S65 Quantification of ‘whole lung’ pulmonary eosinophilic inflammation using radiolabelled autologous human eosinophils

Abstract

Eosinophils are key mediators of allergic inflammation. The ability to localise and quantify eosinophilic inflammation in vivo would facilitate patient endotyping and evaluation of eosinophil-targeted therapeutics. We aimed to quantify eosinophil distribution and organ-specific uptake in healthy subjects, asthmatics, and patients with focal pulmonary eosinophilic inflammation. We injected autologous radiolabelled eosinophils into 8 healthy volunteers, 15 asthmatics (7 obese and 7 non-obese), and 3 patients with focal eosinophilic inflammation and monitored eosinophil distribution (planar imaging, single photon emission computed tomography – SPECT)/CT). Lung accumulation of technetium-99 m-labelled eosinophils was quantified (Patlak-Rutland analysis). Whole body indium-111-labelled eosinophil distribution and loss were further assessed in 5 healthy volunteers and 7 asthmatics using a whole body counter. Pulmonary eosinophil clearance was increased in patients with focal eosinophilia (0·0033 ml/min/ml; 95% CI −0·005–0·011; p=0.02) compared to asthmatics (0·0007 ml/min/ml; 95% CI 0·0003–0·0010; p=0.14) and controls (0·0003 ml/min/ml; 95% CI −7·5 × 10–5–0·0008). Absolute lung eosinophil migration was elevated in patients with focal inflammation (5932 eosinophils/min/ml; 95% CI −14351–26215, p=0.01) and asthma (364 eosinophils/min/ml; 95% CI 38–689; p=0.03) versus healthy volunteers (38 eosinophils/min/ml; 95% CI −11–87). Stratification of asthmatics based on BMI revealed increased pulmonary eosinophil clearance in obese (0·001 ml/min/ml; 95% CI 0·0007–0·001; p=0.02) versus non-obese asthmatics (0·0003 ml/min/ml; 95% CI −0·0002–0·0009). Eosinophil radiolabelling can quantify pulmonary eosinophilic inflammation, with the potential for patient endotyping and testing eosinophil-targeted treatments. Medical Research Council, Wellcome Trust, Asthma UK, Cambridge NIHR Biomedical Research Centre.