Division of Cell Biology, Telethon Institute for Child Health Research and the Centre for Child Health Research, Faculty of Medicine and Dentistry, the University of Western Australia, Perth, Australia.
J Allergy Clin Immunol. 2010 Mar;125(3):653-9, 659.e1-659.e7. doi: 10.1016/j.jaci.2009.12.018.
Atopy and asthma are commonly initiated during early life, and there is increasing interest in the development of preventive treatments for at-risk children. However, effective methods for assessing the level of risk in individual children are lacking.
We sought to identify clinical and laboratory biomarkers in 2-year-olds that are predictive of the risk for persistent atopy and wheeze at age 5 years.
We prospectively studied 198 atopic family history-positive children to age 5 years. Clinical and laboratory assessments related to asthma history and atopy status were undertaken annually; episodes of acute respiratory illness were assessed and classified throughout and graded by severity.
Aeroallergen-specific IgE titers cycled continuously within the low range in nonatopic subjects. Atopic subjects displayed similar cycling in infancy but eventually locked into a stable pattern of upwardly trending antibody production and T(H)2-polarized cellular immunity. The latter was associated with stable expression of IL-4 receptor in allergen-specific T(H)2 memory responses, which was absent from responses during infancy. Risk for persistent wheeze was strongly linked to early sensitization and in turn to early infection. Integration of these data by means of logistic regression revealed that attaining mite-specific IgE titers of greater than 0.20 kU/L by age 2 years was associated with a 12.7% risk of persistent wheeze, increasing progressively to an 87.2% risk with increasing numbers of severe lower respiratory tract illnesses experienced.
The risk for development of persistent wheeze in children can be quantified by means of integration of measures related to early sensitization and early infections. Follow-up studies along similar lines in larger unselected populations to refine this approach are warranted.
特应症和哮喘通常在生命早期开始出现，人们对高危儿童的预防治疗方法越来越感兴趣。然而，缺乏评估个别儿童风险水平的有效方法。
我们旨在确定 2 岁儿童的临床和实验室生物标志物，以预测其在 5 岁时持续性特应症和喘息的风险。
我们前瞻性地研究了 198 名特应性家族史阳性儿童，直至 5 岁。每年进行与哮喘史和特应症状态相关的临床和实验室评估；评估和分类整个时期的急性呼吸道疾病，并按严重程度分级。
非特应性受试者的气源性过敏原特异性 IgE 滴度在低范围内连续循环。特应性受试者在婴儿期也表现出类似的循环，但最终锁定在向上趋势的抗体产生和 T(H)2 极化细胞免疫的稳定模式。后者与过敏原特异性 T(H)2 记忆反应中 IL-4 受体的稳定表达相关，而在婴儿期的反应中则不存在。持续性喘息的风险与早期致敏密切相关，进而与早期感染有关。通过逻辑回归对这些数据进行整合，发现到 2 岁时达到大于 0.20 kU/L 的螨特异性 IgE 滴度与持续性喘息的 12.7%风险相关，随着经历的下呼吸道感染次数的增加，风险逐渐增加至 87.2%。
通过整合与早期致敏和早期感染相关的措施，可以量化儿童持续性喘息的发展风险。需要进行类似的更大未选择人群的随访研究，以进一步完善这种方法。
