Pharmacogenetic Effects of Inhaled Salbutamol on 10-km Time Trial Performance in Competitive Male and Female Cyclists.

OBJECTIVE: To determine the effects of single nucleotide polymorphisms (SNPs) in the adrenergic ß2-receptor gene (ADRB2, rs1042713, and rs1042714) and epithelial Na channel gene (SCNN1A, rs2228576) on cycling performance after the inhalation of salbutamol. DESIGN: Randomized double-blind, mixed-model repeated measures. SETTING: University Research Setting. PARTICIPANTS: Sixty-nine trained (maximal oxygen consumption: 62.3 ± 7.6 mL·kg·min) male and female cyclists, aged 19 to 40 years. INTERVENTIONS: Participants performed two 10-km time trials 60 minutes after the inhalation of 400 µg of salbutamol or placebo. Subjects were genotyped for the three SNPs (rs1042713: AA 8, AG 30 GG 31; rs1042714: CC 19, CG 35, GG 15; rs2228576: GG: 31 GA: 34 AA: 4). MAIN OUTCOME MEASURES: Forced expiratory volume in 1 second (FEV1) was assessed immediately before and 30 minutes after inhalation. Performance was measured by mean power output maintained over the duration of the time trial. RESULTS: There was a significant increase in FEV1 after the inhalation of salbutamol [mean (SD) = 5.68% (4.7)] compared with placebo [0.84% (2.8); P < 0.001]; however, this did not lead to an improvement in 10-km cycling time trial performance. Neither the bronchodilatory response nor the time trial performance after salbutamol was affected by genotype at any of the 3 SNPs. CONCLUSIONS: In cyclists, FEV1 was significantly improved after salbutamol administration regardless of genotypic variation at the ADRB2 (rs1042713 and rs1042714) and SCNN1A (rs2228576) genes. Despite this improvement in lung function, 10-km time trial performance was not altered after the inhalation of salbutamol. CLINICAL RELEVANCE: Our findings did not show genotype-dependent differences in bronchodilatory responses and athletic performance to inhaled salbutamol, suggesting that genotype-specific drug therapy will not improve asthmatic athletes' care nor athletic performance.

Acute Beetroot Juice Supplementation Does Not Improve Cycling Performance in Normoxia or Moderate Hypoxia.

Beetroot juice (BR) has been shown to lower the oxygen cost of exercise in normoxia and may have similar effects in hypoxia. We investigated the effect of BR on steady-state exercise economy and 10-km time trial (TT) performance in normoxia and moderate hypoxia (simulated altitude: ~2500 m). Eleven trained male cyclists (VO 2peak ≥ 60 ml · kg(-1) · min(-1)) completed four exercise trials. Two hours before exercise, subjects consumed 70 mL BR (~6 mmol nitrate) or placebo (nitrate-depleted BR) in a randomized, double-blind manner. Subjects then completed a 15-min self-selected cycling warm-up, a 15-min steady-state exercise bout at 50% maximum power output, and a 10-km time trial (TT) in either normoxia or hypoxia. Environmental conditions were randomized and single-blind. BR supplementation increased plasma nitrate concentration and fraction of exhaled nitric oxide relative to PL (p < .05 for both comparisons). Economy at 50% power output was similar in hypoxic and normoxic conditions (p > .05), but mean power output was greater in the normoxic TT relative to the hypoxic TT (p < .05). BR did not affect economy, steady-state SpO2, mean power output, or 10-km TT completion time relative to placebo in either normoxia or hypoxia (p > .05 in all comparisons). In conclusion, BR did not lower the oxygen cost of steady-state exercise or improve exercise performance in normoxia or hypoxia in a small sample of well-trained male cyclists.

Effects of inhaled bronchodilators on lung function and cycling performance in female athletes with and without exercise-induced bronchoconstriction.

OBJECTIVES: Inhaled ß2-agonists may cause differential effects on lung function and athletic performance in female compared to male athletes. The objective of this study was to compare the effects of inhaled ß2-agonists on lung function and cycling performance between female athletes with and without exercise-induced bronchoconstriction and with previously published data on men. DESIGN: Double-blind crossover randomized controlled trial. METHODS: Twenty-one female athletes (6 with exercise-induced bronchoconstriction and 15 without exercise-induced bronchoconstriction) performed a simulated 10-km time-trial on a cycle ergometer 60 min after the inhalation of either 400 µg of salbutamol or placebo. Forced expiratory volume in 1s, was measured immediately before and 30 min after inhalation. Performance was measured by mean power output over the duration of the time trial. RESULTS: After salbutamol inhalation, Forced expiratory volume in 1s improved significantly in athletes with exercise-induced bronchoconstriction (M (SD) = 6.1% (47.6)) and athletes without exercise-induced bronchoconstriction (4.0% (3.1); p ≤ 0.02). Mean power output was significantly decreased after salbutamol use (204 W (21)) compared to placebo (208 W (17); p = 0.047), regardless of airway hyperresponsiveness. Relative to placebo, salbutamol significantly increased mean oxygen consumption (46.9 mL kg(-1)min(-1) (5.9) vs. 44.8 mL kg(-1)min(-1) (4.0); p = 0.049) and significantly decreased cycling economy (72.8 W L(-1)min(-1) (6.8) vs. 76.4 W L(-1)min(-1) (4.3); p = 0.01). CONCLUSIONS: The inhalation of salbutamol induced a significant increase in lung function in female athletes, but this increased lung function did not translate to improved exercise performance.

Heliox breathing equally influences respiratory mechanics and cycling performance in trained males and females.

In this study we tested the hypothesis that inspiring a low-density gas mixture (helium-oxygen; HeO2) would minimize mechanical ventilatory constraints and preferentially increase exercise performance in females relative to males. Trained male (n = 11, 31 yr) and female (n = 10, 26 yr) cyclists performed an incremental cycle test to exhaustion to determine maximal aerobic capacity (V̇o2max; male = 61, female = 56 ml·kg(-1)·min(-1)). A randomized, single-blinded crossover design was used for two experimental days where subjects completed a 5-km cycling time trial breathing humidified compressed room air or HeO2 (21% O2:balance He). Subjects were instrumented with an esophageal balloon for the assessment of respiratory mechanics. During the time trial, we assessed the ability of HeO2 to alleviate mechanical ventilatory constraints in three ways: 1) expiratory flow limitation, 2) utilization of ventilatory capacity, and 3) the work of breathing. We found that HeO2 significantly reduced the work of breathing, increased the size of the maximal flow-volume envelope, and reduced the fractional utilization of the maximal ventilatory capacity equally between men and women. The primary finding of this study was that inspiring HeO2 was associated with a statistically significant performance improvement of 0.7% (3.2 s) for males and 1.5% (8.1 s) for females (P < 0.05); however, there were no sex differences with respect to improvement in time trial performance (P > 0.05). Our results suggest that the extent of sex-based differences in airway anatomy, work of breathing, and expiratory flow limitation is not great enough to differentially affect whole body exercise performance.

Inhaled salbutamol does not affect athletic performance in asthmatic and non-asthmatic cyclists.

RATIONALE: Salbutamol may affect lung function and exercise performance differently in individuals with and without asthma. OBJECTIVES: To compare the effects of inhaled salbutamol on lung function, exercise performance and respiratory parameters during cycling exercise in athletes with a positive response to a eucapnic voluntary hyperpnoea (EVH+) and negative (EVH-) challenge, indicative of exercise-induced bronchoconstriction. METHODS: In a randomised controlled trial with a crossover design, a total of 49 well-trained male athletes (14 EVH+ and 35 EVH-) performed two simulated 10 km time-trials on a cycle ergometer 60 min after the inhalation of either 400 µg of salbutamol or a placebo. Lung function, assessed by forced expiratory volume in 1 s, was measured immediately before and 30 min after inhalation. Performance was measured by mean power output. MEASUREMENTS & MAIN RESULTS: Despite a significant increase in lung function after the inhalation of salbutamol compared to the placebo (p<0.001), salbutamol did not affect athletes' perceptions of dyspnoea (p>0.05) or leg exertion (p>0.05) during exercise. Salbutamol did not affect mean power output: EVH+ and EVH- athletes averaged 4.0 (0.5) and 4.1 (0.5) W/kg after salbutamol and 4.0 (0.5) W/kg and 4.0 (0.4) W/kg after placebo, respectively (p>0.05 for each comparison). CONCLUSIONS: The inhalation of salbutamol induced a significant increase in resting lung function in EVH+ and EVH- athletes but this improvement in lung function did not translate to improved exercise performance. Salbutamol had no discernible effect on key ventilatory and exercise parameters regardless of EVH challenge outcome.

Inhaled salbutamol and doping control: effects of dose on urine concentrations.

OBJECTIVE: The present study was designed to examine the dose-response relationship of inhaled salbutamol and its concentration in the urine while resting at various times after inhalation, and to compare these values against the current World Anti-Doping Code limits. DESIGN: An interventional, repeated-measures design. SETTING: Sport Medicine Clinic, University of British Columbia (Vancouver, Canada). PARTICIPANTS: Eight healthy, nonasthmatic males participated in this study (age = 28 +/- 6 years, height = 179.4 +/- 5.1 cm, and weight = 77.4 +/- 5.4 kg). INTERVENTION: Administration of three different doses of inhaled salbutamol (800, 400, and 200 microg) in a randomized fashion separated by at least 72 hours. MAIN OUTCOME MEASUREMENT: Urine concentration of nonsulphated salbutamol RESULTS: Urine concentrations were highly variable between subjects and increased as dose increased, with a significant difference noted between 800 and 200 microg at 30, 60, and 120 minutes after inhalation. Urine concentrations of salbutamol peaked at 60 minutes for all doses. No samples exceeded the doping criterion of 1000 ng/mL, and the maximum value observed was 904 ng/mL. CONCLUSION: These results indicate that after inhalation of doses up to 800 microg, urinary concentrations of salbutamol are well below the limits used in doping control.

Dose response of inhaled salbutamol on exercise performance and urine concentrations.

PURPOSE: This study determined the dose-response effects of inhaled salbutamol (SAL) on time-trial performance and urine concentrations of SAL (cSAL). METHODS: Nonasthmatic, trained male cyclists and triathletes (N = 37) were studied. Day 1 consisted of screening for airway hyperresponsiveness, using a eucapnic voluntary hyperpnea test (EVH), followed by an incremental exercise test to determine V O 2max and peak power (P max). On days 2-5, athletes performed a 20-km time trial 15 min after inhalation (PI) of placebo, 200 microg (D2), 400 microg (D4), or 800 microg (D8) of SAL. At 60 min PI, urine samples were provided. All conditions were randomized and double blinded, with repeated-measures ANOVA used to determine effects of dose. Post hoc analysis was done with Tukey's HSD test. RESULTS: Seven subjects had positive responses to the EVH test, resulting in a 19% incidence within this sample; they were excluded from further participation in this study. The remaining subjects (N = 30) had a V O 2max of 67.1 (4.3) mL x kg(-1) x min(-1) and Pmax of 457 (31) W (W). There was no effect of dose on completion time (P > 0.05), mean power (P > 0.05), or mean heart rate (P > 0.05). Similarly, SAL had no effect on any metabolic or ventilatory parameters (P > 0.05). Urine cSAL increased with dose and was highly variable, with the peak value observed being 831 ng x mL(-1) after a dose of 800 microg. Moderate but significant correlations were noted between cSAL and urine specific gravity at higher doses (D4, r = 0.42; D8, r = 0.37). CONCLUSIONS: These findings suggest that inhaled SAL does not enhance time-trial performance, regardless of dose, and that urine cSAL after exercise is related to dose, demonstrates high variability, and is partially related to hydration status.

Lung density is not altered following intense normobaric hypoxic interval training in competitive female cyclists.

Noninvasive imaging techniques have been used to assess pulmonary edema following exercise but results remain equivocal. Most studies examining this phenomenon have used male subjects while the female response has received little attention. Some suggest that women, by virtue of their smaller lungs, airways, and diffusion surface areas may be more susceptible to pulmonary limitations during exercise. Accordingly, the purpose of this study was to determine if intense normobaric hypoxic exercise could induce pulmonary edema in women. Baseline lung density was obtained in eight highly trained female cyclists (mean +/- SD: age = 26 +/- 7 yr; height = 172.2 +/- 6.7 cm; mass = 64.1 +/- 6.7 kg; Vo(2max) = 52.2 +/- 2.2 ml.kg(-1).min(-1)) using computed tomography (CT). CT scans were obtained at the level of the aortic arch, the tracheal carina, and the superior end plate of the tenth thoracic vertebra. While breathing 15% O(2), subjects then performed five 2.5-km cycling intervals [mean power = 212 +/- 31 W; heart rate (HR) = 94.5 +/- 2.2%HRmax] separated by 5 min of recovery. Throughout the intervals, subjects desaturated to 82 +/- 4%, which was 13 +/- 2% below resting hypoxic levels. Scans were repeated 44 +/- 8 min following exercise. Mean lung density did not change from pre (0.138 +/- 0.014 g/ml)- to postexercise (0.137 +/- 0.011 g/ml). These findings suggest that pulmonary edema does not occur in highly trained females following intense normobaric hypoxic exercise.

Human ventilatory responsiveness to hypoxia is unrelated to maximal aerobic capacity.

Ventilatory responsiveness to hypoxia (HVR) has been reported to be different between highly trained endurance athletes and healthy sedentary controls. However, a linkage between aerobic capacity and HVR has not been a universal finding. The purpose of this study was to examine the relationship between HVR and maximal oxygen consumption (VO2 max) in healthy men with a wide range of aerobic capacities. Subjects performed a HVR test followed by an incremental cycle test to exhaustion. Participants were classified according to their maximal aerobic capacity. Those with a VO2 max of >or=60 ml x kg(-1) x min(-1) were considered highly trained (n = 13); those with a VO2 max of 50-60 ml x kg(-1) x min(-1) were considered moderately-trained (n = 18); and those with a VO2 max of <50 ml x kg(-1) x min(-1) were considered untrained (n = 24). No statistical differences were detected between the three groups for HVR (P > 0.05), and the HVR values were variable within each group (range: untrained = 0.28-1.61, moderately trained = 0.23-2.39, and highly trained = 0.08-1.73 l x min.%arterial O2 saturation(-1)). The relationship between HVR and VO2 max was not statistically significant (r = -0.1723; P > 0.05). HVR was also unrelated to maximal minute ventilation and ventilatory equivalents for O2 and CO2. We found that a spectrum of hypoxic ventilatory control is present in well-trained endurance athletes and moderately and untrained men. We interpret these observations to mean that other factors are more important in determining hypoxic ventilatory control than physical conditioning per se.