Multiprobe Nuclear Imaging of the Cystic Fibrosis Lung as a Biomarker of Therapeutic Effect.
Multiprobe Nuclear Imaging of the Cystic Fibrosis Lung as a Biomarker of Therapeutic Effect.
复制标题
囊性纤维化肺的多探针核成像作为治疗效果的生物标志物。
DOI：
10.1089/jamp.2018.1491
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发表时间：
2019
影响因子：
3.4
通讯作者：
Pilewski,JosephM
中科院分区：
文献类型：
--
作者：
Corcoran,TimothyE;Huber,AlexS;Myerburg,MichaelM;Weiner,DanielJ;Locke,LandonW;Lacy,RyanT;Weber,Lawrence;Czachowski,MichaelR;Johnston,DarraghJ;Muthukrishnan,Ashok;Lennox,AlisonT;Pilewski,JosephM
背景：核成像生物标志物阐明了肺生理学的独特方面，并有助于评估囊性纤维化(CF)肺部疾病的治疗效果。我们开发了一种同时测量粘液纤毛清除(MCC)和细胞旁吸收(ABS)的多探针方法。MCC是粘液清除的直接量度。通过先前的体外研究，我们描述了影响呼吸道表面液体吸收的基线因素(n= 22)和吸入7%高渗盐水(HS)和干粉甘露醇的措施的反应(n= 7)。另设健康对照组(n= ，n=15)。基线组和对照组进行MCC/ABS的单项测量。结果：ABS与氯化汗液相关(Spearman‘sρ= 0.5 1，p= 0.0 6)，而微循环与囊性纤维化跨膜传导调节功能的系统性指标氯化汗相关。如我们先前所述，铜绿假单胞菌感染后，基线MCC降低。结论：与HS相比，MCC提供了更敏感的疗效指标，并提示甘露醇的清除能力有所提高。结论：MCC提供了一种有用且成熟的手段，可用于测试旨在改善肺粘液清除的治疗方法。ABS可提供一种检测肺内ASL吸收和CFTR功能局部变化的方法。两者都是研究CF肺病理生理学(ASL高吸收和MCC抑制)的关键方面的有用工具，这些关键方面将CF的基本遗传缺陷与肺部的疾病表现联系起来。
Background:Nuclear imaging biomarkers illustrate unique aspects of lung physiology and are useful for assessing therapeutic effects in cystic fibrosis (CF) lung disease. We have developed a multiprobe method to simultaneously measure mucociliary clearance (MCC) and paracellular absorption (ABS). MCC is a direct measure of mucus clearance. ABS has been related to airway surface liquid (ASL) absorption through previousin vitrostudies.Methods:We describe baseline factors affecting MCC and ABS using data from a retrospectivebaselinegroup (n= 22) and the response of the measures to inhaled 7% hypertonic saline (HS) and dry powder mannitol using data from a prospectiveresponsegroup (n= 7). A retrospective healthycontrolgroup (n= 15) is also described. Thebaselineandcontrolgroups performed single measurements of MCC/ABS. Theresponsegroup performed baseline measurements of MCC/ABS and measurements after each intervention.Results:ABS was correlated (Spearman'sρ= 0.51,p= 0.06) to sweat chloride, a systemic measure of cystic fibrosis transmembrane conductance regulator (CFTR) function, whereas MCC was not. Baseline MCC was depressed afterPseudomonas aeruginosainfection as we have previously described. MCC provided a more sensitive indication of therapeutic effect and indicated improved clearance with mannitol compared with HS.Conclusion:MCC provides a useful and well-established means of testing therapies directed at improving mucus clearance in the lung. ABS may provide a means of detecting local changes in ASL absorption and CFTR function in the lung. Both are useful tools for studying the key aspects of CF lung pathophysiology (ASL hyperabsorption and MCC depression) that link the basic genetic defects of CF to disease manifestations in the lung.