编辑:
我们饶有兴趣地阅读了五月刊上有关内毒素研究的文章欧洲呼吸杂志。通过的Bals社论1恰当地提出了关于时机的还没有答案的问题(急与慢性)和剂量相关的健康和疾病,以及这种接触的结果是始终不利的问题吸入内毒素。
为此,我们希望在第4周增加我们自身的耐受性吸入脂多糖(LPS)在健康人体非特重复曝光的可能性,初步观察。In a double-blind, crossover study, eight healthy human subjects were randomised to receiving either a single inhaled dose of 50 µg salmeterol or placebo prior to being challenged with a 15-µg dose of大肠杆菌血清型026:B6 (Sigma, Poole, UK),分两次就诊,间隔4周。以1周前为基线,LPS刺激后第6 h诱导的痰在两个治疗期间总细胞数的增加没有显著差异(平均差异(95%置信区间)沙美特罗与安慰剂:10.6×106细胞·mL的-1(-9.71-30.9);p = 0.25) or neutrophils (11.7×106细胞·mL的-1(-8.33-31.92);p = 0.20; unpublished data). The assertion that salmeterol does not protect against airway neutrophilic inflammation was subsequently supported in a more robust study, where subjects were randomised to receiving either daily salmeterol for 3 weeks or placebo, prior to inhaled LPS challenge, in a crossover study2。
对我们的研究结果进行回顾性的权力分析,首先提醒我们在序贯吸入LPS挑战的研究设计中存在固有的生物现象的可能性。然后对数据进行重新分析,目的是观察两种吸入挑战之间的痰中性粒细胞的可重复性,治疗单剂量沙美特罗的效果不比安慰剂2。我们的研究结果显示,继第一LPS挑战,平均总痰细胞计数增加31.23×106细胞·mL的-1(95% CI: 13.27-49.20)痰中性粒细胞计数平均上升30.3×106细胞·mL的-1(12.59 - -48.11)。而第二次LPS刺激后,平均痰细胞总数仅增加11.3×106细胞·mL的-1(2.14-24.89),平均痰中性粒细胞计数为10.9×106细胞·mL的-1(1.02 - -22.9)。两组间差异有统计学意义(p = 0.01;平均差:19.8×106细胞·mL的-1(6.16-33.56),用于总痰细胞计数;19.4×106细胞·mL的-1(4.73-34.08)痰中性粒细胞计数;图1⇓)。
利用这种人气道嗜中性粒细胞模型来了解内毒素的吸入效应3,并检查治疗药物的潜在抗炎特性2似乎是一个有效的方法。米歇尔等。3采用的模型每周吸入增量有限合伙人的挑战剂量(0.5µg 5µg和50µg)提供证据有限合伙人的剂量响应气道炎症和系统性影响人体健康。瓦林等。2测试沙美特罗的可能的抗炎作用与安慰剂,通过findings from bronchoscopy, based on a study design of inhaling 50 µg LPS on two occasions separated by ≥3 weeks. However, none of these studies had observed tolerance towards subsequent LPS challenge(s) in their healthy human subjects at doses of LPS described that were higher than ours. It is possible that tolerance in healthy nonatopic human subjects only occurs in exposure to lower doses of inhaled endoxin. In fact, existing literature indicates that exposure of 30–40 µg inhaled LPS is probably the clinical threshold to induce symptoms and lung function changes for healthy subjects4。
需要更多的研究来验证我们的初步观察。
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