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. 2025 Aug 6:S2213-2198(25)00763-9.
doi: 10.1016/j.jaip.2025.07.051. Online ahead of print.

Risk Factors and Mechanisms Leading to Preschool Recurrent Wheeze and Asthma

Jose A Castro-Rodriguez  1 , Alba A B Wolters  2 , Carlos E Rodriguez-Martinez  3 , Jocelyn M Biagini  4 , Juan C Celedón  5 , Adnan Custovic  6 , Gerard H Koppelman  2 , Wanda Phipatanakal  7 , Sejal Saglani  6 , Erick Forno  8
Affiliations

Risk Factors and Mechanisms Leading to Preschool Recurrent Wheeze and Asthma

Jose A Castro-Rodriguez et al. J Allergy Clin Immunol Pract. .

Abstract

Preschool recurrent wheezing is a prevalent and heterogeneous condition that can develop into childhood asthma, significantly damaging public health. Preschool recurrent wheeze and asthma are influenced by a multifactorial interplay of biological, environmental, early life, behavioral, and psychosocial factors. Genes such as Gasdermin B, Orosomucoid 1-like 3, Cadherin-related family member 3, Annexin A1, and IL33/IL1RL1, and the methylation of cell-type-specific CpG sites are associated with airway-remodeling, increased inflammatory responses, and enhanced susceptibility to environmental factors. Biomarkers such as allergen sensitization, blood eosinophil levels, FeNO, and volatile organic compounds may guide treatment decisions based on the type of immune response in wheezing episodes. Several asthma-predicted clinical indices have been developed, and some have been validated. Although lower airway samples obtained through bronchoalveolar lavage and biopsy in young children are limited, they are essential in understanding the pathophysiology and developing personalized treatment of recurrent preschool wheezing. Early evaluations of lung function, airway hyperresponsiveness, and bronchodilator response can be valuable objective tools. However, because of physiologic variability and inconsistent methods and definitions, these tests cannot confirm or rule out a diagnosis of asthma at preschool age. Future research should investigate the interplay of factors across biological, environmental, and social domains to enhance predictive models and inform targeted interventions that promote health equity and reduce the global burden of preschool recurrent wheeze and asthma.

Keywords: Asthma; Epigenetic; Genetic; Lung function; Mechanisms; Preschool; Recurrent wheezing; Risk factors.

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Conflict of interest statement

COI

AAB, CR-M, EF, and JCC have nothing to disclose. GHK reports grants from the Netherlands Lung Foundation, Ubbo Emmius Foundation, European Union, Vertex, GSK, and TEVA, outside the submitted work (money to the institution). His institution received compensation for consultancy to Pure IMS, AZ, GSK, and lectures (Boehringer Ingelheim, Sanofi, AZ). JACR received compensation for lectures and consultancy from AZ, Cassará, and Pfizer. AC reports personal fees from Sanofi, La Roche-Posay, and Reacta Healthcare, outside the submitted work. WP reports personal fees from consultants for Sanofi, Regeneron, GSK, Genentech, AZ, and Novartis.

Figures

Figure 1.
Figure 1.
Factors associated with recurrent wheezing and asthma in preschool children.
See this image and copyright information in PMC

References

    1. Makrinioti H, Fainardi V, Bonnelykke K, Custovic A, Cicutto L, Coleman C, et al. European Respiratory Society statement on preschool wheezing disorders: updated definitions, knowledge gaps and proposed future research directions. Eur Respir J 2024;64(3). - PubMed
    1. Bolat E, Arikoglu T, Sungur MA, Batmaz SB, Kuyucu S. Prevalence and risk factors for wheezing and allergic diseases in preschool children: A perspective from the Mediterranean coast of Turkey. Allergol Immunopathol (Madr). 2017;45(4):362–8. - PubMed
    1. Peroni DG, Piacentini GL, Bodini A, Boner AL. Preschool asthma in Italy: prevalence, risk factors and health resource utilization. Respir Med 2009;103(1):104–8. - PubMed
    1. Yao MM, Wang KM, Xu QY, Wang GL, Liu XT. [Etiology and risk factors of infantile wheezing]. Zhongguo Dang Dai Er Ke Za Zhi 2011;13(3):195–8. - PubMed
    1. Rylander E, Eriksson M, Freyschuss U. Risk factors for occasional and recurrent wheezing after RSV infection in infancy. Acta Paediatr Scand 1988;77(5):711–5. - PubMed

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