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Neutrophil to lymphocyte ratio and clinical outcomes in COPD: recent evidence and future perspectives

Panagiotis Paliogiannis, Alessandro G. Fois, Salvatore Sotgia, Arduino A. Mangoni, Elisabetta Zinellu, Pietro Pirina, Silvia Negri, Ciriaco Carru, Angelo Zinellu
European Respiratory Review 2018 27: 170113; DOI: 10.1183/16000617.0113-2017
Panagiotis Paliogiannis
1Dept of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
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Alessandro G. Fois
1Dept of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
2Dept of Respiratory Diseases, University Hospital Sassari (AOU), Sassari, Italy
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  • For correspondence: fois.ale@libero.it
Salvatore Sotgia
3Dept of Biomedical Sciences, University of Sassari, Sassari, Italy
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Arduino A. Mangoni
4Dept of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Adelaide, Australia
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Elisabetta Zinellu
1Dept of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
2Dept of Respiratory Diseases, University Hospital Sassari (AOU), Sassari, Italy
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Pietro Pirina
1Dept of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
2Dept of Respiratory Diseases, University Hospital Sassari (AOU), Sassari, Italy
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Silvia Negri
1Dept of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
2Dept of Respiratory Diseases, University Hospital Sassari (AOU), Sassari, Italy
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Ciriaco Carru
3Dept of Biomedical Sciences, University of Sassari, Sassari, Italy
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Angelo Zinellu
3Dept of Biomedical Sciences, University of Sassari, Sassari, Italy
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    FIGURE 1

    Neutrophil to lymphocyte ratio (NLR) cut-off values in chronic obstructive pulmonary disease (COPD) identified in the studies reviewed.

Tables

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  • TABLE 1

    Studies investigating the predictive roles of neutrophil to lymphocyte ratio (NLR) in chronic obstructive pulmonary disease (COPD)

    First author [ref.]Patients enrolledStudy designMain findings
    NLR as predictor of exacerbations in stable COPD
     Günay [36]COPD: 178 stable, 91 exacerbations; 50 healthy controlsRetrospectiveNLR significantly different between controls and COPD patients, but not between patients with stable COPD and with exacerbations
     Furutate [37]COPD: 141 stable, 49 exacerbationsRetrospectiveNLR significantly higher in patients with exacerbations. Significant correlations with FEV1, BODE, BMI, 6MWT, mMRC, low-attenuation area and fat-free mass index
     Lee [38]885 COPD, 233 exacerbations (1 year)RetrospectiveNLR significantly higher in patients with exacerbations. NLR predictor of exacerbations. Significant correlation with FEV1
     Taylan [39]COPD: 100 stable with exacerbation; 80 healthy controlsRetrospectiveNLR significantly higher in patients with exacerbations, NLR higher in stable COPD than in controls. NLR ≥3.29 predictor of exacerbation
     Farah [40]COPD: 13 stable, 72 exacerbations; 15 healthy controlsRetrospectiveNLR significantly higher in patients with exacerbations. NLR ≥7.3 predictor of exacerbation
     Kurtipek [41]COPD: 94 male patients, 48 with exacerbationsProspectiveNLR significantly higher in exacerbations. NLR ≥3.3 predictor of exacerbation
     Bilir [42]COPD: 467 patients, 186 with exacerbations; 215 healthy controlsRetrospectiveNLR significantly higher in COPD and in exacerbations. NLR ≥3.35 predictor of exacerbation
     In [43]COPD: 103 patients, 47 with exacerbations; 40 healthy controlsRetrospectiveNLR significantly higher in COPD and in exacerbations. NLR ≥3.34 predictor of exacerbation
    NLR as marker of exacerbation aetiology (infection)
     Tanriverdi [44]COPD: 77 patients with exacerbationsProspectiveBacterial infection in 37.4% of the patients. NLR ≥11.5 significantly associated with bacterial infection
     van de Geijn [45]COPD: 17 stable and 45 exacerbations (22 bacterial and 23 non-bacterial)RetrospectiveNLR determined with different methods significantly higher in exacerbations than in stable, and in bacterial exacerbations than in non-bacterial ones
    NLR in COPD patients with comorbidities
     Vaguliene [46]139 lung cancer; COPD: 40 stable and 55 with lung cancer; 33 healthy controlsProspectiveNLR significantly higher in lung cancer patients. No significant difference in NLR between COPD and healthy patients
     Yasar [47]COPD: 140, 63 with metabolic syndrome; 50 healthy controlsRetrospectiveNLR significantly higher in COPD patients than in controls, NLR significantly higher in those with metabolic syndrome. NLR ≥2.56 predictor of COPD
     Arisou [48]COPD: 40 stable; 40 healthy controlsProspectiveNLR was higher in COPD patients than in the control group. Significant positive correlation between tricuspid atrial conduction time and NLR
    NLR as predictor of hospitalisation
     Lee [49]COPD: 61 stable, 59 exacerbations; 28 healthy controlsProspectiveNLR significantly higher in patients with exacerbations. Significant correlations with mMRC and 6MWT. NLR ≥2.8 predictor of hospitalisation
    NLR as predictor of re-hospitalisation
     Duman [50]COPD: 1704 with exacerbations, 351 with >2% eosinophilsRetrospectiveNLR significantly lower in the eosinophilic group. NLR predictor of re-admission and death
    NLR as predictor of death
     Rahimirad [51]COPD: 315, 70 died in hospitalRetrospectiveNLR significantly higher in patients who died in hospital. NLR ≥4 predictor of in-hospital death
     Yao [52]COPD: 303 with exacerbations, 33 died in hospitalRetrospectiveNLR significantly higher in patients who died in hospital. NLR ≥6.24 predictor of in-hospital death
     Xiong [53]COPD: 368 stable, 96 died during follow-up; 298 healthy controlsProspectiveNLR significantly higher in COPD patients than in controls. NLR significantly higher in those who died during follow-up. NLR ≥3.3 predictor of death
     Kumar [54]COPD: 181 with exacerbation, 16 died within 90 daysRetrospectiveNLR significantly higher in patients who died within 90 days from exacerbation
     Saltürk [55]COPD in ICU: 647, 62 with >2% eosinophilsRetrospectiveNLR significantly lower in the eosinophilic group. NLR ≥16 predictor of death
    NLR and oral corticosteroid therapy in COPD   
     Sørensen [56]COPD: 386, 84 using glucocorticoidsProspectiveNLR significantly lower in patients without glucocorticoids, NLR predictor of death in patients not treated with glucocorticoids

    FEV1: forced expiratory volume in 1 s; BMI: body mass index; BODE: BMI, airflow obstruction, dyspnoea, exercise capacity; 6MWT: 6-min walking test; mMRC: modified Medical Research Council dyspnoea scale; ICU: intensive care unit.

    • TABLE 2

      Studies investigating relationships between neutrophil to lymphocyte ratio (NLR) and other biomarkers in chronic obstructive pulmonary disease (COPD)

      First author [ref.]Main markers investigatedMain findings
      Günay [36]CRP, PDW, RDW, MPVIncreased levels of WBC, CRP, RDW and MPV in COPD. Significant positive correlation of NLR with CRP and RDW, and negative correlation with MPV in COPD
      Furutate [37]CRPCRP significantly increased in COPD. Significant positive correlation between NLR and CRP
      Taylan [39]CRP, WBC, RDW, PDW, MPV, ESRSignificant correlations with CRP, WBC and ESR. High NLR values in AECOPD patients with low CRP, WBC or ESR levels
      Farah [40]CRP, WBC, RDW, MPV, CD64RDW, CRP and CD64 significantly elevated in AECOPD. Significant correlations of NLR with CRP and RDW
      Kurtipek [41]CRP, PLRCRP and PLR are significantly higher in AECOPD. Significant positive correlation with CRP. CRP AUC was better than that of NLR, which was better than AUC for PLR
      Bilir [42]CRPSignificant positive correlation with CRP. CRP AUC better than AUC for NLR
      In [43]CRP, ESRSignificant positive correlation with CRP and ESR
      Tanriverdi [44]CRP, PCTPCT higher in infections. Significant but weak positive correlation with CRP. AUC value of PCT significantly better in predicting bacterial infection compared with the CRP or the NLR
      van de Geijn [45]CRP, PCT and othersCRP and PCT higher in AECOPD, especially bacterial ones. Addition of PCT to CRP increased specificity for bacterial AECOPD compared to CRP alone
      Yasar [47]CRP, RDW, MPV, PDWCRP, RDW and PDW were higher while MPV was lower in COPD. CRP, RDW and PDW were higher and MPV was lower in patients who had metabolic syndrome
      Lee [49]CRPCRP was higher in exacerbations than in healthy controls
      Duman [50]CRP, platelet/MPVCRP was significantly higher in the non-eosinophilic group. The platelet/MPV ratio was not different between the two groups. Survival negatively influenced by elevated CRP in the non-eosinophilic group
      Rahimirad [51]dNLR, MLR, PLRdNLR higher in dead patients than in those discharged alive. MLR and PLR not significant in multivariate analysis
      Yao [52]CRP, PLRNLR levels correlated with serum CRP levels in AECOPD. CRP and PLR levels higher in dead patients than in survivors. CRP AUC higher than that of PLR in predicting death
      Xiong [53]ESR, EBR, CRP, RDWEBR higher in COPD than in controls, and in survivors than in dead patients. EBR and CRP are predictors of mortality, not ESR or RDW
      Kumar [54]PLR, ureaPLR significantly associated to 90-days mortality, AUC poor
      Saltürk [55]CRP, platelet/MPVCRP >50 mg·mL−1 risk factor for mortality
      Sørensen [56]Calprotectin, YKL-40Correlation with calprotectin. In the group not treated with systemic glucocorticoids, plasma calprotectin was significantly associated with mortality. In the group treated with systemic glucocorticoids, higher plasma YKL-40 was significantly associated with mortality

      CRP: C-reactive protein; PDW: platelet distribution width; RDW: red cell distribution width; MPV: mean platelet volume; WBC: white blood cell; ESR: erythrocyte sedimentation rate; PLR: platelet to lymphocyte ratio; PCT: procalcitonin; dNLR: derived neutrophil to lymphocyte ratio; MLR: monocyte to lymphocyte ratio; EBR: eosinophil to basophil ratio; AECOPD: acute exacerbation of COPD; AUC: area under the curve.

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      Neutrophil to lymphocyte ratio and clinical outcomes in COPD: recent evidence and future perspectives
      Panagiotis Paliogiannis, Alessandro G. Fois, Salvatore Sotgia, Arduino A. Mangoni, Elisabetta Zinellu, Pietro Pirina, Silvia Negri, Ciriaco Carru, Angelo Zinellu
      European Respiratory Review Mar 2018, 27 (147) 170113; DOI: 10.1183/16000617.0113-2017

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      Neutrophil to lymphocyte ratio and clinical outcomes in COPD: recent evidence and future perspectives
      Panagiotis Paliogiannis, Alessandro G. Fois, Salvatore Sotgia, Arduino A. Mangoni, Elisabetta Zinellu, Pietro Pirina, Silvia Negri, Ciriaco Carru, Angelo Zinellu
      European Respiratory Review Mar 2018, 27 (147) 170113; DOI: 10.1183/16000617.0113-2017
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      • Article
        • Abstract
        • Abstract
        • Introduction
        • NLR in stable COPD and exacerbations
        • NLR and infections in COPD exacerbations
        • NLR as a prognostic marker in COPD
        • NLR in patients with COPD and other comorbidities
        • NLR and steroid therapy in COPD
        • Future perspectives
        • Conclusions
        • Footnotes
        • References
      • Figures & Data
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      Subjects

      • COPD and smoking
      • Epidemiology, occupational and environmental lung disease
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