Clinical Trials Logo

Clinical Trial 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.


Clinical Trial Description

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.

ECM is a building block between airways and lung parenchyma. It plays a crucial role in the maintenance of pulmonary structure and functions influencing the distribution and adhesion of inflammatory cells, fluid balance, elasticity and can act as a resource of inflammatory mediators. In asthma, predominant eosinophilic airway inflammation can result the dysregulation of ECM, which are identified as altered quantitative and qualitative composition of ECM, activated molecular signaling pathways which are responsible for triggered ECM proteins production. The main sources of ECM proteins in lungs are pulmonary fibroblasts and ASM cells. In asthma, fibroblasts are responsive to many inflammatory cytokines which activate and promote fibroblasts proliferation, contractility and cellular differentiation to myofibroblasts form with up-regulated rate of matrix production. In turn, activated fibroblasts secrete cytokines IL-1β, IL-33, CXC, CC chemokines, various types of matrix metalloproteinases (MMPs) as well as reactive oxygen species. These factors allow fibroblasts to assist in the activation and migration of resident immune cells and endow fibroblast roles in chemical and cell-mediated immunity, acute and chronic inflammation, extravasation of immune cells into connective tissue of the lungs. The ASM cells are also the strong contributor to the ECM protein pool in the lungs - they can produce the variety of ECM proteins contributing to the tissue structure and elasticity which are seen unbalanced in asthma. While fibroblasts and ASM cells determine ECM proteins composition, the ECM in turn can affect the structural cells behavior in lung tissue. The role of cell-matrix interactions represents an area for active investigation on the ability of lung matrix to prime the structural pulmonary cells.

The excess of ECM proteins deposition is associated with activation of profibrotic factor transforming growth factor-beta 1 (TGF-β1) mediated WNT and Smad signaling pathways. Highest levels of TGF-β1 in airways are released by eosinophils - the main inflammatory cells in asthma pathogenesis. During stable asthma and especially allergen provoced acute asthma episodes eosinophils infiltrate into the airways, enhancing local levels of TGF-β1 and other various cytokines, chemokines and growth factors near the connective tissue and ASM bundles. However, how eosinophil-released mediators induce ECM dysregulation leading to development of airway remodeling are not investigated part of asthma pathogenesis.

Asthma still cannot be cured, but appropriate management can control the disease severity. Better understanding in development of asthma is the main objective which must to be pursued. Based on this rationale the investigators aimed to investigate eosinophilic airway inflammation mediated production of ECM proteins and MMPs, activity for their release responsible molecular signaling pathways, and how dysregulated ECM affect fibroblasts and ASM cells proliferation, migration, differentiation and contractility in asthma. Trying to understand and control the development of asthma the investigators will use models of combined cells cultures estimating ECM homeostasis in stable and acute asthma. Blocking with specific inhibitors of WNT and Smad signaling pathways, potentially responsible for ECM proteins and MMPs production, will help to find the controlling mechanisms of ECM dysregulation. Therefore, evaluation of ECM proteins degradation fragments and levels of MMPs will help to estimate an applied value of these circulating biomarkers in asthma patients. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03388359
Study type Interventional
Source Lithuanian University of Health Sciences
Contact Kestutis Malakauskas, Prof., Dr.
Phone +37037326737
Email kestutis.malakauskas@lsmuni.lt
Status Recruiting
Phase N/A
Start date June 1, 2017
Completion date December 8, 2020

See also
  Status Clinical Trial Phase
Completed NCT03850626 - Validation of Combined Symptom Medication Score (cSMS) in Allergic Patients
Completed NCT02911688 - Effect of Gamma Tocopherol Enriched Supplementation on Response to Inhaled O3 Exposure Phase 2
Active, not recruiting NCT01776177 - The REALITY Study - a Real-life Long-term Analysis of Xolair Therapy N/A
Completed NCT00485576 - Safety and Efficacy Study of Eculizumab in Patients With Mild Allergic Asthma Phase 2
Completed NCT00736801 - Effect of Salmeterol on Brain-Derived Neurotrophic Factor (BDNF) Concentrations in Asthma N/A
Completed NCT00515775 - Influence of a Inhaled Corticosteroid Therapy Versus Corticosteroid + LABA Therapy on the FeNO of Asthmatic Children N/A
Completed NCT04259164 - Anti-inflammatory Effects Glycopyrronium Phase 3
Active, not recruiting NCT04619017 - Airway Immune Response to Allergens (Use Lay Language Here) Phase 1
Completed NCT01699594 - Change in Airway Responsiveness After Allergen Exposure N/A
Completed NCT00999466 - The Tolerability and Effects of AZD8848 in Allergic Asthma Subjects Challenged With Inhaled Allergen Phase 2
Completed NCT01353755 - 2nd Pivotal Study rPhleum - Adults and Adolescents With Rhinoconjunctivitis +/-Controlled Asthma Phase 3
Completed NCT00434434 - A Study of Omalizumab in the Prevention of Allergen Induced Airway Obstruction in Adults With Mild Allergic Asthma Phase 2
Completed NCT00492076 - Efficacy and Safety Trial of Subcutaneous Immunotherapy in Mite Induced Asthma Phase 4
Completed NCT00490425 - Prevention of Asthma and Allergy by Probiotic Lactobacillus GG Phase 4
Completed NCT00829179 - Role of RhuMab-E25 in Reducing Exhaled Nitric Oxide (NO) in Allergic Asthma Phase 3
Recruiting NCT04542902 - Non-coding RNAs Analysis of Eosinophil Subtypes in Asthma N/A
Recruiting NCT04109534 - Effect of a Dietary Fatty Acid Supplementation on Symptoms and Bronchial Inflammation in Patients With Asthma N/A
Active, not recruiting NCT05186025 - Tyrosine Allergoid Paediatric and Adult Study
Withdrawn NCT03307278 - House Dust Mite Induced Inflammasome Activation on Corticosteroid Resistance N/A
Enrolling by invitation NCT06151938 - Evaluate Measurement Instruments Relevance in Assessing Effectiveness of ACARIZAX® in House Dust Mite Allergic Rhinitis