Mechanisms of asthma and allergic inflammation
Low IFN-γ production in the first year of life as a predictor of wheeze during childhood

https://doi.org/10.1016/j.jaci.2007.05.050Get rights and content

Background

Diminished cytokine production in infancy has been associated with an increased risk for allergen sensitization and early-life wheeze.

Objective

We sought to assess the effect of low cytokine production in the first year of life on the development of wheeze through age 13 years.

Methods

Cytokine production (IFN-γ and IL-2) by mitogen-stimulated mononuclear cells was determined from peripheral blood samples (9.4 months, n = 118) in a subset of healthy infants enrolled in the Tucson Children's Respiratory Study. The occurrence of wheeze during the previous year was ascertained at ages 2, 3, 6, 8, 11, and 13 years by means of questionnaire. Relative risk for wheeze was computed with generalized estimating equations.

Results

The risk of wheezing between 2 and 13 years was significantly higher for subjects with low 9-month IFN-γ production (relative risk, 2.29; 95% CI, 1.35-3.89) and borderline significant for those with intermediate IFN-γ production (relative risk, 1.59; 95% CI, 0.95-2.68) compared with those who produced high levels of IFN-γ (P value for linear association = .002). Nine-month IL-2 production was unrelated to wheeze. In relation to complex wheezing phenotypes, 9-month IFN-γ production was inversely related to toddler wheeze (occurring only before age 6 years, P = .03) and chronic wheeze (occurring before and after age 6 years, P = .007) but not school-age wheeze (occurring only after age 6 years, P = .06).

Conclusion

The results suggest that characteristics of the immune system present during the first year of life can anticipate the likelihood of development of episodes of airway obstruction characterized by wheezing.

Clinical implications

Immune susceptibility to asthma is established very early during postnatal life.

Section snippets

Subjects

Parents of 1246 infants who were members of a health maintenance organization in Tucson, Arizona, agreed to have their healthy newborns participate in the Tucson Children's Respiratory Study, a longitudinal prospective study of respiratory illness.16 Tucson has a population of about 500,000 (Census 2000) and is located in the desert southwest, and study subjects lived primarily in suburban neighborhoods. Infants were enrolled between May 1980 and October 1984. After February 1983, studies of

Immune study subject characteristics

The infants with immune studies were not significantly different from those without immune studies regarding the distribution of sex, ethnicity, and parental characteristics (Table II). In addition, the prevalence of atopy at age 6 years and wheeze during the previous year at ages 2 through 13 years was similar for both groups. Because the availability of data on current wheeze varied at each age, we assessed any potential bias among the participating children with and without follow-up data.

Discussion

The results of this study strongly suggest that characteristics of the immune system present during the first year of life can anticipate the likelihood of developing episodes of airway obstruction characterized by wheezing. We cannot conclude from these data whether IFN-γ production itself is responsible for our findings or whether IFN-γ production acts as a marker for a more global alteration of the immune system that is present in early life in these children. However, the lack of relation

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    Supported by National Heart, Lung, and Blood Institute grants HL-14136 and HL-56177.

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

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