Treatment by Biomarker-informed Endotype Versus Guideline Care in Children With Difficult-to-treat Asthma

Abstract

To develop a biomarker-informed treatment model for difficult-to-treat (DTT) asthma and conduct a pilot feasibility study of its use.The study included 20 children aged 6 to 17 years with DTT asthma defined as severe persistent asthma or moderate persistent asthma in addition to at least 1 of the following in the last year: 2 asthma control tests (ACT) less than 20, an emergency department visit or hospitalization, or 2 courses of steroids because of asthma.This was a feasibility pilot study with a case-crossover design comparing asthma outcomes before and after the implementation of an individualized biomarker-informed treatment algorithm in addition to guideline-based care. This was developed a priori and included 3 phenotypes defined based on total IgE, specific IgE, skin prick testing, and serum IL-17 level: allergic, nonallergic, and mixed. The algorithm also incorporated IL-6, 25(OH)-vitamin D, an indicator of environmental tobacco smoke (urinary cotinine), tests for DNA methylation in the gene promotors of proteins related to poor asthma phenotypes (OTX2 and LDHC), and a genetic marker of rhinovirus susceptibility (CDHR3 variant rs6967330). Transepidermal water loss and the pediatric sleep questionnaire (to assess for sleep disordered breathing) were also assessed.There was no difference in ACT scores after guideline care only. There was a statistically significant, but not clinically relevant increase in ACT scores compared with baseline by the end of the study and after the personalized, biomarker-informed treatment plans were implemented (22.5 vs 23.0; P = .01). Emergency department visits decreased compared with baseline (1 vs 0; P = .04). The was no difference in the rate of systemic steroids. Pulmonary function tests did not significantly improve over the course of the study.This pilot study demonstrated feasibility of delivering personalized, biomarker-informed care to children with DTT asthma, with all children in the study receiving additional interventions to guideline-based care. Outcomes suggest this may result in superior control. Many molecular endotypes were identified within the broader clinical phenotypes, as well as a minimal number of nonredundant biomarkers that could be used in a larger, future study.This article highlights the heterogeneity of asthma and a novel approach to treating patients with DTT asthma by assimilating multiple biomarkers into a personalized treatment algorithm and studying its clinical impact. The study is limited in its size and generalizability, and some improvements from baseline to the end of the study could have been related to the structure and attention of the program rather than the biomarker-informed interventions. However, this study was innovative and provides a compelling foundation for larger studies in the future to improve asthma management beyond standard care.URL: www.pediatrics.org/cgi/doi/10.1542/peds.10.1016/j.anai.2022.01.030