All About Salbutamol

[Tonton]

Re: Re:

"Discrimination of Prohibited Oral Use of Salbutamol from Authorized Inhaled Asthma Treatment"

http://clinchem.aaccjnls.org/content/46/9/1365

The metabolism of salbutamol is stereoselective, so to know the ratio of S/R enantiomers of salbutamol reveals a lot about how the dose was administered. That would be one good forensic approach

Fascinating study; great thread!

Yes, it's all there.

 

[Oude Geuze]

A couple of thoughts, blood transfusion theory seems unlikely. Half life is 4hours, peak plasma consentration 2 hours and no one would do a transfusion in the morning before a race. Also, as has been pointed out, the dosages would have to be extreme as you take plasma consentration divided by 10 (unless it’s pure hematocrit in which case much lower still), the you need to distribute the reminder to extra vascular space diluting again by a factor 4-5. So it’s a problem if it contained trace amounts of illegal substance, but would never substantially increase consentration in this case.

Froome probably uses a nebulizer, in the ER 2.5mg is a basic dose for COPD patients, 5mg also common and sometimes 7.5mg. This is usually given 4-6 times daily, but this is during critical illness in a patient with high tolerance for the drug. I don’t have any personal experience with elite athletes, but it’s reasonable to think they want large doses, as normal regimen would be designed to control symptoms in an average person. An average person wouldn’t experience the difference between a forced expiratory rate of 0.8 and 0.9/second, but an elite athlete certainly would. Also, breathing heavily would be causing irritation and exacerbation, dry air and allergens would as well. So say your body is adapted somewhat to beta2 agonists from long term use, you are doing a 3 week your, allergens/exertion/dryness/illness flares up your asthma and you might be puffing the inhaler a lot more than usual in order to be symptom free. Also taken into account the various ways in which a urin sample may yield different concentrations of solute based on a wide variety of physiological factors, and freak/anomalous readings might occur.

What I can’t seem to understand is, if you discard all this and approach it with a linear input/output model (rarely seen in biology), why would Froome and his expert medical team knowingly double++ salbutamol on one stage when they know he will be tested? Also, as others have mentioned, a sudden doubling of salbutamol would almost certainly see adverse results with palpitations, feelings of dyspnea, anxiety, perspiration, dry mouth, tremor, and digestion troubles with diarrhea.

Most likely interpretation imo: A combination of greater than usual inhaler use due to a bad day of asthma combined with adverse hydration/diet/exertion/.../.

Or he was having a bad day and said “*** it, give me an oral, I feel like ***” #yolo

Edited because iphone

 

[poupou]

Armstrong like many other dopers knew too that they would be tested, but they had a plan to beat the testing, and they got caught when they failed it.

 

[movingtarget]

Re:

A couple of thoughts, blood transfusion theory seems unlikely. Half life is 4hours, peak plasma consentration 2 hours and no one would do a transfusion in the morning before a race. Also, as has been pointed out, the dosages would have to be extreme as you take plasma consentration divided by 10 (unless it’s pure hematocrit in which case much lower still), the you need to distribute the reminder to extra vascular space diluting again by a factor 4-5. So it’s a problem if it contained trace amounts of illegal substance, but would never substantially increase consentration in this case.

Froome probably uses a nebulizer, in the ER 2.5mg is a basic dose for COPD patients, 5mg also common and sometimes 7.5mg. This is usually given 4-6 times daily, but this is during critical illness in a patient with high tolerance for the drug. I don’t have any personal experience with elite athletes, but it’s reasonable to think they want large doses, as normal regimen would be designed to control symptoms in an average person. An average person wouldn’t experience the difference between a forced expiratory rate of 0.8 and 0.9/second, but an elite athlete certainly would. Also, breathing heavily would be causing irritation and exacerbation, dry air and allergens would as well. So say your body is adapted somewhat to beta2 agonists from long term use, you are doing a 3 week your, allergens/exertion/dryness/illness flares up your asthma and you might be puffing the inhaler a lot more than usual in order to be symptom free. Also taken into account the various ways in which a urin sample may yield different concentrations of solute based on a wide variety of physiological factors, and freak/anomalous readings might occur.

What I can’t seem to understand is, if you discard all this and approach it with a linear input/output model (rarely seen in biology), why would Froome and his expert medical team knowingly double++ salbutamol on one stage when they know he will be tested? Also, as others have mentioned, a sudden doubling of salbutamol would almost certainly see adverse results with palpitations, feelings of dyspnea, anxiety, perspiration, dry mouth, tremor, and digestion troubles with diarrhea.

Most likely interpretation imo: A combination of greater than usual inhaler use due to a bad day of asthma combined with adverse hydration/diet/exertion/.../.

Or he was having a bad day and said “**** it, give me an oral, I feel like ****” #yolo

Edited because iphone

Tremor and palpitations from my own high level Ventolin use are common not so much the others. I would say that sleep was effected as well but he was probably taking something to counteract that.

 

[Merckx index]

This other paper, specifically testing trained cyclists who have asthma, says that the research by Berge,s et al. was important in establishing the 1000ng/ml WADA salbutamol limit:
https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-015-0315-2

and they note about the specific gravity ...

"urine density correction of urine salbutamol concentration must be considered to minimize the effect of this biological condition on the anti-doping judgment criteria [19]. While this correction was not applied to urine salbutamol concentration proposed in the article by Berges et al. [11] that was used to define the actual upper threshold in the WADA prohibition list, we considered this potent bias and we corrected the urine salbutamol concentration for urine density"

... and the authors go on to conclude that the 1000ng/ml limit for salbutamol is too generous and propose reducing the limit to 500ng/ml instead. So, they don't believe that asthmatic cyclists on a normal therapeutic regimen would reach 1000+ ng/ml accidentally.

Either way, Froome will have big trouble in replicating a 2000ng/ml result, in an in-vivo lab test starting with a believable therapeutic dose

Thanks for this link.* It’s important to emphasize that because of the 800 ug/12 hour rule, 800 ug is effectively the largest allowed dose, though 1600/24 hr is allowed. This is because if you take 800 ug, you can’t take any more for 12 hours, and by this time, most of the original dose has been excreted. So maximum urine levels should basically be what is possible after a single 800 ug dose. This is why they find that 500 ug/ml is probably sufficient as a limit, and it’s why I pointed out in my long post above that Froome’s previous test results might be critical. Though he was always below the 1000 ng/ml limit, if he was > 500 very often, he likely was taking more than the allowed. It’s the same point I made with Petacchi, who has admitted (because he doesn’t see the problem) that his levels even before he triggered the positive were sometimes > 500. I’ve seen another study where they recommended an even lower limit, of about 250.

*The authors seemed to have messed up Fig. 3, though. On the figure itself, the dark and light bars are identified as rest and exercise, respectively. But in the legend to the figure, they're said to indicate before and after correction for SG, with a and b of the figure corresponding to rest and exercise, respectively. It seems that the legend is correct, though this is at odds with the use of the color bars in Fig. 2. Don't know how this glaring error got past the peer reviewers. Note that exercise increases the peak urine values relative to rest, as you'd expect due to increased metabolic rate in general. So it is important to run tests like this that apply to athletes on exercising, and one could argue that the rate will increase even more in elite racers. Still, as I note below, Froome and any other rider with a large number of tests in effect provides his own baseline, sort of like a passport.

A couple of thoughts, blood transfusion theory seems unlikely. Half life is 4hours, peak plasma concentration 2 hours and no one would do a transfusion in the morning before a race. Also, as has been pointed out, the dosages would have to be extreme as you take plasma concentration divided by 10 (unless it’s pure hematocrit in which case much lower still), the you need to distribute the reminder to extra vascular space diluting again by a factor 4-5. So it’s a problem if it contained trace amounts of illegal substance, but would never substantially increase concentration in this case.

Yes, this is an excellent summary of the situation. It later occurred to me that I should have mentioned the fact that if Froome did transfuse, there would certainly be more than one half-life between then and when was tested. I don’t think he would do it immediately before the stage began; probably the preceding evening would be preferred, in which case most of the drug would be gone by testing.

Froome probably uses a nebulizer, in the ER 2.5mg is a basic dose for COPD patients, 5mg also common and sometimes 7.5mg. This is usually given 4-6 times daily, but this is during critical illness in a patient with high tolerance for the drug. I don’t have any personal experience with elite athletes, but it’s reasonable to think they want large doses, as normal regimen would be designed to control symptoms in an average person. An average person wouldn’t experience the difference between a forced expiratory rate of 0.8 and 0.9/second, but an elite athlete certainly would. Also, breathing heavily would be causing irritation and exacerbation, dry air and allergens would as well. So say your body is adapted somewhat to beta2 agonists from long term use, you are doing a 3 week your, allergens/exertion/dryness/illness flares up your asthma and you might be puffing the inhaler a lot more than usual in order to be symptom free. Also taken into account the various ways in which a urine sample may yield different concentrations of solute based on a wide variety of physiological factors, and freak/anomalous readings might occur.

More good points, particularly the issue of tolerance, and the fact that small differences in breathing are critical for an elite athlete. Again it raises the question, why not apply for a TUE? I find it very interesting that Froome hasn’t said, “this never would have been an issue if I had a TUE, which I easily could have qualified for.” Why not? As I said before, I think because he couldn’t qualify. In fact, I'm still waiting for evidence that he actually used an inhaler before 2011. The earliest reference I see is in the Kimmage interview in 2014, when he mentions using it in the Dauphine, but says he never mentioned it in his book because he didn't think it was a big deal. OK, maybe, but if he's had asthma since childhood, surely it wouldn't be that difficult to confirm?

I don’t agree with the bolded, though. While there might be considerable variation, I don’t buy that on one single stage this variation is more than double—probably four times what should be typical—the level on any other stage. Again, he should have been tested nearly twenty times in the Vuelta; for that matter, I guess he’s been tested dozens of times in his career, considering how many days he’s worn the MJ. While that does increase the probability of an unusually high value by chance, it also means there will be more somewhat high values. E.g., if, say, 500 ng/ml was his average value, a 2000 ng/ml value might possibly occur as a result of a statistical fluke, but almost certainly in that case there would be one or more other values > 1000 ng/ml. As you increase the number of samples, you increase the probable size of the largest outlier, but you also increase the probable size of the second largest, third largest, etc. A normal curve spreads out.

In fact, though, I doubt that a 2000 ng/ml value could result from a fluke, even over, say, one hundred tests. The standard deviations obtained from testing pools of subjects indicates that individual variation would not result in such a high value except in exceptionally rare circumstances (e.g., in that link I discussed above, the SD of the exercise values corresponds to a level of > 1000 ng/ml occurring only about once in 20,000 individuals). I doubt that the variation within an individual is going to be any greater. Yes, lab conditions avoid some of the factors found on the road, but unless one can specify what these other factors might be, I think it’s mostly hand waving. Dehydration is probably the most important factor, it can have a major effect on values, but as we've discussed, that does not seem to have been an issue with Froome's reading. Note that in that study above, where subjects were encouraged to drink freely--just as riders in a race would attempt to do--their urine SG values were normal in the middle of the exercise session, and actually below normal half an hour after the end of it.

Another way of putting this is to say that the most relevant study bearing on Froome is Froome himself. We presumably have dozens of samples that he gave following performance on the road under all kinds of conditions. Whatever peculiarities may have resulted from either these road conditions, or because of Froome himself, they're all accounted for in his samples. Taken together, they constitute sort of a passport, with an individualized baseline, a point I think Ross Tucker made in his SoS comments on Froome's test. Yet despite all this, one sample has a level more than twice that of any other. This would certainly be a red flag in any passport test, and it should be here, too, regardless of what any lab test of other individuals says.

 

[Rollthedice]

For Froome it's impossible to come up with a logical non-PED justification for the 2000 ng/ml. In order to help his supposedly asthma, one can't reach that level by puffing away all day. If reaching that extremely generous maximum level of 1000 does not help the breathing problem then much more will not help either. So, he was definitely using it for it's fat loss and other performance enhancing properties most probably OOC. One has to take 2 week cycles of taking pills to have the desired effect, similar to clenbuterol. How this concentration popped up in the test after a stage where he came back from the dead is subject to speculation. Maybe Ulissi can be of some help, he was flying in the Giro when he was caught with a similar concentration.

 

[hazaran]

More good points, particularly the issue of tolerance, and the fact that small differences in breathing are critical for an elite athlete. Again it raises the question, why not apply for a TUE? I find it very interesting that Froome hasn’t said, “this never would have been an issue if I had a TUE, which I easily could have qualified for.” Why not? As I said before, I think because he couldn’t qualify. In fact, I'm still waiting for evidence that he actually used an inhaler before 2011. The earliest reference I see is in the Kimmage interview in 2014, when he mentions using it in the Dauphine, but says he never mentioned it in his book because he didn't think it was a big deal. OK, maybe, but if he's had asthma since childhood, surely it wouldn't be that difficult to confirm?

You listed the TUE requirements earlier, but all of that was just standard asthma documentation that he or the medical team would most certainly have available. Nobody objected to cortisone treatment for Wiggins, so I don't think whoever approves the TUEs is particularly critical.

What's the tolerance development like? That seems to be an issue you would have to take into account for a sane limit. If he's taking N+1 doses every day in the stage race to keep the same effect, is stage 18 the point where it triggers the tripwire? I don't think any of the studies we have seen had subjects that did 18 days of 5, 6 hours exercise with lots at VO2max that would have them constantly using their inhaler and develop a tolerance.

You also mention there is all the data from the previous stages on urine concentration. But it cuts the other direction, too: he wasn't notified of the adverse test until *after* the Vuelta and was tested as leader after stages 19 and 20. How did he test at 2000 ng/ml on stage 18 but not >1200 ng/ml for 19 and 20? Doesn't seem likely that the worsened asthma is only stage 18. (Do they test every sample for this? Don't think we had an answer to that yet)

 

[Merckx index]

You listed the TUE requirements earlier, but all of that was just standard asthma documentation that he or the medical team would most certainly have available. Nobody objected to cortisone treatment for Wiggins, so I don't think whoever approves the TUEs is particularly critical.

Did you see the FEV1 requirements that I didn’t post, but which are detailed at the site? If he meets those requirements, why would he not get a TUE? I have no idea how stringent those requirements are, but perhaps someone here with asthma can comment.

What's the tolerance development like? That seems to be an issue you would have to take into account for a sane limit. If he's taking N+1 doses every day in the stage race to keep the same effect, is stage 18 the point where it triggers the tripwire? I don't think any of the studies we have seen had subjects that did 18 days of 5, 6 hours exercise with lots at VO2max that would have them constantly using their inhaler and develop a tolerance.

But again, he’s ridden many GTs before, without this apparently being a problem. And does he use the inhaler only during races? Does he need it when he isn’t racing or training? If so (and this is supported by the fact that he told Kimmage he's had the problem since childhood, before he was racing), then tolerance will constantly develop, and I wouldn’t think there would be much of a change during a race. If he only uses it during races (which he implies, seemingly in contradiction to his from-childhood claims, when he says he needs it only for big efforts) then you would think his condition is fairly mild, and that even when he needs the drug, he doesn’t need much. If he’s only taking it before TTs and a MTF, e.g., I wouldn’t expect a lot of tolerance to develop. But details would certainly be helpful here so we wouldn’t have to speculate and guess.

You also mention there is all the data from the previous stages on urine concentration. But it cuts the other direction, too: he wasn't notified of the adverse test until *after* the Vuelta and was tested as leader after stages 19 and 20. How did he test at 2000 ng/ml on stage 18 but not >1200 ng/ml for 19 and 20? Doesn't seem likely that the worsened asthma is only stage 18.

I’ve said all along there is no simple, slam dunk explanation—neither innocent accident nor intentional doping--for this anomalous result. I just think that the scenario that has the fewest problems is that he was taking high doses all along—such that he usually wasn’t far below the 1000 ng/ml level—then not only took more, but had a problem with timing of the dose, urinating before the end, and perhaps some other factors.

(Do they test every sample for this? Don't think we had an answer to that yet)

Yes, I asked about that upthread, nobody seemed to know, so I fell into assuming that he probably was tested every time. But if not, that potentially makes a big difference. Suppose he’s only tested for salbutamol sporadically, maybe only 2-3 times the entire Vuelta, only a dozen or so times in his career. It would still not be easy for him to explain a large jump in urinary level, from the point of view of avoiding a sanction, but it would be easier to believe he had been taking larger than allowed doses all along. We could now speculate that this was not the first time he had exceeded the threshold, but in previous cases hadn't been tested.

 

[Merckx index]

A link in the Froome thread is to a LeMonde article which confirms that Froome has not yet taken the laboratory test needed to explain his high level. It also says that a Dr. Derick MacLeod told Froome to take three puffs from his inhaler after the stage but before submitting urine for analysis (?) And the final Froome quote is very interesting:

we have a ton of information, in the team, on what I ate every day, on how many times I stopped to urinate in the race every day. We know the number of puffs that I inhaled and what time. There is a lot of detailed information that we were able to give to the authorities, and I hope that we will be able to identify the real cause of the problem.

If they have that information for that stage, where they didn't of course until later that he would exceed the threshold, they must have it for other stages as well, not only for the Vuelta, but for the Tour. I would love to see all these data.

En savoir plus sur http://www.lemonde.fr/cyclisme/article/2017/12/14/cyclisme-le-cas-froome-ne-sera-pas-tranche-avant-plusieurs-mois_5229561_1616656.html#rJ5EkjpPGKWty2LD.99

Could Froome have ingested extra salbutamol through a contaminated supplement? As it happens, one of the most comprehensive reviews of contaminants present in supplements, examining more than 400 studies, with a particular emphasis on substances used to dope, was published just a couple of months ago, and the entire article is accessible. The following link takes you to the abstract, and on that page is linked the full article.

https://www.ncbi.nlm.nih.gov/pubmed/28976928

There’s no mention of salbutamol anywhere in the article, so it appears that there have been no reports of such contamination to date. A search of PubMed also came up negative.

With regard to tolerance, the issue is complex. Several old studies reported no tolerance following several weeks of daily ingestion of mg quantities of salbutamol:

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.1975.tb00557.x/pdf
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.1974.tb00255.x/full
http://www.atsjournals.org/doi/abs/10.1164/arrd.1980.121.6.973

Somewhat more recent studies reported tolerance to the bronchoprotective but no bronchodilatory effects of salbumatol:

http://www.sciencedirect.com/science/article/pii/S0091674999701788
http://www.sciencedirect.com/science/article/pii/014067369392695P

The dilatory effects refer to the expansion of the airways, permitting better breathing. The protective effects I believe refer to prevention of constriction by external substances like pollen,and also to inflammation resulting from such agents, or from the build-up in the lungs of salbutamol itself, particularly the S+ form, which is not pharmacologically active but which is metabolized more slowly than the active R- form.. The dilatory effects are generally the ones that permit better breathing, so there has been some question whether tolerance actually is an issue with regard to use of salbutamol to open the airways during an asthma attack.

Recent studies, however, have suggested that tolerance to the dilatory effects becomes a problem when the constriction of the airways becomes more extreme. In these studies, the substance methacholine is given to induce bronchoconstriction artificially. Then the effect of salbutamol on reversing this constriction is compared in naïve (no previous salbutamol in the study period) vs. chronically treated subjects. The conclusion seems to be that in relatively severe asthma attacks, tolerance can be a problem. It’s not clear to me whether people who suffer relatively mild symptoms would develop significant tolerance. Again, perhaps those who actually have asthma can comment from their own experience. This link to the complete article has a good review as well as experimental results:

http://erj.ersjournals.com/content/21/5/810.long

 

[ScienceIsCool]

I really don't think that tolerance is a common problem. The reason is that therapeutic doses are quite low, and if anyone is relying on their inhaler for relief, then the strategy changes to reliance on an inhalable corticosteroid such as Fluticasone.

I can give a personal anecdote. My four year old is also asthmatic and has a 50 ug inhaler for when he starts wheezing/coughing. Then one day this summer, the Salbutamol didn't seem to be having any effect. After about an hour and 5-6 puffs we were off to the hospital! There he was given a massive dose of a systemic steroid and 5 puffs x 50 ug every 15 minutes and kept in emergency until there was zero signs of any constriction, which took several hours. So in his case that was like 1 mg per hour for ~4 hours. Then he spent the next day in hospital to be monitored for O-Sat and pulse. Two more oral doses of steroid (can't remember which one, but it would have been similar to Prednisone) were given to kick start everything.

Afterwards, his asthma management strategy was switched to taking 2 x 2 puffs daily of Fluticasone, which is a corticosteroid. The risk is HPA axis suppression which can cause a cortisol deficiency. This is offset by the fact that a short course of Prednisone is much, much harder on the body even if it only happens every couple of years. Since going on Fluticasone, my son has only used his inhaler a couple of times in six months. That's what is considered to be "in control" and if Fluticasone doesn't work the strategy will be altered until you are.

Pulmonary function is... kind of fundamental and at least here in Canada, the doctors don't mess around. Which is why it's so very odd that:

A) Froome relies so heavily on Salbutamol. It implies that his management strategy isn't working.
B) He admits he uses Fluticasone, so it's weird that he uses Salbutamol at all.
C) Wiggo's use of Prednisone is shocking. People using that for breathing problems should be in a hospital being monitored closely, because things have gone way off the rails.
D) Prednisone is super risky for athletes in competition because it's an adrenal suppressant. This could turn a nasty crash into something far more serious.
E) If you use Fluticasone and need Salbutamol to race, you need to not race until your doctor has sorted things out

John Swanson

 

[sittingbison]

John youre forgetting the bilharzia ate all Dawgs red blood cells, so he needs triple doses of multiple drugs to catch up to normal non alien folk.

Sir Wiggo has 8 Olympic gold medals and a TdF. He doesn't need a hospital, he's superhuman, and besides everyone knows a few puffs on a joint opens the airways far better than steroids

 

[heartsnotinit]

There isn't there any way for a male athlete to get salbutamol on their hands from using an inhaler and then into his urine sample, is there? The "I had to pee immediately so failed to follow protocol and didn't wash my hands" defence.

 

[sittingbison]

Re:

...
Most likely interpretation imo: A combination of greater than usual inhaler use due to a bad day of asthma combined with adverse hydration/diet/exertion/.../.

Or he was having a bad day and said “**** it, give me an oral, I feel like ****” #yolo...

Except Dawg doesn't have asthma, or bilharzia, or any other debilitating disease. He's a finely tuned athlete capable of superhuman physiological outputs. And the greater than usual inhaler use is more than 40 puffs!!

 

[veganrob]

Has it been mentioed that Salbutamol could be in a finish bottle? Or is it when oral administration is talked about they are including tis method od ingestion. An inhaler does seem impossible to reach such a high limit and orally would seem to get the best results in this circumstance.
We also know Sky likes to do the finish bottles with Tramadol and caffeine. Some Salbutamol also maybe? It seems stupid to do that but we are talking about pro cycling.

 

[movingtarget]

Re:

I really don't think that tolerance is a common problem. The reason is that therapeutic doses are quite low, and if anyone is relying on their inhaler for relief, then the strategy changes to reliance on an inhalable corticosteroid such as Fluticasone.

I can give a personal anecdote. My four year old is also asthmatic and has a 50 ug inhaler for when he starts wheezing/coughing. Then one day this summer, the Salbutamol didn't seem to be having any effect. After about an hour and 5-6 puffs we were off to the hospital! There he was given a massive dose of a systemic steroid and 5 puffs x 50 ug every 15 minutes and kept in emergency until there was zero signs of any constriction, which took several hours. So in his case that was like 1 mg per hour for ~4 hours. Then he spent the next day in hospital to be monitored for O-Sat and pulse. Two more oral doses of steroid (can't remember which one, but it would have been similar to Prednisone) were given to kick start everything.

Afterwards, his asthma management strategy was switched to taking 2 x 2 puffs daily of Fluticasone, which is a corticosteroid. The risk is HPA axis suppression which can cause a cortisol deficiency. This is offset by the fact that a short course of Prednisone is much, much harder on the body even if it only happens every couple of years. Since going on Fluticasone, my son has only used his inhaler a couple of times in six months. That's what is considered to be "in control" and if Fluticasone doesn't work the strategy will be altered until you are.

Pulmonary function is... kind of fundamental and at least here in Canada, the doctors don't mess around. Which is why it's so very odd that:

A) Froome relies so heavily on Salbutamol. It implies that his management strategy isn't working.
B) He admits he uses Fluticasone, so it's weird that he uses Salbutamol at all.
C) Wiggo's use of Prednisone is shocking. People using that for breathing problems should be in a hospital being monitored closely, because things have gone way off the rails.
D) Prednisone is super risky for athletes in competition because it's an adrenal suppressant. This could turn a nasty crash into something far more serious.
E) If you use Fluticasone and need Salbutamol to race, you need to not race until your doctor has sorted things out

John Swanson

Prednisone use for chronic sinusitis is not uncommon but of course it can't be used continuously but it is effective. If Froome is using a preventer, the amount of Ventolin seems abnormal as you say. Since using Pulmicort my Ventolin use dropped off to a minimum or nothing at all but then I'm not an elite athlete ! Even with a cold or bronchitis he wouldn't use that much Ventolin for worsening asthma. Prednisone seems to be one of those over prescribed drugs like anti depressants and painkillers even Ventolin for that matter is often misused. Some people seem to think if they walk up a flight of stairs and they are out of breath they must need Ventolin same with smokers. There is no logical explanation for Froome's Ventolin reading via a puffer and I doubt he has one. I'd be surprised if there was scientific support for it either and it will be interesting to hear how his lawyer defends him at the hearing.

 

[The Hegelian]

I agree that the puffer defense is completely implausible - it simply defies medical logic. And I think it clearly follows that Salbutamol was being used for some kind of 'under the threshold' performance gain. And this would be, perhaps, genuinely quite marginal. But a gain nonetheless.

I would be interested to know what people think of Ulissi's case. Why did he take that amount of Salbutamol and what kind of benefits did it give him?

 

[70kmph]

2 week study on cyclists for oral salbutamol

http://erj.ersjournals.com/content/40/Suppl_56/P854

Conclusions: Two week daily intake of salbutamol taken prior to training improves anaerobic power in elite cyclists.

 

[thehog]

Re:

I agree that the puffer defense is completely implausible - it simply defies medical logic. And I think it clearly follows that Salbutamol was being used for some kind of 'under the threshold' performance gain. And this would be, perhaps, genuinely quite marginal. But a gain nonetheless.

I would be interested to know what people think of Ulissi's case. Why did he take that amount of Salbutamol and what kind of benefits did it give him?

The Froome story, taking the inhaler after the stage is total bunk. There is no way it will pass through your lungs to be absorbed by your liver, kidneys and into your urine that quickly. Not possible, I’d say at least 30-60 minutes before it would register. Perhaps longer.

Perhaps Dawg reached into his pocket mid stage and grabbed the wrong pill?

 

[Merckx index]

Re:

Pulmonary function is... kind of fundamental and at least here in Canada, the doctors don't mess around. Which is why it's so very odd that:

A) Froome relies so heavily on Salbutamol. It implies that his management strategy isn't working.
B) He admits he uses Fluticasone, so it's weird that he uses Salbutamol at all.
C) Wiggo's use of Prednisone is shocking. People using that for breathing problems should be in a hospital being monitored closely, because things have gone way off the rails.
D) Prednisone is super risky for athletes in competition because it's an adrenal suppressant. This could turn a nasty crash into something far more serious.
E) If you use Fluticasone and need Salbutamol to race, you need to not race until your doctor has sorted things out

Thanks for sharing your personal experience, John, but I believe it was Froome, not Wiggins, who used prednisolone. He had TUEs for that in 2013 and 2014. Wiggins had TUEs for salbutamol, formoterol, budenoside, and of course, triamcinolone. Just to be clear, salbutamol is classified as a short-acting b2-agonist; formeterol is a long-acting b2-agonist, which I take it is indicated if salbutamol isn't enough. The other drugs are all glucocorticoids.

I now see that probably the reason Froome didn’t have a TUE for salbutamol is that following the uproar over the revelation that he had a TUE for prednisolone, he wanted to avoid all the bad publicity. I think in fact he said as much. At first I thought he must have been using salbutamol long before the TUE incident; he has said he has been asthmatic since childhood. But no one in this thread has come up with evidence that he used salbutamol in races prior to 2014, about the time that the prednisolone TUE was revealed. Not sure about the timeline, but is it possible he only began using salbutamol following the relevation of the TUE and his vow not to use any more of them? That maybe he saw salbutamol, with its allowed threshold, as the best way to take a potential PED without a TUE? Just speculating here.

All this talk about how elite riders are at higher risk for developing asthma prompts the question: did other great riders of the past have the problem? Hinault? LeMond? Indurain (and in the same Tour, Rominger) tested positive for salbutamol, but it wasn't banned at the time. What about LA, Contador? Contador I know has had allergy problems.

Also, I hadn't realized that Pereiro--who of course was the "real, clean" winner of the 2006 TDF following Floyd's suspension--tested twice for salbutamol in that race. He was eventually cleared, apparently because he had permission from UCI, so I suppose that means a TUE.

The most interesting case might be Piepoli. He was cleared, but I haven't been able to find out why. It's not even mentioned on his Wiki page, which is very strange. But since he also tested positive for CERA, there's no question he would have used salbutamol for PE if he thought it would help.

 

[King Boonen]

Re: Re:

Pulmonary function is... kind of fundamental and at least here in Canada, the doctors don't mess around. Which is why it's so very odd that:

A) Froome relies so heavily on Salbutamol. It implies that his management strategy isn't working.
B) He admits he uses Fluticasone, so it's weird that he uses Salbutamol at all.
C) Wiggo's use of Prednisone is shocking. People using that for breathing problems should be in a hospital being monitored closely, because things have gone way off the rails.
D) Prednisone is super risky for athletes in competition because it's an adrenal suppressant. This could turn a nasty crash into something far more serious.
E) If you use Fluticasone and need Salbutamol to race, you need to not race until your doctor has sorted things out

Thanks for sharing your personal experience, John, but I believe it was Froome, not Wiggins, who used prednisolone. He had TUEs for that in 2013 and 2014. Wiggins had TUEs for salbutamol, formoterol, budenoside, and of course, triamcinolone. Just to be clear, salbutamol is classified as a short-acting b2-agonist; formeterol is a long-acting b2-agonist, which I take it is indicated if salbutamol isn't enough. The other drugs are all glucocorticoids.

I now see that probably the reason Froome didn’t have a TUE for salbutamol is that following the uproar over the revelation that he had a TUE for prednisolone, he wanted to avoid all the bad publicity. I think in fact he said as much. At first I thought he must have been using salbutamol long before the TUE incident; he has said he has been asthmatic since childhood. But no one in this thread has come up with evidence that he used salbutamol in races prior to 2014, about the time that the prednisolone TUE was revealed. Not sure about the timeline, but is it possible he only began using salbutamol following the relevation of the TUE and his vow not to use any more of them? That maybe he saw salbutamol, with its allowed threshold, as the best way to take a potential PED without a TUE? Just speculating here.

All this talk about how elite riders are at higher risk for developing asthma prompts the question: did other great riders of the past have the problem? Hinault? LeMond? Indurain (and in the same Tour, Rominger) tested positive for salbutamol, but it wasn't banned at the time. What about LA, Contador? Contador I know has had allergy problems.

Also, I hadn't realized that Pereiro--who of course was the "real, clean" winner of the 2006 TDF following Floyd's suspension--tested twice for salbutamol in that race. He was eventually cleared, apparently because he had permission from UCI, so I suppose that means a TUE.

The most interesting case might be Piepoli. He was cleared, but I haven't been able to find out why. It's not even mentioned on his Wiki page, which is very strange. But since he also tested positive for CERA, there's no question he would have used salbutamol for PE if he thought it would help.

This paragraph is a little confusing. At first you talk about him not having a TUE for salbutamol after the predisolone discovery and wanting to avoid a scandal, but he wouldn't have needed a TUE for salbutamol in 2014. I believe it's just a declaration of use on the anti-doping control form that was and is still required. Unless you mean for oral doses? At the end of the paragraph you acknowledge that you don't need a TUE for salbutamol (within threshold) so I'm thinking the paragraph just got a little confused?

Asking for evidence of salbutamol use from the forum and using this a lack of this as evidence that he started using these inhalers in 2014 seems a bit disingenuous. I believe that there is 1 photo of Froome using an inhaler that exists, from the 2014 Dauphine? As it's been permitted with a TUE for a long time and without one since 2010 I don't think people would have been desperate to catch a snap of any cyclist using an inhaler, so the absence of evidence isn't really compelling either way. In fact I think the "photo" that exists was just a screen grab from the video cameras anyway.

With regard past riders and diagnosis, there is a steady increase in total number of asthma sufferers, but a large decrease in recent years in number of new cases per year. This would indicate that previous testing and diagnosis was lacking, so it's possible that many cases in the 60's - 90's were missed. I would also speculate that endurance athletes like cyclists were less likely to be diagnosed as well due to their ability to perform on the bike. I'm really not up on the literature from those periods, but if anyone is really interested they'd be able to make a more informed comment.

Specifically with regard to Hinault, I've read Fotheringham's recent book and I don't remember any mention of asthma in it.

 

[bigcog]

Some WADA research docs re: salbutamol

https://www.wada-ama.org/en/search?k=salbutamol&search-category=all&op=Search

https://www.wada-ama.org/sites/default/files/resources/files/backer_0.pdf

 

[Merckx index]

Re: Re:

This paragraph is a little confusing. At first you talk about him not having a TUE for salbutamol after the predisolone discovery and wanting to avoid a scandal, but he wouldn't have needed a TUE for salbutamol in 2014. I believe it's just a declaration of use on the anti-doping control form that was and is still required. Unless you mean for oral doses? At the end of the paragraph you acknowledge that you don't need a TUE for salbutamol (within threshold) so I'm thinking the paragraph just got a little confused?

He would have needed a TUE for salbutamol if he expected to exceed the threshold level of 1000 ng/ml. My point is that he may have wanted to get a TUE so he could take higher doses, but feared the public reaction.

However, what I’m really wondering is whether the salbutamol use began in 2011, and contributed to the transformation. Suppose he didn’t have asthma, or at least did not need to inhale regularly. Then suddenly in 2011, he realizes that he can use salbutamol up to the threshold without a TUE. So he begins taking it.

This raises another question which I wondered aloud about here before: if a rider who doesn’t have asthma or use an inhaler tests for salbutamol, but below the threshold, does WADA care? Do they even know whether the rider takes the drug for therapeutic purposes? Apparently not, because in 2011, the year following the change in rules allowing riders to inhale the drug up to the 1000 ng/ml level without a TUE, WADA also removed the requirement for declaration of use:

https://www.wada-ama.org/sites/default/files/resources/files/11-_mountjoy_margo_-_paris_2014_-medical_issues_asthma.pdf

So beginning in 2011, Froome would have been free to start taking the drug, without having any history of asthma. That is the same year, of course, that the great transformation occurred, so it becomes critical to ask whether he was taking salbutamol before then.

Asking for evidence of salbutamol use from the forum and using this a lack of this as evidence that he started using these inhalers in 2014 seems a bit disingenuous. I believe that there is 1 photo of Froome using an inhaler that exists, from the 2014 Dauphine? As it's been permitted with a TUE for a long time and without one since 2010 I don't think people would have been desperate to catch a snap of any cyclist using an inhaler, so the absence of evidence isn't really compelling either way. In fact I think the "photo" that exists was just a screen grab from the video cameras anyway.

Good grief, is my point really that hard to understand? In the first place, I wasn’t using lack of inhaling pictures as strong evidence that he started in 2014. I just find it very curious that for a rider with such a high profile no one AFAIK, either here or in the media, has actually provided evidence of this use. Wouldn’t you think that as soon as he told Kimmage about it in 2014, journalists would rush to establish he really was using salbutamol throughout his pro cycling career?

Second, as stated right there in your paragraph, a TUE was needed up to 2010. Which means if he has really been taking it since childhood, he had to have a TUE up to that year. I know that Fancy Bears hacked WADA information as far back as 2009, publishing a report that Nadal had a TUE in that year. So isn’t it logical that if Froome had a TUE then, FB would have mentioned this? They publicized his 2013 and 2014 TUEs for prednisolone, but AFAIK they didn’t say anything about TUEs for salbutamol prior to 2010. Now maybe there’s a simple reason for that, but wouldn’t journalists want to know?

 

[sittingbison]

That Dauphine pic caused a ruckus because it was the first time he had been seen using it, and he admitted it was for the "big effort" coming up rather than a therapeutic device for asthma in general ie he was cheating

Think back to 2012 TdF...the camera barely left Dawg and Wiggo the entire Tour. He never once reached for an inhaler, if he had the clinic would have imploded as they were trying to explain both his and Wiggos unheard of transformation, and the wattage being put out by the Sky train leaving everyone in the dust (remember Basso mentioned it, 450W hour after hour etc)

 

[thehog]

Back to my previous question as it keeps getting missed;

How did he record such a high reading at dope control if he only took he medication minutes prior to giving a sample? There’s no way Salbutamol could be ingested via his lungs, then absorbed by his liver, kidneys and into his urine that quickly. Not possible, I’d say at least 30-60 minutes before it would register. Perhaps longer.

 

[Merckx index]

Back to my previous question as it keeps getting missed;

How did he record such a high reading at dope control if he only took he medication minutes prior to giving a sample? There’s no way Salbutamol could be ingested via his lungs, then absorbed by his liver, kidneys and into his urine that quickly. Not possible, I’d say at least 30-60 minutes before it would register. Perhaps longer.

He presumably didn't take all of it then. He took three puffs, which I gather is 300 ug. He could have taken 500 ug additional during or before the stage that day, and still more the previous day.

But your point is still good. A large fraction of his allowable dose would have been "wasted", in the sense that it would have contributed very little to his urine level. In fact, just because of this, the advice to take it then would be reasonable, if in fact he really needed it to stop coughing during the post-stage interview. It wouldn't significantly increase his risk of going over the threshold.

It's only now that it ironically comes back to bite him. I did discuss this upthread, where I noted that even if Froome were able to demonstrate a 2000 ng/ml level in the lab, the conditions under which he did this (800 ug all at once, followed by several hours, then a urine sample) would not be the same as what he must have done on the road. Hence he could get off on a technicality.