Risk Genes and Lung Cells

[al]

Can't find the original source , it's out there if you want to search.



Researchers Reveal Link Between COPD Risk Genes and Lung Cells


It has long been a mystery: Why do breathing difficulties develop in one out of five smokers? What puts these smokers at risk for development of chronic obstructive pulmonary disease (COPD), the third-leading killer of Americans, while 80 percent seem to be protected against the damaging effects to airways of trillions of oxidants and chemicals in each cigarette puff?

A biological link between four genes known to be associated with COPD and lung function may explain the development of the disease.
Image courtesy of Dr. Ronald Crystal

Genetics plays a role, but one that has remained enigmatic — until now. In a study in the Feb. 3 issue of PLoS ONE, a team of researchers at Weill Cornell Medical College has discovered a biological link between genes known to be associated with COPD and lung function that may explain both the development of the disease and the disparate respiratory effects of cigarettes on their users.

They found, when comparing genetic expression between healthy smokers and non-smokers, that four genes previously associated with COPD are being abnormally expressed in the airway basal cells, the progenitor cells critical to airway function. These genes were among the 676 genes the researchers found were either being over- or under-expressed in the basal cells lining the airways in smokers. These basal cells are crucial to the health of the lung, and the first cells that show damage from smoking.

"This is the first demonstration of COPD risk genes to an actual mechanism within cells that are critical for the maintenance of lung health," says Dr. Ronald G. Crystal, chairman of genetic medicine at Weill Cornell Medical College. "We doubt these four genes are completely responsible for COPD. They are likely part of the story — we believe they play a central role in the very early events that lead to COPD, but they act within a very complex genetic-environment interaction."

The researchers also found that not every smoker had the same level of abnormal expression in the four COPD risk genes (as well as in many of the other genes whose expression differed), which may explain inherited susceptibility to COPD.

"We believe that smoking reprograms basal cells, making some smokers with a certain genetic variant more susceptible to COPD, but we don't know the details yet," Dr. Crystal says. "We are now studying how the basal cells are disordered by smoking."

Basal cells make up 5 to 15 percent of the cells that line the branching airways of the lungs, as well as the windpipe. They contain the critical stem cells that produce the other three kinds of cells that make up, and clean, that protective sheath. "The basal cells replace cells in that lining that are injured or that die, so without them, your lungs will become sick," Dr. Crystal says.



Dr. Ronald G. Crystal


"These abnormal biologic changes are going on in the lungs of smokers who appear to be healthy, but whose lungs show evidence of massive reprogramming," says the study's senior investigator," Dr. Crystal adds.

For this study, the researchers studied 10 non-smokers as well as 10 smokers. Both groups were judged to have healthy lungs, based on chest X-rays, lung function tests and the lack of symptoms of breathing difficulty. Using fiberoptic bronchoscopy — a thin, tube-like instrument threaded through the nose or mouth into the lungs — the scientists sampled the lining of the airway in both groups, retrieving basal cells deep in the lungs.

They then sequenced the genome of these cells, looking at genetic expression of messenger RNA — the molecule each gene makes to produce proteins. The researchers found 676 genes that produced aberrant levels of messenger RNA in smokers. "Smoking essentially reprograms basal cells to have an output of messenger RNA that is different from that of non-smokers," Dr. Crystal says.

To their surprise, they found that 166 genes (25 percent) were found in chromosome 19, known to be home to genes linked to COPD. And in the precise location of these risk genes — an area known as 19q13.2 — 13 aberrantly expressed genes were discovered. Four of these genes were previously linked to development of COPD.

When the science is further defined, the researchers may be able to find targets for potential drug therapy that could protect at-risk smokers against COPD.

"It may be possible to protect basal cells from the toxic effects of cigarette smoke if you shield them in some way, perhaps by shutting off, or modifying the output, of certain genes," Dr. Crystal says.

Posted February 4, 2014 9:30 AM | Permalink to this post

[David]

I have always felt like Genetics has a lot to do with which smoker gets it and which ones don't.
Now that my generation has many years of smoking behind them, I know many people who don't have Emphysema and very few that do.


Here is the link to what you posted. Thanks for posting the article.

weill.cornell.edu/news/news/2014/02/researchers-reveal-link-between-copd-risk-genes-and-lung-cells.html

[skate4life]

Thanks Al for posting this very interesting article! I have asked this question for years and could never get a concrete answer. "If smoking causes COPD, then WHY don't all smokers get COPD. There is still much to learn. I personally feel there is a systemic (other body parts) inflammation factor at play too.

[stoker55]

I agree with all of the above and also believe that environmental atmosphere is a large contributing factor. However I have not seen any scientific studies on this. After discussing my situation with the pulmy specialist we both came to the conclusion that my smoking (of course #1 fatctor) and the fact that I lived through Mt. St. Helen's when I lived in WA 30 miles as the crow flies from the blast. We were not allowed to leave the town of Packwood for 3 weeks unless we had breathing problems. I really wanted to leave but was not manifesting symptoms at that time so could not leave until the ban was lifted. We could not even see 3 feet in front of us and could not keep the ash out of anything. I really think that it would be interesting for someone to do a scientific research project on that area in realtionship to genes and environmental attributes of those still there.

[David]

My story I have told in here is a good example of why they don't care how one gets COPD in the USA. It's easy to blame cigarettes and look for nothing else. I am not saying cigarettes are ok. They are not. But 30 years ago the Doctor and I was ready to run a test on why I was allergic to something in crude oil and the Government forbid it. That really burnt me up at the time. It showed me they don't want to look for any answers.

Another incident I learned about in the 90's was how the Government hid facts about Emphysema in Kuwait when all those oil wells was set on fire. How the droplets of crude oil was all in the air and everyone was breathing it. I saw some paper work on how the animals like cattle and sheep was getting Emphysema from it. I will try and find the link. The people was hurt also and so was our troops but the government kept that secret as much as they could.

I hate to say it but looks like to me there is a whole lot that goes on behind closed doors that we don't know about.

Cigarette companies have been giving individual States money for years and years. States spend it recklessly and none of it reaches the people who need it.

[David]

Here is the link if anyone is interested.

OIL FIRES,

PETROLEUM AND GULF WAR ILLNESS

by Craig F. Stead

www.penfield-gill.com/presentations/CDCall-final.htm

[al]

Stoker55,

I find it very curious that you were not to leave for 3 weeks; I would think they would want everyone out of the area to prevent any further health possibilities.



David ! I read some of the report; There are many cover'ups in this country.
I feel for the generations ahead . Looks like a totalaterian government,- we're half way there now.
Thanks for finding the link !

[David]

Yeah, now I am curious why Stoker55 couldn't leave? That had to be horrible breathing that junk.

Al, the part of the article that interested me was B. OIL RAIN. The Lipoid pneumonia. Lipoid pneumomnia can be a progressive disease which continues to reduce lung capacity long after the exposure to the petroleum ceases. Effectively, lipoid pneumonia can lead to a progressive emphysema.

That may be what happened to me.

[stoker55]

It was Marshal Law they locked us down and they would not let anyone in but army and police. They did allow anyone over the passes or the bridge; everything was walked over by military. I have no idea to this day why that was but it made me very angry because I really wanted to leave.