Detection and characterisation of inflammatory agents associated with bioaerosol emitted from biowaste and intensive agriculture

生物废物（如堆肥）和集约化农业（如饲养家禽/猪）工业排放对人类健康具有重要意义的生物气溶胶。虽然在确定这些工业的排放特征方面取得了一些进展，但在相关的研究问题方面却进展甚微：了解公众对生物气溶胶的暴露；将基于过程的暴露置于天然生物气溶胶（或其他人为来源）本底暴露的背景中；量化健康风险并制定基于健康的标准。所有这些领域的一个关键限制因素是缺乏先进的微生物学方法（采样、分析、解释）来量化和鉴定生物气溶胶的排放和扩散。我们目前的证据基础几乎完全依赖于短时间的“快照”采样和依赖培养的微生物学。虽然传统微生物学在特定情况下仍然适用，但需要新的快速有效的方法来了解不可活的生物气溶胶组分的性质和意义，并开发新一代监测方法来处理上述研究问题。在这个NERC计划的背景下，雾化内毒素是一个有吸引力的研究课题。它在生物废弃物和农业排放物中无处不在。以往的职业生物气溶胶研究已经建立了暴露-反应关系。在荷兰，内毒素被视为工人和公众基于健康的生物气溶胶排放限制/接触准则的主要候选者。然而，我们对环境空气中内毒素性质的基本理解存在差距，这反过来又源于测量技术的局限性，因此，对这种生物气溶胶分子的循证调节的开发和实施的信心继续受到限制。在这项研究中，我们的目标是开发能够表征和量化空气中内毒素排放的新方法。目的：发展新的方法来确定内毒素的大小和结构特征；-开发一种新型生物传感器，用于快速检测内毒素；其他炎症因子和细胞（活的/死的）-使用WIBS实时生物气溶胶传感器了解包括内毒素在内的生物气溶胶的排放和扩散-表征堆肥和农场现场特定行业的生物气溶胶排放-使用新方法检测生物废物和集约化农业设施中的微生物病原体-使用分散建模和Openair在生物废物/集约化农业设施周围生成改进的暴露评估。虽然我们的工作计划侧重于新的内毒素检测方法，但我们认识到空气中还有其他生物分子在吸入时会促进炎症。这些将被新型生物传感器检测到，我们的目标是区分信号通路，并展示细胞如何应对不同的生物分子挑战。研究团队在将前沿生物气溶胶科学转化为政策和实践方面拥有无与伦比的经验。受管制的工业过程对健康影响的不确定性对包括公众、监管机构、政府、工业和投资者在内的所有有关利益攸关方都是有害的。公众仍然担心潜在的健康影响。在保护公众健康和鼓励经济发展之间取得适当平衡方面，监管机构面临着不确定性。规划和发放许可证的延误限制了政府的废物战略和经济发展倡议，并给试图实现政府目标和建立可行业务的企业家带来了问题。虽然这项研究将以优秀的新科学为基础，但很明显，影响议程的驱动因素是将其转化为监管科学证据基础、新的监管指导和保护公众健康的模式的潜力。

The biowaste (eg composting) and intensive agriculture (eg housed poultry / pigs) industries emit bioaerosol of significance to human health. Whilst some progress has been made in characterising emissions from these industries relatively little headway has been made regarding the linked research questions of: understanding exposure of the general public to bioaerosol; putting process-based exposures into the context of background exposure to natural bioaerosol (or other anthropogenic sources); quantifying health risk and setting health-based standards. A critical limiting factor in all of these areas is the lack of advanced microbiological methods (sampling, analytical, interpretative) to quantify and qualify bioaerosol emissions and dispersion. Our current evidence base is almost entirely reliant on short duration "snapshot" sampling and culture-dependent microbiology. Whilst traditional microbiology remains fit for purpose in specific circumstances, new fast and efficient methods are needed to understand the nature and significance of non-viable bioaerosol fractions and to develop a new generation of monitoring approaches to deal with the research questions posed above.Aerosolised endotoxin is an attractive research subject in the context of this NERC programme. It is ubiquitous in biowaste and agricultural emissions. Previous occupational bioaerosol research has established an exposure-response relationship. In the Netherlands, endotoxin is regarded as the prime candidate for health-based bioaerosol emission limits / exposure guidelines for workers and the public. Yet, confidence in the development and implementation of evidence-based regulation of this bioaerosol molecule continues to be constrained by gaps in our fundamental understanding of the nature of endotoxin in ambient air which in turn stems from limitations in measurement techniques. In this research we aim to develop new methodologies capable of characterising and quantifying emissions of endotoxin in air.Objectives - develop new methods to size fractionate endotoxin and elucidate structural features;- develop a novel biosensor for rapid detection of endotoxin, other inflammatory agents and cells (live/dead)- use the WIBS real-time bioaerosol sensor to understand emission and dispersion of bioaerosol including endotoxin- characterise industry-specific bioaerosol emissions at composting and farm sites- detect microbial pathogens at biowaste and intensive agricultural facilities using novel methods- generate improved exposure assessments around biowaste / intensive agricultural facilities using dispersion modelling and Openair.Whilst our work plan focuses on new endotoxin detection methods we are cogniscent of the fact that there are other biomolecules in air that promote inflammation when inhaled. These will be detected by the novel biosensor and we aim to distinguish the signalling pathways and demonstrate how the cells respond to different biomolecular challenges.The research team has unparalleled experience in translating cutting edge bioaerosol science into policy and practice. Uncertainty with respect to health effects from regulated industrial processes is deleterious to all stakeholders concerned including the public, regulators, the Government, industry and investors. The public remains fearful of the potential health impacts. Regulators face uncertainty in terms of striking the right balance between public health protection and encouraging economic development. Planning and licensing delays constrain Government waste strategy and economic development initiatives and create problems for entrepreneurs trying to deliver Government targets and establish viable businesses. Whilst this research will be underpinned by excellent new science, it is clear that the impact agenda is driven by the potential for translating this into a regulatory science evidence base, new regulatory guidance and models for the protection of public health.