COCAINE SMOKING EFFECTS ON LUNG PHYSIOLOGY, HOST DEFENSE

吸食可卡因对肺部生理和宿主防御的影响

• 批准号: 2120735
• 负责人: DONALD P TASHKIN
• 金额: $ 33.36万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-06-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2120735
• 关键词: Escherichia coli; Staphylococcus aureus; actins; alveolar macrophages; bactericidal immunity; biopsy; bronchoscopy; crack cocaine; diagnostic respiratory lavage; exercise; histopathology; human subject; marijuana abuse; membrane permeability; respiratory epithelium; respiratory function; tobacco abuse; toxicant interaction

A four-year study is proposed to investigate the effects of current persistent or previous habitual smoking of cocaine on the lung. The proposed study would expand on findings from our previous study of the pulmonary effects of regular smoking of cocaine with and without marijuana and/or tobacco. Specific attention will be paid to possible effects of habitual cocaine smoking on 1) respiratory symptoms and pulmonary physiology, 2) airway epithelial histopathology and alveolar cytology, and 3) pulmonary alveolar host defenses. Pulmonary physiologic effects of cocaine that will be investigated include alterations in ventilatory mechanics, airway reactivity, gas transfer (i.e., diffusing capacity, fractionated into its alveolar-capillary membrane and capillary blood volume components), exercise tolerance, gas exchange during maximum exercise, alveolar epithelial permeability (assessed by measurement of lung clearance of radiolabeled DTPA) and pulmonary and systemic vascular pressures and resistance. These physiologic studies will be carried out in selected cocaine smokers with an without demonstrable diffusion impairment, as well as before and immediately after experimental administration of cocaine (in smoked form or intravenously), to investigate the mechanism and clinical significance of the reduction in single-breath diffusing capacity previously observed by us and others in association with heavy cocaine smoking, even in the absence of marijuana and/or tobacco. To further investigate effects of cocaine smoking on bronchial epithelial histopathology and alveolar cell numbers, type and function, fiberoptic bronchoscopy, bronchial mucosal biopsies and bronchoalveolar lavage (BAL) will be performed in smokers of cocaine alone (n=24), cocaine and marijuana (n=24), cocaine and tobacco (n=24), marijuana only (n=24) and tobacco only (n=24) and 24 nonsmokers. Material obtained from BAL, including pulmonary alveolar macrophages (PAMs) and alveolar epithelial lining fluid (ELF) from these subjects will also be used to investigate the effect of cocaine smoking on pulmonary alveolar host defenses. Specifically, BAL-derived cells and fluid will be used to examine the effect of cocaine smoking on a) cytoskeletal-related functions of PAMs (chemotaxis to bacterial stimuli and complement; phagocytosis of opsonized and opsonized bacteria; O2- dependent and O2-independent mechanisms of bacterial killing and destruction; F-actin content and assembly in response to phagocytic stimuli); b) antibacterial activity of PAMs against S. aureus and E. coli; and c) pulmonary interstitial lymphocytes, epithelial cells and components of alveolar epithelial lining fluid that are important in the lung's defense against infection.

建议进行一项为期四年的研究， 长期或以前习惯性吸食可卡因。 的 拟议的研究将扩大我们以前的研究结果， 经常吸烟的可卡因的肺部影响，有和没有 大麻和/或烟草 将特别注意可能的 习惯性吸食可卡因对1）呼吸道症状和 肺生理学，2）气道上皮组织病理学和肺泡 细胞学和3）肺泡宿主防御。 肺生理学 可卡因的影响，将被调查包括改变， 呼吸力学、气道反应性、气体转移（即，扩散 容量，分为肺泡毛细血管膜和毛细血管 血容量成分），运动耐量，最大时的气体交换 运动，肺泡上皮通透性（通过测量 放射性标记DTPA的肺清除率）以及肺和全身血管 压力和阻力。 这些生理学研究将在 在选定的可卡因吸烟者中， 以及实验前和实验后立即 给予可卡因（以烟熏形式或静脉注射）， 探讨其减少的机制及临床意义。 我们和其他人以前观察到的单次呼吸扩散能力， 与大量吸食可卡因有关，即使没有大麻 和/或烟草。 为了进一步研究吸食可卡因对 支气管上皮组织病理学和肺泡细胞数量、类型和 功能，纤维支气管镜检查，支气管粘膜活检和 将在可卡因吸烟者中进行支气管肺泡灌洗（BAL） 单独（n = 24），可卡因和大麻（n = 24），可卡因和烟草（n = 24）， 仅大麻（n = 24）和仅烟草（n = 24）以及24名非吸烟者。 从BAL中获得的材料，包括肺泡巨噬细胞 （PAM）和肺泡上皮细胞衬里液（ELF） 也将被用来调查可卡因吸烟对 肺泡宿主防御 具体地，BAL-derived细胞和 液体将用于检查可卡因吸烟对a） PAM的细胞毒性相关功能（对细菌刺激的趋化性 和补体;调理和调理细菌的吞噬作用; O2- 依赖和O2非依赖的细菌杀灭机制， F-肌动蛋白含量和组装对吞噬细胞的反应 B）PAM对S. aureus和e. c）肺间质淋巴细胞、上皮细胞和 肺泡上皮细胞衬里液的成分，这些成分在 肺对感染的防御