Sherpa Rinzhin T, Koziol-White Cynthia J, Panettieri Reynold A
Rutgers Institute for Translational Medicine and Science, Rutgers University, 89 French Street, New Brunswick, NJ 08901, USA.
Cells. 2025 Apr 30;14(9):659. doi: 10.3390/cells14090659.
Obstructive airway diseases, including asthma and chronic obstructive pulmonary disease (COPD), evoke significant global health concerns manifested by airway inflammation and obstruction. Despite their differing origins, shared pathophysiological features and responses to therapeutic interventions highlight common molecular mechanisms. Standard treatments include inhaled bronchodilators, with combination therapies offering enhanced symptom control. Cyclic AMP (cAMP) plays a crucial role in airway relaxation. Phosphodiesterase (PDE) decreases cAMP levels, thereby attenuating the relaxation of airway smooth muscle, making it a promising therapeutic target. The balance between cAMP production and degradation is essential for regulating airway tone and function. PDE inhibitors for the treatment of obstructive airway diseases have suffered challenges, with adverse side effects of prospective inhibitors causing clinical failures. Efforts to develop PDE inhibitors with an improved safety profile could prove to be beneficial as an add-on treatment for severe asthma and COPD. The recent FDA approval of Ensifentrine, a dual PDE3/4 inhibitor, can significantly advance COPD management by improving bronchodilation, reducing inflammation, and lowering exacerbation rates with favorable safety outcomes.
阻塞性气道疾病，包括哮喘和慢性阻塞性肺疾病（COPD），引发了重大的全球健康问题，表现为气道炎症和阻塞。尽管它们起源不同，但共同的病理生理特征和对治疗干预的反应突出了共同的分子机制。标准治疗包括吸入支气管扩张剂，联合治疗可增强症状控制。环磷酸腺苷（cAMP）在气道舒张中起关键作用。磷酸二酯酶（PDE）降低cAMP水平，从而减弱气道平滑肌的舒张，使其成为一个有前景的治疗靶点。cAMP产生与降解之间的平衡对于调节气道张力和功能至关重要。用于治疗阻塞性气道疾病的PDE抑制剂面临挑战，潜在抑制剂的不良副作用导致临床失败。开发具有改善安全性的PDE抑制剂的努力可能被证明作为重度哮喘和COPD的附加治疗是有益的。美国食品药品监督管理局（FDA）最近批准的双PDE3/4抑制剂恩昔芬净，可通过改善支气管扩张、减轻炎症和降低急性加重率并取得良好的安全性结果，显著推进COPD的管理。
