Pathogenetic Mechanisms of Chronic Obstructive Pulmonary Diseases
Condition: COPD; Asthma
MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Study type: Interventional

Summary: 
      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: 
      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
    

Intervention name(s): comparison of treatment effect on different markers
Intervention type(s): Drug
Intervention description(s): inhaled budesonide (400 µg BD) or placebo BD
Other intervention name(s): Budesonide
Intervention MeSH terms: Budesonide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Keywords: COPD; Asthma; Pathophysiology; Genetics; Phenotype; Treatment response