线粒体生物标志物、城市居民暴露与6个月以上儿童哮喘结局的关联
2023/11/23
摘要
背景：确定对环境暴露反应的生物标志物并评估其是否可预测呼吸系统结局，可能有助于优化儿童哮喘的环境和医疗方法。相对线粒体(mt)DNA丰度和其他潜在的线粒体氧化应激指标可能为儿童对其变化的环境改变的分子反应提供一个敏感的指标。
方法：我们利用了两个城市儿童队列(儿童哮喘的环境控制作为附加疗法(ECATCh);哥伦比亚儿童环境健康中心(CCCEH))，目的是确定口腔mtDNA中的生物标志物是否与6个月期间的气道炎症和肺功能改变相关，并捕获对多种外部应激源(如室内过敏原和细颗粒物[PM2.5])的生物反应。qPCR法扩增mtDNA相对含量，焦磷酸测序法检测转移RNA苯丙氨酸/rRNA 12S(TF/RNR1)、细胞色素c氧化酶(CO1)和羧肽酶O (CPO)甲基化水平。两个队列的居住暴露和呼吸系统结局数据一致。我们利用重复测量和多元回归模型评估了线粒体生物标志物、呼吸系统结局和住宅暴露(PM2.5、过敏原)之间的关系，并针对潜在混杂因素和随时间变化的哮喘进行了校正。
结果：我们发现，在6个月的随访中，哮喘患者的TF/RNR1甲基化水平比非哮喘患者高0.64倍(参数估计(PE) 0.64，标准误0.28,p=0.03)。在前瞻性分析中，CPO甲基化与随后的用力肺活量(FVC;PE -0.03，标准误0.01,p=0.02)。室内PM2.5与TF/RNR1甲基化水平升高无关(PE 0.015，标准误0.006,p=0.01)。
结论：口腔细胞中选择性的mtDNA检测可能表明儿童对有毒环境暴露的反应，并选择性地与哮喘和肺功能相关。
Associations between mitochondrial biomarkers, urban residential exposures and childhood asthma outcomes over 6 months
Rachel L. Miller, Janelle Rivera, Lydia Lichtiger et al.
Abstract
BACKGROUND:Determining biomarkers of responses to environmental exposures and evaluating whether they predict respiratory outcomes may help optimize environmental and medical approaches to childhood asthma. Relative mitochondrial (mt) DNA abundance and other potential mitochondrial indicators of oxidative stress may provide a sensitive metric of the child’s shifting molecular responses to its changing environment.
METHODS:We leveraged two urban childhood cohorts (Environmental Control as Add-on Therapy in Childhood Asthma (ECATCh); Columbia Center for Children’s Environmental Health (CCCEH)) to ascertain whether biomarkers in buccal mtDNA associate with airway inflammation and altered lung function over 6 months of time and capture biologic responses to multiple external stressors such as indoor allergens and fine particulate matter (PM2.5). Relative mtDNA content was amplified by qPCR and methylation of transfer RNA phenylalanine/rRNA 12S (TF/RNR1), cytochrome c oxidase (CO1), and carboxypeptidase O (CPO) was measured by pyrosequencing. Data on residential exposures and respiratory outcomes were harmonized between the two cohorts. Repeated measures and multiple regression models were utilized to assess relationships between mitochondrial biomarkers, respiratory outcomes, and residential exposures (PM2.5, allergens), adjusted for potential confounders and time-varying asthma.
RESULTS: We found across the 6 month visits, a 0.64 fold higher level of TF/RNR1 methylation was detected among those with asthma in comparison to those without asthma ((parameter estimate (PE) 0.64, standard error 0.28, p = 0.03). In prospective analyses, CPO methylation was associated with subsequent reduced forced vital capacity (FVC; PE -0.03, standard error 0.01, p = 0.02). Bedroom dust mouse allergen, but not indoor PM2.5, was associated with higher methylation of TF/RNR1 (PE 0.015, standard error 0.006, p = 0.01).
CONCLUSIONS: Select mtDNA measures in buccal cells may indicate children’s responses to toxic environmental exposures and associate selectively with asthma and lung function.
背景：确定对环境暴露反应的生物标志物并评估其是否可预测呼吸系统结局，可能有助于优化儿童哮喘的环境和医疗方法。相对线粒体(mt)DNA丰度和其他潜在的线粒体氧化应激指标可能为儿童对其变化的环境改变的分子反应提供一个敏感的指标。
方法：我们利用了两个城市儿童队列(儿童哮喘的环境控制作为附加疗法(ECATCh);哥伦比亚儿童环境健康中心(CCCEH))，目的是确定口腔mtDNA中的生物标志物是否与6个月期间的气道炎症和肺功能改变相关，并捕获对多种外部应激源(如室内过敏原和细颗粒物[PM2.5])的生物反应。qPCR法扩增mtDNA相对含量，焦磷酸测序法检测转移RNA苯丙氨酸/rRNA 12S(TF/RNR1)、细胞色素c氧化酶(CO1)和羧肽酶O (CPO)甲基化水平。两个队列的居住暴露和呼吸系统结局数据一致。我们利用重复测量和多元回归模型评估了线粒体生物标志物、呼吸系统结局和住宅暴露(PM2.5、过敏原)之间的关系，并针对潜在混杂因素和随时间变化的哮喘进行了校正。
结果：我们发现，在6个月的随访中，哮喘患者的TF/RNR1甲基化水平比非哮喘患者高0.64倍(参数估计(PE) 0.64，标准误0.28,p=0.03)。在前瞻性分析中，CPO甲基化与随后的用力肺活量(FVC;PE -0.03，标准误0.01,p=0.02)。室内PM2.5与TF/RNR1甲基化水平升高无关(PE 0.015，标准误0.006,p=0.01)。
结论：口腔细胞中选择性的mtDNA检测可能表明儿童对有毒环境暴露的反应，并选择性地与哮喘和肺功能相关。
（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）
（Environmental Research 239 (2023) 117342 DOI:10.1016/j.envres.2023.117342）
（Environmental Research 239 (2023) 117342 DOI:10.1016/j.envres.2023.117342）
Associations between mitochondrial biomarkers, urban residential exposures and childhood asthma outcomes over 6 months
Rachel L. Miller, Janelle Rivera, Lydia Lichtiger et al.
Abstract
BACKGROUND:Determining biomarkers of responses to environmental exposures and evaluating whether they predict respiratory outcomes may help optimize environmental and medical approaches to childhood asthma. Relative mitochondrial (mt) DNA abundance and other potential mitochondrial indicators of oxidative stress may provide a sensitive metric of the child’s shifting molecular responses to its changing environment.
METHODS:We leveraged two urban childhood cohorts (Environmental Control as Add-on Therapy in Childhood Asthma (ECATCh); Columbia Center for Children’s Environmental Health (CCCEH)) to ascertain whether biomarkers in buccal mtDNA associate with airway inflammation and altered lung function over 6 months of time and capture biologic responses to multiple external stressors such as indoor allergens and fine particulate matter (PM2.5). Relative mtDNA content was amplified by qPCR and methylation of transfer RNA phenylalanine/rRNA 12S (TF/RNR1), cytochrome c oxidase (CO1), and carboxypeptidase O (CPO) was measured by pyrosequencing. Data on residential exposures and respiratory outcomes were harmonized between the two cohorts. Repeated measures and multiple regression models were utilized to assess relationships between mitochondrial biomarkers, respiratory outcomes, and residential exposures (PM2.5, allergens), adjusted for potential confounders and time-varying asthma.
RESULTS: We found across the 6 month visits, a 0.64 fold higher level of TF/RNR1 methylation was detected among those with asthma in comparison to those without asthma ((parameter estimate (PE) 0.64, standard error 0.28, p = 0.03). In prospective analyses, CPO methylation was associated with subsequent reduced forced vital capacity (FVC; PE -0.03, standard error 0.01, p = 0.02). Bedroom dust mouse allergen, but not indoor PM2.5, was associated with higher methylation of TF/RNR1 (PE 0.015, standard error 0.006, p = 0.01).
CONCLUSIONS: Select mtDNA measures in buccal cells may indicate children’s responses to toxic environmental exposures and associate selectively with asthma and lung function.
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抑制HMGB1可过ROS/ AMPK/自噬通路减轻TDI诱导的职业性哮喘
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