Early-life risk factors for childhood wheeze phenotypes in a high-risk birth cohort.
OBJECTIVE
To define longitudinal childhood wheeze phenotypes and identify their early-life risk factors.


METHODS
Current wheeze was recorded 23 times up to age 7 years in a birth cohort at high risk for allergy (n = 620). Latent class analysis of wheeze responses identified 5 classes. Multinomial logistic regression estimated associations of probability-weighted wheezing classes with early-life factors. All phenotypes were compared with never/infrequent wheezers.


RESULTS
Lower respiratory tract infection (LRTI) by 1 year (relative risk [RR], 3.00; 95% CI, 1.58-5.70), childcare by 1 year (RR, 1.51; 95% CI, 1.02-2.22), and higher body mass index (RR, 2.51; 95% CI, 1.09-5.81) were associated with increased risk of early transient wheeze, whereas breastfeeding was protective (RR, 0.54; 95% CI, 0.32-0.90). LRTI (RR, 6.54; 95% CI, 2.55-16.76) and aeroallergen sensitization (RR, 4.95; 95% CI, 1.74-14.02) increased the risk of early persistent wheeze. LRTI (RR, 5.31; 95% CI, 2.71-10.41), eczema (RR, 2.77; 95% CI, 1.78-4.31), aeroallergen sensitization (RR, 5.60; 95% CI, 2.86-10.9), and food sensitization (RR, 2.77; 95% CI, 1.56-4.94) increased the risk of intermediate-onset wheeze, whereas dog exposure at baseline (RR, 0.52; 95% CI, 0.32-0.84) and first-born status (RR, 0.49; 95% CI, 0.32-0.76) were protective. Heavy parental smoking at birth (RR, 3.18; 95% CI, 1.02-9.88) increased the risk of late-onset wheeze, whereas breastfeeding reduced it (RR, 0.34; 95% CI, 0.12-0.96). All wheeze classes except early transient had greater risk of wheeze at age 12 years compared with never/infrequent wheezers.


CONCLUSIONS
We found distinct early-life risk factor profiles for each wheeze phenotype. These findings provide insight into possible wheeze mechanisms and have implications for identifying preventive strategies and addressing clinical management of early-life wheeze.
Center for Molecular, Environmental, Genetic, and Analytic Epidemiology, School of Population and Global Health, University of Melbourne, Melbourne, Australia. Electronic address: clodge@unimelb.edu.au.
Caroline J
CJ
Lodge
Center for Molecular, Environmental, Genetic, and Analytic Epidemiology, School of Population and Global Health, University of Melbourne, Melbourne, Australia.
Sophie
S
Zaloumis
Center for Molecular, Environmental, Genetic, and Analytic Epidemiology, School of Population and Global Health, University of Melbourne, Melbourne, Australia; Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia.
Adrian J
AJ
Lowe
Center for Molecular, Environmental, Genetic, and Analytic Epidemiology, School of Population and Global Health, University of Melbourne, Melbourne, Australia.
Lyle C
LC
Gurrin
Center for Molecular, Environmental, Genetic, and Analytic Epidemiology, School of Population and Global Health, University of Melbourne, Melbourne, Australia.
Melanie C
MC
Matheson
Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia.
Christine
C
Axelrad
Deakin Population Health, Deakin University, Burwood, Australia.
Catherine M
CM
Bennett
Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia.
David J
DJ
Hill
Department of Pediatrics, John Hunter Children's Hospital, Newcastle, Australia.
Clifford S
CS
Hosking
Bergen Respiratory Research Group, Center of International Health, University of Bergen, Bergen, Norway; Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway.
Cecilie
C
Svanes
Department of Epidemiology and Preventive Medicine, The Alfred Hospital, Monash University, Melbourne, Australia.
Michael J
MJ
Abramson
Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia; Department of Allergy and Immunology, Royal Children's Hospital, Parkville, Australia.
Katrina J
KJ
Allen
Center for Molecular, Environmental, Genetic, and Analytic Epidemiology, School of Population and Global Health, University of Melbourne, Melbourne, Australia; Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia.
Shyamali C
SC
Dharmage
D000485:Allergens / Q000009:adverse effects*; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000150:complications* / Q000235:genetics; D007223:Infant; D008297:Male; D010641:Phenotype; D011379:Prognosis; D012135:Respiratory Sounds / Q000209:etiology* / Q000235:genetics; D012141:Respiratory Tract Infections / Q000150:complications* / Q000235:genetics; D012307:Risk Factors; D013997:Time Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D000485:Allergens; D014028:Tobacco Smoke Pollution
BMI; Body mass index; LCA; LRTI; Latent class analysis; Lower respiratory tract infection; MACS; Melbourne Atopy Cohort Study; RR; Relative risk