Airway Macrophages and Sputum Milieu in Adult Subjects With Airflow Obstruction



Status:Completed
Conditions:Bronchitis, Chronic Obstructive Pulmonary Disease, Smoking Cessation, Pulmonary, Tobacco Consumers
Therapuetic Areas:Pulmonary / Respiratory Diseases
Healthy:No
Age Range:50 - 75
Updated:4/2/2016
Start Date:August 2008
End Date:June 2009
Contact:Jill A Poole, MD
Email:japoole@unmc.edu
Phone:402-955-3817

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

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.

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
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