Pulmonary veno-occlusive disease as an occupational lung disease

We read with interest the Review of Paul Cullinan and colleagues1Cullinan P Muñoz X Suojalehto H et al.Occupational lung diseases: from old and novel exposures to effective preventive strategies.Lancet Respir Med. 2017; 5: 445-455Summary Full Text Full Text PDF PubMed Scopus (74) Google Scholar on occupational lung diseases published in The Lancet Respiratory Medicine. The authors proposed a detailed overview of the acute and chronic respiratory diseases associated with established and novel occupational exposures. As reported by the authors, research on the toxic effects of occupational and environmental exposures have largely been focused on airway diseases (chronic obstructive pulmonary disease, emphysema, asthma), parenchymal lung diseases (interstitial lung diseases) and lung cancer. However, the vascular compartment of the lung has largely been ignored and the unique pulmonary alveolar–capillary interface suggests that inhaled exposures could potentially be relevant in the development of pulmonary vascular disease. On the basis of a case-control study, we recently reported2Montani D Lau EM Descatha A et al.Occupational exposure to organic solvents: a risk factor for pulmonary veno-occlusive disease.Eur Respir J. 2015; 46: 1721-1731Crossref PubMed Scopus (66) Google Scholar that occupational exposure to organic solvents, particularly trichloroethylene, is a novel risk factor for the occurrence of pulmonary veno-occlusive disease (PVOD). PVOD is a rare and severe form of pulmonary hypertension characterised by occlusion of small pulmonary veins and pulmonary capillary proliferation. Diagnosis of PVOD is based on the presence of precapillary pulmonary hypertension, characteristic radiological abnormalities on CT of the chest (septal lines, ground-glass opacities, and lymph-node enlargement) and low diffusing capacity for carbon monoxide.3Montani D Lau EM Dorfmüller P et al.Pulmonary veno-occlusive disease.Eur Respir J. 2016; 47: 1518-1534Crossref PubMed Scopus (153) Google Scholar We recently described4Montani D Girerd B Jaïs X et al.Clinical phenotypes and outcomes of heritable and sporadic pulmonary veno-occlusive disease: a population-based study.Lancet Respir Med. 2017; 5: 125-134Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar in The Lancet Respiratory Medicine the genotype–phenotype association in PVOD, showing that this disease has two different presentations. PVOD can occur from early life to middle age in patients with the heritable form of the disease carrying biallelic EIF2AK4 mutations, or occur later in life with a median age of 60 years as sporadic cases without EIF2AK4 mutations.4Montani D Girerd B Jaïs X et al.Clinical phenotypes and outcomes of heritable and sporadic pulmonary veno-occlusive disease: a population-based study.Lancet Respir Med. 2017; 5: 125-134Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar Importantly, we found a very high prevalence of previous occupational exposure to organic solvents in the sporadic form of the disease, accounting for more than 40% of cases. By contrast, a history of organic solvent exposure was absent in patients with heritable PVOD.4Montani D Girerd B Jaïs X et al.Clinical phenotypes and outcomes of heritable and sporadic pulmonary veno-occlusive disease: a population-based study.Lancet Respir Med. 2017; 5: 125-134Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar Systemic sclerosis is an autoimmune condition that is frequently complicated by pulmonary arterial hypertension and pulmonary veno-occlusive disease.4Montani D Girerd B Jaïs X et al.Clinical phenotypes and outcomes of heritable and sporadic pulmonary veno-occlusive disease: a population-based study.Lancet Respir Med. 2017; 5: 125-134Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar Interestingly, an association between trichloroethylene (as well as other organic solvents) and systemic sclerosis has been replicated by many studies.5Marie I Gehanno J-F Bubenheim M et al.Prospective study to evaluate the association between systemic sclerosis and occupational exposure and review of the literature.Autoimmun Rev. 2014; 13: 151-156Crossref PubMed Scopus (99) Google Scholar It remains entirely speculative whether PVOD and systemic sclerosis might represent different spectrums of potential end-organ toxic effects associated with trichloroethylene exposure. Several mechanisms might be involved in the toxicity of trichloroethylene including endothelial dysfunction, oxidative stress, activation of the serotonin pathway, and inflammation and activation of autoimmunity. All of these mechanisms have also been reported in the pathophysiology of pulmonary hypertension, reinforcing the potential link between solvent exposure and pulmonary vascular diseases.6Guignabert C Tu L Girerd B et al.New molecular targets of pulmonary vascular remodeling in pulmonary arterial hypertension: importance of endothelial communication.Chest. 2015; 147: 529-537Summary Full Text Full Text PDF PubMed Scopus (114) Google Scholar Pulmonary vascular diseases should not be excluded from the spectrum of occupational respiratory diseases. Further epidemiological and experimental studies are needed to understand through what mechanisms trichloroethylene might induce specific pulmonary vascular remodelling. We concur with Cullinan and colleagues1Cullinan P Muñoz X Suojalehto H et al.Occupational lung diseases: from old and novel exposures to effective preventive strategies.Lancet Respir Med. 2017; 5: 445-455Summary Full Text Full Text PDF PubMed Scopus (74) Google Scholar that greater physician awareness, thorough surveillance and reporting, and epidemiological research remain important in the identification and monitoring of occupational diseases. We declare no competing interests. Occupational lung diseases: from old and novel exposures to effective preventive strategiesOccupational exposure is an important, global cause of respiratory disease. Unlike many other non-communicable lung diseases, the proximal causes of many occupational lung diseases are well understood and they should be amenable to control with use of established and effective approaches. Therefore, the risks arising from exposure to silica and asbestos are well known, as are the means of their prevention. Although the incidence of occupational lung disease has decreased in many countries, in parts of the world undergoing rapid economic transition and population growth—often with large informal and unregulated workforces—occupational exposures continue to impose a heavy burden of disease. Full-Text PDF