In the Vuelta a España in September, 2017, a urine sample from the British cyclist Chris Froome returned an adverse analytical finding, a concentration of salbutamol higher than 1000 ng/mL, the highest concentration by the World Anti-Doping Agency (WADA). The case lasted several months, and just 2 days before the 2018 Tour de France, the case was resolved by the world governing body of cycling, the Union Cycliste Internationale (UCI), which considered Froome to be innocent and free to compete in the race. Controversially, similar previous cases (eg, that of Alessandro Petacchi or Diego Ulissi) led to official sanctions by the UCI. The issue is also contentious because Froome's team has not made available the scientific arguments used in his defence.

1 Pluim BM

de Hon O

Staal JB

et al. β2-agonists and physical performance. A systematic review and meta-analysis of randomized controlled trials. 2 Martineau L

Horan MA

Rothwell NJ

Little RA Muscling in on salbutamol. Meta-analytical evidence for an enhancing effect of systemic β2 agonists on maximal aerobic performance is weak, but these compounds might benefit sprint or anaerobic performanceand have some muscle anabolic effects.According to WADA, exceeding the aforementioned cutoff would theoretically rule out therapeutic drug usage against asthma or bronchospasm through inhalations at the permitted doses (ie, ≤800 μg/12 h or 1600 μg/24h, with one single puff delivering a dose of about 100 μg), and suggests systemic administration, which is banned in sports. However, several confounding variables might result in the detection of abnormally high amounts of salbutamol despite therapeutic drug usage.

3 Haase CB

Backer V

Kalsen A

Rzeppa S

Hemmersbach P

Hostrup M The influence of exercise and dehydration on the urine concentrations of salbutamol after inhaled administration of 1600 μg salbutamol as a single dose in relation to doping analysis. 4 Heuberger JAAC

van Dijkman SC

Cohen AF Futility of current urine salbutamol doping control. 4 Heuberger JAAC

van Dijkman SC

Cohen AF Futility of current urine salbutamol doping control. 4 Heuberger JAAC

van Dijkman SC

Cohen AF Futility of current urine salbutamol doping control. The combination of exercise and dehydration (eg, during a cycling stage) affects urine salbutamol concentrations and increases the risk of exceeding the WADA threshold after inhalation of maximal permitted doses, even after correction for urine-specific gravity.The results of one study might also support an athlete's innocence.On the basis of a pharmacokinetic model of salbutamol absorption and clearance, the authors concluded that establishing the administered dose from a single untimed urine sample is impossible.This could lead to incorrect assumptions of violation, with urine samples of 15·4% of 1000 virtual subjects who had inhaled therapeutic salbutamol doses surpassing the threshold.

5 Saris WH

Senden JM

Brouns F What is a normal red-blood cell mass for professional cyclists?. Despite the controversy surrounding the resolution of Froome's case and the long history of doping in cycling, an optimistic vision of professional cycling is not necessarily naive. Athletes' temptation for banned substances will always exist, but using doping agents with a clear ability to manipulate sports capabilities, notably those enhancing oxygen supply to working muscles, the main limiting factor for endurance performance, is becoming increasingly difficult—cyclists' haematocrit values now resemble those reported in the so-called pre-erythropoietin era.The ability to endure a gruelling training regime distinguishes cycling champions.

We declare no competing interests.