背景：生命早期的环境暴露可能通过影响免疫发育，进而改变过敏性疾病和哮喘的发病率。已有研究显示，暴露于特定的室内空气过敏原与喘息和儿童哮喘的减少相关。本研究旨在探究生命早期的过敏原暴露是否会促进免疫发育并降低哮喘风险。
方法：在“城市环境与儿童哮喘”研究中，我们对442名儿童从出生至7岁期间，检测了其外周血单个核细胞的细胞因子反应。我们将出生后前3年采集的家庭灰尘中的过敏原及内毒素水平，分别与7岁时的细胞因子反应、特应性体质、纵向过敏致敏轨迹以及哮喘状况进行比较。
结果：脐带血的细胞因子反应具有独特特征，但对后续反应的预测能力较弱。早期暴露于蟑螂、小鼠和猫过敏原，与7岁时对先天刺激物产生的特定IFN-α、IL-12p40和TNF反应、有丝分裂原诱导的IFN-γ反应（蟑螂和小鼠过敏原）以及尘螨诱导的IFN-γ反应（小鼠过敏原）均存在显著相关性。气源性过敏原致敏的早期发生，与在1-3岁时开始、并在5-7岁时增强的过敏原诱导的2型免疫反应呈正相关。在逻辑回归模型中，细胞因子反应对特应性体质有一定的预测能力，但对哮喘的预测能力不强（受试者工作特征曲线下面积分别为0.69±0.14和0.57±0.08）。
结论：学龄前气源性过敏原暴露与直至7岁的细胞因子反应之间存在关联，提示其可能在改变系统性免疫发育中发挥作用。逐步增强的气源性过敏原诱导的2型免疫反应与早发性过敏致敏相关。相比之下，7岁时的哮喘并未与特定的细胞因子反应模式相关联，这可能反映了儿童早发性哮喘涉及多种炎症机制。
Immune development in urban children and its relationship to environmental exposures, allergic sensitization, and asthma
Chang Q, Chen L, Zhu Y, Liu B, Zhou X, Liang H, Lin F, Li D, Zhu Z, Pan Z, Chen X, Liu H, Sun D, Lv J, Li L, Pan P, Yu C, Zhang Y.
Abstract
Abstract
BACKGROUND:Early-life environmental exposures influence the incidence of allergic diseases and asthma, possibly by modifying immune development. Exposure to selected indoor aeroallergens has been associated with reduced wheezing and childhood asthma. We sought to determine whether allergen exposure in early life promotes immune development and reduces asthma risk.
METHODS:From birth through age 7, we measured cytokine responses of peripheral blood mononuclear cells from 442 children in the Urban Environment and Childhood Asthma study. We then compared allergen and endotoxin levels in house dust collected in the first 3 years to cytokine responses, atopy and longitudinal allergic sensitization trajectories, and asthma (age 7).
RESULTS:Cord blood cytokine responses had unique features but were poorly predictive of subsequent responses. Early cockroach, mouse, and cat allergen exposures were significantly associated with selected IFN-α, IL-12p40, and TNF responses to innate stimuli, mitogen-induced IFN-γ (cockroach and mouse), and dust mite-induced IFN-γ (mouse) at age 7. Early onset of aeroallergic sensitization was positively associated with allergen-induced type 2 responses that started at ages 1-3 years and intensified at ages 5-7. In logistic regression models, cytokine responses modestly predicted atopy but not asthma (AUROC 0.69 ± 0.14 and 0.57 ± 0.08, respectively).
CONCLUSION:Associations between preschool aeroallergen exposures and cytokine responses through age 7 years suggest a possible role in modifying systemic immune development. Progressively increasing aeroallergen-induced type 2 responses were associated with early-onset allergic sensitization. In contrast, asthma at age 7 was not associated with distinct cytokine responses, perhaps reflecting the multiple inflammatory mechanisms related to early-onset childhood asthma.
方法：在“城市环境与儿童哮喘”研究中，我们对442名儿童从出生至7岁期间，检测了其外周血单个核细胞的细胞因子反应。我们将出生后前3年采集的家庭灰尘中的过敏原及内毒素水平，分别与7岁时的细胞因子反应、特应性体质、纵向过敏致敏轨迹以及哮喘状况进行比较。
结果：脐带血的细胞因子反应具有独特特征，但对后续反应的预测能力较弱。早期暴露于蟑螂、小鼠和猫过敏原，与7岁时对先天刺激物产生的特定IFN-α、IL-12p40和TNF反应、有丝分裂原诱导的IFN-γ反应（蟑螂和小鼠过敏原）以及尘螨诱导的IFN-γ反应（小鼠过敏原）均存在显著相关性。气源性过敏原致敏的早期发生，与在1-3岁时开始、并在5-7岁时增强的过敏原诱导的2型免疫反应呈正相关。在逻辑回归模型中，细胞因子反应对特应性体质有一定的预测能力，但对哮喘的预测能力不强（受试者工作特征曲线下面积分别为0.69±0.14和0.57±0.08）。
结论：学龄前气源性过敏原暴露与直至7岁的细胞因子反应之间存在关联，提示其可能在改变系统性免疫发育中发挥作用。逐步增强的气源性过敏原诱导的2型免疫反应与早发性过敏致敏相关。相比之下，7岁时的哮喘并未与特定的细胞因子反应模式相关联，这可能反映了儿童早发性哮喘涉及多种炎症机制。
（中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校）
（J Allergy Clin Immunol. 2026 Jan; DOI: 10.1016/j.jaci.2025.08.031 ）
（J Allergy Clin Immunol. 2026 Jan; DOI: 10.1016/j.jaci.2025.08.031 ）
Immune development in urban children and its relationship to environmental exposures, allergic sensitization, and asthma
Chang Q, Chen L, Zhu Y, Liu B, Zhou X, Liang H, Lin F, Li D, Zhu Z, Pan Z, Chen X, Liu H, Sun D, Lv J, Li L, Pan P, Yu C, Zhang Y.
Abstract
Abstract
BACKGROUND:Early-life environmental exposures influence the incidence of allergic diseases and asthma, possibly by modifying immune development. Exposure to selected indoor aeroallergens has been associated with reduced wheezing and childhood asthma. We sought to determine whether allergen exposure in early life promotes immune development and reduces asthma risk.
METHODS:From birth through age 7, we measured cytokine responses of peripheral blood mononuclear cells from 442 children in the Urban Environment and Childhood Asthma study. We then compared allergen and endotoxin levels in house dust collected in the first 3 years to cytokine responses, atopy and longitudinal allergic sensitization trajectories, and asthma (age 7).
RESULTS:Cord blood cytokine responses had unique features but were poorly predictive of subsequent responses. Early cockroach, mouse, and cat allergen exposures were significantly associated with selected IFN-α, IL-12p40, and TNF responses to innate stimuli, mitogen-induced IFN-γ (cockroach and mouse), and dust mite-induced IFN-γ (mouse) at age 7. Early onset of aeroallergic sensitization was positively associated with allergen-induced type 2 responses that started at ages 1-3 years and intensified at ages 5-7. In logistic regression models, cytokine responses modestly predicted atopy but not asthma (AUROC 0.69 ± 0.14 and 0.57 ± 0.08, respectively).
CONCLUSION:Associations between preschool aeroallergen exposures and cytokine responses through age 7 years suggest a possible role in modifying systemic immune development. Progressively increasing aeroallergen-induced type 2 responses were associated with early-onset allergic sensitization. In contrast, asthma at age 7 was not associated with distinct cytokine responses, perhaps reflecting the multiple inflammatory mechanisms related to early-onset childhood asthma.
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