Cytokine levels in nasal and lower airways in young cystic fibrosis (CF) patients were compared with those in controls. Nasal (NLF) and bronchoalveolar (BALF) lavage fluids were obtained from children with or without CF who were undergoing bronchoscopy for clinical indications. In NLF, neither inflammatory cells nor cytokine concentrations differed between patients and controls. However, interleukin (IL)-8 levels in infected BALF from children with CF were markedly elevated compared with levels in infected and uninfected controls, even after standardization of IL-8 concentrations to bacterial counts. BALF IL-6 was modestly elevated in infected CF patients compared with uninfected but not infected controls; IL-10 did not differ among the groups. NLF and BALF IL-8 levels were not significantly correlated. Excessive airway inflammation in early CF thus appears to be confined to the lower respiratory tract, and IL-8 levels are markedly increased in children with CF compared with control children with a bacterial infection of the lower airways.

Airway inflammation is important in the development and progression of many pulmonary disorders, including asthma. We hypothesized that the hydrogen peroxide (H2O2) concentration in expired breath may be a marker of airway inflammation. Expired breath condensate was collected by cooling and the H2O2 concentration was measured fluorimetrically. Thirty-five samples were collected from 22 pediatric patients with asthma who were 7 to 18 yr of age and from 11 healthy, nonasthmatic controls. Asthmatic subjects were determined to be well or sick (acute disease of the upper or lower respiratory tract) by clinical examination. Pulmonary function tests were determined to be abnormal if there was a > 15% reduction in FEV1 or > 20% reduction in FEF25-75 compared with baseline values. Expired breath H2O2 was elevated in asthmatic subjects compared with controls (0.81 +/- 0.70 versus 0.25 +/- 0.27 mumol/L). The difference was primarily due to elevation of H2O2 in sick asthmatic subjects, whose expired breath H2O2 level of 1.5 +/- 0.5 (n = 10) was different from that of well asthmatics (0.54 +/- 0.56, n = 25). There was a high correlation between expired breath H2O2 and clinical status. Elevation of expired H2O2 occurred with either acute upper or lower respiratory tract disease. There was no statistically significant correlation between expired breath H2O2 level and pulmonary function test results. We conclude that elevation of H2O2 in the expired breath condensate is a simple, noninvasive method that can be used as a biochemical marker of airway inflammation.

High levels of neutrophils and the neutrophil-attracting chemokine interleukin (IL)-8 have been observed in the airways of patients with cystic fibrosis (CF). We hypothesized that CF respiratory epithelium produces excessive amounts of IL-8 either at baseline or after stimulation. To test this hypothesis we compared immunoreactive IL-8 release by primary nasal epithelial cell (NEC) cultures established from young children with or without CF, at several time points after stimulation of cultures with tumor necrosis factor-alpha (TNF-alpha) or infection with respiratory syncytial virus (RSV). Both stimuli induced significantly increased IL-8 release by both CF and control cultures. However, there was no difference between CF and control cells in either the magnitude or duration of the IL-8 response. The effect of transduction of CF cells with Ad5-CBCFTR, an adenovirus vector mediating expression of cystic fibrosis transmembrane regulator (CFTR), on IL-8 production was also determined. TNF-alpha stimulated IL-8 production was not different in Ad5-CBCFTR-transduced, -untransduced, or Ad5-CMVLacZ-transduced control cells. Lastly, immortalized CF tracheal epithelial cell lines, both uncorrected and retrovirally corrected with CFTR, were compared. Again, TNF-alpha-stimulated IL-8 production did not differ significantly between cell lines with and without functioning CFTR. Our data suggest that isolated CF NECs cultured under these conditions do not produce more IL-8 than do non-CF control cultures, either at baseline or after incubation with the nonspecific stimuli TNF-alpha and RSV. We conclude that the absence of functioning CFTR alone is not sufficient to cause excessive production of IL-8.

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Objective Accurate discrimination of asthma episodes increases the likelihood they will be managed effectively. The purpose of the study was to examine the effect of feedback in a signal detection task on perception of increased airflow obstruction in children with persistent asthma. Methods The effect of feedback training on the perception of resistive loads was evaluated in 155 children with persistent asthma between 8 and 15 years of age. Each child participated in four experimental sessions that occurred about once every 2 weeks, an initial session followed by three training sessions. During the initial session, the threshold resistance to breathing was determined for each child. Subsequently, each child was randomly assigned to one of two resistive load training conditions in a signal detection paradigm: training with immediate performance feedback or training with no performance feedback. Results The threshold resistance to breathing, determined in the initial session, was equivalent between groups. Children in the feedback condition discriminated more accurately between both the presence and absence of increases in the resistance to breathing (206 ± 48 vs. 180 ± 39 correct responses, p < .001), and differences over time between groups increased reliably as a function of training (139 ± 34 vs. 120 ± 29 correct responses, p < .001). Response times and confidence ratings were equivalent between groups, and no differences in breathing patterns were observed between groups. Conclusion Feedback training results in improved perception of respiratory sensations in children with asthma, a finding with implications for strategies of asthma self-management.

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