In Vivo Biomarker that Identifies Waterpipe Smoking-related Lung Health

识别与水烟吸烟相关的肺部健康的体内生物标志物

• 批准号: 9353458
• 负责人: RONALD G CRYSTAL
• 金额: $ 50.85万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9353458
• 关键词: Address; Age; Air; Biological Assay; Biological Markers; Biology; Blood; Breathing; Carbon Monoxide; Carboxyhemoglobin; Charcoal; Chest; Cigarette; Clinical; Cotinine; Coughing; Cross-Sectional Studies; Data; Diffuse; Environment; Epithelial; Epithelium; Ethnic Origin; Fruit; Future; Gender; Goals; Gold; Health; Image; Knowledge; Light; Link; Lung; Measures; Middle East; Nasal Epithelium; Normalcy; Nose; Organ; Pulmonary function tests; Questionnaires; Regulation; Research Design; Respiratory System; Respiratory physiology; Respiratory tract structure; Risk; Risk Marker; Sampling; Site; Smoke; Smoker; Smoking; Sputum; Tobacco; Tobacco smoke; Tobacco use; Toxic effect; Toxin; Urine; Water; airway epithelium; base; cohort; epidemiology study; hookah; in vivo; instrument; never smoker; non-smoker; respiratory; respiratory health; transcriptome; young adult

Abstract. Waterpipe, an instrument for smoking tobacco, is of increasing use in the US. Many water- pipe smokers believe that water filters out “toxins” and, therefore, is a safer smoking alternative to cigarettes. There is a paucity of data on the health effects of waterpipe smoking, and no federal regu- lations as to its use. Based on the knowledge that the respiratory tract is the organ most directly ex- posed to waterpipe smoke, and thus likely vulnerable to toxicity from waterpipe smoking, and that the biology of the respiratory tract epithelium is highly sensitive to the environment, our goal is to devel- op an in vivo respiratory tract epithelium-based assay sensitive to the toxicity of inhaled wa- terpipe tobacco smoke and predictive of lung health. We are purposefully focused on young adult waterpipe-only smokers. Our strategy is based on a preliminary study assessing the transcriptome of the small airway epithelium (SAE) and lung clinical parameters in n=21 young, light-use waterpipe- only smokers compared to n=19 gender and ethnicity matched healthy never smokers. Strikingly, wa- terpipe smokers had higher cough and sputum scores, lower lung diffusing capacity, and a markedly abnormal SAE transcriptome compared to the healthy nonsmokers. The questions to be addressed are: (1) can we develop a sensitive, easily carried out in vivo respiratory tract epithelial transcriptome- based assay that will serve as surrogate for abnormalities in the SAE; and (2) are the changes in the respiratory tract transcriptome assessed by this assay simply evidence of exposure or do they repre- sent respiratory toxicity that correlates with clinical parameters of lung health? To answer these ques- tions, we propose a cross-sectional study design to assess a cohort of age, gender and ethnicity matched subjects, including: waterpipe-only smokers (n=200) and never smokers (n=100). The cohort will be assessed by: (1) questionnaires to document tobacco use, other exposures, lung health, and cough and sputum scores; (2) urine cotinine and blood carboxyhemoglobin levels; (3) full lung func- tion tests; (4) chest imaging; and (5) the respiratory tract epithelial transcriptome from 2 sites, the SAE (the gold standard, but impractical for large studies) and the nasal epithelium (an epithelium exposed to inhaled smoke, to serve as a surrogate for the SAE). Using standard statistical approaches, the da- ta will be analyzed to determine: (1) abnormalities in the SAE transcriptome (aim 1); (2) abnormalities in the nasal epithelial transcriptome (aim 2); and (3) if the biologic abnormalities correlate with ab- normalities in the lung function, and if so, if the nasal epithelial transcriptome can be a surrogate for the SAE transcriptome in predicting lung toxicity (aim 3). If successful, this data will help inform the FDA of the risk to respiratory health of waterpipe smoking and provide an in vivo biomarker that can be used in future studies to assess wateripipe smoking-associated risk to lung health.

摘要：水烟是一种吸烟工具，在美国越来越多地使用。 吸烟者相信水可以过滤掉“毒素”，因此是比吸烟更安全的替代品 关于吸水烟对健康影响的数据很少，也没有联邦法规。 基于呼吸道是最直接的器官这一知识。 接触水烟烟雾，因此很可能容易受到水烟吸烟的毒性影响，并且 呼吸道上皮细胞的生物学特性对环境高度敏感，我们的目标是开发- op 一种基于呼吸道上皮的体内测定法，对吸入的毒性敏感 terpipe烟草烟雾和肺部健康预测我们有目的地关注年轻人。 我们的策略基于评估转录组的初步研究。 n=21 名经常使用水烟的年轻人的小气道上皮 (SAE) 和肺部临床参数 与 n=19 性别和种族相匹配的健康从不吸烟者相比，只有吸烟者。 吸食terpipe的人咳嗽和咳痰评分较高，肺弥散能力较低，并且肺功能明显下降。 与健康非吸烟者相比异常的 SAE 转录组需要解决的问题。 是：（1）我们能否开发出一种敏感的、易于在体内进行的呼吸道上皮转录组—— 基础检测将作为 SAE 异常的替代；(2) 是 SAE 的变化； 通过这种简单的分析暴露证据评估呼吸道转录组，或者它们是否代表 发送与肺部健康临床参数相关的呼吸道毒性？ 因此，我们提出了一项横断面研究设计来评估一组年龄、性别和种族 匹配的受试者，包括：仅吸水烟者 (n=200) 和从不吸烟者 (n=100)。 将通过以下方式进行评估：(1) 记录烟草使用、其他暴露、肺部健康和 咳嗽和痰液评分；（2）尿液可替宁和血液碳氧血红蛋白水平；（3）全肺功能 化测试；(4) 胸部影像学；(5) 2 个部位的呼吸道上皮转录组，SAE （黄金标准，但对于大型研究来说不切实际）和鼻上皮（暴露的上皮） 吸入烟雾，作为 SAE 的替代）使用标准统计方法，da-。 将分析 ta 以确定：(1) SAE 转录组异常（目标 1）；(2) 鼻上皮转录组（目标 2）；以及（3）生物学异常是否与 ab-相关 肺功能正常，如果是这样，鼻上皮转录组是否可以替代 SAE 转录组预测肺毒性（目标 3）如果成功，该数据将有助于为相关人员提供信息。 FDA 认识到吸水烟对呼吸系统健康的风险，并提供一种体内生物标志物 在未来的研究中用于评估水烟吸烟对肺部健康的相关风险。