|Year : 2021 | Volume
| Issue : 2 | Page : 110-115
Importance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in chronic obstructive pulmonary disease exacerbations
Elif Babaoglu1, Sevinc Sarinc Ulasli1, Emine Keles2, Elif Tugce Korkmaz3, Deniz Koksal1, Salih Emri4
1 Department of Pulmonary Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
2 Department of Pulmonary Medicine, Susehri Hospital, Sivas, Turkey
3 Department of Allergy and Immunology, Faculty of Medicine, Ankara University, Turkey
4 Department of Pulmonary Medicine, Medicana Hospital, Istanbul, Turkey
|Date of Submission||29-Sep-2020|
|Date of Decision||28-Dec-2020|
|Date of Acceptance||04-Jan-2021|
|Date of Web Publication||12-Aug-2021|
Dr. Elif Babaoglu
Department of Pulmonary Medicine, Faculty of Medicine, Hacettepe University, Ankara
Source of Support: None, Conflict of Interest: None
BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of inflammation. Many cells and mediators have been found to be involved in the progression of chronic obstructive pulmonary disease (COPD). We aimed to evaluate the association of the NLR and PLR with treatment options, length of hospital stay, and mortality of patients with COPD exacerbation in this study.
MATERIALS AND METHODS: We retrospectively collected the data of COPD patients who were hospitalized with the diagnosis of COPD exacerbation. Demographic data, NLR, PLR, number of exacerbations in the last year, length of hospital stay, and deceased patients were evaluated. Correlations between NLR and PLR with length of hospital stay and treatment options were analyzed. NLR and PLR values were compared between deceased and survived patients.
RESULTS: One hundred and nineteen patients were included in the study. The mean age of patients was 68.74 ± 9.2 years, and the mean length of hospital stay was 19.5 ± 13.5 days. The median NLR and PLR values were 3.7 (minimum–maximum: 1–10.8) and 109 (minimum–maximum: 7.4–890), respectively. NLR values were found to be higher in patients who required systemic steroid or invasive mechanical ventilation (IMV) (P = 0.001, P = 0.017). The cutoff value of NLR was 2.65 with 73.8% sensitivity and 54.9% specificity (area under the curve [AUC]: 0.675, P = 0.001) for systemic steroid requirement, and the cutoff value of NLR for IMV requirement was 4.19 with 77.8% sensitivity and 70.4% specificity (AUC: 0.741, P = 0.017). However, PLR values were not related with systemic steroid or IMV.
CONCLUSION: NLR seems to be a superior prognostic inflammatory marker than PLR in COPD exacerbation for predicting treatment options.
Keywords: Chronic obstructive pulmonary disease, lymphocyte, neutrophil, platelet
|How to cite this article:|
Babaoglu E, Ulasli SS, Keles E, Korkmaz ET, Koksal D, Emri S. Importance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in chronic obstructive pulmonary disease exacerbations. Eurasian J Pulmonol 2021;23:110-5
|How to cite this URL:|
Babaoglu E, Ulasli SS, Keles E, Korkmaz ET, Koksal D, Emri S. Importance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in chronic obstructive pulmonary disease exacerbations. Eurasian J Pulmonol [serial online] 2021 [cited 2021 Dec 8];23:110-5. Available from: https://www.eurasianjpulmonol.com/text.asp?2021/23/2/110/320427
| Introduction|| |
Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation associated with an abnormal inflammatory response of lungs to noxious particles or gasses., Exacerbation is defined as an acute worsening of respiratory symptoms that result in additional therapy. It is the most important factor in mortality and morbidity. Exacerbations also impact health status, rates of hospitalization, readmission, and disease progression. The mortality rate in COPD patients is 15%–54%, and it is higher in acute exacerbations.,
Several types of inflammatory cells and mediators have been found to be involved in the progression of COPD. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are inexpensive, widely available markers of inflammation.,,, NLR is a beneficial marker for the early detection of potential acute exacerbation in COPD. It is associated with the severity of airflow limitation and an independent predictor of mortality., Furthermore, NLR was associated with Modified medical research Council (mMRC), 6-min walking test, BODE index, and length of hospital stay in COPD patients.,,,
PLR is another easily available marker for evaluating the inflammation during stable period and the disease severity during acute exacerbations in COPD patients.
Recent studies have investigated the usefulness of NLR and PLR for predicting the mortality in COPD. However, there are limited data about the relationship between NLR, PLR, and requirement of systemic steroid, invasive mechanical ventilation (IMV), and non-IMV in COPD exacerbation.
We aimed to evaluate the association of the NLR and PLR with the required treatment options, length of hospital stay, and mortality of patients with COPD exacerbations.
| Materials and Methods|| |
The study was designed as retrospective cross-sectional. All data were collected retrospectively from the hospital database. Between March 2010 and January 2017, hospitalized patients with the diagnosis of COPD exacerbation were enrolled to the study. To collect the data of patients, ICD code “J44” was used. The study protocol was approved by the ethics committee (ethics committee number: GO 16/636-21) and was in accordance with the Declaration of Helsinki.
COPD patients with bronchiectasis, pneumonia, tuberculosis, pulmonary embolism, malignancy, chronic renal failure, and liver failure were excluded. Furthermore, transferred patients from other hospitals or intensive care units (ICUs) were excluded. Patients were previously diagnosed as COPD by a pulmonologist who detected airflow obstruction on spirometry (postbronchodilator forced expiratory volume in 1 [FEV1]/forced vital capacity <70%) with compatible history. The exacerbation was defined as acute worsening of a patient's respiratory symptoms that resulted in additional therapy. Severe symptoms such as sudden worsening of resting dyspnea, high respiratory rate, decreased oxygen saturation, confusion, drowsiness, acute respiratory failure, onset of new clinical signs (cyanosis and peripheral edema), failure of an exacerbation to respond to initial medical management, presence of serious comorbidities (heart failure and newly occurring arrhythmias), or insufficient home support were the indications for hospitalization.
All patients in need of IMV were taken into ICU. Patients' age, gender, mMRC score, smoking behavior, NLR, PLR, time of COPD diagnosis, number of exacerbations in the last year, length of hospital stay, echocardiographic evaluation (presence of cor pulmonale and value of systolic pulmonary arterial pressure), applied treatments, and deceased patients both in ward and ICU were recorded. NLR and PLR were calculated as the ratio of neutrophils to lymphocytes and the ratio of platelets to lymphocytes at the admission to hospital with COPD exacerbation.
Statistical analyses were performed using SPSS software version 20 (IBM SPSS Statistics, IBM Corp., Armonk, NY, USA). The variables were investigated using visual and analytical methods (Kolmogorov–Smirnov test) to determine the distribution status. Descriptive analyses were presented as mean ± standard deviation, median (minimum–maximum), and percentage values.
Nonnormally distributed variables of groups were compared using Mann–Whitney U-test. t-test was used to compare normally distributed variables between groups.
The associations between nonnormally distributed variables were investigated with Spearman correlation coefficient. A 5% type I error level was used to infer statistical significance.
The capacity of NLR in predicting the need of systemic steroid and IMV was analyzed using receiver operating characteristic curve analysis. When a significant cutoff value was observed, sensitivity and specificity values were presented. While evaluating the area under the curve (AUC), a 5% type I error level was used to accept a statistically significant predictive value of NLR.
| Results|| |
Two hundred and sixteen COPD patients were hospitalized between March 2010 and January 2017 with exacerbations, but 97 of them were excluded due to coexistence with comorbidities such as bronchiectasis, pneumonia, tuberculosis, pulmonary embolism, malignancy, chronic renal failure, and liver failure.
One hundred and nineteen hospitalized patients (female/male: 45/74) were included in the study. Twenty-five patients were taken to ICU because they needed IMV. The demographic, clinical, and laboratory findings of the patients are summarized in [Table 1]. Mean pulmonary artery pressure values were higher in deceased patients than discharged patients (P = 0.008). There was no statistically significant difference between deceased and discharged patients in terms of age, sex, mMRC score, smoking status at the admission of hospital, cumulative dose of smoking (package per year), NLR, PLR, time of COPD diagnosis, number of exacerbations in the last year, length of hospital stay, and the presence of cor pulmonale.
The mean NLR and PLR values of subgroups according to gender, age, smoking behavior, echocardiographic evaluation, number of exacerbations in the last year, and applied treatments in hospital are summarized in [Table 2]. NLR values were found higher in patients who required systemic steroid or IMV (P = 0.001, P = 0.017) [Figure 1] and [Figure 2]. PLR values were found to be higher in female patients (P = 0.041) [Table 2].
|Figure 1: Neutrophil-to-lymphocyte ratio values in systemic steroid required and nonrequired patients|
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|Figure 2: Neutrophil-to-lymphocyte ratio values in invasive mechanical ventilation required and nonrequired patients|
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|Table 2: Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio values in subgroups|
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The cutoff value of NLR was 2.65 with 73.8% sensitivity, 54.9% specificity, positive predictive value: 66.4%, and negative predictive value: 58.9% (AUC: 0.675, P = 0.001) for systemic steroid requirement, and for IMV requirement, it was 4.19 with 77.8% sensitivity, 70.4% specificity, positive predictive value: 18.8%, and negative predictive value: 92.5% (AUC: 0.741, P = 0.017) [Figure 3] and [Figure 4].
|Figure 3: Receiver operating characteristic curve of neutrophil-to-lymphocyte ratio for systemic steroid need. Cutoff value: 2.65, sensitivity = 0.738, specificity = 0.549, positive predictive value: 66.4%, negative predictive value: 58.9%, area under the curve = 0.675, P = 0.001|
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|Figure 4: Receiver operating characteristic curve of neutrophil-to-lymphocyte ratio for invasive mechanical ventilation need. Cutoff value = 4.19, sensitivity = 0.778, specificity = 0.704, positive predictive value: 18.8%, negative predictive value: 92.5%, area under the curve = 0.741, P = 0.017|
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There were no statistically significant correlations between NLR and PLR with length of hospital stay, number of exacerbations, pO2, PCO2, and SaO2 values. The correlations are shown in [Table 3].
|Table 3: Correlations of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio with length of hospital, number of exacerbations, pO2, PCO2, and SaO2|
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Twenty-five patients (female/male: 20/5) were admitted to ICU. The mean length of ICU stay was 23 days. ICU mortality was 32%.
| Discussion|| |
In this study, NLR was found to be a useful marker to guide treatment options such as systemic steroid or IMV in hospitalized COPD patients with exacerbation. NLR seems to be more effective than PLR in predicting treatment options during exacerbation period. This is a novel information because there was no data about treatment options in previous studies. Patients with higher NLR values may need systemic steroid or IMV indicating the severity of exacerbations. Although no correlations were found between NLR and arterial blood gas parameters, patients with NLR values higher than 4.19 during COPD exacerbation were found to need intensive care for IMV in the present study. Therefore, patients with higher NLR values should be followed closely for intensive care need before the impairment of arterial blood gas parameters during COPD exacerbations.
Moreover, the cutoff value of NLR for systemic steroid requirement was 2.65 with 73.8% sensitivity and 54.9% specificity (AUC: 0.675, P = 0.001) in our study. To our knowledge, there was no study evaluating the impact of NLR on systemic steroid requirement during COPD exacerbations in the literature till the present study.
In previous studies, NLR was found as an independent predictor for mortality and a prognostic marker for future exacerbations., In accordance with the previous studies, NLR values were also higher in deceased patients than discharged patients in our study. In the study of Taylan et al., for an NLR cutoff of 3.29, sensitivity for detecting exacerbation of COPD was 80.8% and specificity was 77.7%. The cutoff value for NLR in predicting mortality was 3.3 in Xiong et al. study. They followed up the patients for 24 months in stable stage. Furthermore, NLR was found as a prognostic marker for future exacerbations in patients with COPD.
In the literature, there are some other markers which are associated with the risk of COPD exacerbations such as eosinophils and C-reactive protein. Furthermore, eosinophils are associated with mortality, decline in FEV1, and response to both inhaled and systemic corticosteroids. In our study, we did not evaluate these markers.,
Hospitalizations for COPD exacerbations have increased significantly over years, but in contrast, length of hospital stay reduced., In recent studies, the mean length of hospital stay reduces to 4 days. In our study, the mean length of hospital stay was 19.5 ± 13.5, and there was not any correlation between NLR and length of hospital stay. In some studies, length of hospital stay was correlated to NLR in COPD exacerbation. This difference might be due to the severity of exacerbations and comorbidities of different study populations.
PLR was found a useful tool for evaluating the ongoing inflammation during stable period and the disease severity during exacerbations in COPD patients. In another study, COPD patients had a significantly increased platelet count, along with a reduced MPV when compared to healthy controls. Moreover, El-Gazzar et al. reported that NLR and PLR increased in stable COPD patients and further increased during exacerbation which can predict in hospital mortality. Till now, PLR has not been investigated for predicting treatment options. In our study, PLR levels were similar in deceased and discharged patients, and there were no significant correlations between PLR with length of hospital or number of exacerbations.
Furthermore, there are some limitations of our study. As the design of the present study was retrospective, follow-up results were absent in our study. NLR levels were inversely associated with severity of airflow limitation as measured by FEV1% predicted. Unfortunately, we were not able to perform pulmonary function tests to the study population as they had severe exacerbation. Hence, further prospective randomized controlled studies are needed.
| Conclusion|| |
NLR was found as a useful marker for predicting treatment options such as systemic steroid or IMV needs in hospitalized COPD patients with exacerbation. Patients with higher NLR values should be monitored closely for intensive care requirement. However, PLR is an inflammatory marker which was found to be unrelevant in predicting treatment options. Therefore, NLR seems to be a superior inflammatory marker than PLR for predicting treatment options and follow-up during exacerbation period.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Wedzicha JA Ers Co-Chair, Miravitlles M, Hurst JR, Calverley PM, Albert RK, Anzueto A, Criner GJ, Papi A, Rabe KF, Rigau D, Sliwinski P, Tonia T, Vestbo J, Wilson KC, Krishnan JA Ats Co-Chair. Management of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2017 Mar 15;49(3):1600791.
Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease. Fontana, WI, USA; 2020. Available from: https://www.goldcopd.org
. [Last accessed on 01 June 2020].
Wedzicha JA, Seemungal TA. COPD exacerbations: Defining their cause and prevention. Lancet 2007;370:786-96.
Brightling CE. Biomarkers that predict and guide therapy for exacerbations of chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2013 Dec;10 Suppl:S214-9. doi: 10.1513/AnnalsATS.201302-023AW. PMID: 24313775.
Seemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:1418-22.
Tertemiz KC, Kömüs N, Ellidokuz H, Sevinç C, Cımrın AH. Mortality and factors affecting mortality in chronic obstructive pulmonary disease. Tuberk Toraks 2012;60:114-22.
Jouneau S, Roche N. Management of acute exacerbations of chronic obstructive pulmonary disease (COPD). Guidelines from the Société de Pneumologie de Langue Française (Argumentary). Rev Mal Respir 2017;34:323-6.
Günay E, Sarınç Ulaşlı S, Akar O, Ahsen A, Günay S, Koyuncu T, et al
. Neutrophil-to-lymphocyte ratio in chronic obstructive pulmonary disease: A retrospective study. Inflammation 2014;37:374-80.
Ozyalvacli G, Yesil C, Kargi E, Kizildag B, Kilitci A, Yilmaz F. Diagnostic and prognostic importance of the neutrophil lymphocyte ratio in breast cancer. Asian Pac J Cancer Prev 2014;15:10363-6.
Li S, Xu X, Liang D, Tian G, Song S, He Y. Prognostic value of blood neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with gastric cancer. Zhonghua Zhong Liu Za Zhi 2014;36:910-5.
Wu Y, Chen Y, Yang X, Chen L, Yang Y. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were associated with disease activity in patients with systemic lupus erythematosus. Int Immunopharmacol 2016;36:94-9.
Karadeniz G, Aktoğu S, Erer OF, Kır SB, Doruk S, Demir M, et al
. Predictive value of platelet-to-lymphocyte ratio in exacerbation of chronic obstructive pulmonary disease. Biomark Med 2016;10:701-10.
Lee H, Um SJ, Kim YS, Kim DK, Jang AS, Choi HS, et al
. Association of the neutrophil-to-lymphocyte ratio with lung function and exacerbations in patients with chronic obstructive pulmonary disease. PLoS One 2016;11:e0156511.
Xiong W, Xu M, Zhao Y, Wu X, Pudasaini B, Liu JM. Can we predict the prognosis of COPD with a routine blood test? Int J Chron Obstruct Pulmon Dis 2017;12:615-25.
Duman D, Aksoy E, Agca MC, Kocak ND, Ozmen I, Akturk UA, et al
. The utility of inflammatory markers to predict readmissions and mortality in COPD cases with or without eosinophilia. Int J Chron Obstruct Pulmon Dis 2015;10:2469-78.
Furutate R, Ishii T, Motegi T, Hattori K, Kusunoki Y, Gemma A, et al
. The neutrophil to lymphocyte ratio is related to disease severity and exacerbation in patients with chronic obstructive pulmonary disease. Intern Med 2016;55:223-9.
Lee SJ, Lee HR, Lee TW, Ju S, Lim S, Go SI, et al
. Usefulness of neutrophil to lymphocyte ratio in patients with chronic obstructive pulmonary disease: A prospective observational study. Korean J Intern Med 2016;31:891-8.
Taylan M, Demir M, Kaya H, Selimoglu Sen H, Abakay O, Carkanat Aİ, et al
. Alterations of the neutrophil-lymphocyte ratio during the period of stable and acute exacerbation of chronic obstructive pulmonary disease patients. Clin Respir J 2017;11:311-7.
Bafadhel M, Pavord ID, Russell REK. Eosinophils in COPD: Just another biomarker? Lancet Respir Med 2017;5:747-59.
Francis NA, Gillespie D, Wootton M, White P, Bates J, Richards J, et al
. Clinical features and C-reactive protein as predictors of bacterial exacerbations of COPD. Int J Chron Obstruct Pulmon Dis 2020;15:3147-58.
Ford ES. Hospital discharges, readmissions, and ED visits for COPD or bronchiectasis among US adults: Findings from the nationwide inpatient sample 2001-2012 and Nationwide Emergency Department Sample 2006-2011. Chest 2015;147:989-98.
Quon BS, Gan WQ, Sin DD. Contemporary management of acute exacerbations of COPD: A systematic review and metaanalysis. Chest 2008;133:756-66.
Biljak VR, Pancirov D, Cepelak I, Popović-Grle S, Stjepanović G, Grubišić TŽ. Platelet count, mean platelet volume and smoking status in stable chronic obstructive pulmonary disease. Platelets 2011;22:466-70.
El-Gazzar AG, Kamel MH, Elbahnasy OK, El-Naggar ME. Prognostic value of platelet and neutrophil to lymphocyte ratio in COPD patients. Expert Rev Respir Med 2020;14:111-6.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]