Inhaled long-acting β-adrenergic agonists (LABAs) and short-acting β-adrenergic agonists are approved for the treatment of obstructive lung disease via actions mediated by β2 adrenergic receptors (β2-ARs) that increase cellular cAMP synthesis. This review discusses the potential of β2-AR agonists, in particular LABAs, for the treatment of acute respiratory distress syndrome (ARDS). We emphasize ARDS induced by pneumonia and focus on the pathobiology of ARDS and actions of LABAs and cAMP on pulmonary and immune cell types. β2-AR agonists/cAMP have beneficial actions that include protection of epithelial and endothelial cells from injury, restoration of alveolar fluid clearance, and reduction of fibrotic remodeling. β2-AR agonists/cAMP also exert anti-inflammatory effects on the immune system by actions on several types of immune cells. Early administration is likely critical for optimizing efficacy of LABAs or other cAMP-elevating agents, such as agonists of other Gs-coupled G protein–coupled receptors or cyclic nucleotide phosphodiesterase inhibitors. Clinical studies that target lung injury early, prior to development of ARDS, are thus needed to further assess the use of inhaled LABAs, perhaps combined with inhaled corticosteroids and/or long-acting muscarinic cholinergic antagonists. Such agents may provide a multipronged, repurposing, and efficacious therapeutic approach while minimizing systemic toxicity.

中文翻译：

---

吸入 β2 肾上腺素能激动剂和其他 cAMP 升高剂：肺泡损伤和急性呼吸系统疾病综合征的治疗方法？

吸入长效β-肾上腺素能激动剂 (LABAs) 和短效β-肾上腺素能激动剂通过增加细胞 cAMP 合成的β2肾上腺素能受体 ( β2 -ARs)介导的作用被批准用于治疗阻塞性肺病。本综述讨论了β 2-AR 激动剂，特别是 LABAs 治疗急性呼吸窘迫综合征 (ARDS) 的潜力。我们强调肺炎引起的 ARDS，重点关注 ARDS 的病理生物学以及 LABA 和 cAMP 对肺和免疫细胞类型的作用。β2-AR 激动剂/cAMP 具有有益作用，包括保护上皮和内皮细胞免受损伤、恢复肺泡液清除和减少纤维化重塑。β2-AR 激动剂/cAMP 还通过作用于几种类型的免疫细胞对免疫系统发挥抗炎作用。早期给药可能对于优化 LABA 或其他 cAMP 提升剂（例如其他 Gs 偶联 G 蛋白偶联受体的激动剂或环核苷酸磷酸二酯酶抑制剂）的功效至关重要。因此，需要在 ARDS 发展之前早期针对肺损伤的临床研究，以进一步评估吸入 LABA 的使用，可能与吸入皮质类固醇和/或长效毒蕈碱胆碱能拮抗剂联合使用。这样的药剂可以提供一种多管齐下的、再利用的和有效的治疗方法，同时使全身毒性最小化。