PEth Dried Blood Spot Testing

[Clearofclouds12344]

Was curious if there has been any talk within the FAA or with the HIMS AME’s about the legitimacy of these particular tests and possible false positives? @bbchien @lbfjrmd

 

[bbchien]

Too much riding for my airmen in a as yet not well vetted test: “Just a career...”

 

[Clearofclouds12344]

Too much riding for my airmen in a as yet not well vetted test: “Just a career...”

That is wise advice.

 

[Kenny Phillips]

Too much riding for my airmen in a as yet not well vetted test: “Just a career...”

I haven't read any papers on this testing as of yet, and there are many different companies offering the test (different versions, or are they all selling the same one?)
If it is proven to be accurate it would be quite useful; I'm interested in the sensitivity (will it pick up that one uses Listerine?)

 

[KeepWatch]

I haven't read any papers on this testing as of yet, and there are many different companies offering the test (different versions, or are they all selling the same one?)
If it is proven to be accurate it would be quite useful; I'm interested in the sensitivity (will it pick up that one uses Listerine?)

No is my understanding. The PEth test is detecting a metabolite that absorbs into the red blood cell membrane. It takes fairly high concentrations, or low concentrations over a long period of time, to get a detectable amount of the metabolite into the red blood cell membrane. Once present at detectable levels in the membrane, the depletion rate is fairly slow which is what allows for such a long detection time after heavy drinking.

I'll provide an anecdotal example: When Covid precautions hit hard in the US, there was a general sense that half the people you interacted with could be infected and not showing symptoms. There was a heavy emphasis on precautions during the first two weeks since that was the supposed incubation period. I carried hand sanitizer in my pocket and was using it probably more than 30X's per day........ basically any time I touched something and more. In the middle of the 2 week period, I had an unannounced EtG/EtS urine test. Guess what, EtS came back with a low positive, EtG negative. Lab determined it inconclusive and HIMS AME agreed apparently. Nevertheless, they immediately ordered a PEth blood test. I had continued use of the hand sanitizer up until the time I received the inconclusive result; the same day as the PEth test. The PEth test came back negative. (Whew!)

It was kind of unnerving to have been doing all the right things and come that close to getting a false positive. Needless to say, I'm much more careful with the frequency of use on hand sanitizer. I only use it after going to the grocery store and gas stations.

This is getting off-topic, I know. I have no idea of the interferences potentially involved in testing dried blood spots.

 

[Clearofclouds12344]

I haven't read any papers on this testing as of yet, and there are many different companies offering the test (different versions, or are they all selling the same one?)
If it is proven to be accurate it would be quite useful; I'm interested in the sensitivity (will it pick up that one uses Listerine?)

No is my understanding. The PEth test is detecting a metabolite that absorbs into the red blood cell membrane. It takes fairly high concentrations, or low concentrations over a long period of time, to get a detectable amount of the metabolite into the red blood cell membrane. Once present at detectable levels in the membrane, the depletion rate is fairly slow which is what allows for such a long detection time after heavy drinking.

I'll provide an anecdotal example: When Covid precautions hit hard in the US, there was a general sense that half the people you interacted with could be infected and not showing symptoms. There was a heavy emphasis on precautions during the first two weeks since that was the supposed incubation period. I carried hand sanitizer in my pocket and was using it probably more than 30X's per day........ basically any time I touched something and more. In the middle of the 2 week period, I had an unannounced EtG/EtS urine test. Guess what, EtS came back with a low positive, EtG negative. Lab determined it inconclusive and HIMS AME agreed apparently. Nevertheless, they immediately ordered a PEth blood test. I had continued use of the hand sanitizer up until the time I received the inconclusive result; the same day as the PEth test. The PEth test came back negative. (Whew!)

It was kind of unnerving to have been doing all the right things and come that close to getting a false positive. Needless to say, I'm much more careful with the frequency of use on hand sanitizer. I only use it after going to the grocery store and gas stations.

This is getting off-topic, I know. I have no idea of the interferences potentially involved in testing dried blood spots.

Not off topic at all. I am in a similar situation but actually had a false positive come back extremely high on the PEth Dried Blood Spot. I couldn’t believe it and my first thought was the amount of hand sanitizer I had been using due to this COVID 19 situation. I had two follow up tests shortly after (PEth intravenous and Nail-Etg) both negative. Jury is still out on what is going on with these tests.

 

[Cap'n Jack]

Not off topic at all. I am in a similar situation but actually had a false positive come back extremely high on the PEth Dried Blood Spot. I couldn’t believe it and my first thought was the amount of hand sanitizer I had been using due to this COVID 19 situation. I had two follow up tests shortly after (PEth intravenous and Nail-Etg) both negative. Jury is still out on what is going on with these tests.

No is my understanding. The PEth test is detecting a metabolite that absorbs into the red blood cell membrane. It takes fairly high concentrations, or low concentrations over a long period of time, to get a detectable amount of the metabolite into the red blood cell membrane. Once present at detectable levels in the membrane, the depletion rate is fairly slow which is what allows for such a long detection time after heavy drinking.

I'll provide an anecdotal example: When Covid precautions hit hard in the US, there was a general sense that half the people you interacted with could be infected and not showing symptoms. There was a heavy emphasis on precautions during the first two weeks since that was the supposed incubation period. I carried hand sanitizer in my pocket and was using it probably more than 30X's per day........ basically any time I touched something and more. In the middle of the 2 week period, I had an unannounced EtG/EtS urine test. Guess what, EtS came back with a low positive, EtG negative. Lab determined it inconclusive and HIMS AME agreed apparently. Nevertheless, they immediately ordered a PEth blood test. I had continued use of the hand sanitizer up until the time I received the inconclusive result; the same day as the PEth test. The PEth test came back negative. (Whew!)

It was kind of unnerving to have been doing all the right things and come that close to getting a false positive. Needless to say, I'm much more careful with the frequency of use on hand sanitizer. I only use it after going to the grocery store and gas stations.

This is getting off-topic, I know. I have no idea of the interferences potentially involved in testing dried blood spots.

Here's some more evidence:
https://www.sciencedirect.com/science/article/pii/S235200781930099X

I suggest using 2-propanol (isopropanol) based hand sanitizers. No ethanol, no phosphatidylethanol.

 

[Bob Noel]

..

I suggest using 2-propanol (isopropanol) based hand sanitizers. No ethanol, no phosphatidylethanol.

and definitely avoid methanol (the FDA has issued warning about some hand sanitizers with methanol)

edit: finally correcting the typos.

 

[jstone]

Here's some more evidence:
https://www.sciencedirect.com/science/article/pii/S235200781930099X

I suggest using 2-propanol (isopropanol) based hand sanitizers. No ethanol, no phosphatidylethanol.

Which stores would I buy that from? I have never come across isopropyl based hand sanitizers in any pharmacy or convenience store.

The Peth test is ridiculous. No one should have to have their blood drawn for any of these tests, way to invasive especially when urine, hair, or nails are available.

 

[Cap'n Jack]

and definitely avoid methenol (the FDA has issued warning about some hand sanitizers with methenol)

It's "Methanol"
I'm not sure why anyone aside from a scammer would use that as it was never listed as being effective. Or they are buying "denatured alcohol" from the same supplier that makes it for the home improvement stores, and I've found that to be mostly methanol.

Which stores would I buy that from? I have never come across isopropyl based alcohol in any pharmacy or convenience store.

The Peth test is ridiculous. No one should have to have their blood drawn for any of these tests, way to invasive especially when urine, hair, or nails are available.

It's also called "rubbing alcohol", and is sold in concentrations from 70% through 90+ percent. Out here, we have denatured ethanol sold as rubbing alcohol, too. I suppose it is a regional thing, so read the label.
Also, try Pharma-C
https://www.amazon.com/gp/product/B...rs-20&linkId=362790893342c0c80d88962f5f7f4212

I think it is cheaper to get the rubbing alcohol and put it on a paper towel.

 

[Tools]

I’m doing a LOT of research on peth testing, would love to hear from anyone with information.

 

[Clearofclouds12344]

I believe there is a major flaw in the Dried Blood Spot Peth Testing method causing multiple false positives. You can read through this thread describing the multiple cases. There is quite a few Pilots, Pharmacists, Doctors, Nurses, Etc that are being affected by this “perfect” test.

https://connect.mayoclinic.org/disc...lchohol-abuse-be-caused-by-physical-conditio/

 

[lab girl]

Was curious if there has been any talk within the FAA or with the HIMS AME’s about the legitimacy of these particular tests and possible false positives? @bbchien @lbfjrmd

PEth testing is a valid form of long time alcohol abuse/use. It is often combined with other alcohol blood biomarking testing such as EtG, EtS, CDT, MCV and some times GGT. More industries are using this as a method of detecting substance abuse, specifically alcohol.

 

[Clearofclouds12344]

PEth testing is a valid form of long time alcohol abuse/use. It is often combined with other alcohol blood biomarking testing such as EtG, EtS, CDT, MCV and some times GGT. More industries are using this as a method of detecting substance abuse, specifically alcohol.

Thanks for the response, I am aware of what these tests are looking at, my question is in the regards of the legitimacy/false positives. A case for a possible false positive would be a Peth test taken via dried blood spot being positive and an intravenous 14 days later showing negative. Also a nail ETG test 25 days later (with a look back window of 90 days) being negative as well. There have also been documented cases of Peth tests taken the same day as coming back negative and positive. Was curious if any AME’s/lab techs that have heard of cases throughout the community or heard anything informal from the FAA about the test.

 

[MacFly]

There can be a wide gulf between alcohol use, alcohol abuse, and alcohol dependence. Increasingly sophisticated lab testing for such things is not necessarily a good thing to have in the hands of a demonstrably overzealous regulatory agency like the FAA aeromedical branch. They are prone to misuse of the tools that they already have and have demonstrated a distinct willingness to throw out the baby with the bathwater when it comes to airman medical certificates.

 

[Tools]

In my case, the FAA plainly acknowledged a false positive. It’s in my records, written by Dr Sager, consulting with Dr Lomangino.

We also have Talbott Recovery acknowledging a false positive in a pilots case.

Dr Skipper flatly acknowledges false positives exist.

It’s starting to sink in... paradigms are a powerful thing to overcome. The first Ford Trimotors were open cockpit as it was assumed you surely couldn’t fly effectively without actually feeling the wind!!

 

[bbchien]

There can be a wide gulf between alcohol use, alcohol abuse, and alcohol dependence. Increasingly sophisticated lab testing for such things is not necessarily a good thing to have in the hands of a demonstrably overzealous regulatory agency like the FAA aeromedical branch. They are prone to misuse of the tools that they already have and have demonstrated a distinct willingness to throw out the baby with the bathwater when it comes to airman medical certificates.

Incorrect. Caution and discretion are needed by the HIMS AMEs. For example, Dr skipper may be trying to drive the stock price. You never know. There ARE some very good ones out there.

One uses good judgement and discrimination to the best of one's ability.

I have a guy who may be drinking. He is getting all 3 of Soberlinks, Urines and Serum Peths....that is my judgement because he seems to be incapable of getting rid of low level positive ethyl sulfates. We shall see.

 

[ThatOtherGuy]

I'll set the stage with what I consider my well researched knowledge of PEth testing. I'm not defending the test, just summarizing what I've learned from a multitude of research papers and my own personal experience.

The test is looking for the presence of a phospholipid in the red blood cycles called Phosphatidyl ethanol (PEth). PEth is formed when an enzyme (PLD) does it's work in the presence of ethanol. Normally PLD utilizes water, but ethanol is more chemically available/active for the reactions performed by PLD and thus the products are modified in solutions containing ethanol.

Unless one can figure out a way to make a significant number of clean red blood cells (which would have it's own medical consequences) there is no "cheating the system". PEth is effectively sequestered in the cell membrane of RBCs until they die and are recycled, or PEth naturally degrades and is removed from the blood.

There are a few isomers of PEth, with the most common one used for testing being PEth 16:0/18:1 (numbers have to do with bond locations and carbon chain lengths in the molecule). Most intravenous testing is using liquid chromatography with tandem mass spectrometry for analysis. A highly sensitive and accurate methodology with a level of detection and quantification well below the cutoffs.

The typical cutoff for a PEth test is 20ng/ml in the U.S. Being above this cutoff indicates "moderate to heavy drinking". Overseas the cutoffs vary and are much higher. It's not uncommon to see cutoffs in the 200 ng/ml range being considered as "excessive drinking". There is not a lot of consensus that the detected level can be used to quantitatively measure the consumption of alcohol due to differences in PEth production and metabolism varying between individuals. The test is intended to qualitatively measure drinking and most specifically detect binge drinking (1-2 isolated heavy drinking sessions) or long term low level consumption of alcohol (1-2 beers per day across weeks).

The general forensic consensus is that a substance is detectable for 5 half lives in the human body. Most research is showing PEth with approximately a 4-5 day half life. This varies by subject, and there does seem to be evidence that half life is effected by the subject's history of drinking. Given this half life, the standard lookback window for the test is accepted to be a maximum of 28 days.

My opinion is that a test administered 2-5 days after a night out of heavy drinking has a high probability of resulting higher than the 20ng/ml cutoff.

Those interpreting the results are admonished that the test is not the end all be all, but should be used as a data point in the overall clinical and behavioral picture of the subject. Of course, many still view the test as the gold standard single point needed to detect undesired alcohol consumption. Additionally, PEth test are considered "laboratory developed tests" and are not "approved" by the FDA. They do not require the FDA to review trials data or research data before being marketed to the public.

The most common methods of testing are intravenous blood draw, or dried blood spot collection. It is possible to test hair or fingernails for PEth, but testing these mediums are much less common and there is little consensus of cutoffs.

Dried blood spot collection is (as demonstrated here) controversial and many believe the test to be prone to false positives. It appears DBS testing was developed by a company (USDTL) with a long history or marketing substance abuse testing. The protocol for DBS collection is fairly specific, and is not always performed by someone with adequate training. Furthermore, the post collection handling of collected samples can vary wildly as they are returned to the lab for analysis.

A little searching will pull up quite a few people that are not happy with USDTL for one reason or another. Those interested can research USDTL and draw their own conclusions.

I have read research that indicated PEth can form in blood samples outside the body (in vitro) if the sample contains ethanol. Were a sample to be collected from someone with alcohol in their system, or were that sample to be contaminated with ethanol it's feasible that elevated PEth levels would result. Remember, bacteria and fungus form alcohol during their normal metabolic proccess. It's not too far of a stretch to think a DBS sample could encounter alcohol producing bacteria or yeasts post or pre collection.

On the intravenous side, it would be highly inadvisable to allow the collecting phlebotomist to use an ETHYL alcohol swab prior to sticking you with the needle. I have not read anything that indicates other alcohols (isopropyl etc) could be an issue, but I would request an alternative sterilization technique just to be safe. Most practitioners should be happy to accommodate the request with iodine or some other agent.

Ironically, one study found that alcoholic's samples were more sensitive to this in vitro phenomenon.

My opinion is PEth testing is a pretty effective tool in assessing a subject's abstinence. The long lookback and high sensitivity make it very difficult for a substance abuser to game the system by timing tests. It also offers those in recovery a tool to prove compliance when some other much less reliable test produces a false positive (think ETG). If requested to take a dried blood spot PEth test I would refuse and offer to take the intravenous test. If I were "forced" to take a DBS, my next stop would for an intravenous one as backup. I'll take my chance with a medical laboratory over the method of administration for the DBS.

Thanks for the response, I am aware of what these tests are looking at, my question is in the regards of the legitimacy/false positives. A case for a possible false positive would be a Peth test taken via dried blood spot being positive and an intravenous 14 days later showing negative.

Assuming the dried blood spot was accurate, this would be a normal result. The additional 14 days provides the donor with 3 more half lives of time before the intravenous test. I would be even more suspicious if the DBS test quantified the PEth level near the 150 ng/ml range as this would give the normal metabolic processes in most donors time to drop the PEth level below the 20ng/ml cutoff.

Also a nail ETG test 25 days later (with a look back window of 90 days) being negative as well.

Nail ETG has a well documented high false negative rate. I've seen plenty of studies that put it around 70% accurate in catching someone drinking at best. Most of that 70% are those that are either drinking consistently or binging repeatedly during the lookback window. There's a delay between consumption of alcohol and ETG making it into the nail matrix. Some place this delay at up to 3 weeks, some claim it's much sooner. Either way it's not instant. There's also still quite a bit of controversy over just what the nail cutoffs should be for various substances.

There have also been documented cases of Peth tests taken the same day as coming back negative and positive. Was curious if any AME’s/lab techs that have heard of cases throughout the community or heard anything informal from the FAA about the test.

That would definitely indicate a problem with the testing. Assuming different samples (DBS and whole blood), different labs, and the same cutoff values I would accept the whole blood intravenous test as the more accurate result in this case.

 

[ThatOtherGuy]

There can be a wide gulf between alcohol use, alcohol abuse, and alcohol dependence. Increasingly sophisticated lab testing for such things is not necessarily a good thing to have in the hands of a demonstrably overzealous regulatory agency like the FAA aeromedical branch. They are prone to misuse of the tools that they already have and have demonstrated a distinct willingness to throw out the baby with the bathwater when it comes to airman medical certificates.

To be clear, I don't want anyone flying that is bona-fide actively substance dependent, or abusing and putting others at risk.

I somewhat agree with your sentiments. I don't see the the issue isn't so much the tools or even the use of the tools themselves, it's the FAA's definition of the problem. They have a view of substance abuse and dependence that is not in alignment with the modern understanding of the problem. More specifically, they're so black and white and arbitrary with criteria that way too many people are getting lumped into these buckets. Some for behavior that wouldn't even be considered dysfunctional by societal or other medical standards. I'm sorry, but I don't believe that the guy who's managed some form of physical injury after a few beers twice in his life is automatically a "substance abuser".

I also have a real problem with their stance that the FAA doesn't tell you how to treat a condition, and they don't request testing based on medical necessity. They request testing/documentation because they want empirical evidence that you're healthy, and the treatment you're receiving from doctors of your choosing is effective. That's the SOP. That is, UNLESS it's substance dependence/abuse. Then they're effectively acting as treating physician supervisors from afar, mandating what treatment you should receive and who you should receive it from. It's a very enlightening view into what could become as we allow more of the government into the our non-aviation related healthcare.

 

[Tools]

Bravo! Well written and objective. If only the doctors involved in using this had half your understanding... THAT is the problem.

The FAA has SIGNIFICANT culpability. But doctors have the “last clear chance” to avoid the wreck. If they only enforced proper medical protocol rather than folding to faulty administration, which I admit is hard, but ain’t that just life?

Mitigate the problem, we will eventually fix problems in the FAA with, albeit expensive and time consuming, appeals to the NTSB.

HIMS was likely well in the “helped more than it hurt” by safe margins range for years, now I’m not so sure. I have very clear first hand knowledge of MANY whom have had lives, families and careers ruined by it. This was never the intent... To go forward with the “this is how we’ve always done it” philosophy is ignorant.

I screwed up and got myself here. I don’t need to be here, but that’s administration for ya... I have pledged EVERYTHING I have to leave it better than when I found it. EVERYTHING. This PETH testing is the first step. I’m here to tell you something is FLAT wrong. I know that with 100% certainty. But that’s the rub, in my situation I’m the ONLY one who could. Come Hell or high water I’m gonna prove what’s happening so at least this can’t happen to someone else who can’t fight this hard.

 

[Tools]

Oh... your last sentence is SCARY but true... wow!

 

[jbarrass]

...Then they're effectively acting as treating physician supervisors from afar, mandating what treatment you should receive and who you should receive it from...

This summarizes the problem with FAA med far more broadly than just HIMS. There should be far more deference to treating physicians (or at least to their designees) who actually examine their patients. To me, it's actually unethical for a bureaucratic physician to proscribe treatments or tests that they admit are medically unnecessary just because they can.