312:
Biomarkers of Severity in Pediatric Asthma in Memphis, Tennessee
Sunday, March 4, 2018
South Hall A2 (Convention Center)
D. Betty Lew, MD FAAAAI, Amali E. Samarasinghe, PhD, Rhiannon Renkert, Robert Sealy, Catherine Hammond, MD, Patricia J Dubin, MD, Julia L Hurwitz, PhD
RATIONALE:

Asthma is a syndrome that affects over 8% of the pediatric population in the United States, and Memphis, TN, is the “asthma capital.” Le Bonheur Children’s Hospital cares for over 4,000 children with asthma annually of which ~4.5% may require intensive care. Biomarkers of severe disease in this population have not yet been determined. If elucidated, this information will allow clinical endotyping of these patients and promote more effective and personalized care.

METHODS: Blood collected from 100 severe asthmatics and 47 age-matched hospitalized non-asthmatics (per Institutional Review Board approval), was used to collect plasma. Concentrations of antibody isotypes were determined by MILLIPLEX® multiplex assay in 19 matched samples per group, while β-hexosaminidase (HEX) activity was measured by colorimetry and 18 inflammatory mediators by Luminex multiplex assay in all samples.

RESULTS: While IgM, IgG3, IgG4, and IgA were similar between the groups, asthmatics had significantly reduced levels of IgG2 levels (<1 mg/mL) compared to controls (p<0.01). Asthmatics (6/19) and non-asthmatics (1/19) with reduced plasma IgG1 also had reduced IgG2. Beta-HEX levels (>2 IU/L) were higher in asthmatics (p<0.0001) and negatively correlated with IgG1/IgG2-deficiencies. Receptor for advanced glycation end products (RAGE) and surfactant protein (SP)-D were elevated in asthmatics, while granzyme A was reduced (p<0.001) compared to controls.

CONCLUSIONS: Biomarkers of asthma severity in Memphis may be β-HEXhiRAGEhiSP-DhiIgG2loGranzyme Alo. This profile may denote vulnerability to infections thereby triggering asthma exacerbations or respiratory inflammation. Ongoing studies are aimed at identifying pathways to revert this phenotype to reduce asthma morbidity in children.