Diacetyl in e-cigarette flavorings: Acute and subacute pulmonary effects

电子烟香料中的二乙酰：急性和亚急性肺部影响

• 批准号: 8953056
• 负责人: ROB S MCCONNELL
• 金额: $ 20.63万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8953056
• 关键词: Acute; Adolescent; Adolescent and Young Adult; Aerosols; Age; Amphiregulin; Animals; Awareness; Biological Markers; Breathing; Bronchiolitis Obliterans; Cells; Cellular Phone; Chemicals; Child; Chronic; Clara cell; Cotinine; Data; Data Collection; Development; Diacetyl; Dose; Electronic cigarette; Electronics; Enrollment; Epidermal Growth Factor Receptor; Epithelial; Epithelial Cells; Evaluation; Excretory function; Exposure to; Flavoring; Food; Goals; Guidelines; Health Hazards; Human; IL8 gene; Individual; Ingestion; Intervention; Laboratories; Ligands; Liquid substance; Lung; Lung diseases; Marketing; Measurement; Measures; Nicotine; Nicotine Dependence; Nitric Oxide; Obstructive Lung Diseases; Outcome; Persons; Population; Proteins; Public Health; Publishing; Pulmonary Function Test/Forced Expiratory Volume 1; Records; Regulation; Reporting; Research; Respiratory physiology; Role; Running; Safety; Serum; Solutions; System; Testing; Time; Tobacco; Toxic effect; Toxin; Ultrafine; aerosolized; airway inflammation; base; design; diketone; emerging adult; experience; food preparation; hazard; innovation; lung injury; multidisciplinary; public health relevance; respiratory; respiratory health; respiratory toxin; response; vaping

 DESCRIPTION (provided by applicant): Flavorings in liquids used in electronic nicotine delivery systems (ENDS) are a largely unrecognized potential respiratory hazard. There are thousands of such flavors in commercial use in ENDS, including a large proportion of sweet or creamy flavored ENDS solutions (among the most popular flavorings), used in marketing to children and emerging adults. Several diketone compounds (including diacetyl and 2,3-pentanedione), which are "generally recognized as safe" for ingestion, are commonly used in food products to give them a buttery or creamy flavoring, and have recently been shown to be present in sweet-flavored ENDS solutions. When inhaled, high doses of these diketones cause acute-onset bronchiolitis obliterans ("popcorn lung"), a severe and irreversible obstructive lung disease. In the only published study to measure diacetyl or 2,3-pentanedione in ENDS flavorings, these compounds were found to be present in 75% of 159 `sweet flavored' ENDS solutions. However, awareness of this problem is virtually absent from the public health and regulatory discussion of the impact of flavorings on ENDS users, and there has been little study of the pulmonary toxicity of flavorings used in ENDS products, although ENDS are designed to create an ultrafine aerosol that penetrates deeply into the lung. We propose to evaluate the respiratory effects associated with use of sweet- flavored ENDS in 60 users (children and emerging adults) of flavored ENDS solutions likely to contain diketones. We hypothesize that concentrations of diketones in sweet-flavored ENDS will predict adverse acute and subacute effects of ENDS on markers of respiratory health. Acute respiratory effects of using flavored ENDS solutions will be evaluated after a regulated, 5 minute `challenge' with each subject's ENDS solution in a laboratory setting, following a one-week run-in period with a standard ENDS solution without flavor (Specific Aim 1a). Subacute (week-long) respiratory effects will be evaluated after one week of flavored ENDS use (Aim 1b). Outcomes will include potential systemic biological markers of lung damage, including serum levels of club cell secreted protein (CCSP), AREG, and IL-8; and markers of airway inflammation [(fractional excretion of nitric oxide (FeNO)], and of functional changes in FEV1 and FVC. In Aim 2, we will estimate each individual's inhaled dose, based on concentrations of diacetyl and 2,3-pentanedione in each subject's solution, volume of solution used, repeated serum cotinine, and innovative use of data from the Smokio "Smart Vaping" ENDS, which uses an automatic system to record timing, number, and intensity of puffs using a chip within the ENDS that synchronizes data collection to the user's smartphone. Aim 3 will examine the diketone dose-response relationship to adverse respiratory health markers. Diacetyl and related diketone flavorings in ENDS are potentially a major public health threat to children because of widespread use and known respiratory toxicity. Assessment of acute and subacute effects is essential to characterizing this hazard, to the design of subsequent studies to investigate chronic effects, and to evaluation of the need for regulatory intervention.

 描述（由应用提供）：电子尼古丁输送系统（末端）中使用的液体中的调味料是一种很大程度上无法识别的潜在呼吸危害。目的是在商业用途中有成千上万种这种口味，其中包括大量的甜或奶油调味末端解决方案（在最受欢迎的口味中），用于儿童和新兴的成年人。几种二酮化合物（包括二乙酰基和2,3-戊二酮）“通常被认为是安全的”摄入量，通常用于食品中，以给它们提供黄油或奶油的调味料，最近已显示出在甜味味的末端溶液中存在。继承后，高剂量的这些二酮会导致急性发作的细支气管炎（“爆米花肺”），这是一种严重且不可逆的阻塞性肺部疾病。在唯一发表的研究中，用于测量末端调味剂中的二乙酰基或2,3-戊二酮，发现这些化合物存在于159个“甜味味”末端溶液中的75％中。但是，对这个问题的认识实际上是从公共卫生和对末端用户影响的监管讨论中几乎没有的，尽管末端旨在创建一种超铁醇，但几乎没有研究末端产品中使用的调味剂的肺毒性。我们建议评估60种可能包含二酮的火花末端溶液（儿童和新兴成年人）中使用甜味末端的呼吸效应。我们假设在甜味末端的二酮浓度将预测末端对呼吸健康标志物的急性和亚急性影响。在经过一周的一周磨合，具有标准末端溶液没有风味的一周磨合（特定的AIM 1A）之后，将在实验室环境中进行调节的5分钟“挑战”后，将评估使用调味端溶液的急性呼吸效应。一周的风味末端使用后，将评估亚急性（为期一周）的呼吸效应（AIM 1B）。结果将包括肺损伤的潜在系统生物学标志物，包括俱乐部细胞分泌蛋白（CCSP），AREG和IL-8的血清水平；气道注射的标记[（（（feno）极端（feno））以及FEV1和FVC的功能变化。在AIM 2中，我们将根据二乙基的浓度和2,3-戊烷的浓度来估算每个受试者在溶液中使用的溶液中的二乙基和2,3-戊烷的浓度。将数据收集在用户的智能手机中使用的时间，数量和强度，将数据收集到智能手机。设计随后的研究，以研究慢性影响，并评估监管干预的需求。