Am J Respir Crit Care Med. 2011 May 1;183(9):1262-79. doi: 10.1164/rccm.2007-413ST.
Acute lung dysfunction of noninfectious etiology, known as idiopathic pneumonia syndrome (IPS), is a severe complication following hematopoietic stem cell transplantation (HSCT). Several mouse models have been recently developed to determine the underlying causes of IPS. A cohesive interpretation of experimental data and their relationship to the findings of clinical research studies in humans is needed to better understand the basis for current and future clinical trials for the prevention/treatment of IPS.
Our goal was to perform a comprehensive review of the preclinical (i.e., murine models) and clinical research on IPS.
An ATS committee performed PubMed and OVID searches for published, peer-reviewed articles using the keywords "idiopathic pneumonia syndrome" or "lung injury" or "pulmonary complications" AND "bone marrow transplant" or "hematopoietic stem cell transplant." No specific inclusion or exclusion criteria were determined a priori for this review.
Experimental models that reproduce the various patterns of lung injury observed after HSCT have identified that both soluble and cellular inflammatory mediators contribute to the inflammation engendered during the development of IPS. To date, 10 preclinical murine models of the IPS spectrum have been established using various donor and host strain combinations used to study graft-versus-host disease (GVHD). This, as well as the demonstrated T cell dependency of IPS development in these models, supports the concept that the lung is a target of immune-mediated attack after HSCT. The most developed therapeutic strategy for IPS involves blocking TNF signaling with etanercept, which is currently being evaluated in clinical trials.
IPS remains a frequently fatal complication that limits the broader use of allogeneic HSCT as a successful treatment modality. Faced with the clinical syndrome of IPS, one can categorize the disease entity with the appropriate tools, although cases of unclassifiable IPS will remain. Significant research efforts have resulted in a paradigm shift away from identifying noninfectious lung injury after HSCT solely as an idiopathic clinical syndrome and toward understanding IPS as a process involving aspects of both the adaptive and the innate immune response. Importantly, new laboratory insights are currently being translated to the clinic and will likely prove important to the development of future strategies to prevent or treat this serious disorder.
非感染性病因引起的急性肺功能障碍，称为特发性肺炎综合征（IPS），是造血干细胞移植（HSCT）后的严重并发症。最近已经开发了几种小鼠模型来确定 IPS 的潜在原因。需要对实验数据进行综合解释，并将其与人类临床研究的发现联系起来，以便更好地理解当前和未来用于预防/治疗 IPS 的临床试验的基础。
我们的目标是对 IPS 的临床前（即小鼠模型）和临床研究进行全面综述。
一个 ATS 委员会在 PubMed 和 OVID 上使用“特发性肺炎综合征”或“肺损伤”或“肺部并发症”和“骨髓移植”或“造血干细胞移植”等关键词进行了已发表的同行评审文章的搜索。对于本综述，没有事先确定具体的纳入或排除标准。
复制 HSCT 后观察到的各种肺损伤模式的实验模型表明，可溶性和细胞炎症介质都有助于 IPS 发展过程中引发的炎症。迄今为止，已经使用各种供体和宿主株组合建立了 10 种 IPS 谱的临床前小鼠模型，用于研究移植物抗宿主病（GVHD）。这以及在这些模型中 IPS 发展的 T 细胞依赖性表明，肺是 HSCT 后免疫介导攻击的靶标。针对 IPS 的最成熟的治疗策略涉及使用依那西普阻断 TNF 信号，目前正在临床试验中进行评估。
IPS 仍然是一种经常致命的并发症，限制了异基因 HSCT 作为成功治疗方式的广泛应用。面对 IPS 的临床综合征，可以使用适当的工具对疾病实体进行分类，尽管仍会存在无法分类的 IPS 病例。大量的研究工作使人们对 HSCT 后非感染性肺损伤的认识从单纯的特发性临床综合征转变为 IPS 是一个涉及适应性和固有免疫反应的多个方面的过程。重要的是，新的实验室见解正在转化为临床，并可能对开发预防或治疗这种严重疾病的未来策略具有重要意义。
