Comparative Effects of Caffeine and Albuterol on the Bronchoconstrictor Response to Exercise in Asthmatic Athletes

Abstract

The main aim of this study was to evaluate the comparative and additive effects of caffeine and albuterol (short-acting β₂-agonist) on the severity of EIB. Ten asthmatic subjects with EIB (exercise-induced bronchoconstriction) participated in a randomized, double-blind, double-dummy crossover study. One hour before an exercise challenge, each subject was given 0, 3, 6, or 9 mg/kg of caffeine or placebo mixed in a flavored sugar drink. Fifteen minutes before the exercise bout, an inhaler containing either albuterol (180 μg) or placebo was administered to each subject. Pulmonary function tests were conducted pre- and post-exercise. Caffeine at a dose of 6 and 9 mg/kg significantly reduced (p<0.05) the mean maximum % fall in post-exercise FEV₁ to −9.0±9.2% and −6.8±6.5% respectively compared to the double-placebo (−14.3±11.1%) and baseline (−18.4±7.2%). There was no significant difference (p>0.05) in the post-exercise % fall in FEV₁ between albuterol (plus caffeine placebo) (−4.0±5.2%) and the 9 mg/kg dose of caffeine (−6.8±6.5%). Interestingly, there was no significant difference (p>0.05) in the post-exercise % fall in FEV₁ between albuterol (plus caffeine placebo) (−4.0±5.2%) and albuterol with 3, 6 or 9 mg/kg of caffeine (−4.4±3.8, −6.8±5.6, −4.4±6.0% respectively). Similar changes were observed for the post-exercise % fall in FVC, FEF_25–75% and PEF. These data indicate that moderate (6 mg/kg) to high doses (9 mg/kg) of caffeine provide a significant protective effect against EIB. It is feasible that the negative effects of daily use of short-acting β₂-agonists by asthmatic athletes could be reduced simply by increasing caffeine consumption prior to exercise.

Key words

exercise-induced asthma - bronchoconstriction - diet

References

• 1 American Thoracic Society Guidelines for Methacholine and Exercise Challenge Testing – 1999 . Am J Respir Crit Care Med. 2000;  161 309-329
• 2 American Thoracic Society Standardization of spirometry – 1994 update.  Am J Respir Crit Care Med. 1995;  152 1107-1136
• 3 Anderson SD, Caillaud C, Brannan JD. Beta2-agonists and exercise-induced asthma.  Clin Rev Allergy Immunol. 2006;  31 163-180
• 4 Anderson SD, Connolly NM, Godfrey S. Comparison of bronchoconstriction induced by cycling and running.  Thorax. 1971;  26 396-401
• 5 Anderson SD, Lambert S, Brennan JD, Wood RJ, Koskela H, Morton AR, Fitch KD. Laboratory protocol for exercise asthma to evaluate salbutamol given by two devices.  Med Sci Sports Exerc. 2001;  33 893-900
• 6 Anderson SD, Sue-Chu M, Perry CP, Gratziou C, Kippelen P, McKenzie DC, Beck KC, Fitch KD. Bronchial challenges in athletes applying to inhale a beta2-agonist at the 2004 Summer Olympics.  J Allergy Clin Immunol. 2006;  117 767-773
• 7 Beck KC, Offord KP, Scanlon PD. Bronchoconstriction occurring during exercise in asthmatic subjects.  Am J Respir Crit Care Med. 1994;  149 352-357
• 8 Bonini S, Brusasco V, Carlsen KH, Delgado L, Giacco SD, Haahtela T, Rasi G, van Cauwenberge PB. Diagnosis of asthma and permitted use of inhaled beta2-agonists in athletes.  Allergy. 2004;  59 33-36
• 9 Butcher RW, Sutherland EW. Adenosine 3′,5′-phosphate in biological materials. I. Purification and properties of cyclic 3′,5′-nucleotide phosphodiesterase and use of this enzyme to characterize adenosine 3′,5′-phosphate in human urine.  J Biol Chem. 1962;  237 1244-1250
• 10 Chorley BN, Li Y, Fang S, Park JA, Adler KB. (R)-albuterol elicits antiinflammatory effects in human airway epithelial cells via iNOS.  Am J Respir Cell Mol Biol. 2006;  34 119-127
• 11 Duffy P, Phillips YY. Caffeine consumption decreases the response to bronchoprovocation challenge with dry gas hyperventilation.  Chest. 1991;  99 1374-1377
• 12 Evans TM, Rundell KW, Beck KC, Levine AM, Baumann JM. Cold air inhalation does not affect the severity of EIB after exercise or eucapnic voluntary hyperventilation.  Med Sci Sports Exerc. 2005;  37 544-549
• 13 Feoktistov I, Polosa R, Holgate ST, Biaggioni I. Adenosine A2B receptors: a novel therapeutic target in asthma?.  Trends Pharmacol Sci. 1998;  19 148-153
• 14 Fitch KD, Morton AR. Specificity of exercise in exercise-induced asthma.  Br Med J. 1971;  4 577-581
• 15 Fitch KD, Sue-Chu M, Anderson SD, Boulet LP, Hancox RJ, McKenzie DC, Backer V, Rundell KW, Alonso JM, Kippelen P, Cummiskey JM, Garnier A, Ljungqvist A. Asthma and the elite athlete: summary of the International Olympic Committee's consensus conference, Lausanne, Switzerland, January 22–24, 2008.  J Allergy Clin Immunol. 2008;  122 254-260 260 e251-257
• 16 Graham TE. The possible actions of methylxanthines on various tissues.. In: The Clinical Pharmacology of Sports and Exercise. Reilly T, Orme M, (eds) Amsterdam: Elsevier Science; 1997: 257-270
• 17 Hancox RJ, Subbarao P, Kamada D, Watson RM, Hargreave FE, Inman MD. Beta2-agonist tolerance and exercise-induced bronchospasm.  Am J Respir Crit Care Med. 2002;  165 1068-1070
• 18 Haney S, Hancox RJ. Recovery from bronchoconstriction and bronchodilator tolerance.  Clin Rev Allergy Immunol. 2006;  31 181-196
• 19 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
• 20 Inman MD, O’Byrne PM. The effect of regular inhaled albuterol on exercise-induced bronchoconstriction.  Am J Respir Crit Care Med. 1996;  153 65-69
• 21 Kemp JP, Dockhorn RJ, Busse WW. Prolonged effect of inhaled salmeterol against exercise-induced bronchospasm.  Am J Respir Crit Care Med. 1994;  150 1612-1615
• 22 Kivity S, Ben Aharon Y, Man A, Topilsky M. The effect of caffeine on exercise-induced bronchoconstriction.  Chest. 1990;  97 1083-1085
• 23 Martineau L, Horan MA, Rothwell NJ, Little RA. Salbutamol, a beta 2-adrenoceptor agonist, increases skeletal muscle strength in young men.  Clin Sci (Lond). 1992;  83 615-621
• 24 McFadden Jr ER, Gilbert IA. Exercise-induced asthma.  N Engl J Med. 1994;  330 1362-1367
• 25 McKenzie DC, Stewart IB, Fitch KD. The asthmatic athlete, inhaled beta agonists, and performance.  Clin J Sport Med. 2002;  12 225-228
• 26 Mickleborough TD. A nutritional approach to managing exercise-induced asthma.  Exerc Sport Sci Rev. 2008;  36 135-144
• 27 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
• 28 Milanese M, Saporiti R, Bartolini S, Pellegrino R, Baroffio M, Brusasco V, Crimi E. Bronchodilator effects of exercise hyperpnea and albuterol in mild-to-moderate asthma.  J Appl Physiol. 2009;  107 494-499
• 29 Mundell SJ, Olah ME, Panettieri RA, Benovic JL, Penn RB. Regulation of G protein-coupled receptor-adenylyl cyclase responsiveness in human airway smooth muscle by exogenous and autocrine adenosine.  Am J Respir Cell Mol Biol. 2001;  24 155-163
• 30 Nelson JA, Strauss L, Skowronski M, Ciufo R, Novak R, McFadden Jr ER. Effect of long-term salmeterol treatment on exercise-induced asthma.  N Engl J Med. 1998;  339 141-146
• 31 O’Donnell AE, Fling J. Exercise-induced airflow obstruction in a healthy military population.  Chest. 1993;  103 742-744
• 32 Ramage L, Lipworth BJ, Ingram CG, Cree IA, Dhillon DP. Reduced protection against exercise induced bronchoconstriction after chronic dosing with salmeterol.  Respir Med. 1994;  88 363-368
• 33 Ramsdell JW, Colice GL, Ekholm BP, Klinger NM. Cumulative dose response study comparing HFA-134a albuterol sulfate and conventional CFC albuterol in patients with asthma.  Ann Allergy Asthma Immunol. 1998;  81 593-599
• 34 Rundell KW, Im J, Mayers LB, Wilber RL, Szmedra L, Schmitz HR. Self-reported symptoms and exercise-induced asthma in the elite athlete.  Med Sci Sports Exerc. 2001;  33 208-213
• 35 Rundell KW, Wilber RL, Szmedra L, Jenkinson DM, Mayers LB, Im J. Exercise-induced asthma screening of elite athletes: field versus laboratory exercise challenge.  Med Sci Sports Exerc. 2000;  32 309-316
• 36 Simons FE, Gerstner TV, Cheang MS. Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled glucocorticoid treatment.  Pediatrics. 1997;  99 655-659
• 37 Snyder SH, Katims JJ, Annau Z, Bruns RF, Daly JW. Adenosine receptors and behavioral actions of methylxanthines.  Proc Natl Acad Sci USA. 1981;  78 3260-3264
• 38 Sonna LA, Angel KC, Sharp MA, Knapik JJ, Patton JF, Lilly CM. The prevalence of exercise-induced bronchospasm among US Army recruits and its effects on physical performance.  Chest. 2001;  119 1676-1684
• 39 Stephenson PE. Physiologic and psychotropic effects of caffeine on man. A review.  J Am Diet Assoc. 1977;  71 240-247
• 40 Storms WW. Review of exercise-induced asthma.  Med Sci Sports Exerc. 2003;  35 1464-1470
• 41 Sue-Chu M, Karjalainen EM, Altraja A, Laitinen A, Laitinen LA, Naess AB, Larsson L, Bjermer L. Lymphoid aggregates in endobronchial biopsies from young elite cross-country skiers.  Am J Respir Crit Care Med. 1998;  158 597-601
• 42 Tanaka Y, Horinouchi T, Koike K. New insights into beta-adrenoceptors in smooth muscle: distribution of receptor subtypes and molecular mechanisms triggering muscle relaxation.  Clin Exp Pharmacol Physiol. 2005;  32 503-514
• 43 Weiler JM, Bonini S, Coifman R, Craig T, Delgado L, Capao-Filipe M, Passali D, Randolph C, Storms W. American Academy of Allergy, Asthma & Immunology Work Group report: exercise-induced asthma.  J Allergy Clin Immunol. 2007;  119 1349-1358
• 44 Wilber RL, Rundell KW, Szmedra L, Jenkinson DM, Im J, Drake SD. Incidence of exercise-induced bronchospasm in Olympic winter sport athletes.  Med Sci Sports Exerc. 2000;  32 732-737
• 45 Zhong H, Belardinelli L, Maa T, Feoktistov I, Biaggioni I, Zeng D. A(2B) adenosine receptors increase cytokine release by bronchial smooth muscle cells.  Am J Respir Cell Mol Biol. 2004;  30 118-125

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