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Development of a biomarker for lung inflammation in COPD through analysis of labelled leukocyte transit through the lung circulation

By Emma. H. Baker, Andrew Irwin, Amanda. L. Brennan, Brian Trost, Alan Britten, Sue Heenan and Barry Peterson


Measurement of pulmonary leukocyte margination could be a useful biomarker of lung inflammation in COPD, but analysis is complicated by recirculation of labeled leukocytes. 15 minutes of planar nuclear images were obtained after injecting autologous 99mTc-labeled leukocytes in 4 never-smoked controls, 6 stable mild/moderate and 2 exacerbating COPD patients. COPD patients were also imaged for 10 minutes after in vivo red blood cell (RBC) labeling with 99mTc and were re-imaged 2 weeks later to determine reproducibility. Activity as a function of time was measured in regions of interest over lungs and heart. A multi-compartment mathematical model was used to correct for recirculation but failed to provide a biomarker that clearly separated controls from COPD. A simpler model for activity in lungs and heart as a function of time (A(t)) was applied only to time points before recirculation: [A(t) = X1 x (1-exp(-X2 x t)) x exp(-X3 x t), where Xi are adjusted to match the data]. The ratio (R) of X3 (downslope of curve) in the lungs to X3 in the heart was investigated as a biomarker of margination. Values of R were reasonable (1.06±0.08 (SE)) for RBC (i.e. no margination) and 0.76±0.10 for controls (25% margination). In stable COPD patients R was significantly smaller (0.19±0.09, p<0.01) than controls and was reproducible (0.25±0.10). R during exacerbation was surprisingly large (0.88±0.22), possibly due to steroid treatment, but R was similar to stable COPD patients 2 weeks later (0.09±0.04). R requires only 2–3 minutes of imaging and may be a useful biomarker of margination. However it remains to be shown whether R truly reflects inflammation in COPD

Topics: Diseases of the respiratory system, RC705-779, Specialties of internal medicine, RC581-951, Internal medicine, RC31-1245, Medicine, R, DOAJ:Internal medicine, DOAJ:Medicine (General), DOAJ:Health Sciences
Publisher: European Respiratory Society
Year: 2006
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