Respiratory Disease Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, member of ERN Lung, Padova, Italy
Constitutive Reference Center for Rare Pulmonary Diseases, Department of Pulmonary Medicine and Intensive Care Unit, University Hospital, Bourgogne-Franche-Comté, Burgundy University, Dijon, France.
Eur Respir J. 2022 Oct 27;60(4). doi: 10.1183/13993003.02776-2021. Print 2022 Oct.
Interstitial lung disease (ILD) secondary to drug-induced lung injury is an increasingly common cause of morbidity and mortality. The number of drugs associated with the development of ILD continues to rise, mainly due to the use of novel monoclonal antibodies and biologicals for neoplastic and rheumatological diseases, and includes, among others, chemotherapeutics, molecular targeting agents, immune checkpoint inhibitors, antibiotics, antiarrhythmics and conventional or biological disease-modifying antirheumatic drugs. Drug-induced ILD (DI-ILD) manifests with a variety of clinical patterns, ranging from mild respiratory symptoms to rapidly progressive respiratory failure and death. In most cases, there are no pathognomonic clinical, laboratory, radiological or pathological features and the diagnosis of DI-ILD is suspected in the presence of exposure to a drug known to cause lung toxicity and after exclusion of alternative causes of ILD. Early identification and permanent discontinuation of the culprit drug are the cornerstones of treatment with systemic glucocorticoids being used in patients with disabling or progressive disease. However, for certain drugs, such as checkpoint inhibitors, the frequency of lung toxicity is such that mitigation strategies are put in place to prevent this complication, and occurrence of DI-ILD is not necessarily synonymous with permanent drug discontinuation, particularly in the absence of valid therapeutic alternatives.
药物性肺损伤导致的间质性肺病(ILD)是发病率和死亡率日益增加的一个重要原因。与ILD 发生相关的药物数量不断增加,主要与新型单克隆抗体和生物制剂在肿瘤和风湿病中的应用有关,其中包括化疗药物、分子靶向药物、免疫检查点抑制剂、抗生素、抗心律失常药以及常规或生物改善病情抗风湿药物。药物性 ILD(DI-ILD)表现为多种临床类型,从轻度呼吸道症状到快速进展性呼吸衰竭和死亡不等。在大多数情况下,没有特征性的临床、实验室、影像学或病理学特征,并且在存在已知可引起肺毒性的药物暴露和排除ILD 的其他原因后,才怀疑 DI-ILD 的诊断。早期识别和永久停用致病药物是使用全身性糖皮质激素治疗的基石,适用于有失能或进行性疾病的患者。然而,对于某些药物,如检查点抑制剂,肺毒性的发生频率如此之高,以至于需要采取缓解策略来预防这种并发症,而且 DI-ILD 的发生不一定与永久停药同义,特别是在没有有效治疗替代方案的情况下。