In this paper, we review methodological approaches used in studies that evaluated the association between occupational exposure to quaternary ammonium compounds (quats) and occupational asthma. This association is of interest because quats are a common active ingredient of disinfectants and have been linked to work-related asthma in some circumstances. However, any evidence-based assessment of an exposure-outcome association needs to consider both strengths and limitations of the literature. We focus on publications cited by various US and international organizations. Eighteen investigations included in the review fall into two broad categories: case reports and challenge studies of individual patients and population studies that examined the association between quats and asthma occurrence in groups of subjects. We evaluated these studies guided by questions that address whether: exposure data on specific quat(s) and other agents that may cause asthma were included, new asthma cases were differentiated from asthma exacerbation, and information on respiratory sensitivity versus irritation was given. We also assessed consistency across studies. Studies of individual patients, particularly those that provided detailed information on challenge test results, document cases of asthma induced by exposure to quats. By contrast, studies of occupational groups with the highest potential for quats exposure (e.g., cleaners and farmers) do not consistently report increased incidence of asthma due specifically to quats. The unresolved methodological issues include: poor understanding of exposure pathways considering that quats are non-volatile, lack of quantitative data allowing for identification of an asthmagenicity threshold, insufficient information on whether quats are sensitizers or act via dose-dependent irritation or some other mechanism, and inability to quantify risk of new-onset asthma attributable to quats. Another important area of uncertainty is the lack of information on the specific quats being used. There is also a lack of data capable of distinguishing the effects of quats from those of other chemical and biological workplace exposures. The current state-of-the-science does not allow a proper assessment of the potential link between quats and occupational asthma.

中文翻译：

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对哮喘发生性和职业清洁进行人类研究的方法学评估：以季铵盐化合物（“季铵盐”）为例。

在本文中，我们回顾了用于评估职业性季铵盐化合物（季铵盐）与职业性哮喘之间关系的研究中使用的方法学方法。之所以感兴趣，是因为季铵盐是消毒剂的常见活性成分，并且在某些情况下与工作相关的哮喘有关。然而，对暴露-结果关联的任何基于证据的评估都需要考虑文献的优势和局限性。我们专注于美国和国际组织引用的出版物。该评价中包括的18项调查分为两大类：个案研究和针对个别患者的挑战研究，以及人群研究，研究了一组受试者中quat与哮喘发生之间的关系。我们以以下问题为指导对这些研究进行了评估，这些问题解决了以下问题：是否包括了特定季铵盐和其他可能引起哮喘的药物的暴露数据，将新的哮喘病例与哮喘急性发作区分开来，并提供了有关呼吸敏感性与刺激性的信息。我们还评估了研究之间的一致性。个别患者的研究，尤其是提供有关挑战试验结果详细信息的患者的研究，记录了因接触四下喹啉引起的哮喘病例。相比之下，对从事四氯化碳暴露可能性最高的职业群体（例如，清洁工人和农民）的研究并不能始终如一地报告说，由于四氯化碳引起的哮喘发病率增加。未解决的方法学问题包括：考虑到季铵盐是非挥发性的，对暴露途径的了解不足，缺乏定量数据，无法确定哮喘发生阈值；关于季铵盐是否是致敏剂或通过剂量依赖性刺激或其他机制起作用的信息不足，以及无法量化由于季铵盐引起的新发哮喘的风险。不确定性的另一个重要方面是缺少有关所使用的特定季铵盐的信息。也缺乏能够将季铵盐的影响与其他化学和生物工作场所暴露的影响区分开的数据。当前的科学现状无法正确评估夸脱与职业性哮喘之间的潜在联系。以及无法量化由于青枯引起的新发哮喘的风险。不确定性的另一个重要方面是缺少有关所使用的特定季铵盐的信息。也缺乏能够将季铵盐的影响与其他化学和生物工作场所暴露的影响区分开的数据。当前的科学现状无法正确评估夸脱与职业性哮喘之间的潜在联系。以及无法量化由于青枯引起的新发哮喘的风险。不确定性的另一个重要方面是缺少有关所使用的特定季铵盐的信息。也缺乏能够将季铵盐的影响与其他化学和生物工作场所暴露的影响区分开的数据。当前的科学现状无法正确评估夸脱与职业性哮喘之间的潜在联系。