Top

Respiratory Research

Published in:

Open Access 01-12-2010 | Research

Sputum neutrophils as a biomarker in COPD: findings from the ECLIPSE study

Authors: Dave Singh, Lisa Edwards, Ruth Tal-Singer, Stephen Rennard

Published in: Respiratory Research | Issue 1/2010

Abstract

Introduction

The percentage of neutrophils in sputum are increased in COPD patients, and may therefore be a biomarker of airway inflammation. We studied the relationships between sputum neutrophils and FEV₁, health status, exacerbation rates, systemic inflammation and emphysema, and long term variability at 1 year.

Methods

Sputum samples were obtained from 488 COPD patients within the ECLIPSE cohort. 359 samples were obtained at baseline, and 297 after 1 year. 168 subjects provided samples at both visits. Serum interleukin-6 (IL-6), IL-8, surfactant protein D and C-reactive protein levels were measured by immunoassays. Low-dose CT scans evaluated emphysema.

Results

Sputum neutrophil % increased with GOLD stage. There was a weak association between % sputum neutrophils and FEV₁ % predicted (univariate r² = 0.025 and 0.094 at baseline and year 1 respectively, p < 0.05 after multivariate regression). Similar weak but significant associations were observed between neutrophil % and health status measured using the St Georges Respiratory Questionairre. There were no associations between neutrophils and exacerbation rates or emphysema. Associations between sputum neutrophils and systemic biomarkers were non-significant or similarly weak. The mean change over 1 year in neutrophil % was an increase of 3.5%.

Conclusions

Sputum neutrophil measurements in COPD are associated weakly with FEV₁ % predicted and health status. Sputum neutrophil measurements were dissociated from exacerbation rates, emphysema and systemic inflammation.

Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO, Paré PD: The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Eng J Med 2004, 350:2645–2652.CrossRef

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) [http://www.goldcopd.com]

Barnes PJ, Chowdhury B, Kharitonov SA, Magnussen H, Page CP, Postma D, Saetta M: Pulmonary biomarkers in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2006, 174:6–14.CrossRefPubMed

O'Donnell RA, Peebles C, Ward JA, Daraker A, Angco G, Broberg P, Pierrou S, Lund J, Holgate ST, Davies DE, Delany DJ, Wilson SJ, Djukanovic R: Relationship between peripheral airway dysfunction, airway obstruction, and neutrophilic inflammation in COPD. Thorax 2004, 59:837–42.CrossRefPubMedPubMedCentral

Keatings VM, Collins PD, Scott DM, Barnes PJ: Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med 1996, 153:530–4.CrossRefPubMed

Rutgers SR, Timens W, Kaufmann HF, van der Mark TW, Koëter GH, Postma DS: Comparison of induced sputum with bronchial wash, bronchoalveolar lavage and bronchial biopsies in COPD. Eur Respir J 2000, 15:109–15.CrossRefPubMed

Cowburn AS, Condliffe AM, Farahi N, Summers C, Chilvers ER: Advances in neutrophil biology: clinical implications. Chest 2008, 134:606–12.CrossRefPubMedPubMedCentral

Yanbaeva DG, Dentener MA, Spruit MA, Houwing-Duistermaat JJ, Kotz D, Passos VL, Wouters EF: IL6 and CRP haplotypes are associated with COPD risk and systemic inflammation: a case-control study. BMC Med Genet 2009, 10:23.CrossRefPubMedPubMedCentral

Chung KF, Adcock IM: Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction. Eur Respir J 2008, 31:1334–56.CrossRefPubMed

10.

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, 59:574–80.CrossRefPubMedPubMedCentral

11.

Vestbo J, Anderson W, Coxson HO, Crim C, Dawber F, Edwards L, Hagan G, Knobil K, Lomas DA, MacNee W, Silverman EK, Tal-Singer R: ECLIPSE investigators. Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE). Eur Respir J 2008, 31:869–73.CrossRefPubMed

12.

Pizzichini E, Pizzichini MM, Efthimiadis A, Evans S, Morris MM, Squillace D, Gleich GJ, Dolovich J, Hargreave FE: Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med 1996, 154:308–17.CrossRefPubMed

13.

Coxson HO, Rogers RM, Whittall KP, D'yachkova Y, Paré PD, Sciurba FC, Hogg JC: A quantification of the lung surface area in emphysema using computed tomography. Am J Respir Crit Care Med 1999, 159:851–856.CrossRefPubMed

14.

O'Donnell RA, Peebles C, Ward JA, Daraker A, Angco G, Broberg P, Pierrou S, Lund J, Holgate ST, Davies DE, Delany DJ, Wilson SJ, Djukanovic Rl: Relationship between peripheral airway dysfunction, airway obstruction, and neutrophilic inflammation in COPD. Thorax 2004, 59:837–42.CrossRefPubMedPubMedCentral

15.

Roy K, Smith J, Kolsum U, Borrill Z, Vestbo J, Singh D: COPD phenotype description using principal components analysis. Respir Res 2009, 10:41.CrossRefPubMedPubMedCentral

16.

Lapperre TS, Snoeck-Stroband JB, Gosman MM, Stolk J, Sont JK, Jansen DF, Kerstjens HA, Postma DS, Sterk PJ: Dissociation of lung function and airway inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004, 170:499–504.CrossRefPubMed

17.

Donaldson GC, Seemungal TA, Patel IS, Bhowmik A, Wilkinson TM, Hurst JR, Maccallum PK, Wedzicha JA: Airway and systemic inflammation and decline in lung function in patients with COPD. Chest 2005, 128:1995–2004.CrossRefPubMed

18.

Stanescu D, Sanna A, Veriter C, Kostianev S, Calcagni PG, Fabbri LM, Maestrelli P: Airways obstruction, chronic expectoration, and rapid decline of FEV1 in smokers are associated with increased levels of sputum neutrophils. Thorax 1996, 51:267–71.CrossRefPubMedPubMedCentral

19.

Sharafkhaneh A, Hanania NA, Kim V: Pathogenesis of emphysema: from the bench to the bedside. Proc Am Thorac Soc 2008, 5:475–7.CrossRefPubMedPubMedCentral

20.

Boschetto P, Quintavalle S, Zeni E, Leprotti S, Potena A, Ballerin L, Papi A, Palladini G, Luisetti M, Annovazzi L, Iadarola P, De Rosa E, Fabbri LM, Mapp CE: Association between markers of emphysema and more severe chronic obstructive pulmonary disease. Thorax 2006, 61:1037–42.CrossRefPubMedPubMedCentral

21.

Caramori G, Romagnoli M, Casolari P, Bellettato C, Casoni G, Boschetto P, Chung KF, Barnes PJ, Adcock IM, Ciaccia A, Fabbri LM, Papi A: Nuclear localisation of p65 in sputum macrophages but not in sputum neutrophils during COPD exacerbations. Thorax 2003, 58:348–51.CrossRefPubMedPubMedCentral

22.

Papi A, Bellettato CM, Braccioni F, Romagnoli M, Casolari P, Caramori G, Fabbri LM, Johnston SL: Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med 2006, 173:1114–21.CrossRefPubMed

23.

Soler-Cataluña JJ, Martínez-García MA, Román Sánchez P, Salcedo E, Navarro M, Ochando R: Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax 2005, 60:925–31.CrossRefPubMedPubMedCentral

24.

Snoeck-Stroband JB, Postma DS, Lapperre TS, Gosman MM, Thiadens HA, Kauffman HF, Sont JK, Jansen DF, Sterk PJ: Airway inflammation contributes to health status in COPD: a cross-sectional study. Respir Res 2006, 7:140.CrossRefPubMedPubMedCentral

25.

Beeh K, Beier J, Kornmann O, Mander A, Buhl R: Long-term Repeatability of Induced Sputum Cells and Inflammatory Markers in Stable, Moderately Severe COPD. Chest 2003, 123:778–83.CrossRefPubMed

26.

Brightling C, Monteiro W, Green R, Parker D, Morgan MD, Wardlaw AJ, Pavord D: Induced sputum and other outcome measures in chronic obstructive pulmonary disease: safety and repeatability. Respiratory Medicine 2001, 95:999–1002.CrossRefPubMed

27.

Chapman RW, Phillips JE, Hipkin RW, Curran AK, Lundell D, Fine JS: CXCR2 antagonists for the treatment of pulmonary disease. Pharmacol Ther 2009, 121:55–68.CrossRefPubMed

Title: Sputum neutrophils as a biomarker in COPD: findings from the ECLIPSE study
Authors: Dave Singh
Lisa Edwards
Ruth Tal-Singer
Stephen Rennard
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Respiratory Research / Issue 1/2010
Electronic ISSN: 1465-993X
DOI: https://doi.org/10.1186/1465-9921-11-77

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2010

Systems-level comparison of host responses induced by pandemic and seasonal influenza A H1N1 viruses in primary human type I-like alveolar epithelial cells in vitro

Health status in COPD cannot be measured by the St George's Respiratory Questionnaire alone: an evaluation of the underlying concepts of this questionnaire

New methodology for specific inhalation challenges with occupational agents

Systemic inflammation in chronic obstructive pulmonary disease: a population-based study

Interleukin-17 regulation: an attractive therapeutic approach for asthma

Identification of lung cancer with high sensitivity and specificity by blood testing

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials