Effects of montelukast on surrogate inflammatory markers in corticosteroid-treated patients with asthma

TY - JOUR

T1 - Effects of montelukast on surrogate inflammatory markers in corticosteroid-treated patients with asthma

AU - Currie, Graeme P.

AU - Lee, Daniel K. C.

AU - Haggart, Kay

AU - Bates, Caroline E.

AU - Lipworth, Brian J.

N1 - dc.publisher: American Thoracic Society

PY - 2003

Y1 - 2003

N2 - We evaluated whether montelukast conferred additive effects in patients with asthma receiving fluticasone/salmeterol (FP/SM) combination and FP alone. Twenty-two patients with mild to moderate asthma completed a double-blind, placebo-controlled study. After a 2-week run-in using FP 250 µg/SM 50 µg 1 puff twice daily, patients entered a randomized crossover period to receive additional montelukast 10 mg daily or placebo for 3 weeks each. For the first 2 weeks, they received FP/SM 1 puff BID, and then they received FP 250 µg 1 puff BID for the 3rd week. The primary outcome was adenosine monophosphate challenge threshold and recovery time; secondary outcomes included surrogate inflammatory markers and lung function. Compared with FP/SM run-in, adding montelukast to FP/SM was better (p < 0.05) than placebo for inflammatory markers but not for lung function. For adenosine monophosphate threshold, recovery, exhaled nitric oxide, and blood eosinophils, there were 1.4 (95% confidence interval, 1.1–1.8) geometric mean fold, 10 minutes (3–17 minutes), 2.1 parts per billion (0.2–3.9 parts per billion), and 88 (34–172) x 106/L differences, respectively. The combination of FP plus montelukast was superior to FP/SM for inflammatory markers but was inferior for lung function. Thus, in patients taking FP/SM or FP, montelukast conferred complimentary effects on surrogate inflammatory markers, which were dissociated from lung function. Further studies are required to evaluate whether these effects of montelukast translate into clinical benefits.

AB - We evaluated whether montelukast conferred additive effects in patients with asthma receiving fluticasone/salmeterol (FP/SM) combination and FP alone. Twenty-two patients with mild to moderate asthma completed a double-blind, placebo-controlled study. After a 2-week run-in using FP 250 µg/SM 50 µg 1 puff twice daily, patients entered a randomized crossover period to receive additional montelukast 10 mg daily or placebo for 3 weeks each. For the first 2 weeks, they received FP/SM 1 puff BID, and then they received FP 250 µg 1 puff BID for the 3rd week. The primary outcome was adenosine monophosphate challenge threshold and recovery time; secondary outcomes included surrogate inflammatory markers and lung function. Compared with FP/SM run-in, adding montelukast to FP/SM was better (p < 0.05) than placebo for inflammatory markers but not for lung function. For adenosine monophosphate threshold, recovery, exhaled nitric oxide, and blood eosinophils, there were 1.4 (95% confidence interval, 1.1–1.8) geometric mean fold, 10 minutes (3–17 minutes), 2.1 parts per billion (0.2–3.9 parts per billion), and 88 (34–172) x 106/L differences, respectively. The combination of FP plus montelukast was superior to FP/SM for inflammatory markers but was inferior for lung function. Thus, in patients taking FP/SM or FP, montelukast conferred complimentary effects on surrogate inflammatory markers, which were dissociated from lung function. Further studies are required to evaluate whether these effects of montelukast translate into clinical benefits.

KW - Asthma therapy

KW - Leukotriene receptor antagonist

KW - Salmeterol

KW - Fluticasone

U2 - 10.1164/rccm.200209-1116OC

DO - 10.1164/rccm.200209-1116OC

M3 - Article

C2 - 12456382

SN - 1073-449X

VL - 167

SP - 1232

EP - 1238

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

IS - 9

ER -