Airway Macrophages and Sputum Milieu in Adult Subjects With Airflow Obstruction

Study Overview
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Brief Summary
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Airway macrophage impairment is a central feature in the immunopathogenesis of chronic obstructive pulmonary disease, regardless of smoking status.

Detailed Description
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In the United States, a variety of farming operations can generate significant amounts of dust. Chronic organic dust exposure to workers in this industry can result in several respiratory health conditions including chronic bronchitis, chronic obstructive pulmonary disease (COPD), and exacerbations of asthma. Organic dust is a complex mixture containing particulate matter and microbial-associated components from gram positive and gram negative bacteria. Airway macrophages are key innate immune cells that are rapidly activated by exposure to inhaled toxins and organic dust. The literature indicates that subjects with tobacco-induced chronic bronchitis/COPD have alveolar macrophages that have impaired function. It has been hypothesized that the impaired lung macrophage function may contribute to the increased susceptibility to infections and chronic bacterial colonization that is a central feature in subjects with chronic bronchitis/COPD. It is unknown at this time if impaired macrophage function is secondary to tobacco-induced effects, or is a central pathologic feature of chronic bronchitis/COPD. We will explore the expression of innate immune cell surface molecule expression involved in antigen presentation, phagocytic ability, and ex vivo cytokine responses in airway macrophages obtained by induced sputum. We will also collect blood to determine if ex vivo stimulation of blood mimics the inflammatory responses observed with airway macrophages. Comparisons to our past findings in vitro studies, which demonstrated that repetitive organic dust exposure impairs monocyte derived macrophage immune cell surface markers and function, could then be made. This information could lead to future investigations centered on therapeutic interventions to prevent or reverse the underlying lung disease experienced by farmers in this industry.

Official Title
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Airway Macrophages and Sputum Milieu in Adult Subjects With Airflow Obstruction

Conditions
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Pulmonary Disease, Chronic Obstructive, Bronchitis, Chronic, Occupational Diseases, Tobacco Use Disorder

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Medically stable to participate in induced sputums Group One: Smoked less than 100 cigarettes in their lifetime Quit smoking greater than 10 years ago Pre-bronchodilator FEV1/FVC > 70% Pre-bronchodilator FEV1 % predicted > 80% Group Two: Greater than a 20-pack year tobacco history Smoked in the last two years Post-bronchodilator FEV1/FVC < 70% Group Three:Have less than a 20-pack year tobacco history Quit smoking greater than 20 years ago Post-bronchodilator FEV1/FVC < 70% Exclusion Criteria: Personal history of lung cancer Pregnancy Personal history of autoimmune disease Currently taking oral/parental corticosteroids Personal history of upper or lower respiratory tract infection in the prior four weeks

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group One<br>Healthy non-smoking controls | |
| Group Two<br>Smoking adults with chronic bronchitis/chronic obstructive pulmonary disease | |
| Group Three<br>Non-smoking adults with chronic bronchitis/chronic obstructive pulmonary disease | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of airway macrophages for immune cell surface marker expression and phagocytic ability in adults with airflow obstruction & healthy controls | Determine if airway macrophages from adult participants with airflow obstruction demonstrate impaired innate immune cell surface marker expression and phagocytic ability compared to healthy controls. | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of airway macrophages for cytokine responsiveness in adults with airflow obstruction & healthy controls | Determine if airway macrophages from adult participants with airflow obstruction demonstrate impaired cytokine responsiveness compared to healthy controls. | One year | 
| Comparison of airway macrophage cytokine responsiveness to whole blood cytokine responsiveness | Determine if airway macrophage cytokine responsiveness is comparable to whole blood cytokine responsiveness. | One year | 
| Determining if immunomodulators in airway sputum milieu f predict airway macrophage phenotype and function | To determine if airway sputum milieu for potential immunomodulators predict airway macrophage phenotype and function. | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary disease, chronic obstructive, Airway macrophages, Sputum milieu, Airway inflammation, Occupational diseases