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. 2025 Aug;156(2):361-372.
doi: 10.1016/j.jaci.2025.03.021. Epub 2025 Apr 4.

Nasal transcriptome differences preceding recurrent wheezing in infancy

Poshmaal Dhar  1 , Martin O'Hely  1 , Luba Sominsky  2 , Sarah Ashley  3 , Sarath C Ranganathan  3 , Peter D Sly  4 , Fiona Collier  1 , Mimi L K Tang  3 , Rachel Morgan  2 , Toby Mansell  5 , Richard Saffery  5 , David Burgner  5 , Anne-Louise Ponsonby  6 , Peter Vuillermin  7 ; Barwon Infant Study Investigator Group
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Free article

Nasal transcriptome differences preceding recurrent wheezing in infancy

Poshmaal Dhar et al. J Allergy Clin Immunol. 2025 Aug.
Free article

Abstract

Background: Mucosal immune responses and epithelial barrier function are key emerging determinants of susceptibility to wheezing illnesses in early life.

Objective: We sought to investigate the association between nasal transcriptome in healthy infants and the subsequent incidence of recurrent wheeze.

Methods: In a population-derived prebirth cohort study, whole-transcriptome sequencing was performed to compare the nasal transcriptome at 1 month of age from 26 infants who subsequently developed recurrent wheeze (parents' record in symptom diary) in the first year of life with that of 22 infants who remained wheeze-free. Differentially expressed genes (DEGs) were identified using DEseq2, followed by overrepresentation pathway (Gene Ontology [GO] and Kyoto Encyclopedia of Genes and Genomes) and upstream regulator analyses (Ingenuity Pathway Analysis).

Results: A total of 202 DEGs (false discovery rate ≤ 0.1 and absolute log2 fold change > 1; 66 upregulated and 136 downregulated) were associated with recurrent wheeze. Upregulated GO pathways associated with recurrent wheeze included chemokine-mediated signaling and eosinophil and monocyte chemotaxis. The downregulated GO included cilium organization and cellular aldehyde metabolic process. TNF emerged as the key driver (adjusted P value and z score) of DEG patterns in the recurrent wheeze group, with OSMR and IL21 identified as master regulators.

Conclusion: The nasal transcriptome in early infancy is associated with subsequent recurrent wheezes, indicating upregulation of immune cell chemotaxis, decreased epithelial barrier function, and altered cilium organization and mitochondrial function. Future studies are required to evaluate the use of nasal transcriptome in the early detection of infants at risk of recurrent wheeze and to generate new knowledge of antecedent pathways as targets for novel primary prevention strategies.

Keywords: RNA sequencing; Wheeze; asthma; birth cohort; nasal transcriptome.

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Conflict of interest statement

Disclosure statement The establishment work and infrastructure for the BIS was provided by the Murdoch Children’s Research Institute, Deakin University, and Barwon Health, supported by the Victorian Government Operational Infrastructure Program. Funding was also provided by the Australian National Health and Medical Research Council (NHMRC), the Jack Brockhoff Foundation, the Shane O’Brien Memorial Asthma Foundation, the Our Women’s Our Children’s Fund Raising Committee Barwon Health, the Shepherd Foundation, the Rotary Club of Geelong, the Ilhan Food Allergy Foundation, GMHBA Limited, Vanguard Investments Australia Ltd, the Percy Baxter Charitable Trust, Perpetual Trustees, and Minderoo Foundation. In-kind support was provided by the Cotton on Foundation and CreativeForce. Disclosure of potential conflict of interest: M. O’Hely, S. C. Ranganathan, F. Collier, A.-L. Ponsonby, and P. Vuillermin have stocks/options in Prevatex Pty Ltd. S. C. Ranganathan is Director of the Lung Foundation Australia. M. L. K. Tang declares inventorship on patents covering peanut oral immunotherapy; employee and holding share interest and options in Prota Therapeutics; member of the Medical Advisory Board of Allergy & Anaphylaxis Australia; member of the Board of Directors of Asia Pacific Association of Allergy Asthma and Clinical Immunology (APAAACI), AllergyPAL, and Prota Therapeutics; member of expert committees of the American Academy of Allergy Asthma and Immunology, Asia Pacific Association of Allergy Asthma and Clinical Immunology, and Australasian Society of Clinical Immunology. D. Burgner has received an Investigator Grant and Project Grant from the Australian NHMRC. He has an unpaid role on the European Society for Paediatric Infectious Diseases Committee for Research. The rest of the authors declare that they have no relevant conflicts of interest.

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