Bakakos Agamemnon, Ampazis Dimitrios, Papaioannou Andriana I, Loukides Stelios, Bakakos Petros
1st Department of Respiratory Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Respiratory Department, Cavan & Monaghan Hospital & Chronic Disease Management Hub, HSE & RCSI University of Medicine, H12 Y7W1 Cavan, Ireland.
Int J Mol Sci. 2025 Aug 8;26(16):7692. doi: 10.3390/ijms26167692.
Severe asthma imposes a significant burden on public health worldwide, mainly due to its morbidity and high cost. The management of severe asthma has dramatically changed in the past few years with the introduction of biologics. Zero exacerbations, zero systemic corticosteroids, better asthma control, and better lung function are the outcomes that the era of biologics has made attainable in a large proportion of severe asthmatics, ending up in a better quality of life. Still, even today, the changes at the tissue level that reflect these outcomes are not that clear. As a chronic inflammatory disease, asthma often involves airway remodeling in its severe forms; endobronchial biopsies may provide critical insights into these tissue-level changes before and after biologic treatment. However, bronchoscopy is an invasive tool for severe asthma, thus limiting its use in daily clinical practice. This review focuses on summarizing the changes that biologics exert in biopsies obtained from severe asthmatics under biological treatment, providing an opportunity to shed light on what really happens there where it is not easy to see, and especially on what does not happen in patients under biologics who fail to respond as expected. Moreover, the armamentarium of biomarkers used for making the proper choice in patients eligible for more than one biologic needs to be enriched. Biopsy-related markers could be an ideal adjunct to the current ones-blood eosinophils, FeNO, and IgE-to assist the clinician to choose the right biologic for the right patient with severe asthma to achieve disease remission.
重度哮喘给全球公共卫生带来了沉重负担，主要是因其发病率高和成本高昂。在过去几年中，随着生物制剂的引入，重度哮喘的管理发生了巨大变化。生物制剂时代已使很大一部分重度哮喘患者能够实现零发作、零全身使用糖皮质激素、更好地控制哮喘以及改善肺功能，最终提高生活质量。然而，即便在今天，反映这些结果的组织层面变化仍不十分明确。作为一种慢性炎症性疾病，哮喘在严重形式下常伴有气道重塑；支气管活检可能为生物制剂治疗前后的这些组织层面变化提供关键见解。然而，支气管镜检查对于重度哮喘来说是一种侵入性手段，因此限制了其在日常临床实践中的应用。本综述着重总结生物制剂对接受生物治疗的重度哮喘患者活检组织所产生的变化，从而有机会揭示在不易观察到的地方实际发生了什么，特别是在接受生物制剂治疗但未达到预期反应的患者中未发生的情况。此外，需要丰富用于为符合多种生物制剂治疗条件的患者做出恰当选择的生物标志物库。与活检相关的标志物可能是当前血液嗜酸性粒细胞、呼出气一氧化氮（FeNO）和免疫球蛋白E（IgE）等标志物的理想辅助手段，以帮助临床医生为重度哮喘患者选择合适的生物制剂，从而实现疾病缓解。
