Role of Extracellular Matrix in the Development of Airway Remodeling in Asthma

Summary

Asthma is a major noncommunicable chronic inflammatory disorder which is characterized by airway inflammation and related to pathological modifications of the bronchial wall structure so called airway remodeling. Airway remodeling seen in asthma is mainly described by epithelial changes, subepithelial fibrosis, increased airway smooth muscle (ASM) mass, decreased distance between ASM and epithelium, mucous gland and goblet cell hyperplasia, vascular changes and edema. Near these well known pathophysiological changes of the airways, the extracellular matrix (ECM) can be distinguished as a new important factor included in development of airway remodeling in asthma.

Conditions

• Allergic Asthma
• Airway Remodelling
• Extracellular Matrix Alteration

Interventions

PROCEDURE

Bronchial challenge with allergen

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

OTHER

Co-culture formation

Eosinophil and linear bronchial smooth muscle cell or pulmonary fibroblast co-culture formation. Bronchial smooth muscle cell and pulmonary fibroblast proliferation, migration, contractillity, differentiation, eosinophil adhesion to the bronchial smooth muscle cells or pulmonary fibroblast.

OTHER

Inhibition of Wnt and Smad signaling pathways

Wnt and Smad signaling pathways inhibitors effect on development of airway remodelling processes (extracellular matrix production, bronchial smooth muscle cell and pulmonary fibroblast proliferation, contractillity, differentiation, migration).

OTHER

Extracellular matrix turnover and deposition assessment

Eosinophils effect on extracellular matrix proteins (collagen, fibronectin, elastin, versican, decorin, laminin, etc.) and matrix metalloproteinasis (MMP-2,9,12,etc.) production by pulmonary fibroblasts.

BIOLOGICAL

Dermatophagoides pteronyssinus allergen

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

DEVICE

Dosimeter ProvoX (Ganshorn)

Device for allergen bronchial challenge test.

BIOLOGICAL

Eosinophils

Eosinophils are isolated from peripheral blood

BIOLOGICAL

Airway smooth muscle cells

Airway smooth muscle cells from healthy subjects (support from the University of Groningen)

BIOLOGICAL

Fibroblasts

Normal human fibroblast cell lines (commercial fibroblast lines)

Sponsors & Collaborators

• Research Council of Lithuania

  collaborator OTHER

• University of Groningen

  collaborator OTHER

• Lithuanian University of Health Sciences

  lead OTHER

Principal Investigators

• Kęstutis Malakauskas, Prof., Dr. · Lithuanian University of Health Sciences, Department of Pulmonology

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2017-06-01

Primary Completion

2020-11-10

Completion

2020-12-08

Countries

• Lithuania

Study Locations