Clinical Trial: Eosinophil Induced Remodelling in Asthma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Eosinophil Induced Airway Smooth Muscle Remodelling in Asthma

Brief Summary:

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.

Detailed Summary:
Sponsor: Lithuanian University of Health Sciences

Current Primary Outcome:

• Eosinophils and bronchial smooth muscle cell adhesion change assessment [ Time Frame: In 30, 45, 60, 120, 240 minutes time points after eosinophils and bronchial smooth muscle cell interactions start ]
  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.
• Bronchial smooth muscle cell proliferation change assessment by cell viability [ Time Frame: In 48 and 72 hrs time points after eosinophils and linear bronchial smooth muscle co-culture formation ]
  Bronchial smooth muscle cell proliferation is assessed by cell viability

Original Primary Outcome: Same as current

Current Secondary Outcome:

• The change of capacity of eosinophils' integrins to inhibit the bronchial smooth muscle cell proliferation in patients with asthma [ Time Frame: In 48 and 72 hrs time points after eosinophils and linear bronchial smooth muscle co-culture formation ]
  Using the same eosinophils and linear bronchial smooth muscle cell culture, but in this measure is added integrins
• The change of eosinophils' integrins interaction with bronchial smooth muscle cells and Wnt-5A protein production after allergen challenge [ Time Frame: 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 ]
  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

Original Secondary Outcome: Same as current

Information By: Lithuanian University of Health Sciences

Dates:
Date Received: December 21, 2015
Date Started: March 2014
Date Completion: January 2017
Last Updated: January 4, 2016
Last Verified: January 2016