Lifetime excess absolute risk for lung cancer due to exposure to radon: results of the pooled uranium miners cohort study PUMA.

The Pooled Uranium Miners Analysis (PUMA) study is the largest uranium miners cohort with 119,709 miners, 4.3 million person-years at risk and 7754 lung cancer deaths. Excess relative rate (ERR) estimates for lung cancer mortality per unit of cumulative exposure to radon progeny in working level months (WLM) based on the PUMA study have been reported. The ERR/WLM was modified by attained age, time since exposure or age at exposure, and exposure rate. This pattern was found for the full PUMA cohort and the 1960 + sub-cohort, i.e., miners hired in 1960 or later with chronic low radon exposures and exposure rates. The aim of the present paper is to calculate the lifetime excess absolute risk (LEAR) of lung cancer mortality per WLM using the PUMA risk models, as well as risk models derived in previously published smaller uranium miner studies, some of which are included in PUMA. The same methods were applied for all risk models, i.e., relative risk projection up to <95 years of age, an exposure scenario of 2 WLM per year from age 18-64 years, and baseline mortality rates representing a mixed Euro-American-Asian population. Depending upon the choice of model, the estimated LEAR per WLM are 5.38 × 10-4 or 5.57 × 10-4 in the full PUMA cohort and 7.50 × 10-4 or 7.66 × 10-4 in the PUMA 1960 + sub-cohort, respectively. The LEAR per WLM estimates derived from risk models reported for previously published uranium miners studies range from 2.5 × 10-4 to 9.2 × 10-4. PUMA strengthens knowledge on the radon-related lung cancer LEAR, a useful way to translate models for policy purposes.

Mortality among uranium miners in North America and Europe: the Pooled Uranium Miners Analysis (PUMA).

BACKGROUND: The Pooled Uranium Miners Analysis (PUMA) study draws together information from cohorts of uranium miners from Canada, the Czech Republic, France, Germany and the USA. METHODS: Vital status and cause of death were ascertained and compared with expectations based upon national mortality rates by computing standardized mortality ratios (SMRs) overall and by categories of time since first hire, calendar period of first employment and duration of employment as a miner. RESULTS: There were 51 787 deaths observed among 118 329 male miners [SMR = 1.05; 95% confidence interval (CI): 1.04, 1.06]. The SMR was elevated for all cancers (n = 16 633, SMR = 1.23; 95% CI: 1.21, 1.25), due primarily to excess mortality from cancers of the lung (n = 7756, SMR = 1.90; 95% CI: 1.86, 1.94), liver and gallbladder (n = 549, SMR = 1.15; 95% CI: 1.06, 1.25), larynx (n = 229, SMR = 1.10; 95% CI: 0.97, 1.26), stomach (n = 1058, SMR = 1.08; 95% CI: 1.02, 1.15) and pleura (n = 39, SMR = 1.06; 95% CI: 0.75, 1.44). Lung-cancer SMRs increased with duration of employment, decreased with calendar period and persisted with time since first hire. Among non-malignant causes, the SMR was elevated for external causes (n = 3362, SMR = 1.41; 95% CI: 1.36, 1.46) and respiratory diseases (n = 4508, SMR = 1.32; 95% CI: 1.28, 1.36), most notably silicosis (n = 814, SMR = 13.56; 95% CI: 12.64, 14.52), but not chronic obstructive pulmonary disease (n = 1729, SMR = 0.98; 95% CI: 0.93, 1.02). CONCLUSIONS: Whereas there are important obstacles to the ability to detect adverse effects of occupational exposures via SMR analyses, PUMA provides evidence of excess mortality among uranium miners due to a range of categories of cause of death. The persistent elevation of SMRs with time since first hire as a uranium miner underscores the importance of long-term follow-up of these workers.

Miner studies and radiological protection against radon.

Fundamental estimates of radon-associated health risk have been provided by epidemiological studies of miners. In total, approximately 15 studies have been conducted worldwide since the 1960s. These results have contributed directly to radiological protection against radon. The present article summarises the main results, with a focus on analyses of miners exposed more recently, estimates of radon lifetime attributable risk, and interaction between radon and smoking. The potential for the upcoming Pooled Uranium Miner Analysis project to further improve our knowledge is discussed.

A Bayesian hierarchical approach to account for left-censored and missing radiation doses prone to classical measurement error when analyzing lung cancer mortality due to γ-ray exposure in the French cohort of uranium miners.

Epidemiological data on cohorts of occupationally exposed uranium miners are currently used to assess health risks associated with chronic exposure to low doses of ionizing radiation. Nevertheless, exposure uncertainty is ubiquitous and questions the validity of statistical inference in these cohorts. This paper highlights the flexibility and relevance of the Bayesian hierarchical approach to account for both missing and left-censored (i.e. only known to be lower than a fixed detection limit) radiation doses that are prone to measurement error, when estimating radiation-related risks. Up to the authors' knowledge, this is the first time these three sources of uncertainty are dealt with simultaneously in radiation epidemiology. To illustrate the issue, this paper focuses on the specific problem of accounting for these three sources of uncertainty when estimating the association between occupational exposure to low levels of γ-radiation and lung cancer mortality in the post-55 sub-cohort of French uranium miners. The impact of these three sources of dose uncertainty is of marginal importance when estimating the risk of death by lung cancer among French uranium miners. The corrected excess hazard ratio (EHR) is 0.81 per 100 mSv (95% credible interval: [0.28; 1.75]). Interestingly, even if the 95% credible interval of the corrected EHR is wider than the uncorrected one, a statistically significant positive association remains between γ-ray exposure and the risk of death by lung cancer, after accounting for dose uncertainty. Sensitivity analyses show that the results obtained are robust to different assumptions. Because of its flexible and modular nature, the Bayesian hierarchical models proposed in this work could be easily extended to account for high proportions of missing and left-censored dose values or exposure data, prone to more complex patterns of measurement error.

[Genetic and environmental factors of asthma and allergy: Results of the EGEA study]. / Facteurs génétiques et environnementaux de l'asthme et de l'allergie: synthèse des résultats de l'étude EGEA.

INTRODUCTION AND METHODS: The EGEA study (epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), which combines a case-control and a family-based study of asthma case (n=2120 subjects) with three surveys over 20 years, aims to identify environmental and genetic factors associated with asthma and asthma-related phenotypes. We summarize the results of the phenotypic characterization and the investigation of environmental and genetic factors of asthma and asthma-related phenotypes obtained since 2007 in the EGEA study (42 articles). RESULTS: Both epidemiological and genetic results confirm the heterogeneity of asthma. These results strengthen the role of the age of disease onset, the allergic status and the level of disease activity in the identification of the different phenotypes of asthma. The deleterious role of active smoking, exposure to air pollution, occupational asthmogenic agents and cleaning products on the prevalence and/or activity of asthma has been confirmed. Accounting for gene-environment interactions allowed the identification of new genetic factors underlying asthma and asthma-related traits and better understanding of their mode of action. CONCLUSION: The EGEA study is contributing to the advances in respiratory research at the international level. The new phenotypic, environmental and biological data available in EGEA study will help characterizing the long-term evolution of asthma and the factors associated to this evolution.

Mortality analyses in the updated French cohort of uranium miners (1946-2007).

PURPOSE: The objectives are to analyze mortality risks in the extended follow-up of the French uranium miners' cohort and to examine their potential relation to occupational exposure to ionizing radiation (IR). METHODS: The total cohort includes 5,086 uranium miners employed in the CEA-COGEMA group and followed up from 1946 to 2007. Vital status, causes of death, and cumulative radon exposures were recorded. The post-55 subcohort includes 3,377 miners first employed after 1955, for whom long-lived radionuclides (LLR) and external gamma-ray exposure were also recorded. External mortality analyses were performed by computing standardized mortality ratios (SMR). Excess relative risks (ERRs) due to IR exposures were estimated from Poisson regression models. RESULTS: The miners included in the total cohort were followed up for 35.4 years and exposed to 36.6 working level months (WLM) on average. There was no evidence of a difference in overall mortality between miners and the general French male population. Miners had a statistically significant excess mortality rate from lung cancer (SMR = 1.34 [95% CI 1.16-1.53]) and from kidney cancer (SMR = 1.60 [1.03-2.39]). Cumulative radon exposure was significantly associated with lung cancer risk (ERR/100 WLM = 0.71 [0.31-1.30]) and cerebrovascular risk (ERR/100 WLM = 0.41 [0.04-1.03]). In the post-55 subcohort, this excess mortality from lung cancer remained associated with exposure to radon, and also with exposure to LLR and external gamma rays. CONCLUSIONS: The analyses in the extended follow-up strengthen the results previously observed among French uranium miners about their excess risk of mortality and its association with their occupational IR exposure.

Association between modelled traffic-related air pollution and asthma score in the ECRHS.

The aim of our analysis was to study the association between air pollution and asthma among adults. For this goal, a previously developed "asthma score" was used. Persons aged 25-44 yrs were randomly selected (1991-1993) and followed up (2000-2002) within the European Community Respiratory Health Survey (ECRHS I and II, respectively). The asthma score was defined from 0 to 5, based on the positive answers to the following symptoms reported for the last 12 months: wheeze/breathlessness, chest tightness, dyspnoea at rest, dyspnoea after exercise and woken by dyspnoea. Participants' home addresses were linked to outdoor modelled NO2 estimates for 2001. Negative binomial regression was used to model the asthma score. The score from ECRHS II was positively associated with NO2 (ratio of the mean asthma score (RMS) 1.23, 95% CI 1.09-1.38, for an increase of 10 microg x m(-3)). After excluding participants with asthma and symptoms at baseline, the association remained (RMS 1.25, 95% CI 1.05-1.51), and was particularly high among those reporting a high score in ECRHS II. The latter probably reflects incident cases of asthma. Our results suggest that traffic-related pollution causes asthma symptoms and possibly asthma incidence in adults. The asthma score offers an alternative with which to investigate the course and aetiology of asthma in adults.

Air pollution and asthma severity in adults.

BACKGROUND/OBJECTIVES: There is evidence that exposure to air pollution affects asthma, but the effect of air pollution on asthma severity has not been addressed. The aim was to assess the relation between asthma severity during the past 12 months and home outdoor concentrations of air pollution. METHODS: Asthma severity over the past 12 months was assessed in two complementary ways among 328 adult asthmatics from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) examined between 1991 and 1995. The four-class severity score integrated clinical events and type of treatment. The five-level asthma score is based only on the occurrence of symptoms. Nitrogen dioxide (NO(2)), sulphur dioxide (SO(2)) and ozone (O(3)) concentrations were assigned to each residence using two different methods. The first was based on the closest monitor data from 1991 to 1995. The second consisted of spatial models that used geostatistical interpolations and then assigned air pollutants to the geo-coded residences (1998). RESULTS: Higher asthma severity score was significantly related to the 8-hour average of ozone during April-September (O(3)-8 h) and the number of days (O(3)-days) with 8-hour ozone averages above 110 microg.m(-3) (for a 36-day increase, equivalent to the interquartile range, in O(3)-days, odds ratio 2.22 (95% confidence interval 1.61 to 3.07) for one class difference in score). Adjustment for age, sex, smoking habits, occupational exposure, and educational level did not alter results. Asthma severity was unrelated to NO(2). Both exposure assessment methods and severity scores resulted in very similar findings. SO(2) correlated with severity but reached statistical significance only for the model-based assignment of exposure. CONCLUSIONS: The observed associations between asthma severity and air pollution, in particular O(3), support the hypothesis that air pollution at levels far below current standards increases asthma severity.

Total serum IgE levels are associated with ambient ozone concentration in asthmatic adults.

BACKGROUND: Effects of air pollution exposure on IgE-mediated response in asthmatics are poorly investigated. The aim was to examine the relationship between air pollution concentrations and total IgE levels in adult asthmatics. METHODS: The present study relates to the 369 asthmatic adults from the French Epidemiological study on Genetics and Environment of Asthma (EGEA), with availability of data on both total serum IgE measurements and air pollution concentrations. Geo-statistical models were performed on 4 x 4 km grids to assess individual outdoor air pollution exposure. Annual outdoor concentrations of ozone (O(3)), nitrogen dioxide (NO(2)), sulphur dioxide (SO(2)), and particulate matter smaller than 10 microm size (PM(10)), and concentrations of summer ozone were assigned to subject's home address. RESULTS: The geometric mean of total IgE was 161 IU/ml and the average of O(3) exposure was 44.9 +/- 9.5 microg/m(3). Ozone concentrations were positively related to total IgE levels and an increase of 10 microg/m(3) of O(3) resulted in an increase of 20.4% (95% CI = 3.0-40.7) in total IgE levels. Adjustment for age, gender, smoking habits and previous life in the countryside did not change the results, and an increase of 19.1% (2.4-38.6) in total IgE was observed with O(3). Negative associations observed between NO(2) and total IgE levels disappeared after including O(3) in the models. Neither SO(2) nor PM(10) were correlated with total IgE levels. CONCLUSIONS: Results suggest that O(3) or related ambient pollutants may up-regulate total IgE levels among asthmatic adults.

[Environmental factors for asthma severity and allergy: results from the EGEA study]. / Facteurs environnementaux de l'asthme sévère et de l'allergie: résultats de l'étude EGEA.

INTRODUCTION: EGEA (Epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), a case control and family study including 2048 individuals, was initiated to look for environmental and genetic risk factors for asthma. A synthesis of the results obtained since 2002 on phenotypic and environmental aspects of asthma severity and allergy are presented in this article. METHODS AND RESULTS: The results support a role for hormonal factors in asthma severity and in various allergic markers of asthma. A greater body mass index was related to a more severe asthma in women with early menarche. Associations between markers of allergy (eosinophils, IgE and atopy) and hormonal dependent events in women (premenstrual asthma, menopause and oral contraceptive use) have been found. In asthmatics, exposure to agents known to be associated with occupational asthma, active and passive smoking were associated with an increased clinical asthma severity score. The study underlines the protective role of country living and exposure to pets in early life on allergy markers in adulthood, supporting the hygiene hypothesis. CONCLUSIONS: New hypothesis will be tested in the near future from the second stage of this survey.