Granulocyte trafficking in chronic obstructive pulmonary disease

Ruparelia, P; Szczepura, K; Bilton, D; Peters, AM; Chilvers, ER

Abstract

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.

Citation

Ruparelia, P., Szczepura, K., Bilton, D., Peters, A., & Chilvers, E. (2006). Granulocyte trafficking in chronic obstructive pulmonary disease. Thorax, 61(Sup. 2), ii108-ii109

• Journal Article Type: Conference Paper
• Conference Name: Winter British Thoracic Society (BTS) meeting 2006
• Start Date: Dec 1, 2006
• Publication Date: Nov 17, 2006
• Deposit Date: Feb 26, 2021
• Journal: Thorax
• Print ISSN: 0040-6376
• Electronic ISSN: 1468-3296
• Publisher: BMJ Publishing Group
• Volume: 61
• Issue: Sup. 2
• Pages: ii108-ii109
• Publisher URL: https://thorax.bmj.com/content/61/suppl_2/ii57
• Related Public URLs: http://thorax.bmj.com/
• Additional Information: Event Type : Conference; Funders : AstraZeneca