NCT04722835

Lung Macrophage Populations and Functions in Chronic Obstructive Pulmonary Disease (COPD)-Susceptible Smokers

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 40 (estimated)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 40 Years – 75 Years
• Healthy volunteers: Accepted

Summary

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.

Detailed description

This is a pilot observational study of 20 subjects ≥40 years of age with smoking history of at least 20 pack-years (former or current) who have preserved spirometry, as defined by normal Forced Expiratory Volume (FEV1) / Forced Vital Capacity (FVC). Of the 20 subjects, 10 with and 10 without air trapping as determined by high and abnormal versus low and normal Residual Volume (RV) / Total Lung Capacity (TLC) measured by plethysmography. The cohort will undergo extensive clinical characterization including full Pulmonary Function Testing (PFT) and medical, symptom, activity, and quality of life questionnaires assessment including modified Medical Council Research (mMRC), COPD Assessment Test (CAT), Short Form-12 (SF12), and St. George's Respiratory (SGRQ) questionnaires. Subjects will undergo bronchoscopy with bronchoalveolar lavage (BAL) to obtain luminal macrophages and BAL fluid (BALF). Live BAL cells, BALF, and BAL cell RNA will be collected and stored in our biorepository for proposed studies. Molecular, functional, and transcriptomics analyses of luminal (alveolar) macrophages obtained by BAL (Aim 2) and protease activity measurement in serum and BALF will be performed (Aim 2) and will be examined against the clinical phenotype of the subjects, in particular air trapping-phenotype, to see if an underlying biological signature for susceptibility to develop COPD could be identified. To perform a more comprehensive molecular and functional phenotype examination of lung macrophages, additional methodologies will be developed including a second mass cytometry (CyTOF) panel for single-cell proteomics and CyTOF-based phagocytosis and efferocytosis assays to allow for performance of truly single-cell functional phenotyping of myeloid cells from BAL and lung tissue (Aim 1).

Conditions

• Copd
• Smoking
• Tobacco Use

Interventions

Type	Name	Description
PROCEDURE	Bronchoscopy with Bronchoalveolar Lavage (BAL)	1. 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.

Timeline

• Start date: 2021-03-01
• Primary completion: 2022-12-31
• Completion: 2022-12-31
• First posted: 2021-01-25
• Last updated: 2022-06-08

Locations

3 sites across 1 country: United States