Medicine & Science in Sports & Exercise:
Clinical Sciences: Clinical Investigations
Montelukast Has No Ergogenic Effect on Cycle Ergometry in Cold Temperature
RUNDELL, KENNETH W.1; SPIERING, BARRY A.1,2; BAUMANN, JENNIFER M.1; EVANS, TINA M.1
1Human Performance Laboratory, Keith J. O’Neill Center for Healthy Families, Marywood University, Scranton, PA
2Human Performance Laboratory, Department of Kinesiology, University of Connecticut, Storrs, CT
Address for correspondence: Kenneth W. Rundell, Ph.D., Center for Healthy Families, Marywood University, Scranton, PA 18509; E-mail: email@example.com.
Submitted for publication May 2004.
Accepted for publication July 2004.
Purpose: To examine the effects of a single 10-mg dose of ML on physical performance in EIB− and EIB+ athletes.
Methods: Twenty-four male college ice hockey players performed two 6-min maximal work accumulation bouts on an electronically braked cycle ergometer in subfreezing conditions (−2.5 ± 0.4°C) 6–8 h after either ML or placebo (PL) to obtain total work accumulated (kJ); subjects were evaluated for EIB after each exercise trial.
Results: Eight (33%) subjects were identified as EIB+ (23.5 ± 13.35% fall in FEV1); 16 were EIB− (1.8 ± 3.03% fall in FEV1). ML provided a ∼50% protection against postexercise fall in FEV1. No significant differences in kJ were found between PL and ML trials for pooled subjects (95.3 ± 13.69 and 94.8 ± 13.27 kJ, respectively), EIB− subjects (99.6 ± 13.26 and 99.0 ± 11.81 kJ, respectively), or EIB+ subjects (86.8 ± 10.67 and 86.5 ± 12.72 kJ, respectively). Total work accumulated for EIB− subjects was significantly greater than for EIB+ subjects for both PL and ML (P < 0.05).
Conclusion: A single 10-mg dose of ML had no ergogenic effect for EIB− and EIB+ subjects performing short-duration high-intensity exercise in subfreezing temperature, supporting the use of ML as EIB prophylaxis during international sport competition.
Exercise-induced bronchoconstriction (EIB) is a condition characterized by transient airway narrowing during or after exercise (2). The reported prevalence of EIB has reached epidemic proportions both among elite athletes (23,28–30) and the general population (8). Approximately 25% of 1998 U.S. Olympic Winter athletes were identified as EIB positive (EIB+) by spirometry with as many as 50–60% of athletes in certain sport disciplines suffering from EIB (30). Among 1996 U.S. Summer Olympians, 15.3% reported a previous diagnosis of asthma, exercise-induced asthma (EIA), or EIB (29).
Breathing cool and/or dry air during exercise at high minute ventilations (V̇E) may lead to loss of airway surface liquid from warming and humidifying the inspired air. A resulting change in airway cell osmolarity can trigger the release of inflammatory mediators, including cysteinyl leukotrienes, which have been implicated in the pathogenesis of EIB (2). Montelukast (ML), a cysteinyl leukotriene receptor antagonist, has been shown to attenuate EIB and its symptoms (4,6,7,10,13–16,18,20,27).
Although it is apparent that ML can improve airway function, little is known about its acute influence on physical performance. Steinshamn et al. (25) showed that 5 d of treatment with 10 mg of ML improved running time to exhaustion in cold (−15°C) conditions for 11 of 16 EIB+ subjects. Alternately, Sue-Chu et al. (26) found no change in performance or pulmonary function for elite nonasthmatic endurance athletes while running in below-freezing conditions after a single 10-mg dose of ML.
Treatment is important to the EIB+ athlete, as performance can potentially be affected from the airway obstruction characteristic of EIB. However, certain pharmacological interventions have been suspected as ergogenic aids, and their use is disallowed during competition. Athletes are now required to provide evidence of asthma, EIA, or EIB when notifying the International Olympic Committee of β2- agonist use before competition (1) as an attempt to limit unnecessary use of β2-agonists.
Currently, the International Olympic Committee does not index ML on their doping control list. To our knowledge, only two studies, from the same group, examined the effects of ML on exercise performance in EIB− athletes (26) and EIB+ subjects (25). Therefore, the purpose of this study is to examine the effects of ML on physical performance in EIB+ and EIB− athletes during a 6-min high-intensity exercise challenge in cold ambient conditions.
Twenty-four college ice hockey players (19.5 ± 1.1 yr; 177.9 ± 6.3 cm; 83.0 ± 12.1 kg) volunteered to participate in the study. Subjects gave written informed consent and completed a medical history questionnaire. Five subjects reported a prior physician diagnosis asthma and/or EIB; of these five subjects, all reported short acting β2-agonist use; one reported corticosteroid, salmeterol and ML use; and one reported corticosteroid, antihistamine, and ML use. Subjects were asked to abstain from medications beginning 1 wk before and throughout the study duration. Experimental procedures were approved by the Marywood University Institutional Review Board.
A randomized, double blind, placebo-controlled, cross-over design was employed to determine whether 6-min cycling performance in cold/dry ambient conditions improved after a single 10-mg dose of ML (Singulair®, Merck, West Point, PA). Subjects reported to the laboratory for an exercise challenge 6–8 h after taking either placebo (PL) or ML. Testing was separated by ≥48 h. The exercise challenge consisted of a 6-min trial performed in an environmental chamber under cold/dry ambient conditions (−2.5 ± 0.4°C, 50% RH) using an electronically braked cycle ergometer (Lode Excalibur Sport, Lode, Groningen, The Netherlands). Subjects were verbally encouraged to give a maximal effort. Heart rate (beats·min−1) was recorded every minute (Polar s610, Polar Electro Oy, Finland) and total work accumulated (kJ) was recorded upon completion of the 6-min time trial.
Pulmonary function tests.
Pulmonary function was measured by spirometry using a calibrated computerized pneumotachograph spirometer (Jaeger Masterscope PC, Hoechberg, Germany). Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, and the forced expiratory flow through the mid-portion of the vital capacity (FEF25–75) were determined pre- and postchallenge. The procedure for all pulmonary function tests (PFT) was 1) three normal tidal volume breaths, 2) maximal inhalation, 3) forced maximal exhalation lasting at least 6 s, and 4) maximal inhalation. Baseline pulmonary function was established by selecting the best-of-three resting PFT based on the highest sum of FVC and FEV1. Postchallenge pulmonary function was measured at 5, 10, and 15 min after the completion of the 6-min cycle ergometer ride. If any postchallenge time point PFT maneuver was technically unacceptable, it was repeated. Subjects presenting a ≥10% fall in FEV1 from baseline after either challenge (PL or ML) were considered EIB+ (24).
Subjects were grouped according to EIB status. Descriptive statistics for work accumulated and heart rate were calculated for each trial (treatment and placebo) and group (EIB− and EIB+). Additionally, work accumulated was normalized to individual body mass to examine differences between EIB+ and EIB− groups. Repeated measures ANOVA was used to analyze differences between trials and groups. An alpha of P ≤ 0.05 was considered significant.
Resting baseline lung function variables (FVC, FEV1, FEV1/FVC, FEF25–75) were not different between trials (PL or ML), or between groups (EIB− or EIB+). Table 1 shows baseline lung functions for all subjects (N = 24). Eight of the 24 subjects (33.3%) who completed the two 6-min time trials were identified as EIB+ by a ≥10% fall in FEV1; three had a prior diagnosis of asthma. Peak falls in postexercise lung functions are presented in Figure 1 as percent of preexercise baseline values. Significant differences between EIB− and EIB+ subjects were found for FEV1 after PL and for FEF25–75 after PL and ML (P < 0.05). ML provided approximately 50% protection from bronchoconstriction as defined by the attenuated fall in FEV1 and FEF25–75.
No difference in total work accumulated (absolute [kJ] or relative to body weight [kJ·kg−1]) was apparent for pooled subjects after a single 10-mg dose of ML ingested 6–8 h before 6-min cycle ergometry (Table 2). Likewise, exercising peak HR was not different between PL and ML.
When subjects were grouped according to EIB status, no differences in accumulated work between PL and ML were noted (Table 3). However, significant differences were found for work accumulated (kJ and kJ·kg−1) and exercising peak HR between EIB− and EIB+ groups (P < 0.05). Total work accumulated (kJ and kJ·kg−1) was greater and exercising peak HR was lower for EIB− subjects than for EIB+ subjects. Figure 2 presents individual plots of work accumulated for the 19 EIB− (panel A) and eight EIB+ (panel B) subjects for PL and ML trials.
Before this study, no studies had evaluated the effects of ML on performance in an intermittent high power sport such as ice hockey. Although typical play shifts in ice hockey are less than 1 min in duration, the game involves three 20-min periods, and both practice and play require a considerable aerobic contribution. The 6-min cycle ergometer challenge used in this study is a test that has been used to evaluate fitness in ice hockey players and is of a duration sufficient to evaluate an ergogenic effect before a confounding during exercise bronchoconstriction (2,3). A 10-mg dose of ML taken orally 6–8 h before a 6-min maximal intensity bout of cycle ergometry had no ergogenic effect on total work accumulated in cold/dry ambient conditions (−2.5°C) for subjects in this study. Maximal heart rate values were similar between trials for both PL and ML, indicating that subject effort was comparable. When subjects were grouped according to EIB status, no increase in performance after ingestion of ML was noted within either EIB− or EIB+ groups, despite an approximate 50% improvement in postexercise lung function in EIB+ subjects. Interestingly, EIB− subjects demonstrated significantly greater total work accumulation and significantly lower peak HR than EIB+ subjects regardless of PL or ML, even though subject effort was maximal.
Mean resting lung function in the male participants in this study was normal for both EIB− and EIB+ subjects. Although bronchodilation has been reported in asthmatic subjects within 1 h after a 10-fold greater than therapeutic dose of ML (19), bronchodilation was not apparent in either EIB− or EIB+ subjects in this study; this was in agreement with the findings of others (26). In contrast to our previous studies where we identified abnormal resting lung function in approximately 25% of elite women ice hockey players (21,22), only two hockey players in this study exhibited below normal resting lung function. The subjects in our earlier studies (21,22) were elite hockey players who trained over 2 h·d−1, five times per week in a high particulate matter environment; alternately, the hockey players in the present study completed only three 1-h practice sessions per week in a clean air (low [PM1]) rink.
Thirty-three percent of our subjects tested positive for EIB. This is consistent with previous prevalence data reported for ice rink athletes; greater than 30% of figure skaters (13,17), 43% of Olympic short-track speed skaters (30), and 20–35% of elite ice hockey players (11,21) are hyperresponsive to exercise, hyperventilation, or pharmacological challenge. Lumme et al. (11) found 24% of elite Finnish male ice hockey players demonstrated bronchial hyperresponsiveness in a histamine-challenge test, and Rundell et al. (21) found 21% of elite women hockey players were hyperresponsive to exercise.
Postchallenge lung function in EIB− subjects was not altered by 10 mg of ML ingested before exercise; however, in EIB+ subjects, ML ingestion improved postchallenge FEV1 by approximately 50%. This response was similar to findings of others (4,6,7,10,12,14–16,18,20,27), showing approximately 50% improvement in postchallenge lung function by ML in EIB+ and asthmatic subjects. Our results are inconsistent with those reported by Helenius et al. (9), who showed little effectiveness of ML in abating airway hyperresponsiveness in Finnish ice hockey players when challenged with histamine. Our subjects did not undergo a histamine challenge because this challenge lacks sensitivity to EIB (8). The lack of sensitivity and specificity of pharmacological challenges concerning a leukotriene-mediated response are supported by Crimi et al. (5), who found that ML had a significant protective effect against neurokinin A-induced bronchoconstriction but not against a methacholine challenge.
In spite of improved postexercise lung function in EIB+ subjects after ML, no concomitant improvement in high-intensity cycle ergometer performance was noted. This is most likely due to our protocol; by design, our subjects did not warm up with exercise preceding the high-intensity exercise challenge. Because of this, it is probable that bronchoconstriction in the EIB+ subjects did not occur until after the challenge was completed. Beck et al. (3) demonstrated that bronchoconstriction does not occur during short-duration constant-load or high-intensity cycle ergometry in asthmatic subjects. Our study design allowed for a clear picture of the ergogenic effects of ML in EIB+ subjects during exercise, independent of the bronchoconstrictive influence from a prechallenge exercise as previously done (25).
In a previous study evaluating the effects of ML on exercise performance by EIB+ asthmatics, Steinshamn et al. (25) found that 10-mg ML significantly improved running time to exhaustion in cold conditions. However, that study was specifically designed to trigger the bronchoconstrictive response before a “symptom-limited” run to exhaustion by preceding a maximal effort run to exhaustion with a 6-min run at 80% ;V̇O2max and a 4-min recovery period. Consequently, those individuals whose lung function was preserved by ML after the initial 6-min run demonstrated improved performance during the run to exhaustion. The intention of the Steinshamn et al. (25) study was to examine the physiological effects on ML during a running period in which the subjects were suffering from EIB; alternatively, the intention of the present study was to examine the influence of ML independent of bronchoconstriction. The discrepancy between our findings and those of Steinshamn et al. (25) could also be a result the duration of treatment in their study (5 d). Although a single 10-mg dose of ML is adequate to improve lung function in EIB+ subjects, perhaps a longer duration of treatment is needed to see improvements in exercise performance. Finally, our study population consisted of trained collegiate athletes, while those in the Steinshamn et al. (25) study were nonathletes.
In conclusion, a single 10-mg dose of ML ingested 6–8 h before high-intensity exercise did not provide an ergogenic effect during high-intensity cycle ergometry for our group of EIB+ and EIB− athletes. The specific nature of our study design most likely allowed EIB+ subjects to perform the 6-min exercise challenge free of bronchoconstriction, thus abating any performance effect during exercise because of improved lung function. Currently, ML is not on the doping control list of the International Olympic Committee. Our results, taken in consideration with those of Sue-Chu et al. (26), further justify the position that ML is not an ergogenic aid.
This work was supported by Merck and Co., Inc. grant no. SING-U.S.-63-01.
The views, opinions, and findings contained in this report are those of the author and should not be construed as an official position of Marywood University or ACSM.
1. Anderson, S. D., K. Fitch, C. P. Perry, et al. Responses to bronchial challenge submitted for approval to use inhaled beta2 agonists prior to an event at the 2002 Winter Olympics. J. Allergy Clin. Immunol
. 111:44–49, 2003.
2. Anderson, S. D., and E. Daviskas. The mechanism of exercise-induced asthma is. J. Allergy Clin. Immunol
. 106:453–459, 2000.
3. Beck, K. C., K. P. Offord, and P. D. Scanlon. Bronchoconstriction occurring during exercise in asthmatic subjects. Am. J. Respir. Crit. Care Med
. 149:352–357, 1994.
4. Bronsky, E. A., J. P. Kemp, J. Zhang, D. Guerreiro, and T. F. Reiss. Dose-related protection of exercise bronchoconstriction by montelukast, a cysteinyl leukotriene-receptor antagonist, at the end of a once-daily dosing interval. Clin. Pharmacol. Ther
. 62:556–561, 1997.
5. Crimi, N., C. Pagano, F. Palermo, et al. Inhibitory effect of a leukotriene receptor antagonist (montelukast) on neurokinin A-induced bronchoconstriction. J. Allergy Clin. Immunol
. 111:833–839, 2003.
6. Edelman, J. M., J. A. Turpin, E. A. Bronsky, et al. Oral montelukast compared with inhaled salmeterol to prevent exercise-induced bronchoconstriction: a randomized, double-blind trial. Intern. Med
. 132:97–104, 2000.
7. Finnerty, J. P., R. Wood-Baker, H. Thomson, and S. T. Holgate. Role of leukotrienes in exercise-induced asthma. Inhibitory effect of ICI 204219, a potent leukotriene D4 receptor antagonist. Am. Rev. Respir. Dis
. 145:746–749, 1992.
8. Haby, M. M., J. K. Peat, C. M. Mellis, S. D. Anderson, and A. J. Woolcock. An exercise challenge for epidemiological studies of childhood asthma: validity and repeatability. Eur. Respir. J
. 8:729–736, 1995.
9. Helenius, I., A. Lumme, J. Ounap, et al. No effect of montelukast on asthma-like symptoms in elite ice hockey players. Allergy
10. Leff, J. A., W. W. Busse, D. Pearlman, et al. Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction. N. Engl. J. Med
. 339:147–152, 1998.
11. Lumme, A., T. Haahtela, J. Ounap, et al. Airway inflammation, bronchial hyperresponsiveness and asthma in elite ice hockey players. Eur. Respir J
. 22:1–5, 2003.
12. Manning, P. J., R. M. Watson, D. J. Margolskee, V. C. Williams, J. I. Schwartz, and P. M. O’Byrne. Inhibition of exercise-induced bronchoconstriction by MK-571, a potent leukotriene D4-receptor antagonist. N. Engl. J. Med
. 323:1736–1739, 1990.
13. Mannix, E. T., M. O. Farber, P. Palange, P. Galassetti, and F. Manfredi. Exercise-induced asthma in figure skaters. Chest
14. Melo, R. E., D. Sole, and C. K. Naspitz. Exercise-induced bronchoconstriction in children: montelukast attenuates the immediate-phase and late-phase responses. J. Allergy Clin. Immunol
. 111:301–307, 2003.
15. O’Byrne, P. M. Leukotriene bronchoconstriction induced by allergen and exercise. Am. J. Respir. Crit. Care Med
. 161:S68–S72, 2000.
16. Peroni, D. G., G. L. Piacentini, M. Ress, et al. Time efficacy of a single dose of montelukast on exercise-induced asthma in children. Pediatr. Allergy Immunol
. 13:434–437, 2002.
17. Provost-Craig, M. A., K. S. Arbour, D. C. Sestilli, J. J. Chabalko, and E. Ekinol. The incidence of exercise-induced bronchospasm in competitive figure skaters. J. Asthma
18. Reiss, T. F., J. B. Hill, E. Harman, et al. Increased urinary excretion of LTE4 after exercise and attenuation of exercise-induced bronchospasm by montelukast, a cysteinyl leukotriene receptor antagonist. Thorax
19. Reiss, T. F., C. A. Sorkness, W. Stricker, et al. Effects of montelukast (MK-0476); a potent cysteinyl leukotriene receptor antagonist, on bronchodilation in asthmatic subjects treated with and without inhaled corticosteroids. Thorax
20. Riccioni, G., F. Santilli, N. D’Orazio, et al. The role of antileukotrienes in the treatment of asthma. Int. J. Immunopathol. Pharmacol
. 15:171–182, 2002.
21. Rundell, K. W., B. A. Spiering, T. M. Evans, and J. M. Baumann. Baseline lung function, EIB, and asthma-like symptoms in elite women ice hockey players. Med. Sci. Sports Exerc
. 36:405–410, 2004.
22. Rundell, K. W. Pulmonary function decay among women ice hockey players: is there a relationship to ice rink air quality? Inhal. Toxicol
. 16:117–123, 2004.
23. Rundell, K. W., J. Im, L. B. Mayers, R. L. Wilber, L. Szmedra, and H. Schmitz. Self-reported symptoms and exercise-induced asthma in the elite athlete. Med. Sci. Sports Exerc
. 33:208–213, 2001.
24. Rundell, K. W., R. L. Wilber, L. Szmedra, D. M. Jenkinson, L. B. Mayers, and J. Im. Exercise-induced asthma screening of elite athletes: field versus laboratory exercise challenge. Med. Sci. Sports Exerc
. 32:309–316, 2000.
25. Steinshamn, S., M. Sandsund, M. Sue-Chu, and L. Bjermer. Effects of montelukast on physical performance and exercise economy in adult asthmatics with exercise-induced bronchoconstriction. Scand. J. Med. Sci. Sports
26. Sue-Chu, M., M. Sandsund, B. Holand, and L. Bjermer. Montelukast does not affect exercise performance at subfreezing temperature in highly trained non-asthmatic endurance athletes. Int. J. Sports Med
. 21:424–428, 2000.
27. Villaran, C., S. J. O’Neill, A. Helbling, et al. Montelukast versus salmeterol in patients with asthma and exercise-induced bronchoconstriction. J. Allergy Clin. Immunol
. 104:547–553, 1999.
28. Weiler, J. M., and E. J. Ryan III. Asthma in United States Olympic athletes who participated in the 1998 Olympic winter games. J. Allergy Clin. Immunol
. 106:267–271, 2000.
29. Weiler, J., T. Layton, and M. Hunt. Asthma in United States Olympic athletes who participated in the 1996 Summer Games. J. Allergy Clin. Immunol
. 102:722–726, 1998.
30. Wilber, R. L., K. W. Rundell, L. Szmedra, D. M. Jenkinson, J. Im, and S.D. Drake. Incidence of exercise-induced bronchospasm in Olympic Winter Sport athletes. Med. Sci. Sports Exerc
. 32:732–737, 2000.
ASTHMA; ATHLETES; CYSTEINYL-LEUKOTRIENE RECEPTOR ANTAGONIST; EXERCISE-INDUCED BRONCHOCONSTRICTION; EXERCISE PERFORMANCE
©2004The American College of Sports Medicine
Highlight selected keywords in the article text.