Therapeutic use exemptions (TUEs) at the Olympic Games 1992-2012.

The need for therapeutic use exemptions (TUEs) or the permitted use of Prohibited Substances and Prohibited Methods by athletes to treat significant medical conditions arose when several classes of drugs used commonly in medicine were prohibited in sport by the International Olympic Committee (IOC) during the 1980s. However, although the IOC Medical Commission (IOC-MC) gave qualified support for the concept to formally start at the 1992 Barcelona Olympics, the Commission's fears that athletes might abuse the mechanism resulted in minimal publicity and its non-inclusion in the Medical Code of the Olympic Movement for 8 years. TUEs would not be widely publicised until the advent of the World Anti-Doping Agency which not only approved the principles of TUEs as developed by the IOC's Medications Advisory Committee (MAC) in 1991, but also introduced the name of TUE. Several changes to the Prohibited List have resulted in TUEs being necessary for substances that were permitted 20 years ago as disclosed in a review of TUEs approved at the 11 Olympic Games that the IOC's MAC, later the TUE Committee (TUEC), has operated. The IOC and its TUEC played a pivotal role in developing the concept of TUE which is now globally accepted.

An overview of asthma and airway hyper-responsiveness in Olympic athletes.

Data from the past five Olympic Games obtained from athletes seeking to inhale ß2 adrenoceptor agonists (IBA) have identified those athletes with documented asthma and airway hyper-responsiveness (AHR). With a prevalence of about 8%, asthma/AHR is the commonest chronic medical condition experienced by Olympic athletes. In Summer and Winter athletes, there is a marked preponderance of asthma/AHR in endurance-trained athletes. The relatively late onset of asthma/AHR in many older athletes is suggestive that years of endurance training may be a contributory cause. Inspiring polluted or cold air is considered a significant aetiological factor in some but not all sports. During the last five Olympic Games, there has been improved management of athletes with asthma/AHR with a much higher proportion of athletes combining inhaled corticosteroids (ICS) with IBA and few using long-acting IBA as monotherapy. Athletes with asthma/AHR have consistently outperformed their peers, which research suggests is not due to their treatment enhancing sports performance. Research is necessary to determine how many athletes will continue to experience asthma/AHR in the years after they cease intensive endurance training.

Respiratory health of elite athletes - preventing airway injury: a critical review.

Elite athletes, particularly those engaged in endurance sports and those exposed chronically to airborne pollutants/irritants or allergens, are at increased risk for upper and lower airway dysfunction. Airway epithelial injury may be caused by dehydration and physical stress applied to the airways during severe exercise hyperpnoea and/or by inhalation of noxious agents. This is thought to initiate an inflammatory cascade/repair process that, ultimately, could lead to airway hyperresponsiveness (AHR) and asthma in susceptible athletes. The authors review the evidence relating to prevention or reduction of the risk of AHR/asthma development. Appropriate measures should be implemented when athletes exercise strenuously in an attempt to attenuate the dehydration stress and reduce the exposure to noxious airborne agents. Environmental interventions are the most important. Non-pharmacological strategies can assist, but currently, pharmacological measures have not been demonstrated to be effective. Whether early prevention of airway injury in elite athletes can prevent or reduce progression to AHR/asthma remains to be established.

The asthmatic athlete: inhaled Beta-2 agonists, sport performance, and doping.

The asthmatic athlete has a long history in competitive sport in terms of success in performance and issues related to doping. Well documented are detailed objective tests used to evaluate the athlete with symptoms of asthma or airway hyperresponsiveness and the medical management. Initiated at the 2002 Salt Lake City Games, the International Olympic Committee's Independent Asthma Panel required testing to justify the use of inhaled beta-2 agonists (IBAs) in Olympic athletes and has provided valuable guidelines to the practicing physician. This program was educational and documented the variability in prevalence of asthma and/or airway hyperresponsiveness and IBA use between different sports and different countries. It provided a standard of care for the athlete with respiratory symptoms and led to the discovery that asthmatic Olympic athletes outperformed their peers at both Summer and Winter Olympic Games from 2002 to 2010. Changes to the World Anti-Doping Agency's Prohibited List in 2010 permitted the use of 2 IBA produced by the same pharmaceutical company. All others remain prohibited. However, there is no pharmacological difference between the permitted and prohibited IBAs. As a result of these changes, asthmatic athletes are being managed differently based on a World Anti-Doping Agency directive that has no foundation in pharmacological science or in clinical practice.

Medication use by athletes at the Athens 2004 Summer Olympic Games.

OBJECTIVE: To gather data and examine the use by elite Olympic athletes of food supplements and pharmaceutical preparations in total and per sport, country, and gender. DESIGN: Survey study. SETTING: Athens 2004 Olympic Games (OG). PARTICIPANTS: Data from 2 sources were collected: athletes' declaration of medications/supplements intake recorded on the Doping Control Official Record during sample collection for doping control, and athletes' application forms for granting of a therapeutic use exemption (TUE) and through the abbreviated TUE process (aTUE). MAIN OUTCOME MEASURES: Classification of declared food supplements according to the active ingredient and medications according to therapeutic actions and active compounds. RESULTS: 24.3% of the athletes tested for doping control declared no use of medications or food supplements. Food supplements (45.3%) continue to be popular, with vitamins (43.2%) and proteins/aminoacids (13.9%) in power sports being most widely used. Nonsteroidal antiinflammatory agents and analgesics were also commonly used by athletes (11.1% and 3.7%, respectively). The use of the hemoderivative actovegin and several nonprohibited anabolic preparations are discussed. The prevalence of medication use for asthma and the dangers of drug interactions are also presented.Laboratory analysis data reveal that of the aTUEs received for inhaled glucocorticosteroids, only budesonide was detectable in significant percentage (10.0%). Only 6.5% of the 445 athletes approved to inhale beta2-agonists led to an adverse analytical finding. CONCLUSIONS: This review demonstrates that overuse of food supplements was slightly reduced compared to previous OGs and a more rational approach to the use of medication is being adopted.

Asthma and the elite athlete: summary of the International Olympic Committee's consensus conference, Lausanne, Switzerland, January 22-24, 2008.

Respiratory symptoms cannot be relied on to make a diagnosis of asthma and/or airways hyperresponsiveness (AHR) in elite athletes. For this reason, the diagnosis should be confirmed with bronchial provocation tests. Asthma management in elite athletes should follow established treatment guidelines (eg, Global Initiative for Asthma) and should include education, an individually tailored treatment plan, minimization of aggravating environmental factors, and appropriate drug therapy that must meet the requirements of the World Anti-Doping Agency. Asthma control can usually be achieved with inhaled corticosteroids and inhaled beta(2)-agonists to minimize exercise-induced bronchoconstriction and to treat intermittent symptoms. The rapid development of tachyphylaxis to beta(2)-agonists after regular daily use poses a dilemma for athletes. Long-term intense endurance training, particularly in unfavorable environmental conditions, appears to be associated with an increased risk of developing asthma and AHR in elite athletes. Globally, the prevalence of asthma, exercise-induced bronchoconstriction, and AHR in Olympic athletes reflects the known prevalence of asthma symptoms in each country. The policy of requiring Olympic athletes to demonstrate the presence of asthma, exercise-induced bronchoconstriction, or AHR to be approved to inhale beta(2)-agonists will continue.

Androgenic-anabolic steroids and the Olympic Games.

Androgenic-anabolic steroids (AAS) have been misused by athletes at the Olympic Games, both before and after they were prohibited in sport in 1974. Systematic doping with AAS occurred in the German Democratic Republic (GDR) from 1965 to 1989 which assisted that country to win many medals at Olympic Games, especially in female events. Currently, AAS are the most frequent category of prohibited substances detected in the urine of athletes both globally and at the last two Summer Olympic Games. Scientific confirmation that AAS are effective in enhancing sports performance was difficult because ethical approval was difficult for research involving male subjects taking massive doses of androgens as some athletes and bodybuilders did. Methods to detect AAS have evolved gradually over the past three decades and currently, despite an impressive array of sophisticated analytical equipment and methods, anti-doping authorities and analytical scientists continue to face challenges as have occurred from the use by athletes of designer AAS during the past few years. The future development and use of selective androgen receptor modulators (SARMs) can be anticipated to pose problems in the years ahead. Endocrinologists should be aware that on occasions, replacement testosterone (T) therapy may be authorized in sport as a therapeutic use exemption (TUE) and these circumstances are discussed.

Blood doping at the Olympic Games.

INTRODUCTION: The objective of this paper was to review our knowledge of athletes who have, are believed to have or have attempted to engage in blood doping to enhance their performance at an Olympic Games. EVIDENCE ACQUISITION: The paper focused on the Games from Munich 1972 to London 2012 and the author had a medical role at each of the Olympics that is discussed. EVIDENCE SYNTHESIS: The study revealed that Olympic athletes have benefitted from manipulating their blood by re-infusion of autologous or infusion of homologous blood and by administering erythropoiesis stimulating agents, notably the three generations of erythropoietins. Fifty seven athletes have been sanctioned with 12 athletes forfeiting 17 Olympic medals including 12 gold medals because of blood doping. Until 1986, the infusion of blood was not prohibited in sport but considered unethical. Erythropoietin was prohibited by the International Olympic Committee's Medical Commission in 1990. CONCLUSIONS: There has been a change as to how Olympic athletes have enhanced performance by blood doping, commencing with blood infusion and later administering erythropoiesis stimulating agents and significant advances have occurred in detecting such misuse. Currently, the hematological component of World Anti-Doping Agency's athlete biological passport is an important but not infallible mechanism to identify athletes who cheat by blood doping.

beta2-Agonists at the Olympic Games.

The different approaches that the International Olympic Committee (IOC) had adopted to beta2-agonists and the implications for athletes are reviewed by a former Olympic team physician who later became a member of the Medical Commission of the IOC (IOC-MC). Steadily increasing knowledge of the effects of inhaled beta2-agonists on health, is concerned with the fact that oral beta2-agonists may be anabolic, and rapid increased use of inhaled beta2-agonists by elite athletes has contributed to the changes to the IOC rules. Since 2001, the necessity for athletes to meet IOC criteria (i.e., that they have asthma and/or exercise-induced asthma [EIA]) has resulted in improved management of athletes. The prevalence of beta2-agonist use by athletes mirrors the known prevalence of asthma symptoms in each country, although athletes in endurance events have the highest prevalence. The age-of-onset of asthma/EIA in elite winter athletes may be atypical. Of the 193 athletes at the 2006 Winter Olympics who met th IOC's criteria, only 32.1% had childhood asthma and 48.7% of athletes reported onset at age 20 yr or older. These findings lead to speculation that years of intense endurance training may be a causative factor in bronchial hyperreactivity. The distinction between oral (prohibited in sports) and inhaled salbutamol is possible, but athletes must be warned that excessive use of inhaled salbutamol can lead to urinary concentrations similar to those observed after oral administration. This article provides justification that athletes should provide evidence of asthma or EIA before being permitted to use inhaled beta2-agonists.

Exercise-induced bronchoconstriction: celebrating 50 years.

This article examines in detail the history of more than half a century of investigations into elucidating the causation of exercise-induced bronchoconstriction. Despite earnest attempts by many researchers from many countries, answers to some pivotal questions await the next generation of investigators into exercise-induced bronchoconstriction.

Australian association for exercise and sports science position statement on exercise and asthma.

Asthma, a chronic inflammatory disorder of the airways is associated with variable obstruction to the airways and is provoked by many triggers including exercise. The management of asthma is primarily pharmacological, but exercise, despite causing bronchoconstriction in almost all asthmatics, is an important adjunct to treatment. With adequate control of the hyperresponsive airways obtained with inhaled corticosteroids (ICS) and inhaled beta 2 agonists (IBA), used as both a pre-exercise preventive agent and a reliever if necessary, all asthmatics should benefit from an exercise program. Some have realised this benefit with such success as to become Olympic and world champions in many sports. Exercise programs should be individually tailored, follow established guidelines and result in similar benefits to those obtained by non-asthmatics. However asthmatics must try to avoid or minimise triggers whenever possible. A specific benefit of a physical training program is that it allows asthmatics to exercise with less bronchoconstriction at the same exercise stress, although it does not abolish or reduce airway hyperresponsiveness (AHR).

Pharmacotherapy for exercise-induced asthma: allowing normal levels of activity and sport.

Exercise-induced bronchoconstriction (EIB) is experienced by the majority of an estimated 300 million individuals who have asthma, a condition that affects all ages and is increasing globally. Respiratory water loss with dehydration of the airways causing mediator release and airway narrowing is considered the cause of EIB, the severity of which will be increased if the inhaled air is cold or polluted. Adequate control of asthma is essential to minimize or prevent EIB and permit normal levels of physical activity and sport. This is important because exercise is a necessary component of daily living, assists in obtaining and maintaining a healthy body and has been demonstrated to benefit asthmatics. Inhaled glucocorticosteroids and inhaled ß(2)-adrenoceptor agonists (IßA) are the pharmacological agents of choice to manage asthma and minimize EIB, assisted when necessary, by other drugs including leukotriene receptor antagonists and chromones. Tolerance from daily use of IßA is of concern and more flexible drug therapy needs to be considered. Optimal use of inhalers to deliver drugs effectively requires closer attention. Pharmacogenetics may hold the key to future drug therapy.

The asthmatic athlete, inhaled beta agonists, and performance.

INTRODUCTION: The large increase in the number of athletes who apply to use inhaled beta agonists (IBAs) at the Olympic Games is a concern to the medical community. This review will examine the use of IBAs in the asthmatic athlete, the variability that exists between countries and sport, and outline a plan to justify the use of these medications. DATA SOURCES: Much of this article is a result of an International Olympic Committee (IOC) Medical Commission-sponsored meeting that took place in May 2001. Records of the use of IBAs at previous Olympics were reviewed. MEDLINE Searches (PubMed interface) were performed using key words to locate published work relating to asthma, elite athletes, performance, treatment, and ergogenic aids. MAIN RESULTS: Since 1984 there have been significant increases in the use of IBAs at the Olympic Games as well as marked geographical differences in the percentage of athletes requesting the use of IBAs. There are large differences in the incidence of IBA use between sports with a trend towards increased use in endurance sports. There are no ergogenic effects of any IOC-approved IBA given in a therapeutic dose. CONCLUSIONS: In many cases, the prescription of IBAs to this population has been made on empirical grounds. Beginning with the 2002 Winter Games, athletes will be required to submit to the IOC Medical Commission clinical and laboratory evidence that justifies the use of this medication. The eucapnic voluntary hyperpnea test will be used to assess individuals who have not satisfied an independent medical panel of the need to use an IBA.