Self-limiting anti-inflammatory actions of glucocorticoids in asthma

哮喘是一种疾病，其特征是气道管过度狭窄，导致从肺部呼出空气困难。哮喘的症状包括咳嗽、喘息、呼吸短促和呼吸困难。近五分之一的澳大利亚人患有哮喘，在儿童中尤为普遍。每三个澳大利亚人中就有一个人会在一生中的某个时候出现哮喘症状，尽管目前有治疗方法，但每年仍有700多名澳大利亚人死于哮喘。哮喘患者的气管内有更多更大的收缩肌细胞。肌肉质量的增加是由于哮喘发作期间和发作后白细胞迁移到气道中释放的化学物质造成的。这种增厚减缓了通过气管管的气流，因为肌肉团膨胀到气管管的孔中，当肌肉变短时，气管的总直径减小。我们最近的研究表明，哮喘患者使用类固醇来治疗导致疾病的白细胞，可以减少气道肌肉的生长。然而，当肌肉被炎症气道中存在的因子预处理时，类固醇的抗生长作用就被阻止了。类固醇的这种作用是由于一种叫做前列腺素E2的物质的产生减少，这种物质也可以减少肌肉的生长。因此，虽然类固醇可能有助于治疗哮喘的某些症状，但它们在治疗肌肉增厚和涉及细胞分裂和增殖的疾病的其他方面可能不是最佳的。本研究下一阶段的具体问题是，类固醇抑制前列腺素释放是否会损害类固醇对气道管生长的有益作用。本研究的发现将为类固醇在哮喘中的作用提供新的信息，并可能为治疗严重哮喘提供更好的治疗策略。

Asthma is a disease characterised by excessive narrowing of the airway tubes resulting in difficulty exhaling air from the lungs. Symptoms of asthma include coughing, wheezing, shortness of breath and difficulty in breathing. Asthma affects almost 1 in 5 Australians and is especially prevelant in children. One in every three Australians will suffer from symptoms of asthma at some time in their life and despite current therapy, asthma is responsible for the deaths of more than 700 Australians every year. Airway tubes of asthmatics have more and larger contractile muscle cells lining the tubes. This increase in muscle mass results from chemicals that are released from white blood cells that migrate into the airway tubes during and after asthma attacks. This thickening slows airflow through the airway tubes because the muscle mass bulges into the holes of the tubes and when the muscle shortens the total diameter of the tubes decrease. We have recently shown that steroids used by asthmatics to treat the white blood cell contribution to the disease can reduce the growth of airway muscle. However, when the muscle has been pretreated with factors that are present in the inflamed airway, the anti-growth effects of steroids are prevented. This effect of the steroids is due to reduced production of a substance called prostaglandin E2 which can also reduce the growth of muscle. Thus, whilst steroids may help in treating some of the symptoms of asthma, they may be suboptimal in the treatment of muscle thickening and other aspects of the disease which involve cell division and multiplication. Our specific question in the next phase of this research is whether steroid inhibition of the release of prostaglandins compromises the useful actions of steroids on the growth of the airway tubes. The findings of this proposed study will provide new information on the role of steroids in asthma and may lead to better therapeutic strategies for the treatment of severe asthma.