Chronic Obstructive Pulmonary Disease (COPD): From Molecular and Cellular Mechanisms to Therapeutic Opportunities

Dear Colleagues,

Chronic obstructive pulmonary disease (COPD), one of the leading causes of death worldwide, represents a significant healthcare problem. Considerable progress has been achieved in understanding its pathobiology, especially with regard to structural and functional changes in small airways and their contribution to airflow limitation. Recent studies indicate that these changes occur relatively early during disease development. However, specific biologic mechanisms underlying small airway disease in COPD and those linking small airway changes to emphysema, another major pathologic manifestation of COPD, still remain poorly understood. Another important element of COPD pathobiology, vascular remodeling, and its relationship to small airway pathology in COPD, also remain unclear. 

Current advances in technology, including single-cell RNA-sequencing, spatial transcriptomics, and epigenetic profiling, have better elucidated COPD pathobiology at the tissue and single-cell levels. Recent studies using these approaches have identified important novel aspects of disease pathogenesis, leading to a clearer understanding of the role of inflammation and altered tissue maintenance and regeneration in this disease. Many critical aspects of COPD pathophysiology, especially those related to small airway disease, cannot be recapitulated in commonly used animal (such as mouse) models due to significant differences in anatomical and cellular organization of this critical disease niche between human and mouse lungs, emphasizing the need for novel, more representative experimental modeling approaches.  Remarkable progress has been made in this regard by utilizing ex vivo human tissue and disease modeling using organoids and other human cell-based in vitro model systems; these advances enable us to study the mechanisms of COPD pathogenesis within the tissue-specific context of human disease, potentially leading to the discovery of novel therapeutic targets and approaches.

This Special Issue is intended as a platform to present outstanding innovative research focusing on cellular and molecular aspects and mechanisms of COPD and to provide novel insights into disease pathobiology using human tissue-based spatial, single-cell, and/or ex vivo modeling approaches, while also highlighting studies addressing critical aspects of COPD pathogenesis using in vivo models relevant to understanding human disease. Priority will be given to studies focusing on tissue-specific aspects of COPD, especially those linking biologic and clinical phenomena and/or directed toward novel therapies for COPD using models that capture or recapitulate critical elements of COPD pathophysiology. Both original and review articles will be considered. 

Dr. Renat Shaykhiev
Dr. Bradley W. Richmond
Dr. Umadevi Sajjan
Guest Editors

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• chronic obstructive pulmonary disease (COPD)
• small airway disease
• vascular remodeling
• emphysema