Effects of Azithromycin on Airway Oxidative Stress Markers in Patients With Bronchiectasis

Study Overview
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Brief Summary
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The mechanism by which macrolide antibiotics have immune modifying effects independent from its antibacterial activity has not been well established. In the present work, the investigators will analyze the effect of long-term treatment with azithromycin (250 mg three times per week during three months) on airway oxidative stress markers in exhaled breath condensate of adult patients with stable non-CF bronchiectasis.

Detailed Description
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The mechanism by which macrolide antibiotics have immune modifying effects independent from its antibacterial activity has not been well established. In the present work, we will analyze the effect of long-term treatment with azithromycin (AZ) on airway oxidative stress markers in exhaled breath condensate of adult patients with stable non-CF bronchiectasis. Patients will be randomized in an open label model to receive AZ 250 mg three times per week during three months or nothing.Dyspnea (Borg scale), exacerbations (Nº) in the last three months, sputum volume (cc), sputum colour (15-point scale), and health related quality of life (Questionnaire St.George) will be measured in both groups before and after treatment. Lung function, sputum culture, CT scan (Bhalla score) and inflammatory markers in blood (ESR, PCR),exhaled air (Nitric Oxide,) and exhaled condensed air (pH, nitrites, isoprostane) will be assessed before and after treatment. Relationships between clinical and inflammatory markers will be studied

Official Title
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Effects of Long-Term Azithromycin Treatment on Airway Oxidative Stress Markers in Patients With Stable Non-Cystic Fibrosis Bronchiectasis

Conditions
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Bronchiectasis

Intervention / Treatment
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* Drug: Azithromycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previous diagnosis of bronchiectasis based on lung HRCT and clinical symptoms Clinically stable in previous four weeks without exacerbations Informed consent Exclusion Criteria: Bronchiectasis secondary to Cystic fibrosis, pulmonary surgical processes, immune deficiency, emphysema, allergic bronchopulmonary aspergillosis or diffuse interstitial pulmonary diseases Intolerance to macrolides or severe liver disease.

Ages Eligible for Study
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Minimum Age: 16 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 |
| --- | --- |
| No Intervention: Control<br>without azithromycin | |
| Active Comparator: azithromycin<br>treatment with azithromycin during three months | Drug: Azithromycin<br>* 250 mg three times a week during three months<br>* Other names: Before treatment or after treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Nitric oxide,8-isoprostane, pH, nitrites (NO2) and nitrates(NO3) in exhaled breath condensate. | Oxidative stress and NO metabolism in airway were investigated by measuring pH and the concentration of 8-isoprostane, nitrites (NO2-) and nitrates (NO3-) in EBC. Exhaled NO was also determined in all patients. | Before and after three months of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Exacerbations | exacerbations was defined by hospital admissions or antibiotics prescription | Before and after three months of treatment | 
| changes in lung function | Changes in FEV1, FVC. | Before and after three months of treatment | 
| colour and volume sputum, | In order to analyze sputum characteristics, three sterile containers were given to collect all sputum produced during three consecutive days. The average of the three days was calculated and expressed in mL/day. Sputum colour was scored using a scale developed and validated in our laboratory, which ranged from zero to fifteen: transparent (0), white (1), progressive intensities of yellow (2-7), green (8-10) and brown (10-15). Colour scores were decided after agreement between two investigators | Before and after three months of treatment | 
| Impact on functional capacity and health related quality of life | The impact on functional capacity and patient´s daily life was evaluated with the Medical Research Council Dyspnea scale (MRC) and the Spanish version of the Saint George's respiratory questionnaire of quality of life (SGRQ) | Before and after three months of treatment | 
| Changes in HRCT Lung scores | Standard lung HRCT scan was performed to quantify the extension of bronchiectasis | Before and after three months of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bronchiectasis, Oxidative stress markers, Airway inflammation