Lung Macrophage Populations and Functions in COPD-Susceptible Smokers
Abstract
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that affects only a subset of those who smoke tobacco. Recent studies have documented that the susceptible smokers are more likely to show evidence of air trapping before any other pathologies of COPD, such as spirometric airflow obstruction, manifest themselves. However, the underlying biology that predisposes the non-obstructed smokers with air trapping to develop COPD has not been elucidated. The main objective of this proposal is to develop methodology and preliminary data that would lay the foundation for a longitudinal cohort study to examine the underlying biological processes that may render the non-obstructed smokers with air trapping their susceptibility to develop COPD. This pilot project focuses on development of mass cytometry (Cytometry by Time of Flight or CyTOF) methodologies for phenotypical and functional characterization of lung myeloid cells and generating preliminary data on how lung myeloid cells may contribute to disease progression in susceptible smokers. The project had three major aims including development of CyTOF methodologies (Aim 1), followed by deployment of those methodologies for molecular and functional phenotyping of airway myeloid cells (luminal cells obtained by bronchoalveolar lavage or BAL) (Aim 2) and lung tissue cells (tissue resident cells obtained from surgically resected lung samples) (Aim 3). In the previous years, we performed BAL in volunteer human research subjects with history of smoking but without COPD (non-obstructed smokers) with and without air trapping, optimized our CyTOF panel for molecular phenotyping of airway (BAL) myeloid cells, performed CyTOF analysis of BAL myeloid cells, and generated a publication from those data. Over the course of the past year, we continued to collect lung tissue samples from donors who were undergoing surgical lung resection and managed to achieve the target number of subjects planned.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2023
- Accession Number
- AD1215018
Entities
People
- Mehrdad Arjomandi
Organizations
- University of California Regents