1. Introduction
inflammatory disorder of the lungs, COPD
CHRONIC OBSTRUCTIVE PULMONARY DISEASE, INFLAMMATORY DISORDER, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, COPD, PATHOGENESIS
These authors contributed equally to this work.Background: Macrophages and monocytes orchestrate inflammatory processes in the lungs. However, their role in the pathogenesis of chronic obstructive pulmonary disease (COPD), an inflammatory condition, is not well known. Here, we determined the characteristics of these cells in lungs of COPD patients and identified novel therapeutic targets. Methods: We analyzed the RNA sequencing (scRNA-seq) data of explanted human lung tissue from COPD (n = 18) and control (n = 28) lungs and found 16 transcriptionally distinct groups of macrophages and monocytes. We performed pathway and gene enrichment analyses to determine the characteristics of macrophages and monocytes from COPD (versus control) lungs and to identify the therapeutic targets, which were then validated using data from a randomized controlled trial of COPD patients (DISARM). Results: In the alveolar macrophages, 176 genes were differentially expressed (83 up- and 93 downregulated; PChronic obstructive pulmonary disease (COPD) is an inflammatory disorder of the lungs that affects 384 million people and is responsible for over 3 million deaths/year [It is now well established that COPD is an inflammatory disorder [Although, traditionally, macrophages have been classified into the M1/M2 phenotypes, it is now recognized that owing to their plasticity and their ability to adapt to their milieu, this classification scheme is overly simplistic and does not reflect the state of macrophages in vivo [