This is the second of two pieces looking at the use of bronchodilating drugs to treat asthma in athletes – and their changing place on WADA’s prohibited list. The first, published last week, examined the potential of Spiriva, a drug usually used in COPD patients, in treating asthma.
Asthma, a constriction of the airways caused by one or several stimuli and also characterized by chronic airway inflammation, is especially common in winter sports such as skiing. And between the cold weather and the cardiovascular effort required by the sport, it can be difficult for asthmatics to manage their symptoms while competing. There are plenty of asthma medications out there – and yet, until two years ago, athletes had to submit at Therapeutic Use Exemption (TUE) to the appropriate anti-doping organization before they took a puff of their inhalers. Β-2 agonists, a common class of drugs that expand the airways, were categorically banned.
Then in 2011, the World Anti-Doping Agency (WADA) removed salbutamol, one of the most common asthma medications, from its Prohibited List except for in quantities of over 1600 micrograms in 24 hours, and in 2012 gave the same treatment to formoterol, this time with a limit of 36 micrograms in 24 hours. Salmeterol, another β-2 agonist, is also not banned. All of these drugs fall into the category of bronchodilators: substances which relax and expand airways.
“There are really no regulations requiring documentation of asthma to use a bronchodilator – that has really sort of fallen by the wayside,” said Kenneth Rundell, a former member of the International Olympic Committee’s asthma group, in an interview last week.
Was the move simply to accommodate asthmatic athletes and cut down on the amount of TUE paperwork that was submitted, or are the three un-prohibited drugs really different than their fellow β-2 agonists which remain on the list? Other types of medications that relax and expand airways, – the entire category of these drugs are called bronchodilators – are not on the Prohibited List at all, despite achieving the same end result as β-2 agonists. So why were β-2 agonists tagged as performance-enhancing substances?
WADA itself didn’t provide much clarification: “A substance is put on the List if it is deemed to be performance enhancing,” WADA’s Senior Manager of Media Relations and Communications, Terence O’Rourke, wrote in a brief e-mail to FasterSkier.
Exercise and the Normal Athlete
To understand how these drugs work and why they might be banned, one must first understand airways. Lungs respond to exercise by dilating to accommodate the added airflow and reduce constriction. And asthmatic lungs do the same thing, at least initially: for instance, a 1999 paper by Kenneth Beck of the Mayo clinic reported that during steady-state exercise, asthmatics experienced dilation of the airways for the first 15-20 minutes of exercise, before the smooth muscle started constricting. In an incremental VO2 max test, airways continuously expanded, reaching their maximum width at the end of the test and then constricting once the bout was over.
“After a couple of minutes of exercise, even the asthmatics, except for the very severe asthmatics, will bronchodilate, just for mechanical reasons,” Rundell, who was formerly the head of the Human Physiology Laboratory at Marymount University, told FasterSkier. He added that bronchodilating drugs will further help this process in asthmatics for whom the response is lower.
The worst effects of exercise on lung function actually come after the workout is over. In a 2010 report on exercise-induced asthma by the U.S. Department of Health and Human Services (available as PDF), the authors write that
“Vigorous physical exercise can be followed by transient clinical signs and symptoms similar to an asthma attack and are due to post-exercise bronchoconstriction (i.e., a narrowing of the airways). Clinical symptoms include coughing, wheezing, shortness of breath, excessive mucus production, chest tightness, chest pain, or an ‘itching or scratching sensation’ in the chest. Though it is more common in people with asthma, it also occurs in people without asthma.”
There’s a distinction between Exercise-Induced Bronchoconstriction (EIB), as described above, and asthma, which is not necessarily exercise-induced.
So in a normal interval session, skiers with and without asthma might experience very similar lung function. Multiple studies show that non-asthmatics also experience and report coughing, wheezing, and shortness of breath. One cause is that the deeper breathing during exercise brings in more dry, cold air than the upper airways can warm and humidify before sending to the more sensitive lower airways, leading to constriction as self-defense.
“Even with interval-type exercise, if you measure lung function during exercise, you can see some mechanical protection during exercise,” Rundell explained. “Then when they have their resting period you can see the airways narrow a bit, and then they will bronchodilate when they start exercising again, but not as much as, say, after the first four-minute bout. So over time, half an hour of that, you’ll see a gradual decline in lung function during the exercise. With steady-state exercise, you’ll see a decline as well.”
So Why The Bans?
In 2005, WADA chief Dick Pound told the Associated Press that athletes were faking asthma to obtain the medications, and that “we’ve caught on to their scam,” while an IOC board member from Hungary said that “We need to stop this pretending to be ill and taking dope in order to enhance the sporting performance.” Both implied that bronchodilating medications would help minimize the natural decrease in lung function of the course of a workout or race.
It’s true that Β-2 agonists like salbutamol have been shown to help with EIB, as well as asthma. But that doesn’t exactly make them performance enhancing, as Pound had suggested. For instance, the worst bronchoconstriction comes after exercise, not during a competition – meaning that prevention of those symptoms wouldn’t lead to a performance benefit.
“The extensive research on therapeutic doses of inhaled β2-agonsits clearly rules out any ergogenic effects,” researchers from Copenhagen wrote all the way back in 2007. “Only few studies have shown ergogenic effects of inhaled salbutamol, but these are limited by enrollment of recreational subjects. It is now a common opinion that inhaled β2-agonists in therapeutic doses has no advantageous effects in healthy athletes.”
So, if bronchodilators aren’t performance-enhancing in regular athletes – and a large number of studies, some cited by FasterSkier in a 2011 article, have come to the same conclusion as the Copenhagen researchers – there had to be another reason that they were on the list. As it turns out, one criteria for prohibiting a medication is that it is detrimental to athletes’ health. This was a concern for WADA – salbutamol has been shown to have tough side effects when used over the long term – as well as the fact that long-term use of β-2 agonists decreases the drugs’ effectiveness over time.
“Inhaled β2 agonists are the most effective drugs for… relieving intermittent symptoms of asthma,” the IOC’s asthma committee wrote in a 2008 report. “However… athletes who use either short- or long-acting β2-agonists on a daily basis should be advised that their effectiveness to prevent EIB will partially diminish. Frequent use of β2 agonists may also increase the bronchoconstrictor response to exercise and allergens. Strategies to avoid these problems could include restricting β2 agonists to infrequent use…”
According to Rundell, who was part of that committee, the consensus by the IOC’s scientists and doctors seems to have had diverged from the rhetoric by its anti-doping leaders.
“The reason was not because they provided any type of performance enhancement, but that the athletes thought that they provided performance enhancement,” Rundell told FasterSkier of the drugs’ ban. “Clenbuterol has been shown to do that, but that’s not an inhaler. At any rate, there was rampant use of the bronchodilators, so it was more out of concern for the athletes’ health that they had to provide documentation showing that they had hyper-reactive airways.”
Publicly, however, WADA continues to assert that the bans are because the drugs are performance-enhancing, and that the organization will continue to investigate their effects.
“The issue of β-2 agonists will continue to be a focus of WADA’s research activity in order to ensure that the administration of large doses or by systemic routes of these substances is prevented and prohibited,” WADA wrote on their website when they released the 2012 Prohibited List.