a 2nd Respiratory Medicine Department , National and Kapodistrian University of Athens, Medical School, Attikon Hospital , Athens , Greece.
b 1st Respiratory Medicine Department , National and Kapodistrian University of Athens, Medical School, Sotiria Chest Hospital , Athens , Greece.
Expert Opin Investig Drugs. 2019 Mar;28(3):261-266. doi: 10.1080/13543784.2019.1571582. Epub 2019 Jan 24.
Severe, inadequately-controlled asthma remains a clinical challenge. For this reason, clinical trials and preclinical experimental studies on novel agents as an add-on therapies continue emerge. Phosphodiesterases (PDEs) are enzymes that regulate the function of immune cells by hydrolyzing cyclic guanosine monophosphate/cGMP and cyclic adenosine monophosphate/cAMP. PDEs are divided into subfamilies [PDE3, PDE4, PDE5 and PDE7] which are mainly found in the respiratory tract. Inhibitors of PDEs have already been approved for COPD and pulmonary hypertension.
The role of PDE inhibitors in asthma treatment and the possible mechanism of action via their anti-inflammatory and/or bronchodilating effect are discussed.
Novel PDE inhibitors exhibiting fewer adverse events may have a role as add-on therapies in asthma treatment in the future. More clinical trials are necessary to prove their efficacy and evaluate their safety profile before approval by regulatory bodies is granted.
严重且控制不佳的哮喘仍然是一个临床挑战。因此,作为附加疗法的新型药物的临床试验和临床前实验研究不断涌现。磷酸二酯酶(PDEs)是通过水解环鸟苷酸/环 GMP 和环腺苷酸/环 AMP 来调节免疫细胞功能的酶。PDEs 分为亚家族(PDE3、PDE4、PDE5 和 PDE7),主要存在于呼吸道中。PDE 抑制剂已被批准用于 COPD 和肺动脉高压。
讨论了 PDE 抑制剂在哮喘治疗中的作用以及通过抗炎和/或支气管扩张作用的可能作用机制。
未来,具有较少不良反应的新型 PDE 抑制剂可能在哮喘治疗中作为附加疗法发挥作用。在获得监管机构批准之前,有必要进行更多的临床试验来证明其疗效并评估其安全性。