title: International variations in associations of allergic markers and diseases in children: ISAAC Phase Two.
abstract: BACKGROUND
  Circulating allergen-specific IgE (sIgE) and skin prick tests (SPT) are used to define atopy. Downregulation of local inflammatory responsiveness has been proposed to explain a low prevalence of positive SPTs in less affluent countries. We analysed the association between SPTs, total and allergen-specific IgE and their relationships to allergic symptoms in centres with diverse living conditions.
  
  
  METHODS
  Cross-sectional studies of stratified random samples of 8 to 12-year-old children (n = 7461) used the standardized methodology of Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC). Symptoms of asthma, rhinitis and eczema were ascertained by parental questionnaires. Skin examination, hypertonic saline bronchial challenge, six aeroallergen SPTs and measurements of serum total IgE and sIgE were performed.
  
  
  RESULTS
  In nonaffluent countries, a higher proportion of children with positive SPT had no detectable sIgE (range 37-61%) than in affluent countries (0-37%). Total serum IgE was associated with all disease outcomes among children with both positive SPT and sIgE (P < 0.001), but only with self-reported eczema in children with negative SPTs and negative sIgE.
  
  
  CONCLUSIONS
  The international pattern of discordance between SPT and sIgE results did not support the downregulation hypothesis. Among children with no evidence of sensitization to common aeroallergens, increased total IgE contributes little to the risk of wheeze and rhinitis in the general population but may play a role in eczema.
authors.affiliation: Institute of Epidemiology, Ulm University, Helmholtzstrasse 22, Ulm, Germany. gudrun.weinmayr@uni-ulm.de
authors.forename: G
authors.initials: G
authors.lastname: Weinmayr
authors.forename: J
authors.initials: J
authors.lastname: Genuneit
authors.forename: G
authors.initials: G
authors.lastname: Nagel
authors.forename: B
authors.initials: B
authors.lastname: Björkstén
authors.forename: M
authors.initials: M
authors.lastname: van Hage
authors.forename: A
authors.initials: A
authors.lastname: Priftanji
authors.forename: P
authors.initials: P
authors.lastname: Cooper
authors.forename: M-A
authors.initials: MA
authors.lastname: Rijkjärv
authors.forename: E
authors.initials: E
authors.lastname: von Mutius
authors.forename: J
authors.initials: J
authors.lastname: Tsanakas
authors.forename: F
authors.initials: F
authors.lastname: Forastiere
authors.forename: G
authors.initials: G
authors.lastname: Doekes
authors.forename: J B
authors.initials: JB
authors.lastname: Garrido
authors.forename: M M
authors.initials: MM
authors.lastname: Suarez-Varela
authors.forename: L
authors.initials: L
authors.lastname: Bråbäck
authors.forename: D P
authors.initials: DP
authors.lastname: Strachan
mesh_terms: D015415:Biomarkers; D002648:Child; D003430:Cross-Sectional Studies; D004485:Eczema / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis* / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood*; D012135:Respiratory Sounds / Q000276:immunology; D012220:Rhinitis / Q000276:immunology; D012882:Skin Tests / Q000592:standards*; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; D007073:Immunoglobulin E