The value of lymphocyte-to-monocyte ratio and neutrophil-to-lymphocyte ratio in differentiating pneumonia from upper respiratory tract infection (URTI) in children: a cross-sectional study
Tóm tắt
Early and accurate diagnosis of pediatric pneumonia in primary health care can reduce the chance of long-term respiratory diseases, related hospitalizations and mortality while lowering medical costs. The aim of this study was to assess the value of blood biomarkers, clinical symptoms and their combination in assisting discrimination of pneumonia from upper respiratory tract infection (URTI) in children. Both univariate and multivariate logistic regressions were used to build the pneumonia screening model based on a retrospective cohort, comprised of 5211 children (age ≤ 18 years). The electronic health records of the patients, who had inpatient admission or outpatient visits between February 15, 2012 to September 30, 2018, were extracted from the hospital information system of Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang Province, China. The children who were diagnosed with pneumonia and URTI were enrolled and their clinical features and levels of blood biomarkers were compared. Using the area under the ROC curve, both two screening models were evaluated under 80% (training) versus 20% (test) cross-validation data split for their accuracy. In the retrospective cohort, 2548 of 5211 children were diagnosed with the defined pneumonia. The univariate screening model reached predicted AUCs of 0.76 for lymphocyte/monocyte ratio (LMR) and 0.71 for neutrophil/lymphocyte ratio (NLR) when identified overall pneumonia from URTI, attaining the best performance among the biomarker candidates. In subgroup analysis, LMR and NLR attained AUCs of 0.80 and 0.86 to differentiate viral pneumonia from URTI, and AUCs of 0.77 and 0.71 to discriminate bacterial pneumonia from URTI respectively. After integrating LMR and NLR with three clinical symptoms of fever, cough and rhinorrhea, the multivariate screening model obtained increased predictive values, reaching validated AUCs of 0.84, 0.95 and 0.86 for distinguishing pneumonia, viral pneumonia and bacterial pneumonia from URTI respectively. Our study demonstrated that combining LMR and NLR with critical clinical characteristics reached promising accuracy in differentiating pneumonia from URTI, thus could be considered as a useful screening tool to assist the diagnosis of pneumonia, in particular, in community healthcare centers. Further researches could be conducted to evaluate the model’s clinical utility and cost-effectiveness in primary care scenarios to facilitate pneumonia diagnosis, especially in rural settings.
Tài liệu tham khảo
Liu L, Oza S, Hogan D, Chu Y, Perin J, Zhu J, et al. Global, regional, and national causes of under-5 mortality in 2000–15: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet (London, England). 2016;388:3027–35.
Cooke G, Valenti L, Glasziou P, Britt H. Common general practice presentations and publication frequency. Aust Fam Physician. 2013;42:65–8.
Gray D, Willemse L, Visagie A, Czövek D, Nduru P, Vanker A, et al. Determinants of early-life lung function in African infants. Thorax. 2016;72:445–50.
Svanes C, Sunyer J, Plana E, Dharmage S, Heinrich J, Jarvis D, et al. Early life origins of chronic obstructive pulmonary disease. Thorax. 2010;65:14–20.
Chan JYC, Stern DA, Guerra S, Wright AL, Morgan WJ, Martinez FD. Pneumonia in childhood and impaired lung function in adults: a longitudinal study. Pediatrics. 2015;135:607–16.
Martinez FD. Early-life origins of chronic obstructive pulmonary disease. N Engl J Med. 2016;375:871–8.
Cherian T, Mulholland EK, Carlin JB, Ostensen H, Amin R, de Campo M, et al. Standardized interpretation of paediatric chest radiographs for the diagnosis of pneumonia in epidemiological studies. Bull World Health Organ. 2005;83:353–9.
van Vugt SF, Broekhuizen BDL, Lammens C, Zuithoff NPA, de Jong PA, Coenen S, et al. Use of serum C reactive protein and procalcitonin concentrations in addition to symptoms and signs to predict pneumonia in patients presenting to primary care with acute cough: diagnostic study. BMJ. 2013;346:f2450.
Leung AKC, Wong AHC, Hon KL. Community-Acquired Pneumonia in Children. Recent Pat Inflamm Allergy Drug Discov. 2018;12:136–44.
Jain N, Lodha R, Kabra SK. Upper respiratory tract infections. Indian J Pediatr. 2001;68:1135–8.
Jain S, Williams DJ, Arnold SR, Ampofo K, Bramley AM, Reed C, et al. Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med. 2015;372:835–45.
Anand N, Kollef MH. The alphabet soup of pneumonia: CAP, HAP, HCAP, NHAP, and VAP. Semin Respir Crit Care Med. 2009;30:3–9.
Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, et al. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med. 2015;373:415–27.
Mizgerd JP. Inflammation and pneumonia: why are some more susceptible than others? Clin Chest Med. 2018;39:669–76.
Quinton LJ, Walkey AJ, Mizgerd JP. Integrative physiology of pneumonia. Physiol Rev. 2018;98:1417–64.
Cline MJ, Lehrer RI, Territo MC, Golde DW. UCLA conference. Monocytes and macrophages: functions and diseases. Ann Intern Med. 1978;88:78–88.
Gu X, Sun S, Gao X-S, Xiong W, Qin S, Qi X, et al. Prognostic value of platelet to lymphocyte ratio in non-small cell lung cancer: evidence from 3,430 patients. Sci Rep. 2016;6:23893.
Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013;13:159–75.
Köse N, Yıldırım T, Akın F, Yıldırım SE, Altun İ. Prognostic role of NLR, PLR, and LMR in patients with pulmonary embolism. Bosn J basic Med Sci. 2020;20:248–53.
Yevich S, Gaspar N, Tselikas L, Brugières L, Pacquement H, Schleiermacher G, et al. Percutaneous computed tomography-guided thermal ablation of pulmonary osteosarcoma metastases in children. Ann Surg Oncol. 2016;23:1380–6.
Cohen JF, Korevaar DA, Altman DG, Bruns DE, Gatsonis CA, Hooft L, et al. STARD 2015 guidelines for reporting diagnostic accuracy studies: explanation and elaboration. BMJ Open. 2016;6:1–17.
Alcoba G, Keitel K, Maspoli V, Lacroix L, Manzano S, Gehri M, et al. A three-step diagnosis of pediatric pneumonia at the emergency department using clinical predictors, C-reactive protein, and pneumococcal PCR. Eur J Pediatr. 2017;176:815–24.
Özdin S, Sarisoy G, Böke Ö. A comparison of the neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratios in schizophrenia and bipolar disorder patients - a retrospective file review. Nord J Psychiatry. 2017;71:509–12.
Li Z, Hong N, Robertson M, Wang C, Jiang G. Preoperative red cell distribution width and neutrophil-to-lymphocyte ratio predict survival in patients with epithelial ovarian cancer. Sci Rep. 2017;7:43001.
Feng F, Sun L, Zheng G, Liu S, Liu Z, Xu G, et al. Low lymphocyte-to-white blood cell ratio and high monocyte-to-white blood cell ratio predict poor prognosis in gastric cancer. Oncotarget. 2017;8:5281–91.
Pantzaris N-D, Platanaki C, Pierrako C, Karamouzos V, Velissaris D. Neutrophil-to-lymphocyte ratio relation to Sepsis severity scores and inflammatory biomarkers in patients with community-acquired pneumonia: a case series. J Transl Intern Med. 2018;6:43–6.
Kartal O, Kartal AT. Value of neutrophil to lymphocyte and platelet to lymphocyte ratios in pneumonia. Bratisl Lek Listy. 2017;118:513–6.
Huang Y, Liu A, Liang L, Jiang J, Luo H, Deng W, et al. Diagnostic value of blood parameters for community-acquired pneumonia. Int Immunopharmacol. 2018;64:10–5.
Holt PG, Strickland DH, Wikström ME, Jahnsen FL. Regulation of immunological homeostasis in the respiratory tract. Nat Rev Immunol. 2008;8:142–52.
Greenberger PA. 7. Immunologic lung disease. J Allergy Clin Immunol. 2008;121(2 Suppl):S393–7 quiz S418.
Moore TA, Moore BB, Newstead MW, Standiford TJ. Gamma delta-T cells are critical for survival and early proinflammatory cytokine gene expression during murine Klebsiella pneumonia. J Immunol. 2000;165:2643–50.
Funaki T, Miyairi I. Lymphocytosis in a baby with pertussis. Lancet Infect Dis. 2015;15:130.
Venet F, Chung C-S, Huang X, Lomas-Neira J, Chen Y, Ayala A. Lymphocytes in the development of lung inflammation: a role for regulatory CD4+ T cells in indirect pulmonary lung injury. J Immunol. 2009;183:3472–80.
Belotti A, Doni E, Bolis S, Rossini F, Casaroli I, Pezzatti S, et al. Peripheral blood lymphocyte/monocyte ratio predicts outcome in follicular lymphoma and in diffuse large B-cell lymphoma patients in the rituximab era. Clin Lymphoma Myeloma Leuk. 2015;15:208–13.
Lin G-N, Peng J-W, Liu D-Y, Xiao J-J, Chen Y-Q, Chen X-Q. Increased lymphocyte to monocyte ratio is associated with better prognosis in patients with newly diagnosed metastatic nasopharyngeal carcinoma receiving chemotherapy. Tumour Biol. 2014;35:10849–54.
Paik KY, Lee IK, Lee YS, Sung NY, Kwon TS. Clinical implications of systemic inflammatory response markers as independent prognostic factors in colorectal cancer patients. Cancer Res Treat. 2014;46:65–73.
Merekoulias G, Alexopoulos EC, Belezos T, Panagiotopoulou E, Jelastopulu DME. Lymphocyte to monocyte ratio as a screening tool for influenza. Plos Curr. 2010;2:RRN1154.
Atochina-Vasserman EN, Bates SR, Zhang P, Abramova H, Zhang Z, Gonzales L, et al. Early alveolar epithelial dysfunction promotes lung inflammation in a mouse model of Hermansky-Pudlak syndrome. Am J Respir Crit Care Med. 2011;184:449–58.
Gibbons MA, MacKinnon AC, Ramachandran P, Dhaliwal K, Duffin R, Phythian-Adams AT, et al. Ly6Chi monocytes direct alternatively activated profibrotic macrophage regulation of lung fibrosis. Am J Respir Crit Care Med. 2011;184:569–81.
Janssen WJ, Barthel L, Muldrow A, Oberley-Deegan RE, Kearns MT, Jakubzick C, et al. Fas determines differential fates of resident and recruited macrophages during resolution of acute lung injury. Am J Respir Crit Care Med. 2011;184:547–60.
Misharin AV, Morales-Nebreda L, Reyfman PA, Cuda CM, Walter JM, McQuattie-Pimentel AC, et al. Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span. J Exp Med. 2017;214:2387–404.
Tsuchimoto Y, Asai A, Tsuda Y, Ito I, Nishiguchi T, Garcia MC, et al. M2b monocytes provoke bacterial pneumonia and gut Bacteria-associated Sepsis in alcoholics. J Immunol. 2015;195:5169–77.
Casson CN, Doerner JL, Copenhaver AM, Ramirez J, Holmgren AM, Boyer MA, et al. Neutrophils and Ly6Chi monocytes collaborate in generating an optimal cytokine response that protects against pulmonary legionella pneumophila infection. PLoS Pathog. 2017;13:e1006309.
Yong KK, Chang JH, Chien MH, Tsao SM, Yu MC, Bai KJ, et al. Plasma monocyte chemoattractant protein-1 level as a predictor of the severity of community-acquired pneumonia. Int J Mol Sci. 2016;17:179