Granulocyte trafficking in chronic obstructive pulmonary disease

Ruparelia, P, Szczepura, K ORCID:, Bilton, D, Peters, AM and Chilvers, ER 2006, Granulocyte trafficking in chronic obstructive pulmonary disease , in: Winter British Thoracic Society (BTS) meeting 2006, December 2006.

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Introduction: Chronic obstructive pulmonary disease (COPD) is an inflammatory condition of the airways characterised by intense neutrophilia. We have used sub-imaging doses of 111 indium (111In) labelled granulocytes and high sensitivity whole body counting to assess neutrophil (PMN) trafficking and loss in patients with COPD. Methods: Participants were transfused with autologous 111In-labelled PMNs (0.2 mSv) isolated using discontinuous plasma Percoll gradients and subsequently underwent whole body counting over a 10 day period. A single slit collimator was placed on the lower detector in order to obtain a longitudinal profile of PMN distribution. 111In profile and whole body retention data were obtained at 45 minutes, day 1, 2, 4, 7, and 10 in 7 ex smoking (XS)-COPD patients (mean FEV1 0.9 l) and 9 currently smoking (CS)-COPD patients (mean FEV1 1.0 l), 10 bronchiectasis patients, 12 healthy non-smokers, and 5 healthy smokers. Daily sputum samples were counted for 111In. Results: Mean 111In PMN retention (SD) at day 7 were: non-smokers 94.5% (1.9), healthy smokers 93.5% (4.4), XS-COPD 94.2% (1.5), bronchiectasis 89.4% (8) but with a significant loss in the current smoker subgroup of COPD patients of 92.1% +/− 3 (p<0.05 compared to healthy non-smokers). The peak 111In signal in the sputum occurred at day 2 in both patient groups. At the initial scan (45 minutes) PMNs predominantly localised to the liver/spleen region in all patients. Thereafter cells additionally distributed to pelvic and thoracic areas. Thoracic SPECT using imaging doses of 99mTc-labelled PMNs (3 mSv) in 2 controls and 2 COPD subjects demonstrated 18.4% and 18.7% (values expressed as % of total thoracic activity) respectively of the 99mTc-PMN uptake over the lung at 4 hours post injection with the remaining signal in the rib and vertebral body bone marrow (BM) compartment. Patlak analysis demonstrated quantifiable uptake within the lung and bone marrow over 4 hours. Conclusion: Low dose autologous 111In neutrophil retention affords a measure of neutrophil loss through the airways, which appears to be more intense in CS-COPD and may be a useful method for monitoring granulocyte flux in CS COPD. This technique also permits accurate monitoring of PMN trafficking to the liver/spleen and BM compartments. Lung uptake is quantifiable using thoracic SPECT and Patlak analysis with less than 20% of the signal being within the lungs at 4 hours.

Item Type: Conference or Workshop Item (Poster)
Schools: Schools > School of Health and Society
Journal or Publication Title: Thorax
Publisher: BMJ Publishing Group
ISSN: 0040-6376
Related URLs:
Funders: AstraZeneca
Depositing User: K Szczepura
Date Deposited: 26 Feb 2021 13:47
Last Modified: 27 Aug 2021 21:50

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