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Review

Unmasking Pediatric Asthma: Epigenetic Fingerprints and Markers of Respiratory Infections

by
Alessandra Pandolfo
1,2,
Rosalia Paola Gagliardo
2,
Valentina Lazzara
1,2,
Andrea Perri
2,3,
Velia Malizia
2,
Giuliana Ferrante
2,4,
Amelia Licari
2,5,6,
Stefania La Grutta
2 and
Giusy Daniela Albano
2,*
1
Department of Economics, Business and Statistics (dSEAS), University of Palermo (UNIPA), 90128 Palermo, Italy
2
Institute of Translational Pharmacology (IFT), National Research Council (CNR), 90146 Palermo, Italy
3
Department of Earth and Marine Sciences (DiSTeM), University of Palermo (UNIPA), 90123 Palermo, Italy
4
Department of Surgery, Dentistry, Pediatrics and Gynaecology, Pediatric Division, University of Verona, 37134 Verona, Italy
5
Pediatric Unit, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy
6
Pediatric Clinic, Fondazione IRCCS Policlinico, San Matteo, 27100 Pavia, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(15), 7629; https://doi.org/10.3390/ijms26157629
Submission received: 17 June 2025 / Revised: 30 July 2025 / Accepted: 2 August 2025 / Published: 6 August 2025
(This article belongs to the Special Issue Molecular Research in Airway Diseases)

Abstract

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma.
Keywords: pediatric asthma; epigenetics; asthma endotypes; respiratory infections; personalized medicine pediatric asthma; epigenetics; asthma endotypes; respiratory infections; personalized medicine

Share and Cite

MDPI and ACS Style

Pandolfo, A.; Gagliardo, R.P.; Lazzara, V.; Perri, A.; Malizia, V.; Ferrante, G.; Licari, A.; La Grutta, S.; Albano, G.D. Unmasking Pediatric Asthma: Epigenetic Fingerprints and Markers of Respiratory Infections. Int. J. Mol. Sci. 2025, 26, 7629. https://doi.org/10.3390/ijms26157629

AMA Style

Pandolfo A, Gagliardo RP, Lazzara V, Perri A, Malizia V, Ferrante G, Licari A, La Grutta S, Albano GD. Unmasking Pediatric Asthma: Epigenetic Fingerprints and Markers of Respiratory Infections. International Journal of Molecular Sciences. 2025; 26(15):7629. https://doi.org/10.3390/ijms26157629

Chicago/Turabian Style

Pandolfo, Alessandra, Rosalia Paola Gagliardo, Valentina Lazzara, Andrea Perri, Velia Malizia, Giuliana Ferrante, Amelia Licari, Stefania La Grutta, and Giusy Daniela Albano. 2025. "Unmasking Pediatric Asthma: Epigenetic Fingerprints and Markers of Respiratory Infections" International Journal of Molecular Sciences 26, no. 15: 7629. https://doi.org/10.3390/ijms26157629

APA Style

Pandolfo, A., Gagliardo, R. P., Lazzara, V., Perri, A., Malizia, V., Ferrante, G., Licari, A., La Grutta, S., & Albano, G. D. (2025). Unmasking Pediatric Asthma: Epigenetic Fingerprints and Markers of Respiratory Infections. International Journal of Molecular Sciences, 26(15), 7629. https://doi.org/10.3390/ijms26157629

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