Contribution of Inhalation for Human Smoke Exposure

描述（由申请人提供）：吸烟的健康后果与烟雾暴露直接相关。虽然尼古丁、一氧化碳和其他烟草烟雾成分的毒理学和药理学相关暴露发生在下支气管和肺泡组织，但烟雾暴露的定量测量通常是通过雾化参数-口腔暴露测量来确定的。口腔水平的暴露与全身烟雾暴露只有微弱和可变的相关性，这表明吸入措施可能是更好的暴露定量预测指标。本提案将比较烟状地形参数和吸入参数，以确定哪种方法更好地模拟人类烟雾暴露。将使用基于实验室的CReSS系统收集Puff地形测量数据，同时使用最近开发的基于感应容积脉搏波仪（lifesshirt）的呼吸监测系统收集吸入测量数据。血浆尼古丁和呼出一氧化碳的变化将被用作暴露于烟草烟雾的生物标志物。该研究的具体研究目的是：(1)确定一组吸入参数是否比一组雾化参数更能预测尼古丁和一氧化碳的增加；(2)确定戒烟和吸“超轻”高通风卷烟引起的雾化参数和吸入参数的变化（已知可改变雾化参数的操作）；(3)确定在戒烟条件下和在高通风条件下（“低产量”）吸烟时，雾化和吸入参数的变化是否能预测暴露的生物标志物（尼古丁和一氧化碳增加）。这些目标将在以实验室为基础的学科交叉研究中解决。大约135名年龄在18岁或以上、通常抽全口味（焦油= 16毫克）过滤嘴香烟的男性和女性吸烟者将被招募。吸烟状况将通过生化和自我报告进行核实。受试者将参加三个平衡的实验环节。在每个疗程中，他们将穿着“生活衣”，通过吹烟嘴吸一支烟。在一个疗程中，他们将抽自己品牌的香烟；在另一种情况下，他们会在一夜戒烟后抽自己品牌的烟；在另一个阶段，他们将抽一种“超轻香烟”（焦油= 5毫克），其味道与他们自己的品牌（薄荷或非薄荷）相似。这项拟议的研究将作为评估一种新的感应容积描记技术在模拟人类烟雾暴露中的实际应用的第一步。因此，该提案代表了对测量烟雾暴露的额外维度的独特探索。这种方法有可能从根本上改变从口腔到肺部的烟雾暴露的测量、相关药效学活性的部位和许多病理后果的表现。虽然有强有力的流行病学数据将吸烟与成瘾和病理联系起来，但将个人接触与吸烟行为或其病理后果（如成瘾、肺病）联系起来的数据相对较少。以前的暴露测量依赖于描述烟雾进入口腔的雾化行为，然而与病理相关的暴露发生在肺部。目前的建议是第一个参数比较雾化和吸入方法，努力开发更好和更相关的方法来量化烟雾暴露。

DESCRIPTION (provided by applicant): The health consequences of smoking are directly related to smoke exposure. Although toxicologically and pharmacologically relevant exposure to nicotine, carbon monoxide (CO) and other components of tobacco smoke occurs at lower bronchial and lung alveolar tissue, quantitative measures of smoke exposure are ordinarily indexed by puffing parameters - measures of mouth exposure. Mouth-level exposure is only weakly and variably correlated with systemic smoke exposure suggesting that inhalation measures may be better quantitative predictors of exposure. This proposal will compare puff topography parameters and inhalation parameters to determine which method better models human smoke exposure. Puff topography measures will be collected using the lab-based CReSS system, and inhalation measures will be collected concomitantly using a recently-developed respiratory monitoring system based on inductive plethysmography (LifeShirt). Changes in plasma nicotine and exhaled CO (boosts) will be used as biomarkers of exposure to tobacco smoke. The specific research aims of the study are (1) to determine if a set of inhalation parameters is better at predicting nicotine and CO boosts compared to a set of puff parameters; (2) to determine changes in puff and inhalation parameters induced by tobacco abstinence and smoking an "ultra-light" highly ventilated cigarette (manipulations known to change puff parameters); and (3) to determine if changes in puff and inhalation parameters predict biomarkers of exposure (nicotine and CO boosts) in conditions of tobacco abstinence and when smoking a highly ventilated ("low-yield'). These aims will be addressed in a laboratory-based within subject cross-over study. Approximately 135 male and female established smokers, age 18 or over, who usually smoke a full flavored (tar = 16 mg) filtered cigarette will be recruited. Smoking status will be verified biochemically and by self-report. Subjects will participate in three counter-balanced laboratory sessions. In each session they will smoke a single cigarette through a puff topography mouthpiece while wearing the LifeShirt. In one session, they will smoke their own brand of cigarette; in another they will smoke their own brand after overnight abstinence; and in another session they will smoke an "ultra-light cigarette" (tar = 5 mg) that will be flavored similarly to their own brand (menthol or non menthol). The proposed research will serve as an initial step to evaluate the practical application of a new inductive plethysmography technology to model human smoke exposure. As such, this proposal represents a unique exploration of an additional dimension in measuring smoke exposure. This method has the potential to fundamentally change the measurement of smoke exposure from the mouth to the lungs, the site of relevant pharamcodynamic activity and manifestation of many pathological consequences. Although there is strong epidemiological data that links cigarette smoking to addiction and pathology, there is relatively little data that links exposure in an individual to the behavior of smoking or its pathological consequences (e.g. addiction, lung disease). Previous measures of exposure have relied upon puffing behavior which describes the entry of smoke into the mouth, however exposure relevant to pathology occurs in the lung. The present proposal is the first to parametrically compare puffing and inhalation methods in an effort develop better and more relevant methods to quantify smoke exposure.