Association Between Increased Oxidative Stress, Anti-Inflammatory Fatty Acid Formation, and Airway Infection in People With Asthma and Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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Chronic obstructive pulmonary disease (COPD) and asthma are common respiratory diseases in which people experience long-term inflammation of the lungs. Exacerbations, or prolonged worsening of symptoms, of asthma and COPD are often life-threatening and can lead to frequent need for hospitalization. Even with the proper use of bronchodilators, corticosteroids, and other currently available medications, clinical responses among people with COPD and asthma are variable. There remains a significant unmet clinical need for new therapeutic approaches and insights, including the identification of biomarkers to accurately assess the presence of airway infection and intensity of airway inflammation. This study will investigate potential natural biological causes and new biomarkers for increased susceptibility to persistent airway infection in asthma and COPD.

Detailed Description
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COPD and asthma are chronic lung diseases that result in impaired air flow in the lungs, often causing coughing, wheezing, and shortness of breath. In uncontrolled COPD and asthma, people may experience a rapid worsening of symptoms, which may include fever, difficulty breathing, and chest pain. These exacerbations are the most serious expression of asthma and COPD and are usually caused by lung infections or air allergens. However, the biological basis for susceptibility to airway infection and inflammation is not well understood. Increased oxidative stress within the airways has been linked to several airway diseases. This increase in oxidative stress may reduce production of key fatty acid anti-inflammatory mediators. In turn, this may disrupt the airway's natural immune response mechanisms, making the airways more vulnerable to infection or inflammation during COPD and asthma exacerbations. This ancillary study will determine whether susceptibility to persistent airway infection in asthma and COPD stems from increased oxidative stress that impairs the natural formation of protective fatty acid mediators. This ancillary study will use data biological samples, including blood and sputum, from participants currently enrolled in the Macrolides in Asthma (MIA; NCT00318708) and the Antileukotriene Therapy for COPD Exacerbations (KIA; NCT01097694). Biological samples will undergo fatty acid mediator analysis and RNA isolation. There will be no study visits for this study.

Official Title
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Ancillary Study of Oxidative Stress and Anti-Inflammatory Lipids in Airway Disease in the MIA (ACRN) and LEUKO (CCRN) Trials

Conditions
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Asthma, Pulmonary Disease, Chronic Obstructive

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No change from the MIA and LEUKO trials Exclusion Criteria: No change from the MIA and LEUKO trials

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| MIA 1<br>Participants from the MIA trial who are polymerase chain reaction (PCR) negative and have received treatment with placebo | |
| MIA 2<br>Participants from the MIA trial who are PCR negative and have received treatment with the antibiotic clarithromycin | |
| MIA 3<br>Participants from the MIA trial who are PCR positive and have received treatment with placebo | |
| MIA 4<br>Participants from the MIA trial who are PCR positive and have received treatment with the antibiotic clarithromycin | |
| LEUKO 1<br>Participants from the LEUKO trial who have received treatment with placebo | |
| LEUKO 2<br>Participants from the LEUKO trial who have received treatment with zileuton | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 8-isoprostane Levels as Biochemical Markers for Nonenzymatic Oxidative Stress in Asthma | 8-isoprostane levels in sputum | Measured at completion of sample analysis | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Airway, Inflammation, Infection, Lipid Mediators, Oxidative Stress