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

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Azithromycin; Drug: Placebo

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 53

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Community

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Azithromycin-treated; Participants in the COPD Network Macrolide Study who received azithromycin for 1 year.	Drug: Azithromycin; 250 mg daily
Placebo-treated; Participants in the COPD Network Macrolide Study who received placebo for 1 year.	Drug: Placebo; Daily

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: James E. Blalock, PhD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: October 24, 2007
• First Submitted That Met QC Criteria: October 24, 2007
• First Posted (Estimate): October 25, 2007

Study Record Updates

• Last Update Posted (Actual): September 29, 2017
• Last Update Submitted That Met QC Criteria: August 31, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: COPD; Chronic Obstructive Pulmonary Disease; Exacerbation; Macrolide
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Inflammation; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: 1425; R01HL090999-01 (U.S. NIH Grant/Contract); HL090999-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No