Asthma and lower airway disease
Toward improved prediction of risk for atopy and asthma among preschoolers: A prospective cohort study

https://doi.org/10.1016/j.jaci.2009.12.018Get rights and content

Background

Atopy and asthma are commonly initiated during early life, and there is increasing interest in the development of preventive treatments for at-risk children. However, effective methods for assessing the level of risk in individual children are lacking.

Objective

We sought to identify clinical and laboratory biomarkers in 2-year-olds that are predictive of the risk for persistent atopy and wheeze at age 5 years.

Methods

We prospectively studied 198 atopic family history–positive children to age 5 years. Clinical and laboratory assessments related to asthma history and atopy status were undertaken annually; episodes of acute respiratory illness were assessed and classified throughout and graded by severity.

Results

Aeroallergen-specific IgE titers cycled continuously within the low range in nonatopic subjects. Atopic subjects displayed similar cycling in infancy but eventually locked into a stable pattern of upwardly trending antibody production and TH2-polarized cellular immunity. The latter was associated with stable expression of IL-4 receptor in allergen-specific TH2 memory responses, which was absent from responses during infancy. Risk for persistent wheeze was strongly linked to early sensitization and in turn to early infection. Integration of these data by means of logistic regression revealed that attaining mite-specific IgE titers of greater than 0.20 kU/L by age 2 years was associated with a 12.7% risk of persistent wheeze, increasing progressively to an 87.2% risk with increasing numbers of severe lower respiratory tract illnesses experienced.

Conclusion

The risk for development of persistent wheeze in children can be quantified by means of integration of measures related to early sensitization and early infections. Follow-up studies along similar lines in larger unselected populations to refine this approach are warranted.

Section snippets

Patients and sample collection

Subjects in this study were part of an ongoing prospective birth cohort (n = 198), as previously described.3, 9 All subjects were enrolled antenatally and classified as having an atopic family history based on a standard questionnaire3 and a positive doctor's diagnosis of asthma, hay fever, or atopic dermatitis for 1 or both parents. Blood was collected at birth and at 0.5, 1, 2, 3, 4, and 5 years, and children were assessed by one of the authors for the presence of atopic disease. PBMCs and

Postnatal development of IgE responses in atopic and nonatopic children

Fig 1 shows the age-related increase in the frequency of sensitization to inhalant allergens in the study cohort. Forty-six percent of the cohort were sensitized to 1 or more aeroallergens by age 5 years, and 26% were sensitized to food allergens (overall population figures for this age range are 40% and 22%, respectively). The dominant inhalant allergen affecting this population is HDM, and the frequency of sensitization increased progressively over the observation period, reaching 37% at

Discussion

The available evidence indicates that resistance to sensitization to ubiquitous environmental allergens is an active process involving the development of various forms of immunologic tolerance. In the gastrointestinal tract this involves generation of “oral tolerance” to dietary allergens, and in the respiratory tract the corresponding process by which responsiveness to aeroallergens is controlled is known as “inhalation tolerance.”13 Data from a number of cohort studies have established that

References (31)

  • H.L. Rhodes et al.

    A birth cohort study of subjects at risk of atopy: twenty-two-year follow-up of wheeze and atopic status

    Am J Respir Crit Care Med

    (2002)
  • D. Sherrill et al.

    Early sensitization to allergens and development of respiratory symptoms

    Clin Exp Allergy

    (1999)
  • W.H. Oddy et al.

    The effects of respiratory infections, atopy, and breastfeeding on childhood asthma

    Eur Respir J

    (2002)
  • P.G. Holt et al.

    Prevention of allergic respiratory disease in infants: current aspects and future perspectives

    Curr Opin Allergy Clin Immunol

    (2007)
  • M.M. Kusel et al.

    Role of respiratory viruses in acute upper and lower respiratory tract illness in the first year of life: a birth cohort study

    Pediatr Infect Dis J

    (2006)
  • Cited by (129)

    View all citing articles on Scopus

    Supported by the National Health and Medical Research Council of Australia. Reagents for antibody assays were provided by Phadia AB.

    Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

    View full text