Cellular immunity in cigarette smokers

T-lymphocyte counts have been measured and the skin test with amnestic antigens performed in 85 clinically healthy men aged 18-42 (the mean age 34) smoking 15-25 cigarettes daily during 2-25 years and in a reference group of 49 non-smokers aged 17-50 (the mean age 31). The absolute count of circulating lymphocytes has been found increased in 38 subjects who smoked for up to 10 years (the mean period 6.5 years), whereas in the subjects who smoked for more than 10 years (the mean period 18.5 years) the absolute and the relative counts of T-lymphocytes have been decreased, the tuberculin test has been much more often negative (14.9% vs. 6.1 and 5.3%), as well as the distreptase test (19.1% vs. 8.2 and 5.3%). These data confirm the suppressor effect of tobacco smoke, inhaled for a long time, on cell-mediated immunity in humans.     

Pneumococcus-specific immunoglobulin E in cigarette smokers

A relationship between elevated serum immunoglobulin E levels and smoking has been demonstrated in epidemiological studies. Allergy skin test data suggest that the excess immunoglobulin E of smokers is not specific for aeroallergens. It is possible that the excess immunoglobulin E is specific for microorganisms that often infect the lower respiratory tract of smokers. To investigate this possibility we utilized a radioallergosorbent test assay for detecting serum immunoglobulin E specific for Streptococcus pneumoniae, an organism commonly isolated from the respiratory tract of smokers with chronic bronchitis. We assayed sera of thirty smokers and thirty nonsmokers for immunoglobulin E specific for Streptococcus pneumoniae. Individual sera were considered positive for pneumococcus-specific immunoglobulin E if the binding was at least twice the non-specific binding at the total immunoglobulin E concentration of the particular serum. Eleven of the thirty sera of smokers and two of the thirty nonsmokers were positive for pneumococcus-specific immunoglobulin E. By chi-square analysis of these data, the prevalence of pneumococcus-specific immunoglobulin E was significantly greater in the smoking group compared with the non-smoking group (P less than 0.02). These results suggest that the excess immunoglobulin E of smokers is, at least in part, specific for microorganisms that infect the airways.     

Decreased ceruloplasmin ferroxidase activity in cigarette smokers

Ceruloplasmin is one of the most important antioxidant proteins in serum. Ceruloplasmin functions as a ferroxidase that oxidizes iron to the Fe3+ state, thereby preventing Fe2+-catalyzed lipid peroxidation and cellular damage. Despite increased antigenic amounts of ceruloplasmin, cigarette smoker serum has previously been shown to exhibit significantly less antioxidant activity than non-smoker serum. We demonstrate that the decreased antioxidant activity of cigarette smoker serum may be explained by a decrease in ceruloplasmin ferroxidase activity. Smokers had a 14% decrease in serum ceruloplasmin ferroxidase activity (units per milliliter) compared with nonsmokers. There was a 24% decrease in ferroxidase activity per milligram of ceruloplasmin in smokers compared with nonsmokers (0.32 +/- 0.009 U/mg vs 0.42 +/- 0.020 U/mg, p less than 0.005). Smoker serum also contained significantly less ceruloplasmin-specific antioxidant activity than nonsmoker serum. These observations may explain the decrement in smoker serum antioxidant activity that could predispose cigarette smokers to increased oxidant injury.     

Serum angiotensin converting enzyme activity in cigarette smokers

Low activity of angiotensin converting enzyme (ACE) has been reported in patients with smoking related diseases, such as chronic bronchitis, emphysaema and carcinoma of the lung [1] but this has not been reported in healthy, chronic smokers. Serum ACE was measured in 40 healthy cigarette smokers and in 42 healthy non-smokers. The mean value was significantly lower in the smokers. Hence a non-smokers. The mean value was significantly lower in the smokers. Hence a patient's smoking habits should be taken into consideration when assessing the significance of his serum ACE levels.     

Lisinopril improves endothelial function in chronic cigarette smokers.

Cigarette smoking is a pernicious risk factor for the pathogenesis of coronary artery disease, and endothelial dysfunction is an important antecedent event in this process. This is important, as cigarette smoke is directly toxic to endothelial cells. Inhibitors of angiotensin-converting enzyme (ACE) have been shown to improve endothelial function in diabetes and hypercholesterolaemia, and are a promising option in smokers. We treated 23 subjects (age 38+/-12 years; mean+/-S.D.) for 8 weeks with 20 mg of lisinopril in a randomized controlled trial. Endothelial function was assessed by measurement of forearm blood flow responses to intra-arterial infusions of endothelial-dependent and -independent vasodilators and an endothelial-dependent vasoconstrictor [acetylcholine, sodium nitroprusside and monomethyl-L-arginine (L-NMMA) respectively] using venous occlusion plethysmography. Lisinopril significantly increased the forearm blood flow response to acetylcholine by 20% [lisinopril, 3.12+/-0.37 (mean+/-S.E.M.); placebo, 2.58+/-0.25; P=0.02, 95% confidence intervals (CI) 0.09, 1.06] (values given are ratios of flow in the infused arm to that in the control arm); there was no effect on the response to sodium nitroprusside (lisinopril, 3.97+/-0.40; placebo, 3.92+/-0.39; P=0.84; 95% CI -0.50, 0.61). The vasoconstrictor response to L-NMMA demonstrated a significant improvement (lisinopril, 0.77+/-0.06; placebo, 0.95+/-0.05; P<0.001; 95% CI -0.09, -0.27). In conclusion, these results indicate that ACE inhibition can improve endothelial function in cigarette smokers. We show that lisinopril improves both receptor-mediated and tonic NO release. The mechanism could be either that lisinopril limits the angiotensin II-induced production of superoxide radicals which would normally inactivate NO, or that lisinopril may increase bradykinin-mediated NO release.     

Facilitated nitration and oxidation of LDL in cigarette smokers

BACKGROUND: Cigarette smoking increases the risk of developing atherosclerosis and ischaemic heart disease. Smoking-induced oxidative stress is considered to favour oxidation of low-density lipoprotein (LDL) and subsequently promotes the atherogenic process. We investigated whether peroxynitrite, a reaction product of cigarette smoke, is involved in facilitated oxidation of LDL in smokers. MATERIALS AND METHODS: Plasma LDL was obtained from 10 healthy asymptomatic cigarette smokers and 10 healthy nonsmokers. The state of enhanced oxidative stress in the plasma was assessed by LDL subfraction assay using anion-exchange high-performance liquid chromatography (AE-HPLC) and measurements of thiobarbituric acid-reactive substances (TBARS), 8-hydroxydeoxyguanosine (8-OHdG), vitamin E, 3-nitrotyrosine and 3-chlorotyrosine. RESULTS: Smokers showed a significantly higher level of TBARS and 8-OHdG as well as a significantly lower level of vitamin E than nonsmokers, even after stopping smoking for 10 h or more. The LDL subfraction assay demonstrated an increase in oxidatively modified LDL, as expressed by lower levels of LDL1 and higher levels of LDL2. The 3-nitrotyrosine levels in apolipoprotein B in LDL were significantly higher in smokers than nonsmokers, while the 3-chlorotyrosine levels remained unchanged. In addition, these changes observed in the smokers were further accelerated within 30 min after resumption of cigarette smoking when compared with the levels before smoking resumption. CONCLUSION: The present study suggests that peroxynitrite plays a significant role in oxidative modification of plasma LDL induced by cigarette smoking.     

Tissue origin of serum placental-like alkaline phosphatase in cigarette smokers

A variety of solubilised tissue extracts from cigarette smokers and non-smokers have been screened quantitatively for both placental alkaline phosphatase (PLAP) and placental-like alkaline phosphatase (PLAP-like AP) in order to identify the possible tissue origins of the circulating PLAP-like AP found in most smokers. Lung alveolar tissue, and to a lesser extent colonic tissues, contained both PLAP-like AP and PLAP. Tissues from smokers and non-smokers contained comparable proportions and amounts of PLAP and PLAP-like AP. No other tissue source of PLAP-like AP was found other than those previously reported for testicular, endometrial and thymic tissue. Selective release of PLAP-like AP from the lung in cigarette smokers seems likely to be a major source for this isoenzyme in peripheral circulation.     

Enhanced cytotoxic potential of alveolar macrophages from cigarette smokers

Cigarette smoking increases the numbers and oxidative metabolism of alveolar macrophages. Increased production of superoxide (O2-) and H2O2 by alveolar macrophages may contribute to the pathogenesis of cigarette-induced lung diseases. The cytotoxicity mediated by alveolar macrophages from smokers (n = 11) and nonsmokers (n = 13) was compared in an in vitro assay in which the target cells were chromium 51-labeled lung explants. The spontaneous cellular cytotoxicity mediated by smoker macrophages was significantly greater than that of nonsmoker macrophages (cytotoxic index 20.3% +/- 1.9% compared with 5.5% +/- 0.9%, P less than 0.001). Phorbol myristate acetate significantly increased the cytotoxic index of nonsmoker macrophages but did not cause further increases in smoker macrophage killing. The antioxidants superoxide dismutase and catalase produced partial inhibition of smoker macrophage cytotoxicity, suggesting that target cell killing was mediated in part by oxidant mechanisms. Supplementation of smokers' diets with high-dose oral vitamin E failed to decrease smoker alveolar macrophage cytotoxicity. These findings demonstrate that smoker alveolar macrophages possess enhanced cytotoxic potential for normal lung parenchymal cells.     

Mediators of hypersensitivity in the sputum of young, symptomatic cigarette smokers

We have measured the concentrations of mediators of hypersensitivity in the sputum of twenty-five young, symptomatic cigarette smokers who regularly expectorated and twenty-three matched non-smokers with a respiratory infection. The measurements included sputum and blood eosinophils, IgE, IgG, IgA and IgM and also sputum histamine. We found a significant increase of sputum histamine, and a higher sputum/serum ratio of IgE in smokers when compared to non-smokers. These findings support the view that the bronchial inflammatory response in smokers, as in chronic bronchitis, involves the participation of mediators of hypersensitivity.     

Factors associated with nicotine dependence among African American women cigarette smokers

Cigarette smoking contributes to disproportionate morbidity and mortality among African Americans. Purposes of the study were to describe smoking behavior and test a model of nicotine dependence among African American women. Participants (n = 187) smoked a low rate of high nicotine mentholated cigarettes and had a mean salivary cotinine of 402 ng/mL. The proposed model predicted 48% of variance in nicotine dependence with smoking to cope, number of cigarettes/day, positive outcome expectancies about smoking, and interest in quitting, as significant contributors. Suggested interventions include developing alternative coping skills, cognitive restructuring, and techniques focused on the precontemplation stage of smoking cessation. © 1993 John Wiley & Sons, Inc.     

Spontaneous hydrogen peroxide release from alveolar macrophages of some cigarette smokers

Alveolar macrophages were retrieved by bronchoalveolar lavage (BAL) from 30 patients, 24 smokers and six nonsmokers. The macrophages were separated from other cells in the BAL fluid by glass adherence. The amount of hydrogen peroxide released into the media by these macrophages was then measured by a new method of determining hydrogen peroxide concentration. Two groups were found. Group 1, who did not spontaneously release hydrogen peroxide, were mostly nonsmokers (six of nine), and group 2, who spontaneously secreted hydrogen peroxide (87.5 +/- 17.08 nmol/10(6) macrophages [mean +/- SEM]), were all smokers (21 of 21). When the alveolar macrophages in group 1 were stimulated with phorbol myristate acetate, they secreted as much hydrogen peroxide as the stimulated macrophages of group 2 (group 1: 125.0 +/- 92.08 nmol/10(6) macrophages, group 2: 116.7 +/- 14.82 nmol/10(6) macrophages). We conclude that there is a subset of smokers whose alveolar macrophages spontaneously release hydrogen peroxide.     

Altered skeletal muscle glucose transport and blood lipid levels in habitual cigarette smokers

We determined whether habitual cigarette smoking alters insulin-stimulated glucose transport and GLUT4 protein expression in skeletal muscle. Vastus lateralis muscle was obtained from 10 habitual cigarette smokers and 10 control subjects using an open muscle biopsy procedure. Basal 3-O-methylglucose transport was twofold higher (P > 0·01) in muscle from habitual smokers (0·05 ± 0·08 vs. 1·04 ± 0·19 μmol ml^?1 h^?1; controls vs. smokers respectively). Insulin (600 pmol l^?1) increased glucose transport 2·6-fold (P > 0·05) in muscle from control subjects, whereas no significant increase was noted in habitual smokers. Skeletal muscle GLUT4 protein expression was similar between the groups. FFA levels were elevated in the smokers (264 ± 49 vs. 748 ± 138 μmol l^?1 for control subjects vs. smokers; P < 0·05), and serum triglyceride levels were increased in the smokers (0·9 ± 0·2 vs. 2·3 ± 0·6 mmol l^?1 for control subjects vs. smokers; P < 0·05). Skeletal muscle carnitine palmitil (acyl) transferase activity was similar between the groups, indicating that FFA transport into the mitochondria was unaltered by cigarette smoking. In conclusion, cigarette smoking appears to have a profound effect on glucose transport in skeletal muscle. Basal glucose transport is markedly elevated, whereas insulin-stimulated glucose transport is impaired. These changes cannot be explained by altered protein expression of GLUT4, but may be related to increased serum FFA and triglyceride levels. These findings highlight the importance of identifying habitual cigarette smokers in studies aimed at assessing factors that lead to alterations in lipid and glucose homeostasis in people with non-insulin-dependent diabetes mellitus (NIDDM).     

Elevated serum levels of pancreatic secretory proteins in cigarette smokers after secretin stimulation.

The secretory pancreatic proteins in serum were analyzed in a group of cigarette smokers and a control group of nonsmokers before and after intravenous secretin stimulation. None of these persons had any signs of pancreatic disease. In the control group, serum total amylase activity, pancreatic isoamylase, cationic trypsinogen, and pancreatic secretory trypsin inhibitor concentrations varied within the normal range before and after secretin injection. In contrast, the concentrations of these pancreatic proteins in all the cigarette smokers elevated from normal to abnormally high serum concentrations after secretin stimulation. The results indicate a probable toxic effect of cigarette smoking on the exocrine pancreas.     

Effect of nicotine chewing gum on plasma nicotine levels of cigarette smokers

This study was designed to determine whether the use of nicotine chewing gum modifies the inhalation and absorption of nicotine by cigarette smokers. Our subjects, 12 subjects who smoked cigarettes regularly, were studied for 4 days. On the first day, they smoked as usual, and on the second, third, and fourth days they also chewed a placebo gum, 2-mg nicotine gum, or 4-mg nicotine gum. They were instructed to smoke as usual throughout the study. Mean plasma nicotine concentration was 29.5 ng/ml with the placebo gum, 30.9 ng/ml with the 2-mg gum, and 40.7 ng/ml with the 4-mg gum. Peak carbon monoxide level was lower with nicotine gum than with placebo gum. Data indicate self-regulation of blood nicotine levels. The subjects appear to have compensated almost completely for the increased intake of nicotine from the 2-mg nicotine gum by decreasing the inhalation of tobacco smoke. Nicotine compensation provided by the 4-mg nicotine gum is only partial.     

Inhaled smoke volume, puffing indices and carbon monoxide uptake in asymptomatic cigarette smokers

Nine asymptomatic smokers each smoked one cigarette of their usual brand on four separate occasions. The inhaled smoke volume was measured by tracing the smoke with the inert gas 81Krm. Puffing indices were recorded by using an electronic smoking analyser and flowhead/cigarette holder. The expired air carbon monoxide concentration was measured immediately before and within 5 min of finishing smoking. The inhaled smoke percentage (total inhaled smoke volume/total puff volume) averaged 46% to 85% in different subjects. Neither the mean inhaled smoke volume per puff nor the total inhaled smoke volume per cigarette was significantly correlated with any of the puffing indices. Smokers took significantly smaller and shorter puffs, left longer between puffs and inhaled less smoke as the cigarette was smoked (P less than 0.01), although the proportion of the puff which was subsequently inhaled did not change significantly. There was no significant intra-subject difference in any index from one visit to another.     

Ascorbic acid content and accumulation by alveolar macrophages from cigarette smokers and nonsmokers

The lung is at risk for injury from inhaled oxidants, including components of cigarette smoke; therefore, maintaining a chemical antioxidant defense would be advantageous. The potential for ascorbic acid to assume this protective role was investigated by comparing the total ascorbate content of alveolar macrophages obtained from human smokers and nonsmokers, from hamsters that were exposed to cigarette smoke for 4 to 6 weeks, and from a control group of unexposed hamsters. The abilities of alveolar macrophages from these four sources to accumulate 14C-labeled ascorbic acid and dehydroascorbate were also compared. The total ascorbate content in hamster macrophages was 19.5 +/- 1.7 and 44.3 +/- 2.8 nmol/10(7) cells for nonsmokers and smokers, (n = 5) and 73.8 +/- 13.1 nmol/10(7) cells (n = 13, p less than 0.1) for nonsmokers and smokers, respectively. In both humans and hamsters, the rates of accumulation of ascorbic acid and dehydroascorbate were significantly greater (p less than 0.05) for alveolar macrophages from smokers compared with nonsmokers of the same species. After internalization, greater than or equal to 70% of the dehydroascorbate was reduced to ascorbic acid by alveolar macrophages from nonsmokers and smokers of both species. An aqueous extract of cigarette smoke oxidized significantly more ascorbic acid to dehydroascorbate in vitro than a comparable volume of phosphate-buffered saline solution without smoke. The increased content of total ascorbate in alveolar macrophages from smokers and their enhanced ability to accumulate ascorbic acid and dehydroascorbate in vitro may reflect protective utilization of ascorbic acid under conditions of increased oxidant stress, compared with nonsmokers. In addition, alveolar macrophages may internalize dehydroascorbate that has been generated by oxidants in the alveolar space and reduce it to ascorbic acid so it can be reused as an antioxidant.