IUF - Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, Düsseldorf 40225, Germany; Medical Research School Düsseldorf, Heinrich Heine University, Universitätsstraße 1, Düsseldorf 40225, Germany.
Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstädter Landstr. 1, Neuherberg 85764, Germany; Institute for Medical Information Processing, Biometry, and Epidemiology; Pettenkofer School of Public Health, LMU Munich, Geschwister-Scholl-Platz 1, Munich 80539, Germany; Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, University of Munich Medical Center, Lindwurmstr. 4, Munich 80337, Germany.
Sci Total Environ. 2022 Oct 1;841:156655. doi: 10.1016/j.scitotenv.2022.156655. Epub 2022 Jun 11.
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.
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.
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 (NO) 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 NO exposure in never-smoker elderly women and in adolescents without any inflammatory respiratory conditions.
FeNO measurement is a useful biomarker to detect higher risk of NO-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.
呼出气中部分一氧化氮（FeNO）浓度是嗜酸性气道炎症的生物标志物。我们探索了慢性空气污染暴露与气道炎症多基因易感性在不同关键年龄阶段的相互作用。
我们对 GINIplus/LISA 出生队列中（15 岁）的 2434 名青少年和 SALIA 队列中（75 岁，平均年龄）的 220 名老年女性进行了调查，这些女性可进行 FeNO 测量。在 15 年的时间窗口内，使用 ESCAPE 土地利用回归空气污染物浓度的平均值进行环境主要效应的研究，并使用来自全基因组衍生单核苷酸多态性的弹性网回归内部权重进行多基因风险评分（PRS）的主要效应研究。此外，我们通过调整线性回归模型，检查了基因-环境相互作用（GxE）对自然对数转换的 FeNO 水平的影响。
虽然我们在两个年龄组中都没有观察到环境和多基因主要效应对气道炎症的显著影响，但我们发现慢性二氧化氮（NO）暴露在老年女性的 GxE 模型中具有明显的有害影响（FeNO 增加 16.2%，p 值=0.027）。分层分析发现，在从不吸烟的老年女性和没有任何炎症性呼吸道疾病的青少年中，PRS 与慢性 NO 暴露之间存在 GxE 效应。
FeNO 测量是检测老年人群中由 NO 引起的嗜酸性气道炎症的高危人群的有用生物标志物。在青少年或老年人中，对气道炎症的 GxE 影响的证据有限。应在亚人群中进行进一步的 GxE 研究，以调查气道炎症易感性在不同年龄阶段存在差异的假设。
