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.

抽象。水烟筒，一种吸烟的工具，在美国越来越多地使用。很多水- 抽烟斗的人认为，水可以过滤“毒素”，因此， 香烟关于水烟对健康影响的数据很少，也没有联邦法规- 关于其使用。根据呼吸道是最直接排出的器官的知识， 会受到水管烟雾的影响，因此很可能容易受到水管烟雾的毒性，而且 呼吸道上皮细胞的生物学对环境高度敏感，我们的目标是开发 op一种对吸入性水毒性敏感的体内呼吸道上皮细胞测定法， 烟斗烟草烟雾和肺部健康预测。我们有目的地关注年轻人 只抽烟的人我们的策略是基于一项初步研究，评估转录组， 在n=21例年轻、轻度使用水管的患者中， 与n=19相比，只有吸烟者的性别和种族与从不吸烟的健康人相匹配。令人惊讶的是，瓦- 烟斗吸烟者咳嗽和咳痰评分较高，肺弥散功能较低， 与健康非吸烟者相比，SAE转录组异常。需要解决的问题 是：（1）我们是否可以开发一个敏感的，容易进行的体内呼吸道上皮转录组- 作为SAE异常的替代物的基于试验的变化;以及（2） 呼吸道转录组通过该检测评估仅仅是暴露的证据，还是它们代表了 与肺部健康的临床参数相关的呼吸毒性？为了回答这些问题- 因此，我们提出了一个横断面研究设计，以评估年龄，性别和种族的队列 匹配的受试者包括：仅吸烟者（n=200）和从不吸烟者（n=100）。队列 将通过以下方式进行评估：（1）记录烟草使用、其他暴露、肺部健康的问卷，以及 咳嗽和咳痰评分;（2）尿可替宁和血碳氧血红蛋白水平;（3）全肺功能， 来自2个部位的呼吸道上皮转录组，SAE (the金标准，但对于大型研究不切实际）和鼻上皮（暴露于 吸入烟雾，作为SAE的替代）。使用标准统计方法， 分析ta以确定：（1）SAE转录组异常（目的1）;（2）异常 在鼻上皮转录组中（aim 2）;以及（3）如果生物学异常与ab-相关， 如果是的话，如果鼻上皮转录组可以替代肺功能， SAE转录组预测肺毒性（目的3）。如果成功，这些数据将有助于通知 美国食品和药物管理局的风险，呼吸道健康的水管吸烟，并提供了一个体内生物标志物， 在未来的研究中使用，以评估水管吸烟对肺部健康的相关风险。