Assessment of pulmonary neutrophilic inflammation in emphysema by quantitative positron emission tomography

Abstract

Rationale: Neutrophilic inflammation is understood to be of pathogenetic importance in chronic obstructive pulmonary disease (COPD) andmay be quantified using 18-fluorodeoxyglucose positron emission tomography-computed tomography (18FDGPET-CT) as a noninvasive, spatially informative biomarker. Objectives: To assess the potential usefulness of 18FDG PET-CT as a surrogate measure of pulmonary neutrophilic inflammation in patients with usual COPD and α1-antitrypsin deficiency (AATD). Methods: 18FDG PET-CT imaging was performed in 10 patients with usual COPD, 10 patients with AATD, and 10 healthy control subjects. Pulmonary 18FDG uptake was estimated by three-dimensional Patlak graphical analysis as an indicator of pulmonary neutrophilic glycolytic activity. Patients with AATD were treated with 12 weekly intravenous infusions of AAT augmentation therapy before repeat imaging. 18FDG uptake, lung physiology, lung density, and systemic markers of inflammation were compared for all groups at baseline and, in patients with AATD, at baseline and on treatment. Measurements and Main Results: 18FDG uptake in the upper lung of patients with usual COPD was greater compared with the healthy control group (P = 0.009) and correlated with measures of disease severity (FEV1% predicted, r = -0.848, P = 0.001; FEV1/FVC, r = -0.918, P < 0.001; KCO% predicted, r = -0.624, P = 0.027; 15th percentile point, r = -0.709, P = 0.011). No significant difference was observed between measurements at baseline and on treatment in patients with AATD. Conclusions: Quantitative 18FDG PET-CT has a potential role as an imaging biomarker in mechanistic and interventional studies in patients with usual COPD. The data support previous evidence of distinct functional characteristics of neutrophils in COPD. Clinical trial registered with https://eudract.ema.europa.eu/index. html (EudraCT 2007-004869-18). Copyright © 2012 by the American Thoracic Society.