一项随机对照初级保健试验，比较类固醇滴定与甘露醇治疗持续性哮喘的效果：STAMINA 试验。

A randomized primary care trial of steroid titration against mannitol in persistent asthma: STAMINA trial.

机构信息

Asthma and Allergy Research Group, Ninewells Hospital and Medical School, University of Dundee, Dundee.

出版信息

Chest. 2012 Mar;141(3):607-615. doi: 10.1378/chest.11-1748. Epub 2011 Oct 13.

DOI:10.1378/chest.11-1748

PMID:21998259

Abstract

BACKGROUND

We compared titrating inhaled corticosteroid (ICS) against mannitol airway hyperresponsiveness (AHR) or a reference strategy (control) based on symptoms, reliever use, and lung function in primary care.

METHODS

One hundred sixty-four patients with persistent asthma were randomized in parallel group fashion following an initial ICS tapering. Subsequent ICS doses (as ciclesonide) were titrated against either the provocative dose of mannitol causing a 10% fall in FEV(1) (PD(10)) (AHR strategy) or a control group (reference strategy) over a 1-year period.

RESULTS

One hundred nineteen participants (n = 61 AHR, n = 58 control) completed the study. Time to first mild exacerbation was not significantly different: hazard ratio, 1.29; 95% CI, 0.716-2.31; P = .40. Although there were 27% fewer total number of mild exacerbations over 12 months in AHR vs control groups (n = 84 vs n = 115, P = .03), there was no difference in severe exacerbations (n = 12 vs n = 13). No other significant differences were seen between groups with the exception of mannitol PD(10) and ICS dose. There was a 1.52 (95% CI, 0.61-2.42; P = .001) doubling dose difference in mannitol PD(10) between AHR vs control groups. The final mean daily ciclesonide dose was higher (P < .0001) in AHR vs control groups (514 μg vs 208 μg), with no associated significant suppression of overnight urinary cortisol/creatinine. Significant improvements were seen within the AHR group but not the control group for the provocative concentration of methacholine causing a 20% fall in FEV(1) (P < .05), salivary eosinophilic cationic protein (P < .05), exhaled nitric oxide (P < .05), symptoms (P < .005), and reliever use (P < .001).

CONCLUSIONS

Mannitol challenge was well tolerated in a primary care setting. Using mannitol resulted in exposure to a higher dose of ciclesonide, which was associated with equivocal effects on exacerbations without associated adrenal suppression. Large-scale trials using mannitol in patients with more severe disease may now be warranted to further define its role.

TRIAL REGISTRATION

ClinicalTrials.gov; No.: NCT01216579; URL: www.clinicaltrials.gov.

摘要

背景

我们比较了根据症状、缓解药物使用情况和肺功能对吸入性皮质类固醇（ICS）进行滴定与甘露糖醇气道高反应性（AHR）或参考策略（对照组）在初级保健中的作用。

方法

164 例持续性哮喘患者在初始 ICS 减量后，以平行组的方式进行随机分组。随后根据气道高反应性策略（AHR 策略），根据引起 FEV1 下降 10%的甘露糖醇激发剂量（PD10）滴定后续 ICS 剂量（以环索奈德为代表）；或根据对照组（参考策略），在 1 年内滴定后续 ICS 剂量。

结果

119 名参与者（n = 61 AHR，n = 58 对照组）完成了研究。首次轻度加重的时间无显著差异：风险比为 1.29；95%可信区间为 0.716-2.31；P =.40。尽管 AHR 组在 12 个月内的轻度加重总次数减少了 27%（n = 84 比 n = 115，P =.03），但重度加重无差异（n = 12 比 n = 13）。除了甘露糖醇 PD10 和 ICS 剂量外，两组之间没有其他显著差异。与对照组相比，AHR 组的甘露糖醇 PD10 有 1.52 倍（95%可信区间，0.61-2.42；P =.001）的加倍剂量差异。AHR 组的最终平均日环索奈德剂量明显更高（P <.0001）（514μg 比 208μg），但没有与夜间尿皮质醇/肌酐显著抑制相关。在 AHR 组中观察到了显著的改善，但在对照组中则没有观察到：引起 FEV1 下降 20%的乙酰甲胆碱激发浓度（P <.05）、唾液嗜酸性阳离子蛋白（P <.05）、呼气一氧化氮（P <.05）、症状（P <.005）和缓解药物使用（P <.001）。