All About Salbutamol

[King Boonen]

Re: Re:

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.

The converse of this supposition is also relevant. Suppose he did have exercised induced asthma and began taking salbutamol which corresponded with his transformation. It's not going to explain the zero to hero transformation, but it might explain why he was suddenly able to perform.

As to whether WADA cares, I would doubt they know which riders are using salbutamol and whether they have asthma. Testing is blind, so a lab is only going to report an AAF if there is one. I can't imagine WADA collect all the data, de-anonymise it, collate it and check back against medical records to work out if people are using it, especially as it's still up in the air about whether it's a worthwhile PED or not.

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?

Frankly yes, it is hard to understand as we are talking about salbutamol, something any cyclist can use within the threshold limit. Him using it is hardly a smoking gun. Do you happen to know that every other high profile cyclist does/does not use salbutamol? I think it's really easy to see why very few people would waste the time and resource chasing something up that would likely lead to a non-story. Now it is a big story and I'm sure many are chasing it up. The fact that Froome hasn't done what Callum Skinner did would indicate, to me at least, that prior diagnosis and TUEs don't exist, but we'll have to wait and see. But honestly, I really don't think it's curious and I can understand why journalists wouldn't chase it. After all, Kimmage didn't, did he? You'd think if anyone was going to then he would.

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?

Again, this links back to the second point. It's possible that was when he was diagnosed with it. This also might come down to procedure, how the TUEs are registered and what Fancy Bears actually hacked. If it was only WADA then it would only be people who are part of the testing pool for each sport I think. Was Froome part of this in 2008/2009? Barloworld were pro-conti, I'm not sure if they were included at that level. If that's the case then it's likely any TUE was only held by the UCI and his NADO, if he had one.

Journalists will want to know now, I'm sure many are desperately trying to find that information. But back in 2014 I don't think they would have bothered.

 

[King Boonen]

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.

Do we know how long it took for him to give a sample at doping control? It's not unheard of for it to take some time for an athlete to need to pee. Maybe they realised they'd stuffed up and told him to do that in an attempt to cover it? Maybe they've told him recently to say he did that in an attempt to obfuscate?

 

[veganrob]

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.

Do we know how long it took for him to give a sample at doping control? It's not unheard of for it to take some time for an athlete to need to pee. Maybe they realised they'd stuffed up and told him to do that in an attempt to cover it? Maybe they've told him recently to say he did that in an attempt to obfuscate?

Maybe. Is it also possible they told him not to drink any fluids after stage to appear dehydrated and increase concentration of drug?

 

[King Boonen]

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.

Do we know how long it took for him to give a sample at doping control? It's not unheard of for it to take some time for an athlete to need to pee. Maybe they realised they'd stuffed up and told him to do that in an attempt to cover it? Maybe they've told him recently to say he did that in an attempt to obfuscate?

Maybe. Is it also possible they told him not to drink any fluids after stage to appear dehydrated and increase concentration of drug?

I think the opposite would be the case if they knew. If you think he’s going to test high you’ll want to do everything you can to bring it down to something that can be explained. Maybe pretend you don’t need a pee, neck loads of water then hang in as long as possible.

 

[Merckx index]

The converse of this supposition is also relevant. Suppose he did have exercised induced asthma and began taking salbutamol which corresponded with his transformation. It's not going to explain the zero to hero transformation, but it might explain why he was suddenly able to perform.

You mean that like the alleged schisto, asthma was holding him back until he started getting treatment for it? I guess that’s plausible, except if he had asthma all his life, as he claims, why wouldn’t he have been taking it throughout his cycling career? At least with schisto he claimed that he didn’t know he had it for a long time, whereas he claims always to have had asthma and known it. That being the case, it seems to me that the correlation of salbutamol with the transformation only works if he never had asthma, or such a mild form that it wasn’t really a problem in races.

Frankly yes, it is hard to understand as we are talking about salbutamol, something any cyclist can use within the threshold limit. Him using it is hardly a smoking gun. Do you happen to know that every other high profile cyclist does/does not use salbutamol? I think it's really easy to see why very few people would waste the time and resource chasing something up that would likely lead to a non-story.

I guess I just don’t agree with you that it would take a lot of time and resources to confirm that. See below.

Now it is a big story and I'm sure many are chasing it up.

Then how come there isn’t any information? How long does it take a journalist to find this out? Can’t someone ask Froome if he has a picture of himself using an inhaler during a race? Or to name a doctor who will confirm he has been treating Froome for the condition (as he did with schisto?) Or can’t someone ask WADA if he filed a declaration use form when joined Sky in 2010? I can’t believe that something this cut-and-dried can’t be confirmed or denied in very quick order.

It isn’t just that this information hasn’t been provided by anyone, so far. I haven’t seen a single mention of its importance in the ton of stories on Froome that have come out since the AAF was made public. Not a single journalist I’m aware of has given the slightest indication that s/he doesn’t take Froome’s word on this, despite the web of false statements he has made in the past with regard, e.g., to schisto, where the so-called facts are constantly being changed. Many of these journalists now freely admit they question whether Froome is clean, which of course means they question whether he's telling the truth. If you have doubts about his claims he's never taken more of this drug than the allowed amount, why wouldn't you also have doubts that he had asthma all along? I'm not saying he did or didn't, I'm saying it should be far easier to settle this question than how he came to have such a high level.

Again, this links back to the second point. It's possible that was when he was diagnosed with it. This also might come down to procedure, how the TUEs are registered and what Fancy Bears actually hacked. If it was only WADA then it would only be people who are part of the testing pool for each sport I think. Was Froome part of this in 2008/2009? Barloworld were pro-conti, I'm not sure if they were included at that level. If that's the case then it's likely any TUE was only held by the UCI and his NADO, if he had one.

OK, that’s an example of what might be a simple explanation, appreciated. That might be why FB didn’t see anything earlier. But when Froome joined Sky in 2010, he would have had to file a declaration of use form to use salbutamol. There should be a record of that. Maybe FB found it and didn’t think it was a big deal. But even if that’s the case, it should be easy enough to verify.

 

[Craigee]

to make things less complicated. Has anyone tested twice the allowed limit and got off? If not they have to be consistent don't they? Also all these excuses for Froome's high readings such as the dehydration thing or the using of the puffer after the race and not peeing for a long time? Why is there no history of this happening previously? Surely common sense will be used at some point. Yes the bringing in of the allowed limit at 1000 may have come in just a few years ago but that's a long time in pro cycling, the king sport of the world for doping. So why is there no history of the excuses being thrown around for Froome and salbutamol? Salbutamol would be used a lot in cycling. It will probably be used more than ever now if cyclists think it's helped Froome with his success.

 

[King Boonen]

Re:

You mean that like the alleged schisto, asthma was holding him back until he started getting treatment for it? I guess that’s plausible, except if he had asthma all his life, as he claims, why wouldn’t he have been taking it throughout his cycling career? At least with schisto he claimed that he didn’t know he had it for a long time, whereas he claims always to have had asthma and known it. That being the case, it seems to me that the correlation of salbutamol with the transformation only works if he never had asthma, or such a mild form that it wasn’t really a problem in races.

No, I mean he was doping but maybe that's when he started using salbutamol and it allowed him to perform. It's just supposition and unlikely. Maybe it was never really bad enough to allow for a TUE so when it went open to all he tried it or Sky decided he should along with everything else.

I guess I just don’t agree with you that it would take a lot of time and resources to confirm that. See below.

Now it is a big story and I'm sure many are chasing it up.

Then how come there isn’t any information? How long does it take a journalist to find this out? Can’t someone ask Froome if he has a picture of himself using an inhaler during a race? Or to name a doctor who will confirm he has been treating Froome for the condition (as he did with schisto?) Or can’t someone ask WADA if he filed a declaration use form when joined Sky in 2010? I can’t believe that something this cut-and-dried can’t be confirmed or denied in very quick order.

Again, a photo is extremely unlikely for any rider so I think that's a non-starter. As to naming doctors he might have or he might have been told not to. They might have the info so have decided not to bother printing it until they have finished other work. It's not that long since it came out and no-doubt he's been told to pretty much say nothing. Anyway, we were talking about 2014 and before, not since the AAF.

It isn’t just that this information hasn’t been provided by anyone, so far. I haven’t seen a single mention of its importance in the ton of stories on Froome that have come out since the AAF was made public. Not a single journalist I’m aware of has given the slightest indication that s/he doesn’t take Froome’s word on this, despite the web of false statements he has made in the past with regard, e.g., to schisto, where the so-called facts are constantly being changed. Many of these journalists now freely admit they question whether Froome is clean, which of course means they question whether he's telling the truth. If you have doubts about his claims he's never taken more of this drug than the allowed amount, why wouldn't you also have doubts that he had asthma all along? I'm not saying he did or didn't, I'm saying it should be far easier to settle this question than how he came to have such a high level.

As I said, I think the fact he hasn't released any info means it doesn't exist, but the point we were discussing was why this wasn't followed up in 2014 or beforehand. Before the AAF, a cyclist using a perfectly acceptable drug that many cyclists (and other athletes) use is a non-story. They would have had to ring round, get hold of the right people and would likely have been told that's part of his private medical history, he does but you're not getting his records, sod off. They could then try to follow up leads, track down people who might speak and write the article. All they could have printed would be "cyclist uses permitted drug to treat asthma but won't confirm he has asthma". Then if they come out with even a small amount of proof it discredits the journalist in the eyes of the average punter. This is instead of writing articles that have some impact. Chasing down possible doping at Sky yes, but this comes very low down that list before the AAF.

OK, that’s an example of what might be a simple explanation, appreciated. That might be why FB didn’t see anything earlier. But when Froome joined Sky in 2010, he would have had to file a declaration of use form to use salbutamol. There should be a record of that. Maybe FB found it and didn’t think it was a big deal. But even if that’s the case, it should be easy enough to verify.

I don't think it was a form you had to file, I think it was a simple declaration on the doping control form, so unless they got hold of those as well I don't think they would know. If they are kept then yes, that should be easy to verify. You can see the box for prescription meds, supplements on Van Der Poel's form here:

https://twitter.com/mathieuvdpoel/status/823617385211064320/photo/1?ref_src=twsrc%5Etfw&ref_url=http%3A%2F%2Fwww.cyclingnews.com%2Fnews%2Fvan-der-poel-says-riders-should-publish-anti-doping-data-for-transparency%2F

 

[gillan1969]

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.

Do we know how long it took for him to give a sample at doping control? It's not unheard of for it to take some time for an athlete to need to pee. Maybe they realised they'd stuffed up and told him to do that in an attempt to cover it? Maybe they've told him recently to say he did that in an attempt to obfuscate?

Of course this might where you get him....

as is oft pointed out on here, there is no UKAD case for Wiggo and so its the lies that have damned them...here we have a case for the lies to be hung on.....

...if the lies can be teased out the story may get legs with journos...the good doc for example.....have one doc go all sick and silent may be unlucky...having two would be......surely CF would allow some info into the public domain to assure his adoring public...after all these utterances he has made...what was it Armstrong said..."extraordinary proof"

If they thought this would all be an internal matter they may have already damned themselves with UCI...they will, or at least should assuming the conspiracy is not sooooo great, need to keep that story going.....

 

[ScienceIsCool]

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.

Don't forget that the true dosage is based on lung deposition rate and not what was administered. From the photos, he uses a regular inhaler without spacer, so the max deposition rate is ~40%. That means of the three puffs administered, he only would have received a dose of 120 ug, not 300 ug. Possibly less. There is the possibility that some was deposited in the mouth and then swallowed, but that would enter the blood and be metabolized at an even slower rate.

I imagine that most if not all testing with Salbutamol takes special care to measure actual Salbutamol consumption rather than just hand the subjects a puffer.

John Swanson

 

[ScienceIsCool]

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.

Do we know how long it took for him to give a sample at doping control? It's not unheard of for it to take some time for an athlete to need to pee. Maybe they realised they'd stuffed up and told him to do that in an attempt to cover it? Maybe they've told him recently to say he did that in an attempt to obfuscate?

There's definitely a way to find the maximum amount of time that could have occurred between taking the three puffs and the doping control. That's based on some things that we know, such as:

- Riders selected for doping control are met at the finish line by a chaperone that doesn't leave the rider alone until they collect the sample.
- Froome gave a post stage interview, which the chaperone wouldn't have allowed until he had the sample.
- The stage began at 13:14 local time, and the winning time was 4h 10 min, so Froome was met by the chaperone at ~17:25
- Froome gave his interview at 18:34 according to http://www.lavuelta.es/la-vuelta/2017/us/stage-18/news/int/froome-it-s-good-to-bounce-back-again-after-a-difficult-day.html

So there was at most 70 minutes between taking three puffs and when his urine sample was taken.

John Swanson

 

[King Boonen]

Thanks John.

 

[Netserk]

Minus the 10' it took Froome to get to the finish line after the stage winner

 

[yaco]

WADA strongly encourages athletes to fully fill in the doping control form listing any substances they've used in the last 2 weeks. Of course not all athletes fully complete the doping control form when they have doping control - So realistically it's possible the testing agencies would have a history of Froome's use of salbutamol.

 

[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.

Do we know how long it took for him to give a sample at doping control? It's not unheard of for it to take some time for an athlete to need to pee. Maybe they realised they'd stuffed up and told him to do that in an attempt to cover it? Maybe they've told him recently to say he did that in an attempt to obfuscate?

There's definitely a way to find the maximum amount of time that could have occurred between taking the three puffs and the doping control. That's based on some things that we know, such as:

- Riders selected for doping control are met at the finish line by a chaperone that doesn't leave the rider alone until they collect the sample.
- Froome gave a post stage interview, which the chaperone wouldn't have allowed until he had the sample.
- The stage began at 13:14 local time, and the winning time was 4h 10 min, so Froome was met by the chaperone at ~17:25
- Froome gave his interview at 18:34 according to http://www.lavuelta.es/la-vuelta/2017/us/stage-18/news/int/froome-it-s-good-to-bounce-back-again-after-a-difficult-day.html

So there was at most 70 minutes between taking three puffs and when his urine sample was taken.

John Swanson

The time stamp is the time is posted to the site, yes? Not the time he actually gave the interview. If you watch the actual live coverage it is under this time.

 

[Cramps]

Re:

(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.

Doctor interviewed here says salbutamol would be checked routinely.
https://cyclingtips.com/2017/12/certainly-doesnt-look-good-doctor-speaks-froome-case/

"That showing up ten years into a professional career after 100 tests or more is [unusual]. This is one of the substances that is tested for in every test. It is not like some of them where they only test them very now and again. salbutamol levels are checked in every sample that is given."

 

[ScienceIsCool]

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.

Do we know how long it took for him to give a sample at doping control? It's not unheard of for it to take some time for an athlete to need to pee. Maybe they realised they'd stuffed up and told him to do that in an attempt to cover it? Maybe they've told him recently to say he did that in an attempt to obfuscate?

There's definitely a way to find the maximum amount of time that could have occurred between taking the three puffs and the doping control. That's based on some things that we know, such as:

- Riders selected for doping control are met at the finish line by a chaperone that doesn't leave the rider alone until they collect the sample.
- Froome gave a post stage interview, which the chaperone wouldn't have allowed until he had the sample.
- The stage began at 13:14 local time, and the winning time was 4h 10 min, so Froome was met by the chaperone at ~17:25
- Froome gave his interview at 18:34 according to http://www.lavuelta.es/la-vuelta/2017/us/stage-18/news/int/froome-it-s-good-to-bounce-back-again-after-a-difficult-day.html

So there was at most 70 minutes between taking three puffs and when his urine sample was taken.

John Swanson

The time stamp is the time is posted to the site, yes? Not the time he actually gave the interview. If you watch the actual live coverage it is under this time.

Yup! But we can't narrow it any further unless we have better time stamps to work with. I figured an upper limit of an hour was a short enough window as to not warrant much further effort. Less than an hour between puffs and test, which means he was well below peak plasma concentration for that particular dose, let alone urine concentration. So we can safely put to rest that 3 extra puffs after the stage was what caused or even contributed to the AAF.

John Swanson

 

[TheMight]

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.

I'm like Joerg's tweet more and more.

Is there a more simple answser that is plausible? Here is my hypothesis: He uses large amounts of it in the offseason for the anabolic effects, injected. He draws blood during that time and has a fairly sophisticated calendar for use to avoid detection (I know there was a lot of talk about just spinning it down to platelets and dilution and such) Due to his closeness to the double and a bad performance, they modified the protocol and got too aggressive.

Does anyone actually believe that he ingested it via lungs? We can look that the video, I don't recall seeing him houghing up in this race.

 

[hazaran]

I'm like Joerg's tweet more and more.

Is there a more simple answser that is plausible? Here is my hypothesis: He uses large amounts of it in the offseason for the anabolic effects, injected. He draws blood during that time and has a fairly sophisticated calendar for use to avoid detection (I know there was a lot of talk about just spinning it down to platelets and dilution and such) Due to his closeness to the double and a bad performance, they modified the protocol and got too aggressive.

Does anyone actually believe that he ingested it via lungs? We can look that the video, I don't recall seeing him houghing up in this race.

You mention the "talk" but didn't read it? They have 12h intake limits for this stuff because within that timeframe and with regular hydration the vast majority of it is gone from your blood and urine. So please enlighten us as to when this hypothetical blood transfusion took place for it to show up at 2000 ng/ml in the evening.

 

[Merckx index]

Re: Re:

Don't forget that the true dosage is based on lung deposition rate and not what was administered. From the photos, he uses a regular inhaler without spacer, so the max deposition rate is ~40%. That means of the three puffs administered, he only would have received a dose of 120 ug, not 300 ug. Possibly less. There is the possibility that some was deposited in the mouth and then swallowed, but that would enter the blood and be metabolized at an even slower rate.

I imagine that most if not all testing with Salbutamol takes special care to measure actual Salbutamol consumption rather than just hand the subjects a puffer.

This brings up another question. Would Froome or another rider using an inhaler take in consistently the same amount per puff, 40 ug or so? If not—if sometimes more, sometimes less—then wouldn’t he run the constant risk of taking more than allowed amount? If he took in all 100 ug per puff, it would be easy to plan: eight puffs max per twelve hours. But if it’s 40 ug per puff, it would be an average of 20 puffs, but sometimes more and sometimes less. It seems to me that under those circumstances, he would be told to take fewer puffs, as a margin of safety. Then again, even if he went a little over the 800 ug limit, he would still very likely not exceed the 1000 ng/ml threshold.

Doctor interviewed here says salbutamol would be checked routinely.
https://cyclingtips.com/2017/12/certainly-doesnt-look-good-doctor-speaks-froome-case/

Thanks for this link. It’s good that we now know that this is the case. So Froome had fifteen previous tests and three subsequent ones for salbutamol just in the Vuelta, and presumably many more over his career, given the number of days he’s worn a leader’s jersey.

Note that he also dismisses the blood transfusion contamination possibility. Frankly, I would say the possibility of some mistake (mixed up control number of sample) or even intentional spiking by someone who wanted to see Froome busted, is about as likely.

He confirms another important point noted upthread, that at the allowed doses one shouldn’t even be close to the 1000 ng/ml. So as I said before, though Froome’s level was double the allowed limit, it indicates far more than a doubling of the maximum allowable dose.

The portion of the interview in which he estimates the amount of puffs Froome would have to take to reach the 2000 ng/ml level is a little unclear to me. First he says:

It is a little bit hard to say because how much Ventolin you get in depends on how good your inhaling technique is and how long you can hold your breath for. But somewhere between 20-30 puffs would be equivalent to what it is over a 12 hour period.

The “over a 12 hour period” part implies that what he’s talking about here is the amount of puffs that would constitute the maximum allowed level of 800 ug/12 hours. Twenty puffs would correspond to 40 ug/puff, in line with what John said.

But then there is this:

So you are saying that you would need at least 20 puffs to reach double the threshold…

At least that, yes.

Twenty 40 ug puffs would not bring one even close to 2000 ng/ml. So either he misspoke there, didn’t understand the question, or is now assuming 100 ug puff. The latter is also supported by later in the interview, when he says 20 puffs is equivalent to 2.5 mg via nebulizer; and further, when he describes the allowable amount as 8 puffs in 12 hours. But even if this is what he meant, I think that’s an underestimate. As I noted upthread, studies I’ve seen suggest an oral dose of about 8 mg would be needed to produce a level of 2000 ng/ml, on average. For inhaled, it would probably be less, but still more than 20 x 100 ug = 2 mg.

 

[Red Rick]

Yeah I agree that a blood transfusion can't explain the salbutamol positive. That in itself says nothing about it happening or not though

 

[ScienceIsCool]

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.

I'm like Joerg's tweet more and more.

Is there a more simple answser that is plausible? Here is my hypothesis: He uses large amounts of it in the offseason for the anabolic effects, injected. He draws blood during that time and has a fairly sophisticated calendar for use to avoid detection (I know there was a lot of talk about just spinning it down to platelets and dilution and such) Due to his closeness to the double and a bad performance, they modified the protocol and got too aggressive.

Does anyone actually believe that he ingested it via lungs? We can look that the video, I don't recall seeing him houghing up in this race.

Think of it this way. How much alcohol would you have to drink that your blood could make an infused person impaired to the point they can't drive?

Him tripping the wire because of a blood bag is science fiction, not science.

John Swanson

 

[hazaran]

The dehydration study had urine measurements (for 2% body mass loss) of 196.84 +/- 162.93 ng/mL at .8mg inhaled and 1197.58 +/- 1156.35 ng/mL for 1.6mg. That. is. not. a. linear. relationship. Stop extrapolating doses.

(Notice that the study was badly controlled for time between inhalation and measurement, as participants exercised for 50-110 minutes to reach the 2% BM loss and then extra ? minutes till urine was produced. Another study suggests salbutamol concentration in urine peaks at 60 minutes after inhalation. It doesn't matter too much though, since WADA doesn't control for this either and we don't know when Froome took what anyway)

The WADA decision limit classifier is trained for over/under, nothing else. In particular, all sorts of statements akin "you'd have to inhale a boatload" to get 2000 ng/mL are not supported by the available evidence.

But don't despair, I feel we have some more research on this topic incoming!

 

[thehog]

Re:

The dehydration study had urine measurements (for 2% body mass loss) of 196.84 +/- 162.93 ng/mL at .8mg inhaled and 1197.58 +/- 1156.35 ng/mL for 1.6mg. That. is. not. a. linear. relationship. Stop extrapolating doses.

(Notice that the study was badly controlled for time between inhalation and measurement, as participants exercised for 50-110 minutes to reach the 2% BM loss and then extra ? minutes till urine was produced. Another study suggests salbutamol concentration in urine peaks at 60 minutes after inhalation. It doesn't matter too much though, since WADA doesn't control for this either)

The WADA decision limit classifier is trained for over/under, nothing else. In particular, all sorts of statements akin "you'd have to inhale a boatload" to get 2000 ng/mL are not supported by the available evidence.

But don't despair, I feel we have some more research on this topic incoming!

The dehydration study was done at 35 Celsius at 40% relative humidity. Froome was in 20, at 11%. That’s not going to cut it.

 

[hazaran]

Re: Re:

The dehydration study was done at 35 Celsius at 40% relative humidity. Froome was in 20, at 11%. That’s not going to cut it.

Ignore the dehydration, it was just the study that had two fixed doses and gave ranges - unless you can find a hypothesis why the same exact percentage body mass loss in the participants gives this high variability in urine concentration.

If you find the dehydration distracting, try http://sci-hub.tw/10.1097/JSM.0b013e3181705c8c - this has similar crazy standard deviation.

I'm not arguing Froome didn't take too much - the studies support the 1200 ng/ml decision limit for 800 ug inhaled. But the data also makes abundantly clear that you can't just extrapolate from the legal dose to an amount that would yield 2000 ng/ml. A dose that puts one athlete at 2000 ng/ml could very well have another one under 1200, and we haven't identified the confounding factors (neither have the studies). There are a large number of candidates - time between urine and inhalation, amount inhaled in one go vs. spaced out, dehydration, mass, gender, ..

In particular, try not to be *this guy* (and why WADA lets you do a study) :lol:

 

[Merckx index]

Another comment on the blood transfusion scenario. It’s already been rebutted purely on the basis of pharmacokinetics, and there are other problems as well. But the people who are pushing this tend to argue that Froome wouldn’t take large doses of salbutamol during a race, that it would just be used offseason.

Here’s the problem with that. If you take salbutamol during the offseason, then withdraw blood, you either a) separate red cells and freeze them for transfusion during the season, in which case essentially all the salbutamol is removed; or b) store the blood in a refrigerator for a few weeks, then infuse it after another withdrawal. Following b), a rider withdraws fresh blood every few weeks, and immediately replaces it by transfusing previously withdrawn and refrigerated blood, throughout the season.

Do you see the problem? The only way that blood transfused at any time during the season can contain salbutamol is if the rider was using the drug in heavy doses when that blood was withdrawn a few weeks earlier. So the blood transfusion theory—beyond all the other major problems it has—doesn’t even eliminate the need to postulate heavy salbutamol use during the season. It does avoid postulating that Froome was using salbutamol during the Vuelta--give it credit for that--but he would have to be using it shortly before the Vuelta.

It gets even worse. If Froome transfused blood, he surely did it in the Tour as well as the Vuelta. That’s a lot of blood bags needed. It’s doable if he’s withdrawing in the offseason and freezing cells. It’s a problem if he’s withdrawing and transfusing throughout the season. He has to have enough extra bags for both the Tour and the Vuelta, all of which have to be regularly recycled into his system. At a minimum, he needs two bags, one for each GT, if not four, two for each. That means he must withdraw and transfuse more often, since no bag can be stored in the refrigerator for more than a few weeks. In fact, carrying four extra bags wouldn’t be possible, unless he’s withdrawing and transfusing two bags’ worth each time.

So going into the Tour, he must have at least two bags, one of which, which he will not use in the Tour, was withdrawn shortly before the Tour. The other bag he will use during the Tour. After the Tour, when he’s recovering, he has to withdraw again, transfusing the other blood bag. The newly withdrawn bag, if used in the Vuelta, would have to be taken during a period of heavy salbutamol use. Or maybe he withdraws and transfuses again, just before the Vuelta. In that case, the heavy salbutamol use would have to take place then.

Hazaran, in that first dehydration study, while the 2% cohort does not show proportionality from 800 – 1600, the 5% does, for white males, while for white females, it's more the opposite. Since there were just nine of each, one or two outliers could strongly affect the data. I can only add that I have seen many other studies that exhibit an approximate linearity in this dose range. That includes the second article you mention, with 200-400-800 ug studied. And the SDs in that study are not crazy, they’re high, sure, there’s a lot of individual variation, but they’re low enough to support the conclusion that a 2000 ng/ml level would be extremely rare.

Continuing on that other study, the graph you posted is of the corrected values. All the non-corrected values are below 1000 ng/ml. Also, note that "that guy" had dilute, not concentrated urine. His uncorrected value was around 500 ng/ml or a little less. His urine was so dilute that the corrected value was approximately 3x his uncorrected value. No one else in this study was like this. In any case, his situation is not relevant to Froome's, because he would have passed the WADA test easily, since uncorrected values are used.

The authors point this out, but also seem to imply that in a lab test that Froome took to demonstrate he didn't go over the allowable limit, he might be allowed to argue that a corrected value would give him a lower concentration. At the least, I'm sure if he still lost and it went to CAS, he could bring this up.

Also, the peak urine levels were obtained at about an hour. This is very interesting. I had only seen studies where urine was collected after four hours, and wondered how much sooner the drug started to accumulate. This study suggests that those three puffs Froome allegedly took after the stage could contribute significantly to his urine level. They still wouldn't be nearly enough, of course. The maximum value in that study following 400 ug was about 530 ng/ml. (uncorrected)--let's say around 400 ng/ml after 300 ug--and as John noted, Froome probably wasn't inhaling 100 ug with each puff.

Also, of course, Froome presumably was inhaling during the stage. By the rules, he could have taken another 500 ug, or more if one assumes he wasn't inhaling the full 100 ug. But this same study suggests that any salbutamol he took during the stage would contribute relatively less. In the first place, of course, if he urinated after taking it, before the end of the stage, much of it would be lost. But even if he didn’t urinate, this would contribute less, because his volume of urine following several hours would be greater than after just one hour, during which period the excretion into the urine, according to this study, is falling.

This paper does cite two studies in which it's claimed a subject had a very high value in this test. I couldn't find out anything about one of those studies, but here is the abstract of the other:

Beta-2 agonists are on the list of prohibited substances in sport. Salbutamol by inhalation is permitted to treat allergic asthma, and/or exercise-induced asthma or exercise-induced bronchoconstriction. If the level of salbutamol in urine exceeds 1000 ng/mL, the result is considered as a doping violation with an anabolic steroid. We report a case of a track and field athlete who tested well above this limit during a competition. He had a valid therapeutic use exemption for the use of salbutamol by inhalation and he claimed that he never used salbutamol orally. Further studies under controlled application by inhalation showed that this limit was exceeded. We propose that sanctioning bodies in sport should consider this possibility before taking into account a two-year ban for the use of an anabolic steroid.

https://www.ncbi.nlm.nih.gov/pubmed/15377972

From this, we don't know by how much the limit was exceeded, but that other study discussed here also refers to it, and says he had a level of 4000-8000 ng/ml! This must have been an individual with an exceptional metabolism. The problem for Froome, of course, is that he apparently has multiple tests with much lower values. So the argument isn't that no one could possibly have a value this high, it's that such individuals are very rare, and that Froome's past record indicates he isn't one of them.