Erjefält Jonas S
Unit of Airway Inflammation, Department of Experimental Medical Research, Lund University, Lund, Sweden; Department of Allergology and Respiratory Medicine, Skane University Hospital, Lund, Sweden.
Respir Med. 2023 Apr-May;210:107168. doi: 10.1016/j.rmed.2023.107168. Epub 2023 Feb 21.
Asthma is typically characterized by variable respiratory symptoms and airflow limitation. Along with the pathophysiology and symptoms are immunological and inflammatory processes. The last decades research has revealed that the immunology of asthma is highly heterogeneous. This has clinical consequences and identification of immunological phenotypes is currently used to guide biological treatment. The focus of this review is on another dimension of asthma diversity, namely anatomical heterogeneity. Immunopathological alterations may go beyond the central airways to also involve the distal airways, the alveolar parenchyma, and pulmonary vessels. Also, extrapulmonary tissues are affected. The anatomical distribution of inflammation in asthma has remained relatively poorly discussed despite its potential implication on both clinical presentation and response to treatment. There is today evidence that a significant proportion of the asthma patients has small airway disease with type 2 immunity, eosinophilia and smooth muscle infiltration of mast cells. The small airways in asthma are also subjected to remodelling, constriction, and luminal plugging, events that are likely to contribute to the elevated distal airway resistance seen in some patients. In cases when the inflammation extends into the alveolar parenchyma alveolar FCER1-high mast cells, eosinophilia, type 2 immunity and activated alveolar macrophages, together with modest interstitial remodelling, create a complex immunopathological picture. Importantly, the distal lung inflammation in asthma can be pharmacologically targeted by use of inhalers with more distal drug deposition. Biological treatments, which are readily distributed to the distal lung, may also be beneficial in eligible patients with more severe and anatomically widespread disease.
哮喘通常表现为多变的呼吸道症状和气流受限。伴随其病理生理学和症状的是免疫和炎症过程。过去几十年的研究表明，哮喘的免疫学具有高度异质性。这具有临床意义，目前免疫表型的识别被用于指导生物治疗。本综述的重点是哮喘多样性的另一个维度，即解剖学异质性。免疫病理改变可能不仅局限于中央气道，还累及远端气道、肺泡实质和肺血管。此外，肺外组织也会受到影响。尽管哮喘炎症的解剖学分布对临床表现和治疗反应都有潜在影响，但对此的讨论相对较少。如今有证据表明，相当一部分哮喘患者存在2型免疫、嗜酸性粒细胞增多以及肥大细胞平滑肌浸润的小气道疾病。哮喘中的小气道还会发生重塑、收缩和管腔堵塞，这些情况可能导致部分患者远端气道阻力升高。当炎症扩展到肺泡实质时，肺泡FCER1高表达的肥大细胞、嗜酸性粒细胞增多、2型免疫和活化的肺泡巨噬细胞，以及适度的间质重塑，共同构成了一幅复杂的免疫病理图景。重要的是，哮喘患者的远端肺部炎症可以通过使用药物沉积更靠近远端的吸入器进行药理学靶向治疗。能够轻易分布到远端肺部的生物治疗，对于病情更严重且解剖学上病变范围更广的合适患者可能也有益处。
