WEDNESDAY, Jan. 18 -- Smoking activates certain genes and portions of the immune system, which in turn causes inflammation that leads to emphysema.

So say researchers who mapped the destructive path from smoking to the debilitating lung disease in mice.

"Previously, emphysema was thought to be a nonspecific injurious response to long-term smoke exposure," study author Dr. Farrah Kheradmand, a professor of medicine and immunology at Baylor College of Medicine, said in a college news release. "These studies show for the first time that emphysema is caused by a specific immune response induced by smoke."

She and her colleagues spent more than four years unraveling how smoking leads to emphysema. They exposed mice to conditions that closely simulated how humans smoke. The mice developed emphysema within three to four months, and certain inflammatory cells and genes were crucial in the process, Kheradmand said.

"It is a combination of little genes affected by an epigenetic factor," she said.

Epigenetic factors affect the way genes are expressed after DNA forms, the release noted. One environmental epigenetic factor is cigarette smoke.

"DNA is written in pen. Epigenetics is written in pencil," Kheradmand said. "If you have enough genes affected by epigenetic factors strung together, it can tip you over into lung damage and emphysema. The inflammation that drives emphysema could also drive cancer development, a testable hypothesis that we have begun to pursue."

The findings appear online Jan. 18 in the journal Science Translational Medicine.

While studies involving animals can be useful, they frequently fail to produce similar results in humans.

-- Robert Preidt

SOURCE: Baylor College of Medicine, news release, Jan. 16, 2012

But Vitamin D Supplementation May Reduce COPD Flare-ups in People With Severely Low Levels

By Denise Mann
WebMD Health News

Reviewed by Louise Chang, MD

Jan 16, 2012 -- Much hope has been pinned on vitamin D to cure, prevent, or treat a host of diseases, including the lung disease chronic obstructive pulmonary disease (COPD).

New research, however, may dash some of this enthusiasm for people with COPD, an umbrella name for chronic lung diseases, including chronic bronchitis and emphysema. People with COPD often experience a worsening of their breathlessness and other symptoms (exacerbations) throughout the course of their disease.

But vitamin D doesn't seem to reduce the number of these exacerbations. That said, vitamin D did benefit a small group of 30 people in the study who had severely low vitamin D levels when the study began.

The new findings appear in the Annals of Internal Medicine.

Low Vitamin D Levels and COPD

Vitamin D is often referred to as the sunshine vitamin because our bodies produce it when exposed to sunlight. The Institute of Medicine recommends that people aged 1 to 70 take in 600 international units (IUs) of vitamin D per day, and people older than 70 should aim for 800 IUs. Some foods like fish and fortified dairy and juice products are rich in vitamin D, but supplements are also used to raise blood levels.

The new study included 182 people with COPD. Participants orally received 100,000 IU of vitamin D or an inactive placebo monthly for a year. There were 468 exacerbations during the study period, and there was no difference in the numbers between the different groups. There were also no differences in time to the first exacerbation between those who received vitamin D and those who did not.

People who took vitamin D did not report greater improvements in their quality of life or the number of times they were hospitalized for COPD, the study shows. Vitamin D also had no bearing on their lung function and risk of death.

However, in looking at a small subset of people with severely low vitamin D, the rate of exacerbations decreased among people who received vitamin D, the study showed. But the researchers note that the number of people in their study with severely low vitamin D was very small, so future studies to look at a possible benefit from vitamin D in people with severely low vitamin D levels need to be done to support the findings.

Screen for Low Vitamin D in COPD

Screening people with COPD for low vitamin D makes sense, says researcher Wim Janssens, MD, PhD, of the University Hospitals Leuven in Leuven, Belgium. "Be aware that vitamin D deficiency is prevalent in COPD and that it needs supplementation for bone health reasons," he says in an email. Vitamin D helps the body absorb calcium, which is important for bone health.

"Severe deficiency of vitamin D levels ... may even increase the COPD exacerbation rate and needs therefore aggressive supplementation," he says. But "don't think that supplementation will cure your disease."

Barry Make, MD, agrees. He is a pulmonologist at National Jewish Health in Denver. "The study suggests that going forward maybe we should study preventing exacerbations in people that have low vitamin D levels," he says.

His bottom line? "Vitamin D is important to measure and if it is low, it makes sense to supplement," he says.

Adam Wanner, MD, is a pulmonologist at the University of Miami Miller School of Medicine. He says the jury is still out on what role vitamin D supplements have, and in which COPD patients. "There were no benefits in terms of exacerbations in the study, but when they looked at the subset of those who had severe vitamin D deficiency, there was a benefit," he says. "This is an important study in the sense that it helps us design future studies."

The results of the study are in the eye of the beholder, says Michael Holick, MD, PhD. He is the director of the Vitamin D, Skin, and Bone Research Lab at Boston University. Holick has been championing vitamin D for years.

"Vitamin D has benefit above and beyond bone health," he says. "There was a significant benefit for those people in the study who were most deficient."

SOURCES: Michael Holick, MD, PhD, director of Vitamin D, Skin, and Bone Research Lab, Boston University, Boston.Lehouck, A. Annals of Internal Medicine, 2012.Barry Make, MD, pulmonologist, National Jewish Health, Denver.Wim Janssens, MD, PhD, University Hospitals Leuven in Leuven, Belgium.Adam Wanner, MD, pulmonologist, University of Miami Miller School of Medicine, Miami.

20-Year-Long Study Finds No Decline in Lung Function for Occasional Pot Smokers

By Brenda Goodman, MA
WebMD Health News

Reviewed by Laura J. Martin, MD

Jan. 10, 2012 -- Woodstock generation, breathe easy. One of the largest and longest studies ever to look at the effect of marijuana smoking on lung health finds that pot smoking doesn't appear to cause chronic breathing trouble.

The study has followed more than 5,000 young adults in four cities for more than two decades. More than half of the people in the study reported smoking tobacco, marijuana, or both.

Over time, researchers repeatedly checked two measures of lung function: One was a test that measured the amount of air forcefully exhaled in a single second. The second test measured the total amount of air exhaled after taking the deepest possible breath.

Those tests help doctors diagnose chronic, irreversible breathing problems like chronic obstructive pulmonary disease (COPD).

Cigarette smoking is a leading cause of COPD. And marijuana smoke contains many of the same chemicals as tobacco smoke.

As more states legalize marijuana -- 16 states and the District of Columbia now allow its medical use -- experts have worried that the kinds of lung damage caused by cigarettes could also be brought on by pot smoking.

Indeed, cigarette smokers in the study saw their lung function drop significantly over 20 years.

But that didn't happen to people who only smoked marijuana.

In fact, the study found that the lung function of most marijuana smokers actually improved slightly over time.

'These Are Not the Cheech and Chongs of the World'

A healthy adult man can blow out about a gallon of air in one second, says researcher Stefan Kertesz, MD, an assistant professor of medicine at the University of Alabama at Birmingham.

Pot smokers, on average, were able to blow out that gallon of air plus about 50 milliliters.

"That's roughly one-sixth of a size of a can of soda," Kertesz says. "It's not anything anybody would notice."

The results do have to be put into the proper context, though.

Most marijuana users in the study were light smokers. "These are not the Cheech and Chongs of the world," Kertesz says.

The average number of times a person using marijuana in the study said they lit up was two to three times per month.

But even in regular users, researchers say they still saw no evidence of breathing problems.

In fact, researchers estimated that lung capacity would stay slightly elevated even if a person had smoked as much as a joint a day for seven years, or two to three joints a day for three years.

The study is published in the Journal of the American Medical Association.

Marijuana Smoking May Stretch the Lungs

But researchers are quick to say that the small improvement seen in this study may have more to do with the way people smoke marijuana -- by taking and holding deep breaths -- than it does with any actual benefit of the drug.

And although they didn't find any long-term breathing problems associated with occasional pot smoking, it has been linked to some short-term irritation.

"Marijuana does irritate airways, and certainly anyone who's heard someone cough after smoking marijuana knows that," says Kertesz. "Is this actually a real benefit to lung health? Probably not."

What's more, there was some evidence that very heavy users -- those who smoked the equivalent of a joint a day for 40 years or lit up more than 25 times a month -- might lose lung function.

But because the number of heavy users in the study was small, researchers say they aren't sure whether those trends are valid or not.

Kertesz says the study should reassure people who smoke the drug for medical reasons.

But he says the study doesn't mean marijuana is safe. It was narrowly focused on lung function. It didn't look at other possible dangers like cancer.

"One study about one aspect of [lung] function is simply a small part of the puzzle of figuring out what the impacts of this substance are," Kertesz says.

Experts agree that the study shouldn't be a reason for people to light up.

"This is a well-designed, well-described study," says Jeanette M. Tetrault, MD, an assistant professor of medicine at Yale School of Medicine in New Haven, Conn.

"The jury is still out about smoking marijuana, especially with heavy smokers and long-term chronic use," says Tetrault, who has reviewed the health effects of smoking marijuana on the lungs but was not involved in the current study. "There are a lot of studies that are conflicting."

Advice to Patients

Donald P. Tashkin, MD, medical director of the pulmonary function laboratory at the David Geffen School of Medicine at UCLA, has spent his career studying the health effects of marijuana.

He says this study is helpful because it was relatively large and followed people for a long time, which gives him confidence in the results.

"The main thrust of the paper has confirmed previous results indicating that marijuana in the amounts in which it is customarily smoked does not impair lung function," he says.

His own study of heavy, habitual marijuana smokers -- people who smoked the equivalent of a joint a day for 50 years -- found no harmful effect on lung function.

But he says none of these studies should be taken as the last word.

Other experts agree.

Barry J. Make, MD, co-director of the COPD program at National Jewish Health in Denver, says it can take years and even decades for the lungs to become so damaged by smoking that it would affect airflow, the measure of lung function used in the study.

"It's doesn't mean that there isn't more damage that you can't see with these tests," says Make.

Until more is known, experts say if you are using the drug, it might be safer not to smoke it.

"The smoke in marijuana contains thousands of ingredients, many of which are toxic and noxious and have the potential, at least, to cause airway injury," Tashkin says. "In an ideal world, it would be preferable to take it in another form."

SOURCES: Pletcher, M, Journal of the American Medical Association, published Jan. 11, 2012.News release, Journal of the American Medical Association.ProCon.org: "Medical Marijuana."Stefan Kertesz, MD, assistant professor of medicine, division of preventive medicine, University of Alabama at Birmingham.Jeanette Tetrault, MD, assistant professor of medicine, Yale University, New Haven, Conn.Donald P. Tashkin, MD, emeritus professor of medicine, medical director of the pulmonary function laboratory, David Geffen School of Medicine, University of California at Los Angeles.Barry J. Make, MD, co-director of the COPD program, National Jewish Health, Denver, Colo.

MONDAY, Jan. 9 -- Scientists who have started to identify genes and pathways associated with lung cancer in people who have never smoked say it's a first step in the potential development of new treatments.

Never-smokers -- people who've smoked fewer than 100 cigarettes over a lifetime -- account for about 10 percent of lung cancer cases.

But this group of lung cancer patients hasn't been studied as much as smokers who develop lung cancer, according to Timothy Whitsett, a senior postdoctoral fellow in the cancer and cell biology division at the Translational Genomics Research Institute in Phoenix.

He and his colleagues conducted genetic analyses on three female patients with adenocarcinoma of the lung, a form of non-small cell lung cancer. One was a never-smoker with early-stage disease, one was a never-smoker with late-stage disease and one was a smoker with early-stage disease.

"In the never-smoker with early-stage cancer, there were very few mutations in the genome, but when we looked at the whole transcriptome, we saw differences in gene expression," Whitsett said in a news release from the American Association for Cancer Research.

The never-smoker with late-stage disease had mutations in what Whitsett called "classic tumor-suppressor genes." It's possible that mutations of the tumor-suppressor genes may be a factor in late-stage lung cancer in never-smokers, the researchers said.

The tumors in both never-smokers lacked alterations in common genes associated with lung cancer, such as EGFR, KRAS and EML/ALK translocations. This suggests that these patients are ideal cases for the discovery of new mutations associated with lung adenocarcinomas in never-smokers, according to Whitsett and colleagues.

The study was slated for presentation Monday at an AACR/International Association for the Study of Lung Cancer joint conference on lung cancer, held in San Diego.

"This is the starting point. We certainly have a lot of pathways and gene expression alterations that we're going to be very interested in confirming and looking at in larger cohorts of patients," Whitsett said.

He and his colleagues are now validating these findings in a larger group of never-smokers and smokers with lung adenocarcinoma.

Because the current study was presented at a medical meeting, the data and conclusions should be viewed as preliminary until published in a peer-reviewed journal.

-- Robert Preidt

SOURCE: American Association for Cancer Research, news release, Jan. 9, 2012