Anti-inflammatory effects of montelukast in mild cystic fibrosis.

BACKGROUND: Immune-mediated inflammation contributes to progressive pulmonary damage in cystic fibrosis (CF). Sputum cysteinyl leukotriene levels, eosinophil cationic protein (ECP), and interleukin-8 (IL-8) are significantly related to disease severity. OBJECTIVE: The aim of this study was to evaluate the anti-inflammatory and clinical effects of the cysteinyl leukotriene receptor antagonist montelukast in children with CF. METHODS: A double-blind, randomized, crossover design was used. Patients received montelukast (6 to < or = 14 years, 5 mg; > 14 years, 10 mg) or placebo as a once-daily tablet for 21 days and then, after a washout period of at least 4 weeks, crossed over to receive the alternative treatment. Blood and native nasal fluid were taken on days 1 and 21 of each treatment block, and WBC count, ECP, and IL-8 were analyzed using a chemiluminescent immunometric assay. RESULTS: Sixteen CF patients (10 boys, 6 girls; age, 5 to 18 years, median 9.5 years) completed the trial. There was a significant (P < or = 0.02) reduction of serum ECP (median reduction: montelukast 7.7 microg/L vs placebo 0.15 microg/L) and eosinophils (P < or = 0.027; median reduction: montelukast 85/microL vs placebo 0/microL). There was no significant change in nasal ECP, IL-8, or serum IL-8 after a 21-day course of montelukast. Clinical symptom scores did not change significantly. CONCLUSIONS: Montelukast reduces eosinophilic inflammation in CF patients. Multicenter trials providing more patients to create more data to prove the hypothesis that montelukast is an effective tool to cut down disease severity in CF patients are needed.

Serum ECP levels and methacholine challenge in infants with recurrent wheezing.

BACKGROUND: High levels of serum eosinophil cationic protein (sECP) as a marker of eosinophilic airway inflammation have been described as a predictor of childhood asthma. Bronchial hyperreactivity (BHR) appears to be secondary to the release of inflammatory mediators. OBJECTIVE: We investigated the possible correlation between eosinophilic inflammation and BHR in 72 infants with recurrent wheezing. METHODS: To determine bronchial reactivity, lung function measurements with methacholine challenge were performed in 72 infants, aged 12 to 30 months, and the degree of BHR to methacholine was compared with sECP values. Patients were grouped according to low (group 1, <10 microg/L, n = 22), medium (group 2, 10 to 20 microg/L, n = 23), and high (group 3, >20 microg/L, n = 27) sECP values. RESULTS: In group 1, sECP levels ranged from 3.1 to 9.9 microg/L, mean 6.6 microg/L +/- standard deviation [SD] 2.3, in group 2, from 10.3 to 19.8 microg/L, mean 14.3 microg/L +/- SD 2.8, and in group 3 from 23.0 to 66.7 microg/L, mean 34.5 microg/L +/- SD 9.5. Distribution of provocative methacholine concentration among groups was as follows: group 1, 30 to 976 microg, mean 350.9 microg +/- SD 258.3; group 2, 36 to 752 microg, mean 340.7 microg +/- SD 226.3; group 3, 41 to 848 microg, mean 301.3 microg +/- SD 189.8 methacholine. CONCLUSION: There was no significant correlation between sECP levels and bronchial reactivity in all groups (r = -0.076, P = 0.6), indicating that these parameters reflect two independent pathogenic mechanisms in the etiology of childhood asthma.