18F-FDG Uptake Rate Is a Biomarker of Eosinophilic Inflammation and Airway Response in Asthma

Abstract

In asthma, the relationship among airway inflammation, airway hyperresponsiveness, and lung function is poorly understood. Methods to noninvasively assess these relationships in human subjects are needed. We sought to determine whether (18)F-FDG uptake rate (K(i), min(-1)) could serve as a biomarker of eosinophilic inflammation and local lung function. We used PET/CT to assess regional pulmonary perfusion (Q), specific ventilation per unit volume (sV(A)), fractional gas content (Fgas), airway wall thickness, and regional K(i) 10 h after segmental allergen challenge to the right middle lobe in 6 asthmatic subjects with demonstrated atopy. Q, sV(A), and Fgas in the allergen-challenged lobe were compared with the right upper lobe, where diluent was applied as a control. The airway wall thickness aspect ratio (ω) of the allergen-challenged airway was compared with those of similarly sized airways from unaffected areas of the lung. Differences in K(i) between allergen and diluent segments were compared with those in cell counts obtained 24 h after the allergen challenge by a bronchoalveolar lavage of the respective segments. We found systematic reductions in regional Q, sV(A), and Fgas and increased ω in all subjects. The ratio of eosinophil count (allergen to diluent) was linearly related (R(2) = 0.9917, P < 0.001) to the ratio of K(i). Regional K(i) measured with PET is a noninvasive and highly predictive biomarker of eosinophilic airway inflammation and its functional effects. This method may serve to help in the understanding of allergic inflammation and test the therapeutic effectiveness of novel drugs or treatments.