Three-dimensional mapping of human lung fibrosis identifies spatial coupling between tissue microarchitecture and maladaptive repair states

A volumetric multimodal atlas of human lung fibrosis links early alveolar-capillary unit collapse to maladaptive repair programs, including bronchiolised epithelial states and matrix remodelling.

• Why it matters: Structural destruction in fibrosis is known, but how the 3D microenvironment constrains cellular molecular programmes is unclear, limiting spatially targeted understanding of disease progression.
• What they did: The study integrates 3D X-ray histology with spatial omics to build a volumetric atlas, then maps relationships between tissue microarchitecture and spatial molecular programmes across patient cohorts.
• The result: Atlas-defined tissue-state signatures are associated with lung function and mortality, supporting a spatial model where alveolar-capillary collapse coincides with mechanically stabilised fibrogenic niches.

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