Project Details

Defining immune networks that underlie pediatric asthma exacerbated by rhinovirus infection

Sathi Wijeyesinghe, MD, PhD

Summary

BACKGROUND: Pediatric asthma causes millions of hospitalizations every year and is associated with compromised lung function and multiple comorbidities later in life. Despite its considerable morbidity, asthma in children remains incurable and largely unpreventable. GAP: An incomplete understanding of the pathophysiology that underlies human asthma has slowed the development of preventative or curative therapies. HYPOTHESIS: We hypothesize that human nasal organoids (HNOs) derived from children with asthma will express heightened pro-inflammatory cytokines when compared with non-asthmatic controls. Following rhinovirus infection, we hypothesize that dysregulation of pro-inflammatory immune signaling networks catalyzes the acute pediatric asthma attack. METHODS: We are obtaining mid-turbinate swab samples and nasal washes from pediatric patients with and without asthma to generate HNOs. We will characterize their immune landscape using high-parameter cytokine profiling. We will then extend our model to study the kinetics of rhinovirus infection in the asthmatic airway epithelium and examine modifiable epithelial derived cytokines that may precipitate rhinovirus-induced inflammation. RESULTS: The Piedra lab has previously profiled changes to the airway organoid epithelium and epithelial cytokine response following multiple respiratory infections. We have identified inherent differences airway epithelial response to respiratory infection in pediatric and adult samples. IMPACT: A human airway epithelial model of pediatric asthma will augment preclinical testing capacity and accelerate translational asthma research. Clinical endpoints of this proposal include the identification of biomarkers to predict asthmatic disease severity and targeted immunomodulatory therapies to treat asthma personalized to a patient’s HNO endotype.