Christophe Paris

Pleural plaques and asbestosis: dose and time-response relationships based on HRCT data

Most studies on asbestos-related diseases are based on chest radiographs, and dose–response relationships are still controversial. The aim of this study was to describe the most relevant parameters of asbestos exposure linked to pleural plaques and asbestosis diagnosed by high-resolution computed tomography (HRCT). A large screening programme including systematic HRCT examinations was organised from 2003 to 2005 in France for formerly asbestos-exposed workers. The time since first exposure (TSFE), level, duration and cumulative exposure to asbestos were used in adjusted unconditional logistic regression to model the relationships of the two diseases. Analysis of a population of 5,545 subjects demonstrated that TSFE (p<0.0001) and cumulative exposure (p = 0.02) (or level, depending on the models used), were independently associated with the frequency of pleural plaques. Only cumulative exposure (p<0.0001) or level of exposure (p = 0.02) were significantly associated with asbestosis. All trend tests were significant for these parameters. To date and to our knowledge, this study is the largest programme based on HRCT for the screening of asbestos-exposed subjects. Both time–response and dose–response relationships were demonstrated for pleural plaques, while only dose–response relationships were demonstrated for asbestosis. These parameters must be included in the definition of high-risk populations for HRCT-based screening programmes.

Occupational asbestos exposure and digestive cancers - a cohort study.

Background  Although the role of asbestos in the genesis of mesothelioma and primary bronchopulmonary cancers has been established, results from studies focusing on the relationship between occupational exposure to asbestos and digestive cancer remain contradictory.

Prognostic value of exercise pulmonary haemodynamics in pulmonary arterial hypertension

The aim of the study was to investigate the prognostic value of right heart catheterisation variables measured during exercise. 55 incident patients with idiopathic, familial or anorexigen-associated pulmonary arterial hypertension (PAH) underwent right heart catheterisation at rest and during exercise and 6-min walk testing before PAH treatment initiation. Patients were treated according to recommendations within the next 2 weeks. Right heart catheterisation was repeated 3–5 months into the PAH treatment in 20 patients. Exercise cardiac index decreased gradually as New York Heart Association (NYHA) functional class increased whereas cardiac index at rest was not significantly different across NYHA groups. Baseline 6-min walk distance correlated significantly with exercise and change in cardiac index from rest to exercise (r=0.414 and r=0.481, respectively; p<0.01). Change in 6-min walk distance from baseline to 3–5 months under PAH treatment was highly correlated with change in exercise cardiac index (r=0.746, p<0.001). The most significant baseline covariates associated with survival were change in systolic pulmonary artery pressure from rest to exercise and exercise cardiac index (hazard ratio 0.56 (95% CI 0.37–0.86) and 0.14 (95% CI 0.05–0.43), respectively). Change in pulmonary haemodynamics during exercise is an important tool for assessing disease severity and may help devise optimal treat-to-target strategies. Exercise cardiac index correlated with exercise capacity and was associated with long-term survival in PAH http://ow.ly/vG2bb

Comparison of exposure assessment methods in a lung cancer case-control study: performance of a lifelong task-based questionnaire for asbestos and PAHs.

Objective To describe the performance of a lifelong task-based questionnaire (TBQ) in estimating exposures compared with other approaches in the context of a case-control study. Methods A sample of 93 subjects was randomly selected from a lung cancer case-control study corresponding to 497 jobs. For each job, exposure assessments for asbestos and polycyclic aromatic hydrocarbons (PAHs) were obtained by expertise (TBQ expertise) and by algorithm using the TBQ (TBQ algorithm) as well as by expert appraisals based on all available occupational data (REFERENCE expertise) considered to be the gold standard. Additionally, a Job Exposure Matrix (JEM)-based evaluation for asbestos was also obtained. On the 497 jobs, the various evaluations were contrasted using Cohens κ coefficient of agreement. Additionally, on the total case-control population, the asbestos dose-response relationship based on the TBQ algorithm was compared with the JEM-based assessment. Results Regarding asbestos, the TBQ-exposure estimates agreed well with the REFERENCE estimate (TBQ expertise: level-weighted κ (lwk)=0.68; TBQ algorithm: lwk=0.61) but less so with the JEM estimate (TBQ expertise: lwk=0.31; TBQ algorithm: lwk=0.26). Regarding PAHs, the agreements between REFERENCE expertise and TBQ were less good (TBQ expertise: lwk=0.43; TBQ algorithm: lwk=0.36). In the case-control study analysis, the dose-response relationship between lung cancer and cumulative asbestos based on the JEM is less steep than with the TBQ-algorithm exposure assessment and statistically non-significant. Conclusions Asbestos-exposure estimates based on the TBQ were consistent with the REFERENCE expertise and yielded a steeper dose-response relationship than the JEM. For PAHs, results were less clear.

Digestive cancers and occupational asbestos exposure: incidence study in a cohort of asbestos plant workers.

Objective The aim of our study was to estimate the incidence of digestive cancers within a cohort of asbestos-exposed workers. Methods Our study was based on a cohort of 2024 participants occupationally exposed to asbestos. The incidence of digestive cancers was calculated from 1 January 1978 to 31 December 2009 and compared with levels among the local general population using Standardised Incidence Ratios (SIRs). Asbestos exposure was assessed using the company’s job-exposure matrix. Results 119 cases of digestive cancer were observed within our cohort, for an expected number of 77 (SIR=1.54 (1.28 to 1.85)). A significantly elevated incidence was observed for peritoneal mesothelioma, particularly in women. Significantly elevated incidences were also observed among men for: all digestive cancers, even when excluding peritoneal mesothelioma (SIR=1.50 (1.23 to 1.82)), oesophageal cancer (SIR=1.67 (1.08 to 2.47)) and liver cancer (SIR=1.85 (1.09 to 2.92)). Concerning colorectal cancer, a significant excess of risk was observed for men with exposure duration above 25 years (SIR=1.75 (1.05 to 2.73)). Conclusions Our results are in favour of a link between long-duration asbestos exposure and colorectal cancer in men. They also suggest a relationship between asbestos exposure and cancer of the oesophagus in men. Finally, our results suggest a possible association with small intestine and liver cancers in men.

Methyl(R217)HuR and MCM6 are inversely correlated and are prognostic markers in non small cell lung carcinoma.

OBJECTIVES In non small cell lung carcinoma (NSCLC), earlier studies supported a prognostic value of intra-cytoplasmic HuR expression. HuR is a RNA binding protein previously shown to stimulate proliferation, but the link between HuR and proliferation in NSCLC has not yet been evaluated. The first objective of this study was to analyze the expression of HuR in a series of NSCLC and to correlate this to two proliferation markers, Ki-67 and MCM6. As potential post-transcriptional regulatory mechanisms for HuR expression, two miRNAs, miR16 and miR519, were also analyzed. Finally, because HuR methylation could be involved in its nucleocytoplasmic shuttling, the expression of methyl(R217)HuR and its relation to cancer survival were determined. MATERIALS AND METHODS Immunohistochemistry was used to evaluate the expression of HuR, methy(R217)HuR, Ki-67 and MCM6 in a series of 190 NSCLCs. The level of miR16 and miR519 was determined by qRT-PCR. RESULTS Higher cytoplasmic HuR staining was found in tumor vs. control paired normal lung (p<0.0001), but without correlation with survival. The level of methyl(R217)HuR was correlated both significantly with intra-cytoplasmic HuR staining (p<0.001), and overall survival (p=0.01). MCM6 correlated to a poorer overall survival (p<0.01). Both MCM6 and Ki-67 were positively correlated with HuR nuclear staining (p<0.0001 and p<0.001, respectively). On the contrary, MCM6 and Ki-67 correlated inversely to methyl(R217)HuR (p<0.001 and p=0.01, respectively). The levels of miR16 and miR519 were significantly lower in tumor tissue vs. paired normal lung (p<0.0001), but only miR519 correlated inversely to HuR expression (p=0.01). CONCLUSION While overall cytoplasmic HuR level was higher in tumor tissues, we found unexpectedly that methyl(R217)HuR was a marker of good prognosis. Furthermore, our data suggest that HuR level could be regulated by miR519. Finally, we demonstrated that Ki-67 and MCM6, both correlated with HuR, are valuable markers of poor prognosis in NSCLC.

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.

First evidence of occupational asthma to argan powder in a cosmetic factory.

Argan is used worldwide in numerous cosmetic products, as this fruit is supposed to have many beneficial properties on health. New cases of allergy can be expected with the growing use of argan. We investigated all workers (9) employed by a cosmetic factory and exposed to argan powder to identify possible allergies related to exposure to argan powder.

Occupational Asbestos Exposure and Incidence of Colon and Rectal Cancers in French Men: The Asbestos-Related Diseases Cohort (ARDCo-Nut).

Background: The relationships between asbestos exposure and colorectal cancer remain controversial. Objectives: We examined the association between asbestos exposure and colorectal cancer incidence. Methods: Volunteer retired workers previously exposed to asbestos were invited to participate in the French ARDCo screening program between 2003 and 2005. Additional data on risk factors for colorectal cancer were collected from the ARDCo-Nut subsample of 3,769 participants in 2011. Cases of colon and rectal cancer were ascertained each year through 2014 based on eligibility for free medical care following a cancer diagnosis. Survival regression based on the Cox model was used to estimate the relative risk of colon and rectal cancer separately, in relation to the time since first exposure (TSFE) and cumulative exposure index (CEI) to asbestos, and with adjustment for smoking in the overall cohort and for smoking, and certain risk factors for these cancers in the ARDCo-Nut subsample. Results: Mean follow-up was 10.2 years among 14,515 men, including 181 colon cancer and 62 rectal cancer cases (41 and 17, respectively, in the ARDCo-Nut subsample). In the overall cohort, after adjusting for smoking, colon cancer was significantly associated with cumulative exposure (HR = 1.14; 95% CI: 1.04, 1.26 for a 1-unit increase in ln-CEI) and ≥ 20–40 years since first exposure (HR = 4.67; 95% CI: 1.92, 11.46 vs. 0–20 years TSFE), and inversely associated with 60 years TSFE (HR = 0.26; 95% CI: 0.10, 0.70). Although rectal cancer was also associated with TSFE 20–40 years (HR = 4.57; 95% CI: 1.14, 18.27), it was not associated with ln-CEI, but these findings must be interpreted cautiously due to the small number of cases. Conclusions: Our findings provide support for an association between occupational exposure to asbestos and colon cancer incidence in men. Citation: Paris C, Thaon I, Hérin F, Clin B, Lacourt A, Luc A, Coureau G, Brochard P, Chamming’s S, Gislard A, Galan P, Hercberg S, Wild P, Pairon JC, Andujar P. 2017. Occupational asbestos exposure and incidence of colon and rectal cancers in French men: the Asbestos-Related Diseases Cohort (ARDCo-Nut). Environ Health Perspect 125:409–415; http://dx.doi.org/10.1289/EHP153

Prevalence of occupational exposure to asbestos and crystalline silica according to phenotypes of lung cancer from the CaProMat study: A case‐only study

BACKGROUND The objective of the study was to compare the prevalence of occupational exposure to asbestos and crystalline silica according to histological types of lung cancer and age at diagnosis. METHODS CaProMat study is a pooled case-only study conducted between 1996 and 2011. The current study consisted of 6521 lung cancer cases. Occupational exposure to asbestos and crystalline silica was assessed by two Job-Exposure Matrices. A weighted prevalence of exposure was derived and compared according to histological types and age at diagnosis. RESULTS There was no difference of weighted prevalence of exposure to asbestos and crystalline silica according to histological types of lung cancer. There was a statistically significant difference of weighted prevalence of exposure to asbestos and crystalline silica according to age at diagnosis. CONCLUSIONS Due to the limited clinical importance of the difference, neither the histological type, nor the age at diagnosis can be used as an indicator for the occupational exposure to asbestos or crystalline silica.