Asthma represents a chronic respiratory disease affecting millions of children worldwide. The transition from preschool wheezing to school-age asthma involves a multifaceted interplay of various factors, including immunological aspects in early childhood. These factors include complex cellular interactions among different immune cell subsets, induction of pro-inflammatory mediators and the molecular impact of environmental factors like allergens or viral infections on the developing immune system. Furthermore, the activation of specific genes and signalling pathways during this early phase plays a pivotal role in the manifestation of symptoms and subsequent development of asthma. Early identification of the propensity or risk for asthma development, for example by allergen sensitisation and viral infections during this critical period, is crucial for understanding the transition from wheeze to asthma. Favourable immune regulation during a critical ‘window of opportunity’ in early childhood can induce persistent changes in immune cell behaviour. In this context, trained immunity, including memory function of innate immune cells, has significant implications for understanding immune responses, potentially shaping long-term immunological outcomes based on early-life environmental exposures. Exploration of these underlying immune mechanisms that drive disease progression will provide valuable insights to understand childhood asthma development. This will be instrumental to develop preventive strategies at different stages of disease development for (i) inhibiting progression from wheeze to asthma or (ii) reducing disease severity and (iii) uncovering novel therapeutic strategies and contributing to more tailored and effective treatments for childhood asthma. In the long term, this shall empower healthcare professionals to develop evidence-based interventions that reduce the burden of asthma for children, families and society overall.

中文翻译：

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从学龄前喘息到哮喘：免疫学决定因素

哮喘是一种影响全球数百万儿童的慢性呼吸道疾病。从学龄前喘息到学龄哮喘的转变涉及多种因素的多方面相互作用，包括幼儿期的免疫方面。这些因素包括不同免疫细胞亚群之间复杂的细胞相互作用、促炎介质的诱导以及过敏原或病毒感染等环境因素对发育中的免疫系统的分子影响。此外，在此早期阶段特定基因和信号通路的激活在哮喘症状的表现和随后的发展中起着关键作用。早期识别哮喘发展的倾向或风险，例如通过这一关键时期的过敏原致敏和病毒感染，对于了解从喘息到哮喘的转变至关重要。在幼儿期的关键“机会之窗”期间进行有利的免疫调节可以诱导免疫细胞行为的持续变化。在这种情况下，训练有素的免疫力，包括先天免疫细胞的记忆功能，对于理解免疫反应具有重要意义，可能会根据生命早期环境暴露塑造长期免疫结果。探索这些驱动疾病进展的潜在免疫机制将为了解儿童哮喘的发展提供有价值的见解。这将有助于在疾病发展的不同阶段制定预防策略，以（i）抑制从喘息到哮喘的进展，或（ii）降低疾病严重程度，以及（iii）发现新的治疗策略，并有助于为儿童哮喘提供更有针对性和更有效的治疗方法。从长远来看，这将使医疗保健专业人员能够制定循证干预措施，减轻儿童、家庭和整个社会的哮喘负担。