Exploring the Void: Advances in Parenchymal Destruction. Workshop summary of the 2025 Aspen Lung Conference

Emphysema, a heterogeneous and destructive disorder of the lung parenchyma driven by genetic and environmental factors, has long been considered irreversible. The 67th Aspen Lung Conference challenged this paradigm, highlighting emerging cellular, molecular, and structural findings that advance our understanding of emphysema pathogenesis and provide new mechanistic insights into alveolar regeneration. Presentations addressed monogenic forms of lung disease, environmental and sex-related modifiers of disease susceptibility, and pathways linking emphysema progression to impaired regenerative capacity, cellular senescence, and immune dysregulation. The meeting addressed four central themes: shared mechanisms in emphysema across chronic obstructive pulmonary disease and rare lung diseases with similar phenotypes; dynamic cellular and extracellular matrix remodeling underlying distal airspace destruction; innovative approaches to early detection, phenotyping, and endotyping emphysema; and emerging molecular and cellular targets for therapeutic intervention. This report synthesizes key concepts from presentations and discussions among experts regarding the critical remaining gaps in developing disease-modifying therapies.