title: Sex-specific risk factors for childhood wheeze and longitudinal phenotypes of wheeze.
abstract: Although sexual dimorphism in wheeze and asthma prevalence are well documented, sex-specific risk factors for wheeze and longitudinal wheeze phenotypes have not been well elucidated.
  
  
  
  By using a large prebirth cohort, this study aimed to identify sex-specific risk factors for wheeze from birth through midchildhood and identify distinct longitudinal wheeze phenotypes and the sex-specific risk factors associated with these phenotypes.
  
  
  
  Mothers reported child wheeze symptoms over the past year approximately yearly on 9 occasions starting at age 1 year. We identified sex-specific predictors of wheeze, wheeze phenotypes, and sex-specific predictors of these phenotypes by using generalized estimating equations, latent class mixed models, and multinomial logistic analysis, respectively.
  
  
  
  A total of 1623 children had information on wheeze at 1 or more time points. Paternal asthma was a stronger predictor of ever wheezing in boys (odds ratio [OR], 2.15; 95% CI, 1.74-2.66) than in girls (OR, 1.53; 95% CI, 1.19-1.96; P for sex by paternal asthma interaction = .03), whereas being black or Hispanic, birth weight for gestational age z score, and breast-feeding duration had stronger associations among girls. We identified 3 longitudinal wheeze phenotypes: never/infrequent wheeze (74.1%), early transient wheeze (12.7%), and persistent wheeze (13.1%). Compared with never/infrequent wheeze, maternal asthma, infant bronchiolitis, and atopic dermatitis were associated with persistent wheeze in both sexes, but paternal asthma was associated with persistent wheeze in boys only (OR, 4.27; 95% CI, 2.33-7.83; P for sex by paternal asthma interaction = .02), whereas being black or Hispanic was a predictor for girls only.
  
  
  
  We identified sex-specific predictors of wheeze and longitudinal wheeze patterns, which might have important prognostic value and allow for a more personalized approach to wheeze and asthma treatment.
authors.affiliation: Division of Respiratory Medicine, Department of Pediatrics, Sainte-Justine University Hospital Center and University of Montreal, Montreal, Quebec, Canada. Electronic address: sze.man.tse@umontreal.ca.
authors.forename: Sze Man
authors.initials: SM
authors.lastname: Tse
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Mass.
authors.forename: Sheryl L
authors.initials: SL
authors.lastname: Rifas-Shiman
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Mass.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Coull
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
authors.forename: Augusto A
authors.initials: AA
authors.lastname: Litonjua
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Mass.
authors.forename: Emily
authors.initials: E
authors.lastname: Oken
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
authors.forename: Diane R
authors.initials: DR
authors.lastname: Gold
mesh_terms: D001249:Asthma / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype; D015995:Prevalence; D011446:Prospective Studies; D012135:Respiratory Sounds; D012723:Sex; D012727:Sex Characteristics; D012737:Sex Factors; D014481:United States
keywords: Asthma; bronchiolitis; parental asthma; sex differences