Ian T. T. Higgins

Arsenic Exposure, Smoking, and Respiratory Cancer in Copper Smelter Workers

A report by Lee and Fraumeni in 1969 linked exposure to arsenic and other contaminants to a threefold excess of respiratory cancer among 8,047 employees at the Anaconda copper smelter. We established vital status through December 1977 for a sample of 1,800 men from the original cohort. Average arsenic concentrations were estimated for each smelter department based on industrial hygiene measurements made from 1943 to 1965. Departments with similar concentrations were combined into four categories of exposure: 1) low (less than 100 micrograms/m3), 2) medium (100-499 micrograms/m3), 3) high (500-4,999 micrograms/m3) and 4) very high (greater than or equal to 5,000 micrograms/m3). Three indices of individual arsenic exposure were developed: time-weighted average, 30-day ceiling, and cumulative. Exposures to sulfur dioxide and asbestos were also examined. Smoking habits were obtained by questionnaire. Mortality was compared to that of men in the State of Montana using the modified lifetable method. A clear dose-response relationship between arsenic exposure and respiratory cancer was demonstrated. Men in the highest exposure category had a sevenfold excess. Those in the low and medium categories had a risk close to that expected. Ceiling arsenic exposure appeared to be more important than did time-weighted average exposure. Sulfur dioxide and asbestos did not appear to be important in the excess of respiratory cancer, although sulfur dioxide and arsenic exposures could not be separated completely. Smoking did not appear to be as important as arsenic exposure. Our findings suggest that had men worked only in departments with low or medium arsenic exposures (i.e., less than 500 micrograms/m3) there would have been little excess respiratory cancer. Since the estimates of arsenic exposure were based on department averages rather than on concentrations for individual jobs, these results must be interpreted with caution.

Relation of Daily Mortality to Air Pollution: An Analysis of 14 London Winters, 1958/59–1971/72

The relationship between daily deaths and daily concentrations of Smoke and SO2 in London, England for 14 winters during the years 1958-1959 through 1971-1972 has been explored. Three types of analyses were used: (1) year-by-year multiple regression; (2) stratification using nested quartiles of one pollutant within quartiles of the other; and (3) multiple regression of a special subset of high pollution days. An association was found with Smoke, but not with SO2. Whether a linear model with zero threshold or a threshold model best fits could not be determined unambiguously because of a statistical artifact. Reasons for preferring a threshold-type quadratic model are given.

The epidemiology of chronic respiratory disease

Chronic respiratory disease (CRD) is usually understood to include chronic bronchitis, emphysema, asthma, and a number of other chronic bronchopulmonary diseases. This paper will concentrate on the first two. The epidemiology of asthma differs in many ways from that of chronic bronchitis and emphysema, for example, in its age and sex incidence, relationships to social class, allergy, and time trends. But many of the clinical features are common to all three diseases with the result that diagnosis may be difficult. Furthermore the extent to which asthma contributes to emphysema is as yet uncertain. While it would be desirable to consider the epidemiology of the components of CRD separately this is unfortunately not yet possible. A number of conferences and organizations (2,17,104) have suggested definitions and classifications of these diseases. The following definitions, essentially those of the American Thoracic Society, would probably be generally accepted. Chronic bronchitis is a clinical condition characterized by excessive mucous secretion in the bronchi. It is manifested by chronic or recurrent productive cough not attributable to other lung or heart disease. Emphysema refers to an anatomical alteration of the lung characterized by an abnormal enlargement of the air spaces distal to the terminal, nonrespiratory bronchiole, usually accompanied by destructive changes in the alveolar walls. Asthma is a condition characterized by increased responsiveness of the trachea and bronchi to various stimuli. It is manifested by widespread narrowing of the airways which changes in severity either spontaneously or as a result of treatment. During the past 20 years epidemiologists have developed standardized methods for studying CRD (3,35,36,65). Precisely worded questions about respiratory symptoms and chest illnesses have been formulated, simple tests of ventilatory lung function, notably the forced expiratory volume (FEV) and forced vital capacity (FVC), have been widely applied, various objective methods, such as measurement of the volume and quality of the morning sputum during the first hour or half hour after rising, have been recommended (93). Bronchial reactivity has occasionally been measured. More sophisticated testing of lung function and chest radiography have been included in some surveys. The result is a considerable body of knowledge on chronic bronchitis but rather less on emphysema and asthma.

Effects of Cooking Fuels on Lung Function in Nonsmoking Women

A case-control study of 20- to 39-yr-old female participants in the Tecumseh Community Health Study compared use of cooking fuels and other factors in women from the highest and lowest quartiles of the lung function distribution. The forced expiratory volume in 1 second (FEV1.0) was used as the index of ventilatory lung function. The use of a kitchen exhaust fan was significantly associated with low lung function. A larger proportion of women with low FEV1.0 used gas for cooking, but this difference was not statistically significant.

Air pollution and lung cancer: Diesel exhaust, coal combustion☆☆☆

In 1946, when the causes of lung cancer were much less well understood than they are now, a meeting was held by the British Medical Research Council to review hypotheses to explain the remarkable increase in the death rates from lung cancer and to determine strategy. Stocks came away from the meeting to study the community aspects of air pollution, which he did by extending his series of correlation studies, Kennaway to conduct studies of carcinogens in the air, and Hill to carry out a study of smoking in relation to lung cancer. It is now known, of course, that cigarette smoking is by far the most important cause of lung cancer and that about a dozen occupational exposures are also established as causes of this disease. There has been continuing uncertainty about the role of general air pollution. During the past few years, this uncertainty has been compounded with anxiety that the increasing use of diesel-powered vehicles might lead to a deterioration in air quality and, with it, an increase in the incidence of lung cancer. The purpose of this paper is to assess the current role of air pollution as a factor in lung cancer and specifically the contribution of diesel exhaust emissions to the incidence of that disease.

Sulfur oxides and suspended particulates, possible effects of chronic exposure.

The levels of air pollution for sulfur compounds and particulates decreased somewhat between two sampling periods five to six years apart in Berlin, NH. Population surveys showed that there was a lower prevalence of respiratory symptoms in 1967 than in 1961. These differences persisted after age standardization and when comparisons were made within a smoking category. Changes in inhaling habits or the use of filter-tip cigarettes did not seem to be likely explanations for this decrease in prevalence. Tests of pulmonary function were less clear-cut but did indicate that a slight improvement in pulmonary function had possibly occurred. It is believed that these changes may be related to the decrease in the levels of air pollution.

Trends in respiratory cancer mortality in the United States and in England and Wales.

Trends in respiratory cancer mortality from 1940 to 1969 in the United States and in England and Wales are compared. In the United States, male age-specific death rates have increased at a declining rate; female rates have increased dramatically since about 1955. In England and Wales, male rates have declined under 55, have flattened at ages 55 to 64, and have risen only in those aged 65 and over; female rates have increased markedly since about 1957. After allowing for cigarette smoking, an effect of air pollution was sought. There was a slightly greater decline in the lung cancer death rates among men aged 25 to 64 and women aged 45 to 54 in Greater London than in the rest of the country. This is in line with the greater decline in smoke pollution in London than elsewhere.

What is an adverse health effect

An adverse health effect may be defined as a biological change that reduces the level of well being or functional capacity. A wide range of changes from trivial to fatal needs to be considered. In reaching a conclusion about what is adverse, future implications as well as present status must often be assessed. Without such prognosis, it may be impossible to differentiate between a physiological and a pathological change. In such a situation, disagreements are bound to arise about whether the effect is adverse or not. Unfortunately, evidence on the future implications of many questionable effects is largely lacking. Examples, mainly from the respiratory field, are presented to illustrate how gaps in knowledge can be filled. The collection of such data is an important use of epidemiology.

RECENT MORTALITY FROM CANCER OF THE CERVIX IN THE UNITED STATES AND UNITED KINGDOM

Abstract Death-rates from cancer of the cervix in the United States in 1950-67 are compared with similar data for England and Wales. In the United States (unlike England and Wales) statistics show no evidence of a rise in mortality-rates for cancer of the cervix among women under 60 years: they show a decline in all 10-year age-groups from 30 to 79 among White women; among non-White women a similar decline has occurred in those aged 30-59, but the rates have remained relatively constant among those aged 60-79.

Epidemiological research on the relationship of exposure to diesel emissions and the development of respiratory cancer

A meeting was held at Luerhof House, Kampen, on the Island of Sylt, Germany, on June 22-23, 1982, to discuss the relationship between general air pollution and respiratory cancer. More specifically, discussion focused on the risk posed by exposure to diesel emissions and the need for research to more adequately define and assess it. I. T. T. Higgins reviewed the evidence on general air pollution and respiratory cancer. He pointed out that the earlier beliefs of the 1950s that pollution was important now seemed unlikely. At most, it seemed possible that general air pollution might explain up to 5% of all lung cancer. The overwhelming majority of cases were attributable to cigarette smoking with a small, but important fraction being due to a variety of specific occupational exposures. There were few studies which permitted any conclusions about the role of diesel emissions on lung cancer to be drawn. Of the three studies reviewed by the NAS-NRC Health Effects Panel of the Diesel Impacts Study Committee, only one-the Raffle London Transport investigation as followed by Waller (Q-was sufficiently sensitive in terms of both numbers and length of follow-up to permit a reasonably confident conclusion of no excess risk from diesel exposure. Two additional studies, one of heavy equipment operators conducted by Milby and his colleagues and the other of railroad workers conducted by Schenker and Speizer, are in progress. Preliminary accounts of the former do not appear to suggest any increased lung cancer risk from diesel emissions, whereas a pilot study from the latter has suggested a possible small excess risk. To what extent this risk may be due to confounding by asbestos exposure or by cigarette smoking is at present uncertain. Clearly, further analyses and more detailed presentations of the data are awaited with interest. R. E. Waller presented a series of comments regarding associations between emissions from diesel engines and lung cancer. He noted that: (a) There has never been any indication from trends or area contrasts in lung cancer mortality that diesel fumes might be implicated. The rising trend in lung cancer seen in so many countries during this century started before diesel engines came into common use, and, at least so far as males are concerned, the trend