Between 2002 and 2010, the International Olympic Committee (IOC) required athletes to present evidence of current asthma or exercise induced bronchoconstriction (EIB) in order to use inhaled [[beta].sub.2]-Agonists. Initially this was conducted independently by the IOC for the Olympic Games and followed by a global requirement, via the World Anti-Doping Agency (WADA), incorporating it into the Therapeutic Use Exemption (TUE) certificate system. These regulations, guided by the IOC Medical Commission (IOC-MC), were based on health not doping (performance enhancing) concerns for athletes in light of a marked increase in the notification for the use of inhaled short acting [[beta].sub.2]-agonist from 3.7% at the Atlanta Olympic Games, 1996, to 5.7% at the Sydney Olympic Games, 2000 (Fitch et al., 2008). Examining the prevalence of asthma and EIB in Great British Olympic athletes across two summer Olympic cycles (2000 and 2004) we provided support for the health justification of adding inhaled short acting [[beta].sub.2]-agonist to the prohibited list (Dickinson et al., 2005). Our data demonstrated that the requirement for a TUE for the use of inhaled short acting [[beta].sub.2]-agonist had no impact on the proportion of Great British Olympic team athletes presenting with asthma, EIB or AHR between the 2000 Sydney Olympic Games and the 2004 Athens Olympic Games (~21% at both) however; we identified a number of athletes with false positive diagnoses and athletes who had not been previously identified. Accordingly, we concluded, as have others, that the requirement of demonstrable evidence through the TUE process improves the quality of care for athletes (Couto et al., 2013). Furthermore, data from our lab (Dickinson et al., 2006a; 2006b) and others (Anderson et al., 2003; Parsons et al., 2007; Rundell et al., 2004,) has demonstrated the improved diagnostic sensitivity and specificity of incorporating indirect airway challenges into the process of diagnosing an athlete with asthma, EIB or AHR.
The weight of evidence supports the improved health care of athletes following the introduction of the TUE process for inhaled short acting [[beta].sub.2]-agonist (Fitch et al. 2008; Couto et al. 2013). In recent years it has been argued that the requirement of a TUE is not warranted due to the limited evidence to suggest doses of inhaled [[beta].sub.2]-agonist (200 - 800 pg) have a significant ergogenic effect. A meta-analysis, incorporating the small numbers of studies that do exist, reported no performance improvement in endurance performance from up to 800 [micro]g of inhaled short acting [[beta].sub.2]-agonist (Pluim et al., 2011). However the requirement of needing a TUE to use inhaled [[beta].sub.2]-agonist therapist may also lead to athletes requiring inhalers for asthma/EIB not taking them in order to not risk a doping violation.
Whilst there appears to be no ergogenic effect from inhaled salbutamol at low doses, no study has investigated the impact of inhaling the World Anti-Doping Agency (WADA) daily upper limit of 1600 [micro]g (~16 inhalations of a standard salbutamol inhaler; WADA, 2013) on endurance running performance. Furthermore, only a limited number of studies have examined the salbutamol elimination in urine of inhaled doses as high as 1600 [micro]g and have reported urine concentrations close to the WADA upper limit of 1000 ng.[ml.sup.-1]. Of note, these studies have failed to compare high dose administration of short acting [[beta].sub.2]-agonist with an intermediate dose (800pg) and placebo. They have also focussed on multiple dosing regimens such as 4 x 400 [micro]g of salbutamol as opposed to a single high dose (Elers et al., 2011). Whilst athletes are usually prescribed 200-400 [micro]g of inhaled salbutamol our experience suggests that athletes are often prescribed inhaled salbutamol pro re nata (i.e. on an as needed basis) that could be interpreted as a clearance to inhale unlimited amounts of salbutamol to combat respiratory symptoms. Indeed, recently a Rugby League player escaped a doping violation after he inhaled over 1600 [micro]g over the course of a match and then tested positive in the post-match anti-doping test. The players defence was based on the prescription of inhaled salbutamol was on an 'as needed basis' with no guidance on an upper limit to its use. Accordingly, in practice 16 inhalations in a short period of time prior to and during competition may occur in poorly controlled, less informed or unscrupulous athletes. Yet these athletes are working within the recommended limit stated on the 2014 Prohibited List. Furthermore, the impact of exercising in a hot environment, resulting in significant dehydration, may have a profound effect on urine concentrations.
To date, no studies have examined the impact of a hot environment on combined Salbutamol administration (up to 1600 [micro]g) and endurance running performance, or on the resultant salbutamol elimination in urine. Accordingly, the purpose of this study was to contribute to the understanding of the potential ergogenic effect of inhaled short acting [[beta].sub.2]-agonists at doses up to and including the maximal dose as stipulated on the WADA 2014 Prohibited List (WADA, 2014) on endurance exercise. In addition, we examined the salbutamol elimination in urine following exercise in temperate (18[degrees]C) and hot (30[degrees]C) environments.
Prior to the commencing the study ethical approval was obtained from Liverpool John Moores University Local Ethics Committee (ethics no: 09E18GW). Seven male runners (mean [+ or -] SD; age 22.4 [+ or -] 4.3 years; height 1.80 [+ or -] 0.07 m; body mass 76.6 [+ or -] 8.6 kg) volunteered and provided written and verbal informed consent. All participants were free from asthma, EIB and AHR confirmed by no previous history of disease and presenting with a negative Eucapnic Voluntary Hyperpnoea (EVH) challenge (Anderson et al., 2001). All participants were free from chest infection for at least 4 weeks prior to assessment; they were not taking any medication and there were no other health or medical contradictions to them taking part in the study as confirm by information provided on a physical activity readiness questionnaire. All participants were actively engaged in endurance running training (45 minutes continuous running) at least 3 time per week. Participants were required to complete six 5 km timetrials; 3 in a temperate environment (18[degrees]C, 40% Relative Humidity (RH)) and 3 in a hot (30[degrees]C, 40% RH) environment. Fifteen minutes prior the initiation of each 5 km time-trial participants inhaled one of the following treatments, via a pocket chamber, in a randomised, double blind design:
Temperate (18[degrees]C, 40% RH):
Treatment 1: 16 inhalations of placebo (PLA)
Treatment 2: 8 inhalations of 100 [micro]g salbutamol, 8 inhalation of placebo (SAL800)
Treatment 3: 16 inhalations of 100 [micro]g salbutamol (SAL1600)
Hot (30[degrees]C, 40% RH)
Treatment 4: 16 inhalations of placebo (PLA)
Treatment 5: 8 inhalations of 100 [micro]g salbutamol, 8 inhalation of placebo (SAL800)
Treatment 6: 16 inhalations of 100 [micro]g salbutamol (SAL1600)
5 km time trial
Participants were familiarised to running on a nonmotorised treadmill (Woodway Curve, Woodway, USA) prior to initiating the 5 km time-trials. Familiarisation runs took place over a distance of 5 km on at least two occasions. Participants progressed to the recorded 5 km time-trials once they...