Resolution of remodeling in eosinophilic esophagitis correlates with epithelial response to topical corticosteroids.
BACKGROUND
Esophageal remodeling occurs in eosinophilic esophagitis (EE) patients but whether the components of remodeling in the subepithelium are reversible by administration of topical oral corticosteroids is unknown.


METHODS
We quantitated the degree of lamina propria remodeling in esophageal biopsies obtained before and after at least 3 months of therapy with budesonide in 16 pediatric EE subjects. In addition, we investigated whether corticosteroid therapy modulated vascular activation (expression of VCAM-1; level of interstitial edema), TGFbeta(1) activation (levels of TGFbeta(1), phosphorylated Smad2/3), and performed a pilot analysis of a polymorphism in the TGFbeta(1) promoter in relation to EE subjects who had reduced remodeling with budesonide therapy.


RESULTS
EE subjects were stratified based on the presence (n = 9) or absence (n = 7) of decreased epithelial eosinophilia following budesonide. Patients with residual eosinophil counts of <or=7 eosinophils per high power field in the epithelial space (responders) demonstrated significantly reduced esophageal remodeling with decreased fibrosis, TGFbeta(1) and pSmad2/3 positive cells, and decreased vascular activation in association with budesonide therapy. Responders were more likely to have a CC genotype at the -509 position in the TGFbeta(1) promoter.


CONCLUSIONS
Reductions in epithelial eosinophils following budesonide therapy were associated with significantly reduced esophageal remodeling.
Aceves
S S
SS
Divisions of Allergy, Immunology, Rady Children's Hospital San Diego, University of California, San Diego, CA 92123, USA.
Newbury
R O
RO
Chen
D
D
Mueller
J
J
Dohil
R
R
Hoffman
H
H
Bastian
J F
JF
Broide
D H
DH
D000284:Administration, Oral; D000287:Administration, Topical; D000293:Adolescent; D019819:Budesonide / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D004802:Eosinophilia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D004941:Esophagitis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D005260:Female; D005355:Fibrosis / Q000188:drug therapy / Q000209:etiology; D020022:Genetic Predisposition to Disease; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects
D005938:Glucocorticoids; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1; D019819:Budesonide