BACKGROUND: Measurements of pulmonary biomarkers can be used to monitor airway inflammation in chronic obstructive pulmonary disease (COPD), but the variability of sampled biomarkers and their inter-relationships are poorly understood. A study was undertaken to examine the intra- and inter-patient variability in spontaneous sputum samples from patients in the stable state and to describe the relationship between biomarkers, cell counts and markers of disease. METHODS: Sputum interleukin-1beta, tumour necrosis factor alpha, interleukin 8, myeloperoxidase, leucotriene 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 a 1-month period. 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. Using a crossover design of a putative effective treatment, the number needed using one data point per patient was 72, reducing to 23 when a mean of three 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 patients with stable COPD. Sequential sampling reduced the variability of individual mediators and the potential number of patients needed to power proof of concept interventional studies.
BACKGROUND: Measurements of pulmonary biomarkers can be used to monitor airway inflammation in chronic obstructive pulmonary disease (COPD), but the variability of sampled biomarkers and their inter-relationships are poorly understood. A study was undertaken to examine the intra- and inter-patient variability in spontaneous sputum samples from patients in the stable state and to describe the relationship between biomarkers, cell counts and markers of disease. METHODS: Sputum interleukin-1beta, tumour necrosis factor alpha, interleukin 8, myeloperoxidase, leucotriene 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 a 1-month period. 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. Using a crossover design of a putative effective treatment, the number needed using one data point per patient was 72, reducing to 23 when a mean of three 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 patients with stable COPD. Sequential sampling reduced the variability of individual mediators and the potential number of patients needed to power proof of concept interventional studies.
Authors: Elizabeth Sapey; Ali Ahmad; Darren Bayley; Paul Newbold; Noel Snell; Paul Rugman; Robert A Stockley Journal: J Clin Immunol Date: 2009-03-17 Impact factor: 8.317
Authors: Shawn D Aaron; Katherine L Vandemheen; Timothy Ramsay; Chun Zhang; Zafrira Avnur; Tania Nikolcheva; Anthony Quinn Journal: Respir Res Date: 2010-04-22
Authors: Marc Miravitlles; Alicia Marín; Eduard Monsó; Sara Vilà; Cristian de la Roza; Ramona Hervás; Cristina Esquinas; Marian García; Laura Millares; Josep Morera; Antoni Torres Journal: Respir Res Date: 2010-05-14
Authors: Elizabeth Sapey; Hannah Greenwood; Georgia Walton; Elizabeth Mann; Alexander Love; Natasha Aaronson; Robert H Insall; Robert A Stockley; Janet M Lord Journal: Blood Date: 2013-11-04 Impact factor: 22.113