Bennett W D, Wu J, Fuller F, Balcazar J R, Zeman K L, Duckworth H, Donn K H, O'Riordan T G, Boucher R C, Donaldson S H
Center for Environmental Medicine, Asthma, and Lung Biology and
Center for Environmental Medicine, Asthma, and Lung Biology and.
J Appl Physiol (1985). 2015 Jun 15;118(12):1483-90. doi: 10.1152/japplphysiol.00404.2014. Epub 2015 Apr 24.
Inhalation of hypertonic saline (HS) acutely enhances mucociliary clearance (MC) in both health and disease. In patients with cystic fibrosis (CF), repeated use of HS causes a sustained improvement in MC as well as clinical benefit. The pharmacodynamic duration of activity on MC may be an important determinant of its therapeutic potential in other airways diseases. Before moving toward testing the clinical benefits of HS for non-CF indications, we sought to assess the duration of pharmacodynamic effects of HS in healthy subjects by performing radiotracer clearance studies at baseline, 30-min post-HS administration, and 4-h post-HS administration. Indeed, acceleration of MC was observed when measured 30 min after HS inhalation. This acceleration was most pronounced in the first 30 min after inhaling the radiotracer in the central lung region (mean Ave30Clr = 15.5 vs. 8.6% for 30-min post-HS treatment vs. mean baseline, respectively, P < 0.005), suggesting that acute HS effects were greatest in the larger bronchial airways. In contrast, when MC was measured 4 h after HS administration, all indices of central lung region MC were slower than at baseline: Ave30Clr = 5.9% vs. 8.6% (P = 0.10); Ave90Clr = 12.4% vs. 16.8% (P < 0.05); clearance through 3 h = 29.4 vs. 43.7% (P < 0.002); and clearance through 6 h = 39.4 vs. 50.2% (P < 0.02). This apparent slowing of MC in healthy subjects 4-h post-HS administration may reflect depletion of airway mucus following acute HS administration.
吸入高渗盐水（HS）在健康人和患病者中均可急性增强黏液纤毛清除功能（MC）。在囊性纤维化（CF）患者中，重复使用HS可使MC持续改善，并带来临床益处。HS对MC的药效学作用持续时间可能是其在其他气道疾病中治疗潜力的重要决定因素。在尝试测试HS用于非CF适应症的临床益处之前，我们试图通过在基线、HS给药后30分钟和HS给药后4小时进行放射性示踪剂清除研究，评估HS在健康受试者中的药效学作用持续时间。事实上，在HS吸入后30分钟测量时，观察到MC加速。这种加速在吸入放射性示踪剂后的前30分钟在肺中央区域最为明显（HS治疗后30分钟的平均Ave30Clr分别为15.5%和8.6%，而平均基线为8.6%，P < 0.005），这表明急性HS作用在较大的支气管气道中最为显著。相比之下，在HS给药后4小时测量MC时，肺中央区域MC的所有指标均比基线时慢：Ave30Clr = 5.9%对8.6%（P = 0.10）；Ave90Clr = 12.4%对16.8%（P < 0.05）；3小时的清除率 = 29.4%对43.7%（P < 0.002）；6小时的清除率 = 39.4%对50.2%（P < 0.02）。HS给药后4小时健康受试者中MC的这种明显减慢可能反映了急性HS给药后气道黏液的消耗。
