Non-coding RNAs Analysis of Eosinophil Subtypes in Asthma

NCT04542902 | Unknown

• 1 other identifier: LAB-1/2020
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic airway inflammation rich in eosinophils is an important feature seen in asthma. Airway and blood eosinophilia is associated with increased rates of asthma exacerbations and more intense treatment. Recently, the existence of two distinct eosinophils subtypes was revealed-lung-resident eosinophils (rEOS), which maturate independently to interleukin (IL) 5, with the primary function to maintain tissue homeostasis, and inflammatory eosinophils (iEOS), which mature in IL-5-dependent manner and are mainly involved in immune responses. Eosinophils' effect on the airway remodeling in asthma depends not only on the activity but also by their viable number in the lungs. Blood iEOS infiltrate the airways mainly after the environmental stimulus like allergen and leave the airways with bronchial secretions. However, rEOS reside lung tissue for their entire lifetime regulating local immunity. Blood rEOS and iEOS ratio alters in asthma, compared with healthy controls. It is known that the predominant eosinophils subtype in allergic asthma are iEOS, while rEOS are basic subtype in severe eosinophilic asthma patients, moreover, they are different in adhesive properties and survivability as well. Distinct biological properties allows to speculate about their different functions in asthma, however, there are still little information. Data about differently expressed microRNA (miRNA) profiles in eosinophils in asthma suggests, that eosinophils subtypes can be distinct in non-coding RNA (ncRNA) - microRNA (miRNA), piwi-interacting RNA (piRNA) and long non-coding RNA (IncRNA) profiles that could describe their role in asthma pathogenesis and act as biomarkers to discern asthma phenotypes.

Conditions

Allergic Asthma; Severe Eosinophilic Asthma

Keywords

Eosinophils subtypes; Non-coding RNA; Exosome

Outcome Measures

Primary Outcomes (2)

• Fold changes of ncRNA expression between eosinophils subtypes

  Validated ncRNA expression of rEOS and iEOS in severe and non-severe eosinophilic asthma patients and healthy subjects.

  From 6 to 12 months

• ncRNA levels in rEOS- and iEOS-derived exosomes

  Qualitative and quantitative selected ncRNA levels in rEOS- and iEOS-derived exosomes of all investigated groups.

  From 12 to 18 months

Secondary Outcomes (16)

• Fold changes of ncRNA profiles of distinct eosinophil subtypes

  From 6 to 12 months

• The fold changes of rEOS and iEOS surface integrins expression

  From 6 to 12 months

• The fold changes of rEOS and iEOS eosinophilopoietins receptors expression

  From 6 to 12 months

• The efficiency of iEOS and rEOS adhesion

  From 6 to 12 months

• iEOS and rEOS survival differences

  From 6 to 12 months

Study Arms (3)

Allergic asthma patients

EXPERIMENTAL

Allergic asthma patients and sensitization to house dust mites (D. pteronyssinus) allergen.

Biological: Dermatophagoides pteronyssinus allergen; Procedure: Blood sampling; Procedure: Bronchial challenge with allergen

Severe eosinophilic asthma patients

EXPERIMENTAL

Procedure: Blood sampling

Healthy subjects as a control group

ACTIVE COMPARATOR

Healthy subjects without allergic and other chronic respiratory diseases (control group).

Procedure: Blood sampling

Interventions

Dermatophagoides pteronyssinus allergen BIOLOGICAL

Dermatophagoides pteronyssinus allergen is required to perform allergen bronchial challenge test.

Allergic asthma patients

Blood sampling PROCEDURE

An amount of a person's blood taken from their body for use in medical.

Allergic asthma patients; Healthy subjects as a control group; Severe eosinophilic asthma patients

Bronchial challenge with allergen PROCEDURE

Bronchial challenge is performed with D. pteronyssinus allergen. Measurements of differences in eosinophils activity after allergen challenge.

Allergic asthma patients

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women between the ages of 18-70 years;
• Allergic asthma and sensitization to house dust mites (D. pteronyssinus) allergen, approved with: 1) medical history and symptoms more than one year; 2) skin prick test positive for D. pteronyssinus (positive wheals are those exceeding 3 mm in diameter greater than the negative control); 3) positive bronchial challenge with methacholine or documented reversible bronchial obstruction;
• Severe eosinophilic asthma;
• Premenopausal women if pregnancy test is negative;
• Healthy subjects without allergic and other chronic respiratory diseases (control group);
• Participants who gave his/her informed written consent.

You may not qualify if:

• Asthma exacerbation 1 month prior to study;
• Clinically significant permanent allergy symptoms (ex. cat or dog dander induced allergy);
• Contraindications to perform an allergy skin test and/or bronchial provocation test: 1) active airway infection 1 month prior the study; 2) used medicaments: inhaled glucocorticoids intake 1 month prior the study, antihistamines intake 7 days prior the study; 3) short acting β2 agonists 12 hours prior the study; 4) long acting β2 agonists 2 days prior the study; 5) leukotriene receptor antagonists prior 14 days;
• Contraindications for epinephrine;
• Alcohol or narcotic abuse;
• Pregnancy;
• Breast-feeding.

Sponsors & Collaborators

• Lithuanian University of Health Sciences: lead

Study Sites (1)

Lithuanian University of Health Sciences, Pulmonology Department

Kaunas, LT-50009, Lithuania

RECRUITING

Related Publications (10)

• Barnig C, Alsaleh G, Jung N, Dembele D, Paul N, Poirot A, Uring-Lambert B, Georgel P, de Blay F, Bahram S. Circulating Human Eosinophils Share a Similar Transcriptional Profile in Asthma and Other Hypereosinophilic Disorders. PLoS One. 2015 Nov 2;10(11):e0141740. doi: 10.1371/journal.pone.0141740. eCollection 2015.

  PMID: 26524763 BACKGROUND

• Mazzeo C, Canas JA, Zafra MP, Rojas Marco A, Fernandez-Nieto M, Sanz V, Mittelbrunn M, Izquierdo M, Baixaulli F, Sastre J, Del Pozo V. Exosome secretion by eosinophils: A possible role in asthma pathogenesis. J Allergy Clin Immunol. 2015 Jun;135(6):1603-13. doi: 10.1016/j.jaci.2014.11.026. Epub 2015 Jan 21.

  PMID: 25617225 BACKGROUND

• Mesnil C, Raulier S, Paulissen G, Xiao X, Birrell MA, Pirottin D, Janss T, Starkl P, Ramery E, Henket M, Schleich FN, Radermecker M, Thielemans K, Gillet L, Thiry M, Belvisi MG, Louis R, Desmet C, Marichal T, Bureau F. Lung-resident eosinophils represent a distinct regulatory eosinophil subset. J Clin Invest. 2016 Sep 1;126(9):3279-95. doi: 10.1172/JCI85664. Epub 2016 Aug 22.

  PMID: 27548519 BACKGROUND

• Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10513-8. doi: 10.1073/pnas.0804549105. Epub 2008 Jul 28.

  PMID: 18663219 BACKGROUND

• Perry MM, Tsitsiou E, Austin PJ, Lindsay MA, Gibeon DS, Adcock IM, Chung KF. Role of non-coding RNAs in maintaining primary airway smooth muscle cells. Respir Res. 2014 May 16;15(1):58. doi: 10.1186/1465-9921-15-58.

  PMID: 24886442 BACKGROUND

• Rodrigo-Munoz JM, Canas JA, Sastre B, Rego N, Greif G, Rial M, Minguez P, Mahillo-Fernandez I, Fernandez-Nieto M, Mora I, Barranco P, Quirce S, Sastre J, Del Pozo V. Asthma diagnosis using integrated analysis of eosinophil microRNAs. Allergy. 2019 Mar;74(3):507-517. doi: 10.1111/all.13570. Epub 2018 Oct 11.

  PMID: 30040124 BACKGROUND

• Zhu Y, Mao D, Gao W, Han G, Hu H. Analysis of lncRNA Expression in Patients With Eosinophilic and Neutrophilic Asthma Focusing on LNC_000127. Front Genet. 2019 Mar 19;10:141. doi: 10.3389/fgene.2019.00141. eCollection 2019.

  PMID: 30941157 BACKGROUND

• Weller PF, Spencer LA. Functions of tissue-resident eosinophils. Nat Rev Immunol. 2017 Dec;17(12):746-760. doi: 10.1038/nri.2017.95. Epub 2017 Sep 11.

  PMID: 28891557 BACKGROUND

• Rosenberg HF, Dyer KD, Foster PS. Eosinophils: changing perspectives in health and disease. Nat Rev Immunol. 2013 Jan;13(1):9-22. doi: 10.1038/nri3341. Epub 2012 Nov 16.

  PMID: 23154224 BACKGROUND

• Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol. 2006;24:147-74. doi: 10.1146/annurev.immunol.24.021605.090720.

  PMID: 16551246 BACKGROUND

MeSH Terms

Conditions

Pulmonary Eosinophilia

Interventions

Antigens, Dermatophagoides; Blood Specimen Collection; Allergens

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Antigens; Biological Factors; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Kestutis Prof. Dr. Malakauskas

CONTACT

+37037326737; kestutis.malakauskas@lsmuni.lt

Jolita Palacionyte

CONTACT

+37062591727; jolita.palacionyte@lsmuni.lt

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Clinical Professor, Head of Laboratory

Study Record Dates

• First Submitted: August 25, 2020
• First Posted: September 9, 2020
• Study Start: October 1, 2020
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: September 9, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

LI (1)