Airway transcriptome networks identify susceptibility to frequent asthma exacerbations in children - 05/07/23
Graphical abstract |
Abstract |
Background |
Frequent asthma exacerbators, defined as those experiencing more than 1 hospitalization in a year for an asthma exacerbation, represent an important subgroup of individuals with asthma. However, this group remains poorly defined and understudied in children.
Objective |
Our aim was to determine the molecular mechanisms underlying asthma pathogenesis and exacerbation frequency.
Methods |
We performed RNA sequencing of upper airway cells from both frequent and nonfrequent exacerbators enrolled in the Ohio Pediatric Asthma Repository.
Results |
Through molecular network analysis, we found that nonfrequent exacerbators display an increase in modules enriched for immune system processes, including type 2 inflammation and response to infection. In contrast, frequent exacerbators showed expression of modules enriched for nervous system processes, such as synaptic formation and axonal outgrowth.
Conclusion |
These data suggest that the upper airway of frequent exacerbators undergoes peripheral nervous system remodeling, representing a novel mechanism underlying pediatric asthma exacerbation.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, exacerbation, frequent exacerbator, transcriptomics, neuronal, pediatric
Abbreviations used : AE, FC, FDR, FE, Non-FE, OPAR, RAD, RNA-seq, RV, scRNA, scRNA-seq, T2
Plan
| Supported in whole or in part by CAUSE (grant U01AI159087), the Ohio Governor’s Office (grant G-1 213-07-0561), and the Ohio Children's Hospital Association. |
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| Disclosure of potential conflict of interest: D. J. Jackson reports personal fees from Genentech, Pfizer, AstraZeneca, Avilion, Sanofi, and Vifor Pharma, as well as grants and personal fees from GlaxoSmithKline and Regeneron. M. C. Altman reports personal fees from Sanofi-Regeneron outside the submitted work. G. K. Khurana Hershey reports grants from Adare outside the submitted work. L. J. Martin, K. R. Ross, D. J. Jackson, T. Mersha, M. C. Altman, and G. K. Khurana Hershey report grants from the National Institutes of Health outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 152 - N° 1
P. 73-83 - juillet 2023 Retour au numéro
Article précédent
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