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      Association of the Neutrophil-to-Lymphocyte Ratio with Lung Function and Exacerbations in Patients with Chronic Obstructive Pulmonary Disease

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          Abstract

          Background

          The ratio of neutrophils to lymphocytes (NLR) is a widely available marker of inflammation. Several types of inflammatory cells and mediators have been found to be involved in the progression of chronic obstructive pulmonary disease (COPD). We sought to evaluate the association of the NLR with severity of airflow limitation and disease exacerbations in a COPD population.

          Methods

          We analyzed 885 patients from the Korean COPD Subtype Study cohort that recruited subjects with COPD from 44 referral hospitals. We determined the relationship of NLR levels to severity of lung function using a linear regression model. In addition, we analyzed the experiences of COPD exacerbation according to the NLR quartiles.

          Results

          NLR levels were inversely associated with severity of airflow limitation as measured by FEV 1% predicted and absolute values after adjustments for age, gender, body mass index, pack-years of smoking, and the use of inhaled corticosteroid (P<0.001, respectively). In the multivariate binary regression model, the NLR 4th quartile (vs. 1st quartile) was found to be a significant predictor of exacerbations during 1-year follow-up (OR = 2.05, 95% CI = 1.03 to 4.06, P = 0.041). Adding an NLR to FEV 1 significantly improved prediction for exacerbations during 1-year follow-up as measured by the net reclassification improvement (NRI = 7.8%, P = 0.032) and the integrated discrimination improvement (IDI = 0.014, P = 0.021).

          Conclusions

          The NLR showed a significant inverse relationship to airflow limitation and was a prognostic marker for future exacerbations in patients with COPD.

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          Most cited references13

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          Susceptibility to exacerbation in chronic obstructive pulmonary disease.

          John R. Hurst, Jørgen Vestbo, Antonio Anzueto … (2010)
          Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)
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            Persistent lymphopenia after diagnosis of sepsis predicts mortality.

            Anne Drewry, Navdeep Samra, Lee P Skrupky … (2014)
            The objective of this study was to determine whether persistent lymphopenia on the fourth day following the diagnosis of sepsis predicts mortality.
            Article 0 comments Cited 184 times – based on 0 reviews     Review now
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              C-reactive protein as a predictor of prognosis in chronic obstructive pulmonary disease.

              Borge Nordestgaard, Jorgen Vestbo, Peter Lange … (2007)
              Patients with chronic obstructive pulmonary disease (COPD) have an ongoing systemic inflammation, which can be assessed by measuring serum C-reactive protein (CRP). To determine whether increased serum CRP in individuals with airway obstruction predicts future hospitalization and death from COPD. We performed a cohort study with a median of 8-yr follow-up of 1,302 individuals with airway obstruction selected from the ongoing Copenhagen City Heart Study. We measured serum CRP at baseline, and recorded COPD admissions and deaths as outcomes. During follow-up, 185 (14%) individuals were hospitalized due to COPD and 83 (6%) died of COPD. Incidences of COPD hospitalization and COPD death were increased in individuals with baseline CRP > 3 mg/L versus 3 mg/L versus < or = 3 mg/L. After close matching for FEV(1)% predicted and adjusting for potential confounders, baseline CRP was, on average, increased by 1.2 mg/L (analysis of variance: p = 0.002) and 4.1 mg/L (p = 0.001) in those who were subsequently hospitalized or died of COPD, respectively. The absolute 10-yr risks for COPD hospitalization and death in individuals with CRP above 3 mg/L were 54 and 57%, respectively, among those older than 70 yr with a tobacco consumption above 15 g/d and an FEV(1)% predicted of less than 50. CRP is a strong and independent predictor of future COPD outcomes in individuals with airway obstruction.
              Article 0 comments Cited 115 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Stelios Loukides: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 3 June 2016
                Publication date Collection: 2016
                Volume: 11
                Issue: 6
                Electronic Location Identifier: e0156511
                Affiliations
                [1 ]Department of Internal Medicine, Dong-A University College of Medicine, Busan, Republic of Korea
                [2 ]Department of Internal Medicine, Pusan National University College of Medicine, Busan, Republic of Korea
                [3 ]Department of Internal Medicine, Seoul National University College of Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea
                [4 ]Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea
                [5 ]Department of Internal Medicine, Dongguk University Gyeongju Hospital, Gyeongju, Republic of Korea
                [6 ]Department of Internal Medicine, Kyung Hee University Gangdong Hospital, Seoul, Republic of Korea
                [7 ]Department of Internal Medicine, Konkuk University College of Medicine, Seoul, Republic of Korea
                [8 ]Department of Clinical Pharmacology, Konkuk University College of Medicine, Seoul, Republic of Korea
                [9 ]Department of Internal Medicine, Hallym University College of Medicine, Anyang, Republic of Korea
                University of Athens, GREECE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: SJU KSJ KHY YSK. Analyzed the data: SJU HL TEK. Contributed reagents/materials/analysis tools: ASJ DKK HSC YHK. Wrote the paper: HL SJU.

                Article
                Publisher ID: PONE-D-16-01020
                DOI: 10.1371/journal.pone.0156511
                PMC ID: 4892618
                PubMed ID: 27258044
                SO-VID: a4935377-3f47-4caf-b97c-c93e985ad604
                Copyright © © 2016 Lee et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 12 January 2016
                Date accepted : 16 May 2016
                Page count
                Figures: 3, Tables: 4, Pages: 12
                Funding
                Funded by: Dong-A University (research fund)
                Award Recipient :
                This study was supported by research funds from Dong-A University.
                Categories
                Subject: Research Article
                Subject: Medicine and Health Sciences
                Subject: Pulmonology
                Subject: Chronic Obstructive Pulmonary Disease
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Blood Cells
                Subject: White Blood Cells
                Subject: Neutrophils
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Immune Cells
                Subject: White Blood Cells
                Subject: Neutrophils
                Subject: Biology and Life Sciences
                Subject: Immunology
                Subject: Immune Cells
                Subject: White Blood Cells
                Subject: Neutrophils
                Subject: Medicine and Health Sciences
                Subject: Immunology
                Subject: Immune Cells
                Subject: White Blood Cells
                Subject: Neutrophils
                Subject: Medicine and Health Sciences
                Subject: Inflammatory Diseases
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Blood Cells
                Subject: White Blood Cells
                Subject: Lymphocytes
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Immune Cells
                Subject: White Blood Cells
                Subject: Lymphocytes
                Subject: Biology and Life Sciences
                Subject: Immunology
                Subject: Immune Cells
                Subject: White Blood Cells
                Subject: Lymphocytes
                Subject: Medicine and Health Sciences
                Subject: Immunology
                Subject: Immune Cells
                Subject: White Blood Cells
                Subject: Lymphocytes
                Subject: Medicine and Health Sciences
                Subject: Pulmonology
                Subject: Dyspnea
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Physiological Parameters
                Subject: Body Weight
                Subject: Body Mass Index
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Physiological Parameters
                Subject: Body Weight
                Subject: Body Mass Index
                Subject: Medicine and Health Sciences
                Subject: Diagnostic Medicine
                Subject: Signs and Symptoms
                Subject: Lymphopenia
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Signs and Symptoms
                Subject: Lymphopenia
                Subject: Medicine and Health Sciences
                Custom metadata
                Data Availability All relevant data are within the paper and its Supporting Information files. The whole cohort data are available from Korean COPD Subtype Study (KOCOSS) data base. The site URL is http://copd.crf.kr/Pages/Membership/Login.aspx?ReturnUrl=%2f. Contact for data access is Kwang Ha Yoo (Email address: khyou@ 123456kuh.ac.kr ).

                ScienceOpen disciplines: Uncategorized
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                ScienceOpen disciplines: Uncategorized

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