Airway Macrophages and Sputum Milieu in Adult Subjects With Airflow Obstruction

Completed

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

• Registration Number: NCT00871637
• Lead Sponsor: University of Nebraska

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.

Study Timeline

• Study Start: 2008-08-01
• Study First Submitted: 2009-03-26
• Study First Submitted QC: 2009-03-26
• Study First Posted: 2009-03-30
• Primary Completion: 2009-06-01
• Study Completion: 2009-06-01
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-01
• Last Update Posted: 2023-09-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

University of Nebraska; 🇺🇸 Omaha, Nebraska, United States