Arzneimittelforschung 2008; 58(6): 303-309
DOI: 10.1055/s-0031-1296511
Antiallergic Drugs · Antiasthmatics · Antitussives · Bronchodilators · Bronchosecretogogues · Mucolytics
Editio Cantor Verlag Aulendorf (Germany)

Prevention of Exercise-induced Asthma by a Fixed Combination of Disodium Cromoglycate plus Reproterol Compared with Montelukast in Young Patients

Josef Lecheler
1   Asthma-Zentrum Buchenhöhe, Berchtesgaden, Germany
Bernhard Pfannebecker
1   Asthma-Zentrum Buchenhöhe, Berchtesgaden, Germany
Duc Tung Nguyen
2   MEDA Pharma GmbH & Co. KG, Bad Homburg, Germany
Ursula Petzold
2   MEDA Pharma GmbH & Co. KG, Bad Homburg, Germany
Ullrich Munzel
2   MEDA Pharma GmbH & Co. KG, Bad Homburg, Germany
Hans-Joachim Kremer
3   Medical Writing Service, Freiburg/Breisgau, Germany
Joachim Maus
2   MEDA Pharma GmbH & Co. KG, Bad Homburg, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
15 December 2011 (online)



The leukotriene inhibitor montelukast has been recommended against exercise-induced asthma (EIA), however, single-dose agents might be favourable in several aspects.


To compare the protective effects against EIA of a single inhalation of the combination disodium cromoglycate (DSCG, CAS 16110-51-3) and reproterol (REP, CAS 54063-54-6) with 3 days oral treatment of montelukast (MON, CAS 158966-92-8).


Open-label, cross-over, single-centre trial. Twenty-four 6 to 18-year-old children and adolescents, with reversible and stable airway obstruction, baseline FEV1, > 70 %, predicted and proven EIA (i.e. a maximum decrease of FEV1 by ≥ 20% compared with baseline) were treated with MON, orally for 3 days in the evening, or one single inhalation of DSCG/REP 20 min before the exercise challenge. The treatment sequence was randomised. The exercise test on a treadmill was performed under standardised conditions.


24 patients completed both periods. Both treatments clearly provided protection against EIA; however, protection of DSCG/REP was more pronounced than that of MON. This difference was statistically significant even if the data were adjusted for the increase in FEV1 between inhalation of DSCG/REP and challenge (DSCG/REPadjusted). The nadir FEV1, level after exercise following prophylaxis with DSCG/REP was even higher than the pre-inhalation FEV1, value. From these data, protection indices of 66 %, 81 %, and 113% for MON, DSCG/REPadjusted, and DSCG/REPunadjusted, respectively, were estimated.


Inhalation of DSCG/REP before exercise provides significantly better protection against EIA than three days treatment with MON.

  • Literature

  • 1 GINA / Global initiative for asthma. GINA report: Global strategy for asthma management and prevention. National Institutes of Health, National Heart, Lung, and Blood Institute. Update 2007
  • 2 Spooner CH, Spooner GR, Rowe BH. Mast-cell stabilising agents to prevent exercise-induced bronchoconstriction (Cochrane Review). In: The Cochrane Library, (Issue 1) 2006; Oxford: Update Software.
  • 3 Anderson SD. Single-dose agents in the prevention of exercise-induced asthma: a descriptive review. Treat Respir Med. 2004; 3: 365-379
  • 4 Kelly KD, Spooner CH, Rowe BH. Nedocromil sodium versus sodium cromoglycate in treatment of exercise-induced bronchoconstriction: a systematic review. Eur Respir J. 2001; 17: 39-45
  • 5 Fischer H. Ergebnisse einer multizentrischen offenen Pruning mit einer fixen Kombination aus Dinatrium cromoglicicum und Reproterol an 1872 Patienten. Pharmakotherapie. 1984; 7: 67-73
  • 6 Gulyas A. Doppelblindstudie zur therapeutischen Wirk-samkeit von Reproterolhydrochlorid allein und einer Kombination aus Cromoglicinsäure, Dinatriumsalz und Reproterolhydrochlorid. Pharmakotherapie. 1984; 7: 51-59
  • 7 Siemon G, Engel T, Petro W. Intraindividuelle, randomisierte, placebokontrollierte Vergleichsstudie zur bronchodilatatorischen Wirkung des Beta-2-Sympathomimetikums Reproterol und einer Kombination aus Cromoglicinsäure, Dinatriumsalz und Reproterol. Pharmakotherapie. 1984; 7: 18-22
  • 8 Svenonius E, Arborelius M, Wiberg R, Ekberg P. Prevention of exercise-induced asthma by drugs inhaled from metered aerosols. Allergy. 1988; 43: 252-257
  • 9 Debelic M, Hertel G, König J. Double-blind crossover study comparing sodium cromoglycate, reproterol, reproterol plus sodium cromoglycate, and placebo in exercise-induced asthma. Ann Allergy. 1988; 61: 25-29
  • 10 Von Berg A, Albrecht B, Darlath W, Voß HW, Berdel D. Intraindividuelle, randomisierte Doppelblindstudie zum Vergleich des protektiven Effektes zwischen verschiedenen Anwendungsformen von DNCG und reproterol bei Kindern mit Anstrengungsasthma. Allergologie. 2002; 11: 557-564
  • 11 Leff JA, Busse WW, Pearlman D, Bronsky EA, Kemp J, Hendeles L et al. Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction. N Engl J Med. 1998; 339: 147-152
  • 12 Steinshamn S, Sandsund M, Sue-Chu M, Bjermer L. Effects of montelukast and salmeterol on physical performance and exercise economy in adult asthmatics with exercise-induced bronchoconstriction. Chest. 2004; 126: 1154-1160
  • 13 Storms WW, Chervinsky P, Ghannam AF, Bird S, Hustad CM, Edelman JM. Challenge-Rescue Study Group. A comparison of the effects of oral montelukast and inhaled salmeterol on response to rescue bronchodilation after challenge. Respir Med. 2004; 98: 1051-1062
  • 14 Brooks EG, Hayden ML. Exercise-induced asthma. Nurs Clin North Am. 2003; 38: 689-696
  • 15 Tan RA, Spector SL. Exercise-induced asthma: Diagnosis and management. Ann Allergy Asthma Immunol. 2002; 89: 226-235
  • 16 Storms WW. Review of exercise-induced asthma. Med Sci Sprts Exerc. 2003; 35: 1464-1470
  • 17 Massie J. Exercise-induced asthma in children. Paediatr Drugs. 2002; 4: 267-278
  • 18 Netzer N, Steinacker JM, Schuell K, Elser A, Voß HW, Darlath W. Protective effect of oral montelukast and a fixed drug combination of inhaled sodium cromoglycate and reproterol on exercise induced asthma. ATS Int. Conference 2000, Toronto, Canada.
  • 19 Philip G, Villaran C, Pearlman DS, Loeys T, Dass SB, Reiss TF. Protection against exercise-induced bronchoconstriction two hours after a single oral dose of montelukast. J Asthma. 2007; 44: 213-217
  • 20 Summary of product characteristics (Fachinformation): Singulair®. MSD / Dieckmann Arzneimittel, Germany. Status August 2005
  • 21 Zhao JJ, Rogers JD, Holland SD, Larson P, Amin RD, Haesen R et al. Pharmacokinetics and bioavailability of montelukast sodium (MK-0476) in healthy young and elderly volunteers. Biopharm Drug Dispos. 1997; 18: 769-777
  • 22 Richter K, Janicki S, Jorres RA, Magnussen H. Acute protection against exercise-induced bronchoconstriction by for-moterol, salmeterol and terbutaline. Eur Respir J. 2002; 19: 865-871
  • 23 Gronnerod TA, von ABerg, Schwabe G, Soliman S. Formoterol via Turbuhaler gave better protection than terbutaline against repeated exercise challenge for up to 12 hours in children and adolescents. Respir Med. 2000; 94: 661-667
  • 24 Woolley M, Anderson SD, Quigley BM. Duration of protective effect of terbutaline sulfate and cromolyn sodium alone and in combination on exercise-induced asthma. Chest. 1990; 97: 39-5
  • 25 Clarke PS, Ratowsky DA. Effect of fenoterol hydrobromide and sodium cromoglycate individually and in combination on postexercise asthma. Ann. Allergy. 1990; 64: 187-f190