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Inter-relationships between inflammatory markers in stable COPD patients with bronchitis: the intra and inter patient variability
  1. Elizabeth Sapey
  1. University Hospital Birmingham NHS Foundation Trust, United Kingdom
    1. Darren Bayley
    1. University Hospital Birmingham NHS Foundation Trust, United Kingdom
      1. Ali Ahmad
      1. University of Birmingham, United Kingdom
        1. Paul Newbold
        1. AstraZeneca R&D Charnwood, United Kingdom
          1. Noel Snell
          1. AstraZeneca R&D Charnwood, United Kingdom
            1. Robert A Stockley (r.a.stockley{at}bham.ac.uk)
            1. University Hospital Birmingham NHS Foundation Trust, United Kingdom

              Abstract

              Rationale: Measurements of pulmonary biomarkers can be used to monitor airway inflammation in COPD but the variability of sampled biomarkers and their inter relationships are poorly understood.

              Objectives: to describe the intra and inter-patient variability in spontaneous sputum samples from patients in the stable state and to describe the relationships between biomarkers, cell counts and markers of disease.

              Methods: Sputum Interleukin-1beta, Tumour necrosis factor alpha, Interleukin 8, Myeloperoxidase, Leukotriene B4, Growth related oncogene alpha and differential cell counts were measured in patients with moderate to severe stable COPD (n = 14) on 11 occasions over one month.

              Measurements and main results: There was significant variability in all inflammatory indices (median intra-patient coefficient of variation (CV) = 35% (IQR 22 - 69), median inter-patient CV = 102% (IQR 61 - 145)). Variability could be reduced by using a rolling mean of individual patient data points. Sample size calculations were undertaken to determine the number of patients required to detect a 50% reduction in neutrophil count. Utilising a cross-over design of a putative effective therapy, the number needed using one data point per patient was 72, reducing to 23 when the mean of 3 data points was used.

              Significant correlations were demonstrated both between the inflammatory biomarkers themselves and between inflammatory biomarkers and markers of disease. Some relationships were not apparent when results from a single sample were used. The reliability of inter-relationships improved as more data points were used for each patient.

              Conclusions: Clear relationships exist between inflammatory biomarkers in stable COPD patients. Sequential sampling reduced the variability of individual mediators and the potential number of patients needed to power proof of concept interventional studies.

              • COPD
              • Lung disease
              • Obstructive
              • Spontaneous sputum
              • Sputum biomarkers

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