Airway Macrophages and Sputum Milieu in Adult Subjects With Airflow Obstruction

• Determine if airway macrophages from adult subjects with airflow obstruction demonstrate impaired innate immune cell surface marker expression and phagocytic ability compared to healthy controls. [ Time Frame: One year ] [ Designated as safety issue: No ]
  

• Determine if airway macrophages from adult subjects with airflow obstruction demonstrate impaired cytokine responsiveness compared to healthy controls. [ Time Frame: One year ] [ Designated as safety issue: No ]
  
• Determine if airway macrophage cytokine responsiveness is comparable to whole blood cytokine responsiveness. [ Time Frame: One year ] [ Designated as safety issue: No ]
  
• To determine if airway sputum milieu for potential immunomodulators predict airway macrophage phenotype and function. [ Time Frame: One year ] [ Designated as safety issue: No ]
  

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.