Mannitol in the assessment of bronchial responsiveness in airway disease

哮喘患者的气道对各种刺激的反应是太容易和太多地变窄。最常用于测量哮喘气道反应性的试验是药物乙酰甲胆碱和组胺。当吸入时，它们直接作用于支气管肌肉，导致其收缩，从而使气道变窄。我们开发了一种非药理学试验，使用糖-甘露醇的干粉。当吸入甘露醇时，会导致哮喘患者的气道变窄，但对健康受试者影响很小或没有影响。许多哮喘患者对甘露醇有反应，即使他们几乎没有哮喘症状。甘露醇通过引起气道中的炎症细胞释放物质（例如组胺、白三烯和肾上腺素），导致肌肉收缩，从而“间接”导致气道变窄。在炎症清除后，无论是通过吸入类固醇治疗还是自发治疗，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，而反应性的丧失意味着炎症的消退。这一点的意义在于甘露醇试验可用作“炎症测定仪”。如果气道对甘露醇的反应性可用于识别哮喘以外的气道疾病（慢性支气管炎和慢性阻塞性肺病）患者，这些患者可从吸入性类固醇治疗中获益，这将是非常重要的。这将是重要的，因为目前没有测试来识别这些个体，并且使用类固醇会产生不必要的影响。此外，可能使用甘露醇来识别患有其他炎性疾病的个体，这些个体可能有患哮喘的风险。一些患有哮喘、慢性支气管炎和慢性阻塞性肺病的人氧化应激水平增加。我们希望确定这些人，并测量类固醇治疗后的变化。

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.