Counterregulation between the FcepsilonRI pathway and antiviral responses in human plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDCs) play essential roles in directing immune responses. These cells may be particularly important in determining the nature of immune responses to viral infections in patients with allergic asthma as well those with other atopic diseases. The purposes of this study were 1) to compare the functional capacity of pDCs in patients with one type of allergic disorder, allergic asthma, and controls; 2) to determine whether IgE cross-linking affects antiviral responses of influenza-exposed pDCs; and 3) to determine whether evidence of counterregulation of FcepsilonRIalpha and IFN-alpha pathways exists in these cells. pDC function was assessed in a subset of asthma patients and in controls by measuring IFN-alpha production after exposure of purified pDCs to influenza viruses. FcepsilonRIalpha expression on pDCs was determined by flow cytometry in blood samples from patients with allergic asthma and controls. pDCs from patients with asthma secreted significantly less IFN-alpha upon exposure to influenza A (572 versus 2815; p = 0.03), and secretion was inversely correlated with serum IgE levels. Moreover, IgE cross-linking prior to viral challenge resulted in 1) abrogation of the influenza-induced pDC IFN-alpha response; 2) diminished influenza and gardiquimod-induced TLR-7 upregulation in pDCs; and 3) interruption of influenza-induced upregulation of pDC maturation/costimulatory molecules. In addition, exposure to influenza and gardiquimod resulted in upregulation of TLR-7, with concomitant downregulation of FcepsilonRIalpha expression in pDCs. These data suggest that counterregulation of FcepsilonRI and TLR-7 pathways exists in pDCs, and that IgE cross-linking impairs pDC antiviral responses.

Asthma control, adiposity, and adipokines among inner-city adolescents.

BACKGROUND: There is an association between adiposity and asthma prevalence, but the relationship to asthma control is unclear. OBJECTIVES: We sought to understand the relationships among adiposity, sex, and asthma control in inner-city adolescents with asthma. METHODS: We prospectively followed 368 adolescents with moderate-to-severe asthma (ages 12-20 years) living in 10 urban areas for 1 year. Asthma symptoms and exacerbations were recorded, and pulmonary function and exhaled nitric oxide levels were measured every 6 weeks. Adiposity measures (body mass index [BMI] and dual-energy X-ray absorptiometric scans) were made, and blood was collected for measurement of allergy markers, adiponectin, leptin, TNF-alpha, IL-6, and C-reactive protein levels. RESULTS: More than 60% of female subjects and 50% of male subjects were above the 85th percentile of BMI for age. Higher BMI was associated with more symptom days (R = 0.18, P = .02) and exacerbations (R = 0.18, P = .06) among female subjects only. Adiponectin was inversely related to asthma symptoms (R = -0.18, P < .05) and exacerbations (R = -0.20, P < .05) and positively with FEV(1)/forced vital capacity ratio (R = 0.15, P < .05) in male subjects only independent of body size. There was no relationship between adiposity or adipokines and total IgE levels, blood eosinophil counts, and exhaled nitric oxide levels. Dual-energy X-ray absorptiometry provided little additional value in relating adiposity to asthma outcome in this population of adolescents. CONCLUSION: Adiposity is associated with poorer asthma control in female subjects. Adiponectin is associated with improved asthma control in male subjects.

Classification of asthma severity in children: the contribution of pulmonary function testing.

BACKGROUND: Despite increasing awareness of the National Asthma Education and Prevention Program guidelines, the relative contribution of symptom frequency or pulmonary function to the recommended asthma severity levels remains poorly understood. OBJECTIVE: To determine whether adding lung function measurements to clinical history substantially changes the asthma severity classification, thereby influencing treatment decisions. DESIGN: Baseline data were studied from children enrolled in 2 multicenter studies: phase 1 of the National Cooperative Inner-City Asthma Study (1992-1994) (cohort 1) and the Inner-City Asthma Study (1998-2001) (cohort 2). SETTING: Fifteen (8 for cohort 1 and 7 for cohort 2) major metropolitan inner-city areas in the United States. PARTICIPANTS: Inner-city children aged 8 through 11 years with asthma. MAIN OUTCOME MEASURES: Proportion of children reclassified from less severe asthma categories based on symptom frequency into more severe categories because of lung function. RESULTS: Of children with symptoms of mild intermittent asthma, 22.8% in cohort 1 and 27.7% in cohort 2 would be reclassified as having either moderate or severe persistent asthma. Of children with symptoms of mild persistent asthma, 31.2% in cohort 1 and 33.3% in cohort 2 would be similarly reclassified. CONCLUSIONS: In 2 different studies of inner-city children with asthma, approximately one third of the participants were reclassified into higher National Asthma Education and Prevention Program asthma severity categories when pulmonary function was considered in addition to symptom frequency. This may have direct implications for the undertreatment of asthma.