Lungs Of Cigarette Smokers Research Articles

Lung cancer: is the increasing incidence due to radioactive polonium in cigarettes?

This paper presents clinical, experimental, and epidemiologic evidence to help explain the rapidly increasing incidence of primary lung cancer, with recently observed reversal in leading cell type from squamous cell to adenocarcinoma. It postulates that this may be due to changes in modern cigarettes, with or without filters, which allow inhalation of increased amounts of radioactive lead and polonium and decreased amounts of benzopyrene. This hypothesis is based upon measurements of increased concentrations of radioactive polonium in the lungs of cigarette smokers, in modern tobaccos grown since 1950, and in high-phosphate fertilizers used for tobacco farming in industrialized countries. Critical support for this thesis is based upon experimental animal studies in which lung cancers that resemble adenocarcinomas are induced with as little as 15 rads of radioactive polonium, equal to one fifth the dosage inhaled by cigarette smokers who average two packs a day during a 25-year period.

Cigarette smoking and lung destruction. Accumulation of neutrophils in the lungs of cigarette smokers.

It has been hypothesized that lung destruction in persons with emphysema associated with cigarette smoking is mediated by elastase released by neutrophils that have migrated to the alveolar structures in response to cigarette smoke. To directly evaluate this hypothesis, cell suspensions, isolated from bronchoalveolar lavage fluid and from open lung biopsies of nonsmokers and cigarette smokers with normal lung parenchyma and from open lung biopsies of nonsmokers and cigarette smokers who have sarcoidosis were evaluated for the presence of neutrophils. A significantly increased number of neutrophils was present in the cell suspensions isolated from bronchoalveolar lavage fluid and from open lung biopsies of both normal and sarcoid cigarette smokers compared with that in the nonsmokers (p less than 0.01, each comparison). Evaluation of the alveolar macrophages present in lavage fluid suggested a mechanism by which neutrophils may be attracted to the lungs of cigarette smokers: alveolar macrophages of cigarette smokers release a chemotactic factor for neutrophils, whereas alveolar macrophages of nonsmokers do not. In addition, alveolar macrophages of nonsmokers, after exposure to cigarette smoke, in vitro, are stimulated to release this chemotactic factor. These studies demonstrate that an increased number of neutrophils are present in the lungs of cigarette smokers compared with that in nonsmokers and suggest that cigarette smoke may attract neutrophils to the lung by stimulating alveolar macrophages to release a potent chemotactic factor for neutrophils.

Smokers Do Not Have Less Functional Alpha1-Protease Inhibitor in Their Lower Respiratory Tracts Than Nonsmokers

Cigarette smoking is the major risk factor in the development of pulmonary emphysema, a condition thought to result from an imbalance between the elastase and antielastase levels in the lungs. An increased number of neutrophils and alveolar macrophages in the lungs of smokers could account for an elevation of their elastase burden. A decreased level of functional alpha1-protease inhibitor (alpha1-PI) has been reported in the bronchoalveolar lavage (BAL) fluid from smokers as compared with nonsmokers. 1 Gadek JE Fells GA Crystal RG Cigarette smoking induces functional antiprotease deficiency in the lower respiratory tract of humans. Science. 1979; 206: 1315-1316 Crossref PubMed Scopus (264) Google Scholar , 2 Carp H Miller F Hoidal JR Janoff A Potential mechanism of emphysema: α1-proteinase inhibitor recovered from lungs of cigarette smokers contains oxidized methionine and has decreased elastase inhibitory capacity. Proc Natl Acad Sci USA. 1982; 79: 2041-2045 Crossref PubMed Scopus (268) Google Scholar We determined binding and inactivation of 3H-porcine pancreatic elastase and 125I-human neutrophil elastase by alpha1-PI in BAL from volunteers; we also measured the inhibition by BAL of porcine pancreatic elastase-catalyzed solubilization of 3H-elastin. The mean levels of functional alpha1-PI in the BAL of smokers were comparable to those of nonsmokers.

Potential mechanism of emphysema: alpha 1-proteinase inhibitor recovered from lungs of cigarette smokers contains oxidized methionine and has decreased elastase inhibitory capacity.

The elastase inhibitory capacity per mg of alpha 1-proteinase inhibitor (alpha 1 PI) was measured in the bronchoalveolar lavage (BAL) fluid from 26 healthy smokers and 24 nonsmokers. Activity was decreased by 40% in smokers' BAL fluid compared to nonsmokers. This effect was demonstrable by using human neutrophil elastase as well as porcine pancreatic elastase as test enzyme (elastase, EC 3.4.21.11) and was reproducible when selected individuals in each group underwent lavage on repeated occasions. In contrast, the functional activity of alpha 1-antichymotrypsin was not decreased in smokers' BAL fluid. Crossed antigen-antibody electrophoresis confirmed that inactivation of alpha 1 PI was responsible for the decrease in the elastase inhibitory capacity of smokers' BAL fluid. alpha 1 PI purified from smokers' BAL fluids contained methionine sulfoxide (4 mol/mol of inactive alpha 1 PI), whereas alpha 1 PI from nonsmokers' BAL fluid did not. Smokers' alpha 1 PI was indistinguishable from nonsmokers' alpha 1 PI on the basis of electrophoretic mobility, molecular weight, and immunoreactivity. Thus, oxidation of methionine residues in lung alpha 1 PI is associated with cigarette smoking. Because chemical oxidation of alpha 1 PI in vitro causes loss of its elastase inhibitory activity, the present observations suggest that methionine oxidation may also be the cause of decreased functional activity of lung alpha 1 PI in smokers. Oxidative inactivation of alpha 1 PI in the lungs of cigarette smokers may play a role in the development of pulmonary emphysema in this group.

Cigarette Smoking Induces Functional Antiprotease Deficiency in the Lower Respiratory Tract of Humans

Current concepts of the pathogenesis of emphysema suggest that it results from an imbalance of elastase and antielastase activity within the alveolar structures. Although emphysema that is associated with hereditary deficiency of serum alpha 1-antitrypsin conforms to this scheme, the major risk factor in the more common form of emphysema is cigarette smoking. A study was designed to evaluate the premise that cigarette smoking may be associated with an acquired, functional defect in lung alpha 1-antitrypsin. Determination of the antielastase activity of alpha 1-antitrypsin obtained from the lungs of smoking and nonsmoking individuals revealed a nearly twofold reduction in the functional activity of this elastase inhibitor in the lungs of cigarette smokers. These data suggest that cigarette smokers may lose some of the normal antielastase protective screen of the lower respiratory tract, making them more vulnerable to destructive lung disease.

Elastic recoil of the lung in cigarette smokers: the effect of nebulized bronchodilator and cessation of smoking.

The mechanical properties of the lung, forced vital capacity, flow-volume relationships, lung volume, and single-breath N2 curve were determined in 16 nonsmokers and 19 smokers. Pulmonary elastic recoil, Pst (1), was significantly lower at all lung volumes, as were flow parameters, whereas lung volumes were higher in smokers of both sexes. The variables derived from forced vital capacity and single-breath N2 were significantly different from nonsmokers in male smokers but not in female smokers. The inhalation of nebulized bronchodilator was attended by a significant decrease in Pst (1) and in upstream flow resistance in smokers. After cessation of smoking Pst (1) decreased to values similar to those seen after bronchodilator administration, whereas resumption of smoking led to reversal of the pressure-volume curve. The data suggest that the elastic properties of the lungs are altered in cigarette smokers, but the extent of the disturbance is masked by constriction of the alveolar ducts or peripheral airways while smoking, and that these are unmasked by the administration of nebulized bronchodilator or by cessation of smoking.

Influence of cigarette smoke on guinea pigs. Effect of pulmonary cells and serum antitrypsin levels.

A significant increase in the number of polymorphonuclear leukocytes recoverable from the lungs of guinea pigs has been demonstrated to occur in response to exposure to cigarette smoke. This increase was accompanied by no change in serum antitrypsin levels over the ten-week exposure period. These observations., if applicable to man, suggest that a source of proteolytic enzymes in relatively high concentrations may be continuously present in the lungs of cigarette smokers. The depressant effect of cigarette smoke on natural respiratory defenses leaves the system increasingly susceptible to bacterial infections and even greater inflammation results. When this is added to an already excessive number of leukocytes chronically present, the resultant concentration of proteolytic enzymes may be greater than can be counteracted by the available enzyme inhibiting agent.

Polonium-210 activity in the lungs of cigarette smokers.

In an attempt to contribute additional information on the natural radiation burden applied to the human body the polonium-210 content in different parts of the lungs of human cigarette smokers and nonsmokers was measured. The average activity of polonium-210 (210Po) assessed in some brands of cigarettes is summarized in table form. The 210Po inhalation rate was determined to be 2% for an individual smoking 20 cigarettes daily. The 210Po activities found in different parts of the lung tissue of both smoking and nonsmoking individuals are summarized in table form. For these analyses the parenchymal tissue the bifurcation and the bronchial tissue were dissected prior to measurement. The lung tissue dissected from heavy smokers was shown to contain 3-4 times the 210Po activity found in the lungs of nonsmokers.