Rupani Hitasha, Fong Wei Chern Gavin, Kyyaly Aref, Kurukulaaratchy Ramesh J
Department of Respiratory Medicine, University Hospitals Southampton NHS Foundation Trust, Southampton, UK.
Clinical and Experimental Sciences, University of Southampton, Southampton, UK.
J Inflamm Res. 2021 Sep 2;14:4371-4397. doi: 10.2147/JIR.S295038. eCollection 2021.
The present prevailing inflammatory paradigm in asthma is of T2-high inflammation orchestrated by key inflammatory cells like Type 2 helper lymphocytes, innate lymphoid cells group 2 and associated cytokines. Eosinophils are key components of this T2 inflammatory pathway and have become key therapeutic targets. Real-world evidence on the predominant T2-high nature of severe asthma is emerging. Various inflammatory biomarkers have been adopted in clinical practice to aid asthma characterization including airway measures such as bronchoscopic biopsy and lavage, induced sputum analysis, and fractional exhaled nitric oxide. Blood measures like eosinophil counts have also gained widespread usage and multicomponent algorithms combining different parameters are now appearing. There is also growing interest in potential future biomarkers including exhaled volatile organic compounds, micro RNAs and urinary biomarkers. Additionally, there is a growing realisation that asthma is a heterogeneous state with numerous phenotypes and associated treatable traits. These may show particular inflammatory patterns and merit-specific management approaches that could improve asthma patient outcomes. Inhaled corticosteroids (ICS) remain the mainstay of asthma management but their use earlier in the course of disease is being advocated. Recent evidence suggests potential roles for ICS in combination with long-acting beta-agonists (LABA) for as needed use in mild asthma whilst maintenance and reliever therapy regimes have gained widespread acceptance. Other anti-inflammatory strategies including ultra-fine particle ICS, leukotriene receptor antagonists and macrolide antibiotics may show efficacy in particular phenotypes too. Monoclonal antibody biologic therapies have recently entered clinical practice with significant impacts on asthma outcomes. Understanding of the efficacy and use of those agents is becoming clearer with a growing body of real-world evidence as is their potential applicability to other treatable comorbid traits. In conclusion, the evolving understanding of T2 driven inflammation alongside a treatable traits disease model is enhancing therapeutic approaches to address inflammation in asthma.
目前哮喘中普遍流行的炎症模式是由2型辅助淋巴细胞、2型固有淋巴细胞等关键炎症细胞及其相关细胞因子精心编排的2型高炎症反应。嗜酸性粒细胞是这条2型炎症途径的关键组成部分,并已成为关键的治疗靶点。关于重度哮喘主要为2型高炎症性质的真实世界证据正在浮现。临床实践中已采用多种炎症生物标志物来辅助哮喘的特征描述,包括气道检测手段,如支气管镜活检和灌洗、诱导痰分析以及呼出一氧化氮分数。嗜酸性粒细胞计数等血液检测指标也已广泛应用,并且结合不同参数的多组分算法也正在出现。人们对包括呼出挥发性有机化合物、微小RNA和尿液生物标志物在内的潜在未来生物标志物的兴趣也在不断增加。此外,人们越来越认识到哮喘是一种具有多种表型和相关可治疗特征的异质性状态。这些可能表现出特定的炎症模式,值得采用特定的管理方法,从而改善哮喘患者的治疗效果。吸入性糖皮质激素(ICS)仍然是哮喘管理的主要手段,但有人主张在疾病进程中更早使用。最近的证据表明,ICS与长效β受体激动剂(LABA)联合使用在轻度哮喘按需治疗中可能发挥作用,同时维持和缓解治疗方案已得到广泛认可。其他抗炎策略,包括超细颗粒ICS、白三烯受体拮抗剂和大环内酯类抗生素,在特定表型中也可能显示出疗效。单克隆抗体生物疗法最近已进入临床实践,对哮喘治疗效果产生了重大影响。随着越来越多的真实世界证据的出现,对这些药物疗效和使用的理解越来越清晰,它们对其他可治疗合并特征的潜在适用性也是如此。总之,对2型驱动炎症的不断演变的理解以及可治疗特征疾病模型正在加强针对哮喘炎症的治疗方法。