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《中华肺部疾病杂志》[ISSN:1006-6977/CN:61-1281/TN]

卷:

期数:

2024年06期

页码:

869-874

栏目:

论著

出版日期:

2024-12-25

文章信息/Info

Title:

Association of serum S1P with disease severity and immunosuppressive therapy in connective tissue-associated interstitial lung disease

作者:

韩 晓; 汤凤莲; 张友文; 吕高超; 姜 波; 王利江

272000 济宁,济宁医学院附属医院呼吸与危重症医学科

Author(s):

Han Xiao;  Tang Fenglian;  Zhang Youwen;  Lv Gaochao;  Jiang Bo;  Wang Lijiang.

Department of Respiratory and Critical Care Medicine, Jining Medical College Affiliated Hospital, Jining, Shandong 272000, China

关键词:

结缔组织病相关间质性肺病;  血清1-磷酸鞘氨醇;  严重程度;  免疫抑制治疗

Keywords:

Connective tissue disease-associated interstitial lung disease;  Serum sphingosine-1-phosphate;  Severity;  Immunosuppressive therapy

分类号:

R563

DOI:

10.3877/cma.j.issn.1674-6902.2024.06.004

摘要:

目的 分析结缔组织相关间质性肺病(connective tissue disease-associated interstitial lung disease, CTD-ILD)血清1-磷酸鞘氨醇(sphingosine 1-phosphate, S1P)水平与疾病严重程度和免疫抑制治疗的关系。方法 选择2022年12月至2024年1月我院收治的85例CTD-ILD患者为对象。利用一氧化碳弥散量占预计值百分比(carbon monoxide dispersion as a percentage of the expected value, DLCO%)和高分辨率CT(high resolution ct, HRCT)判断CTD-ILD疾病严重程度和肺累及范围。经标准环磷酰胺(cyclophosphamide, CTX)冲击治疗,通过酶联免疫吸附法检测CTD-ILD血清S1P水平。采用Spearman法判断血清S1P与肺功能的关系。结果 85例中轻度CTD-ILD 34例(40.00%)、中度38例(44.71%)和重度13例(15.29%)。中度和重度者较轻度者用力肺活量占预计值百分比(forced vital capacity%, FVC%)、1秒用力呼气容积占预计值百分比(forced expiratory volume in one second, FEV₁%)、DLCO%降低(P<0.05)。轻度CTD-ILD血清S1P水平663.70(249.76,1 045.27)ng/ml、中度CTD-ILD血清S1P水平877.47(705.31,1 861.98)ng/ml和重度CTD-ILD血清S1P水平1 624.38(1 016.52,3 753.87)ng/ml(P<0.001)。Spearman法和多元线性回归分析显示,CTD-ILD血清S1P水平与FVC%(β=-0.009,t=-3.943,P<0.001)、FEV₁%(β=-0.009,t=-3.912,P<0.001)、DLCO%(β=-0.008,t=-3.871,P<0.001)呈负相关。经CTX冲击治疗后缓解64例(75.29%),无效21例(24.71%)。缓解者PLT/LYM比值129.06(88.64,184.32)和CRP水平4.99(3.30,20.07)mg/L低于无效者PLT/LYM比值193.62(120.24,265.94)和CRP水平11.90(3.69,31.07)mg/L(P<0.05)。治疗后缓解者血清S1P水平851.13(412.68,1 497.11)ng/ml低于无效者血清S1P水平962.07(438.99,1 561.03)ng/ml(P<0.05)。结论 经CTX冲击治疗缓解者血清S1P水平降低,血清S1P可识别CTD-ILD疾病严重程度,具有临床意义。

Abstract:

Objective To investigate the relationship between serum sphingosine 1-phosphate(S1P)level, disease severity and immunosuppressive therapy in patients with connective tissue disease-associated interstitial lung disease(CTD-ILD). Methods All of 85 cases of CTD-ILD patients admitted to the Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Jining Medical College from December 2022 to January 2024 were selected as the study objects. The severity of CTD-ILD disease and the extent of lung involvement were assessed using carbon monoxide dispersion as a percentage of expected value(DLCO%)and high-resolution CT(HRCT)scanning. All CTD-ILD patients received standard cyclophosphamide(CTX)impulse therapy and were divided into response subgroup and response subgroup according to treatment effect. Serum S1P levels in CTD-ILD patients were detected by enzyme-linked immunosorbent assay at baseline, 3 months after treatment and 6 months after treatment. Spearman method was used to evaluate the relationship between serum S1P and other indicators. Results In the 85 cases, 34 cases(40.00%)were mild CTD-ILD, 38 cases(44.71%)were moderate CTD-ILD, and 13 cases(15.29%)were severe CTD-ILD. Compared with mild patients, lung function(FVC%, FEV₁%, DLCO%)was significantly decreased in moderate and severe patients(F=20.206, F=33.587, F=71.133, P<0.05). The baseline serum S1P levels of CTD-ILD patients in mild, moderate and severe groups were 663.70(249.76, 1 045.27)ng/ml, 877.47(705.31, 1 861.98)ng/ml and 1 624.38(1 016.52, 3 753.87)ng/ml(H=14.028, P<0.001). Spearman and multivariate linear regression analysis showed that baseline serum S1P level in CTD-ILD patients was correlated with FVC%(β=-0.009, t=-3.943, P<0.001), FEV₁%(β=-0.009, t=-3.912, P<0.001), DLCO%(nonstandardized coefficient β=-0.008, t=-3.871, P<0.001)was still negatively correlated. After CTX shock therapy, all 85 CDT-ILD patients received HRCT scans and PFT at three time points, 64 patients were diagnosed as effective or stable(response subgroup), and the remaining 21 patients(24.71%)were classified as ineffective subgroup. The baseline PLT/LYM ratio[129.06(88.64,184.32)vs. 193.62(120.24,265.94)] and CRP level[4.99(3.30,20.07)mg/L vs. 11.90(3.69,31.07)mg/L] in the remission subgroup were slightly lower than those in the ineffective subgroup(P<0.05). Further trend analysis showed that the serum S1P level in the remission subgroup gradually decreased over time, and at 3 and 6 months after treatment, the serum S1P level[851.13(412.68,1 497.11)ng/ml vs. 962.07(438.99,1 561.03)ng/ml] in the remission subgroup was lower than that in the ineffective subgroup(P<0.05). Conclusion Serum S1P levels tend to decrease in patients who are in remission after CTX shock therapy, S1P may also be a supportive indicator of treatment effectiveness in CTD-ILD patients.

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备注/Memo

备注/Memo:

基金项目: 国家自然科学基金青年科学基金(82400034)
2019年度济宁医学院教师科研扶持基金(JYFC2019FKJ129)
通信作者: 王利江, Email: 18678768301@163.com

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更新日期/Last Update: 2024-12-25