controls | 1 Year |
| Background |
| Dressler M, Friedrich T, Lasowski N, Herrmann E, Zielen S, Schulze J. Predictors and reproducibility of exercise-induced bronchoconstriction in cold air. BMC Pulm Med. 2019 May 16;19(1):94. doi: 10.1186/s12890-019-0845-3. |
| 29526567 | Background | Dressler M, Salzmann-Manrique E, Zielen S, Schulze J. Exhaled NO as a predictor of exercise-induced asthma in cold air. Nitric Oxide. 2018 Jun 1;76:45-52. doi: 10.1016/j.niox.2018.03.004. Epub 2018 Mar 8. |
| 22326606 | Background | Schulze J, Smith HJ, Fuchs J, Herrmann E, Dressler M, Rose MA, Zielen S. Methacholine challenge in young children as evaluated by spirometry and impulse oscillometry. Respir Med. 2012 May;106(5):627-34. doi: 10.1016/j.rmed.2012.01.007. Epub 2012 Feb 10. |
| 19596563 | Background | Schulze J, Rosewich M, Riemer C, Dressler M, Rose MA, Zielen S. Methacholine challenge--comparison of an ATS protocol to a new rapid single concentration technique. Respir Med. 2009 Dec;103(12):1898-903. doi: 10.1016/j.rmed.2009.06.007. Epub 2009 Jul 10. |
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| D000092202 |
| Exercise-Induced Allergies |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D012221 | Rhinitis, Allergic, Perennial |
| D065631 | Rhinitis, Allergic |
| D012220 | Rhinitis |
| D009668 | Nose Diseases |
| D010038 | Otorhinolaryngologic Diseases |