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接受吸入性皮质固醇治疗的持续性气喘病患中,甘露醇挑战与乙酰甲胆碱挑战和发炎指标的关系。

Relationship of mannitol challenge to methacholine challenge and inflammatory markers in persistent asthmatics receiving inhaled corticosteroids.

机构信息

Division of Medical Sciences, Centre for Cardiovascular and Lung Biology, Asthma and Allergy Research Group, Ninewells Hospital & Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK.

出版信息

Lung. 2012 Oct;190(5):513-21. doi: 10.1007/s00408-012-9396-6. Epub 2012 Jun 9.

DOI:10.1007/s00408-012-9396-6
PMID:22684880
Abstract

BACKGROUND

Mannitol is a novel osmotic indirect bronchial challenge agent used to aid asthma diagnosis and management and is thought to reflect underlying inflammatory processes in asthma. Our objective was to evaluate relationships between mannitol airway hyperresponsiveness (AHR) and other measures of airway inflammation as well as direct-acting methacholine challenge in persistent asthmatics receiving inhaled corticosteroids.

METHODS

We analysed screening data of mild to moderate persistent asthmatics, all receiving inhaled corticosteroids (ICS), who had mannitol and/or methacholine challenges, fractional exhaled nitric oxide (FeNO), and salivary eosinophilic cationic protein (ECP) performed as part of the same screen. Mannitol AHR was grouped by PD(10) (cumulative provocative dose required to produce a 10 % fall in FEV(1)): mild (315-635 mg), moderate (75-315 mg), and severe (0-75 mg). FeNO groups were low (<25 ppb), medium (25-50 ppb), and high (> 50 ppb) and methacholine PC(20) (provocative concentration of methacholine required to cause a 20 % fall in FEV(1)) groups were mild (2-8 mg/ml), moderate (0.5-2 mg/ml), and severe (0-0.5 mg/ml).

RESULTS

Mannitol PD(10) groups were significantly different overall for FeNO (p = 0.023): 43 % higher in the severe vs. the mild group. There was a significant overall difference for methacholine PC(20) (p = 0.006): a 2.1 doubling dilution difference between severe vs. mild mannitol groups. FeNO groups were significantly different overall for mannitol PD(10) (p = 0.01) and methacholine PC(20) (p = 0.029). Methacholine PC(20) groups were significantly different overall for mannitol PD(10) (p < 0.001) and FeNO (p = 0.005). No significant differences were found across any groups for salivary ECP, FEV(1) % predicted, or ICS dose. Mannitol PD(10), methacholine PC(20), and FeNO as continuous variables all correlated with each other.

CONCLUSIONS

Mannitol challenge reflects underlying inflammation using FeNO and direct AHR using methacholine. Thus, mannitol may be a useful screening tool for the assessment of asthmatic patients receiving inhaled corticosteroids.

摘要

背景

甘露醇是一种新型的渗透间接支气管激发剂,用于辅助哮喘的诊断和管理,被认为反映了哮喘的潜在炎症过程。我们的目的是评估在接受吸入性皮质激素治疗的持续性哮喘患者中,甘露醇气道高反应性(AHR)与其他气道炎症指标以及直接作用的乙酰甲胆碱激发之间的关系。

方法

我们分析了轻度至中度持续性哮喘患者的筛选数据,所有患者均接受吸入性皮质激素(ICS)治疗,这些患者进行了甘露醇和/或乙酰甲胆碱激发、呼出气一氧化氮分数(FeNO)和唾液嗜酸性阳离子蛋白(ECP)检测,这些检测均作为同一筛选的一部分进行。根据 PD(10)(引起 FEV(1)下降 10%所需的累积激发剂量)将甘露醇 AHR 分组:轻度(315-635mg)、中度(75-315mg)和重度(0-75mg)。FeNO 组分为低(<25ppb)、中(25-50ppb)和高(>50ppb),乙酰甲胆碱 PC(20)(引起 FEV(1)下降 20%所需的乙酰甲胆碱激发浓度)组分为轻度(2-8mg/ml)、中度(0.5-2mg/ml)和重度(0-0.5mg/ml)。

结果

甘露醇 PD(10)组的总体 FeNO 差异有统计学意义(p=0.023):重度组比轻度组高 43%。乙酰甲胆碱 PC(20)的总体差异有统计学意义(p=0.006):重度组与轻度组之间的乙酰甲胆碱激发浓度相差 2.1 倍。甘露醇 PD(10)和乙酰甲胆碱 PC(20)的总体差异有统计学意义(p=0.01 和 p=0.029)。乙酰甲胆碱 PC(20)组的甘露醇 PD(10)和 FeNO 差异有统计学意义(p<0.001 和 p=0.005)。唾液 ECP、FEV(1)%预计值或 ICS 剂量在任何组之间均无显著差异。甘露醇 PD(10)、乙酰甲胆碱 PC(20)和 FeNO 作为连续变量相互之间均有相关性。

结论

甘露醇激发反映了使用 FeNO 的潜在炎症,而直接的乙酰甲胆碱 AHR 则反映了直接的 AHR。因此,甘露醇可能是评估接受吸入性皮质激素治疗的哮喘患者的有用筛选工具。

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