Whistleblowers

Humbert, Marc; Simonneau, Gérald; Dinh-Xuan, Anh Tuan

doi:10.1183/09031936.00075211

Cited by 8 publications

(3 citation statements)

References 28 publications

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“…After worldwide alerts concerning anorexigens, many drugs were suspected to be risk factors for PAH [48]. However, it remains a great challenge to confirm the imputability of a drug, because PAH is always a rare complication occurring only in a very small proportion of exposed patients (usually ,1%).…”

Section: Resultsmentioning

confidence: 99%

Drug-induced pulmonary arterial hypertension: a recent outbreak

Montani¹,

Seferian²,

Savale³

et al. 2013

Eur Respir Rev

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Pulmonary arterial hypertension (PAH) is a rare disorder characterised by progressive obliteration of the pulmonary microvasculature resulting in elevated pulmonary vascular resistance and premature death. According to the current classification PAH can be associated with exposure to certain drugs or toxins, particularly to appetite suppressant intake drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary artery smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used, but are considered possible risk factors, for PAH. Dasatinib, dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, potentially in part reversible after dasatinib withdrawal. Recently, several studies have raised the issue of potential endothelial dysfunction that could be induced by interferon, and a few cases of PAH have been reported with interferon therapy. PAH remains a rare complication of these drugs, suggesting possible individual susceptibility, and further studies are needed to identify patients at risk of drug-induced PAH. @ERSpublications Drug-associated PAH remains a clinical challenge: understanding the mechanisms and identifying drugs at-risk for PAH

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Section: Resultsmentioning

confidence: 99%

Drug-induced pulmonary arterial hypertension: a recent outbreak

Montani¹,

Seferian²,

Savale³

et al. 2013

Eur Respir Rev

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“…Although an additional larger case-control study is required to further strengthen hypothesis of a pathogenic role for benfluorex in the development of PAH, it is unlikely such a study will ever be undertaken given that this agent has now been withdrawn from the market. As PAH is an unequivocal severe consequence of cardiovascular toxicity of several drugs and toxins, one should investigate in great detail all cases referred for so-called unexplained PAH in order to identify whether a toxic exposure may have acted as a trigger for PAH [35]. …”

Section: Discussionmentioning

confidence: 99%

Pulmonary hypertension associated with benfluorex exposure

Savale¹,

Chaumais²,

Cottin³

et al. 2012

Eur Respir J

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Benfluorex was marketed in France until 2009, despite its similar pharmacological properties with fenfluramine and its derivatives known to be a cause of pulmonary arterial hypertension (PAH).The aim of this study is to report clinical and haemodynamic characteristics for patients suffering from pulmonary hypertension (PH) associated with benfluorex exposure that had been identified by the French PAH Network.85 cases of PH associated with benfluorex exposure were identified by the French PAH Network from June 1999 to March 2011. Of these, 70 patients had confirmed pre-capillary PH. The median duration of exposure was 30 months, with a median of 108 months between start of exposure and diagnosis of the pulmonary vascular disease. 33% of all patients also had prior exposure to fenfluramine or dexfenfluramine, and an additional risk factor for PH was identified in 20 (30%) out of 70 patients with pre-capillary PH. A quarter of patients in this current series showed coexisting PH and mild-to-moderate cardiac valve involvement.The results of our study, together with the accumulated data regarding the known toxic effects of fenfluramine and dexfenfluramine, strongly suggest that benfluorex exposure is a potent trigger for PAH.

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“…Publications are a crosscutting segment of ERS activities, moving across science, education, advocacy and international links [14][15][16][17][18][19]. Based on the 5-year strategy presented by the Publications Committee in 2011, several core topics were discussed including further professionalising European Respiratory Journal editors and its Editorial Board, a possible future extension of the Chief Editor's mandate, and rationalisation of the location of publications.…”

Section: Strategic Decision 6: Improving Publicationsmentioning

confidence: 99%