a Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine , University of California , Davis , CA , USA.
b NIH West Coast Metabolomics Center, Genome and Biomedical Sciences Facility , University of California , Davis , CA , USA.
Expert Rev Respir Med. 2018 Jun;12(6):461-473. doi: 10.1080/17476348.2018.1457437. Epub 2018 May 3.
Asthma manifests as chronic airflow obstruction with persistent inflammation and airway hyperresponsiveness. The immunomodulatory and anti-inflammatory properties of the HMG-CoA reductase (HMGCR) inhibitors (a.k.a. statins), suggest a therapeutic role in chronic inflammatory lung diseases. However, despite positive laboratory investigations and promising epidemiological data, clinical trials using statins for the treatment of asthma have yielded conflicting results. Inadequate statin levels in the airway compartment could explain these findings. Areas covered: HMGCR is in the mevalonate (MA) pathway and MA signaling is fundamental to lung biology and asthma. This article will discuss clinical trials of oral statins in asthma, review lab investigations relevant to the systemic versus inhaled administration of statins, address the advantages and disadvantages of inhaled statins, and answer the question: is there a role for inhaled statins in the treatment of asthma? Expert commentary: If ongoing investigations show that oral administration of statins has no clear clinical benefits, then repurposing statins for delivery via inhalation is a logical next step. Inhalation of statins bypasses first-pass metabolism by the liver, and therefore, allows for delivery of significantly lower doses to the airways at greater potency. Statins could become the next major class of novel inhalers for the treatment of asthma.
哮喘表现为慢性气流阻塞,伴有持续炎症和气道高反应性。HMG-CoA 还原酶(HMGCR)抑制剂(又名他汀类药物)具有免疫调节和抗炎特性,提示其在慢性炎症性肺部疾病中有治疗作用。然而,尽管实验室研究结果积极,且有有前景的流行病学数据,但使用他汀类药物治疗哮喘的临床试验结果却存在矛盾。气道中他汀类药物水平不足可能解释了这些发现。
HMGCR 位于甲羟戊酸(MA)途径中,MA 信号对肺生物学和哮喘至关重要。本文将讨论口服他汀类药物治疗哮喘的临床试验,回顾与他汀类药物系统与吸入给药相关的实验室研究,探讨吸入性他汀类药物的优缺点,并回答以下问题:吸入性他汀类药物在哮喘治疗中有作用吗?
如果正在进行的研究表明口服他汀类药物没有明显的临床益处,那么将他汀类药物重新用于吸入给药是合乎逻辑的下一步。吸入性他汀类药物绕过了肝脏的首过代谢,因此可以以更高的效力将显著更低剂量的药物递送至气道。他汀类药物可能成为治疗哮喘的下一类新型吸入剂。