Athletes explain the differences in Olympic success

Athletes are more susceptible to
exercise-induced bronchoconstriction (EIB) than the general population 1.
Roughly 8% of all competing Olympic athletes suffer from EIB, making it the
most common medical condition among elite athletes.  Indeed, at the 2004 and 2008 Olympic
games, an average of 17% of cyclists and 25% of triathletes were approved by
the International Olympic Committee to treat their asthma with inhaled
adrenergic B2-agonists (IBAs) 2. Exercise acts as a
trigger of EIB, due to the hyperpnoea associated with exercise, causing the
narrowing of the airways. Therefore, endurance athletes are more at-risk due to
the provocative nature of repeated hyperpnoea in unfriendly, irritant filled
environments.

There are many pharmaceutical and
non-pharmaceutical treatment strategies that exist for EIB. Short-acting B2-agonists
and long-acting B2-agonists are used as preventive or acute
treatments for EIB 3. Inhaled salbutamol, a short-acting B2-agonist,
is the most common therapy used among elite athletes. However, elite athletes
must be aware of inhaled salbutamol’s existence on the World-Anti-Doping Agency
(WADA) prohibited list. In fact, more changes have been made to the status of
inhaled salbutamol on the WADA prohibited list than to any other substance in
the last 50 years 3.

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IBAs, such as salbutamol, act on
adrenergic B2-receptors which are distributed in the lungs, heart
and skeletal muscles 2. IBAs relax the smooth muscles surrounding the
airways, causing bronchodilation, increased heart rate and increased blood flow
in the coronary and skeletal arteries. All these aid on relieving asthma
symptoms, such as coughing, wheezing and chest tightness. Therefore, these
agents act as powerful bronchodilators by decreasing obstructions in the
airways 3; however, they also have the potential to affect physiological
factors that can limit athletic performance. Due to this, all IBAs are on the
WADA prohibited list, except inhaled salbutamol (Maximum: 1600 µg/day, without
exceeding 800 µg in 12 hours), formoterol and salmeterol 3.

Interestingly, asthmatic athletes tend
to be more successful at major sporting events compared to non-asthmatic
athletes 4,5. In the 2008 Beijing Olympic games, only 17%
of the cyclists were asthmatic, but these athletes won 29% of the individual
medals available 2. Several studies have investigated the potential
performance-enhancing effects of IBAs in asthmatic and non-asthmatic athletes,
but a mechanism to explain the differences in Olympic success between athletes
with and without asthma remains unclear. 2

In non-asthmatic athletes, studies have
found that IBAs have no effect on VO2max , anaerobic threshold,
strength performance, blood lactate, peak power and rate of perceived exertion
(RPE) even when supra-therapeutic doses of salbutamol were inhaled 6,7.
However, the odd study has seen an improvement in endurance cycling performance
when taking supra-therapeutic doses of salbutamol 8, indicating
that this route of
administration does not exclude the possibility of an ergogenic effect of IBAs 8.

Therefore,
many studies have investigated the effect of IBAs on non-asthmatic,
well-trained individuals, but it’s likely that the effects are more pronounced
in participants who suffer from asthma given their impaired lung function 2.
Hence, in 2013, a study from Koch et al 2 investigated the effect of
inhaled salbutamol on lung function and time-trial performance in well-trained
athletes with and without EIB 2.

 

 

 

 

 

 

 

What were the key
findings?

 

The study screened seventy-five
experienced male cyclists and triathletes between 19 and 40 years of age. The
participants performed two simulated 10 km time-trials on a cycle ergometer 60
minutes after the inhalation of either 400 µg of salbutamol or a placebo 2.
The performance outcomes measured included, mean power output relative to body
weight, heart rate, oxygen consumption, tidal volume, minute ventilation,
respiratory rate, dyspnoea and RPE.

Of the 75 athletes screened, only 49
athletes managed to complete the study. Of these 49 athletes, 14 were asthmatic
and 35 were not. The results showed that thirty minutes after salbutamol-use,
the mean forced expiratory volume (FEV1) increased by 4.7% compared
to 2.9% after the inhalation of the placebo. The improvement in lung function
due to salbutamol was significantly greater in the asthmatic athletes (7.0%)
compared to non-asthmatic athletes (2.7%).

However, when focusing on the effect
that salbutamol has on time-trial performance, mean power output after salbutamol-use
was not significantly different from the mean power output produced in the placebo
group. Indeed, the inhalation of salbutamol caused 18 athletes to increase mean
power output by more than 1%, however 17 athletes had a decrease in mean power
output by more than 1%. Furthermore, no correlation was found between fitness
level, assessed VO2max on the screening day and the difference
between mean power output between the two time-trials.

Salbutamol didn’t seem to affect fatigue
in either of the two time-trials, as neither EVH+ or EVH- perceived a
difference in RPE. Likewise, neither EVH+ or EVH- perceived a difference in
dyspnoea during the two time-trials. Therefore, salbutamol did not affect
time-trial performance in asthmatic athletes or non-asthmatic athletes despite
seeing a significant improvement in FEV1. This study therefore, supports
previous literature that demonstrated significant improvement in lung function
after the inhalation of IBAs in non-asthmatic athletes without any effects on
athletic performance 2.

As this study was the first of its kind,
the findings on asthmatic athletes are novel. Athletes with asthma had a
significantly greater bronchodilatory response to inhaled salbutamol, however,
this greater response did not affect power output, exercise ventilation, RPE
and dyspnoea during the time-trial.

 

How could the study
have been improved?

 

There is limited data to
suggest whether exercise performance is affected in athletes with no history of
EIB. Performance can improve considerably when focusing on time-trials to
exhaustion when asthmatic patients receive inhaled corticosteroids, which is
largely due to an improvement in lung function and protection against
bronchoconstriction 9. Therefore, it’s assumed that athletes with a
positive hyperpnoea challenge will experience an improved endurance performance
if they inhale salbutamol prior to exercise. However, this study reports that
the inhalation of 400 µg salbutamol prior to a 10-km time-trial performance did
not influence cycling performance in athletes with an EVH positive challenge 2.
A possible limitation is that the 10-km time-trial was completed in laboratory
conditions, which has been shown to be an environment that is not provocative
for EIB and perhaps in a more provocative environment this study may have
reported a performance detriment in EVH positively challenged athletes 1.
Therefore, the study may have been improved by using an environmental chamber
to decrease the humidity, due to dry air being more provocative to EIB 20.
This would allow for a more provocative environment as the dry air would
increase the burden on the lower airways in conditioning the inspired air,
possibly increasing the benefit of inhaled salbutamol.

The effects of IBAs on
athletic performance have been investigated in male athletes in multiple
studies, however, despite sex-based pulmonary anatomical differences causing
differing respiratory responses to exercise 3, highly
trained female participants have been overlooked. Women on average have smaller
lung sizes, lung volumes, maximal expiratory flow rates and decreased diffusion
surfaces 3.  Therefore, due to
these anatomical differences, female athletes may benefit more from the use of
IBAs compared to male athletes; thus, IBAs could lead to greater relative
improvements in FEV1 and athletic performance. Consequently, the
findings from the current study should not be generalised to female athletes. Future
studies should focus on the effects of IBAs on female athletes to see if the
findings of this current study can be applied to women.

Whilst there were no differences in the
performance parameters between the two time-trials, the study could have been
improved by adding a familiarisation time-trial. Adding a familiarisation time-trial
would allow for the learning effect, typically sufficient pacing information is
gained from the first time-trial to enable participants to adopt an appropriate
pacing strategy in the subsequent trials 10,11. Also, feedback such
as distances, cadences and gears were visible to the athlete during the 10-km
time-trial. It has been seen that different pacing strategies can emerge
depending on the sources of information available to the athletes 12.
Therefore, the negative results may be due to athletes concentrating on a
consistent pacing strategy rather than seeing no effect of inhaled
salbutamol. 

The methodology could have been improved
by adding a power calculation. Power analysis can be used to calculate the
minimum sample size required so that a given effect size can be detected. The
power calculation can also calculate what percentage is required to see a
significant improvement in performance. Furthermore, the study does not comment
on whether a warm-up was present. Including a warm-up comes with benefits and
limitations, a warm-up will allow the athletes to cycle at their maximal
time-trial performance but also may induce a refractory period during the
time-trial and bronchoconstriction may not be evident for this reason.

Another limitation is the relatively low
number of EVH+ cyclists compares to EVH- cyclists. However, the ergogenic
effect of inhaled salbutamol on 10-km time-trial performance was independent of
EVH status. Indeed, both EVH- and EVH+ athletes presented similar performance
increases and decreases. Therefore, while adding more EVH+ cyclists would
increase the power and reliability of the study, the results would most likely
have remained the same

Therefore, whilst the results of Koch et
al 2 are novel, the study does come with some limitations. This
study would have benefited from experimenting with an environmental chamber to
allow for a more provocative environment for EIB and by using female athletes
to focus on whether inhaled salbutamol would have a greater effect due to the
differences in pulmonary anatomy. Future studies should take these limitations
into consideration.

 

Does salbutamol make a difference at
all?

 

There is no compelling evidence that
salbutamol and other IBAs can increase performance in healthy athletes 1,2,3,6,7,13,14,18,19.
However, in spite of this, salbutamol required a “declaration of use in
accordance with the International Standard for Therapeutic Use Exemptions”
under the 2010 WADA Prohibited List, which has since been relaxed in the 2011
edition to a maximum use of 1600 µg over 24 hours when taking by inhalation.
Whilst Koch et al 2 focused on a therapeutic dose of 400 µg, recent
studies have since been concentrating on a supra-therapeutic dose up to the
maximum threshold of 1600 µg.

Even though there doesn’t seem to be an
ergogenic effect for salbutamol at low or moderate doses 1,2, there
is potential for the maximally allowed daily dose of 1600 µg of inhaled
salbutamol to be ergogenic in elite athletes 3. Dickinson et al 13
investigated the impact of the acute inhalation of 1600 µg on endurance running
performance and reported that despite an increase in VE of 10 L/min at every
kilometre over a 5-km cycling time-trial, inhalation did not lead to an
improvement in running performance. Furthermore, only a limited number of
studies have examined the salbutamol elimination in urine of inhaled doses as
high as 1600 µg and have reported urine concentrations close to the WADA upper
limit of 1000 ng.ml-1 13.
This
study demonstrated the
possibility of a urinary salbutamol concentration above the threshold of 1000 ng.ml-1.
However,
whilst the WADA prohibited list threshold is 1000 ng.ml-1,
salbutamol
should only be reported as an adverse analytical finding (AAF) when detected at
a concentration greater than 1200 ng.ml-1 14.
Therefore, on this basis, this study would not warrant any sample to be
reported as an AAF.

In a second
study by Dickinson et al 14 investigating the ergogenic effect of long-term use of high
dosage salbutamol, found that inhaling 1600 ?g daily over 6 weeks does not
result in significant improvements in peak oxygen consumption, 3-km running
performance or a one-repetition maximum for bench and leg press 14.
To what extent these results from Dickinson et al 13-14 can be
extrapolated to elite athletes is debatable due to a small sample size (n = 7) 13,
low cardiovascular fitness levels 13,14 and a heterogeneous athletic
background of the participants 14. In contrast to these findings,
are the results from a study combining maximal doses of multiple IBAs in
swimmers with and without airway hyperresponsiveness 15.
Swim ergometer sprint performance and MVC was significantly improved
after the inhalation of 1600 µg
salbutamol, 200 µg salmeterol and 36 µg formoterol, regardless of airway hyperresponsiveness. In addition, a
study investigating the inhalation of an acute salbutamol dose following a
quadriceps fatigue test showed that an intermediate
dose (800 ?g) of salbutamol induced a significant improvement in quadricep
endurance despite similar amounts of fatigue and had a positive effect
regarding the capacity to maintain intermittent isometric contractions 16.
Other inhaled B2-agonists, such as terbutaline, have also shown a
significant increase in maximal voluntary contraction, which has led to an
enhancement in muscle strength and sprint performance 17.

Therefore, while there
does not seem to be an ergogenic effect with inhaled doses at low or moderate
doses, there is potential for a high, supra-therapeutic dose to have an
ergogenic effect on athletic performance. Furthermore,
it’s unclear if there is a relationship between the relative IBA dose and
ergogenic potential 3. The maximum allowed daily use of IBAs are not
normalised by body mass in the WADA guidelines, therefore a lighter athlete may
benefit more from a greater IBA dose per kg than a heavier athlete, however, a lighter athlete may also be at a
greater risk of breaching the maximum threshold when administering high doses
compared to a heavier athlete

While a few studies have
showed a possible ergogenic effect when inhaling the maximum amount of
salbutamol, other studies, show no ergogenic effect. Koch et al 18 continued
from their previous study, but focusing on the impact that a supra-therapeutic
dose had on 10-km time-trial performance. Trained male cyclists with and
without EIB were analysed and found that the
inhalation of 1600 ?g salbutamol improved FEV1 regardless of EVH status but did
not improve 10-km time trial performance regardless of relative dose per
kilogram of body weight or EVH status 17.  Later that same year, Koch et al 19
focused on how inhaled salbutamol affected female athletes with and without
EIB, to allow the present study and their two previous to be applied to women.
Much like their study in 2013, participants performed a simulated 10-km cycling
time-trial after the inhalation of either 400 ?g or placebo. Despite a
significant increase in lung function after the inhalation of salbutamol in
female athletes, mean power output maintained over the duration of the
time-trial was significantly reduced. This is the first study to report an
increase in lung function after IBA use with a decrease in athletic performance
19. This reduction in mean power output represents a potential
ergolytic effect of salbutamol on female athletes and could be explained by an
overstimulation of the adrenergic B2-agonist system impairing
athletic performance 3. Therefore, this suggests that despite sex
differences in pulmonary anatomy, the inhalation of 400 ?g salbutamol does not
increase cycling time-trial performance in men or women.

However, much like their previous two
studies, this study was also performed in laboratory conditions, and therefore
still has similar limitations. Due to this, Molphy et al 1
investigated the effect that 400 ?g of inhaled
salbutamol on 3 km running time-trial performance in an EIB provocative
environment 1, in line with the notion that dry air is more
provocative for EIB 20. Despite significantly increased heart rate
and FEV1, the administration of 400 ?g of inhaled salbutamol did not
improve 3-km time-trial performance in athletes who do or do not suffer from EIB.
While in general higher doses of inhaled salbutamol have shown no improvements
in athletic performance, a reason for not seeing an ergogenic effect in this
study could be due to the comparatively small doses used. There also remains
the possibility that performance improvements may not have been seen because
this study solely focused on endurance performance. Recent studies have
indicated that inhaled B2-agonists may enhance strength and power
performance rather than endurance performance 15-17.

 

Recommendations and
conclusions

 

Oral B2-agonists
administration in humans has substantial effects on muscle function 21 and
exercise performance 22. Doses of inhaled B2-agonists of
salbutamol, however, are more than 20 times smaller (100 ?g/puff) than oral (2
mg per pill up to 12-20 mg/day) 16 doses. In general, most studies
having tested the effect of inhalation of therapeutic (400 ?g), intermediate
(800 ?g) or even supra-therapeutic (1600 ?g) doses of salbutamol on exercise
performance revealed no ergogenic effect 16.

These findings suggest that the current
WADA guidelines, which allows athletes to inhale up to 1600 ?g is sufficient to avoid pharmaceutical enhancement
during athletic competition. However, a dose of 1600 ?g suggests poor
management of asthma and increases the risk of an athlete violating the current
maximum threshold 13.

In conclusion, previous studies, such as Koch et al 2, have
showed that small therapeutic doses of inhaled salbutamol have no effect on
athletic performance, however, the odd study has found that a possible
ergogenic effect of inhaled salbutamol at the maximum dose. Therefore, while
the current WADA guidelines are sufficient, inhaled salbutamol at the maximum
dose should continue to be monitored, especially during strength and power
performances.