We propose a role for Th17 and Th2 T cells in chronic inflammation in lungs of patients with CF. High concentrations of these cytokines/chemokines in CF airways precede infection with P. aeruginosa.
Colonization with Aspergillus fumigatus (Af) constitutes a common finding in children with cystic fibrosis (CF). The relationship between sensitization to Af and lung functon (LF) was studied in 118 patients with CF (61 girls and 57 boys; mean age: 14.3 yr; SD: 7 yr). Mean follow up was 2.2 yr. On average, 8.1 (SD: 4.8) LF tests were performed per patient. Measurement of total IgE and specific IgE antibodies to Af, and a skin prick test (SPT) for Af, were done once a year. Thirty-one children (26%) were sensitized to Af. On average, LF parameters were not significantly different in Af-sensitized children than in nonsensitized children. Linear regression analyses were performed, using the repeated measures design. With adjustment for gender, age, height, and weight, sensitization to Af was associated with lower values of FEV1 (beta = -0.209; p < 0.05) and FEF(25-75) (beta = -0.356; p < 0.01). Analysis of different subgroups of sensitization demonstrated the effect on LF only in Af-sensitized patients with elevated total IgE levels, and not in Af-sensitized patients with normal IgE levels. Furthermore, there was evidence for a more rapid decline in LF for Af-sensitized patients with elevated total IgE levels than in those with normal IgE levels. We conclude that sensitization to Af in the presence of increased IgE values is associated with lower LF values in children with CF.
Background-Patients with cystic fibrosis (CF) have significantly decreased plasma concentrations of nutrient antioxidant vitamins, especially of -carotene, which is thought to result from fat malabsorption and chronic pulmonary inflammation. The aim of this double blind, placebo controlled study was to investigate the eVect of oral -carotene supplementation for six months on clinical parameters. Methods-Twenty four patients with CF were randomised to receive -carotene 1 mg/kg/day (maximum 50 mg/day) for three months (high dose supplementation) and 10 mg/day for a further three months (low dose supplementation) or placebo. At monthly follow up visits the plasma -carotene concentration, total antioxidant capacity, malondialdehyde (MDA) as a marker of lipid peroxidation, and clinical parameters (ShwachmannKulczycki score, body mass index (BMI), height, and lung function (FEV 1 )) were assessed. The number of pulmonary exacerbations requiring antibiotic treatment (in days) three months before and during the study were evaluated. Results-The plasma concentration of -carotene increased significantly to the normal range during the three months of high dose supplementation (baseline 0.08 (0.04) µmol/l to 0.56 (0.38) µmol/l; p<0.001) but decreased to 0.32 (0.19) µmol/l in the period of low dose supplementation. Initially raised plasma levels of MDA fell to normal levels and the total antioxidant capacity showed a nonsignificant trend towards improvement during high dose supplementation. Antibiotic treatment decreased significantly in the supplementation group from 14.5 (14.9) days/patient during the three months before the study to 9.8 (10.3) days/ patient during high dose supplementation (p=0.0368) and to 10.5 (9.9) days/patient during low dose supplementation, but increased in the placebo group. The Shwachmann-Kulczycki score, lung function, and BMI did not show any changes in either of the treatment groups. No adverse events were observed during the study period. Conclusion-Oral -carotene supplementation in a dose of 1 mg/kg/day only was eVective in normalising the plasma concentration of -carotene and resulted in a decrease in pulmonary exacerbations. These data suggest that patients with CF may benefit clinically from supplementation with -carotene and further studies are warranted. (Thorax 2001;56:48-52)
To investigate the efficacy of long-term oral β-carotene supplementation for optimizing the antioxidant status and pulmonary function in patients with cystic fibrosis (CF), 24 patients (aged 12.8 ± 6.3 years) were randomized to a CF supplementation or to a CF placebo group. As controls 14 healthy age-matched subjects (aged 14.7 ± 6.2 years) were studied. Patients of the CF supplementation group received 1 mg β-carotene/kg body weight (BW)/day (maximally 50 mg β-carotene/day) for the first 12 weeks; during the following 12 weeks, dosage was reduced to 10 mg β-carotene/day. At study entry, plasma β-carotene concentrations were significantly lower in CF patients than in controls (p < 0.001). In the CF supplementation group, plasma β-carotene concentrations were significantly increased (baseline: 0.08 ± 0.04 μmol/l) at the end of high-dose treatment (12th week; 0.6 ± 0.4 μmol/l; p < 0.001), but decreased again during supplementation with 10 mg β-carotene/day to 0.3 ± 0.2 μmol/l at the end of the study (p < 0.001). β-Carotene supplementation did not affect plasma concentrations of other carotenoids and retinol, but an increase in plasma α- and γ-tocopherol concentrations was noticed. During high-dose treatment, a significant decrease in TBA-MDA complexes and a correction of total antioxidative capacity was observed. During the treatment, pulmonary exacerbation could be corrected significantly (p < 0.05). We conclude that CF patients can be efficiently supplemented with 1 mg β-carotene/kg BW/day (maximally 50 mg β-carotene/day) to achieve plasma concentrations of healthy control subjects and to minimize oxidative stress, improving the quality of life of CF patients.
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