{
  "abstract": "Rationale Early childhood represents a critical window for asthma susceptibility, marked by developmental and molecular changes, yet their longitudinal pattern remains unclear. Objectives To identify differences in longitudinal whole-blood gene expression during early childhood in future asthmatics compared to healthy children. Methods We conducted a longitudinal whole-blood transcriptomic analysis at 4 timepoints (1, 4.5, 6, 10.5 years) in a sample of the birth cohort Protection against Allergy Study in Rural Environments (PASTURE) (n = 378), comparing children who developed asthma between ages 6 and 10.5 years with nonasthmatic controls (83/295). Analyses included longitudinal differential gene expression, weighted gene co-expression network analysis, and cis-expression quantitative trait loci analysis. Measurements and main results At age 1 year, 42 genes, mostly upregulated in future asthmatics, were associated with neutrophilic inflammation and NLRP3 inflammasome-markers. By 4.5 years, this shifted to a novel eosinophil-related signature (40 genes), remaining increased in asthmatics until 10.5 years. Co-expression analysis confirmed a neutrophilic module at 1 year and eosinophilic modules at 4.5, 6, and 10.5 years, all associated with asthma. Fractional exhaled nitric oxide was associated with the eosinophilic module at age 6 years (P = .003). A total of 86 SNPs were identified modulating the expression of 10 eosinophil-associated genes and GSDMB from this eosinophilic signature. A variant-based genetic risk score was associated with asthma diagnosis (adjusted odds ratio [aOR], 1.47; 95% CI, 1.13-1.93). Conclusions We identified a shift from a neutrophil-driven gene signature at age 1 year to a persistent eosinophilic signature at 4.5-10.5 years in asthmatic children, highlighting the 1- to 4.5-year period as the most vulnerable period. Genetic variants strongly influenced the persistent eosinophilic gene signature, comprising potential novel therapeutic targets.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 28,
  "authors": [
    {
      "name": "Francesco Foppiano"
    },
    {
      "name": "Andreas Böck"
    },
    {
      "name": "Claudia Beerweiler"
    },
    {
      "name": "Kathrin Urner"
    },
    {
      "name": "Markus Ege"
    },
    {
      "name": "Elisabeth Schmausser-Hechfellner"
    },
    {
      "name": "Chrysanthi Skevaki"
    },
    {
      "name": "Urs Frey"
    },
    {
      "name": "Josef Riedler"
    },
    {
      "name": "Remo Frei"
    },
    {
      "name": "Roger Lauener"
    },
    {
      "name": "Caroline Roduit"
    },
    {
      "name": "Anne M Karvonen"
    },
    {
      "name": "Marjut Roponen"
    },
    {
      "name": "Juha Pekkanen"
    },
    {
      "name": "Amandine Divaret-Chauveau"
    },
    {
      "name": "Cindy Barnig"
    },
    {
      "name": "Erika von Mutius"
    },
    {
      "name": "Bianca Schaub"
    },
    {
      "name": "Cmartin Depner"
    },
    {
      "name": "Sabina Illi"
    },
    {
      "name": "Caroline Kliem"
    },
    {
      "name": "Giulia Pagani"
    },
    {
      "name": "Sonali Pechlivanis"
    },
    {
      "name": "Martin Täubel"
    },
    {
      "name": "Kirjavainen Pirkka"
    },
    {
      "name": "Ritter Ophelie"
    },
    {
      "name": "Marie Laure Dalphin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3gysmesf58g81.bib",
  "cited_by": 1,
  "doi": "10.1093/ajrccm/aamag142",
  "fulltext_url": null,
  "id": "3gysmesf58g81",
  "issns": [
    "1073-449X",
    "1535-4970"
  ],
  "landing_url": "https://hal.univ-lorraine.fr/hal-05762347v1",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2737|Asthma and respiratory diseases"
    ]
  ],
  "openalex": "W7151081064",
  "pdf_url": "https://hal.univ-lorraine.fr/hal-05762347/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-06-01",
  "publisher": "American Thoracic Society",
  "ris": "https://research.draconitic.com/paper/3gysmesf58g81.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:40Z",
      "native_id": "hal-05762347",
      "source": "hal",
      "url": "https://hal.univ-lorraine.fr/hal-05762347v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Asthma and respiratory diseases",
      "subfield": "physiology"
    }
  ],
  "title": "Early neutrophil and persistent eosinophil-associated gene signature in childhood asthma",
  "title_text": "Early neutrophil and persistent eosinophil-associated gene signature in childhood asthma",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:40Z",
  "url": "https://research.draconitic.com/paper/3gysmesf58g81",
  "venue": "American Journal of Respiratory and Critical Care Medicine",
  "versions": []
}