In Vivo Biomarker that Identifies Waterpipe Smoking-related Lung Health

抽象的。水烟斗，一种吸烟的工具，在美国越来越多地使用。很多水- 烟斗吸烟者认为，水能过滤“毒素”，因此是一种更安全的吸烟替代品。 香烟。关于水烟斗吸烟对健康影响的数据很少，而且没有联邦法规。 关于它的用法的文章。基于这样一种认识，即呼吸道是除肺炎以外最直接的器官。 对水管烟雾构成的危害，因此很可能容易受到水管吸烟的毒性影响，而且 呼吸道上皮生物学对环境高度敏感，我们的目标是发展- 以呼吸道上皮为基础的活体呼吸道试验对吸入水杨酸的毒性敏感 烟斗吸烟和肺部健康的预测。我们有目的地专注于年轻人 只吸水烟斗的人。我们的策略是基于一项初步研究，评估了 21例年轻、轻用水管患者的小气道上皮(SAE)和肺临床参数 只有与n=19性别和种族相比较的吸烟者与健康的从不吸烟者匹配。令人惊讶的是，哇- 烟斗吸烟者咳嗽和痰积分较高，肺弥散能力较低，且显著 与健康的非吸烟者相比，SAE转录组异常。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- 将作为SAE异常的替代物的检测；以及(2)是 用这种方法评估的呼吸道转录组仅仅是暴露的证据，还是代表了 是否发出与肺健康临床参数相关的呼吸毒性？为了回答这些问题-- ，我们提出了一项横断面研究设计，以评估年龄、性别和种族的队列 匹配的受试者包括：仅吸水烟者(n=200)和从不吸烟者(n=100)。这群人 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 咳嗽和痰记分；(2)尿可替宁和血中碳氧合血红蛋白水平；(3)全肺功能。 测试；(4)胸部成像；(5)来自两个站点的呼吸道上皮转录组，即SAE (金标准，但不适用于大型研究)和鼻黏膜上皮(暴露的上皮 吸入烟雾，作为SAE的替代品)。使用标准的统计方法，数据-- 将分析TA以确定：(1)SAE转录组的异常(目标1)；(2)异常 在鼻腔上皮转录组中(目标2)；以及(3)生物异常是否与ab-1相关。 肺功能是否正常，如果是的话，鼻腔上皮转录组是否可以替代 SAE转录组在预测肺毒性中的作用(目标3)。如果成功，这些数据将有助于向 FDA对吸食水烟对呼吸健康的风险，并提供了一种体内生物标志物，可以 将在未来的研究中用于评估与吸烟有关的水嘴对肺部健康的风险。

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.