a Department of Pulmonary Medicine , Canisius-Wilhelmina Hospital , Nijmegen , Netherlands.
b Department of Respiratory Medicine , Maastricht University Medical Centre , Maastricht , Netherlands.
Expert Rev Respir Med. 2018 May;12(5):349-360. doi: 10.1080/17476348.2018.1460206. Epub 2018 Apr 2.
Current pharmacologic therapy of chronic obstructive pulmonary disease (COPD) can reduce respiratory symptoms and exacerbation frequency. However, no single COPD intervention except for lung transplantation has proven effective in recovering lung function. Lung elasticity is reduced in COPD lungs, which is for a large part due to chronically enhanced elastin degradation. Elastin calcification and formation of advanced glycation end products (AGEs) may also contribute to this. Areas covered: We propose inhalation therapy to induce repair of damaged pulmonary elastin fibers by stimulating tropoelastin synthesis, assembly and crosslinking in order to improve lung function in patients with COPD. Decelerating elastinolysis is another treatment objective, as well as decalcification and deglycation of the extracellular matrix. Expert commentary: Studies should be conducted to test whether it is feasible to restore pulmonary elastin fibers with inhalation therapy. We expect that the optimal formulation will turn out to be a combination of copper, epigallocatechin-(3-)gallate or pentagalloyl glucose, vitamin A/D/K, magnesium, heparin or heparan sulfate, minoxidil and one or more AGEs inhibitors. Establishing a treatment that has the proven ability to facilitate regain of lost lung function in COPD patients would cause a major paradigm shift in this debilitating disease.
目前,慢性阻塞性肺疾病(COPD)的药物治疗可以减轻呼吸症状和减少加重频率。然而,除了肺移植以外,没有任何单一的 COPD 干预措施被证明可以有效恢复肺功能。COPD 肺中的肺弹性降低,在很大程度上是由于弹性蛋白的慢性降解增强。弹性蛋白的钙化和晚期糖基化终产物(AGEs)的形成也可能促成这一点。
我们建议通过刺激原弹性蛋白的合成、组装和交联来进行吸入治疗,以诱导受损的肺弹性纤维修复,从而改善 COPD 患者的肺功能。减缓弹性蛋白水解是另一个治疗目标,以及细胞外基质的脱钙和去糖化。
应该进行研究以测试吸入疗法是否可以恢复肺弹性纤维。我们期望最佳配方将是铜、表没食子儿茶素-3-没食子酸酯或五没食子酰葡萄糖、维生素 A/D/K、镁、肝素或硫酸肝素、米诺地尔和一种或多种 AGEs 抑制剂的组合。建立一种能够促进 COPD 患者失去的肺功能恢复的治疗方法,将引起这种使人衰弱的疾病的重大范式转变。