1. Occupational exposure to organic solvents: a risk factor for pulmonary veno-occlusive disease.
- Author
-
Montani D, Lau EM, Descatha A, Jaïs X, Savale L, Andujar P, Bensefa-Colas L, Girerd B, Zendah I, Le Pavec J, Seferian A, Perros F, Dorfmüller P, Fadel E, Soubrier F, Sitbon O, Simonneau G, and Humbert M
- Subjects
- Adult, Age of Onset, Aged, Aged, 80 and over, Bone Morphogenetic Protein Receptors, Type II genetics, Case-Control Studies, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Humans, Hypertension, Pulmonary epidemiology, Hypertension, Pulmonary genetics, Logistic Models, Lung pathology, Male, Middle Aged, Multivariate Analysis, Pulmonary Veno-Occlusive Disease genetics, Pulmonary Veno-Occlusive Disease pathology, Risk Factors, Surveys and Questionnaires, Young Adult, Occupational Exposure statistics & numerical data, Protein Serine-Threonine Kinases genetics, Pulmonary Veno-Occlusive Disease epidemiology, Solvents, Trichloroethylene
- Abstract
Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension characterised by predominant remodelling of pulmonary venules. Bi-allelic mutations in the eukaryotic translation initiation factor 2α kinase 4 (EIF2AK4) gene were recently described as the major cause of heritable PVOD, but risk factors associated with PVOD remain poorly understood. Occupational exposures have been proposed as a potential risk factor for PVOD, but epidemiological studies are lacking.A case-control study was conducted in consecutive PVOD (cases, n=33) and pulmonary arterial hypertension patients (controls, n=65). Occupational exposure was evaluated via questionnaire interview with blinded assessments using an expert consensus approach and a job exposure matrix (JEM).Using the expert consensus approach, PVOD was significantly associated with occupational exposure to organic solvents (adjusted OR 12.8, 95% CI 2.7-60.8), with trichloroethylene being the main agent implicated (adjusted OR 8.2, 95% CI 1.4-49.4). JEM analysis independently confirmed the association between PVOD and trichloroethylene exposure. Absence of significant trichloroethylene exposure was associated with a younger age of disease (54.8±21.4 years, p=0.037) and a high prevalence of harbouring bi-allelic EIF2AK4 mutations (41.7% versus 0%, p=0.015).Occupational exposure to organic solvents may represent a novel risk factor for PVOD. Genetic background and environmental exposure appear to influence the phenotypic expression of the disease., (Copyright ©ERS 2015.)
- Published
- 2015
- Full Text
- View/download PDF