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

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

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.

Trial registration: ClinicalTrials.gov NCT00292552.

Figures

Figure 1
Figure 1
Sputum neutrophil % shown according to GOLD stage at baseline and year 1. Medians (lines), interquartile ranges (boxes) and ranges (error bars) are shown.
Figure 2
Figure 2
Bland Altman plots of the mean measurements at baseline and 1 year (x-axis) and the difference between the measurements (year 1 - baseline shown on y-axis) for (a) log10 sputum neutrophil numbers/ml and (b) sputum neutrophil % counts.
Figure 3
Figure 3
Power calculations for a reduction in sputum neutrophil % in a parallel group study. Y axis is the number of subjects required. X axis is the effect size (e.g. 0.9 = 10% reduction).

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