Comparison of Alveolar Macrophages in Healthy Individuals Versus Individuals With COPD
Condition: Pulmonary Disease, Chronic Obstructive; Lung Diseases, Obstructive
MeSH terms: Lung Diseases; Pulmonary Disease, Chronic Obstructive; Lung Diseases, Obstructive
Study type: Observational

Summary: 
      This study group forms the normal subject control group in an experiment designed to
      determine whether the alveolar macrophages (AMø) of patients with chronic obstructive
      pulmonary disease (COPD) show abnormal responsiveness to bacterial and viral products.
      Specifically, the study will determine the dose-response characteristics of AMø for
      production of interleukin (IL)-6, IL-18, and IL-23 (pro-inflammatory cytokines) on
      stimulation by purified lipopolysaccharide, a synthetic lipopeptide (PAM3-Cys), or poly I:C.
      These stimuli mimic the response to Gram-negative bacteria, Gram-positive bacteria, and RNA
      viruses, respectively. Results of the AMø from these healthy volunteers will be compared with
      AMø of COPD patients and smokers (or ex-smokers) with normal pulmonary function; those
      samples are being obtained during clinically indicated bronchoscopies under a separate
      consent form.
    

Detailed description: 
      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.
    

Intervention name(s): blood drawing; fiberoptic bronchoscopy
Intervention type(s): Procedure; Procedure
Intervention description(s): blood will be drawn on the entry visit and will starting the intravenous (IV) line on the day of bronchoscopy; A flexible instrument will be passed through the mouth and into the lungs. Portions of the lungs will be washed, by injecting and immediately suctioning out a small amount of fluid. The entire return will be used for research purposes, and no results will be reported to the participant. Bronchoscopy is performed once.
Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Healthy volunteers
      
Keywords: Chronic Obstructive Pulmonary Disease; COPD