Allergic Asthma Clinical Trial
Official title:
Non-coding RNAs Analysis of Eosinophil Subtypes in Asthma
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.
Status | Recruiting |
Enrollment | 80 |
Est. completion date | October 1, 2023 |
Est. primary completion date | October 1, 2023 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility |
Inclusion Criteria: - 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. Exclusion Criteria: - 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 ß2 agonists 12 hours prior the study; 4) long acting ß2 agonists 2 days prior the study; 5) leukotriene receptor antagonists prior 14 days; - Contraindications for epinephrine; - Other significant mental and / or internal diseases and conditions, which could be as exclusion criteria due to the opinion of the researcher; - Alcohol or narcotic abuse; - Pregnancy; - Breast-feeding. |
Country | Name | City | State |
---|---|---|---|
Lithuania | Lithuanian University of Health Sciences, Pulmonology Department | Kaunas |
Lead Sponsor | Collaborator |
---|---|
Lithuanian University of Health Sciences |
Lithuania,
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Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | |
Primary | 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 | Fold changes of ncRNA profiles of distinct eosinophil subtypes | Non-validated whole ncRNA profiles of distinct eosinophil subtypes in severe and non-severe eosinophilic asthma patients and healthy subjects. | From 6 to 12 months | |
Secondary | The fold changes of rEOS and iEOS surface integrins expression | The gene expression of selected outer-membrane integrins in eosinophil subtypes. | From 6 to 12 months | |
Secondary | The fold changes of rEOS and iEOS eosinophilopoietins receptors expression | The gene expression of interleukin (IL)-5, IL-3, and granulocyte-macrophage colony-stimulating factor in eosinophil subtypes. | From 6 to 12 months | |
Secondary | The efficiency of iEOS and rEOS adhesion | The differences in stable adhered iEOS and rEOS quantity in the combined cell culture with airway smooth muscle (ASM) cells or pulmonary fibroblasts compared between the investigated groups. | From 6 to 12 months | |
Secondary | iEOS and rEOS survival differences | Viable iEOS and rEOS number after an appropriate period of time in combined cell culture with ASM cells or pulmonary fibroblasts. | From 6 to 12 months | |
Secondary | Quantity of iEOS and rEOS synthesized reactive oxygen species | Relative differences between iEOS and rEOS synthesized reactive oxygen species quantity after an appropriate period of incubation alone or with ASM cells or pulmonary fibroblasts. | From 6 to 12 months | |
Secondary | Apoptotic iEOS and rEOS number | The number of apoptotic iEOS and rEOS after an appropriate period of time in combined cell culture with ASM cells or pulmonary fibroblasts. | From 6 to 12 months | |
Secondary | Concentrations of iEOS and rEOS produced proteins in investigated subjects' body fluids. | Selected iEOS and rEOS proteins concentrations, measured in investigated subjects body fluids, expressed as the amount of protein in the respective amount of fluid sample. | From 6 to 12 months | |
Secondary | iEOS and rEOS effect on airway smooth muscle cells or pulmonary fibroblasts proliferation | The quantity of ASM cells or pulmonary fibroblasts after several repeats of proliferation in the presence or absence of eosinophil subtypes. | From 6 to 12 months | |
Secondary | iEOS and rEOS effect on apoptotic ASM cells and pulmonary fibroblasts number | The number of apoptotic ASM cells and pulmonary fibroblasts after an appropriate period of time in combined cell culture with iEOS and rEOS. | From 6 to 12 months | |
Secondary | iEOS and rEOS effect on migration of ASM cells. | The migrated ASM cells number after an appropriate period of time in combined cell culture with iEOS and rEOS | From 6 to 12 months | |
Secondary | iEOS and rEOS effect on migration of pulmonary fibroblasts | The migrated pulmonary fibroblasts number after an appropriate period of time in combined cell culture with iEOS and rEOS | From 6 to 12 months | |
Secondary | iEOS and rEOS effect on ASM cells contractility | The relative efficiency of ASM cells' ability to contract collagen gel after an appropriate period of time in combined cell culture with iEOS and rEOS, expressed as reduced poured gel size in percentage, compared with control ASM cells without incubation with eosinophils. | From 6 to 12 months | |
Secondary | iEOS and rEOS effect on pulmonary fibroblasts contractility | The relative efficiency of pulmonary fibroblasts ability to contract collagen gel after an appropriate period of time in combined cell culture with iEOS and rEOS. expressed as reduced poured gel size in percentage, compared with control pulmonary fibroblasts, without incubation with eosinophils. | From 6 to 12 months | |
Secondary | iEOS and rEOS effect on fold changes of ASM cells and pulmonary fibroblasts proteins expression; | Altered selected ASM cells and pulmonary fibroblasts proteins expression, after incubation with iEOS and rEOS, expressed as fold changes in comparison with control cells, without incubation with eosinophils | From 6 to 12 months | |
Secondary | iEOS and rEOS effect on fold changes of ASM cells and pulmonary fibroblasts proteins gene expression; | Altered selected ASM cells and pulmonary fibroblasts proteins gene expression, after incubation with iEOS and rEOS, expressed as fold changes in comparison with control cells, without incubation with eosinophils | From 6 to 12 months |
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