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F D Liddell

Publications and source records attributed to F D Liddell.

At least 19 recordsLinked to original sources
PubMed2001

The interaction of asbestos and smoking in lung cancer.

Both cigarette smoke and inhaled asbestos fibres can cause lung cancer, but the assessment of how these agents act in combination is a matter of great difficulty. In non-smokers, the condition is so rare that, in any cohort of asbestos workers, the standardised mortality ratio (SMR, that is the ratio of the numbers of deaths observed and expected) is quite imprecise. The SMR for smokers, with which it has to be compared, is also subject to sampling error, making the interaction even more unstable. This accounts for much of the variation that has bedevilled evaluation. The debate has been concentrated on two hypotheses: additive (asbestos and cigarette smoke act independently) and multiplicative (asbestos produces an effect proportional to the effect of smoking). The very few data available until 1977 failed to fit the former and fitted the latter only poorly. They would have fitted better a hypothesis of greater synergism, but the only one proposed was too convoluted. So the multiplicative model appeared the only alternative, and was deemed 'accepted'. The ratio of lung cancer SMRs for non-smokers and smokers was generalised into the relative asbestos effect, RAE, with all the advantages of a parametric statistic (Berry et al., 1985, British Journal of Industrial Medicine 42, 12). On the multiplicative hypothesis, RAE=1, while RAE>1 indicates less synergism. The RAEs for the three most recent of the six results then available were >1; for one, P<0.005. From the six results combined, it was concluded that 'overall non-smokers have a relative risk of lung cancer due to asbestos that is 1.8 times that of smokers'. Some admitted uncertainty about the figure 1.8 was seized upon and even the thrust of the conclusion has been very largely disregarded. So too has the RAE and all its benefits. As a result, all later reviewers have been led into error, much of it serious: in particular, they have failed to appreciate how much of the variation arises from the inevitable imprecision of all RAEs. This failure led reviewers in 1994 to discard, quite without justification, those interactions which were less than multiplicative and came from cohort studies. Although case-referent studies seemed to support the multiplicative hypothesis, the information from them is essentially unreliable. Thus it cannot weaken the conclusions from the cohort studies, that the multiplicative hypothesis is untenable and that the relative risk of lung cancer from asbestos exposure is about twice as high in non-smokers as in smokers; the best estimate of RAE is 2.04, with 95% confidence interval 1.28-3.25. This finding is not only of high statistical significance but of great social and scientific importance.

Asbestos↗
PubMed1998

Dust exposure and lung cancer in Quebec chrysotile miners and millers.

A large cohort of men born between 1891 and 1920 and employed for at least a month in the chrysotile producing industry of Quebec has been under study since 1966. These men were followed from first employment (the earliest in 1904) to 1992, by which time over 8000 had died, 657 from lung cancer. The current study is of 488 cases of lung cancer formerly employed at three places, viz. a major complex, here called Company 3, in the region of Thetford Mines (243 cases), the mine and mill in the town of Asbestos (206) and a small asbestos-products factory in the same town (39). For each case, four referents were sought by random selection from among survivors to a greater age, after matching on place of employment, age of starting work, smoking habit and date of birth. This process was highly successful, although six cases had less than four referents. For each man (the 488 cases with 1941 referents) and for each calendar year of employment, we obtained the fraction of the year worked at various levels of intensity, assessed in 13 'dust categories' of mpcf (million particles per cubic foot). We then calculated how many years each man spent at these various levels; these years, adjusted for the length of the working week (66 h until 1937; 48 h 1938-1949; and 40 h 1950-1985), were accumulated up to ten years before the death of the case. The men were classified according as they were non- or ex-smokers, or smokers, of cigarettes. For each man at Company 3 and one referent for each, his years of work in a central area of five mines and in a peripheral area of ten mines were differentiated; contamination of the chrysotile by fibrous tremolite was known to be much greater in the central than in the peripheral area. Case-referent comparisons, within place of employment, were made by conditional logistic regression. As anticipated from earlier subject-years analyses, lung cancer risks were found to be negligible for years worked in dust categories 1 and 2 (averaging 0.5 and 2 mpcf), regardless of place; as the upper limit of category 1 is considerably higher than permitted nowadays, the lung cancer risk from exposure to chrysotile at permitted levels can be taken as extremely small. Patterns of exposure-response for higher categories were irregular. At Company 3, some risks appeared elevated for years spent in the higher dust categories: 3-4, 5-7, 8-10 and 11-13, with averages around 9, 20, 36 and 92 mpcf, respectively. For categories 3-4 and 8-10, the odds ratios were high for some or all work in the central area, but minimal for years spent in the peripheral area only. Odds ratios were fairly low for cigarette smokers who worked in categories 5-7 and also for years spent in the highest categories (11-13). At the mine and mill in Asbestos, all risks were low except for years worked by non- and ex-smokers in categories 7-13 (ca. 40 mpcf). There were no increased risks at the factory. It was known from the subject-years analyses that most of the excess had occurred at Company 3, but it is now clear that for all practical purposes it was confined to the central area there, probably due largely to fibrous tremolite and in dust conditions of at least dust category 3. The average of this category was 7 mpcf or very roughly 24 fibres/ml, about two orders of magnitude higher than today's hygiene standards.

Aged↗
PubMed1997

The 1891-1920 birth cohort of Quebec chrysotile miners and millers: development from 1904 and mortality to 1992.

This paper draws together the mortality experience for a cohort of some 11000 male Quebec Chrysotile miners and millers, reported at intervals since 1971 and now again updated. Of the 10918 men in the complete cohort, 1138 were lost to view, almost all never traced after employment of only a month or two before 1935; the other 9780 men were traced into 1992. Of these, 8009 (82%) are known to have died: 657 from lung cancer, 38 from mesotheliona, 1205 from other malignant disease, 108 from pneumoconiosis and 561 from other non-malignant respiratory diseases (excluding tuberculosis). After early fluctuations. SMRs (all causes) against Quebec rates have been reasonably steady since about 1945. For men first employed in Asbestos, mine or factory, they were very much what might have been expected for a blue collar population without any hazardous exposure. SMRs in the Thetford Mines area were almost 8% higher, but in line with anecdotal evidence concerning socio-economic status. At exposures below 300 (million particles per cubic foot) x years, (mpcf.y), equivalent to roughly 1000 (fibres/ml) x years-or, say, 10 years in the 1940s at 80 (fibres/ml)-findings were as follows. There were no discernible associations of degree of exposure and SMRs, whether for all causes of death or for all the specific cancer sites examined. The average SMRs were 1.07 (all causes), and 1.16, 0.93, 1.03 and 1.21, respectively, for gastric, other abdominal, laryngeal and lung cancer. Men whose exposures were less then 300 mpcf.y suffered almost one-half of the 146 deaths from pneumoconiosis or mesothelioma; the elimination of these two causes would have reduced these men's SMR (all causes) from 1.07 to approximately 1.06. Thus it is concluded from the viewpoint of mortality that exposure in this industry to less than 300 mpcf.y has been essentially innocuous, although there was a small risk or pneumoconiosis or mesothelioma. Higher exposures have, however, led to excesses, increasing with degree of exposure, of mortality from all causes, and from lung cancer and stomach cancer, but such exposures, of at least 300 mpcf.y, are several orders of magnitude more severe than any that have been seen for many years. The effects of cigarette smoking were much more deleterious than those of dust exposure, not only for lung cancer (the SMR for smokers of 20+ cigarettes a day being 4.6 times higher than that for non-smokers), but also for stomach cancer (2.0 times higher), laryngeal cancer (2.9 times higher), and-most importantly-for all causes (1.6 times higher).

Aged↗
PubMed1993

The 1891-1920 birth cohort of Quebec chrysotile miners and millers: mortality 1976-88.

A cohort of some 11,000 men born 1891-1920 and employed for at least one month in the chrysotile mines and mills of Quebec, was established in 1966 and has been followed ever since. Of the 5351 men surviving into 1976, only 16 could not be traced; 2508 were still alive in 1989, and 2827 had died; by the end of 1992 a further 698 were known to have died, giving an overall mortality of almost 80%. This paper presents the results of analysis of mortality for the period 1976 to 1988 inclusive, obtained by the subject-years method, with Quebec mortality for reference. In many respects the standardised mortality ratios (SMRs) 20 years or more after first employment were similar to those for the period 1951-75--namely, all causes 1.07 (1951-75, 1.09); heart disease 1.02 (1.04); cerebrovascular disease 1.06 (1.07); external causes 1.17 (1.17). The SMR for lung cancer, however, rose from 1.25 to 1.39 and deaths from mesothelioma increased from eight (10 before review) to 25; deaths from respiratory tuberculosis fell from 57 to five. Among men whose exposure by age 55 was at least 300 million particles per cubic foot x years (mpcf.y), the SMR (all causes) was elevated in the two main mining regions, Asbestos and Thetford Mines, and for the small factory in Asbestos; so were the SMRs for lung cancer, ischaemic heart disease, cerebrovascular disease, and respiratory disease other than pneumoconiosis. Except for lung cancer, however, there was little convincing evidence of gradients over four classes of exposure, divided at 30, 100, and 300 mpcf.y. Over seven narrower categories of exposure up to 300 mpcf.y the SMR for lung cancer fluctuated around 1.27 with no indication of trend, but increased steeply above that level. Mortality form pneumoconiosis was strongly related to exposure, and the trend for mesothelioma was not dissimilar. Mortality generally was related systematically to cigarette smoking habit, recorded in life from 99% of survivors into 1976; smokers of 20 or more cigarettes a day had the highest SMRs not only for lung cancer but also for all causes, cancer of the stomach, pancreas, and larynx, and ischaemic heart disease. For lung cancer SMRs increased fivefold with smoking, but the increase with dust exposure was comparatively slight for non-smokers, lower again for ex-smokers, and negligible for smokers of at least 20 cigarettes a day; thus the asbestos-smoking interaction was less than multiplicative. Of the 33 deaths from mesothelioma in the cohort to date, 28 were in miners and millers and five were in employees of a small asbestos products factory where commercial amphiboles had also been used. Preliminary analysis also suggest that the risk of mesothelioma was higher in the mines and mills at Thetford Mines than in those at Asbestos. More detailed studies of these differences and of exposure-response relations for lung cancer are under way.

Aged↗
PubMed1992

The mortality of amphibole miners in South Africa, 1946-80.

A cohort was established in 1981 of all 7317 white male employees in the amosite and crocidolite mines in South Africa whose names had appeared in the personnel records (initiated between 1945 and 1955) of the major companies. Some of the men had been employed as early as 1925, but only 8% had had more than 10 years of service. Three subcohorts were defined: 3212 men whose only exposure to asbestos was to amosite; 3430 exposed to crocidolite; and 675 to both amphiboles. No deaths or losses to view occurred before 1946, and 5925 men (81%) were known to be alive at the end of 1980. Losses to view numbered 167 (2%), and there had been 1225 deaths (17%), an excess of 331 over the number of deaths expected on the basis of the mortality of all white South African males. The fibre related excesses were of mesothelioma, lung cancer, and other respiratory diseases, but there were other excesses perhaps mainly related to socioeconomic factors including lifestyle. When cause of death was determined according to "best evidence" (after study of clinical, radiological, biopsy, and necropsy reports in conjunction with the death certificate), there were 30 deaths due to mesothelioma (22 pleural, six peritoneal, two other) and 65 due to cancer of trachea, bronchus, and lung. Various analyses of these deaths showed that crocidolite had higher toxicity than amosite for lung cancer and this was most pronounced for mesothelioma; there can now be no question that crocidolite is far more dangerous than amosite at least in so far as mesothelioma is concerned. Nevertheless, crocidolite induced mesothelioma appeared only in men who had been exposed for long periods, at least 12 months, but on average about 15 years.

Asbestos↗
PubMed1988

The development of cohort studies in epidemiology: a review.

An historical outline of the evolution of cohort (or incidence) studies spans well over 100 years, from the work of Farr and Snow in the 1850s, through an appraisal of analytical methods in 1977, after which the literature mushroomed. Since the early 1950s, analysis has conventionally taken the form of comparing subcohorts that had suffered varying degrees of exposure to factor(s) under investigation. For this purpose, the "subject-years" approach to data reduction has now become virtually universal. Usually, some population's mortality (or morbidity) experience is used as reference, but there is continuing controversy over the choice of reference population, while difficulties arise in relation to study intervals, periods over which exposures should be measured, etc. The material for analysis becomes age- and periodic-specific ratios of disease, which, collapsed over ages and periods, lead to Standardized Mortality (or Morbidity) Ratios. For the analysis itself, Poisson regression models are efficient. From the late 1970s, analysis by case-referent methods has become common; here, the debate centres on how closely, and in what ways, referents should be matched with the cases. Logistic regression is the most common form of analysis. As there have been excellent recent summaries of methods of analysis (for both approaches), little emphasis is placed here on those aspects of development. Comparisons are made of research designs, and some possibilities for future development are outlined.

Cohort Studies↗
PubMed1985

Relations between asbestos exposure and lung cancer SMRs in occupational cohort studies.

It has long been accepted that excessive exposure to asbestos may produce lung cancer but not that there is a consistent "biological gradient." This can only be evaluated reliably in studies where, for every individual, exposure has been measured in terms of both duration and intensity. Even now, there are only at most eight such cohort studies of asbestos workers, while femoral methods of analysis have been available only recently. These methods, applied in these studies, yield good evidence that the "exposure-response" relation between accumulated exposure to asbestos and standardised mortality ratios (SMRs) for lung cancer may be taken as linear, but that at zero exposure the lung cancer SMR is not always unity--not surprising, because of well known difficulties with the choice of reference population and selection problems. This leads to a concept of "relative slopes" that take account of the background mortality in the cohort and make what appears to be the best use of the available data. Other approaches to the same data, and indeed to all cohort data known, are also considered. Each study is examined as closely as is possible in a short review, and the concepts of linearity and relative slopes appear justified. The relative slopes (b/a) in the line SMR = a[1 + (b/a) . (exposure)] vary much more widely than can be accounted for by differences in epidemiological methodology; as discussed elsewhere, reasons for the variation seem to lie rather in type and dimensions of asbestos fibre, industrial process, etc. Slopes in the line SMR = 1 + b1 . (exposure) vary about twice as much as do the relative slopes.

Asbestos↗
PubMed1984

Simple exact analysis of the standardised mortality ratio.

The standardised mortality ratio is the ratio of deaths observed, D, to those expected, E, on the basis of the mortality rates of some reference population. On the usual assumptions--that D was generated by a Poisson process and that E is based on such large numbers that it can be taken as without error--the long established, but apparently little known, link between the Poisson and chi 2 distributions provides both an exact test of significance and expressions for obtaining exact (1-alpha) confidence limits on the SMR. When a table of the chi 2 distribution gives values for 1-1/2 alpha and 1/2 alpha with the required degrees of freedom, the procedures are not only precise but very simple. When the required values of chi 2 are not tabulated, only slightly less simple procedures are shown to be highly reliable for D greater than 5; they are more reliable for all D and alpha than even the best of three approximate methods. For small D, all approximations can be seriously unreliable. The exact procedures are therefore recommended for use wherever the basic assumptions (Poisson D and fixed E) apply.

Humans↗
PubMed1984

Fibre exposure and mortality from pneumoconiosis, respiratory and abdominal malignancies in chrysotile production in Quebec, 1926-75.

To define the relationships between chrysotile exposure in fibre terms and death from specific cancers, and pneumoconiosis, all 11,379 persons born 1891-1920 who had worked in the asbestos mines and mills of Quebec for a month or more before 1967 were followed to the end of 1975. Among the 10,939 men, there had been 4,463 deaths, 634 from these causes. For each death, referents were randomly selected from among men in the cohort born in the same year as the case and known to have survived to a greater age. For each case and his referents, exposures accumulated up to nine years before the death of the case had been obtained as (million particles per cubic foot) x years. Fibre counts were estimated for each work-place so that all exposures could be expressed in (fibres/ml) x years. The ratio of the means for all 2,586 accumulated exposures was 3.46 (f/ml)/mpcf. Relative Risks (RR) were related to exposure by matched analysis. For pneumoconiosis and lung cancer, RR = 1 + b.(f/ml).y fitted well, with b estimated as 0.00647 and 0.00038, respectively. For cancers of upper and of lower G.I. tract, severe exposure was associated with elevated RRs, but rather unclearly. For other abdominal cancers, and laryngeal cancer, risks and exposure were not positively associated. The asbestos-smoking interaction in lung cancer was closer to multiplicative than to additive.

Abdominal Neoplasms↗
PubMed1983

Simplified exact analysis of case-referent studies: matched pairs; dichotomous exposure.

In a case-referent study of matched pairs with a single dichotomous exposure variable, the relative risk R is estimated from the "discordant pairs," r and s, by R = r/s. In this paper the exact (1 - alpha) confidence limits, RL and RU, have been simplified, and a new exact test of the null hypothesis that R = 1 has been derived. The exact methods depend on the F distribution; they are simple to calculate and all have been fully validated. Even after simplification, methods for obtaining approximations to RL and RU remain more unwieldy than the exact methods, and an evaluation shows that these approximations may occasionally be far from the truth. It is argued that there is no excuse for not using the exact methods.

Epidemiologic Methods↗
PubMed1982

Motor vehicle accidents (1973-6) in a cohort of Montreal drivers.

In 1973-4 nearly 10 000 Montreal drivers, interviewed by telephone, provided information about medical and associated factors and about driving habits, in particular annual mileage. Records of accidents suffered by these drivers in the Province of Quebec over 39 months (1973-6) were also collected. The 7634 current drivers, with appropriate permits, and all of whose data passed reliability edits, were placed into nine sets-that is, three classes: women; men with the usual permit; and men with a chauffeur's permit to drive taxis, heavy vehicles, etc; further subdivided into three age groups. Accident rates depended on mileage, but after allowance for differences in mileage, accident rates still varied with sex, type of permit, and age. No association of the risk of accidents and a medical or related factor was consistent over all nine sets of drivers. Of the 7634 drivers, 347 had had at least one accident causing injury or death in the 39 months from 1 January 1973. These "cases" were compared with 347 "referents," closely matched for sex, type of permit, age, and reported mileage, but without accident causing injury or death. Cases included higher proportion who worked irregular shifts, who were overweight, and who reported smoking while driving. Relative to the chance of a referent suffering any accident in the 39-month period, a case had at least double the risk of having an accident in addition to the index accident.

Accidents, Traffic↗
PubMed1980

Dust exposure and mortality in chrysotile mining, 1910-75.

We report a further follow-up of a birth cohort of 11 379 workers exposed to chrysotile. The cohort consisted of 10 939 men and 440 women, born 1891-1920, who had worked for at least a month in the mines and mills of Asbestos and Thetford Mines in Quebec. For all subjects, length of service and estimates of accumulated dust exposure were obtained, with a smoking history for the vast majority. Three methods of analysis, two based on the "man-years" methods, the other a "case-and-multiple-controls" approach, gave results consistent with one another and with previous analyses. By the end of 1975, 4463 men and 84 women had died. Among men, the overall excess mortality, 1926-75 was 2% at Asbestos and 10% at Thetford Mines, much the dustier region. The women, mostly employed at Asbestos, had a standardised mortality ratio (SMR) all causes, 1936-75) of 0.90. Analysis of deaths 20 years or more after first employment showed that in men with short service (less than five years) there was no discernible correlation with dust exposure. Among men employed at least 20 years, there were clear excesses in those exposed to the heaviest dust concentrations. Reanalysis in terms of exposure to age 45 showed definite and consistent trends for SMRs for total mortality, for lung cancer, and for pneumoconiosis to be higher the heavier the exposure. The response to increasing dose was effectively linear for lung cancer and for pneumoconiosis. Lung cancer deaths occurred in non-smokers, and showed a greater increase of incidence with increasing exposure than did lung cancer in smokers, but there was insufficient evidence to distinguish between multiplicative and additive risk models. There were no excess deaths from laryngeal cancer, but a clear association with smoking. Ten men and one woman died from pleural mesothelioma. If the only subjects studied had been the 1904 men with at least 20 years' employment in the lower dust concentrations, averaging 6.6 million particles per cubic foot (or about 20 fibres/cc), excess mortality would not have been considered statistically significant, except for pneumoconiosis. The inability of such a large epidemiological survey to detect increased risk at what, today, are considered unacceptable dust concentrations, and the consequent importance of exposure-response models are therefore emphasised.

Accidents↗
PubMed1980

Radiological findings as predictors of mortality in Quebec asbestos workers.

Two cohorts of chrysotile miners and millers in Quebec were selected to study the extent to which chest radiographs taken while still employed predict mortality. The paper presents mainly findings in much the larger cohort, which consisted of 4559 men (two-thirds past workers) whose latest radiograph had been assessed by one of six experienced readers into what became the UICC/Cincinnati (U/C) classification; by the end of 1975 there had been 1543 deaths in this cohort. The findings were generally confirmed in the other cohort, comprising 988 current male workers, who had been examined in 1967-8 by questionnaires on respiratory symptoms and smoking and by lung function tests, and for whom all six readers had assessed their 1966 radiographs into the U/C classification; 130 men had died by the end of 1975. Men with any radiographic abnormality, heavy dust exposure, or a history of cigarette smoking had relative risks (RRs) of total mortality greater than unity. Death from pneumoconiosis was associated with small parenchymal opacities, usually irregular, of profusion l/l or more, and with heavy dust exposure but not with smoking. Most who died from lung cancer had smoked cigarettes, or had been heavily exposed to dust, or both. Small parenchymal opacities were present in most but not all the excess deaths due to lung cancer. Deaths from other malignant diseases showed no consistent dust or x-ray patterns. RRs of deaths from most other causes were raised for certain radiographic features. Failures in forecasting mortality were primarily due to deaths in which asbestos-related disease was not the primary cause but may have been a contributing factor. The main findings validated the U/C classification convincingly, particulary as the films had been taken as routine and were of modest quality. Despite objective rules for the reading and the fact that all six readers were contributing to the development of the classification, there was inevitably some observer variation. The importance of radiographic technique and the need for careful control of the reading is evident. Our results provide support for the use of the chest radiograph for surveillance of asbestos workers, and for environmental monitoring. Its protective value for individual workers, however, is limited to the extent that radiological progression continues after withdrawal from exposure, and by the carcinogenic risk associated with dust already retained.

Adult↗