Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous disease that affects only a fraction of those who smoke tobacco. The origin of this variability in susceptibility to develop COPD is unclear, but understanding its underlying biology has important implications for our ability to design suitable preventative and therapeutic strategies for its management. This Department of Defense (DOD) discovery research proposes to develop methodologies and generate preliminary data needed to lay the foundation for a large study that would investigate the underlying biological susceptibility of those who smoke tobacco to develop COPD.
Ages between 40 to 75 years old.
History of at least 20 pack-years of smoking.
No diagnosis of COPD or asthma.
No spirometric evidence of airflow obstruction as determined by FEV1/FVC ratio ≥0.7.
Any history of IV drug use or inhalation of recreational drugs other than marijuana: A- within the past 20 years. B- more than 100 times IV drug usage. C- longer than 1 year usage.
Marijuana use >400 joints in lifetime or any within past 6 months.
Inability to walk briskly, run on treadmill, or pedal on ergometer to perform the study-required exercise level.
Pregnant/breast feeding.
The investigators will recruit both healthy, non-smoking subjects as well as subjects with at least 20 pack-years of smoking and air trapping.
Cohort
Prospective
Bronchoscopy with Bronchoalveolar Lavage (BAL)
Procedure/Surgery1. Bronchoscopy w/ (BAL): The bronchoscope will be introduced through mouth and directed into the right middle lobe bronchus for bronchial lavage. The BAL will be performed with two 60-mL aliquots (total of 120 ml) of saline in each of medial and lateral segments of Right Middle Lobe (RML) (total 240 ml lavage). 2. Albuterol Administration: The subjects will inhale 2 puffs of respiratory medication albuterol, then repeat the breathing test. 3. Peak Flow Measurement: Subjects will breathe in fully then out forcefully into the handheld device. 4. Pulmonary Function Test w/ Spirometry: will be used for determination of COPD and its severity. The PFT measures breathing capacity and lung function with different types of breathing maneuvers including flow-volume curve, single breath CO diffusing capacity, and total lung capacity. 5. Blood draw 6. Medical Health and Symptom Questionnaires 7. Physical Exam by study doctor to determine suitability and safety for participation.
Prevalence of macrophage sub-populations in airway lumen.
Number of macrophages measured by flow cytometry.
Functional status of macrophage sub-populations in airway lumen.
Relative percentage of macrophages measured by flow cytometry.
Symptomatic responses
Evidence for presence of mild exacerbation as measured by changes at or above the level of minimally clinically important difference (MCID) in each of the questionnaire's symptom score, 1-6, for the number of flare-ups in the past 3 years, with 6 being the worst outcome.
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University of California, San Francisco
Lead sponsor
United States Department of Defense
Collaborator
