{
  "abstract": "The different mechanisms underlying distinct phenotypes of asthma remain poorly understood. While scRNA sequencing has improved our understanding of the cellular diversity in asthma, it lacks spatial context. To address this limitation, we applied high-resolution spatial transcriptomics to airway biopsies from healthy individuals and clinically stratified asthmatic patients from two specific phenotypes.Methods We recruited 42 participants to a bronchoscopy study: 16 healthy control participants, 13 with early-onset atopic asthma with strong host dust mite sensitisation, 13 with adult-onset eosinophilic asthma. Bronchial biopsies were analysed by 10X Xenium with 389 predesigned and custom selected probes focussing on type 2 immune and remodelling pathways.Results Early-onset asthma vs late-onset asthma had mean age of onset 5.6 vs 45 years, worse lung function (FEV174% vs 90% predicted), lower FeNO (30 ppb vs 80 ppb), lower blood eosinophils (0.3 vs 0.44 cells/mL) higher total IgE (376 IU/L vs 66 IU/L). We performed quality control, segmentation, and cell type annotation using Seurat and Xenium software. Healthy tissues showed higher transcript capture per cell and more consistent segmentation compared to asthmatic tissues. Cell type annotation revealed the spatial distribution of key cell types, including T cells, B cell lineage cells, fibroblasts, and smooth muscle cells, in both asthmatic and healthy samples.Within epithelial cells genes differentially upregulated in late-onset asthma included POSTN, NOS2, CCL26, and TSLP consistent with strong epithelial type 2 inflammatory signalling. By contrast early-onset, highly atopic asthma was associated with upregulation of genes including DMBT1 (which can suppress IL4, IL5 and cilial motility), LTF, genes involved in mucin hypersecretion including MUC5B, SOX9 (a transcription factor involved in goblet cell metaplasia) and KDR (the SOX9-modulated VEGF receptor), the wnt b-catenin signalling modulator SFRP1, and the mast cell receptor KIT. Whilst the alarmin TSLP was upregulated in late-onset asthma, IL33 expression was higher in health, linking its expression more closely with therapeutic steroids than asthma pathology. Neighbourhood analyses are ongoing to reveal spatial interactions between cell types.Conclusion Spatial transcriptomics identifies features of disease-specific inflammation and remodelling underlying differences between phenotypes, and enabling characterisation of spatial relationships between epithelial, inflammatory and stromal cells.",
  "authors": [
    {
      "affiliations": [
        "University of Oxford, Oxford, UK"
      ],
      "name": "J Melhorn"
    },
    {
      "affiliations": [
        "University of Oxford, Oxford, UK"
      ],
      "name": "RY Yamani"
    },
    {
      "affiliations": [
        "University of Oxford, Oxford, UK"
      ],
      "name": "B Brassanyi"
    },
    {
      "affiliations": [
        "University of Oxford, Oxford, UK"
      ],
      "name": "E Bridges"
    },
    {
      "affiliations": [
        "University of Southampton, Southampton, UK"
      ],
      "name": "J Norman"
    },
    {
      "affiliations": [
        "University of Oxford, Oxford, UK"
      ],
      "name": "ID Pavord"
    },
    {
      "affiliations": [
        "University of Oxford, Oxford, UK"
      ],
      "name": "S Taylor"
    },
    {
      "affiliations": [
        "University of Oxford, Oxford, UK"
      ],
      "name": "E Marchi"
    },
    {
      "affiliations": [
        "University of Oxford, Oxford, UK"
      ],
      "name": "TSC Hinks"
    }
  ],
  "title": "S106 Spatial transcriptomic profiling of airway inflammation and structural changes in asthma",
  "uid": "b9efdac7-4c3f-5efa-8a4a-8294db20f17f"
}