Increased sputum levels of eosinophil granule proteins have been reported despite normal eosinophil numbers in peripheral blood and in the lung in cystic fibrosis (CF). Mechanisms of eosinophil priming and activation are still unclear in CF. In the present study we investigated whether ion concentrations in the sputa of CF patients are related to eosinophil activity. We assessed concentrations of eosinophil cationic protein (ECP), eosinophil protein X (EPX), major basic protein (MBP) and ions (Na+, Cl-, Ca2+, Mg2+) in sputum samples of 29 children with CF as well as in 10 controls with bronchial asthma. Patients with CF demonstrated significantly higher levels of ECP, Na+, Cl- and Ca2+ levels than asthmatics (P < 0.04, P < 0.0001, P < 0.0001, P < 0.02). No differences were seen between concentrations of EPX and Mg2+ in the two groups. In CF, eosinophil granule proteins correlated significantly with Ca2+ and Mg2+ concentrations (ECP, P < 0.0001, r = 0.65, P < 0.0001, r = 0.66; MBP, P < 0.03, r = 0.41, P < 0.03, r = 0.42), furthermore inversely with Cl- concentrations (ECP, P < 0. 0003, r = - 0.63; EPX, P < 0.02, r = - 0.45; MBP, P < 0.03, r = - 0. 41) but not with Na+ levels. ECP, Na+ and Cl- were also correlated with lung function variables (FVC, P < 0.04, r = - 0.38, P < 0.02, r = 0.44, P < 0.03, r = 0.41; FEV1, P < 0.007, r = - 0.49, P < 0.006, r = 0.5, P < 0.008, r = 0.48; MEF50, P < 0.003, r = - 0.54, NS, P < 0.03, r = 0.42; MEF25, P < 0.039, r = - 0.4, P < 0.005, r = 0.51, P < 0.05, r = 0.37). Our results demonstrated a significant relationship of eosinophil degranulation and ions in CF, indicating that ion composition in CF sputa may be at least partly be responsible for high levels of eosinophil products despite low eosinophil numbers.
Previous adult studies demonstrated the clinical efficacy of an additional treatment with leukotriene receptor antagonists on steroid-dependent asthma, but there is little knowledge about anti-inflammatory add-on effects within the lung. In this study, we hypothesized that steroid-treated children exhibit a decrease in bronchial inflammation in induced sputum under additional treatment with montelukast. Twenty-five asthmatic children aged 6 to 14 y, who had been taking inhaled corticosteroids (400 -800 g/d budesonide) regularly for at least 12 wk, were randomized to receive additional treatment with either montelukast (5 mg orally, once daily) or placebo over a 4-wk period. As primary efficacy variable, eosinophil cationic protein (ECP) in induced sputum as direct measurement of bronchial inflammation was assessed before and after treatment. To assure a baseline level of inflammation, an ECP concentration above 100 g/L was required. Sputum eosinophil count, concentration of exhaled nitric oxide, urinary excretion of eosinophil protein X, and quality-oflife items were considered as secondary outcome variables. After treatment with montelukast, ECP in sputum was significantly reduced (montelukast: median Ϫ975 g/L [5 to 95% confidence interval: Ϫ4295 to 583 g/L]; placebo: 561 g/L [Ϫ1335 to 3320 g/L]; p Ͻ 0.01) and the quality-of-life score had significantly improved (p Ͻ 0.05) compared with placebo. Partly explained by low baseline levels, no statistically significant change in concentration of exhaled nitric oxide (p Ͼ 0.05), urinary excretion of eosinophil protein X (p Ͼ 0.05), or eosinophil count (p Ͼ 0.05) was found. In conclusion, add-on treatment with montelukast can suppress sputum ECP in children with steroid-dependent asthma, while at the same time an improvement in quality of life items occurs. Asthma is the most common chronic disease in children and results in a considerable burden in the child's daily life (1). Inhaled glucocorticosteroids are the most potent antiinflammatory drugs currently available and are the first-line therapy in patients with chronic asthma (2). However, longterm side effects of inhaled corticosteroids in young children cannot be fully excluded (3). Moreover, several studies have shown a persistent inflammation in steroid-treated asthmatics (4 -7), and it has been postulated that inadequate treatment of airway inflammation may lead to irreversible changes in airway function (8). LTRA such as zafirlukast, pranlukast, and montelukast are able to reduce effects of Cys-LT (leukotriene C4, D4, and E4) and are increasingly used as additional anti-inflammatory drugs. The local pulmonary efficacy of zafirlukast was demonstrated in bronchoscopy-based studies (9, 10). Recently, it has been shown that pranlukast is able to reduce bronchial inflammation assessed by sputum markers in asthmatic adults (11).Montelukast, although frequently used for children, has been evaluated on the basis of indirect measurements (e.g. eosinophils in serum, FeNO) (12-15) but not on the basis of direct measurem...
Children of elementary school age with pollen sensitization and a history of hay fever are at considerable risk of getting pollen asthma, but they are not quickly diagnosed as such. Specific immunotherapy might be a means of preventing asthma completely in such a situation. Our data helps to estimate the sample size for intervention studies of this kind.
The nature of the fern allergens identi®ed needs to be elucidated. IgE antibodies in our patient did not seem to be directed against cross-reacting carbohydrate determinants on glycoproteins that can be commonly found in pollens and foods and also in Ficus benjamina (®g) leaf extract (unpublished observations).Diagnosis of fern allergy is simple: the most important step is to consider it. As no commercial extracts are available, testing should be performed with fresh fern leaves by the prick-to-prick method. Therapy is simple and consists of removal of all ferns, as there seems to be cross-reactivity between different fern species (2).
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