Does Chronic Obstructive Pulmonary Disease Originate from Different Cell Types?

Authors

Yohannes Tesfaigzi
Jeffrey L Curtis
Irina Petrache
Francesca Polverino
Farrah Kheradmand
Ian M Adcock
Stephen I Rennard

Publication Date

11-1-2023

Journal

American Journal of Respiratory Cell and Molecular Biology

DOI

10.1165/rcmb.2023-0175PS

PMID

37584669

PMCID

PMC10633838

PubMedCentral® Posted Date

8-16-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Endothelial Cells, Genome-Wide Association Study, Proteomics, Pulmonary Disease, Chronic Obstructive, Lung, lung cell types, single nucleotide polymorphisms, single-cell transcriptomics, lineage tracing, gene-and-environment interaction

Abstract

The onset of chronic obstructive pulmonary disease (COPD) is heterogeneous, and current approaches to define distinct disease phenotypes are lacking. In addition to clinical methodologies, subtyping COPD has also been challenged by the reliance on human lung samples from late-stage diseases. Different COPD phenotypes may be initiated from the susceptibility of different cell types to cigarette smoke, environmental pollution, and infections at early stages that ultimately converge at later stages in airway remodeling and destruction of the alveoli when the disease is diagnosed. This perspective provides discussion points on how studies to date define different cell types of the lung that can initiate COPD pathogenesis, focusing on the susceptibility of macrophages, T and B cells, mast cells, dendritic cells, endothelial cells, and airway epithelial cells. Additional cell types, including fibroblasts, smooth muscle cells, neuronal cells, and other rare cell types not covered here, may also play a role in orchestrating COPD. Here, we discuss current knowledge gaps, such as which cell types drive distinct disease phenotypes and/or stages of the disease and which cells are primarily affected by the genetic variants identified by whole genome-wide association studies. Applying new technologies that interrogate the functional role of a specific cell type or a combination of cell types as well as single-cell transcriptomics and proteomic approaches are creating new opportunities to understand and clarify the pathophysiology and thereby the clinical heterogeneity of COPD.