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People with HIV at Increased Risk of Debilitating Lung Disease

, by Emily Land

lungsTrailing only behind heart disease and stroke, chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the world and in the U.S.  Yet public awareness about this debilitating lung disease is low. Many people either have never heard of it, aren’t aware of how to prevent it, or don’t know how severe its symptoms can be. It’s a growing concern especially for people aging with HIV—who appear to be more likely to get COPD and may experience a faster decline if they do get it.

“In the early days of the AIDS epidemic, the lung was clearly a focus and a leading area of research because patients were presenting with things like Pneumocystis pneumonia,” said Ken Kunisaki, MD, a pulmonary disease specialist at the Minneapolis Veterans Affairs Health Care System. “With better HIV treatments, we don’t see much of that anymore. But now as patients are aging, two big concerns are COPD and lung cancer. In the long-term, being aware of the non-infectious lung complications of HIV—like COPD and lung cancer—will enable us to help people with HIV age successfully.”

COPD is a catch-all name for progressive lung disease—encompassing conditions like emphysema and chronic bronchitis—that prevents a person from breathing and exhaling air normally from the lungs. People with COPD experience symptoms like shortness of breath, wheezing, chronic coughing and fatigue.

Jan Karlbon (Credit: American Lung Association in Arizona)

Jan Karlbon (Credit: American Lung Association of Arizona)

“It’s like somebody put duct tape over your mouth and your nose, and someone cut a little hole, and you’re breathing through a straw,” said Jan Karlbon, in a video created by the American Lung Association of Arizona. “Something as simple as getting dressed can wear me out. There’s some nights when I can cook a meal, there are times that I can’t. Something as easy as boiling a pot of water to make spaghetti—by the time I get the water from the sink to the stove—can have me short of breath.”

In the general population, the prevalence is 6.3%, with 12.7 million people diagnosed with COPD and almost twice that (24.1 million) estimated to have impaired lung function. A few studies that have compared people living with HIV to HIV-negative people have found that the rates of COPD are higher among people with HIV.

The majority of this risk probably comes from cigarette smoking—the leading cause of COPD—since a higher percentage of people with HIV smoke compared to the general population. But Kunisaki says the difference extends beyond behavior.

“When studies control for history of smoking, it does look like patients with HIV are at a higher risk of developing COPD,” he explained.

One large-scale observational study with over 1,500 veterans found that HIV infection was a risk factor for COPD even after adjusting for smoking, and that veterans with HIV were between 50 and 60% more likely to have COPD than HIV-negative veterans. Another study found that 16% of people with HIV and no history of smoking developed emphysema—a rate the researchers say is much higher than what would be expected among non-smokers.

Alison Morris and colleagues, in a review published in Proceedings of the American Thoracic Society, speculate that the effects of HIV, “particularly as individuals with HIV age and experience longer exposures to HIV” compound and interact with risk from smoking—leading to increased COPD risk.

Kunisaki explained that inflammation may be at the heart of this increased risk. It has been well-established that people with HIV experience chronic, long-lasting inflammation—a damaging over-reaction of the body’s immune system—at higher rates. And this happens even when people are being successfully treated with ART. Because COPD is associated with an abnormal inflammatory response, localized in the lungs, it is possible that HIV might contribute to this—stimulating the COPD-caused inflammation and worsening its effects.

Other researchers are investigating the possible causative roles of factors like the gut microbiome, antiretrovirals, oxidative stress, and respiratory infections. “Right now, we don’t understand exactly why people with HIV may be at a higher risk of COPD [when the difference in cigarette smoking is accounted for]. There’s a lot of different theories, and no clear mechanism yet. But there’s a lot of work going on in this area,” said Kunisaki.

Viral load also may play a role. In an analysis of participants in the AIDS Linked to the Intravenous Experience (ALIVE) study, which included over 1,000 people who were followed for a median of 7.1 years, people with higher viral loads experienced faster lung function decline than people with lower viral loads—independent of smoking. Participants with uncontrolled viral loads—over 200,000 copies/mL—were 3.4 times more likely to develop COPD than HIV-negative participants.

It appeared that successful antiretroviral therapy reduced COPD risk in the study. In a separate evaluation of a smaller group of about 300 people with HIV, people with viral loads greater than 200,000 copies/mL were four times more likely to develop COPD than those with viral loads less than 200,000 copies/mL.

The ALIVE study did not establish a cause-and-effect relationship between viral load and COPD, so more evidence is needed before conclusions can be drawn. Kunisaki says that a recently-completed lung function sub-study, which was nested within the larger START study, will likely provide some answers. In the study of HIV-positive people with CD4 counts over 500 cells/mm3, the rate of lung function decline in people with HIV who begin antiretroviral therapy immediately will be compared to lung function decline in people who delay ART until CD4 counts decline to 350 cells/mm3. “It will essentially be a comparison of the difference in viral load just by the nature of that randomized ART strategy,” said Kunisaki.

At this point in time, although there are treatments to alleviate symptoms, COPD isn’t curable—it’s a chronic disease that people live with for the rest of their lives. So prevention is key, said Kunisaki. Public health efforts that continue to reduce the number of people that start smoking—or help people quit if they want to—will go a long way in reducing COPD since it’s estimated that upwards of 75% of COPD cases are due to cigarette smoking.

Kunisaki also believes that building awareness about COPD is important. “It’s surprising that COPD is the third leading cause of death but a lot of people haven’t heard of it. From a public health standpoint, awareness campaigns that educate providers and patients about the symptoms of COPD are important so people know what symptoms to look out for and what to screen for.”

People with COPD have difficulty breathing with symptoms that get worse over time. Coughing, wheezing, shortness of breath, chest tightness, and fatigue can all be symptoms of COPD. Read more information about COPD here, and find out more about the painless spirometry test that’s used to diagnose COPD here

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