Modification Of Disease Outcome In COPD

Study Overview
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Brief Summary
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The hypothesis to be tested of this study is that treatment with fluticasone propionate leads to an initial improvement in symptoms, quality of life and lungfunction and a reduction in airways hyperresponsiveness. The continued decline of lungfunction in COPD may not be influenced by longer lasting treatment. Addition of salmeterol will augment the initial benefits of fluticasone without changing the longterm decline in lungfunction.

Detailed Description
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Aim The primary aim of this study was to investigate whether short-term treatment with inhaled corticosteroids in COPD results in greater improvements in airway pathology, thereby leading to larger clinical benefits, than continuous long-term treatment. To that end, the outcome variables included features of airways inflammation and remodelling as well as clinical symptoms, exacerbations, quality of life, decline in FEV1, bronchial responsiveness, and pharmaco-economics. The secondary aim of the study was to examine the histopathological and clinical benefits of the combined treatment with an inhaled steroid and a long-acting ß2-agonist in COPD. Methods Patients. Patients with COPD (45-75 yr, >10 pckyr) not using inhaled steroids for the past 3 months were recruited. Design. In a prospective, longitudinal, double blind, 4-arm study, the patients were followed during 2.5 years (Figure 1). They were treated with high dose inhaled corticosteroids (500 g fluticasone bid), combined inhaled steroids+long-acting ß2-agonist (500 µg fluticasone+50 µg salmeterol) or placebo for 6 months. Half of the patients in the steroid group continued their treatment with steroids for another 2 years, whereas the other half received placebo. The combination therapy and placebo groups remained unaltered treatment up to 2.5 years. Measurements. Symptoms, exacerbations, QOL questionnaires and spirometry were monitored every 3 months. Peripheral blood eosinophils, IgE, exhaled NO, bodyplethysmography, CO-diffusion capacity, PC20 methacholine, sputum induction and bronchoscopy were performed at 0, 6, and 30 months. In BAL and induced sputum we are measuring cell differentials and their state of activation. Immunohistochemistry is being performed in bronchial biopsy specimens, staining for markers on infiltrative and resident cells, and morphometric analysis will allow airway remodelling to be quantified, by using a computerized image analysis system. The effects of treatment will be analyzed by relating the observed changes in clinical and pathophysiological outcome, to those in cellular and histological outcome by using linear mixed statistical models.

Official Title
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Modification of Disease Outcome in COPD. Shortterm Versus Longterm Treatment With Inhaled Corticosteroids, Either or Not Combined With a Long-Acting Beta2-Agonist.

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: fluticasone 500 mcg
* Drug: fluticasone 500 mcg + salmeterol 50 mcg


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: COPD patients with > 10 pack years. Written informed consent. Able to complete a diary card. At least one of the following symptoms: chronic cough, chronic sputum production, frequent exacerbations, or dyspnoea at exertion. Postbronchodilator FEV1 below 90% confidence interval of predicted and postbronchodilator FEV1/FVC below 90% confidence interval of predicted. Exclusion criteria: No oral corticosteroids 3 months prior to the study or maintenance treatment with corticostroids 6 months prior to the study. No history of asthma, lung diseases other than COPD, other diseases likely to interfere with the study.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: fluticasone 500 mcg|nan|
|Drug: fluticasone 500 mcg + salmeterol 50 mcg|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammation: localisation, numbers and profile of neutrophils, eosinophils, macrophages, and CD8+T cells in bronchial biopsy specimens after 6 months and 2.5 years treatment. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical: symptoms, exacerbations, quality of life, lung function, 6 min walking test. Inflammation: markers in sputum and BAL, profile of epithelial cells, remodeling. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD inflammation sputum lung function biopsy