Effects of Inhaled Corticosteroids on Sputum Bacterial Load in COPD

Study Overview
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Brief Summary
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Exacerbations are important events in the natural history of chronic obstructive pulmonary disease (COPD). Beside the acute (and prolonged) clinical impact, there is evidence that exacerbations negatively affect the natural history of the disease; e.g. lung function decline is accelerated in patients with frequent exacerbations. Bacteria are considered the most relevant cause of exacerbations, but there is evidence that viral infections are equally contributing. Either alone or in combination with viruses, airway bacterial load in stable COPD correlates with both the frequency of exacerbations and the decline in lung function. A long-term clinical trial recently showed that the regular treatment with inhaled corticosteroids (ICS) increases the risk of infectious events such as pneumonia, whereas it reduces the frequency of acute COPD exacerbations in COPD. In a recent study it was found that airway bacterial load increases over time (1 yr follow up) in stable COPD. In this study, virtually all patients (93%) were treated with ICS. This study is designed to evaluate whether long-term (1 year) ICS treatment increases viral and/or bacterial load in the sputum of COPD patients.

Official Title
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Long-term Effects of Inhaled Corticosteroids (ICS) Treatment on Sputum Bacterial and Viral Loads in Chronic Obstructive Pulmonary Disease (COPD) Patients

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Salmeterol/Fluticasone combination
* Drug: Salmeterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sixty stable moderate COPD patients (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2) requiring regular treatment with long-acting bronchodilators, according to international guidelines. GOLD stage 2 COPD patients will be enrolled providing they were steroid-free for the last 4 months Exclusion Criteria: Atopy Asthma Concomitant lung diseases (e.g. lung cancer) Acute infections of the respiratory tree in the previous 3 months including COPD exacerbation.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ICS/LABA group<br>Patients assigned to this arm will take bid 50/500 mcg fluticasone/salmeterol combination | Drug: Salmeterol/Fluticasone combination<br>* Salmeterol/Fluticasone 50/500 mcg 1 inhalation bid<br>|
| Active Comparator: LABA group<br>Patients assigned to this arm will take bid 50 mcg salmeterol | Drug: Salmeterol<br>* Salmeterol 50 mcg 1 inhalation bid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| comparison between groups of bacterial load in sputum | The primary outcome will measure changes in sputum bacterial load of COPD patients treated with inhaled corticosteroids in combination with long acting beta-2 bronchodilators (ICS/LABA group) compared with COPD treated only with long acting beta-2 bronchodilators (LABA group) | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlations between clinical outcomes and sputum viral and/or bacterial load | To evaluate whether sputum viral and/or bacterial load correlate with symptoms and need for rescue medication in stabile COPD. | 1 year | 
| Sputum viral and/or bacterial load and exacerbation rate | To evaluate whether changes in sputum viral and/or bacterial load (end of the study vs baseline) correlate with exacerbation rate in COPD patients | 1 year | 
| Sputum viral and/or bacterial load and lung function | To evaluate correlations between changes in sputum viral and/or bacterial load and changes in lung function over 1 year. | 1 year | 
| Airway inflammation and viral/bacterial load in COPD | To evaluate correlations between sputum inflammatory cell profiles and markers of airway inflammation (interleukin-6) and viral/bacterial load at stable stable conditions in COPD paetints. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Bacteria, Virus, Inhaled Corticosteroids