目的 合并肺纤维化的慢性阻塞性肺疾病（COPD）是COPD的特殊亚型，患者兼具气流受限与肺组织纤维化病理特征，临床症状更严重、肺功能下降更快，且现有单一治疗方案难以同时改善气流受限与纤维化进展，预后较差。基于此，本研究旨在分析尼达尼布联合格隆溴铵治疗合并肺纤维化的COPD患者的效果及对肺功能的影响，为优化临床治疗方案提供依据。方法 选取2022年3月—2024年12月收治的96例合并肺纤维化的COPD患者，采用前瞻性随机对照研究设计，应用随机数字表法分为试验组与对照组。所有患者均采取常规治疗，对照组48例采取尼达尼布治疗，试验组采取尼达尼布联合格隆溴铵治疗。两组均治疗24周后，比较治疗前后症状评分、肺功能、纤维化指标、炎症指标，并分析两组治疗安全性。结果 治疗后，两组CAT评分、mMRC评分及VAS降低（P＜0.05）；且与对照组比较，试验组CAT评分、mMRC评分及咳嗽VAS评分较低（P＜0.05）。治疗后，两组FVC、FEV₁、DLCO及FEV₁/FVC比值均较治疗前改善（P＜0.05）；且与对照组比较，试验组FVC、FEV₁、DLCO及FEV₁/FVC比值较优（P＜0.05）。治疗后，两组血清KL-6、SP-D水平及CT纤维化评分均降低（P＜0.05）；且与对照组比较，试验组血清KL-6、SP-D水平及CT纤维化评分较低（P＜0.05）。治疗后，两组血清IL-6、TNF-α及TGF-β1水平降低（P＜0.05）；且与对照组比较，试验组血清IL-6、TNF-α及TGF-β1水平较低（P＜0.05）。试验组总不良反应发生率为8.33%（4/48），对照组为10.42%（5/48），两组比较差异无统计学意义（P＞0.05）。结论 尼达尼布联合格隆溴铵治疗合并肺纤维化的COPD效果良好，可减轻患者临床症状，改善肺功能与肺纤维化，降低机体炎症反应，安全性较高。

   Objective To analyze the effects of the combination of nintedanib and glycopyrrolate in treating chronic obstructive pulmonary disease（COPD）patients with associated pulmonary fibrosis and its impact on lung function，providing a basis for optimizing clinical treatment strategies．Methods Ninety-six COPD patients with pulmonary fibrosis admitted from March 2022 to December 2024 were selected，and divided into experimental group and control group using a random number table method．Using a prospective randomized controlled study design，all patients received conventional treatment，with 48 cases in the control group receiving treatment with nintedanib and the experimental group receiving treatment with nintedanib combined with glycopyrrolate bromide．After 24 weeks of treatment in both groups，the symptom scores，lung function，fibrosis indicators，and inflammation indicators were compared before and post-treatment，and the drug safety of the two groups was analyzed．Results Post-treatment，CAT score，mMRC score and VAS decreased in both groups（P＜0.05）．Compared with the control group，CAT score，mMRC score and cough VAS score were lower in the experimental group（P＜0.05）．Post-treatment，FVC，FEV₁，DLCO and FEV₁/FVC ratio of both groups improved compared with that before treatment（P＜0.05）．Compared with the control group，FVC，FEV₁，DLCO and FEV₁/FVC ratio of the experimental group were better（P＜0.05）．Post-treatment，serum KL-6，SP-D levels and CT fibrosis scores of both groups decreased（P＜0.05）．Compared with the control group，serum KL-6，SP-D levels and CT fibrosis scores of the experimental group were lower（P＜0.05）．Post-treatment，serum IL-6，TNF-α and TGF-β1 levels in both groups decreased（P＜0.05）．Compared with the control group，serum IL-6，TNF-α and TGF-β1 levels in the experimental group were lower（P＜0.05）．The incidence of total adverse reactions in the experimental group was 8.33%（4/48），and that in the control group was 10.42%（5/48）．There was no difference between the two groups（P＞0.05）．Conclusions The combination of nintedanib and glycopyrrolate has a significant effect on the treatment of COPD complicated with pulmonary fibrosis，which can alleviate its clinical symptoms，improve lung function and pulmonary fibrosis，reduce the body’s inflammatory response，which is relatively safe．

目的 探讨特发性肺纤维化(IPF)患者和结缔组织病相关性纤维化间质性肺疾病(CTD-fILD)患者急性加重(AE)的短期内死亡的危险因素。方法 回顾性分析2017年10月—2019年9月在深圳大学和广州医科大学附属第一医院住院的25例 AE-CTD-fILD和26例AE-IPF患者临床信息,Kaplan-Merier法对两组患者进行生存分析,Cox回顾分析年龄、性别、吸烟、白细胞总数、C反应蛋白、红细胞沉降率及肿瘤指标在急性加重患者死亡中的作用。结果 与AE-CTD-fILD比较,AE-IPF患者组男性比例、年龄、吸烟比例较高,红细胞沉降率较低(24/26 vs 10/25,P<0.001;63.77±9.97 vs 58.00±10.32,P=0.048;16/26 vs 9/25,P=0.02;28.07±29.45 vs 64.35±40.34,P=0.002 );90天内,26例AE-IPF患者11例死亡,25例AE-CTD-fILD患者5例死亡,死亡率无明显差异(42.3% vs 20%,P=0.073);Cox回归分析显示,白细胞计数是AE-IPF和AE-CTD-fILD患者的死亡危险因素(HR=1.305,P=0.001;HR=1.529,P=0.009);CA15-3是AE-IPF患者死亡危险因素(HR=1.015,P=0.005)。结论 急性加重IPF和CTD-fILD患者短期内死亡风险相似,白细胞计数及外周CA15-3水平可能是肺纤维化急性加重患者短期内死亡的危险因素。

Objective To explore the risk factors for acute exacerbation (AE) in patients with idiopathic pulmonary fibrosis (IPF) and connective tissue disease associated with fibrotic interstitial lung disease (CTD-fILD). Methods We retrospectively reviewed 25 patients with AE-CTD-fILD and 26 patients with AE-IPF, and Kaplan-Merier was used to analyze the survival of the two groups of patients. The impact of age,gender, smoking,WBC,CRP,ESR and tumor markers on acute exacerbation death were performed by Cox regression analysis. Results The AE-IPF patients had a higher proportion of men,age and smoking,and a lower ESR compared with AE-CTD-fILD patients(24/26 vs 10/25,P<0.001;63.77±9.97 vs 58.00±10.32,P=0.048;16/26 vs 9/25,P=0.02;28.07±29.45 vs 64.35±40.34,P=0.002 ). 11 cases of 26 patients with AE-IPF and 5 cases of 25 patients with AE-CTD-fILD died within 90 days, Log-rank tests showed patients with CTD-fILD had similar mortality rate compared with IPF patients after AE(42.3% vs 20%,P=0.073). The WBC count was negatively correlated with survival and the independent predictors for patients with AE-IPF and AE-CTD-fILD after adjusting for other clinical variates in Cox regression models(HR=1.305,P=0.001;HR=1.529,P=0.009). CA15-3 may be a risk factor for death of AE-IPF patients(HR=1.015,P=0.005). Conclusion AE-CTD-fILD and AE-IPF were associated with similar poor short-term survival, WBC count and plasma CA15-3 may be the independent survival predictors respectively for patients with acute exacerbation of pulmonary fibrosis in short term.