Mannitol in the assessment of bronchial responsiveness in airway disease

甘露醇评估气道疾病的支气管反应性

• 批准号: nhmrc : 245502
• 负责人: Prof John Seale
• 金额: $ 24.35万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/mannitol-assessment-bronchial-airway-disease/98693
• 关键词: Mannitol; assessment; bronchial; responsiveness; airway

The airways of people with asthma respond by narrowing too easily and too much to a wide range of stimuli. The tests most commonly used to measure airway responsiveness in asthma are the pharmacological agents methacholine and histamine. When inhaled, they act directly on bronchial muscle causing it to contract and hence the airways to narrow. We have developed a non-pharmacological test using a dry powder of a sugar - mannitol. When inhaled, mannitol causes narrowing of the airways in asthmatics but little or no effect in healthy subjects. Many asthmatics respond to mannitol even when they have few symptoms of asthma. Mannitol causes the airways to narrow 'indirectly' by causing the release of substances from inflammatory cells in the airways (e.g. histamine, leukotrienes and prostaglandins) that cause the muscle to contract. After the inflammation has cleared, either by treatment with inhaled steroids or spontaneously, the response to mannitol is close to healthy subjects. Thus the response to mannitol depends on the presence of inflammation and loss of responsiveness means resolution of inflammation. The significance of this is that the mannitol test may be used as an 'inflammometer'. It would be important if airway responsiveness to mannitol could be used to identify individuals with airway diseases other than asthma, (chronic bronchitis, and chronic obstructive lung disease) who could benefit from treatment with inhaled steroids. This would be significant as there is currently no test to identify those individuals and there are unwanted effects from using steroids. Further, it may be possible to use mannitol to identify individuals with other inflammatory diseases who may be at risk of developing asthma. Some people with asthma, chronic bronchitis and chronic obstructive lung disease have increased levels of oxidative stress. We wish to identify those people and to measure change after treatment with steroids.

哮喘患者的呼吸道通过太容易缩小而对广泛的刺激做出反应。用于测量哮喘气道反应性的最常用的测试是药理学剂甲基胆碱和组胺。吸入后，它们直接作用于支气管肌肉，导致其收缩，从而使气道变窄。我们已经使用糖 - 甘露醇的干粉进行了非药物测试。吸入时，甘露醇会导致哮喘患者的气道变窄，但在健康受试者中几乎没有影响。即使哮喘的症状很少，许多哮喘患者即使它们的哮喘症状也会反应。甘露醇通过导致气道中的炎症细胞（例如组胺，白细胞和前列腺素）从炎症细胞中释放物质而导致气道“间接”狭窄。在炎症清除后，通过吸入类固醇或自发治疗，对甘露醇的反应接近健康受试者。因此，对甘露醇的反应取决于炎症的存在和反应性丧失意味着解决炎症。其意义是甘露醇测试可以用作“炎症计”。如果可以使用对甘露醇的气道反应能力来鉴定哮喘以外的气道疾病患者（慢性支气管炎和慢性阻塞性肺部疾病），他们可以从吸入类固醇的治疗中受益。这将是重要的，因为目前尚无测试来识别这些人，并且使用类固醇会产生不必要的影响。此外，可能有可能使用甘露醇来识别患有可能患有哮喘风险的其他炎症性疾病的人。有些患有哮喘，慢性支气管炎和慢性阻塞性肺疾病的人的氧化应激水平增加。我们希望确定这些人并在用类固醇治疗后测量变化。