House dust mite sensitization in toddlers predicts current wheeze at age 12 years

doi:10.1016/j.jaci.2011.06.038

Journal of Allergy and Clinical Immunology

Volume 128, Issue 4, October 2011, Pages 782-788.e9

https://doi.org/10.1016/j.jaci.2011.06.038 Get rights and content

Background

Identification of children at risk of developing asthma provides a window of opportunity for risk-reducing interventions. Allergen sensitization might identify high-risk children.

Objective

We sought to determine whether skin prick tests (SPTs) to individual allergens up to age 2 years predict wheeze at age 12 years.

Methods

In a birth cohort of 620 children oversampled for familial allergy, sensitization was assessed by using SPTs (monosensitized, polysensitized, or either) to 6 allergens at ages 6, 12, and 24 months. Wheeze and eczema were recorded 18 times during the first 2 years. Current wheeze was recorded at age 12 years. Adjusted associations were evaluated by multiple logistic regression.

Results

A positive SPT to house dust mite (HDM) at age 1 or 2 years predicted wheeze at age 12 years (adjusted odds ratio: 1 year, 3.31 [95% CI 1.59-6.91]; 2 years, 6.37 [95% CI, 3.48-11.66]). Among wheezy 1-year-olds, those who were HDM sensitized had a 75% (95% CI, 51% to 91%) probability of wheeze at age 12 years compared with a 36% (95% CI, 23% to 50%) probability among those not sensitized. Among eczematous 1-year-olds, those who were HDM sensitized had a 67% (95% CI, 45% to 84%) probability of wheeze at age 12 years compared with a 35% (95% CI, 25% to 45%) probability among those not sensitized. Among 1-year-old children with both eczema and wheeze, the probability of wheeze at age 12 years was 64% (95% CI, 35% to 87%) if HDM sensitized and 50% (95% CI, 26% to 74%) if not.

Conclusion

HDM sensitization at age 1 or 2 years in wheezing and eczematous children at increased familial allergy risk predicts asthma and may inform management of these high-risk groups.

Section snippets

Study population

The Melbourne Atopy Cohort study (MACS) is a longitudinal, birth cohort study comprising 620 babies enrolled before birth by recruiting pregnant women living in Melbourne, Australia. Eligible babies had at least 1 first-degree family member with a history of eczema and/or asthma and/or allergic rhinitis and/or severe food allergy. The 620 children were born between March 24, 1990, and November 1, 1994.

Data collection

An allergy-trained research nurse conducted telephone surveys with the babies’ mothers every 4

Results

Baseline demographics of MACS have already been published.21, 22, 23, 24 Briefly, parents of the MACS cohort were predominantly well educated (59% of mothers and 61% of fathers attended university), Australian born (87% of mothers and 83% of fathers), and of high socioeconomic status (4% of mothers and 3% of fathers were receiving social security benefits at baseline). More than half (51%) of the participants were male, and all children had at least 1 immediate family member with “allergic

Discussion

Our study showed HDM sensitization was associated with current wheeze at age 12 years in both monosensitized and polysensitized HDM-sensitized children. However, we were unable to derive any conclusions on similar associations in relation to other single allergens tested in this study because of the small number of positive SPT responses. Furthermore, when we considered children with sensitization profiles excluding HDM, we were unable to demonstrate an association with 12-year wheeze,

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Infants have a higher risk of developing allergic asthma than adults. However, the underlying mechanism remains unknown. We show here that sensitization of mice with house-dust mites (HDMs) in the presence of low-dose lipopolysaccharide (LPS) prevented T helper 2 (Th2) cell allergic responses in adult, but not infant, mice. Mechanistically, adult CD11b⁺ migratory dendritic cells (mDCs) upregulated the transcription factor T-bet in response to tumor necrosis factor-α (TNF-α), which was rapidly induced after HDM + LPS sensitization. Consequently, adult CD11b⁺ mDCs produced interleukin-12 (IL-12), which prevented Th2 cell development by promoting T-bet upregulation in responding T cells. Conversely, infants failed to induce TNF-α after HDM + LPS sensitization. Therefore, CD11b⁺ mDCs failed to upregulate T-bet and did not secrete IL-12 and Th2 cell responses normally developed in infant mice. Thus, the availability of TNF-α dictates the ability of CD11b⁺ mDCs to suppress allergic Th2-cell responses upon dose-dependent endotoxin sensitization and is a key mediator governing susceptibility to allergic airway inflammation in infant mice.
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: Initial support for the study was from Nestlé Australia, and the 12-year follow-up was supported by the Asthma Foundation of Victoria. C.J.L. is supported by the Sidney Myer Health Fund and the National Health and Medical Research Council of Australia (NHMRC). A.J.L., L.C.G., J.L.H., M.C.M., and S.C.D. are supported by the NHMRC. K.J.A. is supported by the Charles and Sylvia Viertel Charitable Foundation.

: Disclosure of potential conflict of interest: M. J. Abramson was part of the Landmark Symposium for GlaxoSmithKline and receives research support from Reckitts Benckiser. D. Hill has received past support from Nutricia, SHS International, and Nestlé for research, and has presented lectures at sponsored meetings. The rest of the authors have declared that they have no conflict of interest.

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Asthma and lower airway diseaseHouse dust mite sensitization in toddlers predicts current wheeze at age 12 years

Background

Objective

Methods

Results

Conclusion

Section snippets

Study population

Data collection

Results

Discussion

Lancet

Paediatr Respir Rev

Lancet

Control Clin Trials

Lancet

Lancet

Immunol Lett

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy

The global burden of asthma: executive summary of the GINA Dissemination Committee Report

Allergy Asthma Proc

Asthma and wheezing in the first six years of life

N Engl J Med

Defining childhood atopic phenotypes to investigate the association of atopic sensitization with allergic disease

Allergy

Dynamic evolution of serum immunoglobulin E to airborne allergens throughout childhood: results from the Multi-Centre Allergy Study birth cohort

Clin Exp Allergy

Sensitization to different pollens and allergic disease in 4-year-old Swedish children

Clin Exp Allergy

A longitudinal, population-based, cohort study of childhood asthma followed to adulthood

N Engl J Med

Asthma during the primary school ages—prevalence, remission and the impact of allergic sensitization

Allergy

Allergen exposure and the development of asthma

Thorax

International study of asthma and allergies in childhood (ISAAC): rationale and methods

Eur Respir J

Asthma and lower airway disease
House dust mite sensitization in toddlers predicts current wheeze at age 12 years