Sputum neutrophils as a biomarker in COPD: findings from the ECLIPSE study.
BACKGROUND
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.
Singh
Dave
D
University of Manchester, Medicines Evaluation Unit, South Manchester University Hospitals Trust, Southmoor Road, Manchester M23 9QZ, UK. dsingh@meu.org.uk
Edwards
Lisa
L
Tal-Singer
Ruth
R
Rennard
Stephen
S
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002170:Canada; D005060:Europe; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007118:Immunoassay; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D016014:Linear Models; D008137:Longitudinal Studies; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009504:Neutrophils / Q000276:immunology*; D009520:New Zealand; D011379:Prognosis; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000000981:diagnostic imaging / Q000276:immunology* / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging / Q000276:immunology; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013183:Sputum / Q000166:cytology / Q000276:immunology*; D011795:Surveys and Questionnaires; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014481:United States
D015415:Biomarkers; C508606:CXCL8 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D037663:Pulmonary Surfactant-Associated Protein D; D002097:C-Reactive Protein