炎性肌病相关肺间质病变及血清学生物标志物研究

发布时间：2018-06-30 19:29

本文选题：炎性肌病 + 肺间质病变　；参考：《北京协和医学院》2016年博士论文

【摘要】：目的：探索与炎性肌病(Inflammatory myopathy, IM)合并肺间质病变(interstitial lung disease, ILD)相关的临床危险因素。方法：对北京协和医院2012年5月至2016年4月纳入中国风湿病数据中心(ChineseRheumatism Data Center, CRDC) IM随访队列的患者进行横断面分析。比较皮肌炎(dermatomyositis, DM)和多发性肌炎(polymyositis, PM)合并ILD(IM-ILD组)和未合并ILD (IM-non-ILD组)患者的临床表现、实验室检查、辅助检查以及活动性和损伤评分。采用多因素Logistic回归分析确定与ILD相关的独立危险因素。结果：共218例IM患者纳入北京协和医院的CRDC随访队列。其中ILD组105例(48.2%)。ILD组与non-ILD组患者的年龄(48.8±12.4岁vs.45.6±15.3岁,P=0.089)、性别(女性比例,68.6%vs.76.1%,P=0.213)、IM病程(21.4±29.3月vs.22.4±29.8月,P=0.798)和疾病类型(DM比例,85.7%vs.77.9%,P=0.135)均未见显著性差异。多因素Logistic回归表明抗Jo-1抗体阳性(OR=9.146,95%CI 1.614-51.818,P=0.012)、皮肤红斑(OR=6.326,95%CI 2.528-15.831,P0.001)、技工手(OR=3.311,95%CI 1.450-7.559,P=0.004)、皮肤破溃(OR=3.277,95%CI 1.235-8.696,P=0.017)、关节炎(OR=2.830,95%CI 1.265-6.333,P=0.011)、皮疹分布(OR=2.130,95%CI1.407-2.882,P0.001)、既往最重功能状态分级(OR=1.695,95%CI 1.189-2.415,P=0.004)具有统计学差异。结论：在IM患者伴抗Jo-1抗体阳性、广泛特征性皮疹、关节炎及既往最重功能状态分级高时,应注意筛查潜在的ILD,并需要紧密随访ILD的发生。目的：探究与炎性肌病(inflammatory myositis, IM)合并肺间质病变(interstitial lung disease, ILD)相关的血清标志物及其临床意义。方法：检测北京协和医院纳入中国风湿病数据中心(Chinese Rheumatism Data Center, CRDC)IM队列的患者血清中Krebs von den Lungen 6(KL-6)、肺表面活性蛋白A(SP-A)、肺表面活性蛋白D(SP-D)、几丁质酶3样蛋白1(YKL-40/CH3L1)、卵泡抑素样蛋白1 (FSTL-1)、金属蛋白酶7(MMP-7)的表达水平,比较IM合并ILD者(IM-ILD组)、未合并ILD者(IM-nonILD组)及健康对照人群(HC组)间上述血清标记物的表达差异,及其与IM其他临床特征的相关性。根据血清标志物水平诊断肺间质病变的敏感性和特异性绘制ROC曲线,确定cut-off值。结果：共纳入IM患者149例,其中合并ILD者71例(47.7%%)。IM-ILD组KL-6水平较IM-nonILD组升高(1g KL-6,2.88±0.38 vs 2.51±0.31,P0.001)而IM患者两组血清FSTL-1则显著低于健康对照组(9.07±6.84,11.04±13.83 vs 23.47±9.40,P=0.001)。以ROC曲线确定KL-6水平461.5 U/mI作为诊断ILD的cut-off值,则其诊断敏感性为73.2%,特异性为78.2%。血清SP-A、SP-D、YKL-40、MMP-7血清水平在IM-ILD、IM-nonILD及健康对照组间差异均无统计学显著性。结论：KL-6可以作为预测IM患者合并ILD的血清学指标。SP-A、SP-D、YKL-40、FSTL-1及MMP-7与IM-ILD的相关性及其在ILD发生中的机制尚有待进一步研究。目的：探究炎性肌病(Inflammatory myopathies, IM)并发恶性肿瘤的患病率、临床特点和可能的危险因素。方法：收集2008年-2014年在北京协和医院诊断为多发性肌炎(Polymyositis, PM)或皮肌炎(Dermatomyositis, DM)并发恶性肿瘤的的患者住院资料(肿瘤组),并以未合并恶性肿瘤的IM患者按1：2进行性别和年龄匹配(对照组)。比较IM并发肿瘤组及对照组间的临床和实验室检查特点的差异。采用多因素Logistic回归确定与IM并发恶性肿瘤相关的独立危险因素。结果：共纳入IM患者753例。并发恶性肿瘤者40例(5.3%),其中男性14例,女性26例。PM 7例,DM 32例,1例伴抗合成酶综合征(Anti-synthetase syndrome,ASS)。肿瘤组患者入院平均年龄为56.2±13.4岁。14例(35%)患者肿瘤诊断时间早于IM(42.10±59.35月),8例(20%)患者同时诊断,18例(45%)患者肿瘤的诊断时间晚于IM(19.10±35.03月)。肿瘤好发部位前4位依次为：乳腺癌(n=9,17.5%)、卵巢癌(n=7,15%)、肺癌(n=5,12.5%)和鼻咽癌(n=4,10.0%)。多因素Logistic回归显示胃肠道受累(包括出血、穿孔、溃疡、梗阻等)是IM并发肿瘤的独立危险因素(OR=4.604,95%CI 1.146-18.501,P=0.031),而肺间质病变则是其保护性因素(OR=0.150,95%C10.049-0.455,P=0.001)。结论：部分IM患者可并发恶性肿瘤。对于出现胃肠道受累且未合并肺间质病变的患者应积极筛查肿瘤。
[Abstract]:Objective: To explore the clinical risk factors associated with Inflammatory myopathy (IM) combined with interstitial lung disease (ILD). Methods: transection of patients in Peking Union Medical College Hospital from May 2012 to April 2016, which were included in the follow-up cohort of the Chinese rheumatism data center (ChineseRheumatism Data Center, CRDC) IM. Surface analysis. Comparison of clinical manifestations, laboratory tests, auxiliary examinations, activity and injury scores in patients with dermatomyositis (DM) and polymyositis (polymyositis, PM) combined with ILD (group IM-ILD) and unincorporated ILD (IM-non-ILD group). Multiple factor Logistic regression analysis was used to determine independent risk factors associated with ILD. A total of 218 patients with IM were included in the CRDC follow-up cohort in Peking Union Medical College Hospital, of which 105 (48.2%) group.ILD and non-ILD group were (48.8 + 12.4, vs.45.6 + 15.3, P=0.089), sex (female ratio, 68.6%vs.76.1%, P=0.213), IM course (21.4 + 29.3 months vs.22.4 + 29.8 months, P=0.798) and disease types. No significant difference was found. Multiple factor Logistic regression showed that anti Jo-1 antibody positive (OR=9.146,95%CI 1.614-51.818, P=0.012), skin erythema (OR=6.326,95%CI 2.528-15.831, P0.001), technician hands (OR=3.311,95%CI 1.450-7.559, P=0.004), skin rupture (OR=), arthritis OR=2.130,95%CI1.407-2.882 (P0.001), OR=1.695,95%CI 1.189-2.415, P=0.004 (P=0.004) have statistical differences. Conclusion: in IM patients with anti Jo-1 antibody positive, extensive characteristic rash, arthritis, and previous most severe functional status classification, attention should be paid to screening potential ILD and need to be closely followed. Visit ILD. Objective: To explore the serum markers associated with inflammatory myositis (IM) combined with interstitial lung disease (ILD) and its clinical significance. Methods: Peking Union Medical College Hospital was included in the patients' serum of the Chinese rheumatic data center (Chinese Rheumatism Data Center). Krebs von den Lungen 6 (KL-6), lung surface active protein A (SP-A), lung surface active protein D (SP-D), chitinase 3 like protein 1 (YKL-40/CH3L1), follicle statin like protein 1 (FSTL-1), and metalloproteinase 7 (MMP-7) The difference in the expression of the clear markers and the correlation with other clinical features of IM. According to the sensitivity and specificity of the diagnosis of pulmonary interstitial lesions by the serum markers level, the ROC curve was plotted and the cut-off value was determined. Results: a total of 149 patients with IM were included, of which 71 (47.7%%).IM-ILD group had a higher KL-6 level than the IM-nonILD group (1g KL-6,2.88 + 0.38). Vs was 2.51 + 0.31, P0.001), while the serum FSTL-1 in two groups of IM patients was significantly lower than that in the healthy control group (9.07 + 6.84,11.04 + 13.83 vs 23.47 + 9.40, P=0.001). The KL-6 level 461.5 U/mI was determined as the cut-off value of the ILD, and the sensitivity was 73.2%. The difference between onILD and the healthy control group was not statistically significant. Conclusion: KL-6 can be used as a serological index for predicting ILD in IM patients.SP-A, the correlation between SP-D, YKL-40, FSTL-1 and MMP-7 and IM-ILD and the mechanism in the occurrence of ILD are still to be further studied. The prevalence, clinical characteristics, and possible risk factors of tumor. Methods: data of hospitalized patients (tumor groups) diagnosed with Polymyositis (PM) or dermatomyositis (Dermatomyositis, DM) in Peking Union Medical College Hospital in -2014 2008 were collected, and IM patients who were not combined with malignant tumors were given sex and sex according to 1:2. Age matching (control group). Compare the differences in clinical and laboratory characteristics between IM and control groups. Multiple factor Logistic regression was used to determine independent risk factors associated with IM complicated with malignant tumors. Results: a total of 753 cases of IM patients were included. 40 cases of malignant tumors (5.3%), including 14 males, 26.PM 7 cases, DM 3. 2 cases, 1 cases with Anti-synthetase syndrome (ASS). The average age of the tumor group was 56.2 + 13.4 years old (35%), the diagnosis time of the tumor was earlier than IM (42.10 + 59.35 months), 8 (20%) patients were simultaneously diagnosed, 18 (45%) patients were later than IM (19.10 + 35.03 months). Breast cancer (n=9,17.5%), ovarian cancer (n=7,15%), lung cancer (n=5,12.5%) and nasopharyngeal carcinoma (n=4,10.0%). Multifactorial Logistic regression shows that gastrointestinal involvement (including bleeding, perforation, ulcers, obstruction, etc.) is an independent risk factor for IM complicated with tumors (OR=4.604,95%CI 1.146-18.501, P=0.031), and interstitial lung disease is a protective factor (OR=0.150,95%C1). 0.049-0.455, P=0.001) conclusion: some IM patients may be associated with malignant tumors. Patients with gastrointestinal involvement and no pulmonary interstitial lesions should be actively screened for cancer.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R563;R593.2

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