Guideline topic: Pharmacological management of asthma
Evidence table 4.3d: Leukotriene receptor antagonists in exercise induced asthma

Author

Adults

Edelman et al¹

2000

Randomised.
Double-blind parallel group, comparing montelukast to salmeterol

++

15 – 45 years, FEV1 > 65%, fall in FEV1 of at least 20% with exercise, not taking inhaled steroids or recent exacerbations

1.Max % fall in FEV1 after exercise at end of 8 wk period (1ary)

2.Max % fall in FEV1 at days 1 to 3 and wk 4.

3.Time required after max fall to 5% of baseline

4.Auc 0-60 MIN 1.

Days 1-3.

Inhibition 37%vs 36.6% (MON vs SAL); At wks 4 and 8, the effect of MON persisted at same level, but SAL effect was reduced at wks 4 and 8 (approx 30% only), sign less than inhibition by MON

Mean +/-SEM on graphs.

P=0.015 at wk4;

P=0.002 at wk8.

Groups were comparable (sl less AUC with the sal gp). 93% completion rate. Interestingly, the bronchodilator response measured at first dose and at wks 4 and 8 were: MON: 0.14, 0.09 and 0.07L; SAL; 0.17, 0.14. 0.15L, all values not sign, but the effect of mon seems to be lost with usage! (while the protective effect was lost with SAL). Also, the bronchodilator response is very small (only 5% increase). Large number of patients. Results convincing regarding the inhibitory effects of MON and SAL on EIA.

Leff et al²

1998

Randomised, double-bline placebo-controlled, paralled groups

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15 – 45 years, using only b-agonists, BHR< 4 mg/ml methacholine, and > 20% fall in FEV 1 on 2 consecutive exercise challenge

1.AUC for FEV1 in 60 min (1ary)

2.Maximal fall in FEV1

3.Time for return from max fall to within 5% of baseline FEV1

4.PC20 5.Global assessment of asthma control

% inhibition of 47.4%

31.6%

26.9

0.45 vs0.14 (MTL vs PLAC) Difficult to assess

95%C1 for diff between treatment groups: -818 to-196. P=0.002-12.4 to –2.6; p=0.003-28.4 to –1.0; p=0.04

NS

P=0.009

The groups were comparable at baseline, although the MTL group has less EIA but not sign. Large group of patients, powerful study to detect a 50% difference in AUC at a powere of 90% or more. The degree of inhibition was sustained throughout the 12 week period (3 measurements done at 4, 8 and 12 wks.