Asthma and Airway Hyperresponsiveness in Children with Eosinophilic Esophagitis: EGF and FGF-2 As a Link

Rationale:
Asthma is prevalent in children with eosinophilic esophagitis (EoE), previously estimated at 24-42% versus 9% for the general population.  However, studies of pulmonary function and airway hyperresponsiveness (AHR) in children with EoE are lacking.

Methods:
A cross-sectional study was conducted of children aged 6-18 years with EoE and healthy controls. Methacholine challenge (AHR defined as provocative concentration of methacholine <8mg/ml), and exhaled nitric oxide were performed.  Peripheral blood was analyzed for total IgE, eosinophil count, eotaxin, and serum cytokines. 

Results:
Baseline spirometry was normal and not significantly different for EoE subjects (n=33) and healthy controls (n=37).  AHR was present in 33% of children with EoE and 10.8% of healthy controls (p=0.04).  20% of EoE subjects with asthma (n=15) had AHR, versus 44% of EoE subjects without asthma (n=18). Overall, 69.7% of EoE subjects had either asthma or AHR. AHR correlated strongly with serum IgE (p<0.0001) and exhaled nitric oxide (p=0.0002).

Epidermal growth factor (EGF) and fibroblastic growth factor 2 (FGF-2) were elevated in subjects with EoE and asthma , compared to healthy controls and those with EoE but no asthma (p<0.05).  Subjects with EoE and asthma who were on asthma controller medications had similar levels of EGF and FGF-2 as healthy controls.  Th₂ cytokines and eotaxin did not differ significantly among any groups.

Conclusions:
Asthma and AHR may be more prevalent than previously estimated in children with EoE. Serum elevations of EGF and FGF-2 were seen in EoE subjects with asthma, but not in subjects on asthma controller medications.