%0期刊文章%A Jason Weatherald %A Louise Bondeelle %A Marie-Camille Chaumais %A Christophe Guignabert %A Laurent Savale %A Xavier Jaïs %A Olivier Sitbon %A Philippe Rousselot %A Marc Humbert %A Anne Bergeron %A David Montani %T Bcr-Abl酪氨酸激酶抑制剂的肺部并发症%D 2020 %R 10.1193 /13993003.00279-2020 %J欧洲呼吸杂志%P 2000279% X针对Bcr-Abl癌蛋白的酪氨酸激酶抑制剂(TKIs)彻底改变了慢性疾病的治疗粒细胞性白血病。继伊马替尼成功之后，第二代和第三代分子被开发出来。不同TKIs的激酶抑制和脱靶效应不同，这导致了广泛的潜在毒性。达沙替尼最常出现肺部并发症，但所有其他Bcr-Abl TKIs都涉及肺部并发症。胸腔积液是TKIs最常见的肺部并发症，通常与达沙替尼和博舒替尼相关。肺动脉高压是达沙替尼不常见但严重的并发症，停药后通常是可逆的。博舒替尼和ponatinib也与肺动脉高压有关，而伊马替尼没有。间质性肺疾病很少与TKIs相关，主要与伊马替尼相关。在机制上，达沙替尼通过产生线粒体氧化应激、诱导内皮细胞凋亡和损害血管通透性以剂量依赖的方式影响正常肺内皮完整性的维持。其他tki相关并发症的机制在很大程度上尚不清楚。 Awareness and early diagnosis of the pulmonary complications of Bcr-Abl TKIs is essential given their seriousness, potential reversibility, and impact on future treatment options for the underlying chronic myelogenous leukemia.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Weatherald reports grants, personal fees and non-financial support from Janssen Inc., grants, personal fees and non-financial support from Actelion, personal fees and non-financial support from Bayer, personal fees from Novartis, grants from Alberta Lung Association, grants from Canadian Vascular Network, grants from European Respiratory Society, grants from Canadian Thoracic Society, outside the submitted work.Conflict of interest: Dr. Chaumais reports personal fees from Actelion, non-financial support from Bayer, non-financial support from Boehringer Ingelheim, outside the submitted work.Conflict of interest: Dr. Guignabert has nothing to disclose.Conflict of interest: Dr. Savale reports personal fees from Actelion, grants and personal fees from Bayer, grants and personal fees from GSK, outside the submitted work.Conflict of interest: Dr. Jaïs reports grants and personal fees from Actelion, grants and personal fees from MSD, grants from Bayer, outside the submitted work.Conflict of interest: Dr. Sitbon reports grants, personal fees and non-financial support from Actelion Pharmaceuticals, personal fees and non-financial support from Acceleron Pharmaceuticals, grants, personal fees and non-financial support from Bayer HealthCare, personal fees from Ferrer, grants from GlaxoSmithKline, personal fees from Gossamer Bio, grants, personal fees and non-financial support from MSD, personal fees from United Therapeutics, outside the submitted work.Conflict of interest: Dr. ROUSSELOT reports grants and personal fees from Pfizer, grants and personal fees from Incyte, grants from Britol Myers Squibb, outside the submitted work.Conflict of interest: Dr. Humbert reports personal fees from Acceleron, grants and personal fees from Actelion, grants and personal fees from Bayer, grants and personal fees from GSK, personal fees from Merck, personal fees from Morphogen IX, personal fees from United Therapeutics, outside the submitted work.Conflict of interest: Dr. Bergeron reports grants from SOS oxygene, personal fees from Shire, personal fees from Pfizer, personal fees from MSD, personal fees from Gilead, outside the submitted work.Conflict of interest: Dr. MONTANI reports grants and personal fees from Actelion, grants and personal fees from Bayer, personal fees from GSK, personal fees from Pfizer, personal fees from MSD, personal fees from Chiesi, outside the submitted workConflict of interest: Dr. Bondeelle has nothing to disclose. %U //www.qdcxjkg.com/content/erj/early/2020/06/08/13993003.00279-2020.full.pdf