青少年和老年妇女的气道炎症:慢性空气污染暴露和多基因易感性
2022/09/20
摘要
背景：呼出的一氧化氮(FeNO)浓度分数是嗜酸性粒细胞性气道炎症的生物标志物。我们探讨了在不同关键年龄阶段，长期暴露于空气污染和多基因易感性之间的相互作用。
方法：纳入GINIplus/LISA出生队列的青少年(15岁)(n = 2434)和纳入SALIA队列的220名老年妇女(平均75岁)(FeNO测量可用)进行了调查。研究了15年时间窗内SCAPE土地利用回归空气污染物浓度均值的环境主要效应，以及使用全基因组衍生单核苷酸多态性弹性净回归的内部权重进行多基因风险评分（PRS）的主要效应。此外，我们通过调整的线性回归模型研究了基因 - 环境相互作用（GxE）对自然对数转化FeNO水平的影响。
结果：虽然我们在两个年龄组中均未观察到显著的环境和多基因对气道炎症的主要影响，但在老年妇女的GxE模型中，我们发现长期暴露于二氧化氮(NO2)的强烈有害影响(FeNO增加16.2%，p值= 0.027)。分层分析发现，PRS与慢性NO2暴露之间的GxE效应，适用于从不吸烟的老年妇女和没有任何炎症性呼吸系统的青少年。
结论：FeNO测量是一种有用的生物标志物，可检测老年人NO2诱导的嗜酸性粒细胞性气道炎症的高风险。GxE对青少年或老年人气道炎症的影响的证据有限。应在亚群中进行进一步的GxE研究，以调查年龄阶段对气道炎症易感性不同的假设。
Airway inflammation in adolescents and elderly women: Chronic air pollution exposure and polygenic susceptibility
Kress S, Kilanowski A, Wigmann C, et al.
Abstract
BACKGROUND：The fractional exhaled nitric oxide (FeNO) concentration in the exhaled breath is a biomarker for eosinophilic airway inflammation. We explored the interplay between chronic air pollution exposure and polygenic susceptibility to airway inflammation at different critical age stages.
METHODS：Adolescents (15 yr) enrolled in the GINIplus/LISA birth cohorts (n = 2434) and 220 elderly women (75 yr on average) enrolled in the SALIA cohort with FeNO measurements available were investigated. Environmental main effects of the mean of ESCAPE land-use regression air pollutant concentrations within a time window of 15 years and main effects of the polygenic risk scores (PRS) using internal weights from elastic net regression of genome-wide derived single nucleotide polymorphisms were investigated. Furthermore, we examined gene-environment interaction (GxE) effects on natural log-transformed FeNO levels by adjusted linear regression models.
RESULTS：While we observed no significant environmental and polygenic main effects on airway inflammation in either age group, we found robust harmful effects of chronic nitrogen dioxide (NO2) exposure in the GxE models for elderly women (16.2 % increase in FeNO, p-value = 0.027). Stratified analyses found GxE effects between the PRS and chronic NO2 exposure in never-smoker elderly women and in adolescents without any inflammatory respiratory conditions.
CONCLUSIONS：FeNO measurement is a useful biomarker to detect higher risk of NO2-induced eosinophilic airway inflammation in the elderly. There was limited evidence for GxE effects on airway inflammation in adolescents or the elderly. Further GxE studies in subpopulations should be conducted to investigate the assumption that susceptibility to airway inflammation differs between age stages.
背景：呼出的一氧化氮(FeNO)浓度分数是嗜酸性粒细胞性气道炎症的生物标志物。我们探讨了在不同关键年龄阶段，长期暴露于空气污染和多基因易感性之间的相互作用。
方法：纳入GINIplus/LISA出生队列的青少年(15岁)(n = 2434)和纳入SALIA队列的220名老年妇女(平均75岁)(FeNO测量可用)进行了调查。研究了15年时间窗内SCAPE土地利用回归空气污染物浓度均值的环境主要效应，以及使用全基因组衍生单核苷酸多态性弹性净回归的内部权重进行多基因风险评分（PRS）的主要效应。此外，我们通过调整的线性回归模型研究了基因 - 环境相互作用（GxE）对自然对数转化FeNO水平的影响。
结果：虽然我们在两个年龄组中均未观察到显著的环境和多基因对气道炎症的主要影响，但在老年妇女的GxE模型中，我们发现长期暴露于二氧化氮(NO2)的强烈有害影响(FeNO增加16.2%，p值= 0.027)。分层分析发现，PRS与慢性NO2暴露之间的GxE效应，适用于从不吸烟的老年妇女和没有任何炎症性呼吸系统的青少年。
结论：FeNO测量是一种有用的生物标志物，可检测老年人NO2诱导的嗜酸性粒细胞性气道炎症的高风险。GxE对青少年或老年人气道炎症的影响的证据有限。应在亚群中进行进一步的GxE研究，以调查年龄阶段对气道炎症易感性不同的假设。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Science of the Total Environment, 2022, 841. doi: ARTN 15665510.1016/j.scitotenv.2022.156655）
（Science of the Total Environment, 2022, 841. doi: ARTN 15665510.1016/j.scitotenv.2022.156655）
Airway inflammation in adolescents and elderly women: Chronic air pollution exposure and polygenic susceptibility
Kress S, Kilanowski A, Wigmann C, et al.
Abstract
BACKGROUND：The fractional exhaled nitric oxide (FeNO) concentration in the exhaled breath is a biomarker for eosinophilic airway inflammation. We explored the interplay between chronic air pollution exposure and polygenic susceptibility to airway inflammation at different critical age stages.
METHODS：Adolescents (15 yr) enrolled in the GINIplus/LISA birth cohorts (n = 2434) and 220 elderly women (75 yr on average) enrolled in the SALIA cohort with FeNO measurements available were investigated. Environmental main effects of the mean of ESCAPE land-use regression air pollutant concentrations within a time window of 15 years and main effects of the polygenic risk scores (PRS) using internal weights from elastic net regression of genome-wide derived single nucleotide polymorphisms were investigated. Furthermore, we examined gene-environment interaction (GxE) effects on natural log-transformed FeNO levels by adjusted linear regression models.
RESULTS：While we observed no significant environmental and polygenic main effects on airway inflammation in either age group, we found robust harmful effects of chronic nitrogen dioxide (NO2) exposure in the GxE models for elderly women (16.2 % increase in FeNO, p-value = 0.027). Stratified analyses found GxE effects between the PRS and chronic NO2 exposure in never-smoker elderly women and in adolescents without any inflammatory respiratory conditions.
CONCLUSIONS：FeNO measurement is a useful biomarker to detect higher risk of NO2-induced eosinophilic airway inflammation in the elderly. There was limited evidence for GxE effects on airway inflammation in adolescents or the elderly. Further GxE studies in subpopulations should be conducted to investigate the assumption that susceptibility to airway inflammation differs between age stages.
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