Innate Immunity in Ozone-induced Airway Inflammation in COPD

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States. Patients with COPD are routinely exposed to indoor and outdoor air pollution, which appears to cause escalation of their respiratory symptoms, a process called exacerbation, with resulting need to seek medical attention. This research plan proposes to evaluate the impact of lung immune cells in susceptibility to develop exacerbation through an experimental model of inhalational exposure using ambient levels of a component of air pollution (ozone) in COPD patients and longitudinal sampling of their lung immune cells.

A major cause of morbidity and mortality in COPD is exacerbation. The mechanisms underlying COPD exacerbation are poorly understood, but airway innate immune system has been implicated in its development. Air pollution contributes to development of COPD exacerbation, and exposure to ozone, a major component of air pollution, is associated with increased healthcare utilization among patients with COPD. Inhalation of ambient levels of ozone is known to affect airway innate immune system. This proposal sets out to characterize and investigate the role of innate immune system and in particular airway macrophages in ozone-induced COPD exacerbation through establishing an experimental model that employs controlled ozone exposure and longitudinal sampling via bronchoscopy. The research plan proposes to examine human immune cells trafficking in airways during the process of ozone-induced airway injury and inflammation in patients with COPD. The investigator's overall hypothesis is that inhalational challenge to a high ambient level of ozone in patients with COPD provides a safe human model of airway injury with resulting intraluminal shifts in the population and polarization of macrophages to study innate immunity processes relevant to ozone-induced COPD exacerbation.

Eligibility Criteria:
Inclusion Criteria:

Group 1:

1. No diagnosis of COPD or asthma.
2. No spirometric evidence of airflow obstruction as determined by FEV1/FVC ratio = or \>0.7.
3. Less than 1 pack year history of tobacco smoking and no tobacco use within the past 12 months.

Group 2:

1. No diagnosis of COPD or asthma.
2. No spirometric evidence of airflow obstruction as determined by FEV1/FVC ratio = or \>0.7.
3. Current smoker with history of at least 20 pack-years smoking.

Group 3:

1. Diagnosis of COPD as determined by GOLD criteria (FEV1/FVC ratio \<0.7).
2. COPD severity of GOLD stage II or III (FEV1 \>40% predicted).
3. Smoking Status: Former smokers with history of at least 20 pack-years smoking.

Group 4:

1. Diagnosis of COPD as determined by GOLD criteria (FEV1/FVC ratio \<0.7).
2. COPD severity of GOLD stage II or III (FEV1 \>40% predicted).
3. Smoking Status: Current smokers with history of at least 20 pack-years smoking.

During subject screening visit, Albuterol is used to determine whether the subjects have COPD based on the Global Initiative on Obstructive Lung Diseases (GOLD) criteria. Regardless of whether the subject has reversibility to Albuterol or not, if they have an abnormal ratio after inhalation of Albuterol, they would meet the GOLD criteria for COPD and will be included in the study.

Exclusion Criteria:

1. History of IV drug use or inhalation of recreational drugs other than marijuana:

   A- within the past 20 years. B- more than 100 usage. C- longer than 1 year.
2. COPD severity of GOLD stage IV.
3. Inability to walk briskly or run on treadmill or pedal on ergometer to perform the study-required moderate exercise level (achieve minute ventilation of 15 to 20 L/min/m2 body surface area).
4. Pregnant/breast feeding.
5. Serious and active heart conditions - defined by stable or unstable angina, recent myocardial infarction (within the last 2 years), active congestive heart failure, ischemic cardiomyopathy.
6. Malnourishment - determined by BMI less than 19. If subject has BMI greater or equal to 19, but has a history of malnourishment, study staff will measure albumin level of subject's blood after initial blood draw. Albumin level must be greater than 2.5 mg per deciliter, or subject will be excluded.
7. Liver cirrhosis.
8. History of chronic active Hepatitis B or C
9. On visits where moderate sedation is preformed, subject are required to have an escort home. Inability to secure a ride home will result in the subject being ineligible for the study.