title: Relationships among aeroallergen sensitization, peripheral blood eosinophils, and periostin in pediatric asthma development.
abstract: BACKGROUND
  Biomarkers, preferably noninvasive, that predict asthma inception in children are lacking.
  
  
  OBJECTIVE
  Little is known about biomarkers of type 2 inflammation in early life in relation to asthma inception. We evaluated aeroallergen sensitization, peripheral blood eosinophils, and serum periostin as potential biomarkers of asthma in children.
  
  
  METHODS
  Children enrolled in the Childhood Origins of ASThma study were followed prospectively from birth. Blood samples were collected at ages 2, 4, 6, and 11 years, and serum-specific IgE levels, blood eosionophil counts, and periostin levels were measured in 244 children. Relationships among these biomarkers, age, and asthma were assessed.
  
  
  RESULTS
  Serum periostin levels were approximately 2- to 3-fold higher in children than previously observed adult levels. Levels were highest at 2 years (145 ng/mL), and did not change significantly between 4 and 11 years (128 and 130 ng/mL). Age 2 year periostin level of 150 ng/mL or more predicted asthma at age 6 years (odds ratio [OR], 2.3; 95% CI, 1.3-4.4). Eosinophil count of 300 cells/μL or more and aeroallergen sensitization at age 2 years were each associated with increased risk of asthma at age 6 years (OR, 3.1; 95% CI, 1.7-6.0 and OR, 3.3; 95% CI, 1.7-6.3). Children with any 2 of the biomarkers had a significantly increased risk of developing asthma by school age (≥2 biomarkers vs none: OR, 6.6; 95% CI, 2.7-16.0).
  
  
  CONCLUSIONS
  Serum periostin levels are significantly higher in children than in adults, likely due to bone turnover, which impairs clinical utility in children. Early life aeroallergen sensitization and elevated blood eosinophils are robust predictors of asthma development. Children with evidence of activation of multiple pathways of type 2 inflammation in early life are at greatest risk for asthma development.
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, University of Wisconsin School of Medicine & Public Health, Madison, Wis. Electronic address: Handerson@pediatrics.wisc.edu.
authors.forename: Halie M
authors.initials: HM
authors.lastname: Anderson
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, University of Wisconsin School of Medicine & Public Health, Madison, Wis.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Lemanske
authors.affiliation: Genentech, Inc, South San Francisco, Calif.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Arron
authors.affiliation: Genentech, Inc, South San Francisco, Calif.
authors.forename: Cecile T J
authors.initials: CTJ
authors.lastname: Holweg
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine & Public Health, Madison, Wis.
authors.forename: Victoria
authors.initials: V
authors.lastname: Rajamanickam
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine & Public Health, Madison, Wis.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gangnon
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, University of Wisconsin School of Medicine & Public Health, Madison, Wis.
authors.forename: James E
authors.initials: JE
authors.lastname: Gern
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, University of Wisconsin School of Medicine & Public Health, Madison, Wis.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Jackson
mesh_terms: D000367:Age Factors; D000393:Air Pollutants / Q000276:immunology; D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000097:blood* / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D015815:Cell Adhesion Molecules / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004804:Eosinophils; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D019570:Inhalation Exposure; D007958:Leukocyte Count; D008297:Male; D016017:Odds Ratio
chemical_list: D000393:Air Pollutants; D000485:Allergens; D015415:Biomarkers; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; D007073:Immunoglobulin E
keywords: Biomarkers; aeroallergen sensitization; asthma development; children; periostin; peripheral blood eosinophils