Abstract

RATIONALE
Neutrophilic inflammation is understood to be of pathogenetic importance in chronic obstructive pulmonary disease (COPD) and may be quantified using 18-fluorodeoxyglucose positron emission tomography-computed tomography ((18)FDG PET-CT) as a noninvasive, spatially informative biomarker.
OBJECTIVES
To assess the potential usefulness of (18)FDG PET-CT as a surrogate measure of pulmonary neutrophilic inflammation in patients with usual COPD and α(1)-antitrypsin deficiency (AATD).
METHODS
(18)FDG PET-CT imaging was performed in 10 patients with usual COPD, 10 patients with AATD, and 10 healthy control subjects. Pulmonary (18)FDG 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. (18)FDG 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
(18)FDG 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 (FEV(1)% predicted, r = -0.848, P = 0.001; FEV(1)/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 (18)FDG 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).

Links

Publisher Full Text

Authors

Subramanian DR, Jenkins L, Edgar R, Quraishi N, Stockley RA, Parr DG

Institution

Department of Respiratory Medicine, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry, CV2 2DX, UK.

Source

American journal of respiratory and critical care medicine 186:11 2012 Dec 1 pg 1125-32

MeSH

Aged
Bronchitis
Cohort Studies
Cross-Sectional Studies
Female
Fluorodeoxyglucose F18
Forced Expiratory Volume
Great Britain
Humans
Inflammation Mediators
Male
Middle Aged
Neutrophil Activation
Positron-Emission Tomography and Computed Tomography
Pulmonary Disease, Chronic Obstructive
Reference Values
Respiratory Function Tests
Sensitivity and Specificity
Severity of Illness Index
Statistics, Nonparametric
alpha 1-Antitrypsin Deficiency

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22837375