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早产对小儿哮喘发病率以及与环境污染和遗传易感性相关指标的影响。

The impact of prematurity on pediatric asthma morbidity and indices with environmental pollution and genetic susceptibility.

作者信息

Kelchtermans Jelte, Mentch Frank, Qu Huiqi, McGrath-Morrow Sharon A, Hakonarson Hakon

机构信息

Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

出版信息

Commun Med (Lond). 2025 Jul 31;5(1):324. doi: 10.1038/s43856-025-01041-z.

Abstract

BACKGROUND

Prematurity, fine particulate matter (PM), and genetic variables are linked to asthma incidence in children. However, to capture the contributions of these variables and their involvement in asthma pathogenesis, we need to understand how they interact. Here, we aim to assess the impact of prematurity on asthma exacerbations and explore interactions with PM exposure and genetic risk.

METHODS

Pediatric patients with asthma and at least 5 years of follow-up data were identified from the Center for Applied Genomics biobank. Subjects were classified as full term (FT), late preterm (LPT), or extremely/very preterm (E/VPT). PM exposure was calculated as the proportion of days between diagnosis and last recorded follow up exceeding 8 µg/m³, and a polygenic risk score (sPRS) was used to assess genetic PM susceptibility. Regression models evaluated predictors of asthma exacerbations.

RESULTS

Among 5982 patients, 16% are LPT and 4% E/VPT. The latter patient group experiences 20.5% more exacerbations than FT patients (P = 0.04). E/VPT patients have 43.3% more exacerbations per unit increase in PM exposure (P = 0.001) and LPT patients with a high sPRS experienced 24.0% more exacerbations (P = 0.04) compared to what would be expected from the sum of the independent effects. Additionally, LPT and E/VPT patients have 24% (P = 0.012) and 61% (P = 0.005) higher odds of exacerbations beyond 6 years of age, respectively.

CONCLUSIONS

Interactions between prematurity, PM exposure, and genetic susceptibility exacerbate asthma morbidity, underscoring the urgent need for targeted interventions in high-risk populations with overlapping vulnerabilities.

摘要

背景

早产、细颗粒物(PM)和基因变量与儿童哮喘发病率相关。然而,为了了解这些变量的作用及其在哮喘发病机制中的参与情况,我们需要明白它们是如何相互作用的。在此,我们旨在评估早产对哮喘发作的影响,并探讨其与PM暴露及基因风险的相互作用。

方法

从应用基因组学中心生物样本库中识别出患有哮喘且有至少5年随访数据的儿科患者。受试者被分类为足月(FT)、晚期早产(LPT)或极早早产/非常早产(E/VPT)。PM暴露量通过诊断至最后一次记录随访期间超过8μg/m³的天数比例来计算,并且使用多基因风险评分(sPRS)来评估基因PM易感性。回归模型评估哮喘发作的预测因素。

结果

在5982名患者中,16%为LPT,4%为E/VPT。后一组患者的发作次数比FT患者多20.5%(P = 0.04)。E/VPT患者每单位PM暴露量增加,发作次数多43.3%(P = 0.001),与独立效应之和预期相比,sPRS高的LPT患者发作次数多24.0%(P = 0.04)。此外,LPT和E/VPT患者在6岁以后发作的几率分别高24%(P = 0.012)和61%(P = 0.005)。

结论

早产、PM暴露和基因易感性之间的相互作用会加剧哮喘发病率,凸显了对具有重叠易损性的高危人群进行针对性干预的迫切需求。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/711c/12314037/e2984e1fd779/43856_2025_1041_Fig1_HTML.jpg

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