- Paediatr Drugs. 2005;7(6):353-63.
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Leukotriene receptor antagonists in children with cystic fibrosis lung disease : anti-inflammatory and clinical effects.
Department of Pediatrics, University of Bonn, Bonn, Germany. s.schmitt.grohe@uni-bonn.de
Cystic fibrosis (CF) lung disease is characterized by chronic endobronchial infection resulting in progressive pulmonary destruction; this is a major cause of mortality and morbidity. Neutrophils are the primary effector cells responsible for the progressive deterioration of lung function. Peptido-leukotriene B4 antagonists, new anti-inflammatory agents that block the neutrophil-dominated inflammation, could have had the potential for long-term use.
A trial on the pharmacokinetics of amelubant administered orally as a single dose of up to 75 mg in pediatric patients with CF and 300 mg in adults, and as a repeated dose of 75 mg and 150 mg, respectively, once daily for 15 days provided evidence that amelubant metabolism in adult and pediatric patients with CF is similar to that in healthy adults. In another study using the same dosage regimen, amelubant appeared to be safe and well tolerated.
Safety measures included physical examination, vital signs, spirometry, oximetry, ECG, and clinical laboratory testing. However, a randomized, double-blind, placebo-controlled, multinational, phase II trial (Boehringer Ingelheim 543.45) was conducted to investigate the clinical efficacy of 24 weeks of treatment with amelubant in patients with CF with mild-to-moderate lung disease. Two doses of amelubant (75 and 150 mg) were tested in adult patients (> or = 18 years) and one dose of amelubant (75mg) was tested in pediatric (6-17 years) patients. The trial was terminated early due to a statistically significant increase in the risk of pulmonary-related, serious adverse events in adults receiving amelubant.
Cysteinyl leukotrienes, eosinophilic inflammation, and viral infections also contribute to progressive pulmonary destruction in CF. Cysteinyl leukotrienes are potential targets for cysteinyl leukotriene receptor antagonist use. A study on the pharmacokinetics of montelukast in children with CF provided evidence that the dose of montelukast and the administration interval does not need to be modified if the goal is to mimic the serum concentrations used to treat asthma.
In a randomized, double-blind, crossover, placebo-controlled study, 16 children with mild CF (median age 9.5 years; vital capacity [VC] >70%) were treated with montelukast (5 to < or ="14">14 years; 10 mg) or placebo as a once-daily tablet for 21 days. There was a significant (p < or = 0.02) reduction in serum eosinophil cationic protein levels and eosinophils (p < or = 0.027) with montelukast. However, neither lung function tests (VC, forced expiratory volume in 1 second [FEV1], maximum expiratory flow at 25% of forced VC), nor clinical symptom scores changed significantly.
In another study, 26 patients aged 6-18 years with moderate CF (VC between 40% and 69% predicted) received montelukast or placebo for 8 weeks in a 20-week, randomized, double-blind, crossover, placebo-controlled trial. After treatment with montelukast there was a significant improvement in FEV1, peak expiratory flow, and forced expiratory flow between 25% and 75%, and a significant decrease in cough and wheezing scale scores (p <>
Tuesday, March 3, 2009
Singulair in CF 3
Another Singulair Study in CF
- Ann Allergy Asthma Immunol. 2005 Oct;95(4):372-80.
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Effects of montelukast treatment on clinical and inflammatory variables in patients with cystic fibrosis.
Department of Pediatrics and Allergy, M Curie Hospital, Zgierz, Poland. interna@wss.izerz.pl
BACKGROUND: In cystic fibrosis (CF), the inflammatory process contributes to progressive lung tissue damage. Cysteinyl leukotrienes have been found in the sputum of patients with CF at high concentrations sufficient to cause potent biological effects. OBJECTIVE: To evaluate the effect of anti-inflammatory treatment with montelukast sodium in patients with CF.
METHODS: Twenty-six patients aged 6 to 18 years were recruited to this 20-week, randomized, double-blind, placebo-controlled, crossover trial. Patients received montelukast or placebo for 8 weeks in addition to their regular CF treatment. Before and after treatment, findings from spirometry, whole-body plethysmography, and the clinical wheezing and cough scales were evaluated. At the same time, serum and sputum samples were obtained for the measurement of eosinophil cationic protein, interleukin 10 (IL-10), IL-8, and myeloperoxidase levels.
RESULTS: Twenty-three patients completed the study. Compared with placebo use, montelukast treatment significantly improved forced expiratory volume in I second, peak expiratory flow, and forced expiratory flow between 25% and 75% and significantly decreased cough and wheezing scale scores (P < .001 for all). There were no significant changes in vital capacity, thoracic gas volume, airway resistance, and residual volume after treatment. Compared with placebo use, montelukast treatment decreased serum and sputum levels of eosinophil cationic protein and IL-8, decreased sputum levels of myeloperoxidase, and increased serum and sputum levels of IL-10 (P < .001 for all).
CONCLUSIONS: Montelukast may have measurable anti-inflammatory properties in patients with CF.
Singulair in CF
- Ann Allergy Asthma Immunol. 2002 Dec;89(6):599-605.
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- Comment in:
- Respir Med. 2007 Mar;101(3):684.
Anti-inflammatory effects of montelukast in mild cystic fibrosis.
Children's Hospital Medical Center, University of Bonn, Bonn, Germany. s.schmitt.grohe@uni-bonn.de
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"> 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.