Elisabet Johansson1, Jocelyn M Biagini Myers1, Lisa J Martin2, Hua He2, Patrick Ryan3, Grace K LeMasters3, David I Bernstein4, James Lockey3, Gurjit K Khurana Hershey1. 1. Department of Pediatrics, University of Cincinnati, Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 2. Department of Pediatrics, University of Cincinnati, Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 3. Department of Environmental Health, University of Cincinnati, Cincinnati, Ohio. 4. Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio.
Abstract
BACKGROUND: The "atopic march" has been considered a linear progression starting with eczema and culminating with development of asthma. Not all asthma cases, however, are preceded by eczema, and not all children with eczema go on to develop asthma. OBJECTIVE: The aim of this study was to explore the impact of allergic sensitization patterns on the association between early eczema and later childhood asthma. Given the numerous reported associations of the ciliary gene KIF3A with the atopic march, we also examined the impact of KIF3A risk allele rs12186803 on our analyses. METHODS: We studied 505 participants in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), a prospective birth cohort, with longitudinal eczema and asthma outcomes as well as prospective data regarding timing of sensitization to foods and aeroallergens. KIF3A genotypes were available on all children. RESULTS: Two high-risk groups were identified: one with and one without early eczema. The high-risk group with early eczema was more likely to be sensitized to food allergens, while the group without early eczema was more likely to be polysensitized to aeroallergens. The KIF3A rs12186803 risk allele interacted with food sensitization to increase asthma risk in children with eczema (P = 0.02). In children without eczema, asthma was associated with the interaction between rs12186803 and aeroallergen sensitization (P = 0.007). CONCLUSIONS & CLINICAL RELEVANCE: KIF3A interacted differentially with sensitization pattern to increase the risk of asthma in two high-risk groups of children with and without early eczema. Given the reported role of KIF3A in epithelial cell functioning, the results add evidence to the hypothesis that an impaired epithelial barrier is a key aspect in the development of allergic disease.
BACKGROUND: The "atopic march" has been considered a linear progression starting with eczema and culminating with development of asthma. Not all asthma cases, however, are preceded by eczema, and not all children with eczema go on to develop asthma. OBJECTIVE: The aim of this study was to explore the impact of allergic sensitization patterns on the association between early eczema and later childhood asthma. Given the numerous reported associations of the ciliary gene KIF3A with the atopic march, we also examined the impact of KIF3A risk allele rs12186803 on our analyses. METHODS: We studied 505 participants in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), a prospective birth cohort, with longitudinal eczema and asthma outcomes as well as prospective data regarding timing of sensitization to foods and aeroallergens. KIF3A genotypes were available on all children. RESULTS: Two high-risk groups were identified: one with and one without early eczema. The high-risk group with early eczema was more likely to be sensitized to food allergens, while the group without early eczema was more likely to be polysensitized to aeroallergens. The KIF3Ars12186803 risk allele interacted with food sensitization to increase asthma risk in children with eczema (P = 0.02). In children without eczema, asthma was associated with the interaction between rs12186803 and aeroallergen sensitization (P = 0.007). CONCLUSIONS & CLINICAL RELEVANCE: KIF3A interacted differentially with sensitization pattern to increase the risk of asthma in two high-risk groups of children with and without early eczema. Given the reported role of KIF3A in epithelial cell functioning, the results add evidence to the hypothesis that an impaired epithelial barrier is a key aspect in the development of allergic disease.
Authors: Theresa W Guilbert; Wayne J Morgan; Robert S Zeiger; David T Mauger; Susan J Boehmer; Stanley J Szefler; Leonard B Bacharier; Robert F Lemanske; Robert C Strunk; David B Allen; Gordon R Bloomberg; Gregory Heldt; Marzena Krawiec; Gary Larsen; Andrew H Liu; Vernon M Chinchilli; Christine A Sorkness; Lynn M Taussig; Fernando D Martinez Journal: N Engl J Med Date: 2006-05-11 Impact factor: 91.245
Authors: Grace K LeMasters; Kimberly Wilson; Linda Levin; Jocelyn Biagini; Patrick Ryan; James E Lockey; Sherry Stanforth; Stephanie Maier; Jun Yang; Jeff Burkle; Manuel Villareal; Gurjit K Khurana Hershey; David I Bernstein Journal: J Pediatr Date: 2006-10 Impact factor: 4.406
Authors: Jocelyn M Biagini; Grace K LeMasters; Patrick H Ryan; Linda Levin; Tiina Reponen; David I Bernstein; Manuel Villareal; Gurjit K Khurana Hershey; Jeffrey Burkle; James Lockey Journal: Pediatr Allergy Immunol Date: 2006-06 Impact factor: 6.377
Authors: Jayanta Gupta; Emilie Grube; Mark B Ericksen; Michelle D Stevenson; Anne W Lucky; Anita P Sheth; Amal H Assa'ad; Gurjit K Khurana Hershey Journal: J Allergy Clin Immunol Date: 2008-02-04 Impact factor: 10.793
Authors: Jocelyn M Biagini Myers; Michael G Sherenian; Asel Baatyrbek Kyzy; Rosario Alarcon; Amen An; Zachary Flege; David Morgan; Tammy Gonzalez; Mariana L Stevens; Hua He; John W Kroner; Daniel Spagna; Brittany Grashel; Lisa J Martin; Andrew B Herr; Gurjit K Khurana Hershey Journal: J Allergy Clin Immunol Pract Date: 2020-04-14
Authors: Elisabet Johansson; Jocelyn M Biagini; Lisa J Martin; Hua He; John W Kroner; Cassandra Almasri; Veronica Velasquez; Maud Sonzogni; Stanley B DeVore; Daniel Spagna; Brittany Grashel; Gurjit K Khurana Hershey Journal: Ann Allergy Asthma Immunol Date: 2022-01-23 Impact factor: 6.248
Authors: Tammy Gonzalez; Mariana L Stevens; Asel Baatyrbek Kyzy; Rosario Alarcon; Hua He; John W Kroner; Daniel Spagna; Brittany Grashel; Elaine Sidler; Lisa J Martin; Jocelyn M Biagini Myers; Gurjit K Khurana Hershey; Andrew B Herr Journal: Allergy Date: 2020-08-09 Impact factor: 13.146