Spatially resolved airway niches: mapping epithelial-immune microenvironments in asthma

Spatially resolved omics has reconceptualized the bronchial wall as a mosaic of epithelial - immune microenvironments whose local molecular circuits drive asthma heterogeneity and medication responsiveness.

We searched PubMed, Embase, Web of Science, and Scopus (January 2005 - July 2025) using platform-specific and disease-related keywords and identified studies that employed spatial transcriptomics, multiplex-imaging proteomics, or spatial metabolomics on human airway biopsies, ex vivo lung slices, and murine asthma models. We synthesize niches revealed by Visium-HD, Xenium, CosMx SMI, MERFISH, Imaging Mass Cytometry, MIBI, and high-resolution MALDI-MSI - IL-13-rich goblet-cell hubs, mast-cell - smooth-muscle loops, IL-17-driven neutrophil pockets, and fibroblast-remodeling zones. These investigations expose chemokine, alarmin, and lipid gradients that delineate disease-defining niches overlooked by dissociation-based assays, thereby uncovering therapeutic targets.

Spatial omics links molecular programmes to micro-anatomy with near-single-cell accuracy and is poised for integration into precision-medicine pipelines. Cost-effective, high-throughput 'spatial biopsies,' combined with graph-based artificial intelligence, are expected to stratify patients for biologic therapies within five years. Nonetheless, broad clinical adoption will require reduced assay costs, mitigation of RNA diffusion, harmonized FFPE workflows, and multi-omic integration across global cohorts to produce reproducible, clinically actionable airway atlases capable of personalizing prevention and treatment.