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Usefulness of neutrophil to lymphocyte ratio in patients with chronic obstructive pulmonary disease: a prospective observational study

  • Lee, Seung Jun (Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine) ;
  • Lee, Hyang Rae (Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine) ;
  • Lee, Tae Won (Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine) ;
  • Ju, Sunmi (Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine) ;
  • Lim, Sujin (Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine) ;
  • Go, Se-Il (Division of Hematology and Oncology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine) ;
  • You, Jung-Wan (Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine) ;
  • Cho, Yu Ji (Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine) ;
  • Lee, Gyeong-Won (Division of Hematology and Oncology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine) ;
  • Jeong, Yi Yeong (Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine) ;
  • Kim, Ho Cheol (Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine) ;
  • Lee, Jong Deog (Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine)
  • 투고 : 2015.03.31
  • 심사 : 2015.05.22
  • 발행 : 2016.09.01

초록

Background/Aims: Neutrophil to lymphocyte ratio (NLR) in peripheral blood is a useful systemic inflammatory response biomarker. However, NLR has not been studied in patients with chronic obstructive pulmonary disease (COPD). This study was aimed to evaluate the usefulness of NLR in patients with COPD. Methods: NLR was prospectively measured and compared in patients with COPD exacerbation (n = 59), patients with stable COPD (n = 61), and healthy controls (n = 28). NLR in patients with COPD exacerbation was repeatedly measured in the convalescent period. The correlation between NLR and clinical parameters was evaluated, and the predictors for respiratory hospitalization were analyzed by multivariate logistic regression. Results: NLR values were significantly higher in patients with COPD exacerbation compared with stable COPD patients and controls ($12.4{\pm}10.6$, $2.4{\pm}0.7$, $1.4{\pm}0.5$, respectively; p < 0.001). NLR was significantly decreased during the convalescent period in patients with COPD exacerbation ($4.5{\pm}4.6$ vs. $11.5{\pm}8.8$, p < 0.001). NLR exhibited a significant correlation with the body mass index, degree of airway obstruction, dyspnea, and exercise capacity (BODE) index, the 6-minute walk test, and the modified Medical Research Council scale. NLR ${\geq}2.8$ was an independent predictor with a borderline significance for respiratory hospitalization (odds ratio, 2.083; p = 0.079). Body mass index and forced expiratory volume in 1 second were independent predictors for respiratory hospitalization. Conclusions: NLR is a straightforward and effective biomarker of COPD exacerbation that may serve as a predictor for respiratory hospitalization in patients with COPD.

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참고문헌

  1. World Health Organization. The top 10 causes of death [Internet]. Geneva: World Health Organization, c2015 [cited 2015 Dec 10]. Available from: http://who.int/mediacentre/factsheets/fs310/en/.
  2. Vestbo J, Hurd SS, Agusti AG, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2013;187:347-365. https://doi.org/10.1164/rccm.201204-0596PP
  3. Franciosi LG, Page CP, Celli BR, et al. Markers of disease severity in chronic obstructive pulmonary disease. Pulm Pharmacol Ther 2006;19:189-199. https://doi.org/10.1016/j.pupt.2005.05.001
  4. Franciosi LG, Page CP, Celli BR, et al. Markers of exacerbation severity in chronic obstructive pulmonary disease. Respir Res 2006;7:74. https://doi.org/10.1186/1465-9921-7-74
  5. Barnes PJ, Chowdhury B, Kharitonov SA, et al. Pulmonary biomarkers in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2006;174:6-14. https://doi.org/10.1164/rccm.200510-1659PP
  6. Sinden NJ, Stockley RA. Systemic inflammation and comorbidity in COPD: a result of 'overspill' of inflammatory mediators from the lungs? Review of the evidence. Thorax 2010;65:930-936. https://doi.org/10.1136/thx.2009.130260
  7. Walter RE, Wilk JB, Larson MG, et al. Systemic inflammation and COPD: the Framingham Heart Study. Chest 2008;133:19-25. https://doi.org/10.1378/chest.07-0058
  8. Vestbo J. Systemic inflammation and progression of COPD. Thorax 2007;62:469-470. https://doi.org/10.1136/thx.2007.077792
  9. Williams KA, Labidi-Galy SI, Terry KL, et al. Prognostic significance and predictors of the neutrophil-to-lymphocyte ratio in ovarian cancer. Gynecol Oncol 2014;132:542-550. https://doi.org/10.1016/j.ygyno.2014.01.026
  10. Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol 2010;6:149-163. https://doi.org/10.2217/fon.09.136
  11. Kacan T, Babacan NA, Seker M, et al. Could the neutrophil to lymphocyte ratio be a poor prognostic factor for non small cell lung cancers? Asian Pac J Cancer Prev 2014;15:2089-2094. https://doi.org/10.7314/APJCP.2014.15.5.2089
  12. Walsh SR, Cook EJ, Goulder F, Justin TA, Keeling NJ. Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer. J Surg Oncol 2005;91:181-184. https://doi.org/10.1002/jso.20329
  13. Azab B, Bhatt VR, Phookan J, et al. Usefulness of the neutrophil-to-lymphocyte ratio in predicting short- and long-term mortality in breast cancer patients. Ann Surg Oncol 2012;19:217-224. https://doi.org/10.1245/s10434-011-1814-0
  14. Stotz M, Gerger A, Eisner F, et al. Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer. Br J Cancer 2013;109:416-421. https://doi.org/10.1038/bjc.2013.332
  15. Guasti L, Dentali F, Castiglioni L, et al. Neutrophils and clinical outcomes in patients with acute coronary syndromes and/or cardiac revascularisation: a systematic review on more than 34,000 subjects. Thromb Haemost 2011;106:591-599. https://doi.org/10.1160/TH11-02-0096
  16. Bhat T, Teli S, Rijal J, et al. Neutrophil to lymphocyte ratio and cardiovascular diseases: a review. Expert Rev Cardiovasc Ther 2013;11:55-59. https://doi.org/10.1586/erc.12.159
  17. MacNee W. Systemic inflammatory biomarkers and co-morbidities of chronic obstructive pulmonary disease. Ann Med 2013;45:291-300. https://doi.org/10.3109/07853890.2012.732703
  18. Agustí AG, Noguera A, Sauleda J, Sala E, Pons J, Busquets X. Systemic effects of chronic obstructive pulmonary disease. Eur Respir J 2003;21:347-360. https://doi.org/10.1183/09031936.03.00405703
  19. Gan WQ, Man SF, Senthilselvan A, Sin DD. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax 2004;59:574-580. https://doi.org/10.1136/thx.2003.019588
  20. Agusti AG. COPD, a multicomponent disease: implications for management. Respir Med 2005;99:670-682. https://doi.org/10.1016/j.rmed.2004.11.006
  21. Berger JS, Sanborn TA, Sherman W, Brown DL. Effect of chronic obstructive pulmonary disease on survival of patients with coronary heart disease having percutaneous coronary intervention. Am J Cardiol 2004;94:649-651. https://doi.org/10.1016/j.amjcard.2004.05.034
  22. Curkendall SM, DeLuise C, Jones JK, et al. Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients. Ann Epidemiol 2006;16:63-70. https://doi.org/10.1016/j.annepidem.2005.04.008
  23. Mannino DM, Aguayo SM, Petty TL, Redd SC. Low lung function and incident lung cancer in the United States: data from the first National Health and Nutrition Examination Survey follow-up. Arch Intern Med 2003;163:1475-1480. https://doi.org/10.1001/archinte.163.12.1475
  24. Schols AM. Pulmonary cachexia. Int J Cardiol 2002;85:101-110. https://doi.org/10.1016/S0167-5273(02)00238-3
  25. Biskobing DM. COPD and osteoporosis. Chest 2002;121:609-620. https://doi.org/10.1378/chest.121.2.609
  26. Yao Y, Yuan D, Liu H, Gu X, Song Y. Pretreatment neutrophil to lymphocyte ratio is associated with response to therapy and prognosis of advanced non-small cell lung cancer patients treated with first-line platinum-based chemotherapy. Cancer Immunol Immunother 2013;62:471-479. https://doi.org/10.1007/s00262-012-1347-9
  27. Yilmaz H, Uyfun M, Yilmaz TS, et al. Neutrophil-lymphocyte ratio may be superior to C-reactive protein for predicting the occurrence of postmenopausal osteoporosis. Endocr Regul 2014;48:25-33. https://doi.org/10.4149/endo_2014_01_25
  28. Kang MH, Go SI, Song HN, et al. The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer. Br J Cancer 2014;111:452-460. https://doi.org/10.1038/bjc.2014.317
  29. Hurst JR, Donaldson GC, Perera WR, et al. Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2006;174:867-874. https://doi.org/10.1164/rccm.200604-506OC
  30. Celli BR, Cote CG, Marin JM, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med 2004;350:1005-1012. https://doi.org/10.1056/NEJMoa021322
  31. Marin JM, Carrizo SJ, Casanova C, et al. Prediction of risk of COPD exacerbations by the BODE index. Respir Med 2009;103:373-378. https://doi.org/10.1016/j.rmed.2008.10.004
  32. Pinto-Plata V, Toso J, Lee K, et al. Profiling serum biomarkers in patients with COPD: associations with clinical parameters. Thorax 2007;62:595-601. https://doi.org/10.1136/thx.2006.064428
  33. Liu SF, Chin CH, Wang CC, Lin MC. Correlation between serum biomarkers and BODE index in patients with stable COPD. Respirology 2009;14:999-1004. https://doi.org/10.1111/j.1440-1843.2009.01608.x
  34. Gaki E, Kontogianni K, Papaioannou AI, et al. Associations between BODE index and systemic inflammatory biomarkers in COPD. COPD 2011;8:408-413. https://doi.org/10.3109/15412555.2011.619599
  35. Hallin R, Koivisto-Hursti UK, Lindberg E, Janson C. Nutritional status, dietary energy intake and the risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Respir Med 2006;100:561-567. https://doi.org/10.1016/j.rmed.2005.05.020
  36. Pouw EM, Ten Velde GP, Croonen BH, Kester AD, Schols AM, Wouters EF. Early non-elective readmission for chronic obstructive pulmonary disease is associated with weight loss. Clin Nutr 2000;19:95-99. https://doi.org/10.1054/clnu.1999.0074
  37. Bahadori K, FitzGerald JM. Risk factors of hospitalization and readmission of patients with COPD exacerbation: systematic review. Int J Chron Obstruct Pulmon Dis 2007;2:241-251.
  38. inganayagam A, Schembri S, Chalmers JD. Predictors of mortality in hospitalized adults with acute exacerbation of chronic obstructive pulmonary disease. Ann Am Thorac Soc 2013;10:81-89. https://doi.org/10.1513/AnnalsATS.201208-043OC

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