Bronchitis, Chronic, Occupational Diseases, Pulmonary Disease, Chronic Obstructive, Tobacco Use Disorder
Conditions
Keywords
Pulmonary disease, chronic obstructive, Airway macrophages, Sputum milieu, Airway inflammation, Occupational diseases
Brief summary
Airway macrophage impairment is a central feature in the immunopathogenesis of chronic obstructive pulmonary disease, regardless of smoking status.
Detailed description
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.
Interventions
None listed
Sponsors
VA Nebraska Western Iowa Health Care System
University of Nebraska
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of airway macrophages for immune cell surface marker expression and phagocytic ability in adults with airflow obstruction & healthy controls | One year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of airway macrophages for cytokine responsiveness in adults with airflow obstruction & healthy controls | One year | Determine if airway macrophages from adult participants with airflow obstruction demonstrate impaired cytokine responsiveness compared to healthy controls. |
| Comparison of airway macrophage cytokine responsiveness to whole blood cytokine responsiveness | One year | Determine if airway macrophage cytokine responsiveness is comparable to whole blood cytokine responsiveness. |
| Determining if immunomodulators in airway sputum milieu f predict airway macrophage phenotype and function | One year | To determine if airway sputum milieu for potential immunomodulators predict airway macrophage phenotype and function. |
Countries
United States
Outcome results
None listed