Brannan John D, Anderson Sandra D, Perry Clare P, Freed-Martens Ruth, Lassig Anna R, Charlton Brett
Department of Respiratory Medicine, 11 West, Royal Prince Alfred Hospital, Camperdown NSW 2050, Australia.
Respir Res. 2005 Dec 9;6(1):144. doi: 10.1186/1465-9921-6-144.
Inhaled mannitol is a new bronchial provocation test (BPT) developed to improve portability and standardisation of osmotic challenge testing. Osmotic challenge tests have an advantage over the traditional methods of measuring airway hyperresponsiveness using methacholine as they demonstrate higher specificity to identify asthma and thus the need for treatment with inhaled corticosteroids (ICS). The safety and the efficacy of mannitol (M) as a BPT to measure airway hyperresponsiveness were compared to hypertonic (4.5%) saline (HS) in people both with and without signs and symptoms of asthma.
A phase III, multi-centre, open label, operator-blinded, crossover design, randomised trial, with follow-up. Asthmatics and non-asthmatics (6-83 yr) were recruited and 592 subjects completed the study. Mannitol was delivered using a low resistance dry powder inhaler and HS was delivered using an ultrasonic nebuliser. The FEV1 was measured 60 seconds after each dose of mannitol (5,10,20,40,80,160,160,160 mg) and after each exposure to HS (0.5,1.0,2.0,4.0,8.0 minutes). A 15% fall in FEV1 defined a positive test. Adverse events were monitored and diaries kept for 7 days following the tests.
Mean pre-test FEV1 (mean +/- SD) was 95.5 +/- 14% predicted. 296 were positive to mannitol (M+) and 322 positive to HS (HS+). A post study physician conducted clinical assessment identified 82.3% asthmatic (44% classified mild) and 17.7% non-asthmatic. Of those M+, 70.1% were taking ICS and of those mannitol negative (M-), 81.1 % were taking ICS. The % fall in FEV1 for mannitol in asthmatics was 21.0% +/- 5.7 and for the non-asthmatics, 5.5% +/- 4.8. The median PD15 M was 148 mg and PD15 HS 6.2 ml. The sensitivity of M to identify HS+ was 80.7% and the specificity 86.7%. The sensitivity of M compared with the clinical assessment was 59.8% and specificity 95.2% and increased to 88.7% and 95.0% respectively when the M- subjects taking ICS were excluded. Cough was common during testing. There were no serious adverse events. The diarised events were similar for mannitol and HS, the most common being headache (17.2%M, 19%HS), pharyngolaryngeal pain (5.1%M, 3%HS), nausea (4.3%M, 3%HS), and cough (2.2%M, 2.4%HS).
The efficacy and safety of mannitol was demonstrated in non-asthmatic and clinically diagnosed asthmatic adults and children.
吸入性甘露醇是一种新开发的支气管激发试验（BPT），旨在提高渗透激发试验的便携性和标准化。与使用乙酰甲胆碱测量气道高反应性的传统方法相比，渗透激发试验具有优势，因为它们在识别哮喘以及确定吸入性糖皮质激素（ICS）治疗需求方面具有更高的特异性。将甘露醇（M）作为测量气道高反应性的BPT的安全性和有效性与高渗（4.5%）盐水（HS）在有或无哮喘体征和症状的人群中进行了比较。
一项III期、多中心、开放标签、操作者盲法、交叉设计的随机试验，并进行随访。招募了哮喘患者和非哮喘患者（6 - 83岁），592名受试者完成了研究。使用低阻力干粉吸入器递送甘露醇，使用超声雾化器递送HS。在每次给予甘露醇剂量（5、10、20、40、80、160、160、160毫克）后60秒以及每次暴露于HS（0.5、1.0、2.0、4.0、8.0分钟）后测量第一秒用力呼气容积（FEV1）。FEV1下降15%定义为阳性试验。监测不良事件，并在试验后记录7天的日记。
测试前FEV1的平均预测值（平均值±标准差）为95.5±14%。296人对甘露醇呈阳性反应（M +），322人对HS呈阳性反应（HS +）。研究后医生进行的临床评估确定82.3%为哮喘患者（44%分类为轻度），17.7%为非哮喘患者。在M +者中，70.1%正在使用ICS，在甘露醇阴性（M -）者中，81.1%正在使用ICS。哮喘患者中甘露醇导致的FEV1下降百分比为21.0%±5.7，非哮喘患者为5.5%±4.8。PD15 M的中位数为148毫克，PD15 HS为6.2毫升。M识别HS +的敏感性为80.7%，特异性为86.7%。与临床评估相比，M的敏感性为59.8%，特异性为95.2%，当排除正在使用ICS的M -受试者时，敏感性和特异性分别提高到88.7%和95.0%。测试期间咳嗽很常见。没有严重不良事件。甘露醇和HS记录的事件相似，最常见的是头痛（17.2%M，19%HS）、咽喉疼痛（5.1%M，3%HS）、恶心（4.3%M，3%HS）和咳嗽（2.2%M，2.4%HS）。
在非哮喘和临床诊断的哮喘成人及儿童中证实了甘露醇的有效性和安全性。
