Pathogenetic Mechanisms of Chronic Obstructive Pulmonary Diseases

Study Overview
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Brief Summary
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Asthma and chronic obstructive pulmonary disease(COPD) are common diseases, which tend to even increase in many countries. Both from a clinical and a pathophysiological point of view, this is an important issue. However, an understanding of the relationship between the complex array of cells and mediators involved in asthma and COPD is not yet fully dissected which makes difficult to find a specific and sensitive panel of biomarkers that can reflect intensity of these pathological processes and can help to predict the individual outcome.

Detailed Description
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Objectives: To evaluate the patterns of pathophysiology and genetic predisposition of COPD and asthma Tasks: To evaluate patients that respond to corticosteroids and those who do not Compare the inflammatory markers: of COPD and asthma patients before and after treatment with inhaled glucocorticoids of COPD and asthma patients that respond to inhaled glucocorticoids and those who do not of nonsmokers and smokers asthma patients To identify a small set of markers that can be used to predict corticosteroid-treatment response in patients with COPD. To evaluate epigenetic factors To compare gene mutation and polymorphism between study groups To evaluate the relationship between genetic predisposition and pathophysiology, clinical symptoms To evaluate the relationship between patterns of pathophysiology and clinical symptoms, lung function, quality of life in patients with chronic obstructive pulmonary diseases. Visit 1 Written informed consent will be obtained A full medical, surgical, smoking, labour history. A physical examination will be performed Resting SaO2 will be measured, exhaled nitric oxide (FENO) Chest X-ray Patient will fulfil questionnaires Spirometry and bronchodilatation test Sputum induction and samples will be performed Visit 2 • Blood samples for blood clotting test and immunological markers will be taken• Cough inhalation challenge Visit 3 Patient will be hospitalized to the Department of Pulmonology and Immunology Blood samples for genetic analysis will be taken Urinary samples will be taken• Methacholine challenge test Polysomnography Bronchoscopy (biopsy and BAL) Study drug administration Visit 4 and 5 Adverse events, COPD or asthma exacerbation, concomitant medications will be recorded, exhaled nitric oxide (FENO) Spirometry Patient will fulfil questionnaires Cough inhalation challenge Visit 6 Patient will fulfil questionnaires Spirometry and bronchodilatation test. Sputum induction and samples will be performed Visit 7 • Blood samples for blood clotting test, immunological and genetic analysis will be taken• Cough inhalation challenge Visit 8 Patient will be hospitalized to the Department of Pulmonology and Immunology Urinary samples will be taken• Methacholine challenge test Polysomnography Bronchoscopy (biopsy and BAL) Further treatment administration

Official Title
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Evaluation of Pathogenetic Mechanisms of Chronic Obstructive Pulmonary Diseases

Conditions
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COPD, Asthma

Intervention / Treatment
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* Drug: comparison of treatment effect on different markers


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female outpatients aged 40-80 years inclusive. An established clinical history of COPD as defined by the GOLD guidelines. COPD patients with a baseline (pre-bronchodilator) FEV1 40-80% of predicted normal value; post-bronchodilator FEV1/FVC ratio ≤ 70% predicted. COPD patients with a smoking history (current or ex-smoker) of ≥10 pack years or those who have exposure to occupational dust and chemicals An established clinical history of asthma defined by the GINA recommendations. Subjects with out hypoxemia (all subjects must have an O2 saturation ≥88% on room air). Control (healthy) subjects with baseline FEV1 >80% of predicted normal value A female is eligible to participate this study if she is of non-childbearing potential, or childbearing potential has a negative pregnancy test. Patients who did not use inhaled and oral corticosteroids 6 weeks and/or long acting bronchodilators 4 weeks before study. Exclusion Criteria: There is a current respiratory disorder other than COPD and asthma (e.g. lung cancer, sarcoidosis, active tuberculosis etc.) Subjects who have had a COPD and asthma exacerbation or respiratory infection in the 4 weeks before Visit 1. Subjects with a chest X-ray indicating diagnosis other than COPD or asthma that might interfere with the study. Subjects who are unable to stop treatment with inhaled, and oral corticosteroids 6 weeks and/or long acting bronchodilators 4 weeks before study. Subjects receiving treatment with cromolyn sodium or nedocromil, oral beta2 - agonists, long acting anticholinergic, leucotriene modifiers Subjects who have had lung surgery. Subjects with bleeding diathesis. Subjects receiving treatment with long-term oxygen therapy. Subjects with serious, uncontrolled diseases those are uncontrolled on permitted therapy.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Budesonide<br>patients who gave their agreement were randomised to 3 months treatment with either inhaled budesonide (400 µg BD) or placebo | Drug: comparison of treatment effect on different markers<br>* inhaled budesonide (400 µg BD) or placebo BD<br>* Other names: Budesonide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in inflammatory cell numbers and inflammatory markers at 3 months | inflammatory cell numbers and inflammatory markers (cytokines, chemokines, etc.) in different tissue compartments (induced sputum, BAL, bronchial biopsies, blood) will be measured at baseline and 3 months after treatment with budesonide and compared with those from healthy subjects | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| network analysis of quantitative proteomics of bronchial biopsies | pathways analysis will be performed on proteins obtained from bronchial biopsies from asthmatics and COPD patients at baseline and 3 months after treatment | 3 months | 
| change of lung function, exNO after 3 months of treatment | lung function measurements (spirometry, bronchial responsiveness measurement, capsaicin test) at baseline and 3 months after treatment with budesonide | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Asthma, Pathophysiology, Genetics, Phenotype, Treatment response