montelukast and Cystic-Fibrosis

Inflammation is a major component of the vicious cycle characterizing cystic fibrosis pulmonary disease. If untreated, this inflammatory process irreversibly damages the airways, leading to bronchiectasis and ultimately respiratory failure. Antiinflammatory drugs for cystic fibrosis lung disease appear to have beneficial effects on disease parameters. These agents include oral corticosteroids and ibuprofen, as well as azithromycin, which, in addition to its antimicrobial effects, also possesses antiinflammatory properties. Inhaled corticosteroids, colchicine, methotrexate, montelukast, pentoxifylline, nutritional supplements, and protease replacement have not had a significant impact on the disease. Therapy with oral corticosteroids, ibuprofen, and fish oil is limited by adverse effects. Azithromycin appears to be safe and effective, and is thus the most promising antiinflammatory therapy available for patients with cystic fibrosis. Pharmacologic therapy with antiinflammatory agents should be started early in the disease course, before extensive irreversible lung damage has occurred.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adult; Anti-Inflammatory Agents; Azithromycin; Child; Clinical Trials as Topic; Cyclopropanes; Cystic Fibrosis; Deoxyribonuclease I; Dietary Supplements; Humans; Methotrexate; Pentoxifylline; Quinolines; Sulfides

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.. To evaluate the effect of anti-inflammatory treatment with montelukast sodium in patients with CF.. 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.. 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).. Montelukast may have measurable anti-inflammatory properties in patients with CF.

Topics: Acetates; Adolescent; Airway Resistance; Anti-Asthmatic Agents; Child; Cough; Cross-Over Studies; Cyclopropanes; Cystic Fibrosis; Double-Blind Method; Eosinophil Cationic Protein; Female; Forced Expiratory Volume; Humans; Interleukin-10; Interleukin-8; Male; Peroxidase; Quinolines; Respiratory Sounds; Sputum; Sulfides; Treatment Outcome

Inflammatory process contributes to progressive lung tissue damage in cystic fibrosis (CF). Cysteinyl leukotrienes have been found in the sputum of CF patients at concentrations sufficient to cause potent biological effect. This study was designed to assess the effect of anti-inflammatory treatment with montelukast sodium in CF patients. Twelve patients, aged 6-29 were recruited. It was 20 week, placebo-controlled, and randomized, double blind, crossover trial. At first and last week of each treatment course spirometry and whole body plethysmography parameters (FEV1, PEF, FEF25/75%, VC, TGV, Raw and RV) and clinical wheezing and cough scale were measured. In montelukast group significant improvement in FEV1 (mean +/- SD, 54.6 +/- 22.6 before and 62 +/- 19.0 after treatment, p=0.0112) and FEF25/75% (28.9 +/- 23.0 before and 37.5 +/- 25.5 after treatment, p=0.0053) were observed. Compared with placebo montelukast significantly improved FEV1 (p=0.0032), PEF (p=0.0298) and FEF25/75% (p=0.0091). There was no significant difference in VC, TGV, Raw and RV. Montelukast compared with placebo significantly decreased cough (p<0.0001) and wheezing (p=0.0002) score. In summary, therapy with montelukast may provide clinical benefit to patients with CF.

Topics: Acetates; Adolescent; Adult; Child; Cross-Over Studies; Cyclopropanes; Cystic Fibrosis; Double-Blind Method; Female; Humans; Leukotriene Antagonists; Male; Plethysmography, Whole Body; Quinolines; Spirometry; Sulfides; Treatment Outcome

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.. 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.. 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.. 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.. 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.

Topics: Acetates; Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Blood Proteins; Child; Cross-Over Studies; Cyclopropanes; Cystic Fibrosis; Double-Blind Method; Eosinophil Granule Proteins; Eosinophilia; Humans; Inflammation; Interleukin-8; Leukocyte Count; Leukotriene Antagonists; Membrane Proteins; Pilot Projects; Quinolines; Receptors, Leukotriene; Respiratory Function Tests; Ribonucleases; Sulfides; Treatment Outcome

Topics: Acetates; Allergens; Anaphylaxis; Anti-Infective Agents; Antibiotic Prophylaxis; beta-Lactams; Cetirizine; Cyclopropanes; Cystic Fibrosis; Desensitization, Immunologic; Drug Hypersensitivity; Extracorporeal Membrane Oxygenation; Famotidine; Female; Humans; Immune Tolerance; Male; Quinolines; Respiratory Insufficiency; Sulfides

Topics: Acetates; Adult; Aminophenols; Androstadienes; Anti-Allergic Agents; Cyclopropanes; Cystic Fibrosis; Female; Fluticasone; Humans; Leukotriene Antagonists; Paranasal Sinus Diseases; Quinolines; Quinolones; Rhinitis, Allergic, Perennial; Sulfides; Treatment Outcome; Young Adult

Topics: Acetates; Adolescent; Child; Cyclopropanes; Cystic Fibrosis; Female; Humans; Leukotriene Antagonists; Long-Term Care; Male; Quinolines; Sulfides; Treatment Outcome

To determine if patients with cystic fibrosis (CF) have an altered pharmacokinetic profile of montelukast, we studied the single-dose pharmacokinetics in 12 patients with CF and 12 age- and gender-matched controls after they received a 10-mg oral dose.. Plasma samples were collected before dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours after drug administration. The specimens were analyzed by high-performance liquid chromatography (HPLC).. The mean systemic clearance (mL/min) values (+/- SD) were not statistically different between the CF subjects (55.53 +/- 44.0 mL/min) and the controls (57.12 +/- 18.42 mL/min), nor were the results significantly different when normalized to body surface area or body weight. The mean value for elimination half-life, elimination rate constant, area under the plasma concentration versus time curve, and maximum concentration for controls was 2.37 +/- 0.38 hours, 0.30 +/- 0.05 hours(-1), 2,680.0 +/- 693.6 ng. min/mL, and 448.9 +/- 165.3 ng/mL; and for the CF patients it was 2.97 +/- 1.21 hours, 0.28 +/- 0.13 hrs(-1), 3976.1 +/- 2073.4 ng. min/mL, 606.7 +/- 237.8 ng/mL. There were no statistically significant differences (all P >.05) in the measured pharmacokinetic parameters between the CF and control subjects.. We conclude that the dose of montelukast and the dosing interval does not need to be modified if the goal is to mimic the serum concentration used to treat asthma. The effectiveness of these concentrations for the inflammatory lung disease of patients with CF is unknown.

Topics: Acetates; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Case-Control Studies; Chromatography, High Pressure Liquid; Cyclopropanes; Cystic Fibrosis; Drug Administration Schedule; Female; Humans; Leukotriene Antagonists; Male; Quinolines; Sulfides

Topics: Acetates; Adolescent; Adult; Asthma; Cyclopropanes; Cystic Fibrosis; Exercise Tolerance; Female; Humans; Leukotriene Antagonists; Male; Quinolines; Sulfides; Treatment Outcome