The atopic march refers to the co-expression and progression of atopic diseases in childhood, often beginning with atopic dermatitis, although children may not “progress” through each atopic disease. We hypothesized that future atopic disease expression is modified by atopic dermatitis phenotype, and that these differences result from underlying dysregulation of cytokine signaling. Children (n=285) were enrolled into the Childhood Origins of ASThma birth cohort and followed prospectively. Rates of atopic dermatitis, food allergy, allergic rhinitis, and asthma were assessed longitudinally from birth to 18 years of age. Associations between atopic dermatitis phenotype and food allergy, allergic rhinitis, asthma, allergic sensitization, exhaled nitric oxide, and lung function were determined. Peripheral blood mononuclear cell responses (IL-5, IL-10, IL-13, IFN-γ) to dust mite, phytohemagglutinin, Staphylococcus aureus Cowan I, and tetanus toxoid were compared among atopic dermatitis phenotypes. Atopic dermatitis at year 1 was associated with an increased risk of food allergy (p=0.004). Both persistent and late-onset atopic dermatitis were associated with an increased risk of asthma (p=<0.001), rhinitis (p<0.001), elevated total IgE (p=<0.001), percentage of aeroallergens with detectable IgE (p<0.001), and elevated exhaled nitric oxide (p=0.002). Longitudinal analyses did not reveal consistent differences in PBMC responses among dermatitis phenotypes. Atopic dermatitis phenotype is associated with differential expression of other atopic diseases. Our findings suggest peripheral blood cytokine dysregulation is not a mechanism underlying this process, and immune dysregulation may be mediated at mucosal surfaces or in secondary lymphoid organs.

中文翻译：

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尽管单核细胞细胞因子反应相似，特应性皮炎表型仍影响特应性疾病的表达

特应性进行曲是指儿童期特应性疾病的共表达和进展，通常从特应性皮炎开始，尽管儿童可能不会在每种特应性疾病中“进展”。我们假设未来特应性疾病的表达会受到特应性皮炎表型的影响，并且这些差异是由细胞因子信号传导的潜在失调引起的。儿童 (n=285) 被纳入 ASThma 出生队列的童年起源并进行前瞻性随访。对从出生到 18 岁的特应性皮炎、食物过敏、过敏性鼻炎和哮喘的发病率进行纵向评估。确定了特应性皮炎表型与食物过敏、过敏性鼻炎、哮喘、过敏性致敏、呼出一氧化氮和肺功能之间的关联。比较特应性皮炎表型之间的外周血单核细胞对尘螨、植物血凝素、金黄色葡萄球菌 Cowan I 和破伤风类毒素的反应（IL-5、IL-10、IL-13、IFN-γ）。第一年的特应性皮炎与食物过敏风险增加相关 (p=0.004)。持续性和迟发性特应性皮炎均与哮喘 (p=<0.001)、鼻炎 (p<0.001)、总 IgE 升高 (p=<0.001)、可检测到 IgE 的空气过敏原百分比 (p<0.001) 风险增加相关）和呼出一氧化氮升高（p=0.002）。纵向分析并未揭示皮炎表型之间 PBMC 反应的一致差异。特应性皮炎表型与其他特应性疾病的差异表达相关。我们的研究结果表明，外周血细胞因子失调并不是这一过程的潜在机制，免疫失调可能是在粘膜表面或次级淋巴器官中介导的。