Athletes are more susceptible to exercise induced bronchoconstriction (EIB) than the general population, with those affected being permitted to use up to 1600 [micro]g (max of 800 [micro]g in a 12 hour period) of inhaled salbutamol per day on an as needed basis for the relief of symptoms (Dickinson et al., 2006; 2011; Molphy et al., 2014; WAD A, 2017). Inhaled salbutamol is the most common therapy used by athletes to provide acute prevention and reversibility for EIB (Fitch, 2006).
The eucapnic voluntary hyperpnoea (EVH) challenge is recognized as a sensitive and specific indirect airway challenge to assist in the diagnosis of EIB in athletic populations (Parsons et al., 2013). When EVH challenges are used as part of a screening program for EIB in athletes, some may present with an EVH positive challenge (EVH+ve) without having any previous history of EIB (Dickinson et al., 2006; Molphy et al., 2014). Our groups previous work has demonstrated that some athletes with a positive EVH challenge do not present with EIB following a field based exercise challenge (Dickinson et al., 2006). Recently Price et al., (2015) demonstrated that mild EVH challenge responses are not repeatable, demonstrating the transient nature of mild EIB. Moreover, the environment in which sporting performance takes place can be a contributing factor for EIB, perhaps individuals with mild EVH+ve challenges would exhibit with EIB in a more bronchoprovocative environment, such as that of low humidity (Sue-Chu et al., 2012).
Limited data exist to suggest whether exercise performance is affected in athletes with no history of EIB, who present with a mild EVH+ve challenge (10%-25% fall in [FEV.sub.1]; Price et al., 2014). Performance in time trials to exhaustion can improve considerably (50%) when asthmatic patients receive conventional inhaled corticosteroid therapy, largely due to an improvement in lung function and protection against bronchoconstriction (Haverkamp et al., 2007). It is therefore reasonable to assume that athletes with a mild EVH+ve challenge will experience improved endurance performance if they inhale salbutamol prior to exercise. However, Koch et al., (2015a; 2015b) reported inhalation of 400 [micro]g salbutamol prior to 10 km cycling did not influence performance in EVH+ve cyclists. The 10 km cycling trial was completed in laboratory conditions, which has been shown to be an environment that is not particularly provocative for EIB (Dickinson et al., 2006) and perhaps in a more bronchoprovocative environment the studies by Koch et al., (2015a; 2015b) would have seen a performance decrement in EVH+ve cyclists. Accordingly, the purpose of this study was to investigate the effect of 400 [micro]g of inhaled salbutamol on 3 km running time-trial performance in an EIB provocative environment (humidity 20-25% the minimum humidity attainable in the environmental chamber) in EVH+ve and EVH negative (EVH-ve) individuals, in line with the notion outlined by Sue-Chu et al., (2012) that dry air is more provocative for EIB.
Following ethical approval from Liverpool John Moores University research ethics committee (Ethics No. P13SPS041), 14 male participants (age: 22.4 [+ or -] 1.6 years; weight: 76.4 [+ or -] 8.7 kg; height: 1.80 [+ or -] 0.07 m) volunteered to participate in the study providing their written informed consent. All participants were in good health, nonsmokers and took part in recreational sport and exercise activities for at least 3 hours per week. No participant had previously been diagnosed with asthma and/or EIB, all participants were free from chest infection for at least two weeks prior to testing. Participants were informed about the nature and the risks of the experimental procedures before their informed consent was obtained.
Participants completed an EVH challenge to identify them as either EVH+ve or EVH-ve. Following two familiarization sessions participants completed 3 km running time trials on three occasions over three consecutive weeks, to allow sufficient wash-out and recovery. Prior to each 3 km time trial participants either inhaled 400 [micro]g salbutamol, a placebo (inactive inhalant) or nothing (control); the 3km time-trials were randomized using a Latin square design.
Eucapnic Voluntary Hyperpnoea (EVH) Challenge
All participants undertook maximal flow-volume maneuvers using a spirometer (Microlab ML3500, Cardinal Health, Basingstoke, UK). Flow-volume measures recorded from each maximal flow-volume loop were; Forced Expiratory Volume in one second ([FEV.sub.1]), Forced Vital Capacity (FVC), [FEV.sub.1] :FVC ratio ([FEV.sub.1]/FVC%), Peak Expiratory Flow (PEF) and forced expiratory flow between 25% and 75% of FVC (FEF25-75). Three maximal flow-volume loops were measured to gain baseline measures and were accepted in accordance with European Respiratory Society and American Thoracic Society criteria (Miller et al., 2005).
If [FEV.sub.1] was above 70% of the predicted value, participants completed an EVH challenge (Anderson et al., 2001). The EVH challenge required participants to maintain target minute ventilation ([[??].sub.E]) of 85% of their predicted maximal voluntary ventilation rate (MVV) for 6 minutes, calculated by multiplying their resting [FEV.sub.1] by 30. Participants inhaled air from a compressed gas cylinder (19[dergees]C and 2% humidity) containing 21% Oxygen, 5% Carbon Dioxide and 74% Nitrogen, via a two way valve. Expired air passed through a dry gas meter to enable [[??].sub.E] to be calculated. Following the completion of the EVH challenge maximal flow volume loops were measured in duplicate at 3, 5, 7, 10 and 15 minutes with the best [FEV.sub.1] for each time point being recorded. If participants [FEV.sub.1] fell [greater than or equal to] 10% from baseline on two consecutive time points following the EVH challenge they were deemed EVH+ve. Once consecutive falls of 10% or more in [FEV.sub.1] from the resting value were observed, participants inhaled 200 [micro]g salbutamol, with spirometry measured 10 minutes post inhalation to confirm bronchoconstriction was reversible. Participants who did not experience a [greater than or equal to] 10% fall in [FEV.sub.1] were placed in the EVH-ve group.
3 km Running Time-Trial
Following two familiarization sessions, each participant completed a 3 km time-trial, on a Woodway Curve nonmotorized treadmill (Woodway, Wisconsin), on three occasions in a randomized, single blind (salbutamol and placebo trials only), repeated measures design with a minimum of 7...