Elsevier

The Journal of Pediatrics

Volume 164, Issue 2, February 2014, Pages 289-294.e2
The Journal of Pediatrics

Original Article
Early-Life Risk Factors for Childhood Wheeze Phenotypes in a High-Risk Birth Cohort

Portions of this study were presented as a poster during the European Respiratory Society Conference, Vienna, Austria, September 1-5, 2012.
https://doi.org/10.1016/j.jpeds.2013.09.056Get rights and content

Objective

To define longitudinal childhood wheeze phenotypes and identify their early-life risk factors.

Study design

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.

Conclusion

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.

Section snippets

Methods

The MACS began as a randomized controlled trial investigating associations between 3 infant formulas at weaning on subsequent allergies.9 It comprised 620 infants enrolled by recruiting pregnant women from Melbourne, Australia between 1990 and 1994. Eligible infants had at least 1 first-degree family member with a history of eczema, asthma, allergic rhinitis, and/or severe food allergy. The recruitment process has been described previously.10 The Mercy Maternity Hospital Ethics Committee

Results

Baseline demographic and clinical characteristics are presented in Table I. Parents were predominantly Australian born (85%) and of high socioeconomic status (1 or both parents tertiary educated in 72% of couples). Approximately one-half of the children (51%) were male. All children had at least 1 immediate family member with “allergic disease,” and 74% had 2 or more affected family members.

During the first 2 years of life, the 4-week current wheeze prevalence (ie, wheeze in the previous 4

Discussion

This study established a distinct profile of potentially etiologically important early-life risk factors for each childhood wheeze phenotype identified using LCA. All wheeze phenotypes except early transient predicted current wheeze at age 12 years, the time at which children have outgrown transient wheeze and remaining wheeze is likely to persist.19 Importantly, the risk factor profiles, in combination with existing mechanistic hypothesis, identify possible causative mechanisms for each of

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      When interpreting our results, definitions of exposure and outcome need to be considered. For both outcomes, different disease trajectories have been found [38–45]. As we investigated symptoms of wheeze and eczema during the first year of life, our results only apply to phenotypes with early symptoms (early-transient or early-persistent symptoms).

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    Funding for the first 6 years of the study was from Nestec (a subsidiary of Nestlé Australia). The 12-year follow-up was supported by the Asthma Foundation of Victoria. C.L. is funded by the Sidney Myer Health Fund. C.L. A.L., L.G., M.M., and S.D. are funded by the National Health and Medical Research Council of Australia. K.A. is funded by the Charles and Sylvia Viertel Charitable Foundation. M.A. holds an investigator initiated grant from Pfizer for unrelated research. The other authors declare no conflicts of interest.

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