Effects of Ipratropium on Exercise-Induced Bronchospasm

Abstract

Exercise-induced bronchospasm (EIB) is the transient narrowing of the airways that follows vigorous exercise. Ipratropium bromide may be used to prevent EIB, but its effect varies among individuals. We hypothesized that time of administration of ipratropium interferes with its action. This was a prospective, double-blind, cross-over study carried out to evaluate the bronchoprotective and bronchodilatory effect of ipratropium at different times of day. The study consisted of 4 exercise challenge tests (2 at 7 am and 2 at 6 pm). In the morning, one of the tests was performed after placebo administration and the other one after ipratropium (80 μg) and the two tests (placebo and ipratropium) were repeated in the evening. Twenty-one patients with severe or moderate asthma and previous confirmation of EIB were enrolled in this prospective trial. The bronchodilatory effect of ipratropium was 0.25±0.21 L or 13.11±10.99% (p=0.001 compared to baseline values) in the morning, and 0.14±0.25 L or 7.25±11.37% (p>0.05) in the evening. In the morning, EIB was 0.58±0.29 L on the placebo day and 0.38±0.22 L on the treatment day (p=0.01). In the evening, EIB was 0.62±0.28 L on the placebo day and 0.51±0.35 L on the treatment day (p>0.05). We suggest that the use of ipratropium for the treatment of asthma and EIB should take into consideration the time of administration.

Key words

circadian rhythm - bronchial hyperreactivity - lung function tests - anticholinergics - autonomic nervous system

References

• 1 American Thoracic Society . Medical Section of the American Lung Association.  Am Rev Respir Dis. 1991;  144 1202-1218
• 2 Anderson SD, Daviskas E. The mechanism of exercise-induced asthma.  J Allergy Clin Immunol. 2000;  106 453-459
• 3 Borut TC, Tashkin DP, Fischer TJ, Lee E, Harper C. Comparison of aerosolized atropine sulfate and SCH 1000, on exercise-induced bronchospasm in children.  J Allergy Clin Immunol. 1997;  60 127-133
• 4 Brusasco V, Crimi E. Allergy and sports: exercise-induced asthma.  Int J Sports Med. 1994;  15 (S 03) S184-S186
• 5 Bundgaard A, Andersen KK. Diurnal variation in exercise-induced asthma.  Eur J Respir Dis. 1983;  64 424-426
• 6 Cropp GJA. The exercise bronchoprovocation test: standardization of procedures and evaluation of response.  J Allergy Clin Immunol. 1979;  64 627-633
• 7 D’Alonzo GE, Crocetti JG, Smolensky MH. Circadian rhythms in the pharmacokinetics and clinical effects of beta-agonist, theophylline, and anticholinergic medications in the treatment of nocturnal asthma.  Chronobiol Int. 1999;  16 663-682
• 8 Eggleston PA, Guerrant JL. A standardized method of evaluating exercise-induced asthma.  J Allergy Clin Immunol. 1976;  58 414-425
• 9 Eggleston PA, Rosenthal RR, Anderson SA, Anderton R, Bierman CW, Bleecker ER, Chai H, Cropp GJ, Johnson JD, Konig P, Morse J, Smith LJ, Summers RJ, Trautlein JJ. Guidelines for the methodology of exercise challenge testing of asthmatics.  J Allergy Clin Immunol. 1979;  64 642-645
• 10 Harriss DJ, Atkinson G. International Journal of Sports Medicine – Ethical Standards in Sport and Exercise Science Research.  Int J Sports Med. 2009;  30 701-702
• 11 Hartley JPR, Davies BH. Cholinergic blockade in the prevention of exercise-induced asthma.  Thorax. 1980;  35 680-685
• 12 Hetzel MR, Clark TJH. Comparison of normal and asthmatic circadian rhythms in peak expiratory flow rate.  Thorax. 1980;  35 732-738
• 13 Knöpfli BH, Bar-Or O. Vagal activity and airway response to ipratropium bromide prior to and after exercise in ambient and cold conditions, in healthy cross-country runners.  Clin J Sport Med. 1999;  9 170-176
• 14 Knöpfli BH, Bar-Or O, Araújo CGS. Effect of ipratropium bromide on EIB in children depends on vagal activity.  Med Sci Sports Exerc. 2005;  37 354-359
• 15 Martin RJ. Location of airway inflammations in asthma and the relationship to circadian change in lung function.  Chronobiol Int. 1999;  16 623-630
• 16 Martin RJ, Banks-Schlegel S. Chronobiology of asthma. NHLBI Workshop Summary.  Am J Respir Crit Care Med. 1998;  158 1002-1007
• 17 McFadden ER. Exercise-induced asthma.  N Engl J Med. 1994;  330 1362-1367
• 18 McFadden ER, Ingran RH, Haynes RL, Wellman JJ. Predominant site of flow limitation and mechanisms of postexertional asthma.  J Appl Physiol. 1977;  42 746-752
• 19 Mickleborough TD, Lindley MR, Turner LA. Comparative effects of a high-intensity interval warm-up and salbutamol on the bronchoconstrictor response to exercise in asthmatic athletes.  Int J Sports Med. 2007;  28 456-462
• 20 National Institutes of Health .Global strategy for asthma management and prevention: global initiative for asthma (GINA). Bethesda: National Heart, Lung and Blood Institute Publication; 2002
• 21 Pichon A, Roulaud M, Denjean A, de Bisschop C. Airway tone during exercise in healthy subjects: effects of salbutamol and ipratropium bromide.  Int J Sports Med. 2005;  26 321-326
• 22 Pincus DJ, Szefler J, Ackerson LM, Martin RJ. Chronotherapy of asthma with inhaled steroids: the effect of dosage timing on drug efficacy.  J Allergy Clin Immunol. 1995;  95 1172-1178
• 23 Poppius H, Salorinne Y. Comparative trial of salbutamol and an anticholinergic drug, SCH 1000, in prevention of exercise-induced asthma.  Scand J Respir Dis. 1973;  54 142-147
• 24 Poppius H, Salorinne Y, Viljanen AA. Inhalation of a new anticholinergic drug SCH 1000, in asthma and chronic bronchitis: effects on airway resistance, thoracic gas volume, blood gases and exercise-induced asthma.  Bull Physiopathol Respir. 1972;  8 643-652
• 25 Reimberg A, Gervais P, Chaussade M, Fraboulet G, Dubarque B. Circadian changes in effectiveness of corticosteroids in eight patients with allergic asthma.  J Allergy Clin Immunol. 1983;  71 425-433
• 26 Rodrigo GJ, Rodrigo C. The role of anticholinergics in acute asthma treatment.  Chest. 2002;  121 1977-1987
• 27 Smolensky MH. Chronobiology and chronotherapeutics: applications to cardiovascular medicine.  Am J Hypertens. 1996;  9 S11-S21
• 28 Thonson NC, Patel KR, Kerr JW. Sodium cromoglycate and ipratropium bromide in exercise-induced asthma.  Thorax. 1978;  33 694-699
• 29 Vianna EO, Boaventura LC, Terra-Filho J, Nakama G Y, Martinez JAB, Martin RJ. Morning-to-evening variation in exercise-induced bronchospasm.  J Allergy Clin Immunol. 2002;  110 236-240
• 30 Westby M, Benson M, Gibson P. Anticholinergic agents for chronic asthma in adults.  Cochrane Database Syst Rev. 2004;  3 CD003269

Correspondence