Purpose of the Study. To determine if variations in clinical asthma phenotypes are the result of differences in underlying T-cell immune responses to inhalant allergens.
Study Population. One hundred forty-seven children (aged 8.6–13.5 years) and 25 of their siblings (aged 7.4–17.4 years) were recruited from 194 members of a birth cohort studied prospectively for asthma development.
Methods. Wheeze and asthma were defined by parental questionnaire. Atopy was defined as at least 1 positive skin-prick test for environmental or food allergens. Increased bronchial hyperreactivity (BHR) was defined as a ≥20% drop in forced expiratory volume in 1 second after inhaled histamine up to 7.8 μmol/L. T-cell responses to allergens and mitogens, blood eosinophils, and immunoglobulin E (IgE) were measured and compared with clinical phenotypes.
Results. Ninety-five (55.2%) of the children were atopic, sensitized predominantly to house dust mite (42.4%). Asthma was present in 26 (15.1%) children, of whom 22 (85%) were atopic; BHR was present in 62 (35.9%) children, of whom 45 (73%) were atopic. Atopy was associated with T-helper 2 (Th2) cytokine responses (interleukin-4 [IL-4], IL-5, IL-9, IL-13), whereas Th1 responses (IL-10, interferon-γ [IFN-γ], tumor necrosis factor-α [TNF]) occurred in all children. Skin-prick test wheal size was positively associated with house dust mite allergen-induced IL-5 (P < .0001) and IFN-γ (P = .003) and negatively associated with IL-10. Asthma was associated with eosinophilia and elevated house dust mite–specific IL-5, IL-9, IL-13, and IgE. BHR was associated with eosinophilia, elevated allergen-specific IL-5 and IgE, increased total IgE, and a polyclonal cytokine response (IL-5, IL-13, IFN-γ, and TNF-α). In atopics, current asthma or wheeze was associated with house dust mite allergen-specific IL-5 and IL-13; BHR was associated with IL-5 and IgE. In nonatopics, BHR was associated with increased house dust mite allergen-specific and polyclonal IL-10 and polyclonal IFN-γ and TNF-α.
Conclusions. In atopic and nonatopic children, distinctive immune-response patterns were identified for asthma and BHR. Immunologic Th1 and Th2 hyperresponsiveness was identified as a hallmark of BHR.
Reviewer Comments. Modification of T-cell responses has become an increasingly important focus in the investigation of treatments for atopic disease. Although this study further highlights the prominence of Th2-driven responses in atopic individuals, the results also demonstrate allergen-specific and polyclonal Th1 responses associated with BHR in atopic and nonatopic children. These findings suggest a nonantagonistic interaction between Th1 and Th2 pathways in the production of asthma symptoms. Further understanding of the associations between T-cell response patterns and clinical wheezing phenotypes in children may lead to future asthma therapies in this population.
- Copyright © 2006 by the American Academy of Pediatrics