Effect of Macrolide Antibiotics on Airway Inflammation in People With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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Chronic obstructive pulmonary disease (COPD) is a chronic lung disease. Azithromycin, an antibiotic, may be beneficial at reducing the symptoms and severity of the disease. This study will analyze previously collected study data to evaluate the anti-inflammatory properties of azithromycin and determine how azithromycin affects the frequency and severity of COPD exacerbations.

Detailed Description
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COPD is a disease in which the lung airways are partly damaged and obstructed, making it difficult to breathe. The most common cause is cigarette smoking, but breathing in other types of lung irritants, including pollution, dust, and chemicals, over a long period of time may also contribute to COPD. It is the fourth leading cause of death in the United States. Symptoms include coughing, excess mucus production, shortness of breath, wheezing, and chest tightness. Some bacterial infections may worsen COPD exacerbations. Current studies are examining if the macrolide antibiotic azithromycin may be beneficial at reducing the frequency and/or severity of COPD exacerbations. Azithromycin also has anti-inflammatory properties that may reduce the severity of COPD exacerbations by inhibiting the matrix metalloprotease (MMP)-catalyzed breakdown of collagen and the subsequent generation of proline-glycine-proline (PGP), a substance produced in response to collagen breakdown. An increase in PGP levels may indicate an increase in inflammation, which can worsen COPD symptoms. NHLBI's COPD Network Macrolide study includes people with COPD who were randomly assigned to receive either azithromycin or placebo for 1 year. For this current study, researchers will examine the Macrolide participants' previously collected blood samples, sputum samples, and study data, including information on COPD exacerbations and azithromycin effects. The purpose of this study is to examine the anti-inflammatory properties of azithromycin in people with COPD.

Official Title
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Effect of Macrolide Treatment on a Novel Pathway of Neutrophilic Inflammation in COPD

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Azithromycin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participating in the COPD Network Macrolide study Clinical diagnosis of at least moderate COPD Cigarette consumption of 10 pack years or more Exclusion Criteria: Diagnosis of asthma Predicted life expectancy of less than 3 years History of hypersensitivity to macrolide antibiotics Long-term kidney insufficiency Long-term liver insufficiency Prolonged QT interval Use of medications that may prolong the QT interval

Ages Eligible for Study
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Minimum Age: 40 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Azithromycin-treated<br>Participants in the COPD Network Macrolide Study who received azithromycin for 1 year. | Drug: Azithromycin<br>* 250 mg daily<br>|
| Placebo-treated<br>Participants in the COPD Network Macrolide Study who received placebo for 1 year. | Drug: Placebo<br>* Daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of PGP From Sputum Samples of COPD Patients Being Treated With Azithromycin. | Nasopharyngeal swabs were obtained to determine if there is a reduction in PGP levels (including both PGP & Neutrophil-PGP) after chronic treatment with azithromycin. Unblinding of the parent trial revealed that there were 18 sputum samples from 13 placebo-treated participants and 14 sputum samples from 8 azithromycin-treated participants collected at months 1 through 12 of treatment (with sputum samples not being available, this greatly reduced the sample size). | Baseline to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease, COPD, Exacerbation, Macrolide