Neutrophil-lymphocyte ratio as a prognostic factor in severe hand, foot and mouth disease

doi:10.3877/cma.j.issn.1674-1358.2018.06.008

Abstract

Abstract:

Objective

To investigate the clinical implication of the neutrophil to lymphocyte ratio (NLR) in predicting the severity of hand, foot and mouth disease (HFMD).

Methods

From May 2008 to December 2017, a total of 1 593 children with HFMD were collected from The Second Affiliated Hospital of Xi’an Jiaotong Univesity and Xi’an Children’s Hospital. According to the degree of illness, they were divided into mild HFMD group (929 cases) and severe HFMD group (664 cases). The best critical value of neutrophil/lymphocyte ratio (NLR) for predicting the severity of HFMD was calculated by receiver operating characteristic curve (ROC curve). According to NLR, 1 593 children were divided into high NLR group and low NLR group. Multivariate two-classification Logistic regression analysis was used to analyze the correlation between the factors and the severity of children with HFMD.

Results

Fever, hyperpyrexia, nervous system symptom, circulatory system symptom, leukocyte (WBC), NLR, procalcitonin (PCT), blood sugar, enterovirus 71 IgM antibody (EV71-IgM) positive and infection with Epstein-Barr virus (EBV) were all with significant differences in severe HFMD group compared with those of mild HFMD group (all P < 0.05). The optimal critical value of NLR ratio to predict severity was 1.59 detected by ROC curve. Multivariate Logistic regression analysis showed that high fever (> 39 ℃), positive EV71-IgM, complicated with EBV infection, blood glucose > 8.3 mmol/L, PCT > 0.1 ng/ml and NLR > 1.59 were all risk factors for severe HFMD. The ratio of odds ratio (OR) were 1.557, 5.124, 3.533, 7.323, 1.727 and 2.031, respectively (all P < 0.01).

Conclusions

NLR > 1.59 is closely related to the severity of HFMD, which has important predictive value. NLR is one of the clinical indexes to guide the clinical decision and treatment of children with HFMD.

Key words: Hand, foot and mouth disease, Neutrophil-to-lymphocyte ratio, Severity, Risk factor

Yaping Li, Song Zhai, Mei Li, Yuan Wang, Huiling Deng, Xin Zhang, Shuangsuo Dang. Neutrophil-lymphocyte ratio as a prognostic factor in severe hand, foot and mouth disease[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2018, 12(06): 559-564.

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References 33

[1]	中国疾病预防控制中心. 2017年法定传染病报告[EB/OL]. URL
[2]	Guthrie GJ, Charles KA, Roxburgh CS, et al. The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer[J]. Crit Rev Oncol Hematol,2013, 88(1):218-230.
[3]	Bekdas M, Goksugur SB, Sarac EG, et al. Neutrophil/lymphocyte and C-reactive protein/mean platelet volume ratios in differentiating between viral and bacterial pneumonias and diagnosing early complications in children[J]. Saudi Med J,2014,35(5):442-447.
[4]	Yang Y, Cao ZL, Zhou XY, et al. Does neutrophil/lymphocyte ratio have good diagnostic value in neonatal necrotizing colitis?[J]. J Matern Fetal Neonatal Med,2018,20:1-11.
[5]	王宪波，高方媛，刘尧. 中性粒细胞与淋巴细胞比值:一项评价肝细胞癌患者预后的新指标[J]. 临床肝胆病杂志,2016,32(4):649-652.
[6]	Wilson JRF, Saeed F, Tyagi AK, et al. Pre-operative neutrophil count and neutrophil-lymphocyte count ratio (NLCR) in predicting the histological grade of paediatric brain tumours: a preliminary study[J]. Acta Neurochir (Wien),2018,160(4):793-800.
[7]	Gul U, Kayani AM, Munir R, et al. Neutrophil Lymphocyte Ratio: A prognostic marker in acute ST elevation myocardial infarction[J]. J Coll Physicians Surg Pak,2017,27(1):4-7.
[8]	Kurtipek E, Bekci TT, Kesli R, et al. The role of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in exacerbation of chronic obstructive pulmonary disease[J]. J Pak Med Assoc, 2015,65(12):1283-1287.
[9]	Khandare SA, Chittawar S, Nahar N, et al. Study of neutrophil-lymphocyte ratio as novel marker for diabetic nephropathy in type 2 diabetes[J]. Indian J Endocrinol Metab,2017,21(3): 387-392.
[10]	中华人民共和国国家卫生和计划生育委员会．手足口病诊疗指南(2010年版)[DB/OL]. (2010-04-20)[2017-05-15]. URL
[11]	Gui J, Liu Z, Zhang T, et al. Epidemiological characteristics and spatial-temporal clusters of hand, foot, and mouth disease in Zhejiang Province, China, 2008-2012[J]. PLoS One,2015,10(9):e0139109.
[12]	Li YP, Dang SS, Deng HL, et al. Breastfeeding, previous Epstein-Barr virus infection, Enterovirus 71 infection, and rural residence are associated with the severity of hand, foot, and mouth disease[J]. Eur J Pediatr,2013,172(5):661-666.
[13]	Esposito S, Principi N. Hand, foot and mouth disease: current knowledge on clinical manifestations, epidemiology, aetiology and prevention[J]. Eur J Clin Microbiol Infect Dis,2018,37(3):391-398.
[14]	Imtiaz F, Shafique K, Mirza SS, et al. Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population[J]. Int Arch Med,2012,5(1):2.
[15]	Ha YJ, Hur J, Dong JG, et al. Baseline peripheral blood neutrophil-tolymphocyte ratio could predict survival in patients with adult polymyositis and dermatomyositis: A retrospective observational study[J]. PLoS One,2018,13(1) e019041.
[16]	Gao SQ, Huang LD, Dai RJ, et al. Neutrophil-lymphocyte ratio: a controversial marker in predicting Crohn’s disease severity[J]. Int J Clin Exp Pathol,2015,8(11):14779-14785.
[17]	Navarro J F, Mora C, Maca M, et al. Inflammatory parameters are independently associated with urinary albumin in type 2 diabetes mellitus[J]. Am J Kidney Dis,2003,42(1):53-61.
[18]	Huang W, Huang J, Liu Q, et al.Neutrophil-lymphocyte ratio is a reliable predictive marker for early-stage diabetic nephropathy[J]. Clin Endocrinol (Oxf),2015,82(2):229-233.
[19]	Shimada H, Takiguchi N, Kainuma O, et al. High preoperative neutrophil-lymphocyte ratio predicts poor survival in patients with gastric cancer[J]. Gastric Cancer,2010,13(3):170-176.
[20]	Gao F, Li X, Geng M, et al.Pretreatment neutrophil-lymphocyte ratio: an independent predictor of survival in patients with hepatocellular carcinoma[J]. Medicine (Baltimore),2015,94(11):e639.
[21]	Ohno Y, Nakashima J, Ohori M, et al. Pretreatment neutrophil-to-lymphocyte ratio as an independent predictor of recurrence in patients with nonmetastatic renal cell carcinoma[J]. J Urol,2010,184(3):873-878.
[22]	Tamhane UU, Aneja S, Montgomery D, et al. Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome[J]. Am J Cardiol,2008,102(6):653-657.
[23]	Motomura T, Shirabe K, Mano Y , et al. Neutrophil–lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment[J]. J Hepatol,2013,58(1):58-64.
[24]	Chen L, Lou Y. Chen, et al. Prognostic value of the neutrophil-to-lymphocyte ratio in patients with acute-on-chronic liver failure[J]. Int J Clin Pract,2014,68(8):1034-1040.
[25]	李乔，郭宏华. 血中性粒细胞/淋巴细胞比率与相关肝脏疾病预后关系的研究进展[J]. 临床肝胆病杂志,2017,33(4):780-784.
[26]	Miyamoto M, Prause O, Sjostrand M, et al. Endogenous IL-17 as a mediator of neutrophil recruitment caused by endotoxin exposure in mouse airways[J]. J Immunol,2003,170(9):4665-4672.
[27]	Duksal F, Alaygut D, Güven AS, et al. Neutrophil-lymphocyte ratio in children with familial Mediterranean fever: Original article[J]. Eur J Rheumatol,2015,2(1):20-23.
[28]	Lee JW, Park JS, Park KB, et al. Prediction of renal cortical defect and scar using neutrophil-to-lymphocyte ratio in children with febrile urinary tract infection[J]. Nuklearmedizin,2017,56(3):109-114.
[29]	Mentis AA, Kyprianou MA, Tzanakaki G. Age-specific application of neutrophil-to-lymphocyte ratio in meningitis: a nationwidestudy[J]. Eur J Clin Microbiol Infect Dis,2017,36(9):1553-1557.
[30]	Shang WZ, Qian SY, Fang LJ, et al. Association study of inﬂammatory cytokine and chemokine expression in hand foot and mouth disease[J]. Oncotarget,2017,8(45):79425-79432.
[31]	Li Y, Zhu R, Qian Y, Deng J. The characteristics of blood glucose and WBC counts in peripheral blood of cases of hand foot and mouth disease in China: a systematic review[J]. PLoS One,2012,7(1):e29003.
[32]	Wesche DE, Lomas-Neira JL, Perl M, et al. Leukocyte apoptosis and its significance in sepsis and shock[J]. J Leukoc Biol,2005,78(2):325-337.
[33]	Deng HL, Zhang YF, Li YP, et al. N-terminal pro-brain natriuretic peptide levels associated with severe hand, foot and mouth disease[J]. BMC Infect Dis,2016,16(1):585.

临床特征	普通病例（929例）	重症病例（664例）	统计量	P值
男/女（例）	568/361	418/246	χ² = 0.538	0.463
年龄≤ 3岁[例（%）]	726（78.1）	526（79.2）	χ² = 0.263	0.608
皮疹[例（%）]	929（100.0）	664（100.0）	—	—
发热[例（%）]	836（89.9）	663（99.8）	χ² = 59.812	< 0.001
热程> 3 d [例（%）]	328（38.1）	520（78.4）	χ² = 246.915	< 0.001
高热> 39 ℃ [例（%）]	325（38.9）	363（63.5）	χ² = 51.289	< 0.001
嗜睡[例（%）]	29（3.2）	385（67.4）	χ² = 714.127	< 0.001
易惊[例（%）]	404（44.7）	549（96.1）	χ² = 404.521	< 0.001
肢体抖动[例（%）]	62（6.9）	475（83.2）	χ² = 879.832	< 0.001
抽搐[例（%）]	15（1.7）	117（20.5）	χ² = 152.111	< 0.001
呕吐[例（%）]	257（19.6）	506（63.4）	χ² = 330.970	< 0.001
病理反射[例（%）]	0（0.0）	656（98.8）	—	—
呼吸困难[例（%）]	0（0.0）	120（18.0）	—	—
循环障碍[例（%）]	0（0.0）	137（20.6）	—	—
WBC > 15 × 10⁹/L [例（%）]	146（15.7）	194（29.2）	χ² = 42.044	< 0.001
NLR [M（R）]	1.43（0.11～15.52）	2.04（0.20～19.35）	Z = 4.581	< 0.001
NLR（±s）	1.91 ± 1.68	2.90 ± 2.55	t =－9.288	< 0.001
NLR> 1.59 [例（%）]	392（42.2）	424（63.9）	χ² = = 72.709	< 0.001
降钙素原> 0.1 μg/ml [例（%）]	267（28.7）	292（44.0）	χ² = 39.461	< 0.001
空腹血糖> 8.3 mmol/L [例（%）]	21（2.3%）	164（24.7）	χ² = 189.935	< 0.001
EV71-IgM阳性[例（%）]	253（27.2）	450（67.8）	χ² = 258.088	< 0.001
合并EBV IgG阳性[例（%）]	190（20.5）	396（59.6）	χ² = 255.708	< 0.001
^a死亡[例（%）]	0（0.0）	97（14.6）	—	—

临床特征	普通病例（929例）	重症病例（664例）	统计量	P值
男/女（例）	568/361	418/246	χ² = 0.538	0.463
年龄≤ 3岁[例（%）]	726（78.1）	526（79.2）	χ² = 0.263	0.608
皮疹[例（%）]	929（100.0）	664（100.0）	—	—
发热[例（%）]	836（89.9）	663（99.8）	χ² = 59.812	< 0.001
热程> 3 d [例（%）]	328（38.1）	520（78.4）	χ² = 246.915	< 0.001
高热> 39 ℃ [例（%）]	325（38.9）	363（63.5）	χ² = 51.289	< 0.001
嗜睡[例（%）]	29（3.2）	385（67.4）	χ² = 714.127	< 0.001
易惊[例（%）]	404（44.7）	549（96.1）	χ² = 404.521	< 0.001
肢体抖动[例（%）]	62（6.9）	475（83.2）	χ² = 879.832	< 0.001
抽搐[例（%）]	15（1.7）	117（20.5）	χ² = 152.111	< 0.001
呕吐[例（%）]	257（19.6）	506（63.4）	χ² = 330.970	< 0.001
病理反射[例（%）]	0（0.0）	656（98.8）	—	—
呼吸困难[例（%）]	0（0.0）	120（18.0）	—	—
循环障碍[例（%）]	0（0.0）	137（20.6）	—	—
WBC > 15 × 10⁹/L [例（%）]	146（15.7）	194（29.2）	χ² = 42.044	< 0.001
NLR [M（R）]	1.43（0.11～15.52）	2.04（0.20～19.35）	Z = 4.581	< 0.001
NLR（±s）	1.91 ± 1.68	2.90 ± 2.55	t =－9.288	< 0.001
NLR> 1.59 [例（%）]	392（42.2）	424（63.9）	χ² = = 72.709	< 0.001
降钙素原> 0.1 μg/ml [例（%）]	267（28.7）	292（44.0）	χ² = 39.461	< 0.001
空腹血糖> 8.3 mmol/L [例（%）]	21（2.3%）	164（24.7）	χ² = 189.935	< 0.001
EV71-IgM阳性[例（%）]	253（27.2）	450（67.8）	χ² = 258.088	< 0.001
合并EBV IgG阳性[例（%）]	190（20.5）	396（59.6）	χ² = 255.708	< 0.001
^a死亡[例（%）]	0（0.0）	97（14.6）	—	—

相关因素	未调整[OR（95%CI）]	调整[OR（95%CI）]	P值
性别	0.938（0.735～1.197）	0.966（0.745～1.252）	0.791
年龄< 3岁	0.926（0.754～1.137）	0.803（0.591～1.091）	0.161
高热> 39 ℃	2.124（1.726～2.614）	1.557（1.206～2.011）	0.001
EV71 IgM阳性	5.619（4.520～6.984）	5.124（3.954～6.639）	< 0.001
合并EBV感染	5.747（4.601～7.178）	3.533（2.726～4.580）	< 0.001
WBC > 15 × 10⁹/L	2.214（1.736～2.823）	1.262（0.916～1.738）	0.155
血糖> 8.3 mmol/L	14.182（8.889～22.628）	7.323（4.297～12.478）	< 0.001
降钙素原> 0.1 ng/ml	1.946（1.579～2.399）	1.727（1.321～2.258）	< 0.001
NLR > 1.59	2.420（1.972～2.971）	2.031（1.564～2.637）	< 0.001

相关因素	未调整[OR（95%CI）]	调整[OR（95%CI）]	P值
性别	0.938（0.735～1.197）	0.966（0.745～1.252）	0.791
年龄< 3岁	0.926（0.754～1.137）	0.803（0.591～1.091）	0.161
高热> 39 ℃	2.124（1.726～2.614）	1.557（1.206～2.011）	0.001
EV71 IgM阳性	5.619（4.520～6.984）	5.124（3.954～6.639）	< 0.001
合并EBV感染	5.747（4.601～7.178）	3.533（2.726～4.580）	< 0.001
WBC > 15 × 10⁹/L	2.214（1.736～2.823）	1.262（0.916～1.738）	0.155
血糖> 8.3 mmol/L	14.182（8.889～22.628）	7.323（4.297～12.478）	< 0.001
降钙素原> 0.1 ng/ml	1.946（1.579～2.399）	1.727（1.321～2.258）	< 0.001
NLR > 1.59	2.420（1.972～2.971）	2.031（1.564～2.637）	< 0.001

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