Montelukast added to budesonide in children with persistent asthma: a randomized, double-blind, crossover study.

OBJECTIVE We tested the hypothesis that adding montelukast to budesonide would improve asthma control in children with inhaled glucocorticoid-dependent persistent asthma. STUDY DESIGN In a multicenter, randomized, double-blind, crossover study, we compared the benefit of adding montelukast, 5 mg, or placebo once daily to budesonide, 200 microg, twice daily. RESULTS After a 1-month run-in with budesonide, 200 microg, twice daily, 279 children were randomized to montelukast or placebo. The mean +/- SD age was 10.4 +/- 2.2 years, the mean forced expiratory volume in 1 second (FEV(1)) was 77.7% +/- 10.6% predicted, and reversibility was 18.1% +/- 12.9%. Compared with adding placebo to budesonide, adding montelukast produced significant improvements in mean percent change from baseline FEV(1) (P =.062 [P =.010 for per-protocol analysis]), mean absolute change from baseline FEV(1) (P =.040), mean increase from baseline in morning (P =.023) and evening (P =.012) peak expiratory flows, decrease in exacerbation days by approximately 23% (P <.001), decreased beta2-agonist use (P =.013), and reduced blood eosinophil counts (P <.001). The treatments did not differ significantly with regard to safety. CONCLUSIONS Montelukast, 5 mg, added to budesonide improved asthma control significantly, indicated by a small additive effect on lung function and a clinically relevant decrease in asthma exacerbation days.

[1]  R. Pauwels,et al.  Low-dose inhaled corticosteroids and the prevention of death from asthma. , 2000, The New England journal of medicine.

[2]  N Franklin Adkinson,et al.  Long-term effects of budesonide or nedocromil in children with asthma. , 2000, The New England journal of medicine.

[3]  D. Stempel Montelukast added to inhaled beclomethasone in treatment of asthma. , 2000, American journal of respiratory and critical care medicine.

[4]  H. Bisgaard,et al.  Montelukast or salmeterol combined with an inhaled steroid in adult asthma: design and rationale of a randomized, double-blind comparative study (the IMPACT Investigation of Montelukast as a Partner Agent for Complementary Therapy-trial). , 2000, Respiratory medicine.

[5]  S. Shrewsbury,et al.  Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA) , 2000, BMJ : British Medical Journal.

[6]  C. White,et al.  Exhaled nitric oxide before and after montelukast sodium therapy in school‐age children with chronic asthma: A preliminary study , 1999, Pediatric pulmonology.

[7]  H. Bisgaard,et al.  NO in exhaled air of asthmatic children is reduced by the leukotriene receptor antagonist montelukast. , 1999, American journal of respiratory and critical care medicine.

[8]  E. Israel,et al.  Randomised, placebo controlled trial of effect of a leukotriene receptor antagonist, montelukast, on tapering inhaled corticosteroids in asthmatic patients , 1999, BMJ.

[9]  L. Boulet,et al.  Montelukast reduces airway eosinophilic inflammation in asthma: a randomized, controlled trial. , 1999, The European respiratory journal.

[10]  F. Simons,et al.  Benefits and risks of inhaled glucocorticoids in children with persistent asthma. , 1998, Journal of Allergy and Clinical Immunology.

[11]  S. Malozowski,et al.  Comparison of beclomethasone, salmeterol, and placebo in children with asthma. , 1998, The New England journal of medicine.

[12]  J. Kemp,et al.  Montelukast once daily inhibits exercise-induced bronchoconstriction in 6- to 14-year-old children with asthma. , 1998, The Journal of pediatrics.

[13]  S. Szefler,et al.  Dose-related efficacy of budesonide administered via a dry powder inhaler in the treatment of children with moderate to severe persistent asthma. , 1998, The Journal of pediatrics.

[14]  J. Bernstein,et al.  Montelukast for Chronic Asthma in 6- to 14-Year-Old Children A Randomized, Double-blind Trial , 1998 .

[15]  J. Donahue,et al.  Inhaled Steroids and the Risk of Hospitalization for Asthma , 1998 .

[16]  F. Simons,et al.  A comparison of beclomethasone, salmeterol, and placebo in children with asthma. Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group. , 1997, The New England journal of medicine.

[17]  K. Chung,et al.  A comparison of low-dose inhaled budesonide plus theophylline and high-dose inhaled budesonide for moderate asthma. , 1997, The New England journal of medicine.

[18]  Third Expert Panel on theDiagnosis,et al.  Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma , 1997 .

[19]  J. Baker,et al.  Dexamethasone increases expression of 5-lipoxygenase and its activating protein in human monocytes and THP-1 cells. , 1997, European journal of biochemistry.

[20]  S. Pedersen,et al.  Budesonide treatment of moderate and severe asthma in children: a dose-response study. , 1995, The Journal of allergy and clinical immunology.

[21]  J. Oates,et al.  Effect of oral prednisone on airway inflammatory mediators in atopic asthma. , 1994, American journal of respiratory and critical care medicine.