title: Sensitization trajectories in childhood revealed by using a cluster analysis.
abstract: BACKGROUND
  Assessment of sensitization at a single time point during childhood provides limited clinical information. We hypothesized that sensitization develops as specific patterns with respect to age at debut, development over time, and involved allergens and that such patterns might be more biologically and clinically relevant.
  
  
  OBJECTIVE
  We sought to explore latent patterns of sensitization during the first 6 years of life and investigate whether such patterns associate with the development of asthma, rhinitis, and eczema.
  
  
  METHODS
  We investigated 398 children from the at-risk Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) birth cohort with specific IgE against 13 common food and inhalant allergens at the ages of ½, 1½, 4, and 6 years. An unsupervised cluster analysis for 3-dimensional data (nonnegative sparse parallel factor analysis) was used to extract latent patterns explicitly characterizing temporal development of sensitization while clustering allergens and children. Subsequently, these patterns were investigated in relation to asthma, rhinitis, and eczema. Verification was sought in an independent unselected birth cohort (BAMSE) constituting 3051 children with specific IgE against the same allergens at 4 and 8 years of age.
  
  
  RESULTS
  The nonnegative sparse parallel factor analysis indicated a complex latent structure involving 7 age- and allergen-specific patterns in the COPSAC2000birth cohort data: (1) dog/cat/horse, (2) timothy grass/birch, (3) molds, (4) house dust mites, (5) peanut/wheat flour/mugwort, (6) peanut/soybean, and (7) egg/milk/wheat flour. Asthma was solely associated with pattern 1 (odds ratio [OR], 3.3; 95% CI, 1.5-7.2), rhinitis with patterns 1 to 4 and 6 (OR, 2.2-4.3), and eczema with patterns 1 to 3 and 5 to 7 (OR, 1.6-2.5). All 7 patterns were verified in the independent BAMSE cohort (R2> 0.89).
  
  
  CONCLUSIONS
  This study suggests the presence of specific sensitization patterns in early childhood differentially associated with development of clinical outcomes. Using such patterns in future research might provide more robust and clinically relevant results.
authors.affiliation: COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ann-Marie M
authors.initials: AM
authors.lastname: Schoos
authors.affiliation: COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bo L
authors.initials: BL
authors.lastname: Chawes
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Sachs Children's Hospital, Södersjukhuset, Stockholm, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Melén
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Bergström
authors.affiliation: Sachs Children's Hospital, Södersjukhuset, Stockholm, Sweden; Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Inger
authors.initials: I
authors.lastname: Kull
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Sachs Children's Hospital, Södersjukhuset, Stockholm, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Wickman
authors.affiliation: COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Bønnelykke
authors.affiliation: COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: bisgaard@copsac.com.
authors.forename: Hans
authors.initials: H
authors.lastname: Bisgaard
authors.affiliation: COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Food Science, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Morten A
authors.initials: MA
authors.lastname: Rasmussen
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D001249:Asthma / Q000453:epidemiology / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D015331:Cohort Studies; D004485:Eczema / Q000453:epidemiology / Q000276:immunology*; D005260:Female; D006801:Humans; D007114:Immunization / Q000706:statistics & numerical data*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011446:Prospective Studies; D065631:Rhinitis, Allergic / Q000453:epidemiology / Q000276:immunology*; D012306:Risk; D013548:Sweden / Q000453:epidemiology
keywords: Sensitization; asthma; children; eczema; patterns; rhinitis; specific IgE