National Heart and Lung Institute, Imperial College, London, UK.
Respiration. 2010;80(2):89-95. doi: 10.1159/000315416. Epub 2010 May 26.
Inhaled corticosteroids (ICS) are now very widely used in high doses in the management of COPD patients. In sharp contrast to the situation in asthma, ICS provide little or no benefit in COPD patients and may have long-term detrimental effects. High doses of ICS fail to reduce disease progression or mortality, even when combined with a long-acting beta(2)-agonist (LABA). Several trials have demonstrated that ICS reduce exacerbations by 20-25%, particularly in patients with more severe disease, but these studies are confounded by poor trial design and more appropriate analysis shows no benefit. Indeed, the benefit of combination inhalers seems to be largely due to the effect of the LABA, and long-acting bronchodilators--including tiotropium--provide similar benefits in reducing exacerbations. However, there may be some COPD patients, for example those with concomitant asthma, who benefit from ICS. Yet it has not been possible to identify any clinical factors that predict corticosteroid responsiveness in COPD patients in the large clinical trials. There is increasing evidence that high doses of ICS may have detrimental effects on bones and may increase the risk of pneumonia. ICS fail to suppress inflammation in COPD patients because there is a marked reduction in histone deacetylase-2, the nuclear enzyme that corticosteroids require to switch off activated inflammatory genes. In the future, alternative anti-inflammatory treatments will be needed for COPD or therapeutic strategies which reverse the molecular pathways that causes corticosteroid resistance.
吸入性皮质类固醇（ICS）目前在 COPD 患者的治疗中被广泛地以高剂量使用。与哮喘的情况形成鲜明对比的是，ICS 对 COPD 患者几乎没有益处，甚至可能存在长期的不良影响。高剂量 ICS 无法降低疾病进展或死亡率，即使与长效β2-激动剂（LABA）联合使用也是如此。几项试验表明，ICS 可将恶化率降低 20-25%，尤其是在病情较重的患者中，但这些研究受到试验设计不佳的影响，更合适的分析表明没有益处。实际上，联合吸入器的益处似乎主要归因于 LABA 的作用，长效支气管扩张剂（包括噻托溴铵）在减少恶化方面提供了相似的益处。然而，可能有一些 COPD 患者，例如同时患有哮喘的患者，受益于 ICS。然而，在大型临床试验中，尚未能够确定任何可预测 COPD 患者对皮质类固醇反应的临床因素。越来越多的证据表明，高剂量 ICS 可能对骨骼有不良影响，并可能增加肺炎的风险。ICS 在 COPD 患者中无法抑制炎症，因为组蛋白去乙酰化酶-2（核酶）的含量显著减少，而皮质类固醇需要这种核酶来关闭激活的炎症基因。在未来，需要替代的抗炎治疗来治疗 COPD，或者需要逆转导致皮质类固醇抵抗的分子途径的治疗策略。
