Medical and pharmacological approach to adjust the salbutamol anti-doping policy in athletes.

BACKGROUND: Salbutamol abuse detection by athletes is based on a urinary upper threshold defined by the World Anti-Doping Agency (WADA). However, this threshold was determined in healthy, untrained individuals and after a dose of salbutamol inhaled that might not really mirror the condition of asthmatic athletes and the experts's guidelines for asthma management. We aimed to revise this threshold in accordance with recommended clinical practice (that appear to be different from the actual WADA recommendation) and in exercise conditions. METHODS: For the present open-label design study, we included 12 trained male cyclists (20 to 40 y/o) with asthma. Differently from the previous pharmacokinetic study supporting the actual salbutamol urinary upper threshold, we decided to administer a close to recommended clinical practice daily dose of 3x200 µg.d(-1) inhaled salbutamol (instead of 1600 µg.d(-1) as authorized by the anti-doping policy). Urine salbutamol concentration was quantified by liquid chromatography-tandem ion trap mass spectrometry and corrected for urine density, at rest and after a 90-min cycling effort at 70-80 % of the maximal aerobic power. RESULTS: The maximum urine salbutamol concentration value peaked after the cycling effort and was 510 ng.mL(-1). That is twice lower than the actual WADA threshold to sanction salbutamol abuse, this "legal" threshold being based on pharmacokinetic data after a daily dose that is 8 fold the total dose sequentially administrated in our study. Considering its 95 % confidence interval, this threshold value could be more stringent. CONCLUSION: By using conditions in accordance with the experts' clinical and safety guidelines for asthma management in athletes undergoing an intense exercise bout, our study suggests that the urine salbutamol concentration threshold could be lowered to redefine the rule supporting the decision to sanction an athlete for salbutamol abuse.

Physical activity and sarcopenia.

Physical activity can be a valuable countermeasure to sarcopenia in its treatment and prevention. In considering physical training strategies for sarcopenic subjects, it is critical to consider personal and environmental obstacles to access opportunities for physical activity for any patient with chronic disease. This article presents an overview of current knowledge of the effects of physical training on muscle function and the physical activity recommended for sarcopenic patients. So that this countermeasure strategy can be applied in practice, the authors propose a standardized protocol for prescribing physical activity in chronic diseases such as sarcopenia.

Nitric oxide and carbon monoxide lung transfer in patients with advanced liver cirrhosis.

In advanced cirrhosis, decreased lung transfer for carbon monoxide (TLCO) and increased alveolar-arterial oxygen tension difference (PA-aO(2) >or=15 mmHg while breathing ambient air) are frequently detected. Pulmonary membrane diffusion capacity for CO (DmCO) and pulmonary capillary blood volume (Vcap) can be derived from the simultaneous measurement of TLCO and lung transfer for nitric oxide (TLNO). Measurements of single-breath TLNO and TLCO were performed in 49 cirrhotic patients with advanced liver cirrhosis and in 35 healthy controls to derive Vcap, DmCO, and TLNO:TLCO ratio. Twenty-five patients had increased PA-aO(2), of whom 11 had hepatopulmonary syndrome (HPS). Compared with controls, non-HPS patients with normal PA-aO(2) had a significant approximately 10% decrease in TLCO, DmCO, and Vcap but similar TLNO:TLCO ratios. Compared with non-HPS patients with normal PA-aO(2), non-HPS patients with increased PA-aO(2) had lower Vcap and higher TLNO:TLCO ratio but similar DmCO. HPS patients had lower Vcap and higher TLNO:TLCO ratios than both subgroups of non-HPS patients. In cirrhotic patients, TLNO:TLCO ratios correlated positively, and TLCO (percentage of the predicted value) and Vcap (percentage of the predicted value) correlated negatively with PA-aO(2) (r(2) = 0.25, P = 0.0003, r(2) = 0.48, P < 0.0001 and r(2) = 0.57, P < 0.0001, respectively). We concluded that, in cirrhotic patients, lower TLCO and increased PA-aO(2) are associated with lower Vcap. In addition, high TLNO:TLCO ratios in patients with increased PA-aO(2) suggest a decreased thickness of the capillary blood layer in these patients.

Effect of treatment on maxillary sinus and nasal nitric oxide concentrations in patients with nosocomial maxillary sinusitis.

STUDY OBJECTIVES: In maxillary nosocomial sinusitis (MNS) related to severe sepsis, nitric oxide (NO) concentration in the maxillary sinuses is drastically reduced secondarily to a downregulation of type-2 NO synthase. NO plays a major role in nonspecific immune defense of sinuses. We therefore aimed to study maxillary NO concentration during the treatment of MNS with drainage, daily lavage, and removal of any nasally introduced tube. PATIENTS AND METHODS: Nine patients were studied during the first 4 days of treatment of MNS. We measured the concentration of NO gas in the maxillary sinus and in the nasal cavity, and the NO metabolite levels (nitrites/nitrates [NOx]) in the sinus lavages. MEASUREMENTS AND RESULTS: Maxillary NO concentration (median [25 to 75 percentile]) increased from 70 parts per billion (ppb) [40 to 100 ppb] to 2,050 ppb (1,700 to 3,000 ppb) after 4 days of treatment of MNS (p < 0.0001). In the meantime, nasal NO increased from a median of 100 ppb (98 to 148 ppb) to 180 ppb (180 to 188 ppb) [p < 0.001]. At any time, there was a correlation between maxillary NO (logarithmic value) and nasal NO (r2 = 0.57, p < 0.0001). NOx levels remained stable in the lavages. CONCLUSIONS: We conclude that the treatment of the sinusitis with drainage, daily lavage, and removal of the gastric tube lead to a spectacular increase of maxillary and nasal NO concentrations.

Improvement after lung volume reduction surgery: a role for inspiratory muscle adaptation.

In severe emphysema, lung volume reduction surgery (LVRS) can improve lung function and exercise tolerance. The maximal changes of forced expiratory volume in 1s (FEV(1)) and lung volume occur early after surgery, whereas maximal improvement of exercise tolerance occurs later. We tested the hypothesis that secondary adaptation of inspiratory muscles could explain this delayed clinical improvement. In that purpose, we evaluated nine consecutive patients before LVRS and up to 9 months post-operatively. Six weeks after LVRS, we observed an increase in FEV(1) and 6 min walk distance (6MWD). The gain in sniff nasal inspiratory pressure (SNIP) was inversely proportional to lung volume loss. Values of FEV(1) and lung volume were maintained throughout follow-up whereas SNIP values significantly increased from 6 weeks to 6 months post-LVRS. In the meantime, we observed an increase in 6MWD correlated with the SNIP increase. This suggests that in patients undergoing LVRS, early improvement of SNIP is proportional to decrease in lung volume whereas the further delayed improvement may be due, at least in part, to adaptation of the inspiratory muscles.