Occupational exposure to organic solvents: a risk factor for pulmonary veno-occlusive disease.

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.

• Authors: David Montani, Edmund M Lau, Alexis Descatha, Xavier Jaïs, Laurent Savale, Pascal Andujar, Lynda Bensefa-Colas, Barbara Girerd, Inès Zendah, Jerome Le Pavec, Andrei Seferian, Frédéric Perros, Peter Dorfmüller, Elie Fadel, Florent Soubrier, Oliver Sitbon, Gérald Simonneau, Marc Humbert
• Journal: The European respiratory journal (Eur Respir J) Vol. 46 Issue 6 Pg. 1721-31 (Dec 2015) ISSN: 1399-3003 [Electronic] England
• PMID: 26541523 (Publication Type: Journal Article)
• Copyright: Copyright ©ERS 2015.

Chemical References

• Solvents
• Trichloroethylene
• EIF2AK4 protein, human
• Protein Serine-Threonine Kinases
• BMPR2 protein, human
• Bone Morphogenetic Protein Receptors, Type II

Topics

• 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, genetics)
• Logistic Models
• Lung (pathology)
• Male
• Middle Aged
• Multivariate Analysis
• Occupational Exposure (statistics & numerical data)
• Protein Serine-Threonine Kinases (genetics)
• Pulmonary Veno-Occlusive Disease (epidemiology, genetics, pathology)
• Risk Factors
• Solvents
• Surveys and Questionnaires
• Trichloroethylene
• Young Adult