| Autor: |
Farahi, N, Loutsios, S, Tregay, N, Wright, AKA, Lok, LSC, Gillett, D, Cullum, I, Simmonds, RP, Summers, C, Wong, A, Solanki, CK, Buscombe, J, Pang, PH, Thavakumar, A, Peters, AM, Brightling, CE, Condliffe, AM, Chilvers, ER |
| Zdroj: |
Thorax; 2017, Vol. 72 Issue: Supplement 3 pA41-A41, 1p |
| Abstrakt: |
BackgroundEosinophils are key mediators of allergic inflammation. The ability to localise and quantify eosinophilic inflammation in vivowould 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.MethodsWe 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.FindingsPulmonary 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).InterpretationEosinophil radiolabelling can quantify pulmonary eosinophilic inflammation, with the potential for patient endotyping and testing eosinophil-targeted treatments.FundingMedical Research Council, Wellcome Trust, Asthma UK, Cambridge NIHR Biomedical Research Centre. |
| Databáze: |
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