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A four-year follow-up study of lung mechanics in smokers.

We performed a prospective study of pulmonary function in 21 smokers, 9 ex-smokers, and 12 nonsmokers. The smokers and ex-smokers were preselected, because they were participants in a smoking cessation clinic. An average interval of 4 years separated the first and second (follow-up) studies. The smoking group showed a significant decrease in maximal expiratory flow measured at low lung volume, loss of elastic recoil, increase in lung compliance, increase in total lung capacity; increase in the ratio of residual volume to total lung capacity, and an increase in the ratio of functional residual capacity to total lung capacity. The ex-smokers showed changes similar to those of the smokers, but of lesser magnitude. The nonsmoking group demonstrated few changes in function during the study interval. Commonly measured parameters of function, including the ratio of the forced expiratory volume in 1 sec to the forced vital capacity and the maximal expiratory flow after exhalation of 50 per cent of the vital capacity, did not change significantly in any group. Sensitive tests of lung function were abnormal in a very high percentage of the combined group of smokers and ex-smokers when measured at the time of the second study; only a small number of abnormalities in these parameters were noted in the nonsmoking group. We conclude that there was a deterioration of lung function in smokers far in excess of that predicted by age. These changes suggest the development of emphysema and were predictable for the group as a whole by a high prevalence of abnormality of dynamic compliance, closing volume, maximal mid-expiratory flow, and residual volume at the time of the initial study.

Adult

Humoral immunity to herpes simplex viral-induced antigens in smokers.

Antibodies to herpes simplex viral-induced antigens (HSVIA) were assayed by an indirect immunofluorescent technique in 93 regular cigarette smokers, 75 of whom also imbibed alcoholic beverages. Controls were 94 nonsmoking, nondrinking volunteers matched with the smoker for age and sex. IgA antibodies to HSVIA were detected six times more frequently in the sera of smokers than in nonsmoking controls, p less than .0005. IgG and IgM anti-HSVIA were detected with comparable frequencies in both groups, but the antibody titers were significantly higher in the smoking group than in controls, p less than .05. IgA anti-HSVIA was detected more frequently in smokers with 10 or more pack-years of cigarette exposure than in smokers with 10 or more pack-years of smoking (p less than .05) or in matched nonsmokers (p less than .02). IgA antibody titers to HSVIA were significantly higher in cigarette smokers who drank alcoholic beverages than in smokers who did not drink, p less than .025. This study demonstrates that cigarette smoking and the use of alcoholic beverages are associated with heightened humoral immunity to HSV-induced antigens in a population at high risk for development of squamous cell carcinomas of the head and neck region.

Age Factors

Visual processes of smokers and nonsmokers at different ages.

Forty smokers and forty nonsmokers were matched for age over the range from 21 to 76 yr. The battery of tests included: optometric refraction for near vision, scotopic sensitivity, simple and choice reaction time, visually evoked cortical potentials to targets flashing at 1 and 16 times/sec, EEG, and a perimetric test of color detection. Roughly the same number of smokers and nonsmokers required spectacle corrections, but smokers tended to require more plus correction. The mean scotopic sensitivity of the smokers was significantly worse than that of the nonsmokers. Reaction time tended to be poorer for the smokers. There were no differences on the perimetry test and in the EEGs of the smokers and nonsmokers, and no significant changes in the visually evoked responses to either 1 or 16 flashes/sec. There was virtually no evidence of an increasing difference between the smokers and nonsmokers with increasing age.

Adult

Gross differences observed in the placentas of smokers and nonsmokers.

Gross placental characteristics of 7651 smokers and nonsmokers are compared in light of the previous finding that placentas of smokers are heavier for the weight of their fetuses than are those of nonsmokers. Subchorionic fibrin deposits and placental calcification are more prevalent in the placentas of smokers than in those of nonsmokers. While mean placental weights and placental weight distributions for light and heavy smokers combined do not differ from those of nonsmokers, other placental measurements do differ. Smokers have thinner, rounder placentas than nonsmokers and the distance from the edge of rupture of the membranes to the placental margin is reduced among smokers. These findings are discussed in relation to placental changes observed at high altitudes and complications of pregnancy that differ for smokers and nonsmokers.

Birth Weight

Skeletal muscle metabolism, morphology and function in sedentary smokers and nonsmokers.

Smokers and nonsmokers of a homogeneous population of sedentary men have been compared with respect to skeletal muscle (vastus lateralis) morphological, metabolic and functional characteristics. The percentage type I fibres was lower and that of type IIB fibres higher in the smokers. Fibre areas were almost equal in the two groups. Muscle oxidative capacity was lowered in the smokers, as judged from decreased mitochondrial enzyme activities and a lowered fibrillar space mitochondrial volume fraction. Isometric and dynamic strengths were lower in the smokers, except at the highest velocity of movement studied. Dynamic strengths expressed in relation to isometric strength were similar at all velocities except the highest, where the smokers were relatively stronger. Muscular endurance, measured in short-term isometric and dynamic tests, was not different. It is suggested that the lowered muscle oxidative capacity and strength in the smokers may be partly a consequence of the different fibre type distribution. A possibly lower physical activity level, and tobacco smoke constituents (e.g. carbon monoxide) may also be instrumental. It is not clear whether the different fibre type distribution in the smokers is an effect of smoking per se, or if background factors are responsible.

Adult

Reversible impairment of the adherence of alveolar macrophages from cigarette smokers.

The nylon fiber adherence in vitro of alveolar macrophages (AM) from cigarette smokers was uniformly decreased. The mean adherence of AM from 16 cigarette smokers was 53 +/- 3.0 per cent, compared to a mean adherence of 77.2 +/- 1.7 per cent for AM from control nonsmokers. The defect was not present after the subjects quit smoking, was not a result of factors in lavage fluids from smokers, and was not apparent in polymorphonuclear leukocytes. The morphologic features of the surface of AM were examined with scanning electron microscopy to determine whether morphologic changes paralleled the decreased adherence of AM from smokers. Marked alterations in the surface of AM from cigarette smokers, which could affect the ability of AM to adhere optimally, were demonstrated before attachment to the fiber. In summary, there exists a reversible, intrinsic defect in the structure and adherence of AM from cigarette smokers that may influence their function and may accout, in part, for the increased yield of AM from the lavage fluid of cigarette smokers.

Cell Adhesion

Stopping smoking. Symptoms and objective assessment in ex-smokers.

The results of a respiratory questionnaire and spirometric tests of 133 ex-smokers out of 649 male public servants aged 15--64 years have been analysed. When the population was adjusted for age, height and the presence or absence of chronic respiratory symptoms the FEV1 of the ex-smokers had not returned to normal but fell between that of the light (less than 10 a day) and moderate cigarette smokers. Factors contributing to this have been investigated. Factors affecting the FEV1 of the ex-smokers were found to include duration of smoking, quantum smoked and years since smoking ceased. An interactive effect has been demonstrated between quantum smoked and duration of smoking such that ex-smokers who used to smoke 10 or more cigarettes a day for more than 10 years had the lowest lung function but duration of smoking was not important if less than 10 cigarettes a day had been smoked. Only just over a third of the ex-smokers gave health related reasons for giving up smoking, a proportion which is considerably lower than has been found in other studies. Possible reasons for this difference are discussed. As in other studies less than 10 percent gave up smoking because of its cost. Respiratory screening to include questions on cough, phlegm and wheeze together with measurement of the FEV1 is an important way of demonstrating to individual smokers evidence of any damage caused by their smoking.

Adolescent

Cigarette smoking habits and urine characteristics: urinalysis abnormalities are more common is smokers, but the reasons are unclear.

Voided urines of 53,000 white and 9,3000 black cigarette smokers and nonsmokers were studied. Proteinuria was found to be commoner in smokers of both races and sexes. Heavy smokers showed proteinuria more frequently than light smokers. Of eight possible explanatory variables, one, alcohol consumption history, showed some interrelationship in that the smoking status-proteinuria association disappeared among heavy drinkers. Stopping smoking was not associated with a relative decline in proteinuria prevalence. Proteinuria associated with smoking did not appear to be indicative of more serious renal disease. There was a smoker-nonsmoker difference in urine glucose response to oral glucose challenge, apparently explained by higher average 1-hour serum glucose values for smokers, of unknown mechanism but partially explained by differences in alcohol usage. Hematuria, bacteriuria, and high urine acidity tended to be more prevalent in smokers, though these relationships were not consistently significant.

Adult

[Fluorescein angiographic study on the retinal vessels of young cigarette smokers (author's transl)].

Caliber irregularities of the small retinal vessels may usually be observed as an early sign of vascular disturbance in young cigarette smokers. A randomized blind study on 28 smokers and 30 non-smokers aged between 17 and 39 years, which were entirely healthy according to the results of physical and ophthalmoscopical examination, was undertaken with the aid of fluorescence angiography. Only smokers with a consumption of at least 15 cigarettes daily and a history of smoking of at least 5 years were taken into account for the study. The angiograms were read as fluorescein angiographic negatives under a stereomicroscope. To the person interpreting the angiograms, name or date of the angiograms were not know. Caliber irregularities of the retinal arteries, veins, arterioles and venoles were found in 18 of the smokers and 2 of the non-smokers. The incidence of vascular irregularity in smokers is highly significant at the 1% level.

Adolescent

Fine-mapping the CYP2A6 regional association with nicotine metabolism among African American smokers.

The nicotine metabolite ratio (NMR; 3'hydroxycotinine/cotinine) is a stable biomarker for CYP2A6 enzyme activity and nicotine clearance, with demonstrated clinical utility in personalizing smoking cessation treatment. Common genetic variation in the CYP2A6 region is strongly associated with NMR in smokers. Here, we investigated this regional association in more detail. We evaluated the association of CYP2A6 single-nucleotide polymorphisms (SNPs) and * alleles with NMR among African American smokers (N = 953) from two clinical trials of smoking cessation. Stepwise conditional analysis and Bayesian fine-mapping were undertaken. Putative causal variants were incorporated into an existing African ancestry-specific genetic risk score (GRS) for NMR, and the performance of the updated GRS was evaluated in both African American (n = 953) and European ancestry smokers (n = 933) from these clinical trials. Five independent associations with NMR in the CYP2A6 region were identified using stepwise conditional analysis, including the deletion variant CYP2A6*4 (beta = -0.90, p = 1.55 × 10-11). Six putative causal variants were identified using Bayesian fine-mapping (posterior probability, PP = 0.67), with the top causal configuration including CYP2A6*4, rs116670633, CYP2A6*9, rs28399451, rs8192720, and rs10853742 (PP = 0.09). Incorporating these putative causal variants into an existing ancestry-specific GRS resulted in comparable prediction of NMR within African American smokers, and improved trans-ancestry portability of the GRS to European smokers. Our findings suggest that both * alleles and SNPs underlie the association of the CYP2A6 region with NMR among African American smokers, identify a shortlist of variants that may causally influence nicotine clearance, and suggest that portability of GRSs across populations can be improved through inclusion of putative causal variants.

Adult

Blood and Urinary nicotine in non-smokers.

Of 39 urban non-smokers about half had measurable quantities of nicotine in their plasma (range 0 to 5times5 ng. per ml.) and almost all had nicotine in their urine during the early afternoon. The average concentration of urinary nicotine in non-smokers under natural conditions was 10times7 ng. per ml., but after deliberate exposure to tobacco smoke (mean duration seventy-eight minutes) in an unventilated room (38 p.p.m. of carbon monoxide) the average urinary nicotine level (80 ng. per ml.) was significantly higher than in non-smokers who had not been deliberately exposed to smoke (P less than 0times 001). Under natural conditions there was no overlap between the urine levels of non-smokers and the far higher levels of 18 smokers (mean 1236 ng. per ml.), suggesting that urinary nicotine may provide a more accurate assessment of an individual's smoking-status than blood-carboxyhaemoglobin. It is concluded that, as a result of passive smoking, most urban non-smokers have measurable amounts of nicotine in their bodyfluids for most of their lives.

Air Pollution

Pulmonary function in young smokers: male-female differences.

To delineate the pattern of pulmonary function abnormalities and associated pathophysiologic mechanisms in young smokers, 205 volunteers between the ages of 18 and 25 were studied with a variety of pulmonary function tests. Differences between male and female smokers were observed. Pulmonary function abnormalities consistent with small airway dysfunction were noted in male smokers, but not in female smokers. Decreased forced expiratory flows at high lung volumes suggesting large airway dysfunction were noted in both male and female smokers. Decreases in diffusing capacity for CO consistent with abnormalities of the pulmonary vascular system were seen in smokers of both sexes, but were more prominent in females. Because men develop chronic obstruction pulmonary disease more frequently than do women even when adjustments for smoking are made, and because women develop primary pulmonary hypertension more frequently than do men, these chronic diseases may reflect distinct pathophysiologic response of the 2 sexes to agents such as cigarettes.

Adolescent

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.

Adult

Changes in the forced expiratory spirogram in young male smokers.

Forced expiratory spirograms and peak expiratory flow were measured in 102 resident male medical students (60 nonsmokers and 42 smokers). Forced vital capacity; forced expiratory volume in 1 sec; forced expiratory volume in 1 sec expressed as a percentage of forced vital capacity; forced expiratory flows between 80 and 70 per cent, between 55 and 45 per cent, between 30 and 20 per cent, and between 15 and 5 per cent of the forced vital capacity; forced expiratory time for the last 0.5 liter of the forced vital capacity; and maximal mid-expiratory flow were determined from the forced expiratory spirogram. Peak expiratory flow, all forced expiratory flows (except the forced expiratory volume in 1 sec), and the ratio of forced expiratory volume in 1 sec to forced vital capacity were significantly lower, and forced expiratory time for the last 0.5 liter of the forced vital capacity was significantly higher in the heavy smokers (those who had smoked a lifetime total of more than 10,000 cigarettes) than the nonsmokers. The light smokers (those who smoked a lifetime total of fewer than 10,000 cigarettes) had values between those of nonsmokers and the heavy smokers. Thus, a definite dose-related response to smoking was seen. Flows at lower lung volumes showed greater percentage changes than flows at higher lung volumes. The forced expiratory flow between 30 and 20 per cent of the forced vital capacity was the most sensitive test for detecting abnormality in smokers. Among heavy smokers, 58 per cent had abnormally low forced expiratory flow between 30 and 20 per cent of the forced vital capacity, whereas only 47 per cent had abnormally low ratio of forced expiratory volume in 1 sec to forced vital capacity, and 32 percent had abnormally low maximal mid-expiratory flow. The results show that even subjects with short smoking histories may have changes in pulmonary function that probably reflect narrowing of small airways. Moreover, these changes can easily be detected by simple tests, such as evaluation of a forced expiratory spirogram.

Adult