J Bignon’s research while affiliated with French Institute of Health and Medical Research and other places

The respiratory effects of environmental pollution by asbestos inside university buildings were studied by comparing radiographic, clinical, and functional parameters among three groups of workers with different levels of exposure. Eight hundred and twenty-eight (828) people who worked for at least 15 yr in asbestos-insulated buildings and who were without known occupational exposure to asbestos (environmentally exposed group [EE]) were compared to a group of 252 workers with occupational exposure (occupationally exposed group [OE]), used as positive control; and to a group of 350 people with no known exposure to asbestos (nonexposed group [NE]), within the same university. After adjustment for confounding variables, no differences could be seen between groups EE and NE. Group OE exhibited a higher prevalence of pleural changes and lower lung functions than groups EE and NE.

The number of cases of pleural mesothelioma in France has varied substantially according to methods of assessment. We collected information from certifying physicians about 316 subjects who died between 1 July 1992 and 30 June 1993 in three regions of France with a cause of death coded as ICD-9 category 163. The ICD codes selected as the cause of death for 178 deaths between 1 January 1987 and 31 December 1992 histologically confirmed and diagnosed as pleural mesothelioma by an expert committee were examined. Finally, we used this information to estimate the number of deaths from pleural mesothelioma in France in 1992. In Part I, 45% (men: 54%; women: 28%) of the cases coded as ICD-9 section 163 were definitely or probably mesothelioma; 18% (men: 16%; women: 21%) possibly mesothelioma; and 37% (men: 30%; women: 51%) other tumors, primarily adenocarcinoma metastases. In Part II, 74% of the confirmed pleural mesotheliomas were coded in category 163 (men: 75%; women: 70%). Extrapolation nationwide indicated that 902 deaths were coded as ICD-9 163 in 1992: 521 cases involved definite or probable mesothelioma and 724 definite, probable, and possible cases. The analysis of this sample suggests that estimating the number of mesothelioma cases from the cause-of-death statistics may overestimate their incidence, but that death certificates appeared to report the diagnosis of histologically confirmed mesothelioma accurately.

Unlike thoracocentesis and closed pleural biopsy (CPB), medical thoracoscopy permits biopsy with direct visualization. In a 6-year retrospective study of patients having undergone at least one medical thoracoscopy, we analyzed the diagnostic yield of thoracoscopy and its value in the management of pleural disease. From January 1, 1989, to December 31, 1994, 168 medical thoracoscopies were performed on 154 patients (123 men; mean age +/- SE, 61 +/- 1 years), of which 149 were diagnostic and 19 were indicated for therapeutic assessment in malignant mesothelioma (MM). Prior to thoracoscopy, at least one CPB had been performed in 120 of 149 cases, yielding a diagnosis in 96 cases. Thoracoscopy challenged the CPB-based diagnosis in 43 of 96 cases. In 66 cases of nonspecific inflammation diagnosed by CPB, thoracoscopy revealed MM in 16 cases, adenocarcinoma in 10 cases, undetermined carcinoma in 3 cases, and pleural tuberculosis in 3 cases. In 18 cases in which the CPB diagnosis was MM, thoracoscopy, performed for precise staging, challenged the diagnosis in 4 cases. In 12 cases of carcinoma diagnosed by CPB, thoracoscopy specified the histologic type in 7 cases. Thoracoscopic diagnoses were found to be erroneous in 10 of 149 cases, mainly owing to pleural adhesions that limited access to the pleural cavity. There was one thoracoscopy-related death, one case of sepsis, and six cases of empyema. Medical thoracoscopy appears to be efficient and relatively safe in the management of pleural disease. Pleural adhesions can lower its diagnostic value.

Occupational lung cancers are underestimated by the number of cases compensated in the French National Insurance System. Rules of compensation of occupational diseases were recently modified in France. Therefore a study was conducted on incident cases of lung cancer in a general hospital in the Paris area. The aim was to evaluate the exposure to carcinogens using data of a detailed specific occupational questionnaire, and to determine the number of cases who could receive compensation. Two hundred and seven subjects (171 males, 36 females, mean age = 64.5 years) were eligible in 1996, and 122 had an occupational questionnaire. Definite exposure to one or more occupational carcinogens in at least one job was identified in 50 subjects, the most frequent agent was asbestos (42 subjects). Claim for compensation was done in 32 subjects, mainly for asbestos (30 subjects). This study emphasizes the frequency of occupational exposure to carcinogens, and the usefulness of systematic occupational questionnaire in subjects having lung cancer. Social and financial consequences are important for these subjects. Further studies are needed, with recruitement of control subjects to allow calculation of the attributable risk to occupational factors in lung cancer.

We conducted a case-control study to examine the risk of lung cancer in relation to GSTM1 polymorphism and cigarette smoking (primarily of black tobacco) in a French population. The 611 subjects were 301 incident lung cancer cases and 310 hospital controls. We were able to constitute a DNA bank for 547 subjects (89.5%) and gather detailed information on smoking history for all of them. Results presented here concern 247 cases and 254 controls. Taking non- or light smokers as the reference category, we estimated odds ratios (OR) of 4.2 (95% CI: 2.6-6.7) and 5.2 (95% CI: 3.3-8.3) for the medium and heavy smokers respectively. On the other hand we estimated that the crude OR associating GSTM1 with lung cancer was 1.3 (95% CI: 0.9-1.8). Furthermore our data do not depart significantly from a multiplicative model of the combined effects of smoking and GSTM1 deficiency. We conclude that smoking and the GSTM1 gene are each a risk factor for lung cancer, and that their combined effect does not differ significantly from that of a multiplicative model.

Firstly to evaluate future mortality from mesothelioma in France with an age-period-cohort approach and evaluate different hypotheses on risk of mesothelioma for the most recent birth cohort. Secondly to compare the results with a British and an American study. Thirdly to study if any trends were detectable on data for women which would be consistent with the consequences of increasing environmental exposure to asbestos. Estimates of mortality from mesothelioma among men and women in France from 1950 to 1995 were based on the analysis of the pleural cancer mortality data coded 163 in the ninth revision of the international classification of diseases (ICD-9). Correction factors were used to derive the mortality from mesothelioma from these data, based on two regional registries. The analysis of the past mortality data has been performed by an age-cohort model (with a maximum likelihood technique). Predictions of deaths from mesothelioma over the next 50 years were based on four different assumptions on the risk of death from mesothelioma in future birth cohorts. The predicted lifetime probability of dying from mesothelioma increases until the last birth cohort 1964-8 among men whereas it decreases strongly from the 1954-8 birth cohort among women. The projected numbers of deaths from mesothelioma in France until 2020 are similar, whichever hypothesis is considered: around 20,000 deaths from mesothelioma might occur among men and 2900 among women from 1996 to 2020. French data show an increasing lifetime probability of death from mesothelioma in the more recent male cohorts. Although the mortality burden can be predicted until 2020, and is intermediate between the United Kingdom and United States estimates, there is still high uncertainty on the figures after 2020. No increase is found in women, and this does not support the hypothesis that current environmental exposure to asbestos could be associated with a detectable risk of death. Specific surveillance should be set up to monitor future trends or their absence.

Objectives: Firstly to evaluate future mortality from mesothelioma in France with an age-period-cohort approach and evaluate different hypotheses on risk of mesothelioma for the most recent birth cohort. Secondly to compare the results with a British and an American study. Thirdly to study if any trends were detectable on data for women which would be consistent with the consequences of increasing environmental exposure to asbestos. Methods: Estimates of mortality from mesothelioma among men and women in France from 1950 to 1995 were based on the analysis of the pleural cancer mortality data coded 163 in the ninth revision of the international classification of diseases (ICD-9). Correction factors were used to derive the mortality from mesothelioma from these data, based on two regional registries. The analysis of the past mortality data has been performed by an age-cohort model (with a maximum likelihood technique). Predictions of deaths from mesothelioma over the next 50 years were based on four different assumptions on the risk of death from mesothelioma in future birth cohorts. Results: The predicted lifetime probability of dying from mesothelioma increases until the last birth cohort 1964-8 among men whereas it decreases strongly from the 1954-8 birth cohort among women. The projected numbers of deaths from mesothelioma in France until 2020 are similar, whichever hypothesis is considered: around 20,000 deaths from mesothelioma might occur among men and 2900 among women from 1996 to 2020. Conclusions: French data show an increasing lifetime probability of death from mesothelioma in the more recent male cohorts. Although the mortality burden can be predicted until 2020, and is intermediate between the United Kingdom and United States estimates, there is still high uncertainty on the figures after 2020. No increase is found in women, and this does not support the hypothesis that current environmental exposure to asbestos could be associated with a detectable risk of death. Specific surveillance should be set up to monitor future trends or their absence.

The application of new decrees concerning the protection of individuals against sanitary risks linked to the various possible expositions to asbestos dusts is leading to a growing involvement of pulmonologists in diagnosis procedures not only for active workers regularly examined via the occupational medicine healthcare system, but also for those who are no longer, the unemployed or retired previously exposed to asbestos fibres. The present chapter presents and comments the revised guidelines about the compensation procedures for occupational diseases, and provides useful recommendations for establishing the records leading to their medical assessment. It emphasises the importance of a close cooperation between pulmonologists and radiologists in order to avoid radiation overdosing, which could increase the risk of lung cancer, as much as possible.

A hospital-based case-control study of the association between past occupational exposure to asbestos and pleural mesothelioma was carried out in five regions of France. Between 1987 and 1993, 405 cases and 387 controls were interviewed. The job histories of these subjects were evaluated by a group of experts for exposure to asbestos fibers according to probability, intensity, and frequency. A cumulative exposure index was calculated as the product of these three parameters and the duration of the exposed job, summed over the entire working life. Among men, the odds ratio increased with the probability of exposure and was 1.2 (95% confidence interval (CI) 0.8-1.9) for possible exposure and 3.6 (95% CI 2.4-5.3) for definite exposure. A dose-response relation was observed with the cumulative exposure index: The odds ratio increased from 1.2 (95% CI 0.8-1.8) for the lowest exposure category to 8.7 (95% CI 4.1-18.5) for the highest. Among women, the odds ratio for possible or definite exposure was 18.8 (95% CI 4.1-86.2). We found a clear dose-response relation between cumulative asbestos exposure and pleural mesothelioma in a population-based case-control study with retrospective assessment of exposure. A significant excess of mesothelioma was observed for levels of cumulative exposure that were probably far below the limits adopted in most industrial countries during the 1980s.