Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Ann Allergy Asthma Immunol. 2022 May;128(5):535-543.e6. doi: 10.1016/j.anai.2022.01.030. Epub 2022 Feb 3.
Asthma is heterogeneous, contributing to difficulty in disease management.
To develop a biomarker-informed treatment model for difficult-to-treat (DTT) asthma and conduct a pilot feasibility study.
School-aged children (n = 21) with DTT asthma were enrolled and completed 3 medical visits (V1-V3). V2 and V3 were completed approximately 3.5 months and 12 months after V1, respectively. At V1, guideline care and adherence interventions were initiated, and blood samples were collected for asthma biomarker assessment. A personalized treatment algorithm was developed based on biomarkers (treatment by endotype) and was implemented at V2. Asthma outcomes were compared from V1 to V2 (guideline-based care) to V2 to V3 (guideline + biomarker-informed care).
Overall retention was 86%. There was an even distribution of participants with allergy, without allergy, and with mixed allergies. The participants received an average of 5.9 interventions (range, 3-9). The allergic phenotype was characterized by increased CDHR3 risk genotype and high transepidermal water loss. High serum interleukin-6 level was most notable in the mixed allergic subgroup. The nonallergic phenotype was characterized by vitamin D deficiency and poor steroid treatment responsiveness. The personalized treatment plans were associated with decreased emergency department visits (median, 1 vs 0; P = .04) and increased asthma control test scores (median, 22.5 vs 23.0; P = .01).
The biomarker-based treatment algorithm triggered interventions on top of guideline care in all children with DTT asthma studied, supporting the need for this type of multipronged approach. Our findings identify the minimal biomarker set that is informative, reveal that this treatment-by-endotype intervention is feasible and may be superior to guideline care alone, and provide a strong foundation for a definitive trial.
ClinicalTrials.gov identifier: NCT04179461.
哮喘具有异质性，导致疾病管理困难。
为治疗困难（DTT）哮喘开发一种基于生物标志物的治疗模型，并进行初步可行性研究。
招募了 21 名患有 DTT 哮喘的学龄儿童，并完成了 3 次就诊（V1-V3）。V2 和 V3 分别在 V1 后约 3.5 个月和 12 个月完成。在 V1 时，启动了指南治疗和依从性干预措施，并采集血液样本进行哮喘生物标志物评估。根据生物标志物（根据表型治疗）制定个性化治疗算法，并在 V2 时实施。比较 V1 至 V2（基于指南的护理）和 V2 至 V3（指南+基于生物标志物的护理）的哮喘结果。
总体保留率为 86%。参与者的过敏、无过敏和混合过敏的分布均匀。参与者接受了平均 5.9 次干预（范围为 3-9 次）。过敏表型的特点是 CDHR3 风险基因型增加和经皮水分丢失增加。混合过敏亚组中，血清白细胞介素-6 水平升高最为显著。非过敏表型的特点是维生素 D 缺乏和类固醇治疗反应不佳。个性化治疗计划与减少急诊就诊次数（中位数，1 次比 0 次；P=0.04）和增加哮喘控制测试评分（中位数，22.5 比 23.0；P=0.01）相关。
在研究的所有 DTT 哮喘儿童中，基于生物标志物的治疗算法在指南治疗的基础上触发了干预措施，这支持了这种多管齐下方法的必要性。我们的发现确定了信息丰富的最小生物标志物集，表明这种针对表型的干预是可行的，并且可能优于单独的指南治疗，为确定性试验提供了坚实的基础。
ClinicalTrials.gov 标识符：NCT04179461。
