Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
J Nucl Med. 2011 Nov;52(11):1713-20. doi: 10.2967/jnumed.110.086355. Epub 2011 Oct 11.
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.
在哮喘中,气道炎症、气道高反应性和肺功能之间的关系尚不清楚。需要有非侵入性的方法来评估人类受试者的这些关系。我们旨在确定(18)F-FDG 摄取率(K(i),min(-1))是否可作为嗜酸性粒细胞炎症和局部肺功能的生物标志物。
我们使用 PET/CT 评估了 6 例特应性哮喘患者的右中叶节段性过敏原挑战后 10 小时的区域性肺灌注(Q)、单位体积特异性通气(sV(A))、气体分数(Fgas)、气道壁厚度和区域性 K(i)。将过敏原挑战叶的 Q、sV(A)和 Fgas 与应用稀释剂作为对照的右上叶进行比较。将过敏原挑战气道的壁厚度比(ω)与肺内未受影响区域的相似大小气道进行比较。将过敏原和稀释剂节段之间的 K(i)差异与各自节段支气管肺泡灌洗后 24 小时获得的细胞计数进行比较。
我们发现所有患者的区域性 Q、sV(A)和 Fgas 均系统性降低,ω 增加。在所有患者中,嗜酸粒细胞计数(过敏原与稀释剂)的比值与 K(i)的比值呈线性相关(R(2)= 0.9917,P <0.001)。
使用 PET 测量的局部 K(i)是非侵入性的,可高度预测嗜酸性气道炎症及其功能效应的生物标志物。该方法可能有助于了解过敏炎症,并测试新型药物或治疗方法的治疗效果。