Asbestos exposure, pleural plaques, and the risk of death from lung cancer.

RATIONALE: Although asbestos is a well-known lung carcinogen, the pleural plaque-lung cancer link remains controversial. OBJECTIVES: This study was designed to examine this link in asbestos-exposed workers. METHODS: A 6-year follow-up was conducted to study lung cancer mortality in the 5,402 male subjects participating in an asbestos-related disease screening program conducted from October 2003 to December 2005 in four French regions. Chest computed tomography (CT) scan was performed in all subjects with randomized, independent, double reading of CT scans focusing on benign asbestos-related abnormalities. Cox model survival regression analysis was used to model lung cancer mortality according to the presence of pleural plaques, with age as the main time variable, adjusting for smoking and asbestos cumulative exposure index. All statistical tests were two-sided. MEASUREMENTS AND MAIN RESULTS: Thirty-six deaths from lung cancer were recorded. Lung cancer mortality was significantly associated with pleural plaques in the follow-up study in terms of both the unadjusted hazard ratio of 2.91 (95% confidence interval = 1.49-5.70) and the adjusted hazard ratio of 2.41 (95% confidence interval = 1.21-4.85) after adjustment for smoking and asbestos cumulative exposure index. CONCLUSIONS: Pleural plaques may be an independent risk factor for lung cancer death in asbestos-exposed workers and could be used as an additional criterion in the definition of high-risk populations eligible for CT screening.

Inter-reader agreement in HRCT detection of pleural plaques and asbestosis in participants with previous occupational exposure to asbestos.

OBJECTIVES: To investigate inter-reader agreement for the detection of pleural and parenchymal abnormalities using CT in a large cross-sectional study comprising information on individual cumulative exposure to asbestos. METHODS: The project was approved by the hospital ethics committee, and all patients received information on the study and gave their written informed consent. In 5511 CT scans performed in a cohort of retired workers previously exposed to asbestos and volunteering to participate in a multiregional survey programme (Asbestos Related Diseases Cohort, ARDCO), double randomised standardised readings, triple in case of disagreement, were performed by seven trained expert radiologists specialised in thoracic imaging and blind to the initial interpretation. Inter-reader agreement was evaluated by calculating the κ-weighted coefficient between pairs of expert readers and results of routine practice and final diagnosis after expert reading. RESULTS: κ-Weighted coefficients between trained experts ranged from 0.28 to 0.52 (fair to good), 0.59 to 0.86 (good to excellent) and 0.11 to 0.66 (poor to good) for the diagnosis of asbestosis, pleural plaques and fibrosis of the visceral pleura, respectively. κ-Weighted coefficients between results of routine practice and final diagnosis after expert reading were 0.13 (poor), 0.53 (moderate) and 0.11 (poor) for the diagnosis of asbestosis, pleural plaques and fibrosis of the visceral pleura, respectively. CONCLUSIONS: Interpretation of benign asbestos-related thoracic abnormalities requires standardisation of the reading and trained readers, particularly for participants asking for compensation, and with a view to the longitudinal survey of asbestos-exposed workers.

Occupational asthma and occupational rhinitis: the united airways disease model revisited.

OBJECTIVES: Whereas accumulating evidence indicates close associations between rhinitis and asthma, little is known about the relationships between occupational rhinitis (OR) and occupational asthma (OA). This study analyses the prevalence of OR associated with OA, globally and according to the various causal agents, and investigates the temporal relationships between these two conditions. METHODS: Data on incident cases of OA (2008-2010) were collected through the French national occupational disease surveillance and prevention network, using a standardised form including information on occupation, causal agents, presence of OR, and respective dates of occurrence of rhinitis and asthma. RESULTS: Among the 596 reported OA cases with latency period, 555 could be attributed to identified agents: high molecular weight (HMW) agents (n=174); low molecular weight (LMW) agents (n=381). Overall, OR was associated with OA in 324 (58.4%) cases. The frequency of association was significantly higher for HMW agents than for LMW agents (72.2% vs 51.5%, p<0.001). OR occurred before OA significantly more frequently for HMW agents than for LMW agents (p<0.01). CONCLUSIONS: These results show that OR is frequently associated with OA, especially when HMW agents are involved. They are consistent with the hypothesis that OR, in conjunction with OA, is more likely to be caused by sensitisers that cause disease via IgE-mediated mechanisms and suggest that symptoms of OR should be taken into account in the medical surveillance of workers exposed to HMW agents.

Work-related asthma in France: recent trends for the period 2001-2009.

OBJECTIVE: Knowledge on the time-course (trends) of work-related asthma (WRA) remains sparse. The aim of this study was to describe WRA trends in terms of industrial activities and the main causal agents in France over the period 2001-2009. METHOD: Data were collected from the French national network of occupational health surveillance and prevention (Réseau National de Vigilance et de Prévention des Pathologies Professionnelles (RNV3P)). Several statistical models (non-parametric test, zero-inflated negative binomial, logistic regression and time-series models) were used and compared with assess trends. RESULTS: Over the study period, 2914 WRA cases were included in the network. A significant decrease was observed overall and for some agents such as isocyanates (p = 0.007), aldehydes (p = 0.01) and latex (p = 0.01). Conversely, a significant increase was observed for cases related to exposure to quaternary ammonium compounds (p = 0.003). The health and social sector demonstrated both a growing number of cases related to the use of quaternary ammonium compounds and a decrease of cases related to aldehyde and latex exposure. CONCLUSIONS: WRA declined in France over the study period. The only significant increase concerned WRA related to exposure to quaternary ammonium compounds. Zero-inflated negative binomial and logistic regression models appear to describe adequately these data.

Asbestos-related diseases in automobile mechanics.

PURPOSE: Automobile mechanics have been exposed to asbestos in the past, mainly due to the presence of chrysotile asbestos in brakes and clutches. Despite the large number of automobile mechanics, little is known about the non-malignant respiratory diseases observed in this population. The aim of this retrospective multicenter study was to analyse the frequency of pleural and parenchymal abnormalities on high-resolution computed tomography (HRCT) in a population of automobile mechanics. METHODS: The study population consisted of 103 automobile mechanics with no other source of occupational exposure to asbestos, referred to three occupational health departments in the Paris area for systematic screening of asbestos-related diseases. All subjects were examined by HRCT and all images were reviewed separately by two independent readers; who in the case of disagreement discussed until they reached agreement. Multiple logistic regression models were constructed to investigate factors associated with pleural plaques. RESULTS: Pleural plaques were observed in five cases (4.9%) and interstitial abnormalities consistent with asbestosis were observed in one case. After adjustment for age, smoking status, and a history of non-asbestos-related respiratory diseases, multiple logistic regression models showed a significant association between the duration of exposure to asbestos and pleural plaques. CONCLUSIONS: The asbestos exposure experienced by automobile mechanics may lead to pleural plaques. The low prevalence of non-malignant asbestos-related diseases, using a very sensitive diagnostic tool, is in favor of a low cumulative exposure to asbestos in this population of workers.

Do asbestos-related pleural plaques on HRCT scans cause restrictive impairment in the absence of pulmonary fibrosis?

BACKGROUND: It is uncertain whether isolated pleural plaques cause functional impairment. OBJECTIVE: To analyse the relationship between isolated pleural plaques confirmed by CT scanning and lung function in subjects with occupational exposure to asbestos. METHODS: The study population consisted of 2743 subjects presenting with no parenchymal interstitial abnormalities on the high-resolution CT (HRCT) scan. Asbestos exposure was evaluated by calculation of an individual cumulative exposure index (CEI). Each subject underwent pulmonary function tests (PFTs) and HRCT scanning. Variables were adjusted for age, smoking status, body mass index, CEI to asbestos and the centres in which the pulmonary function tests were conducted. RESULTS: All functional parameters studied were within normal limits for subjects presenting with isolated pleural plaques and for those presenting with no pleuropulmonary abnormalities. However, isolated parietal and/or diaphragmatic pleural plaques were associated with a significant decrease in total lung capacity (TLC) (98.1% predicted in subjects with pleural plaques vs. 101.2% in subjects free of plaques, p=0.0494), forced vital capacity (FVC) (96.6% vs. 100.4%, p<0.001) and forced expiratory volume in 1 s (FEV(1)) (97.9% vs. 101.9%, p=0.0032). In contrast, no significant relationship was observed between pleural plaques and FEV1/FVC ratio, forced expiratory flow at 25-75% FVC and residual volume. A significant correlation was found between the extent of pleural plaques and the reduction in FVC and TLC, whereas plaque thickness was not related to functional impairment. CONCLUSIONS: The results show a relationship between isolated parietal and/or diaphragmatic pleural plaques and a trend towards a restrictive pattern, although the observed decrease in FVC and TLC is unlikely to be of real clinical relevance for the majority of subjects in this series.

Does asbestos exposure cause airway obstruction, in the absence of confirmed asbestosis?

RATIONALE: Whether occupational exposure to asbestos causes airway obstruction remains controversial. OBJECTIVES: This study evaluated lung function in relation to cumulative exposure to asbestos in a large cohort of retired or unemployed workers exposed to asbestos. METHODS: The study population consisted of 3,660 volunteer subjects. An individual cumulative exposure index to asbestos was calculated for each subject, and information was obtained on smoking status. Pulmonary function tests were performed in all subjects; high-resolution chest computed tomography was also performed in 3,335 subjects. MEASUREMENTS AND MAIN RESULTS: Values of FEV(1)/FVC and FEF(25-75%) did not differ between five classes (quintiles) of cumulative exposure to asbestos, and no significant correlation was observed between cumulative exposure to asbestos and pulmonary function parameters, after adjustment for sex, tobacco consumption, emphysema, and body mass index. Furthermore, the proportion of abnormal pulmonary function tests did not differ between the five classes of cumulative exposure to asbestos. CONCLUSIONS: The results do not support a causal relationship between asbestos exposure alone and airway obstruction. However, the study sample may not be representative of all people occupationally exposed to asbestos, because a fraction of subjects with previously diagnosed asbestosis probably did not participate in this screening program.

Programmed health surveillance and detection of emerging diseases in occupational health: contribution of the French national occupational disease surveillance and prevention network (RNV3P).

OBJECTIVE: The French national occupational disease surveillance and prevention network (RNV3P) includes the 30 occupational disease consultation centres in university hospitals to which patients are referred for potentially work-related diseases, and an occupational health service. The aim of this work is to demonstrate the contribution of RNV3P to national health surveillance. METHODS: Data from consultations are recorded in standardised occupational health reports and coded using international or national classifications. Programmed health surveillance is carried out through annual follow-up of annual referrals to experts for pre-selected disease-exposure associations, as well as incidence estimations for the well characterised working population followed by the occupational health service. Hypotheses on new emerging diseases are generated using statistical methods employed in pharmacosurveillance and by modelling as an exposome to analyse multiple exposures. RESULTS: 58,777 occupational health reports were collected and analysed from 2001 to 2007. Referrals to the 30 university hospital centres increased significantly for asbestos-related diseases, mood disorders and adjustment disorders related to psychological and organisational demands, and for elbow and shoulder disorders related to manual handling. Referrals significantly decreased for asthma and for rhinitis related to exposure to organic dusts (vegetable or animal) or chemicals, except for cosmetics and cleaning products. Estimation of incidences by the occupational health services showed different patterns in different sectors of activity. The methods for detecting emerging diseases are presented and illustrated using the example of systemic sclerosis, identifying new exposures and new sectors of activity to be investigated. CONCLUSION: The RNV3P collects data from two complementary samples: 30 university hospital centres (workers or former workers) and an occupational health service (current workers). This dual approach is useful for surveillance and for hypothesis generation on new emerging disease-exposure associations.

Outcome of occupational asthma.

PURPOSE OF REVIEW: Occupational asthma is often associated with serious work and financial consequences. Correct management of occupational asthma must be based on a good knowledge of the natural history of the disease and of its prognostic factors. RECENT FINDINGS: Longitudinal studies have demonstrated that improvement of symptoms and airway hyperresponsiveness may be prolonged after cessation of exposure. Severity of asthma at diagnosis is the best predictor of clinical symptoms and functional impairment at follow-up. The molecular weight of the causal agent does not seem to be a prognostic factor. Airway inflammation is associated with persistence of symptoms and airway hyperresponsiveness after cessation of exposure. Reduction of exposure has proved to be effective in improvement of latex-induced asthma. SUMMARY: Further studies are needed to investigate the prognostic value of sputum eosinophils and neutrophils, and to determine whether some specific agents are associated with a better prognosis than others.

Is forced oscillation technique useful in the diagnosis of occupational asthma?

OBJECTIVE: The aim of the study was to determine whether the forced oscillation technique (FOT), which does not require active cooperation, may be useful to assess bronchial responsiveness in patients with suspected occupational asthma (OA). METHODS: Changes in resistances evaluated by FOT, and DeltaFEV1 measured during methacholine challenge test were compared in 77 adults referred for suspected OA. Spearman correlations and ROC curves were used. RESULTS: R0 at the final dose of methacholine (R0hmd) and DeltaR0 were strongly correlated with DeltaFEV1 (p < 0.001). The ROC curves showed that R0hmd >or= 240% predicted was the best cut-off value to discriminate subjects with OA from nonasthmatic subjects (sensitivity: 80%, specificity: 76%). CONCLUSION: FOT can be proposed as an alternative method for the assessment of bronchial responsiveness in subjects with suspected OA, unable to correctly perform forced expiratory maneuvers.

Factors associated with early-stage pulmonary fibrosis as determined by high-resolution computed tomography among persons occupationally exposed to asbestos.

OBJECTIVES: Asbestosis remains difficult to diagnose, particularly in its early stages. The aim of this study was to determine criteria for independently associated features of pulmonary fibrosis in high-resolution computed tomograms among persons occupationally exposed to asbestos. METHODS: Retired persons with documented occupational asbestos exposure and no known asbestos-related diseases were assessed for occupational, clinical, functional respiratory, and chest X-ray criteria. In addition, they all underwent high-resolution computed tomography (HRCT) in the prone position. RESULTS: Altogether 51 (7.2%) of the 706 enrolled participants had features of pulmonary fibrosis consistent with asbestosis in the HRCT. Among those with small irregular opacities of <1/0 according to the 1980 International Labour Office Classification (ILO-C) in their X-rays, 5% had asbestosis in the HRCT. In a multivariate analysis, only age [odds ratio (OR) per year 1.08, 95% confidence interval (95% CI) 1.02-1.14], cumulative-exposure index (CEI) for asbestos (OR 6.4, 95% CI 1.5-28.4 for a CEI of > or =100 fibers/ml x years), and the presence of small irregular X-ray opacities of > or =1/0 ILO-C (OR 3.0, 95% CI 1.6-6.0) were independently associated with HRCT asbestosis. No combinations of these criteria simultaneously yielded high sensitivity and specificity for the diagnosis of early-stage HRCT asbestosis. Moreover, only 2% of the persons with a CEI of <25 fibers/ml x years had HRCT asbestosis, the finding confirming the low incidence of asbestosis for such low exposure, as previously reported on the basis of X-ray data. CONCLUSIONS: Additional research is needed to better identify the persons most likely to benefit from HRCT screening for asbestosis.

[Occupational asthma]. / Asthmes professionnels.

BACKGROUND: Occupational asthma (OA) is a frequent work-related disease in industrialised countries. It often leads to severe social and medical consequences. TWO TYPES OF OA: A distinction must be made between OA with a latency period, the origin of which is essentially allergic, and OA without a latency period or Reactive airways dysfunction syndrome (RADS), induced by acute inhalation of irritant substances. PREVALENCE: This is currently estimated as one case of asthma of occupational origin in one adult out of ten. In many cases its diagnosis is missed because it is not systematically searched for. REGARDING DIAGNOSIS: Diagnosis, initiated on the results of questioning, must be supported by immunological tests whenever possible and notably on functional respiratory explorations (longitudinal monitoring of peak flow or spirometry, repeated measurements of non-specific bronchial reactivity), which objectifies significant variations in the parameters measured and related to professional activity. Bronchial challenge tests specifically identify the causal agent, but such examinations are long, expensive, potentially dangerous and therefore cannot be used in routine. MANAGEMENT OF OA: Both social and medical, the management is aimed at stopping the exposure to the risk whilst protecting the person's employment. The declaration of occupational diseases is one of the principle measures of the medico-social care.

[Asbestos-related occupational cancers]. / Cancers professionnels liés à l'amiante.

Due to its remarkable physical properties asbestos has been widely used in the industry. It is estimated that 25% of present French retired workers have been occupationally exposed to asbestos. A causal relationship between asbestos exposure and respiratory cancers is established since 1955 for lung cancer, and since 1960 for pleural mesothelioma. A causal relationship is also demonstrated for peritoneal and pericardic mesotheliomas, and strongly suspected for laryngeal cancers. It is estimated that occupational exposure to asbestos could be responsible for 5 to 20% of lung cancers and 80 to 90% of pleural mesothelioma, in men, in industrialized countries. The risk of cancer is positively correlated to cumulated exposure. No threshold has been demonstrated below which there is no increased risk of respiratory cancer.

[How to identify an occupational exposure to carcinogens and in which cases?]. / Comment repérer une exposition professionnelle à des cancérogènes et chez qui?

Different tools may be used to evaluate previous occupational exposures, either in epidemiological studies or in clinical practice: occupational questionnaire followed by an expertise or the use of a job-exposure matrix; metrology; biometrology. In routine clinical practice, the main tool is an individual questionnaire to identify if a patient has worked in one of the main jobs or tasks known to be associated with an exposure to a definite carcinogen. As individual and collective consequences are important in case of recognition as an occupational disease, looking for the previous main occupational activities entailing exposure to carcinogens should be systematic in some sites of cancer: mesothelioma, lung, ethmoid, bladder and leukemia.

Pleural plaques and the risk of pleural mesothelioma.

BACKGROUND: The association between pleural plaques and pleural mesothelioma remains controversial. The present study was designed to examine the association between pleural plaques on computed tomography (CT) scan and the risk of pleural mesothelioma in a follow-up study of asbestos-exposed workers. METHODS: Retired or unemployed workers previously occupationally exposed to asbestos were invited to participate in a screening program for asbestos-related diseases, including CT scan, organized between October 2003 and December 2005 in four regions in France. Randomized, independent, double reading of CT scans by a panel of seven chest radiologists focused on benign asbestos-related abnormalities. A 7-year follow-up study was conducted in the 5287 male subjects for whom chest CT scan was available. Annual determination of the number of subjects eligible for free medical care because of pleural mesothelioma was carried out. Diagnosis certification was obtained from the French mesothelioma panel of pathologists. Survival regression based on the Cox model was used to estimate the risk of pleural mesothelioma associated with pleural plaques, with age as the main time variable and time-varying exposure variables, namely duration of exposure, time since first exposure, and cumulative exposure index to asbestos. All statistical tests were two-sided. RESULTS: A total of 17 incident cases of pleural mesothelioma were diagnosed. A statistically significant association was observed between mesothelioma and pleural plaques (unadjusted hazard ratio (HR) = 8.9, 95% confidence interval [CI] = 3.0 to 26.5; adjusted HR = 6.8, 95% CI = 2.2 to 21.4 after adjustment for time since first exposure and cumulative exposure index to asbestos). CONCLUSION: The presence of pleural plaques may be an independent risk factor for pleural mesothelioma.

Occupational asthma: new deleterious agents at the workplace.

This article summarizes the main new categories of occupational agents responsible for causing occupational asthma, with and without a latency period reported in the last 10 years. It also reports examples of occupational agents for which the fabrication processing or use have influenced the outcome of occupational asthma.

[Epidemiology of COPD in France]. / Epidémiologie de la bronchopneumopathie chronique obstructive en France.

CONTEXT: Chronic obstructive pulmonary disease (COPD) is a frequent and disabling disease but epidemiologic data remain fragmentary. OBJECTIVE: The objective of this work was to bring together and describe the French epidemiologic data about COPD. METHODS: This review of the literature was performed by querying the NLM PubMed database in French and in English with the key words "chronic obstructive pulmonary disease", "epidemiology", "mortality", and "France". The studies including French data were selected. RESULTS: Four prevalence studies and one mortality study were identified. Prevalence was estimated between 1.0 and 11.1% in the general population. The mean mortality rate between 2000 and 2002 was 84.3/100,000 in men and 19.1/100,000 in women. Smoking is the best documented risk factor and a dose-response relationship has been established. The attributable risk fraction for occupational exposure is assessed at 15 to 20%. DISCUSSION: Prevalence studies are rare and do not always include objective measures of respiratory function. There are no specific French data in populations of smokers. COPD is a major public health issue. The main risk factor is smoking but the risk fraction attributable to occupational exposure is substantial. Epidemiologic knowledge of COPD should advance as the results of studies and screening program for at-risk subjects currently underway as part of the national COPD plan become available.