Risk Factors and Mechanisms Leading to Preschool Recurrent Wheeze and Asthma

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.