Tobacco Documents Online

Section VII ( J Respiratory System i Summary Introduction-This sectionlocuses on non-neoplas- tic respiratory diseases and disorders of pulmonary function. Relationships to the inhalation of tobacco smoke have been intensively investigated. Studies summarized here may be broadly encompassed un- der six sub-sections: A. Airways Retention and Clearance Studies, B. Effects of Tobacco Smoke, Smoking and Smoke Components on Function of Pulmonary Cilia, Macrophages, and Surfactant, C. Pulmonary Function Studies, D. Epidemiological Studies, E. Tobacco Smoke and Pulmonary Infec- tion, F. Other Pulmonary Related Studies. A. Airways Retention and Clearance Studies Retention A number of studies related to airways retention of tobacco smoke and certain of its constituents have been conducted. With smoking of cigarettes labelled with 1-131 paraiodobenzoic acid with or without inhaling radioactivity could not be detected beyond coryna with scintillation camera, except in one instance of abnormally deep inspiration (1). In another study in humans a smoke-dosage apparatus was used to deliver a standard puff of cigarette smoke which was inhaled and subsequently exhaled into cold traps. Acetaldehyde, isoprene, acetone, acetonitrile, toluene, particulate matter, and carbon monoxide were measured and compared with the amounts found in noninhaled smoke. A 86% to 99% retention was found for all compounds except car- bon monoxide of which 54% was retained (2). Using similar procedures, mouth absorption (2-second du- ration) of these volatile and aerosol components in cigarette smoke were determined. Absorption was higher for water-soluble compounds (around 80%) than for non-water soluble compounds (around 20%) (3). Since most of the long-term tobacco smoke exposure experiments have been performed with animals inhaling through their noses, it is of im- portance to know to what extent the smoke is resorbed in the nasal cavities. In a study on rabbits the results suggested that a significant amount of smoke is absorbed. The mean value from eight animals of organic matter absorbed was 32% (4). A series of studies have been reported on the respiratory tract retention of individual constituents of the vapor phase of cigarette smoke. In the first of these, single-breath retention of acetaldehyde was determined in man. Under the most physiological conditions of rate and tidal volume the respiratory tract retention was about 60% (5). Subsequently, an animal model was sought that would duplicate the above findings in man. This was found in the dog, in (6), which total respiratory tract retention values also have been reported for formaldehyde, propionalde- hyde and acrolein (7); acetone and ammonia (8); isoprene and menthol (9); furan (10); toluene and benzene (11). Particle deposition in the human tracheobron- chial tree has also been studied by means of hollow silastic casts extending from the trachea through the segmental bronchi using a monodisperse test aero- sol. The reported distribution of sites of bronchial carcinoma was related to the distribution of sites of impaction observed in this study (12). Estimates have also been presented of the range of alveolar deposition of coal and quartz dust by nose and mouth breathing in a representative coal mine atmosphere which suggests that the marked individual differences that exist in the effective penetration of particles into the alveoli may have a bearing on susceptibility to pneumoconiosis among miners. Relatively little difference was apparent in head or alveolar deposition data between smokers and nonsmokers (13). The distribution of cadmium and nickel of tobacco during cigarette smoking has also been reported, the results suggesting to the authors a potential health hazard from these released elements to nonsmokers as well as smokers (14). The intriguing problem of the nature of the black pigment of the human lung has been examined chemically and with electron microscope. It is a mixture of inorganic materials (silicates, aluminates, and other trace metals), some elemental carbon, and a highly insoluble pigment, probably organic in nature. Concerning its origin, comparison of its composition with the medical history of the individ- ual failed to reveal any correlation in the group studied. Also, when the case histories of the pa- tients, their smoking histories, and their occupations were compared with the patterns of lung pigments observed in the electron microscope, no correlation was found between them (15). 291

® Respiratory System These data suggest that cigarette smoke modi- fies those metabolic activities of alveolar macro- phages required for uptake and killing of bacteria as well as the acellular material coating the macro- phage. 52. Peroxidation of lipids in alveolar macrophages; Production by aqueous extracts of cigarette smoke Patrick E. Lentz, and Nicholas R. DiLuzio Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana Archives of Environmental Health 28:279-282, 1974 This study was undertaken to investigate the peroxidation of lipids in alveolar macrophages, membrane, and supernatant fractions of alveolar macrophages, and pulmonary protective factor by aqueous extracts of cigarette smoke (AECS). Since lipid peroxidation has been demonstrated to alter markedly the integrity of cell and subcellular mem- branes with resultant loss of subcellular expression, the peroxidation of polyunsaturated lipids by free radicals or highly reactive chemical components of cigarette smoke could well contribute to the ob- served functional derangement of alveolar cells that results from cigarette smoke. Incubation of sonicates of rabbit alveolar macro- phages and pulmonary protective factor with AECS resulted in peroxidation of lipids, as estimated by the 2-thiobarbiturate acid reaction. The accumula- tion of malonaldehyde was not reduced by sup- plementing the incubation media with cysteine. These studies suggest that oxidants or free radicals in AECS-induce peroxidation of unsatu- rated lipids in alveolar macrophages and in an acellular material that coats the cells in the lung. 53. Alveolar cells: Depressant effect of cigarette smoke on protein synthesis Henry Yeager, Jr. (Herbert O. Sieker) Department of Medicine, Duke University School of Medicine and Veterans Administration Hospital, Durham, North Carolina Proceedings of the Society for Experimental Biology and Medicine 131:247-250, 1969 A study was made on the effect of cigarette smoke on protein synthesis in alveolar macrophages obtained from the lungs of rabbits, using incorpora- tion of uniformly labeled L-leucine-'*C as the in- dicator. Cigarette smoke solution was found to cause a dose-dependent decrease in the amount of ra- dioactivity appearing in acid-insoluble material, Alveolar cells pulse-labeled with leucine-'.'C and then incubated with smoke solution showed no more rapid decrease in acid insoluble radioactivity than control cells, indicating that the smoke solution had no effect on turnover of newly synthesized radioactive protein. Washing the cells after incuba- tion with smoke solution eliminated almost half of the smoke solution effect. Also, there was no dif- ference in viability between control cells and those treated with a volume of smoke solution causing 41% inhibition of protein synthesis, leading to the conclusion that cigarette smoke solution is capable of depressing protein synthesis in nonlethal doses and that this effect is partially reversible. When the particulate phase was removed by a Cambridge absolute filter, the resultant gas phase solution caused almost as much depression of protein synthe- sis as whole smoke solution. Relevance of these findings to in vivo con- ditions is noted to not be clear, since the con- centrations of smoke achieved in alveolar cells in the intact organism are unknown. Other support: The American Thoracic Society. 54. Altered morphology and increased acid hydrolase content of pulmonary macrophages f rom cigarette smokers R. Russell Martin Departments of Medicine, Indiana University School of Medicine, Indianapolis, and Baylor College of Medicine, Houston, Texas American Review of Respiratory Disease 107:596-601, 1973 Pulmonary alveolar macrophages were obtained by saline lavage from 24 healthy male volunteers, of whom 13 were nonsmokers and 11 were cigarette smokers with a mean cumulative exposure of 9.6 pack-years. Fewer than 5 per cent of macrophages from nonsmokers contained crystalloid, refractile cytoplasmic inclusions of autofluorescent material, whereas 30 to 95 per cent of macrophages from smokers contained this material. Multinucleated giant cells were present in the lavage from 3 of 11 smokers, but giant cells were not lavaged from any of the 13 nonsmokers. Acid hydrolase concentrations were increased to as much as 6 times normal in the 314