Research shows lasting effects of smoking after quitting

Here is a link to the study and the associated press release.

https://www.nature.com/articles/s41586-023-06968-8

https://pasteur.fr/en/home/press-area/press-documents/smoking-has-long-term-effects-immune-system

I followed both, due to some interest in this study, and some curiosity over our all-important yet complicated immune system to have a ‘memory’ of past exposure. And these researchers link long-term effects of smoking on such immune responses, to be linked to differences in/on DNA inside an apparent addition of a member of the methyl group. With the potential to modify the expression of genes involved in immune cell metabolism. Thus changing the way a the genome is read in the cell.

But I keep coming back to several things. Both admitted limitations. That I just keep coming back to.

First one is “the absence of a replication cohort to validate these findings.”

The other: “our analyses were conducted on a population of similar genetic background.”

Specifically: 1,000 healthy donors “of the same genetic background (Western European) . . . restricted to individuals whose parents and grandparents were born in Metropolitan France.” With “no history or evidence of severe, chronic or recurrent [disease],” and also no “pregnant and peri-menopausal women.”

But also no “recent use of drugs, recent vaccine administration and recent use of immune modulatory agents.”

So there! It is proper to present all, for readers to be able to weigh and determine for themselves, what they think of this study and it’s implications.

Many thanks.

So there! It is proper to present all, for readers to be able to weigh and determine for themselves, what they think of this study and it’s implications

The requirement for not use of drugs, no recent vaccination and no use of modulatory agents (as well as most of the other negative requirements for recruiting volunteers) are quite standard and necessary to eliminate background noise when examining immune response, if anything this indicate that the study has taken proper care of confounding factors that could reduce the implications of the study, making it more reliable. That would not be a limitation but an advantage.

What is smoking and what is quitting? It's not really clear. It's obvious that 20 or ten a day is smoking but is there some level of smoking that makes no difference over and above, say, the background pollution you may inhabit? It could be one a day or one a week or one a month or one a year. Have you quit if you smoke once a year? Once a month?

@ virusrex.

Well, your comments are, as usual, insightful and helpful for readers. And you have helped inspire inside of me several areas of inquiry over the selection process in this study, along the line with with reducing variables.

First, no mention of the subjects’ exposure to passive smoking [secondhand smoke exposure], a Group 1 carcinogen. Which we have indications for their potential mutagenic properties, plus an overall tumor mutational burden remains largely unknown. Anyone who has ever visited France is well aware of ubiquitous presence of secondhand smoke exposure. And the compounds implicated in this study being widely found within secondhand smoke (https://www.ncbi.nlm.nih.gov/books/NBK219569/).

We also come to environmental factors, such air pollution. Which we understand to be a factor leading to various diseases, for various reasons, but also now understood to be implicated in negatively affecting the body’s immune system. Metropolitan France is a big place, with variables as to pollutants.

Next is dietary intake of common anti-mutagenic foods and drinks. Some of which are frequently found on French plates on a regular basis. And have acknowledged impacts on the body’s immune system. Leading us, naturally, to alcohol. Specifically wine. And not at a level of “abuse” of any type, but mearly adult background intake. Whose mutagenic, anti-mutagenic, and cytotoxic properties remain little understood. But implicated in a negative manner towards overall impact on the immune system. And has a presence which is also ubiquitous inside French society. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165118/). And https://www.researchgate.net/publication/276149194_Antimutagenic_and_immunomodulatory_properties_of_quercetin_glycosides_Antimutagenicity_and_immunomodulation_of_quercetin_glycosides.

Remains to be outlined how much was factored in, surrounding all of the above. But if you can suggest to us with confidence that researchers meticulous enough to eliminate all other “confounding factors,” (including meds and vaccines) would have certainly done so for the above, then I, at least, will need to agree with you. But this study, either way, still remains an interesting read for those interested in immune responses.

What is smoking and what is quitting? It's not really clear. It's obvious that 20 or ten a day is smoking but is there some level of smoking that makes no difference over and above, say, the background pollution you may inhabit? It could be one a day or one a week or one a month or one a year. Have you quit if you smoke once a year? Once a month?

Based on the article, the more you smoke, the more your body starts to learn to adapt. Are you probably ok if you have one cigarette a year? Probably, but you're still inserting foreign pollutants and chemicals into your body, so you could be unlucky and get a genetic mutation (cancer) from that one cigarette. Extremely unlikely, but not impossible. If you smoke one cigarette a month, are you ok? Probably. But again, you're upping your odds of something going wrong. If you smoke one cigarette a day are you ok? Maybe - some people smoke their entire lives and are fine.

I don't think there are people actively trying to figure out the 'safe line' for tobacco. I think the idea is that the only real safe amount of tobacco is none, and after that, you're increasing your risk.

First, no mention of the subjects’ exposure to passive smoking [secondhand smoke exposure], a Group 1 carcinogen. Which we have indications for their potential mutagenic properties, plus an overall tumor mutational burden remains largely unknown

There is no mention because the study is using a cohort already investigated so they only make a short description of the parameters of inclusion/excusion, the original study:

https://www.sciencedirect.com/science/article/pii/S152166161400271X?via%3Dihub

...mentions how second-hand smoke exposure can be inferred by statistical methods and used to reach conclusions specific for this group, the present study is focused on the two bigger categories.

We also come to environmental factors, such air pollution

Which can be uncontrolled, which is not the same as different between the groups. Unless a relationship can be made between smoking and exposure to other environmental factors it is not justified to just assume there must be a difference, recruitment bias may be another source of difference but the methods followed in the construction of the original cohort do not seem to indicate this as likely. Pollution can have an effect, but it would come independently from the effect of smoking.

Next is dietary intake of common anti-mutagenic foods and drinks

This is already considered inside the possible sources of selection bias that were accounted for in the original article, together with survivor bias, alcoholic consumption, professional exposure, etc. So it is natural to assume any bias between groups would be reduced below significant levels and the conclusions of the populations studied able to be generalized without problem.

I can understand having an interest on many other factors that can affect immunity or tobacco related pathology, but to be fair this study is focused specifically on one category of consequences, so it is understandable they eliminated as much as possible all other variables (even if important) just to be able to have a conclusion about this outcome in particular.

Almost all the men smoke at my company. It reeks.

Secondary smoke exposure is no joke. Get out of that company, David.

Gave up smoking over 50 years ago. Many things I have done wrong, but giving up smoking was not one of them.

By the way, I still love cigarette smoke. I just try to avoid it.

Never liked Cigs, hated the smell, and smoked once or twice and that was enough for me, never understood the fascination with cigs, and wouldn't even date a woman who smokes. When I first came to Japan, it was a miserable time for me the first few years because so many people smoked, I didn't go out as much in those days, glad to see fewer and fewer people not smoking that crap anymore.

Secondary smoke exposure is no joke. Get out of that company, David.

Absolutely, just the worst.