Cytokine response after severe respiratory syncytial virus bronchiolitis in early life.

BACKGROUND: Immune response after viral infection usually involves T(H)1-mediated response; however, severe respiratory syncytial virus (RSV) infection appears to be associated with the development of asthma, a T(H)2-predominant phenotype. OBJECTIVE: To understand the early and subsequent immunologic response to a serious RSV infection in children over time. METHODS: A total of 206 previously healthy infants hospitalized with severe RSV bronchiolitis were enrolled in a prospective cohort called the RSV Bronchiolitis in Early Life study. Peripheral blood T cells were obtained immediately after RSV infection and at 2, 4, and 6 years of age, stimulated with phorbol 12-myristate 13-acetate and ionomycin, and analyzed for IL-2, IL-4, IL-13, and IFN-gamma by flow cytometry and real-time PCR. RESULTS: Of the children, 48% (n = 97) developed asthma (physician-diagnosed), and 48% (n = 97) had eczema by age 6 years; 32% (n = 48 of 150) developed allergic sensitization by 3 years of age. Children with asthma had lower IL-13 expression at 6 years of age than those without (P = .001). IFN-gamma, IL-2, and IL-4 levels did not differ by asthma or eczema status during follow-up (all P > .05). Allergic sensitization was not associated with differences in cytokine levels during follow-up (all P > .05). CONCLUSION: Severe RSV infection early in life is associated with a high incidence of asthma and eczema. Contrary to expectations, subsequent immunologic development in those who developed asthma, eczema, or allergic sensitization was not associated with a T(H)2 phenotype in the peripheral blood.

Airway remodeling measured by multidetector CT is increased in severe asthma and correlates with pathology.

BACKGROUND: To prospectively apply an automated, quantitative three-dimensional approach to imaging and airway analysis to assess airway remodeling in asthma patients. METHODS: Using quantitative software (Pulmonary Workstation, version 0.139; VIDA Diagnostics; Iowa City, IA) that enables quantitative airway segment measurements of low-dose, thin-section (0.625 to 1.25 mm), multidetector-row CT (MDCT) scans, we compared airway wall thickness (WT) and wall area (WA) in 123 subjects participating in a prospective multicenter cohort study, the National Institutes of Health Severe Asthma Research Program (patients with severe asthma, n = 63; patients with mild-to-moderate asthma, n = 35); and healthy subjects, n = 25). A subset of these subjects underwent fiberoptic bronchoscopy and endobronchial biopsies (n = 32). WT and WA measurements were corrected for total airway diameter and area: WT and WA, respectively. RESULTS: Subjects with severe asthma had a significantly greater WT% than patients with mild-to-moderate asthma and healthy subjects (17.2 +/- 1.5 vs 16.5 +/- 1.6 [p = 0.014] and 16.3 +/- 1.2 [p = 0.031], respectively) and a greater WA percentage (WA%) compared to patients with mild-to-moderate asthma and healthy subjects (56.6 +/- 2.9 vs 54.7 +/- 3.3 [p = 0.005] and 54.6 +/- 2.4 [p = 0.003], respectively). Both WT% and WA% were inversely correlated with baseline FEV(1) percent predicted (r = -0.39, p < 0.0001 and r = -0.40, p < 0.0001, respectively) and positively correlated with response to a bronchodilator (r = 0.28, p = 0.002 and r = 0.35, p < 0.0001, respectively). The airway epithelial thickness measure on the biopsy sample correlated with WT% (r = 0.47; p = 0.007) and WA% (r = 0.52; p = 0.003). In the same individual, there is considerable regional heterogeneity in airway WT. CONCLUSION: Patients with severe asthma have thicker airway walls as measured on MDCT scan than do patients with mild asthma or healthy subjects, which correlates with pathologic measures of remodeling and the degree of airflow obstruction. MDCT scanning may be a useful technique for assessing airway remodeling in asthma patients, but overlap among the groups limits the diagnostic value in individual subjects.