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.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
Project #
Application #
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Los Angeles
Internal Medicine/Medicine
Schools of Medicine
Los Angeles
United States
Zip Code
Chao, Chun; Jacobson, Lisa P; Tashkin, Donald et al. (2009) Recreational amphetamine use and risk of HIV-related non-Hodgkin lymphoma. Cancer Causes Control 20:509-16
Chao, Chun; Jacobson, Lisa P; Jenkins, Frank J et al. (2009) Recreational drug use and risk of Kaposi's sarcoma in HIV- and HHV-8-coinfected homosexual men. AIDS Res Hum Retroviruses 25:149-56
Chao, Chun; Jacobson, Lisa P; Tashkin, Donald et al. (2008) Recreational drug use and T lymphocyte subpopulations in HIV-uninfected and HIV-infected men. Drug Alcohol Depend 94:165-71
Roth, Michael D; Whittaker, Katherine M; Choi, Ruth et al. (2005) Cocaine and sigma-1 receptors modulate HIV infection, chemokine receptors, and the HPA axis in the huPBL-SCID model. J Leukoc Biol 78:1198-203
Roth, Michael D; Whittaker, Katherine; Salehi, Ken et al. (2004) Mechanisms for impaired effector function in alveolar macrophages from marijuana and cocaine smokers. J Neuroimmunol 147:82-6
Gardner, Brian; Zhu, Li X; Roth, Michael D et al. (2004) Cocaine modulates cytokine and enhances tumor growth through sigma receptors. J Neuroimmunol 147:95-8
Zhu, Li X; Sharma, Sherven; Gardner, Brian et al. (2003) IL-10 mediates sigma 1 receptor-dependent suppression of antitumor immunity. J Immunol 170:3585-91
Shay, Angela Hanchi; Choi, Ruth; Whittaker, Katherine et al. (2003) Impairment of antimicrobial activity and nitric oxide production in alveolar macrophages from smokers of marijuana and cocaine. J Infect Dis 187:700-4
Baldwin, Gayle Cocita; Choi, Ruth; Roth, Michael D et al. (2002) Evidence of chronic damage to the pulmonary microcirculation in habitual users of alkaloidal (""crack"") cocaine. Chest 121:1231-8
Kleerup, Eric C; Koyal, Sankar N; Marques-Magallanes, Jose A et al. (2002) Chronic and acute effects of ""crack"" cocaine on diffusing capacity, membrane diffusion, and pulmonary capillary blood volume in the lung. Chest 122:629-38

Showing the most recent 10 out of 23 publications