北京大学学报(医学版) ›› 2025, Vol. 57 ›› Issue (6): 1101-1106. doi: 10.19723/j.issn.1671-167X.2025.06.013

• 论著 • 上一篇    下一篇

老年结缔组织病相关间质性肺病临床特征及抗纤维化治疗的疗效和安全性

兰静雯, 陈哲, 程永静, 赵丽珂*()   

  1. 北京医院风湿免疫科, 国家老年医学中心, 中国医学科学院老年医学研究院, 北京 100730
  • 收稿日期:2025-08-13 出版日期:2025-12-18 发布日期:2025-10-28
  • 通讯作者: 赵丽珂
  • 基金资助:
    中央高水平医院临床研究基金专项项目(BJ-2025-251); 中国医学科学院医学与健康科技创新工程项目(2021-I2M-1-001)

Clinical characteristics, efficacy and safety of antifibrotic agents in elderly patients with connective tissue disease-associated interstitial lung disease

Jingwen LAN, Zhe CHEN, Yongjing CHENG, Like ZHAO*()   

  1. Department of Rheumatology and Immunology, Beijing Hospital; National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
  • Received:2025-08-13 Online:2025-12-18 Published:2025-10-28
  • Contact: Like ZHAO
  • Supported by:
    the National High-Level Hospital Clinical Research Funding(BJ-2025-251); Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-001)

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摘要:

目的: 探讨老年结缔组织病相关间质性肺病(connective tissue disease-associated interstitial lung disease, CTD-ILD)的疾病特征、治疗方案及抗纤维化药物疗效与安全性。方法: 采用单中心回顾性队列研究, 纳入2016年6月至2024年6月北京医院确诊的129例老年(≥60岁)CTD-ILD患者。通过电子病历系统收集基线资料, 包括合并症、结缔组织病(connective tissue disease, CTD)亚型、治疗方案(糖皮质激素、免疫抑制剂、抗纤维化药物)、肺功能参数、高分辨率CT(high-resolution computed tomography, HRCT)及不良事件数据。疗效评估参照2022年《美国胸科学会/欧洲呼吸学会进行性肺纤维化标准》, 统计学分析使用SPSS 26.0软件, 组间比较使用χ2检验或t检验。结果: (1) 临床特征: CTD亚型以类风湿关节炎(rheumatoid arthritis, RA)、原发性干燥综合征(primary Sjögren syndrome, pSS)、多发性肌炎/皮肌炎(polymyositis/dermatomyositis, PM/DM)为主; 45.7%患者合并高血压, 体现老年人群多病共患特点。(2)CTD治疗方案: 76.0%患者使用糖皮质激素, 83.7%使用各类免疫抑制剂/传统合成改善病情抗风湿药, 其中环磷酰胺使用率最高(47.3%), 31.8%患者联用抗纤维化药物(尼达尼布16.3%, 吡非尼酮10.1%, 5.4%两者均有使用)。(3)抗纤维化疗效: 抗纤维化组与未使用抗纤维化组6个月HRCT进展率差异无统计学意义(31.3% vs. 45.2%, P=0.193), 但抗纤维化组肺功能恶化比例显著低于未使用抗纤维化组(34.1% vs. 53.4%, P=0.041), 提示抗纤维化药物可能延缓肺功能衰退。(4)抗纤维化药物安全性: 39.0%抗纤维化治疗患者出现胃肠道不良反应(腹泻26.8%, 恶心22.0%), 17.1%发生肝功能异常。(5)长期预后: 2年随访期间, 67.4%患者发生感染(其中肺部感染47.3%), 14.0%进展为呼吸衰竭, 全因死亡率为2.3%。结论: 老年CTD-ILD以RA、pSS、PM/DM为主要亚型, 常合并高血压; 抗纤维化药物可显著延缓肺功能恶化, 但需警惕胃肠道不良反应及肝毒性; 感染是主要并发症, 临床需权衡免疫抑制治疗的获益与感染风险, 制定个体化治疗策略。

关键词: 老年, 结缔组织病相关间质性肺病, 抗纤维化药物

Abstract:

Objective: To investigate the clinical characteristics, treatment regimens, and the efficacy and safety of antifibrotic agents in elderly patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). Methods: This single-center retrospective cohort study enrolled 129 elderly patients (≥60 years) with a confirmed diagnosis of CTD-ILD at Beijing Hospital from June 2016 to June 2024. Baseline data, including comorbidities and CTD subtypes, treatment regimens (glucocorticoids, immunosuppressants, antifibrotic agents), pulmonary function parameters, high-resolution computed tomography (HRCT) imaging features, and adverse events were retrieved from the electronic medical record system. Treatment efficacy was evaluated according to the 2022 American Thoracic Society/European Respiratory Society criteria for progressive pulmonary fibrosis. Statistical analyses were performed using SPSS 26.0, with χ2 tests or t-tests applied for between-group comparisons. Results: (1) Clinical characteristics: The predominant CTD subtypes were rheumatoid arthritis (RA), primary Sjögren syndrome (pSS), and polymyositis or dermatomyositis (PM/DM). Hypertension was present in 45.7% of the patients, reflecting the characteristics of multiple comorbidities in the elderly population. (2) CTD treatment regimens: 76.0% of the patients received glucocorticoid therapy, 83.7% used immunosuppressants (IS)/conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), among which cyclophosphamide had the highest usage rate (47.3%); 31.8% of the patients were combined with antifibrotic drugs (nintedanib 16.3%, pirfenidone 10.1%, and 5.4% used both). (3) Efficacy of antifibrotic therapy: There was no statistically significant difference in the 6-month HRCT progression rate between the antifibrotic and non-antifibrotic groups (31.3% vs. 45.2%, P=0.193). However, the proportion of the patients with pulmonary function deterioration in the antifibrotic group was significantly lower than that in the non-antifibrotic group (34.1% vs. 53.4%, P=0.041), suggesting a potential role in delaying pulmonary function deterioration. (4) Safety of antifibrotic agents: Gastrointestinal adverse events occurred in 39.0% of the patients receiving antifibrotics (26.8% diarrhea, 22.0% nausea), and abnormal liver function was observed in 17.1%. (5) Long-term outcomes: During a 2-year follow-up, 67.4% of the patients experienced infections (47.3% pulmonary infections), 14.0% progressed to respiratory failure, and the all-cause mortality rate was 2.3%. Conclusion: The main subtypes of CTD-ILD in the elderly are RA, pSS, and PM/DM, which are often complicated with hypertension. Antifibrotic agents may significantly delay the deterioration of pulmonary function, but attention should be paid to the risks of gastrointestinal adverse effects and hepatotoxicity. Infection remains the primary complication, emphasizing the need to balance benefits of immunosuppressive therapy and the risk of infection to formulate treatment strategies.

Key words: Elderly, Connective tissue disease-associated interstitial lung disease, Antifibrotic agents

中图分类号: 

  • R593.2

表1

老年CTD-ILD患者的基线特征"

Baseline characteristics Value
Demographic and clinical characteristics
  Female 94 (72.9)
  Male 35 (27.1)
  Smoking history 27 (20.9)
  Age/years 69.69±5.81
  Disease duration/years 10.51±10.11
CTD subtypes
  RA 37 (28.7)
  pSS 30 (23.3)
  PM/DM 28 (21.7)
  SSc 18 (14.0)
  AAV 12 (9.3)
  SLE 4 (3.1)
Common comorbidities
  Hypertension 59 (45.7)
  Diabetes mellitus 29 (22.5)
  Coronary artery disease 28 (21.7)
  Pulmonary neoplasms 3 (2.3)

表2

老年CTD-ILD患者抗CTD治疗药物分布"

Therapeutic classification Value, n (%) Total, n (%)
Glucocorticoids 98 (76.0)
IS/csDRAMDs 108 (83.7)
  CTX 61 (47.3)
  TGT 58 (45.0)
  MTX 36 (27.9)
  LEF 26 (20.2)
  HCQ 21 (16.3)
  MMF 20 (15.5)
  TAC 17 (13.2)
  CsA 4 (3.1)
bDRAMDs 17 (13.2)
  Tocilizumab 8 (6.2)
  Adalimumab 5 (3.9)
  Rituximab 4 (3.1)
tsDRAMDs 22 (17.1)
  Tofacitinib 15 (11.6)
  Baricitinib 7 (5.4)

表3

老年CTD-ILD患者肺功能进展"

Pulmonary function parameters Non-antifibrotic group (n=88) Antifibrotic group (n=41) χ2 P
FVC% pred decline ≥5% 34 (38.6) 13 (31.7)
DLCO% pred decline ≥10% 25 (28.4) 10 (24.4)
Total 47 (53.4) 14 (34.1) 4.163 0.041

表4

老年CTD-ILD患者2年内的主要不良事件发生情况"

Adverse event classification Value, n (%) Total, n (%)
Infection 87 (67.4)
  Pulmonary infection 61 (47.3)
  Upper respiratory tract infection 53 (41.1)
  Urinary tract infection 15 (11.6)
  VZV infection 4 (3.1)
Cardiovascular events 15 (11.6)
  Heart failure 9 (7.0)
  Pulmonary hypertension 6 (4.7)
Respiratory failure 18 (14.0)
RP-ILD 7 (5.4)
All-cause mortality 3 (2.3)
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