The overall goal of this project is to understand the atopic march and the role of the skin in this process of systemic allergen sensitization in children with atopic dermatitis (AD). Our overall hypothesis is that AD results in increased skin allergen absorption and systemic allergen sensitization reflected in high IgE levels. This makes patients with AD prone to the development of respiratory allergy (Atopic March). Improving skin barrier function with prophylactic topical pimecrolimus would reduce allergen absorption, allergen sensitization and reduce the prevalence of asthma. This would be evidenced by a decreased expression of cutaneous leukocyte antigen (CLA)+ TH2 cells in the pimecrolimus treated group. The clinical trial of pimecrolimus """"""""A 3-year, randomized, double-blind vehicle controlled study to evaluate the safety and efficacy of Elidel 1% cream in modifying the course of AD in infants"""""""" is being supported by Novartis Pharmaceutical Co. provides an unique opportunity to study the mechanism of atopic dermatitis and the atopic march. Our proposed study has three aims in examining the atopic march and possible prevention.
The first aim will examine specific and total allergen sensitization by allergen-specific and total IgE.
The second aim will be examining mechanistic parts of this study. We will explore the frequency of skin homing T cells, their cytokine expression and the effect of staphylococcal superantigen on their expression.
In third aim of the trial, we explore the effects of pimecrolimus as a disease-modifying agent in the prevention of asthma. Asthma phenotype will be examined by spirometry per and post-beta-2-agonist and exhaled nitric oxide.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI062698-03
Application #
7169879
Study Section
Special Emphasis Panel (ZRG1-ITHA (55))
Program Officer
Plaut, Marshall
Project Start
2005-08-15
Project End
2009-01-31
Budget Start
2007-02-01
Budget End
2008-01-31
Support Year
3
Fiscal Year
2007
Total Cost
$348,969
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Schneider, Lynda; Hanifin, Jon; Boguniewicz, Mark et al. (2016) Study of the Atopic March: Development of Atopic Comorbidities. Pediatr Dermatol 33:388-98
Brown-Whitehorn, Terri F; Spergel, Jonathan M (2010) The link between allergies and eosinophilic esophagitis: implications for management strategies. Expert Rev Clin Immunol 6:101-9
Spergel, Jonathan M (2010) From atopic dermatitis to asthma: the atopic march. Ann Allergy Asthma Immunol 105:99-106; quiz 107-9, 117