Pierre Mouillot, N. Favrolt, C. Khouri, Aurélie Grandvuillemin, M. Chaumais, D. Schenesse, A. Seferian, X. Jais, L. Savale, G. Beltramo, Olivier Sitbon, J. Cracowski, Marc Humbert, Marjolaine Georges, Philippe Bonniaud, D. Montani
{"title":"吉西他滨相关性肺动脉高压的特征和预后","authors":"Pierre Mouillot, N. Favrolt, C. Khouri, Aurélie Grandvuillemin, M. Chaumais, D. Schenesse, A. Seferian, X. Jais, L. Savale, G. Beltramo, Olivier Sitbon, J. Cracowski, Marc Humbert, Marjolaine Georges, Philippe Bonniaud, D. Montani","doi":"10.1183/23120541.00654-2023","DOIUrl":null,"url":null,"abstract":"Despite its known cardiac and lung toxicities, the chemotherapy drug gemcitabine has only rarely been associated with pulmonary hypertension (PH), and the underlying mechanism remains unclear.To assess the association between gemcitabine and PH.We identified incident cases of precapillary PH confirmed by right heart catheterisation in patients treated with gemcitabine from the French PH Registry between January 2007 to December 2022. The etiology, clinical, functional, radiologic, and hemodynamic characteristics of PH were reviewed at baseline and during follow-up. A pharmacovigilance disproportionality analysis was conducted using the WHO pharmacovigilance database.We identified nine cases of PAH, either induced (in eight patients) or exacerbated (in one patient) by gemcitabine. Patients exhibited severe precapillary PH, with a median mean pulmonary arterial pressure of 40 (min-max 26–47) mmHg, a cardiac index of 2.4 (1.6–3.9) L·min−1·m−2, and pulmonary vascular resistance of 6.3 (3.1–12.6) WU. The median time from the initiation of gemcitabine to the onset of PH was 7 (4–50) months, with patients receiving a median of 16 (6–24) gemcitabine injections. Six patients showed clinical improvement upon discontinuation of gemcitabine. In the WHO pharmacovigilance database, we identified a significant signal with 109 cases reporting at least one adverse event related to PH with gemcitabine.Both clinical cases and pharmacovigilance data substantiate a significant association between gemcitabine use and the onset or worsening of precapillary PH. The observed improvement following the discontinuation of treatment underscores the importance of PH screening in gemcitabine-exposed patients experiencing unexplained dyspnea.","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Characteristics and outcomes of gemcitabine-associated pulmonary hypertension\",\"authors\":\"Pierre Mouillot, N. Favrolt, C. Khouri, Aurélie Grandvuillemin, M. Chaumais, D. Schenesse, A. Seferian, X. Jais, L. Savale, G. Beltramo, Olivier Sitbon, J. Cracowski, Marc Humbert, Marjolaine Georges, Philippe Bonniaud, D. Montani\",\"doi\":\"10.1183/23120541.00654-2023\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Despite its known cardiac and lung toxicities, the chemotherapy drug gemcitabine has only rarely been associated with pulmonary hypertension (PH), and the underlying mechanism remains unclear.To assess the association between gemcitabine and PH.We identified incident cases of precapillary PH confirmed by right heart catheterisation in patients treated with gemcitabine from the French PH Registry between January 2007 to December 2022. The etiology, clinical, functional, radiologic, and hemodynamic characteristics of PH were reviewed at baseline and during follow-up. A pharmacovigilance disproportionality analysis was conducted using the WHO pharmacovigilance database.We identified nine cases of PAH, either induced (in eight patients) or exacerbated (in one patient) by gemcitabine. Patients exhibited severe precapillary PH, with a median mean pulmonary arterial pressure of 40 (min-max 26–47) mmHg, a cardiac index of 2.4 (1.6–3.9) L·min−1·m−2, and pulmonary vascular resistance of 6.3 (3.1–12.6) WU. The median time from the initiation of gemcitabine to the onset of PH was 7 (4–50) months, with patients receiving a median of 16 (6–24) gemcitabine injections. Six patients showed clinical improvement upon discontinuation of gemcitabine. In the WHO pharmacovigilance database, we identified a significant signal with 109 cases reporting at least one adverse event related to PH with gemcitabine.Both clinical cases and pharmacovigilance data substantiate a significant association between gemcitabine use and the onset or worsening of precapillary PH. The observed improvement following the discontinuation of treatment underscores the importance of PH screening in gemcitabine-exposed patients experiencing unexplained dyspnea.\",\"PeriodicalId\":11739,\"journal\":{\"name\":\"ERJ Open Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-05-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ERJ Open Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1183/23120541.00654-2023\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RESPIRATORY SYSTEM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ERJ Open Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1183/23120541.00654-2023","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
Characteristics and outcomes of gemcitabine-associated pulmonary hypertension
Despite its known cardiac and lung toxicities, the chemotherapy drug gemcitabine has only rarely been associated with pulmonary hypertension (PH), and the underlying mechanism remains unclear.To assess the association between gemcitabine and PH.We identified incident cases of precapillary PH confirmed by right heart catheterisation in patients treated with gemcitabine from the French PH Registry between January 2007 to December 2022. The etiology, clinical, functional, radiologic, and hemodynamic characteristics of PH were reviewed at baseline and during follow-up. A pharmacovigilance disproportionality analysis was conducted using the WHO pharmacovigilance database.We identified nine cases of PAH, either induced (in eight patients) or exacerbated (in one patient) by gemcitabine. Patients exhibited severe precapillary PH, with a median mean pulmonary arterial pressure of 40 (min-max 26–47) mmHg, a cardiac index of 2.4 (1.6–3.9) L·min−1·m−2, and pulmonary vascular resistance of 6.3 (3.1–12.6) WU. The median time from the initiation of gemcitabine to the onset of PH was 7 (4–50) months, with patients receiving a median of 16 (6–24) gemcitabine injections. Six patients showed clinical improvement upon discontinuation of gemcitabine. In the WHO pharmacovigilance database, we identified a significant signal with 109 cases reporting at least one adverse event related to PH with gemcitabine.Both clinical cases and pharmacovigilance data substantiate a significant association between gemcitabine use and the onset or worsening of precapillary PH. The observed improvement following the discontinuation of treatment underscores the importance of PH screening in gemcitabine-exposed patients experiencing unexplained dyspnea.
期刊介绍:
ERJ Open Research is a fully open access original research journal, published online by the European Respiratory Society. The journal aims to publish high-quality work in all fields of respiratory science and medicine, covering basic science, clinical translational science and clinical medicine. The journal was created to help fulfil the ERS objective to disseminate scientific and educational material to its members and to the medical community, but also to provide researchers with an affordable open access specialty journal in which to publish their work.