Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France.
PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France.
Allergy. 2021 Aug;76(8):2395-2406. doi: 10.1111/all.14688. Epub 2020 Dec 26.
Asthma exacerbations are inflammatory events that rarely result in full hospitalization following an ER visit. Unfortunately, certain patients require prolonged support, including occasional external lung support through ECMO or ECCOR (with subsequent further exposure to other life-threatening issues), and some die. In parallel, biologics are revolutionizing severe asthma management, mostly in T2 high patients.
We extensively reviewed the current unmet needs surrounding ICU-admitted asthma exacerbations, with a focus on currently available drugs and the underlying biological processes involved. We explored whether currently available T2-targeting drugs can reasonably be seen as potential players not only for relapse prevention but also as candidate drugs for a faster resolution of such episodes. The patient's perspective was also sought.
About 30% of asthma exacerbations admitted to the ICU do not resolve within five days. Persistent severe airway obstruction despite massive doses of corticosteroids and maximal pharmacologically induced bronchodilation is the main cause of treatment failure. Previous ICU admission is the main risk factor for such episodes and may eventually be considered as a T2 surrogate marker. Fatal asthma cases are hallmarked by poorly steroid-sensitive T2-inflammation associated with severe mucus plugging. New, fast-acting T2-targeting biologics (already used for preventing asthma exacerbations) have the potential to circumvent steroid sensitivity pathways and decrease mucus plugging. This unmet need was confirmed by patients who reported highly negative, traumatizing experiences.
There is room for improvement in the management of ICU-admitted severe asthma episodes. Clinical trials assessing how biologics might improve ICU outcomes are direly needed.
哮喘恶化是炎症事件,在急诊室就诊后很少导致完全住院。不幸的是,某些患者需要长期支持,包括偶尔通过 ECMO 或 ECCOR 进行外部肺部支持(随后进一步面临其他危及生命的问题),有些患者死亡。与此同时,生物制剂正在彻底改变重症哮喘的管理,主要针对 T2 高患者。
我们广泛回顾了目前围绕 ICU 收治的哮喘恶化的未满足需求,重点关注目前可用的药物和涉及的潜在生物学过程。我们探讨了目前可用的 T2 靶向药物是否可以合理地被视为不仅预防复发而且可能更快解决此类发作的潜在药物。还寻求了患者的观点。
约 30%入住 ICU 的哮喘恶化在五天内未得到缓解。尽管大剂量皮质类固醇和最大药理学诱导的支气管扩张后仍持续存在严重气道阻塞是治疗失败的主要原因。先前的 ICU 入院是此类发作的主要危险因素,最终可能被视为 T2 的替代标志物。致命性哮喘病例的特点是与严重黏液栓形成相关的对类固醇反应不佳的 T2 炎症。新型、快速作用的 T2 靶向生物制剂(已用于预防哮喘恶化)有可能绕过类固醇敏感性途径并减少黏液栓形成。这一未满足的需求得到了报告高度负面、创伤性经历的患者的证实。
在管理 ICU 收治的严重哮喘发作方面仍有改进的空间。急需评估生物制剂如何改善 ICU 结局的临床试验。