Low IFN-γ production in the first year of life as a predictor of wheeze during childhood

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.