Early neutrophil and persistent eosinophil-associated gene signature in childhood asthma
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.
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BibTeX
@article{foppiano2026early,
title = {{Early neutrophil and persistent eosinophil-associated gene signature in childhood asthma}},
author = {Francesco Foppiano and Andreas Böck and Claudia Beerweiler and Kathrin Urner and Markus Ege and Elisabeth Schmausser-Hechfellner and Chrysanthi Skevaki and Urs Frey and Josef Riedler and Remo Frei and Roger Lauener and Caroline Roduit and Anne M Karvonen and Marjut Roponen and Juha Pekkanen and Amandine Divaret-Chauveau and Cindy Barnig and Erika von Mutius and Bianca Schaub and Cmartin Depner and Sabina Illi and Caroline Kliem and Giulia Pagani and Sonali Pechlivanis and Martin Täubel and Kirjavainen Pirkka and Ritter Ophelie and Marie Laure Dalphin},
journal = {American Journal of Respiratory and Critical Care Medicine},
year = {2026},
month = jun,
doi = {10.1093/ajrccm/aamag142},
url = {https://hal.univ-lorraine.fr/hal-05762347v1},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Early neutrophil and persistent eosinophil-associated gene signature in childhood asthma
AU - Francesco Foppiano
AU - Andreas Böck
AU - Claudia Beerweiler
AU - Kathrin Urner
AU - Markus Ege
AU - Elisabeth Schmausser-Hechfellner
AU - Chrysanthi Skevaki
AU - Urs Frey
AU - Josef Riedler
AU - Remo Frei
AU - Roger Lauener
AU - Caroline Roduit
AU - Anne M Karvonen
AU - Marjut Roponen
AU - Juha Pekkanen
AU - Amandine Divaret-Chauveau
AU - Cindy Barnig
AU - Erika von Mutius
AU - Bianca Schaub
AU - Cmartin Depner
AU - Sabina Illi
AU - Caroline Kliem
AU - Giulia Pagani
AU - Sonali Pechlivanis
AU - Martin Täubel
AU - Kirjavainen Pirkka
AU - Ritter Ophelie
AU - Marie Laure Dalphin
PY - 2026
DA - 2026/06/01
JO - American Journal of Respiratory and Critical Care Medicine
DO - 10.1093/ajrccm/aamag142
UR - https://hal.univ-lorraine.fr/hal-05762347v1
AB - 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.
SN - 1073-449X
SN - 1535-4970
ER -