TY - JOUR
T1 - 18F-FDG uptake rate is a biomarker of eosinophilic inflammation and airway response in asthma
AU - Harris, R. Scott
AU - Venegas, José G.
AU - Wongviriyawong, Chanikarn
AU - Winkler, Tilo
AU - Kone, Mamary
AU - Musch, Guido
AU - Vidal Melo, Marcos F.
AU - De Prost, Nicolas
AU - Hamilos, Daniel L.
AU - Afshar, Roshi
AU - Cho, Josalyn
AU - Luster, Andrew D.
AU - Medoff, Benjamin D.
PY - 2011/11/1
Y1 - 2011/11/1
N2 - 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 18F-FDG uptake rate (K i, min -1) could serve as a biomarker of eosinophilic inflammation and local lung function. Methods: We used PET/CT to assess regional pulmonary perfusion (Q̇), specific ventilation per unit volume (sV̇ 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. Q̇, sV̇ 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. Results: We found systematic reductions in regional Q̇, sV̇ A, and Fgas and increased v 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. Conclusion: 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.
AB - 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 18F-FDG uptake rate (K i, min -1) could serve as a biomarker of eosinophilic inflammation and local lung function. Methods: We used PET/CT to assess regional pulmonary perfusion (Q̇), specific ventilation per unit volume (sV̇ 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. Q̇, sV̇ 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. Results: We found systematic reductions in regional Q̇, sV̇ A, and Fgas and increased v 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. Conclusion: 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.
KW - Airway constriction
KW - Emission-computed tomography
KW - Fluorine isotopes
KW - Nitrogen isotopes
KW - Pulmonary gas exchange
KW - Ventilation-perfusion ratio
UR - http://www.scopus.com/inward/record.url?scp=80455168443&partnerID=8YFLogxK
U2 - 10.2967/jnumed.110.086355
DO - 10.2967/jnumed.110.086355
M3 - Article
C2 - 21990575
AN - SCOPUS:80455168443
SN - 0161-5505
VL - 52
SP - 1713
EP - 1720
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 11
ER -