All About Salbutamol

[Merckx index]

Re:

According to Times article about this new study and Froome's case, Froome's adjusted reading was 1429ng/mL under the new WADA rules. Dr Rabin science director of WADA has read Leiden paper and says WADA will defend it's current threshold and they have also done their own tests in preparation for Froome's case.

Have a link? If his adjusted reading was 1429, then his USG was 1.028. I was wondering what it was, and if it would help him. It does. He could now use the corrected figure, together with the theoretical study, to argue that there is some probability--5%?--of his urine level if he inhaled 800 ug in the last hour of the stage. Also, the data in the literature might show a value that low for 800 ug. I need to check that. Still a stretch, but better for him than 2000 ng/ml.

Edit: Still doesn't look good for him. In five studies of subjects inhaling 800 ug, only 4/344 samples were > 1000 ng/ml, and only 1 was > 1200 ng/ml. That sample was 1387 ng/ml, but only as a result of correction of a raw value of around 560 ng/ml. The subject had very dilute urine, which can result in a very large correction factor.

I have a better idea of why the case is taking so long, though. The 1429 ng/ml level is close enough to the decision limit that Froome's team is probably arguing for some other factors to push it down a little more.

 

[70kmph]

Dr Olivier Rabin, Wada’s science director, told The Times that the organisation would vigorously defend its position and had already read the Leiden paper. “I read the article you refer to, and no, no concern at all. Nothing new as their model is based on three well-known studies,” Rabin said.

He added: “Wada has conducted several studies on salbutamol and continues to conduct studies on beta-2 agonists. We believe the current threshold is solid considering the scientific literature published on salbutamol over the past 20 years. Based upon the published and unpublished information in our possession, we see no reason to change the salbutamol threshold.”

The Team Sky rider has said that he increased his puffs during the race under the guidance of the team doctor, believed to have gone from two puffs per day up to ten during the last week of the Vuelta because he felt worsening asthma conditions.

https://www.thetimes.co.uk/edition/...about-chris-froomes-salbutamol-test-ldbsx5sdn

 

[fasthill]

Re: Re:

No, we're still waiting for the police to hand out the ticket.

Let's not go with the analogy too far. The Tribunal does not punish automatically after the discovery of the infringement as a police officer would. The fact of the infringement goes to the Tribunal to give the offender the opportunity to explain the infringement. The Tribunal's function is nothing like the police's.

 

[Brullnux]

Dr Olivier Rabin, Wada’s science director, told The Times that the organisation would vigorously defend its position and had already read the Leiden paper. “I read the article you refer to, and no, no concern at all. Nothing new as their model is based on three well-known studies,” Rabin said.

He added: “Wada has conducted several studies on salbutamol and continues to conduct studies on beta-2 agonists. We believe the current threshold is solid considering the scientific literature published on salbutamol over the past 20 years. Based upon the published and unpublished information in our possession, we see no reason to change the salbutamol threshold.”

The Team Sky rider has said that he increased his puffs during the race under the guidance of the team doctor, believed to have gone from two puffs per day up to ten during the last week of the Vuelta because he felt worsening asthma conditions.

https://www.thetimes.co.uk/edition/...about-chris-froomes-salbutamol-test-ldbsx5sdn

I'm no expect here, but if 15% are found to be false positives over 1000mg, isn't that why there is the 1200mg limit in place as well? And a 1500mg finding would have a statistically negligible chance of being a false positive? So this study and its findings are actually nothing new, and basically irrelevant to the case?

 

[fasthill]

Ross Tucker chimes in on the Let-Froome-Go paper:

https://twitter.com/Scienceofsport/status/993413989890707457

 

[Robert5091]

And these are the same people who claimed EPO was no good? Lucky for Froome they decided to do this study after Froome's "troubles" were leaked to the press. Smells ...

 

[Bolder]

Re:

Ross Tucker chimes in on the Let-Froome-Go paper:

https://twitter.com/Scienceofsport/status/993413989890707457

That saved me a lot of head scratching. THanks.

However, this is probably the key takeaway, from Tucker: I think the point is that this is how Sky and Froome need it to be, and this study is a big bullet in their chamber. It’s all about sowing doubt. Attack the foundations, then jump out the window when the house falls down.

So, probably not Froome's life preserver, but definitely something that he can clutch at.

 

[Djoop]

Deleted post

 

[Merckx index]

I'm no expect here, but if 15% are found to be false positives over 1000mg, isn't that why there is the 1200mg limit in place as well? And a 1500mg finding would have a statistically negligible chance of being a false positive? So this study and its findings are actually nothing new, and basically irrelevant to the case?

The 1200 DL is to account for possible uncertainty in the measurement, is not relevant to the 15%. And 1500 (1429) would not be negligible in their model, but somewhere between 5-10%. To repeat what I said earlier, 4/344 samples in five well-known studies were> 1000, only 1 > 1200, and that was a corrected value. The reason why there are so few--and the answer to Tucker's question of why there are so few positives in the peloton--is because it would be quite rare that a rider would take 800 ug in a short period of time, then give a sample within an hour. Most of the studies in the literature assayed urine after four hours, some even longer. It would be fairly easy at this point to run a study in which subjects all took 800 ug and were tested one hour later, and someone should do that. My prediction is that there will definitely be > 1% > 1000, and maybe > 1% > Froome's value, but unless Froome can prove he took 800 ug within an hour of the end of the stage, that doesn't help him. Mostly it shows that if a rider wanted to go out of his way to stay within the limit allowed to inhale, and still test over the limit in urine concentration, he could do it! Sorry but the computer I'm on now doesn't allow me to make new paragraphs, just should add that such a study should look at one hour, two hours, and four hours. It would be very easy to test this model.

 

[fasthill]

Re: Re:

However, this is probably the key takeaway, from Tucker: I think the point is that this is how Sky and Froome need it to be, and this study is a big bullet in their chamber. It’s all about sowing doubt.

It's not that simple. Sowing doubt won't help them and they know that. If the paper has anything to do with the case (and I think it does), they're gunning for that 15% possibility of a sample being a false positive.

I'm assuming this is all happening in preparation for the appeal. If that's the case, Froome's burden of proof will be on the balance of probabilities (s 3.1 of the UCI Anti-Doping Rules). He'll have to show that the sum total of his arguments tips the balance in his favor and that paper will be one of the arguments. How much weight the panel will give it, we don't know and neither do they but it's worth raising the argument in court. Marginal gains, every little bit helps.

 

[Merckx index]

I had a chance to look at those five studies a little more closely, considering only the samples that were analyzed four hours (or earlier) after inhaling 800 ug. Only 3/168 subjects were > 1000, and only one, corrected for USG, was > 1200 ng/ml. Also, two of the studies reported samples at earlier times, including 30 minutes (8 samples, none > 1000); 1 hour (40 samples, none > 1000); and two hours (40 samples, one USG-corrected sample was > 1200). So 1/88 samples > 1000 and > 1200.

Heuberger et al. say their model predicts 15% of samples > 1000 at one hour, and 3% > 1000 at four hours. The only empirical evidence they cite is one study in which 1/28 samples was > 1000, close to their 3% prediction. But in the much larger sample size* of five studies I looked at—which includes the one Heuberger et al referred to plus four others—less than 2% of the samples were > 1000, and about half of the samples in this pool were taken at two hours or sooner, which should have increased the proportion > 1000. Particularly damning are the 48 samples taken at one hour or earlier. If the predicted proportion > 1000 is 15%, it’s highly improbable that 0/48 by chance would be > 1000.

*The effective sample size is even larger than I've indicated, because for many samples, two values are reported--uncorrected and corrected for USG. I count these two values as corresponding to one sample.

Elers1: http://sci-hub.tw/10.1249/MSS.0b013e3181b2e87d
Elers2: http://sci-hub.tw/10.1097/JSM.0b013e31823513e1
Mareck: http://sci-hub.tw/10.1002/dta.367
Dickinson: http://sci-hub.tw/10.1097/jsm.0000000000000072
Sporer: http://sci-hub.tw/10.1097/JSM.0b013e3181705c8c

Everyone has pointed out that this is just a theoretical model, but there’s another very important point that’s generally missed. Their case is based on the conclusion that the concentration of salbutamol in the urine reaches a peak very fast—within thirty minutes to an hour. They don’t say this, or at least emphasize it, but most of the empirical salbutamol studies are based on longer times before the urine sample is taken—four hours or more.

This is critical, because it allows them to make this claim of 15% over the threshold without an apparent contradiction with the empirical data. They’re implying the reason most studies don’t show many samples > 1000 is because they don’t take the samples early enough. But as I’ve just shown, there are enough data at these earlier times to call into serious question this premise.

These other studies do support Heuberger’s conclusion that urine level of salbutamol peaks at about one hour after inhalation, but it doesn’t appear to drop dramatically between then and four hours. The Sporer paper reports that the mean urine concentration at 2 hours is 70-80% that at one hour, a difference that is not significant.

A generally similar decrease of mean values was found from 1.5 to 4 hr in the Haase study, which was the one supplying some of the data Heuberger et al used to construct their model. Haase et al tested inhalation of 1600 ug only. In that study, more samples > 1000 were generally found at 1.5 hr than 4 hr, but the difference was not that great. Across all three conditions, and including corrected and uncorrected values, there was a total of 28 samples > 1000 at 1.5 hr vs. 23 at 4 hr. Using the 1200 ng/ml DL, it was 21 vs. 18. This is not consistent with Heuberger et al's prediction that the proportion of samples > 1000 after 1 hr is five times that at four hr. (N.B.: The Haase values are take from Table 2 of their paper; the same values are nominally included in Fig. 2, but several of them are wrong, as easily can be seen by counting the number of points above the threshold line; I don't know how this got past the reviewers).

Haase: http://sci-hub.tw/10.1002/dta.1828

 

[gillan1969]

I am presuming that the strategy is, that knowing they will never replicate the levels, they are going down Froome's 'point of view' approach. For the fans the headlines will be enough...exactly the same as 'he just lost the fat'...use the media and the academics (or 'usefool fools') to create the narrative.....

Sky can claim that there is enough doubt to maintain the charade that they are clean, they don't need to fire Froome and Froome can continue to express innocence whilst having to take a short ban on the chin....

 

[Wiggo's Package]

I am presuming that the strategy is, that knowing they will never replicate the levels, they are going down Froome's 'point of view' approach. For the fans the headlines will be enough...exactly the same as 'he just lost the fat'...use the media and the academics (or 'usefool fools') to create the narrative.....

Sky can claim that there is enough doubt to maintain the charade that they are clean, they don't need to fire Froome and Froome can continue to express innocence whilst having to take a short ban on the chin....

That's the second line of defence, assuming Froome is banned, trying to keep the fanboys onside, just a PR exercise really

The first line of defence, the legal battle, is Mike Morgan opening multiple fronts on the AAF in the hope that something sticks. So as well a legal/procedural arguments (chain of custody, etc) Morgan also has medical/scientific arguments (kidney malfunction/antibiotics and, on a more fundamental level, trying to undermine the test itself - an approach that worked in Morgan's defence of footballer Mamadou Sahko)

Morgan has no idea if the LADS/ADT will latch onto any of these multiple fronts or whether cumulatively they might sway the judge. The fact that Froome's defence is so exhaustive suggests that Morgan doesn't have an obvious knockout blow. That doesn't mean Morgan isn't going to get the Dawg a free pass, btw. All contentious legal matters have a high degree of uncertainty built in

Incidentally, it's always worth bearing in mind that this matter could have been resolved very quickly if only our hero was able to go into a lab, take a legal dose of salbutamol and repeat the AAF level that tripped the wire

 

[ferryman]

I am presuming that the strategy is, that knowing they will never replicate the levels, they are going down Froome's 'point of view' approach. For the fans the headlines will be enough...exactly the same as 'he just lost the fat'...use the media and the academics (or 'usefool fools') to create the narrative.....

Sky can claim that there is enough doubt to maintain the charade that they are clean, they don't need to fire Froome and Froome can continue to express innocence whilst having to take a short ban on the chin....

That's the second line of defence, assuming Froome is banned, trying to keep the fanboys onside, just a PR exercise really




The first line of defence, the legal battle, is Mike Morgan opening multiple fronts on the AAF in the hope that something sticks. So as well a legal/procedural arguments (chain of custody, etc) Morgan also has medical/scientific arguments (kidney malfunction/antibiotics and, on a more fundamental level, trying to undermine the test itself - an approach that worked in Morgan's defence of footballer Mamadou Sahko)

Morgan has no idea if the LADS/ADT will latch onto any of these multiple fronts or whether cumulatively they might sway the judge. The fact that Froome's defence is so exhaustive suggests that Morgan doesn't have an obvious knockout blow. That doesn't mean Morgan isn't going to get the Dawg a free pass, btw. All contentious legal matters have a high degree of uncertainty built in

Incidentally, it's always worth bearing in mind that this matter could have been resolved very quickly if only our hero was able to go into a lab, take a legal dose of salbutamol and repeat the AAF level that tripped the wire

I think if LADS have referred this on to the next stage, they a) were confident of their case and b) most likely took legal advice themselves from a higher source (trust me from a previous life this happens more than you might think).

 

[Wiggo's Package]

I am presuming that the strategy is, that knowing they will never replicate the levels, they are going down Froome's 'point of view' approach. For the fans the headlines will be enough...exactly the same as 'he just lost the fat'...use the media and the academics (or 'usefool fools') to create the narrative.....

Sky can claim that there is enough doubt to maintain the charade that they are clean, they don't need to fire Froome and Froome can continue to express innocence whilst having to take a short ban on the chin....

That's the second line of defence, assuming Froome is banned, trying to keep the fanboys onside, just a PR exercise really




The first line of defence, the legal battle, is Mike Morgan opening multiple fronts on the AAF in the hope that something sticks. So as well a legal/procedural arguments (chain of custody, etc) Morgan also has medical/scientific arguments (kidney malfunction/antibiotics and, on a more fundamental level, trying to undermine the test itself - an approach that worked in Morgan's defence of footballer Mamadou Sahko)

Morgan has no idea if the LADS/ADT will latch onto any of these multiple fronts or whether cumulatively they might sway the judge. The fact that Froome's defence is so exhaustive suggests that Morgan doesn't have an obvious knockout blow. That doesn't mean Morgan isn't going to get the Dawg a free pass, btw. All contentious legal matters have a high degree of uncertainty built in

Incidentally, it's always worth bearing in mind that this matter could have been resolved very quickly if only our hero was able to go into a lab, take a legal dose of salbutamol and repeat the AAF level that tripped the wire

I think if LADS have referred this on to the next stage, they a) were confident of their case and b) most likely took legal advice themselves from a higher source (trust me from a previous life this happens more than you might think).

I can imagine there's all kinds of back traffic on a case like this!

Btw, what do you mean by "higher source"?

Counsel's opinion? One of the ADT judges? (But not the one chosen I would hope)

 

[ferryman]

I am presuming that the strategy is, that knowing they will never replicate the levels, they are going down Froome's 'point of view' approach. For the fans the headlines will be enough...exactly the same as 'he just lost the fat'...use the media and the academics (or 'usefool fools') to create the narrative.....

Sky can claim that there is enough doubt to maintain the charade that they are clean, they don't need to fire Froome and Froome can continue to express innocence whilst having to take a short ban on the chin....

That's the second line of defence, assuming Froome is banned, trying to keep the fanboys onside, just a PR exercise really




The first line of defence, the legal battle, is Mike Morgan opening multiple fronts on the AAF in the hope that something sticks. So as well a legal/procedural arguments (chain of custody, etc) Morgan also has medical/scientific arguments (kidney malfunction/antibiotics and, on a more fundamental level, trying to undermine the test itself - an approach that worked in Morgan's defence of footballer Mamadou Sahko)

Morgan has no idea if the LADS/ADT will latch onto any of these multiple fronts or whether cumulatively they might sway the judge. The fact that Froome's defence is so exhaustive suggests that Morgan doesn't have an obvious knockout blow. That doesn't mean Morgan isn't going to get the Dawg a free pass, btw. All contentious legal matters have a high degree of uncertainty built in

Incidentally, it's always worth bearing in mind that this matter could have been resolved very quickly if only our hero was able to go into a lab, take a legal dose of salbutamol and repeat the AAF level that tripped the wire

I think if LADS have referred this on to the next stage, they a) were confident of their case and b) most likely took legal advice themselves from a higher source (trust me from a previous life this happens more than you might think).

I can imagine there's all kinds of back traffic on a case like this!

Btw, what do you mean by "higher source"?

Counsel's opinion? One of the ADT judges? (But not the one chosen I would hope)

A lawyer is a lawyer (solicitor in Scotland), but yes we would take QC advice on particularly complex situations. It's not as expensive as you may think and not always in your favour (despite how you may put your case to them!!)

 

[Wiggo's Package]

I am presuming that the strategy is, that knowing they will never replicate the levels, they are going down Froome's 'point of view' approach. For the fans the headlines will be enough...exactly the same as 'he just lost the fat'...use the media and the academics (or 'usefool fools') to create the narrative.....

Sky can claim that there is enough doubt to maintain the charade that they are clean, they don't need to fire Froome and Froome can continue to express innocence whilst having to take a short ban on the chin....

That's the second line of defence, assuming Froome is banned, trying to keep the fanboys onside, just a PR exercise really




The first line of defence, the legal battle, is Mike Morgan opening multiple fronts on the AAF in the hope that something sticks. So as well a legal/procedural arguments (chain of custody, etc) Morgan also has medical/scientific arguments (kidney malfunction/antibiotics and, on a more fundamental level, trying to undermine the test itself - an approach that worked in Morgan's defence of footballer Mamadou Sahko)

Morgan has no idea if the LADS/ADT will latch onto any of these multiple fronts or whether cumulatively they might sway the judge. The fact that Froome's defence is so exhaustive suggests that Morgan doesn't have an obvious knockout blow. That doesn't mean Morgan isn't going to get the Dawg a free pass, btw. All contentious legal matters have a high degree of uncertainty built in

Incidentally, it's always worth bearing in mind that this matter could have been resolved very quickly if only our hero was able to go into a lab, take a legal dose of salbutamol and repeat the AAF level that tripped the wire

I think if LADS have referred this on to the next stage, they a) were confident of their case and b) most likely took legal advice themselves from a higher source (trust me from a previous life this happens more than you might think).

I can imagine there's all kinds of back traffic on a case like this!

Btw, what do you mean by "higher source"?

Counsel's opinion? One of the ADT judges? (But not the one chosen I would hope)

A lawyer is a lawyer (solicitor in Scotland), but yes we would take QC advice on particularly complex situations. It's not as expensive as you may think and not always in your favour (despite how you may put your case to them!!)

Thanks, understood

IME you'd need a QC well versed in sports doping litigation to make the exercise worthwhile. And with Froome having spent $1m+ on legal fees the binders would be daunting!

Again IME counsel's opinions almost always favoured the side paying for it (a cynic might suggest the QC has an eye on more work down the line!). And usually came with many qualifiers (more understandable given how unpredictable litigation can be)

Slight digression but in Froome's case there have been suggestions (can't recall the source now) that LADS were referring elements of the case to the ADT while LADS still had jurisdiction. That seems odd if true but of course we don't know the context or the details

 

[Merckx index]

There are some real empirical problems for Heuberger et al. Sporer et al. studied 37 subjects—the largest pool in any salbutamol study testing the WADA limits that I’m aware of—took urine samples after 1 hour, and none was > 1000, not even close (highest was 831). The same group also performed another study of 8 subjects, taking samples at 30m and 1 hr, and again, no samples > 1000. That’s 53 samples with none > 1000, whereas Heuberger’s model predicts there should be eight. The probability of getting none in a pool that size would be about one in five thousand.

http://sci-hub.tw/10.1097/JSM.0b013e3181705c8c
https://sci-hub.tw/10.1249/mss.0b013e3181591df7

There’s also a total of 187 samples from seven studies, including the two Sporer ones, in which urine samples were taken at 4 hr or sooner, and only 3 were > 1000. That would be roughly consistent with the 3% Heuberger et al predict for four hours, except that almost 30% of these are the aforementioned 1 hr samples, and another 20+% of these samples were taken after two hours. Though Heuberger doesn’t report what the model predicts for that time, it would probably be in the range of 5-10%. So one would predict more than a dozen samples in this pool should be > 1000.

The biggest problem with Heuberger’s study is that they don’t provide essential information. They say that the 15.4% value is shown in Fig. 3, but it isn’t. All Fig. 3 shows is the predicted mean value of salbutamol concentration, and the 99.9% limits. This information, alone, is not enough to allow one to tell what % of samples will be > 1000, 1200, or any other arbitrary level. My guess from what Fig. 3 does show is that the predicted one hour values are very sensitive to small changes in conditions or parameters, and that they have overestimated the difference between 1 hr and 4 hr levels. In fact, the mean values at those times are virtually identical.

I assume that when the paper is actually published, the details will be provided in an Appendix. While they’re at it, they should also correct the glaring error in the first paragraph, in which they state that the 800 ug dose is the maximum allowed with a TUE, and that Froome had a TUE. I guess not being aware that no TUE has been required for salbutamol up to that level for several years is at least evidence that they aren’t too close to Froome and his team.

 

[70kmph]

Froomes defence for a failed PK test:

"While the results of a pharmacokinetic study would seem to clear Froome, the study from British Journal of Clinical Pharmacology claimed that based on their simulations a large number of trials could be needed to trigger the same result in any one individual, a process the researchers claimed would be ‘expensive and time consuming’."

http://www.cyclist.co.uk/news/4723/what-the-newest-salbutamol-study-means-for-froome

 

[TubularBills]

Re:

There are some real empirical problems for Heuberger et al. Sporer et al. studied 37 subjects—the largest pool in any salbutamol study testing the WADA limits that I’m aware of—took urine samples after 1 hour, and none was > 1000, not even close (highest was 831). The same group also performed another study of 8 subjects, taking samples at 30m and 1 hr, and again, no samples > 1000. That’s 53 samples with none > 1000, whereas Heuberger’s model predicts there should be eight. The probability of getting none in a pool that size would be about one in five thousand.

http://sci-hub.tw/10.1097/JSM.0b013e3181705c8c
https://sci-hub.tw/10.1249/mss.0b013e3181591df7

There’s also a total of 187 samples from seven studies, including the two Sporer ones, in which urine samples were taken at 4 hr or sooner, and only 3 were > 1000. That would be roughly consistent with the 3% Heuberger et al predict for four hours, except that almost 30% of these are the aforementioned 1 hr samples, and another 20+% of these samples were taken after two hours. Though Heuberger doesn’t report what the model predicts for that time, it would probably be in the range of 5-10%. So one would predict more than a dozen samples in this pool should be > 1000.

The biggest problem with Heuberger’s study is that they don’t provide essential information. They say that the 15.4% value is shown in Fig. 3, but it isn’t. All Fig. 3 shows is the predicted mean value of salbutamol concentration, and the 99.9% limits. This information, alone, is not enough to allow one to tell what % of samples will be > 1000, 1200, or any other arbitrary level. My guess from what Fig. 3 does show is that the predicted one hour values are very sensitive to small changes in conditions or parameters, and that they have overestimated the difference between 1 hr and 4 hr levels. In fact, the mean values at those times are virtually identical.

I assume that when the paper is actually published, the details will be provided in an Appendix. While they’re at it, they should also correct the glaring error in the first paragraph, in which they state that the 800 ug dose is the maximum allowed with a TUE, and that Froome had a TUE. I guess not being aware that no TUE has been required for salbutamol up to that level for several years is at least evidence that they aren’t too close to Froome and his team.

I belive in MI.

Doubt him at your peril.

 

[Cloxxki]

Getting close to my usual summer asthma season and still breathing freely. Went for a group run today, 12-13kph, 98kg dry. Untrained other than relatively tame bike communiting.

What do you asthma wussies do to aleviate symptoms without going for the lazy drugger's first choice?

 

[Merckx index]

If Froome receives a ban, expect a lot of talk about how he might have accidentally inhaled too much salbutamol, but he couldn’t have benefitted from it. Experts will cite studies showing that inhaled salbutamol doesn’t have performance enhancing effects. This is not strictly true, however. Most inhaled salbutamol—up to 60-80%--is not deposited in the lungs; it’s swallowed. IOW, using an inhaler is actually a form of oral dosing, and if one inhales enough, there is certainly the potential for performance enhancement.

Studies of inhaled salbutamol have generally used doses within the range of the allowed amount, 800 ug. Inhalation of 800 is equivalent to taking an oral dose of about 0.5 mg, which is relatively little. It’s because of these low doses, not because of inhalation per se, that performance enhancing effects are usually not seen. I’ve seen one study where there was no effect on performance of 1600 ug inhaled, but the researchers looked for an immediate benefit, performance in a 5 km time trial. There might be effects over longer periods, so I would not rule out the possibility that inhaled salbutamol, even within the required limits, might have some benefit. Keep in mind also that with a TUE, athletes can use a nebulizer, which provides much higher doses.

 

[movingtarget]

Re:

If Froome receives a ban, expect a lot of talk about how he might have accidentally inhaled too much salbutamol, but he couldn’t have benefitted from it. Experts will cite studies showing that inhaled salbutamol doesn’t have performance enhancing effects. This is not strictly true, however. Most inhaled salbutamol—up to 60-80%--is not deposited in the lungs; it’s swallowed. IOW, using an inhaler is actually a form of oral dosing, and if one inhales enough, there is certainly the potential for performance enhancement.

Studies of inhaled salbutamol have generally used doses within the range of the allowed amount, 800 ug. Inhalation of 800 is equivalent to taking an oral dose of about 0.5 mg, which is relatively little. It’s because of these low doses, not because of inhalation per se, that performance enhancing effects are usually not seen. I’ve seen one study where there was no effect on performance of 1600 ug inhaled, but the researchers looked for an immediate benefit, performance in a 5 km time trial. There might be effects over longer periods, so I would not rule out the possibility that inhaled salbutamol, even within the required limits, might have some benefit. Keep in mind also that with a TUE, athletes can use a nebulizer, which provides much higher doses.

I think inhaled gives little benefit at any time except for temporarily stopping the wheezing in other words bringing the lungs back to normal not improving their performance above the average non asthmatic. The so called inhaled amount was impossible anyway and that much inhaled would have stopped benefiting the user as well as giving them a much increased heart rate from my own experience. Doctors realize that constant Ventolin use is pointless and useless without the preventers which should stop excess Ventolin use anyway. The only time Ventolin use should increase is if the user had a cold or flu or worse. Exercise induced asthma is helped by a puff before the exercise and maybe one or two during it depending on the length of the exercise but having 10 or 20 puffs isn't going to increase performance. If you were inclined to reach for the Ventolin that often you wouldn't be exercising anyway. Ventolin is very short term in benefit, it's the preventers which do the longer term job. Becotide, Pulmicort etc.......moderate wheezing means you will need Ventolin every two hours or more maybe if exercising, still nowhere near the level Froome had in his system. The weight loss benefits I can't comment on but only elite athletes might notice the difference in that area and how effective it actually is.

 

[Merckx index]

Froome’s argument, as far as I can tell, hinges on a claim that a) peak urinary salbutamol levels occur within one hour of inhaling the substance (Heuberger’s theoretical model); and b) he inhaled the maximally allowed amount of 800 ug within one hour of the finish on stage 18, where he tested positive. With regard to a), the model estimates that roughly 7-8% of the time that 800 ug is inhaled (my estimate from the figures Heuberger actually published) within one hour of providing a sample, the concentration in the urine will exceed the 1430 ng/ml value that is Froome’s 2000 ng/ml, corrected for a urine specific gravity of 1.028. I’ve already pointed out that the studies that look at salbutamol concentrations at this time don’t support this, but let’s ignore this for the moment, to follow the rest of the argument.

With regard to b), Froome has claimed he took 2-3 puffs after the stage was over. He would further have to argue that he took 5-6 puffs within an hour of the end of the stage. If you look at the stage, it wasn’t considered that difficult. There was a steep climb at the finish, but it was fairly short, not a typical long climb that might result in large time gaps between contenders. In fact, an hour from the finish, Froome was almost to the top of a preceding climb, and after that, there was a long descent, followed by a gradual climb, and finally the short, steep climb at the end. So it would not appear to be the kind of stage that would require an unusual amount of salbutamol, given that he has said he only takes it during “great efforts”. He did imply, of course, that he suffered an unusually severe attack that day, but even if we accept this, it doesn’t suggest that he would have taken 5-6 puffs in the final hour, as opposed, e.g., to taking some of it earlier in the race.

But let’s assume he did. Now I pointed out that there are several studies indicating that inhaling 800 ug, followed by providing a sample one hour later, does not in fact result in the high levels claimed by Heuberger, et al. But Froome himself might be used to test this notion. If he generally takes salbutamol only during “great efforts”, one would expect his highest urinary salbutamol levels would come following mountain top finishes. Not only would they require the greatest efforts, but since they come at the end of the stage, they would soon be followed by providing a sample. The inhaled drug would be at peak concentration, and because the finish is so close, he presumably wouldn’t be urinating, which would reduce the concentration in a subsequent sample.

How many such finishes has Froome recorded? Looking just at the six GTs that he has won, I counted 32 mountain top finishes which he either won and/or completed while in the leader’s jersey, which would ensure he would be tested. I would think that in many if not all of those finishes, he would take a substantial amount of salbutamol within an hour or two of being tested. If the variation is as great as Heuberger claims, some of those samples ought to have pretty high salbutamol levels. Maybe Froome never took 800 ug before, but the model is certainly capable of predicting the pattern of variation expected from a fewer amount of puffs. But it doesn’t appear that the variation was that great. Not only has Froome never exceeded the decision limit for salbutamol before—unless he somehow was able to convince UCI that there was an innocent explanation—but IIRC, it was reported that none of his other Vuelta samples exceeded 600 ng/ml.

So though I would have to see more data, I’m guessing that Froome’s own samples are not going to support the model very well. If they don’t, then along with the published studies—not to mention the theoretical problems with Heuberger’s study—I don’t see how the argument will succeed. An argument based on large variation has to show more than one outlier.

 

[Robert5091]

If I was the judge here, I'd say tell me everything Froome took from the day before (when Froome seemed "dead on his bike") until he gave the sample. An overnight transformation from losing time to taking time from GC guys. This was not "doing a Landis" like this years Giro, but it's the same scenario.

Salbutamol? Yeah, and ...