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All About Salbutamol

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What will the verdict in Froome's salbutamol case?

He will be cleared
43
34%
3 month ban
4
3%
6 month ban
15
12%
9 month ban
24
19%
1 year ban
16
13%
2 year ban
21
17%
4 year ban
3
2%
 
Total votes : 126

16 Dec 2017 13:03

Froome is lying if he sticks to his puffer story. Ventolin in puffer form only offers temporary relief so if he took a huge amount of spray the night before or before the race the effect would have worn off before the stage started or early in the stage which is why the average asthmatic is allowed to take 12 puffs per day or so as the standard dosage when wheezing.You have to keep taking it. Froome would have been puffing throughout the stage and even then a certain amount would be lost as he is taking it while exercising which means the dosage would have to be extremely high and the use of the puffer would have been noticeable to his team mates and other riders and if you really need that much in a short period of time then as an asthmatic you are not in any sort of shape to do what Froome normally does. If he sticks to this story he doesn't have a leg to stand on because it's impossible to inhale that much and have those types of results just from using a puffer. The only other explanations are that the testing is flawed or he has used other means to get that much Ventolin in his system but I still wonder if he would get much benefit from an injection or tablets as the Ventolin effect of opening the airway wears off quite quickly and doesn't last for long before you need more.
movingtarget
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Re:

16 Dec 2017 14:11

ClassicomanoLuigi wrote:"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!
Alpe73
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16 Dec 2017 14:43

Concur, microdose using the pill stay under the 1000 threshold and you are safe from triggering a positive, you can say I have asthma and as a cover story use the inhaler. You will get the benefit of anabolic Salbutermol increased strength, weight loss- just don't make a mistake during a race with your levels !
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Re: Re:

16 Dec 2017 15:00

Alpe73 wrote:
ClassicomanoLuigi wrote:"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!


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.

If the Froome case were to come down to the clinical chemistry, such that additional tests could be performed on the samples, then... nowadays it appears that oral vs. inhaler administered salbutamol could be discriminated. Proof of the use of salbutamol tablet or injection would make all the huffing-and-puffing on inhalers moot.

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
ClassicomanoLuigi
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Re: Re:

16 Dec 2017 15:02

Alpe73 wrote:
ClassicomanoLuigi wrote:"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.
SOLO LA VITTORIA È BELLA
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16 Dec 2017 19:46

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
«Sky helped for the GC, so did BMC - a lot of teams tried but one rider isn't enough. Not against De Gendt. He's like 10 riders.»
Oude Geuze
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Re:

16 Dec 2017 20:23

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?

Yes, what was the motive ? That's a question that has left a lot of people stumped. Since the Stage 18 of the Vuelta was not among the most difficult, and Froome and the team would not have seen it as being especially critical. In 2014, Froome was quoted as saying he took more salbutamol in advance of "big efforts", meaning according to his own admission, his use of the drug was situational.

One thing that occurred to me is that Froome could also have taken some other drug which interferes with the metabolism of salbutamol - such that that the real motive was some hidden substance, but tripped him up on the salbutamol accidentally. By prolonging the half-life of a large dose. But reading through lists of drug-drug interactions with salbutamol, I couldn't find anything that would block / compete for the metabolic pathways to that extent. Just does not seem likely at all. And especially not any drugs that would be useful for doping, among major known interactions.

Therefore, what happened why would they do this in the first place? Since Froome was certain to 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..

Somehow, these athletes are dosing up to levels I find hard to imagine... how it is possible without becoming disabling... maybe as you said, athletes on habitually high dosage develop tolerance to the drug, making the side-effects more acceptable.
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16 Dec 2017 20:36

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.
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Re:

16 Dec 2017 23:05

Oude Geuze wrote: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.
movingtarget
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Re: All About Salbutamol

16 Dec 2017 23:10

ClassicomanoLuigi wrote:
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.

Oude Geuze wrote: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.
Last edited by Merckx index on 17 Dec 2017 01:20, edited 4 times in total.
Merckx index
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16 Dec 2017 23:34

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.
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Re: All About Salbutamol

17 Dec 2017 01:23

Merckx index wrote: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)
hazaran
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17 Dec 2017 02:06

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
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Re: All About Salbutamol

17 Dec 2017 04:50

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
Merckx index
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17 Dec 2017 11:33

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
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17 Dec 2017 12:42

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
User avatar sittingbison
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17 Dec 2017 12:51

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.
heartsnotinit
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Re:

17 Dec 2017 13:23

Oude Geuze wrote:...
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!!
User avatar sittingbison
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17 Dec 2017 13:37

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.
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Re:

17 Dec 2017 13:59

Rollthedice wrote: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 its fat loss and other performance enhancing properties OOC. One has to take 2 week cycles of taking pills to have the desired effect, similar to clenbuterol.

This. Have to agree this is the most likely motive and scenario. The aerobic benefit in a given event is not really why these athletes are abusing the asthma drugs. There can be individuals who have various degrees of innate or exercise-induced asthma, who then exaggerate the severity, in order to use more of the drugs, as PED.
An explanation which fits the profile is: taking salbutamol as tablets for years, while making a public show of using the inhalers ("Look, everyone, I've got asthma ! See, I need this PED and I'm going to flaunt it, without a TUE"). As a cover story for the more hardcore use.
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.

Whether it is really helping their immediate aerobic performance or not, the dopers will tend to like the sensation of taking salbutamol, and feel as if they are missing something if they are not on their habitual dose. And maybe get the idea that "more is better", even if they have already maxxed out any in-competition benefit. Also, Froome said in 2014 that he would take more of his salbutamol in anticipation of some "big effort"... he sees it not as a standard maintenance dose for a medical condition, but as performance-related, according to the race situation.

Nearing the end of the GT stage race, with the Tour-Vuelta 'double' becoming ever-more likely... not feeling very well on the morning of September 7... but the Vuelta is almost in the bag... got too excited, and took some salbutamol tablets without calculating the total dose. Maybe something like that.
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