Bedi Pallavi, Chalmers James D, Graham Catriona, Clarke Andrea, Donaldson Samantha, Doherty Catherine, Govan John R W, Davidson Donald J, Rossi Adriano G, Hill Adam T
University of Edinburgh/MRC Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, Scotland.
School of Medicine, University of Dundee, Dundee, Scotland.
Chest. 2017 Aug;152(2):368-378. doi: 10.1016/j.chest.2017.05.017. Epub 2017 May 26.
There are no randomized controlled trials of statin therapy in patients with severe bronchiectasis who are chronically infected with Pseudomonas aeruginosa.
Thirty-two patients chronically infected with P aeruginosa were recruited in this double-blind cross-over randomized controlled trial. Sixteen patients were recruited in each arm, were given atorvastatin 80 mg or placebo for 3 months followed by a washout period for 6 weeks, and then crossed over and administered the alternative therapy for 3 months.
Twenty-seven patients completed the study. Atorvastatin did not significantly improve the primary end point of cough as measured by the Leicester Cough Questionnaire (mean difference, 1.92; 95% CI for difference, -0.57-4.41; P = .12). However, atorvastatin treatment resulted in an improved St. Georges Respiratory Questionnaire (-5.62 points; P = .016) and reduced serum levels of CXCL8 (P = .04), tumor necrosis factor (P = .01), and intercellular adhesion molecule 1 (P = .04). There was a trend toward improvement in serum C-reactive protein and serum neutrophil counts (P = .07 and P = .06, respectively). We demonstrated in vitro that atorvastatin 10 μM reduced formyl-methionyl-leucyl phenylalanine-induced upregulation of CD11b expression and changes in calcium flux, reflecting an ability to decrease neutrophil activation.
We demonstrated that atorvastatin reduced systemic inflammation and improved quality of life in patients with bronchiectasis who were infected with P aeruginosa. These effects may be due to an ability of atorvastatin to modulate neutrophil activation.
ClinicalTrials.gov; No.: NCT01299194; URL: www.clinicaltrials.gov.
对于长期感染铜绿假单胞菌的严重支气管扩张症患者，尚无他汀类药物治疗的随机对照试验。
在这项双盲交叉随机对照试验中招募了32例长期感染铜绿假单胞菌的患者。每组招募16例患者，给予阿托伐他汀80毫克或安慰剂治疗3个月，随后有6周的洗脱期，然后交叉使用另一种治疗3个月。
27例患者完成了研究。根据莱斯特咳嗽问卷测量，阿托伐他汀未显著改善咳嗽这一主要终点（平均差异为1.92；差异的95%置信区间为-0.57至4.41；P = 0.12）。然而，阿托伐他汀治疗使圣乔治呼吸问卷评分得到改善（-5.62分；P = 0.016），并降低了血清CXCL8水平（P = 0.04）、肿瘤坏死因子水平（P = 0.01）和细胞间黏附分子1水平（P = 0.04）。血清C反应蛋白和血清中性粒细胞计数有改善趋势（分别为P = 0.07和P = 0.06）。我们在体外证明，10 μM阿托伐他汀可降低甲酰甲硫氨酰亮氨酰苯丙氨酸诱导的CD11b表达上调和钙通量变化，这反映出其具有降低中性粒细胞活化的能力。
我们证明，阿托伐他汀可减轻感染铜绿假单胞菌的支气管扩张症患者的全身炎症并改善生活质量。这些作用可能归因于阿托伐他汀调节中性粒细胞活化的能力。
ClinicalTrials.gov；编号：NCT01299194；网址：www.clinicaltrials.gov。
