Indoor air pollution, tobacco smoke, and public health.

An experimental and theoretical investigation is made into the range and nature of the exposure of the nonsmoking public to respirable suspended particulates from cigarette smoke. A model incorporating both physical and sociological parameters is shown to be useful in understanding particulate levels from cigarette smoke in indoor environments. Observed levels of particulates correlate with the predictions of the model. It is shown that nonsmokers are exposed to significant air pollution burdens from indoor smoking. An assessment of the public health policy implications of these burdens is presented.

Artificial sweetener use and bladder cancer: a case-control study.

In a case-control study of 302 male and 65 female bladder cancer patients and an equal number of other patients matched to them in age, sex, hospital, and hospital-room status, no association was found between use of artificial sweeteners or diet beverages and bladder cancer. No dose-response was observed with respect to quantity or duration of use of the two combined. No evidence was found to suggest that artificial sweeteners or diet beverages promote the tumorigenic effect of tobacco smoking. Artificial sweetener and diet beverage use strongly reflected socioeconomic status among controls with various diagnoses.

Low-risk cigarettes: a prescription.

Antismoking education campaigns in out society have met with only partial success: today 55 to 60 million Americans smoke, and the habit is increasing among teenagers and women. It is important to protect individuals who continue to smoke despite all warnings. There is evidence that this can be accomplished in at least two ways. First, it may be possible to remove toxic smoke components and thus reduce specific hazards. Second, the doseresponse evidence suggests that, if the total intake of smoke can be reduced, after an appropriate time a reduction in disease incidence should occur. The technology to achieve these results has been developed and can be applied to the manufacture of commercial cigarettes. These cigarettes will not conform to traditional flavour patterns, but consumer perception can be made to change and compensating flavours and fragrances can be added. The feasibility of less hazardous cigarettes raises the question of whether there are limits of cigarette and smoke composition that may approach relative safety. These limits can be defined as the smoke intake doses at which the risk of disease in smokers approaches that in nonsmokers. Such values can be extimated by dose-response analysis of several epidemiological studies and by extrapolation of blood concentrations at different rates of intake for certain smoke components, such as carbon monoxide. Critical values determined by these methods should not be interpreted as indicators of safe smoking levels; they do imply, however, that a rapid shift in cigarette consumption habits toward the proposed range of values will make possible a substantial reduction in the current epidemic proportions of smoking-related diseases.

Cigarette smoking associated with sleep difficulty.

A group of 50 smokers experienced greater sleep difficulty than a group of 50 nonsmokers matched by age and sex. The two groups did not differ in personality patterns or drug consumption. Also, sleep patterns significantly improved in a group of eight chronic smokers when they abstained from cigarette smoking. These findings are consistent with reports on the stimulant effects of nicotine.

Carbon monoxide: effects on oxygenation of the fetus in utero.

The partial pressure of oxygen in fetal blood decreases in proportion to the carboxyhemoglobin concentrations in fetal and maternal blood. Because fetal oxygen tensions normally equal 20 to 30 percent of the values for adults, this reduction can result in severe hypoxia of vital tissues. Decreases in oxygen tension may be a factor in the lower birth weights of infants born to women who smoke or are exposed to severe air pollution.

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.

Elastase release from human alveolar macrophages: comparison between smokers and nonsmokers.

Alveolar macrophages from smokers, in contrast to those of non-smokers, release elastase into serum-free culture medium. Since enzymes that digest elastin produce pulmonary emphysema in experimental animals, release of elastase by alveolar macrophages from smokers suggests that these cells are important in the pathogenesis of emphysema of smokers.

Identifying environmental chemicals causing mutations and cancer.

Damage to DNA appears to be the major cause of most cancer and genetic birth defects and may contribute to aging and heart disease as well. The agents that cause this damage must be identified. Many of these agents are natural chemicals present in the human diet as complex mixtures. The tens of thousands of man-made chemicals that have been introduced into the environment in the last few decades must also be tested for their ability to damage DNA. Existing animal tests and human epidemiology alone are inadequate for this task because of time, expense, and the difficulty of dealing with complex mixtures, Newly developed short-term tests, most of them assaying for mutagenicity, are discussed as key tools in identifying environmental mutagens and carcinogens.

Lung cancer induced in hamsters by low doses of alpha radiation from polonium-210.

Lung cancers have been induced in 9 to 53 percent of hamsters given multiple intratracheal instillations of polonium-210 in amounts yielding lifetime exposures of 15 to 300 rads to the lungs. Cigarette smokers have previously been estimated to receive 20 rads to areas of the bronchial epithelium from deposited polonium-210. This finding thus supports the hypothesis that alpha radiation resulting from the polonium-210 or lead-210 present in cigarette smoke may be a significant causative factor in human lung cancer.

Risk factor intervention for health maintenance.

Risk factors for disease consist of (i) personal habits, such as cigarette smoking and excessive alcohol consumption, and (ii) bodily characteristics, such as hypertension and high serum cholesterol. Progress in identifying and quantifying risk factors is opening the way to the prevention of disease and maintenance of health. Systematic, controlled trials of intervention against risk factors are beginning to produce evidence on the extent of success in reducing both the factors and the mortality from associated diseases.

Toxicity of mild prenatal carbon monoxide exposure.

Rats prenatally exposed to a low concentration of carbon monoxide which results in carboxyhemoglobin levels equivalent to those maintained by human cigarette smokers, show reduced birth weight and decreased weight gain. Neuro-behavioral and biochemical testing of the offspring reveals lower behavioral activity levels through the preweaning period, altered central catecholamine activity, and reduction in total brain protein at birth.

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.

Induction of aryl hydrocarbon hydroxylase in human pulmonary alveolar macrophages by cigarette smoking.

Pulmonary alveolar macrophages were obtained from healthy volunteers by saline pulmonary lavage, and aryl hydrocarbon hydroxylase was measured in the cells. Enzyme activity was low in cells from five nonsmokers with a mean of 0.008+/-0.004 U/10(6) cells. Cells obtained from nine cigarette smokers contained higher enzyme levels, with a mean of 0.095+/-0.024 U/10(6) cells. A former cigarette smoker was lavaged on five occasions. Enzyme activity during two lavages 4 mo apart were 0.010 and 0.009 U/10(6) cells, respectively. 1 wk after smoking was resumed, the enzyme activity rose slightly to 0.013, and reached 0.041 U/10(6) cells by 1 mo. Upon cessation of smoking, the enzyme activity returned to control levels by the next lavage, 2 mo later. These data indicate that aryl hydrocarbon hydroxylase may be induced in pulmonary alveolar macrophages of subjects chronically exposed to cigarette smoke.

Inhalation bioassay chemistry--Walton Horizontal Smoking Machine for inhalation exposure of rodents to cigarette smoke.

Studies of experimental tobacco smoke carcinogenesis have suffered from the lack of a conveniently available and well-characterized device for exposing animals to tobacco smoke for inhalation. The Walton Horizontal Smoking Machine, a commercially available system designed to expose up to 20 mice to the smoke of a single cigarette, may fulfill this need. This system produced a uniform smoke aerosol of predictable concentration and appropriate composition for cigarettes with high delivery of nicotine (40 mg total particulate matter, 2.6 mg nicotine, and 17 cm3 carbon monoxide per cigarette) and with low delivery of nicotine (30 mg total particulate matter, 0.3 mg nicotine, and 17 cm3 carbon monoxide). In this experiment C57BL and DBA/2Bd strains of mice were used. Limitations of the concept of exposing animals to standing smoke were defined.

Cancer mortality in a cohort of naval shipyard workers in Hawaii: early findings.

A retrospective cohort study was performed in Hawaii among 4,779 male shipyard workers exposed to asbestos and 2,757 similar male workers without known asbestos exposure. Observed deaths from cancer and other causes in the 2 groups were compared with expected deaths on the basis of the general population of Hawaii by the use of a modified life-table method of analysis. A risk ratio for lung cancer of 1.7 was found for the exposed group after 20 or more years of follow-up. No increased risk for lung cancer was seen in the nonexposed group. These findings could not be attributed to differences in smoking habits in the 2 shipyard groups or between the shipyard groups and the general population. Because the maximum duration of follow-up for this analysis was 24 years, greater risks for lung cancer may be seen in the exposed group when the follow-up period is extended.

Dentition, diet, tobacco, and alcohol in the epidemiology of oral cancer.

Interview and dental examination data were gathered on 584 males with cancer of the oral cavity and on 1,222 control patients with nonneoplastic diseases at Roswell Park Memorial Institute, Buffalo, New York. No dietary characteristics distinguished cancer patients from controls. However, a higher risk of developing oral cancer was associated with heavy smoking, heavy drinking, and poor dentition. When controlled for the other factors, each factor carried a higher risk. Moreover, heavy smokers and heavy drinkers with poor dentition and males with all three traits had a substantially higher risk than would have been expected, if the traits were considered additively. The risk for males with all three traits was 7.7 times that of men with none of these traits.

Impact of long-term filter cigarette usage on lung and larynx cancer risk: a case-control study.

A case-control study was conducted among 1.034 white male and female hospital patients with histologically proved lung cancer (Kreyberg type l) or larynx cancer. After adjustment for duration of the smoking habit, inhalation, and butt length, relative risks of developing lung or larynx cancer were consistently lower among long-term smokers of filter cigarettes than among smokers of nonfilter cigarettes, irrespective of quantity smoked. Relative risks in all groups declined with increased years of smoking cessation. The observed risk reduction among current smokers of filter cigarettes was consistent with that expected, considering that these persons had smoked the older high-tar nonfilter cigarettes for a large proportion of their lives.

Vitamin A and lung cancer.

Retrospective dietary and smoking data were gathered by interview of 292 white male patients with lung cancer and 801 control patients with nonrespiratory, nonneoplastic diseases at Roswell Park Memorial Institute, Buffalo, New York. A computed index of vitamin A intake was used to differentiate lung cancer patients from controls. Lung cancer patients had lower values than did controls. The reduced relative risk (RR) of lung cancer associated with vitamin A was most evident among men who smoked heavily. For them, a dose-response relationship increasing to an RR of 2.4 for low values of the index was observed. Frequency of daily milk drinking was lower among patients with lung cancer. Lower RR was found among the men who smoked heavily and frequently consumed carrots. These findings are consistent with evidence from animal studies on inhibition of tumor incidence by retinoids and with previous findings in prospective and retrospective epidemiologic studies.

Cigarette smoke inhalation studies in inbred Syrian golden hamsters.

Invasive carcinoma of the larynx was induced in 36.8% of inbred Syrian golden hamsters from strain B10 15.16, susceptible to this type of cancer when exposed to smoke from reference filter cigarettes for 59-80 weeks. Nearly half the animals (47.4%) showed laryngeal cancer, including noninvasive carcinoma and carcinoma in situ, which occurred with daily smoke exposures (twice a day for 12 min each time, for 27 sec out of each min) 7 days a week at smoke concentrations of 22%. When the smoke concentration was reduced to 11%, the number of induced lesions was reduced proprotionately. When a portion of tobacco was replaced in the cigarettes by a tobacco supplement, Cytrel (a trademark of the Celanese Corp., Charlotte, N.C.), a reduction of carcinogenesis proportionate to the Cytrel content of the cigarette took place. Smoke from cigarettes containing only Cytrel and no tobacco induced no carcinomas under the conditions used. Other dose-related changes observed were laryngeal papillomas, laryngeal epithelial hyperplasia, tracheal epithelial hyperplasia, and metaplasia and accumulation of alveolar macrophages. Tar deposition in lungs and accumulation of alveolar macrophages. Tar deposition in lungs and larynges was determined in a separate study by means of a marker, decachlorobiphenyl, added to the cigarettes. Admixture of Cytrel to cigarettes reduced tar deposition in the respiratory tract, which paralleled the decrease in the incidence of laryngeal carcinoma. However, the amounts of tar deposited in the larynx when 100% Cytrel was smoked were still significant, even though no carcinomas were observed. Thus smoke from Cytrel tobacco supplement may be less carcinogenic than equal amounts of tobacco smoke.

Chronic inhalation of cigarette smoke by F344 rats.

Specific-pathogen-free female F344 rats were exposed by inhalation to what was considered a maximal tolerated dose of cigarette smoke. Total pulmonary deposition of smoke particulates from a single cigarette was 0.25 mg in young rats. Rats were exposed to smoke from 7 cigarettes/day for as long as 2.5 years, at which time 30% of the rats remained alive. Mortality of smoke-exposed animals was not different from that of untreated or sham-exposed controls. Hyperplastic and metaplastic areas in the epithelium of the nasal turbinates, larynges, and tracheae of exposed animals were observed at death. The lungs of exposed rats contained areas of focal alveolitis consisting of accumulated pigmented macrophages, epithelial hyperplasia, fibrosis, and disrupted alveolar structure. Smoke exposure did not change the total number of tumor-bearing animals relative to controls; however, exposed rats had significantly fewer tumors in the hypophyses, hematopoietic-lymphoid systems, uteri, and ovaries but an increased number of tumors in the respiratory tracts and dermes. Only 1 of 93 (1%) control rats had a tumor (an alveologenic carcinoma) in the respiratory tract as opposed to 7 of 80 (9%) exposed animals (nasal tumors: 1 adenocarcinoma and 1 squamous cell carcinoma; pulmonary tumors: 5 adenomas, 2 alveologenic carcinomas, and 1 squamous carcinoma).