Preliminary study on establishing the diagnostic model for smear negative tuberculosis and stage Ⅰ/Ⅱ sarcoidosis with hilar/mediastinal lymphadenopathy and positive T-SPOT.TB results

doi:10.3969/j.issn.1000-6621.2020.08.010

Abstract

Abstract:

Objective To establish diagnostic models of mediastinal lymph node tuberculosis patients and stage Ⅰ/Ⅱ sarcoidosis patients, who were both positive in tuberculosis infection T lymphocyte spot (T-SPOT.TB) test and with negative sputum smear, to improve the clinical sensitivity and specificity of the differential diagnosis of the two diseases. Methods Clinical and laboratory examination data of 100 mediastinal lymph node tuberculosis and 50 stage Ⅰ/Ⅱ sarcoidosis patients diagnosed by chest CT examination and biopsy histopathology (n_{stage Ⅰ}=8, n_{stage Ⅱ}=42) from Shanghai Pulmonary Hospital between January 2013 and December 2018 were retrospectively analyzed, their T-SPOT.TB test were positive and were not be treated with glucocorticoid or anti-tuberculosis treatment, in a logistic regression model for differential diagnosis of the two diseases was established. The diagnostic efficiency of the model was evaluated by the area under the ROC curve (AUC), sensitivity and specificity. Results Multivariate unconditional logistic regression analysis showed that serum angiotensin-converting enzyme (SACE) (Wald χ²=5.826, P=0.016, OR (95%CI)=0.968 (0.942-0.994)), erythrocyte sedimentation rate (ESR) (Wald χ²=5.583, P=0.018, OR (95%CI)=1.036 (1.006-1.068)) and lymphocyte count (Wald χ²=4.074, P=0.044, OR (95%CI)=4.487 (1.044-19.279)) were independent factors related for the identification of mediastinal lymph node tuberculosis and stageⅠ/Ⅱ sarcoidosis. The established logistic regression model was logit (P)=-0.418-0.033×SACE+0.036×ESR+1.501×Lym. The AUC of diagnostic efficiency of the model were 0.850 (95%CI: 0.773-0.927), the optimal cut-off value was 1.307, the sensitivity was 82.4%, and specificity was 80.9%, respectively. Conclusion The diagnostic model established in this study has high sensitivity and specificity, and is auxiliary for the differentially diagnose of mediastinal lymph node tuberculosis and stageⅠ/Ⅱsarcoidosis with positive T-SPOT.TB test.

Key words: Mediastinal diseases, Tuberculosis, lymph node, Sarcoidosis, Diagnosis, differential, Logistic models, ROC curve, Evaluation studies

CHEN Feng-fang, MA Jun, HUANG Jin, YIN Hong-yun, SHA Wei, YANG Guang-hong, FENG Yong-hong. Preliminary study on establishing the diagnostic model for smear negative tuberculosis and stage Ⅰ/Ⅱ sarcoidosis with hilar/mediastinal lymphadenopathy and positive T-SPOT.TB results[J]. Chinese Journal of Antituberculosis, 2020, 42(8): 832-837. doi: 10.3969/j.issn.1000-6621.2020.08.010

Figures/Tables 5

References 20

[1]	Scadding JG. Prognosis of intrathoracic sarcoidosis in England. A review of 136 cases after five years’ observation. Br Med J, 1961,2(5261):1165-1172.doi: 10.1136/bmj.2.5261.1165. doi: 10.1136/bmj.2.5261.1165 URL pmid: 14497750
[2]	王昌国, 曾大雄, 蒋军红, 等. 气道内超声特征在纵隔淋巴结结核与结节病鉴别诊断中的作用. 中国内镜杂志, 2017,23(8):1-6.doi: 10.3969/j.issn.1007-1989.2017.08.001.
[3]	尹洪云, Tan W, 马俊, 等. 结核感染T细胞斑点试验在不同患者群中的检测结果分析. 中国防痨杂志, 2018,40(4):358-364.doi: 10.3969/j.issn.1000-6621.2018.04.004.
[4]	阴晴, 刘大东, 邢虎, 等. 应用Logistic回归模型和ROC曲线评价外周血感染性指标在脓毒症中的诊断价值. 中国老年学杂志, 2019,39(12):2955-2957.doi: 10.3969/j.issn.1005-9202.2019.12.042.
[5]	Ying C, Jingchun Y, Hua H, et al. The Value of Contrast-Enhanced Ultrasonography Combined with Real-Time Strain Elastography in the Early Diagnosis of Prostate Cancer. Aging Dis, 2018,9(3):480-488.doi: 10.14336/AD.2017.0704. doi: 10.14336/AD.2017.0704 URL pmid: 29896435
[6]	邵建国, 罗蕾蕾, 陈琳, 等. 多项腹水指标 Logistic 回归模型对腹水性质的鉴别诊断价值. 胃肠病学, 2012,17(3):156-160.doi: CNKI:SUN:WIEC.0.2012-03-007.
[7]	王志刚, 陈丁莉, 李守霞, 等. 采用Logistic回归模型联合的肿瘤标志物在胃癌诊断中的价值. 标记免疫分型与临床, 2019,26(11):1898-1902.doi: 10.11748/bjmy.issn.1006-1703.2019.11.024.
[8]	中华医学会呼吸病学分会间质性肺疾病学组, 中国医师协会呼吸医师分会间质性肺疾病工作委员会. 中国肺结节病诊断和治疗专家共识. 中华结核和呼吸杂志, 2019,42(9):685-693.doi: 10.3760/cma.j.issn.1001-0939.2019.09.007.
[9]	刘淼淼. 中性粒细胞与淋巴细胞比值在肺结节病与肺结核鉴别诊断中的应用. 郑州:郑州大学, 2018.doi: CNKI:CDMD:2.1018.105818.
[10]	杨景茹. NLR和TB-IGRA在肺结节病与肺结核病鉴别诊断中的应用价值. 济南:山东大学, 2015.doi: 10.7666/d.Y2793447.
[11]	Dastoori M, Fedele S, Leao JC, et al. Sarcoidosis-a clinically orientated review. J Oral Pathol Med, 2013,42(4):281-289.doi: 10.1111/j.1600-0714.2012.01198.x. doi: 10.1111/j.1600-0714.2012.01198.x URL pmid: 22845844
[12]	翁跃颂, 王华英, 吕定丰, 等. 结节病患者辅助性T细胞17和调节性T细胞与疾病活动的关系. 浙江大学学报(医学版), 2015,44(2):154-161.doi: 10.3785/j.issn.1008-9292.2015.03.006. doi: 10.3785/j.issn.1008-9292.2015.03.006 URL
[13]	Hyldgaard C, Kaae S, Riddervold M, et al. Value of s-ACE, BAL lymphocytosis, and CD4⁺/CD8⁺ and CD103⁺CD4⁺/CD4⁺ T-cell ratios in diagnosis of sarcoidosis. Eur Respir J, 2012,39(4):1037-1039.doi: 10.1183/09031936.00144311. doi: 10.1183/09031936.00144311 URL pmid: 22467726
[14]	Ungprasert P, Carmona EM, Crowson CS, et al. Diagnostic Utility of Angiotensin-Convert ing Enzyme in Sarcoidosis: A Population-Based Study. Lung, 2016,194(1):91-95.doi: 0.1 007/s00408-015-9826-3. URL pmid: 26563332
[15]	Kargaltseva NM, Kotcherovets VI, Mironov AY, et al. Inflammation markers and bloodstream infection (review of literature). Klin Lab Diagn, 2019,64(7):435-442.doi: 10.18821/0869-2084-2019-64-7-435-442. doi: 10.18821/0869-2084-2019-64-7-435-442 URL pmid: 31408597
[16]	Enver Yalnız, Gülistan Karadeniz, Fatma Demirci Üçsular, et al. Predictive value of platelet-to-lymphocyte ratio in patients with sarcoidosis. Biomark Med, 2019,13(3):197-204.doi: 10.2217/bmm-2018-0252. doi: 10.2217/bmm-2018-0252 URL pmid: 30604642
[17]	Groen-Hakan F, Eurelings L, Rothova A, et al. Lymphopaenia as a predictor of sarcoidosis in patients with a first episode of uveitis. Br J Ophthalmol, 2019,103(9):1296-1300.doi: 10.1136/bjophthalmol-2018-313212. doi: 10.1136/bjophthalmol-2018-313212 URL pmid: 30442816
[18]	Jones NP, Tsierkezou L, Patton N. Lymphopenia as a predictor of sarcoidosis in patients with uveitis. Br J Ophthalmol, 2016,100(10):1393-1396.doi: 10.1136/bjophthalmol-2015-307455. doi: 10.1136/bjophthalmol-2015-307455 URL pmid: 26729767
[19]	Sweiss NJ, Rafah S, Seema G, et al. Significant CD4, CD8, and CD19 lymphopenia in peripheral blood of sarcoidosis patients correlates with severe disease manifestations. PLoS One, 2010,5(2):e9088.doi: 10.1371/journal.pone.0009088. doi: 10.1371/journal.pone.0009088 URL pmid: 20140091
[20]	Du SS, Zhao MM, Zhan Y, et al. Screening for Differentially Expressed Proteins Relevant to the Differential Diagnosis of Sarcoidosis and Tuberculosis. PLoS One, 2015,10(9):e0132466.doi: 10.1371/journal.pone.0132466. doi: 10.1371/journal.pone.0132466 URL pmid: 26368286

观察项目	纵隔淋巴结结核组(100例)	结节病组(50例)	统计检验值	P值
性别			χ²=0.349	0.555
男	41(41.00)	18(36.00)
女	59(59.00)	32(64.00)
年龄(岁,$\bar{x}$±s)	54.36±11.15	54.56±9.51	t=0.109	0.914
BMI($\bar{x}$±s)	21.45±2.60	24.88±2.82	t=6.636	0.000
症状与体征
咳嗽	27(27.00)	32(64.00)	χ²=19.124	0.000
咳痰	14(14.00)	12(24.00)	χ²=2.326	0.127
胸痛	5(5.00)	5(10.00)	χ²=1.339	0.247
咯血	2(2.00)	0(0.00)	χ²=1.014	0.314
发热	22(22.00)	5(10.00)	χ²=3.252	0.071

观察指标	纵隔淋巴结结核组(100例)	结节病组(50例)	检验值	P值
WBC[×10⁹/L,M(Q₁,Q₃)]	5.77(5.04,7.29)	5.03(4.20,6.08)	Z=-3.154	0.002
Neu[×10⁹/L,M(Q₁,Q₃)]	3.56(2.98,4.78)	3.15(2.48,3.90)	Z=-2.372	0.018
Lym[×10⁹/L,M(Q₁,Q₃)]	1.56(1.16,1.92)	1.39(1.03,1.56)	Z=-2.293	0.022
Mon[×10⁹/L,M(Q₁,Q₃)]	0.47(0.38,0.59)	0.41(0.31,0.48)	Z=-2.861	0.004
NLR[M(Q₁,Q₃)]	2.41(1.74,3.45)	2.42(1.68,3.36)	Z=-0.155	0.876
MPV[fl,M(Q₁,Q₃)]	10.20(9.60,11.10)	10.70(9.90,11.50)	Z=-2.235	0.025
CRP[mg/L,M(Q₁,Q₃)]	5.20(3.15,18.40)	3.10(2.38,4.10)	Z=-4.040	0.000
ESR[mm/1h,M(Q₁,Q₃)]	41.00(21.00,69.00)	15.00(8.00,29.00)	Z=-5.386	0.000
SACE[IU/L,M(Q₁,Q₃)]	36.50(28.00,46.00)	54.50(38.00,69.25)	Z=-4.287	0.000
血钙(mmol/L,$\bar{x}$±s)	2.26±0.12	2.29±0.12	t=1.421	0.157
sIL-2R[U/ml,M(Q₁,Q₃)]	650.00(494.25,1067.50)	791.50(546.75,1262.25)	Z=-1.425	0.154

实验室指标	临界值	AUC	P值	95%CI		敏感度 (%)	特异度 (%)
实验室指标	临界值	AUC	P值	上限	下限	敏感度 (%)	特异度 (%)
MPV (fl)	10.25	0.600	0.052	0.503	0.698	70.0	51.8
Lym (×10⁹/L)	1.56	0.627	0.020	0.525	0.728	51.1	78.0
Neu (×10⁹/L)	2.79	0.642	0.009	0.539	0.746	80.4	48.8
Mon (×10⁹/L)	0.34	0.655	0.004	0.554	0.756	85.9	39.0
WBC (×10⁹/L)	4.72	0.679	0.001	0.576	0.782	84.8	53.7
CRP (mg/L)	3.25	0.712	0.000	0.623	0.802	63.0	73.2
SACE (IU/L)	53.00	0.724	0.000	0.630	0.819	52.0	89.4
ESR (mm/1h)	31.00	0.781	0.000	0.698	0.865	67.4	82.9

变量	β值	$S_{\bar{x}}$值	Wald χ²值	P值	OR(95%CI)值
SACE (IU/L)	-0.033	0.014	5.826	0.016	0.968(0.942~0.994)
ESR (mm/1h)	0.036	0.015	5.583	0.018	1.036(1.006~1.068)
Lym (×10⁹/L)	1.501	0.744	4.074	0.044	4.487(1.044~19.279)
常量	-0.418	3.162	0.018	0.895	0.658