特发性肺纤维化急性加重肺损伤免疫调控机制及干预研究

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a fatal condition with high mortality (over 80%). The clinical and radiological observation showed there were acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) based on pulmonary fibrosis. Its etiology and pathogenesis remain unknown. There is a lack of effective treatment for it. Based on our long-term clinical observation, most cases of AE-IPF are induced by "cold" and progress very rapidly. In the previous study we found that there were some obviously imbalanced immune responses in IPF patients. We also found high detection rates of pathogens, especially virus in AE-IPF patients. These findings strongly suggested that acute exacerbation of IPF might be associated with virus-induced acute lung injury. In the current study we will utilize advanced technological methods including molecular, cell, and animal models to analyze immunologic characteristics of IPF patients, search for key pathogens for ALI during AE-IPF, interpret the immunologic and pathological mechanisms of virus-induced ALI during AE-IPF, and investigate the new strategies/methods for intervention of ALI during AE-IPF. This study will provide general insights for pathogenesis of AE-IPF, which also has significant value for other ILDs study.

特发性肺纤维化急性加重（ AE-IPF）在临床和影像学上表现为在肺纤维基础上发生的急性肺损伤（ALI)）和/或急性呼吸窘迫综合征（ARDS）,病死率高达80%以上，病因和发生机制尚不明，缺乏有效的治疗手段。我们长期的临床观察发现AE-IPF患者多因“感冒”诱发肺内病灶快速进展；同时发现AE-IPF患者免疫功能存在明显失衡，多种病原体检出率高，尤以病毒为多，强烈提示病情加重可能与上述呼吸道病毒感染所诱发的急性肺损伤有关。本课题综合运用免疫、分子、细胞和动物模型等多种方法，全面分析患者天然及适应性免疫应答变化特征；筛查与AE-IPF肺损伤密切相关的病原体；重点研究病毒感染引起肺损伤进而诱发AE-IPF的免疫调控分子机制；探索AE-IPF防治新思路、新策略、新方法。预期成果对解析AE-IPF肺损伤的发病机制具有重要意义，对于其他类型肺损伤的基础研究和临床诊治也具有同样重要的借鉴意义。

特发性肺纤维化急性加重（ AE-IPF）在临床和影像学上表现为在肺纤维基础上发生的急性肺损伤（ALI)）和/或急性呼吸窘迫综合征（ARDS）,病死率高达80%以上，病因和发生机制尚不明，缺乏有效的治疗手段。我们长期的临床观察发现AE-IPF患者多因“感冒”诱发肺内病灶快速进展；同时发现AE-IPF患者免疫功能存在明显失衡，多种病原体检出率高，尤以病毒为多，强烈提示病情加重可能与上述呼吸道病毒感染所诱发的急性肺损伤有关。本课题综合运用免疫、分子、细胞和动物模型等多种方法，全面分析患者天然及适应性免疫应答变化特征；筛查与AE-IPF肺损伤密切相关的病原体；重点研究病毒感染引起肺损伤进而诱发AE-IPF的免疫调控分子机制；探索AE-IPF防治新思路、新策略、新方法。项目负责人以通讯作者发表标注项目资助号的SCI论文18篇，总IF=110；授权发明专利3项（国内2项，国际1项），软件著作权登记1项；培养研究生8人。项目成果有望转化为实际临床应用，将加深我们对特发性肺纤维化及急性加重的发病机制的了解，而且可为临床治疗提供理论及实验依据；综上，本项目的研究成果不仅对于解析AE-IPF发病的免疫分子机制具有重要意义，对于其他类型肺损伤的基础研究和临床诊治也具有同样重要的借鉴意义。