title: Differential factors associated with challenge-proven food allergy phenotypes in a population cohort of infants: a latent class analysis.
abstract: BACKGROUND
  Food allergy, eczema and wheeze are early manifestations of allergic disease and commonly co-occur in infancy although their interrelationship is not well understood. Data from population studies are essential to determine whether there are differential drivers of multi-allergy phenotypes. We aimed to define phenotypes and risk factors of allergic disease using latent class analysis (LCA).
  
  
  METHODS
  The HealthNuts study is a prospective, population-based cohort of 5276 12-month-old infants in Melbourne, Australia. LCA was performed using the following baseline data collected at age 12 months: food sensitization (skin prick test ≥ 2 mm) and allergy (oral food challenge) to egg, peanut and sesame; early (< 4 months) and late-onset eczema; and wheeze in the first year of life. Risk factors were modelled using multinomial logistic regression.
  
  
  RESULTS
  Five distinct phenotypes were identified: no allergic disease (70%), non-food-sensitized eczema (16%), single egg allergy (9%), multiple food allergies (predominantly peanut) (3%) and multiple food allergies (predominantly egg) (2%). Compared to the baseline group of no allergic disease, shared risk factors for all allergic phenotypes were parents born overseas (particularly Asia), delayed introduction of egg, male gender (except for single egg allergy) and family history of allergic disease, whilst exposure to pet dogs was protective for all phenotypes. Other factors including filaggrin mutations, vitamin D and the presence of older siblings differed by phenotype.
  
  
  CONCLUSIONS
  Multiple outcomes in infancy can be used to determine five distinct allergy phenotypes at the population level, which have both shared and separate risk factors suggesting differential mechanisms of disease.
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Vic., Australia.|Department of Paediatrics, University of Melbourne, Parkville, Vic., Australia.
authors.forename: R L
authors.initials: RL
authors.lastname: Peters
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Vic., Australia.|Department of Paediatrics, University of Melbourne, Parkville, Vic., Australia.|Department of Allergy and Immunology, Royal Children's Hospital, Parkville, Vic., Australia.|School of Inflammation and Repair, The University of Manchester, Manchester, UK.
authors.forename: K J
authors.initials: KJ
authors.lastname: Allen
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Vic., Australia.|Melbourne School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne, Parkville, Vic., Australia.
authors.forename: S C
authors.initials: SC
authors.lastname: Dharmage
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Vic., Australia.|Melbourne School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne, Parkville, Vic., Australia.
authors.forename: C J
authors.initials: CJ
authors.lastname: Lodge
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Vic., Australia.|Melbourne School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne, Parkville, Vic., Australia.
authors.forename: J J
authors.initials: JJ
authors.lastname: Koplin
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Vic., Australia.|Melbourne School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne, Parkville, Vic., Australia.
authors.forename: A-L
authors.initials: AL
authors.lastname: Ponsonby
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Vic., Australia.|Department of Paediatrics, University of Melbourne, Parkville, Vic., Australia.
authors.forename: M
authors.initials: M
authors.lastname: Wake
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Vic., Australia.|Melbourne School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne, Parkville, Vic., Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: Lowe
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Vic., Australia.|Department of Paediatrics, University of Melbourne, Parkville, Vic., Australia.|Department of Allergy and Immunology, Royal Children's Hospital, Parkville, Vic., Australia.
authors.forename: M L K
authors.initials: MLK
authors.lastname: Tang
authors.affiliation: Melbourne School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne, Parkville, Vic., Australia.
authors.forename: M C
authors.initials: MC
authors.lastname: Matheson
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Vic., Australia.|Melbourne School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne, Parkville, Vic., Australia.
authors.forename: L C
authors.initials: LC
authors.lastname: Gurrin
mesh_terms: D000485:Allergens / Q000276:immunology; D001315:Australia / Q000453:epidemiology; D015331:Cohort Studies; D004777:Environment; D005260:Female; D000091344:Filaggrin Proteins; D005502:Food / Q000009:adverse effects*; D005512:Food Hypersensitivity / Q000175:diagnosis* / Q000453:epidemiology* / Q000276:immunology; D006801:Humans; D007223:Infant; D007381:Intermediate Filament Proteins / Q000276:immunology; D008297:Male; D015233:Models, Statistical; D010641:Phenotype; D011159:Population Surveillance; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D014807:Vitamin D / Q000276:immunology
chemical_list: D000485:Allergens; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D014807:Vitamin D
keywords: eczema; food allergy; latent class analysis; phenotypes; population study