A harmonized protocol for an international multicenter prospective study of nanotechnology workers: the NanoExplore cohort

Nanotechnology applications are fast-growing in many industrial fields. Consequently, health effects of engineered nanomaterials (ENMs) should be investigated. Within the EU-Life project NanoExplore, we developed a harmonized protocol of an international multicenter prospective cohort study of workers in ENM-producing companies. This article describes the development of the protocol, sample size calculation, data collection and management procedures and discusses its relevance with respect to research needs. Within this protocol, workers’ ENM exposure will be assessed over four consecutive working days during the initial recruitment campaign and the subsequent follow-up campaigns. Biomonitoring using noninvasive sampling of exhaled breath condensate (EBC), exhaled air, and urine will be collected before and after 4-day exposure monitoring. Both exposure and effect biomarkers, will be quantified along with pulmonary function tests and diagnosed diseases reported using a standardized epidemiological questionnaire available in four languages. Until now, this protocol was implemented at seven companies in Switzerland, Spain and Italy. The protocol is well standardized, though sufficiently flexible to include company-specific conditions and occupational hygiene measures. The recruitment, to date, of 140 participants and collection of all data and samples, enabled us launching the first international cohort of nanotechnology workers. All companies dealing with ENMs could join the NanoExplore Consortium, apply this harmonized protocol and enter in the cohort, concieved as an open cohort. Its protocol meets all requirements of a hypotheses-driven prospective study, which will assess and reassess effects of ENM exposure on workers’ health by updating the follow-up of the cohort. New hypothesis could be also considered.

纳米技术应用在诸多工业领域中增速迅猛。因此，有必要针对工程化纳米材料（engineered nanomaterials, ENMs）的健康效应开展研究。在EU-Life项目NanoExplore的框架下，我们为工程化纳米材料生产企业的劳动者制定了一项国际多中心前瞻性队列研究的标准化方案。本文详述了该方案的制定过程、样本量测算方法、数据采集与管理流程，并探讨了其契合相关研究需求的适用性。在本方案中，于首次招募阶段及后续随访阶段，我们将连续四个工作日对劳动者的工程化纳米材料暴露情况进行评估。我们将在4天暴露监测的前后，采集呼出气冷凝物（exhaled breath condensate, EBC）、呼出气以及尿液的无创样本用于生物监测。我们将对暴露生物标志物与效应生物标志物进行定量检测，同步开展肺功能测试，并通过一份涵盖四种语言的标准化流行病学问卷收集已确诊疾病的相关信息。截至目前，该方案已在瑞士、西班牙与意大利的七家企业落地实施。该方案具备高度的标准化程度，同时拥有足够的灵活性以适配企业的特定条件与职业卫生管理要求。截至目前，本次研究已招募140名参与者，并完成了全部数据与样本的采集，从而得以启动首个纳米技术劳动者国际队列研究。所有涉及工程化纳米材料的企业均可加入NanoExplore联盟，采用本标准化方案并加入该队列——本队列定位为开放队列。本方案符合假说驱动型前瞻性研究的全部要求，将通过更新队列随访情况，对工程化纳米材料暴露对劳动者健康的影响进行评估与再评估。同时，本研究也可纳入新的研究假说。