Chronic rhinosinusitis: Endotypes, biomarkers, and treatment response
Chronic rhinosinusitis: Endotypes, biomarkers, and treatment response
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DOI：
10.1016/j.jaci.2017.10.006
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发表时间：
2017-12-01
影响因子：
14.2
通讯作者：
Borish, Larry
中科院分区：
文献类型：
--
作者：
Gurrola, Jose, II;Borish, Larry
人们越来越认识到，慢性鼻-鼻窦炎(CRS)包括一系列不同的疾病，具有不同的临床表现和发病机制。明确CRS的不同表型和内型影响预后，最重要的是，作为做出治疗决定的基础是必要的。在开始治疗之前，需要对致病机制进行个性化的定义，这几乎延伸到了所有的治疗考虑。这对抗生素来说显然是至关重要的，在抗生素中，除非受到其非靶标抗炎药理作用的影响，否则对单个生物群的作用的了解可以预测治疗益处的可能性。然而，这种确定个体表型和内型的需要也延伸到了目前被认为是CRS治疗的主要药物，特别是糖皮质激素。与哮喘一样，人们认识到，大多数CRS患者具有类固醇耐药表型，这种表型的确定将排除这些具有潜在副作用的药物的使用。内型鉴定也变得越来越迫切，因为靶向生物治疗药物，如抗IgE和抗细胞因子抗体，正在变得可用。这些药物可能使患者受益，在这些患者中，靶向介体不仅表达，而且明显地推动了患者的中枢机制。总而言之，CRS的治疗正处于一个令人兴奋的十字路口。积极的一面是，许多治疗方法正在开发中，似乎可能对我们的这种情况的患者产生积极的影响。挑战在于，这些疗法将需要基于识别具有相关内型的受试者的有针对性的个体化治疗。
It is increasingly recognized that chronic rhinosinusitis (CRS) comprises a spectrum of different diseases with distinct clinical presentations and pathogenic mechanisms. Defining the distinct phenotypes and endotypes of CRS affects prognosis and, most importantly, is necessary as the basis for making therapeutic decisions. The need for individualized definitions of pathogenic mechanisms before initiating therapy extends to virtually all therapeutic considerations. This is clearly crucial with antibiotics, where, barring an influence from their off-target anti-inflammatory pharmacologic effects, an understanding of the role of the individual biome predicts likelihood of therapeutic benefit. However, this need for identifying individual phenotypes and endotypes also extends to the agent that is currently considered the mainstay of treatment of CRS, specifically glucocorticoids. As with asthma, it is recognized that a large minority of patients with CRS have a steroid-resistant phenotype, identification of which will preclude use of these agents with their potential side effects. Identification of endotypes is also becoming increasingly imperative because targeted biotherapeutic agents, such as anti-IgE and anti-cytokine antibodies, are becoming available. These agents are likely to benefit patients in whom the targeted mediator is not only expressed but demonstrably driving a central mechanism in that patient. In summary, the treatment of CRS is at an exciting crossroad. On the positive side, numerous therapeutics are in development that seem likely to have a positive effect in our patients with this condition. The challenge is that these therapies will require targeted individualized treatments based on identifying subjects with the relevant endotype.