Department of Respiratory Sciences, Leicester NIHR BRC, Institute for Lung Health, University of Leicester, Leicester, UK.
Wellcome-Wolfson Centre for Experimental Medicine, School of Medicine, Dentistry, and Biological Sciences, Belfast, UK.
Allergy. 2022 Nov;77(11):3362-3376. doi: 10.1111/all.15425. Epub 2022 Jul 15.
In T2-mediated severe asthma, biologic therapies, such as mepolizumab, are increasingly used to control disease. Current biomarkers can indicate adequate suppression of T2 inflammation, but it is unclear whether they provide information about airway microbial composition. We investigated the relationships between current T2 biomarkers and microbial profiles, characteristics associated with a Proteobacteria microbial profile and the effects of mepolizumab on airway ecology.
Microbiota sequencing was performed on sputum samples obtained at stable and exacerbation state from 140 subjects with severe asthma participating in two clinical trials. Inflammatory subgroups were compared on the basis of biomarkers, including FeNO and sputum and blood eosinophils. Proteobacteria subjects were identified by Proteobacteria to Firmicutes ratio ≥0.485. Where paired sputum from stable visits was available, we compared microbial composition at baseline and following ≥12 weeks of mepolizumab.
Microbial composition was not related to inflammatory subgroup based on sputum or blood eosinophils. FeNO ≥50 ppb when stable and at exacerbation indicated a group with less dispersed microbial profiles characterised by high alpha-diversity and low Proteobacteria. Proteobacteria subjects were neutrophilic and had a longer time from asthma diagnosis than Proteobacteria subjects. In those studied, mepolizumab did not alter airway bacterial load or lead to increased Proteobacteria.
High FeNO could indicate a subgroup of severe asthma less likely to benefit from antimicrobial strategies at exacerbation or in the context of poor control. Where FeNO is <50 ppb, biomarkers of microbial composition are required to identify those likely to respond to microbiome-directed strategies. We found no evidence that mepolizumab alters airway microbial composition.
在 T2 介导的严重哮喘中，生物疗法，如美泊利珠单抗，越来越多地被用于控制疾病。目前的生物标志物可以表明 T2 炎症得到充分抑制，但尚不清楚它们是否提供有关气道微生物组成的信息。我们研究了当前 T2 生物标志物与微生物谱之间的关系，与变形菌门微生物谱相关的特征，以及美泊利珠单抗对气道生态的影响。
对参加两项临床试验的 140 例严重哮喘患者稳定期和加重期的痰样进行了微生物组测序。根据生物标志物（包括 FeNO 和痰及血嗜酸性粒细胞）比较炎症亚组。通过变形菌门/厚壁菌门比值≥0.485 确定变形菌门患者。对于稳定期可获得配对痰样的患者，我们比较了基线和接受≥12 周美泊利珠单抗治疗后的微生物组成。
微生物组成与基于痰或血嗜酸性粒细胞的炎症亚组无关。稳定期和加重期 FeNO≥50 ppb 表明微生物谱分布较不分散，具有较高的 alpha 多样性和较低的变形菌门。变形菌门患者为中性粒细胞性，从哮喘诊断到现在的时间比变形菌门患者长。在研究中，美泊利珠单抗并未改变气道细菌负荷或导致变形菌门增加。
高 FeNO 可能表明在加重期或控制不佳的情况下，严重哮喘的一个亚组不太可能从抗菌策略中获益。在 FeNO<50 ppb 的情况下，需要微生物组成的生物标志物来识别可能对微生物组靶向策略有反应的患者。我们没有发现美泊利珠单抗改变气道微生物组成的证据。
