Understanding the response to asthma biological therapy.,Clinical & Experimental Allergy

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Understanding the response to asthma biological therapy.
Clinical & Experimental Allergy ( IF 6.3 ) Pub Date : 2020-09-09 , DOI: 10.1111/cea.13724
G Roberts _{1,

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Affiliation

While we use biomarkers to assess the eligibility of patients for specific biological therapies, we do not routinely reassess these biomarkers on therapy. Upham and Jurak review the data on how biomarkers such as eosinophils, exhaled nitric oxide, and total IgE change with biological therapy in severe asthma.1, 2 They discuss how this knowledge may inform the challenging situation of the patient who does not respond to a biological therapy.

In a separate severe asthma study in this issue, Upchurch et al3 look at how omalizumab responders and non‐responders differ. They look at transcriptional variations4 between these groups to understand the mechanisms of action of omalizumab. They identify eight clusters of genes (Figure 1). The changes seen in responders were maintained with them becoming more similar to the control subjects. In contrast, non‐responders tended to remain similar to their pre‐treatment patterns. Neutrophil/eosinophil pathways were especially up‐regulated in non‐responders and did not change with omalizumab therapy. Understanding response to therapy at this endotype level has a potential to help us better personalize therapy for severe asthma.5

House dust endotoxin is thought to have a protective effect on the development of allergic sensitization in early childhood.6, 7 Gehring et al8 look at whether these effects extend into later childhood in the PIAMA birth cohort. They found that higher living room floor dust endotoxin at three months of age was associated with the lower prevalence of asthma only until four years of age in children of mothers with allergies (Figure 2). There was no association with allergic sensitization.

**Figure 1**
Open in figure viewerPowerPoint

Allergic asthma blood transcriptional profiles with omalizumab treatment. Unsupervised analysis of differentially expressed transcripts between non‐asthmatic healthy controls (green), omalizumab non‐responders (NR, blue), and omalizumab responders (R, red). See figure 1, Upchurch et al, Clin Exp Allergy 2020; 50(9):1017‐1034. [Color figure can be viewed at wileyonlinelibrary.com]

**Figure 2**
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Association between living room dust endotoxin aged three months and later asthma. Age‐specific adjusted associations between asthma at ages 1 and 17 years and endotoxins in living room floor dust samples collected at age 3 months. See figure 1, Gehring et al, Clin Exp Allergy 2020; 50(9):1055‐1064.

中文翻译：

了解对哮喘生物治疗的反应。

虽然我们使用生物标志物来评估患者接受特定生物治疗的资格，但我们不会定期重新评估这些生物标志物的治疗。Upham 和 Jurak 回顾了有关生物标志物（如嗜酸性粒细胞、呼出的一氧化氮和总 IgE）如何随着严重哮喘的生物治疗而变化的数据。1, 2他们讨论了这些知识如何告知对生物治疗没有反应的患者的挑战性情况。

在本期的另一项重度哮喘研究中，Upchurch 等人3研究了奥马珠单抗应答者和非应答者之间的差异。他们查看这些组之间的转录变异4以了解奥马珠单抗的作用机制。他们确定了八个基因簇（图 1）。在响应者中看到的变化保持不变，他们变得与对照受试者更相似。相比之下，无反应者往往与他们的治疗前模式相似。中性粒细胞/嗜酸性粒细胞通路在无反应者中特别上调，并且不会随着奥马珠单抗治疗而改变。了解在这种内型水平上对治疗的反应有可能帮助我们更好地对严重哮喘进行个性化治疗。5

屋尘内毒素被认为对儿童早期过敏性致敏的发展具有保护作用。6, 7 Gehring 等人8研究这些影响是否会延伸到 PIAMA 出生队列中的儿童后期。他们发现，三个月大时较高的客厅地板灰尘内毒素与过敏母亲的孩子直到四岁的哮喘患病率较低有关（图 2）。与过敏性致敏无关。