纤维化性间质性肺疾病抗纤维化治疗的单中心真实世界研究

A Single-Center Real-World Study of Anti-Fibrotic Therapy for Fibrotic Interstitial Lung Disease

目的:分析真实世界中纤维化性间质性肺疾病(FILD)患者经抗纤维化治疗后的疗效及安全性,疾病进展的风险因素。方法:纳入首次诊断为FILD且开始口服吡非尼酮或尼达尼布抗纤维化治疗的患者。随访2年,收集患者的临床资料,分析其基线特征,包括性别、年龄、吸烟史、基础肺功能[用力肺活量(FVC)、一氧化碳弥散量(DLCO)],合并症及共用药物等。记录患者抗纤维化起始时、抗纤维化治疗12个月、24个月3个时间点的肺功能,分析FVC及DLCO的年下降率。收集药物相关的不良反应及耐受情况。建立Logistic回归模型分析临床变量与疾病进展的关系。结果:167例FILD患者经抗纤维化治疗12个月后,FVC及DLCO与治疗前相比均无统计学差异(P>0.05)。67例FILD患者经抗纤维化治疗24月后FVC及DLCO相较治疗前分别下降,但无统计学差异(P>0.05)。110名接受吡非尼酮治疗的患者出现98例不良事件,57名接受尼达尼布治疗的患者共出现70例不良事件,仅部分不良事件导致停药。两种抗纤维化药物最常见的副作用都是腹泻。与吡非尼酮相比,尼达尼布因不良事件导致的停药率明显更高(P<0.05)。Logistic回归分析显示抗纤维化治疗后12月内疾病进展的风险因素为吸烟、特发性肺纤维化(IPF)患者,而DLCO是疾病进展的保护因素。结论:真实世界中抗纤维化治疗可维持FILD患者FVC及DLCO稳定,抗纤维化药物相关不良反应均可耐受,安全性较高。吸烟及IPF患者更容易出现疾病进展,较高的DLCO是FILD患者疾病进展的保护因素。

Objective:To analyze the efficacy and safety of anti-fibrosis therapy in patients with fibrotic interstitial lung disease(FILD)in the real world and the risk factors of disease progression.Methods:Patients who were first diagnosed with FILD and started oral pirfenidone or nintedanib anti-fibrosis treatment were included.The patients were followed up for 2 years.The clinical data of the patients were collected and the baseline characteristics were analyzed,including gender,age,smoking history,basic lung function[forced vital capacity(FVC),diffusing capacity of the lungs for carbon monoxide(DLCO)],complications and shared drugs.Lung function was recorded at the beginning of anti-fibrosis,12 months and 24 months after anti-fibrosis treatment,and the annual decline rates of FVC and DLCO were analyzed.Drug-related adverse reactions and tolerance were collected.Logistic regression model was established to analyze the relationship between clinical variables and disease progression.Results:After 12 months of anti-fibrosis treatment,there was no significant difference in FVC and DLCO between 167 patients with FILD and before treatment(P>0.05).The FVC an d DLCO of 67 patients with FILD decreased after 24 months of anti-fibrosis treatment,but there was no statistical difference(P>0.05).A total of 98 adverse events occurred in 110 patients treated with pirfenidone,and 70 adverse events occurred in 57 patients treated with nintedanib.Only some adverse events led to drug withdrawal.The most common side effect of both anti-fibrosis drugs was diarrhea.Compared with pirfenidone,the discontinuation rate of nintedanib due to adverse events was significantly higher(P<0.05).Logistic regression analysis showed that the risk factors of disease progression within 12 months after anti-fibrosis treatment were smoking and patients with idiopathic pulmonary fibrosis(IPF),while DLCO was a protective factor for disease progression.Conclusion:In the real world,anti-fibrosis therapy can maintain the stability of FVC and DLCO in FILD patients,and the adverse reactions related to anti-fibrosis drugs can be tolerated with high safety.Smoking and IPF patients are more prone to disease progression,and higher DLCO is a protective factor for disease progression in FILD patients.