Baseline values, between and within subject variability of non-invasive biomarkers of inflammation and oxidative stress - Switzerland

Abstract
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In the field of engineered nanomaterials (ENMs) exposure biomonitoring, oxidative stress biomarkers measured in urine and exhaled breath condensate (EBC) appear promising to detect early effects. However, baseline values for the oxidative stress biomarkers are still not known. For human biomonitoring, different matrices can be used. Blood seems to be the ideal matrix for most chemicals but has an important disadvantage of being invasive. Our matrices permit a non-invasive biomonitoring.
We focus on four oxidative stress biomarkers: 8-OHdG, 8-isoprostane, malondialdehyde and H2O2. These biomarkers seems to be the most relevant for biomonitoring and for detecting early effects in workers handling ENMs.
A systematic literature review was performed to determine the baseline values of these biomarkers in urine and EBC in a healthy non-smoking adult (≥18 years) population. Searches were conducted for literature published since journal inception and up to April 2019 in the following bibliographic electronic databases: The Cochrane Central Register of controlled Trials, EMBASE, PubMed, and Web of Science. Two reviewers screened the titles and abstracts with disagreements resolved by consensus. The full-text review and the data extraction are ongoing.
A meta-analysis will be performed for each biomarker. As most of the selected studies include few participants and use non-standardized analytical methods, the results need to be harmonized to be able to establish baselines values and inter / intra individual variations.
We plan to carry out subgroup analysis by gender, by age and by country of origin. In addition, subgroup analyses will be done for people with respiratory diseases (COPD, asthma, lung cancer), for smokers and for workers exposed to ENMs.To our knowledge, this systematic review is the first providing baseline values for these four oxidative stress biomarkers. It is essential for enabling meaningful interpretation of the results from biomonitoring programs conducted in occupational and environmental settings.

Universe
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Healthy non-smoking adults (≥18 years) of both sexes.

Kind of data
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Text data / Systematic review requests

Mode of data collection
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Bibliographic electronic databases: The Cochrane Central Register of controlled Trials (CENTRAL, Cochrane Library), EMBASE, PubMed, and Web of Science.

Cleaning operations
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Two reviewers will independently performed in Rayyan QCRI a first screening of titles and abstracts retrieved during the searches. Abstracts that have provided insufficient information with regard to the inclusion and exclusion criteria will be retained and downloaded in the EndNote software for full-text analysis and re-assessed by two researchers independently. In case of disagreement on the inclusion/exclusion of one or more papers, the two reviewers will discuss their points of view; if no consensus is reached a third reviewer is consulted. This process allows to finalize the list of studies to be included in the review. Throughout this process, A PRISMA (Preferred Reporting Items for systematic Reviews and Meta-Analyses) flow diagram will be completed.

A data extraction form will be designed in advance according to the research objectives and contents of the articles. It will be tested by two independent researchers and validated by a statistician with strong experience in meta-analysis.
Two researchers will independently extract and check the published data.
The information extracted will be as follows: first author name, publication time, study type, analytic method, the sample time, the number of participants, the gender, the mean age, the mean BMI, their smoking status, season, occupation, pregnancy, diet, vitamin, exercise, outcomes, references, DOI.

摘要
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在工程纳米材料（ENMs）暴露生物监测领域，尿液和呼出气冷凝物（EBC）中测量的氧化应激生物标志物显示出检测早期效应的潜力。然而，氧化应激生物标志物的基线值仍不明确。对于人体生物监测，可以使用不同的基质。血液似乎是最理想的基质，适用于大多数化学物质，但其重要缺点是侵入性。我们的基质允许非侵入性生物监测。
我们专注于四种氧化应激生物标志物：8-OHdG、8-异前列腺素、丙二醛和H2O2。这些生物标志物似乎与生物监测和检测处理ENMs的工人早期效应最为相关。
为了确定健康非吸烟成人（≥18岁）群体中这些生物标志物在尿液和EBC中的基线值，我们进行了一项系统文献综述。搜索了自期刊创刊以来至2019年4月发表的文献，包括以下文献电子数据库：Cochrane中央对照试验注册、EMBASE、PubMed和Web of Science。两位审阅者筛选了标题和摘要，通过协商解决分歧。全文审查和数据提取正在进行中。
将对每个生物标志物进行荟萃分析。由于大多数选定的研究参与者数量较少且使用非标准化分析方法，因此需要对这些结果进行协调，以便建立基线值和个体间/个体内变异。
我们计划按性别、年龄和原籍国进行亚组分析。此外，还将对患有呼吸系统疾病（COPD、哮喘、肺癌）、吸烟者和暴露于ENMs的工人进行亚组分析。据我们所知，这项系统综述是首次提供这四种氧化应激生物标志物基线值的综述。这对于在职业和环境设置中进行的生物监测项目结果的合理解释至关重要。
总体
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健康非吸烟成人（≥18岁），不分性别。
数据类型
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文本数据/系统综述请求
数据收集方式
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文献电子数据库：Cochrane中央对照试验注册（CENTRAL，Cochrane图书馆）、EMBASE、PubMed和Web of Science。
数据清洗操作
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两位审阅者将独立地在Rayyan QCRI进行检索到的标题和摘要的初步筛选。关于纳入和排除标准的不足信息摘要将被保留，并下载到EndNote软件中进行全文分析和独立重新评估。如果对一篇或多篇论文的纳入/排除存在分歧，两位审阅者将讨论他们的观点；如果无法达成共识，将咨询第三位审阅者。此过程允许最终确定要纳入综述的研究列表。在整个过程中，将完成PRISMA（系统综述和荟萃分析首选报告项目）流程图。
将预先设计一个数据提取表，根据研究目标和文章内容。将由两位独立研究人员进行测试，并由具有丰富荟萃分析经验的统计学家进行验证。
两位研究人员将独立提取和检查已发表的数据。
提取的信息如下：第一作者姓名、发表时间、研究类型、分析方法、样本时间、参与者数量、性别、平均年龄、平均BMI、吸烟状况、季节、职业、怀孕、饮食、维生素、运动、结果、参考文献、DOI。