Allergic Asthma Clinical Trial
— ERAOfficial title:
Eosinophil Induced Airway Smooth Muscle Remodelling in Asthma
Verified date | February 2020 |
Source | Lithuanian University of Health Sciences |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Asthma is a chronic, inflammatory disease of the lung characterized by intermittent airway
obstruction, airway hyperresponsiveness, presence of activated inflammatory cells,
inflammatory mediators, and airway structural changes. Airway smooth muscle (ASM) cells
actively participate in the remodelling and inflammatory processes through proliferation,
release of proinflammatory cytokines, chemokines, and extracellular matrix (ECM) proteins.
Eosinophils as essential inflammatory cells may be of importance in ASM remodelling. It is
known that eosinophil induces ASM cells proliferation via the secretion of cysteinyl
leukotrienes in asthmatics. However there is a possible direct eosinophil-ASM cells
functional interaction by adhesion processes. It has been shown that integrins modulate ASM
proliferation and contractile protein expression demonstrating allergen-induced ASM
remodelling in an animal model of allergic asthma.
Wingless/integrase-1 (WNT) signaling regulates not only a wide range of developmental
processes, but its aberrant activation can lead to disease. Recently, it was confirmed that
genes polymorphisms in the WNT signaling pathway are associated with impaired lung function
in childhood asthma. It was also found for the first time a relevant role of noncanonical WNT
signaling in TGFβ-induced ECM expression by ASM cells and identified WNT-5A is the most
abundant WNT ligand with increased expression in asthmatics. It demonstrates that WNT-5A
could contribute to remodelling of the airways. Unfortunately, the effect of eosinophil on
WNT secretion by ASM cells at present is unknown.
Despite the widely acknowledged significance of eosinophils in asthma pathogenesis, the
mechanism of eosinophil induced ASM remodelling is unsolved.
Status | Completed |
Enrollment | 20 |
Est. completion date | January 2017 |
Est. primary completion date | October 2016 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 50 Years |
Eligibility |
Inclusion Criteria: 1. Men and women between the ages of 18-50 years; 2. Allergic asthma and sensitization to house dust mites (D. pteronyssinus) allergen, approved with: 2.1. Medical history and symptoms more than one year and 2.2. skin prick test positive for D. pteronyssinus (positive wheals are those exceeding 3mm in diameter greater than the negative control) and 2.3. Positive bronchial challenge with methacholine or documented completely reversible bronchial obstruction; 3. Stable lung function (FEV1=70 perc.); 4. Postmenopausal women. Premenopausal women if pregnancy test is negative and they agree to use an effective contraceptive measures during the study; 5. Healthy subjects without allergic and other chronic respiratory diseases (control group); 6. Non- smokers; 7. Participants who gave his/her informed written consent. Exclusion Criteria: 1. Asthma exacerbation 1 month prior to study 2. Clinically significant permanent allergy symptoms (ex. cat or dog dander induced allergy) 3. Contraindications to perform an allergy skin test and/or bronchial provocation test 3.1. Active airway infection 1 month prior the study; 3.2. Used medicaments: 3.2.1. Inhaled glucocorticoids intake 1 month prior the study; 3.2.2. Antihistamines intake 7 days prior the study; 3.2.3. Short acting ß2 agonists 12 hours prior the study; 3.2.4. Long acting ß2 agonists 2 days prior the study; 3.2.5. Leukotriene receptor antagonists prior 14 days; 4. If the histamine mean wheal diameter is <= 3 mm or control mean wheal diameter is >= 3 mm; 5. Contraindications for epinephrine; 6. Other significant mental and / or internal diseases and conditions, which could be as exclusion criteria due to the opinion of the researcher; 7. Alcohol or narcotic abuse; 8. Pregnancy; 9. Breast-feeding. |
Country | Name | City | State |
---|---|---|---|
Lithuania | Lithuanian University of Health Sciences, Pulmonology and Immunology Department | Kaunas |
Lead Sponsor | Collaborator |
---|---|
Lithuanian University of Health Sciences | Research Council of Lithuania, University of Groningen |
Lithuania,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Eosinophils and bronchial smooth muscle cell adhesion change assessment | There are used the individual eosinophil and airway smooth muscle cell co-culture. It is compared the strength of eosinophil adhesion to the bronchial smooth muscle cells in patients with asthma and healthy. | In 30, 45, 60, 120, 240 minutes time points after eosinophils and bronchial smooth muscle cell interactions start | |
Primary | Bronchial smooth muscle cell proliferation change assessment by cell viability | Bronchial smooth muscle cell proliferation is assessed by cell viability | In 48 and 72 hrs time points after eosinophils and linear bronchial smooth muscle co-culture formation | |
Secondary | The change of capacity of eosinophils' integrins to inhibit the bronchial smooth muscle cell proliferation in patients with asthma | Using the same eosinophils and linear bronchial smooth muscle cell culture, but in this measure is added integrins | In 48 and 72 hrs time points after eosinophils and linear bronchial smooth muscle co-culture formation | |
Secondary | The change of eosinophils' integrins interaction with bronchial smooth muscle cells and Wnt-5A protein production after allergen challenge | The results are compared with the before and after bronchial provocation with Dermatophagoides pteronyssinus allergen. It is measured the integrins as specific adhesion molecules attachments to the bronchial smooth muscle cells after allergen challenge | Up to 72 hrs time points after eosinophils (collected from blood of patients before and after bronchial provocation with an allergen) and linear bronchial smooth muscle co-culture formation |
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