Comparison of Alveolar Macrophages in Healthy Individuals Versus Individuals With COPD

BACKGROUND:

COPD is one of the most pressing healthcare problems facing our nation. Acute exacerbations
of COPD (AE-COPD) are responsible for the bulk of healthcare costs, and much of the
morbidity and decline in health status among individuals with this common disease. The lack
of accepted animal models of AE-COPD necessitates novel approaches using human samples.
Advances in the understanding of the pathogenesis have been slowed, in part, due to
controversy as to how exacerbations should be defined. The prevailing paradigm has defined
AE-COPD as event-based. Such definitions clearly identify groups of patients with
accelerated loss of pulmonary function and increased mortality. However, limited data show
that symptom-based definitions of AE-COPD also capture episodes inducing significant
morbidity and functional decline, and hence of concern to patients. Fundamental mechanisms
are lacking to explain AE-COPD defined by either means.

Controversy also surrounds triggers of AE-COPD. Bacteria and viruses are involved in some
episodes, but the relative importance of each is intertwined with disputes over the
definition of AE-COPD. Progress at linking specific pathogens to molecular pathogenesis has
been slow, both due to their diversity, and to the high rates of bacterial colonization of
patients with COPD, even in the stable state. Moreover, in many AE-COPD cases, no pathogen
can be identified. Without negating the value of analyzing infections with specific
species of pathogens, it appears that progress in molecular pathogenesis could be
accelerated by focusing on unifying features of the pulmonary immune response during
AE-COPD.

DESIGN NARRATIVE:

Bronchoscopies will be performed on healthy volunteers. Subjects are reimbursed $30 for the
initial visit and $150 at completion of the bronchoscopy to help defray travel expenses and
for the time spent participating as a volunteer.

Inclusion criteria:

- Healthy individuals with normal pulmonary function as defined by ATS criteria (entry
spirometry)

Exclusion criteria:

- Unstable cardiovascular disease

- Other systemic disease in which survival of more than 2 years is unlikely

- Mental incompetence or active psychiatric illness

- Currently taking more than 20 mg/day of Prednisone

- Participation in another experimental protocol within 6 weeks of study entry

- Asthma

- Cystic fibrosis

- Clinically significant bronchiectasis

- Lung cancer

- Other inflammatory or fibrotic lung disease