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Emphysema tied to cough and slower walking with HIV but not without HIV.

HIV-positive people with emphysema (em-fuh-ZEE-ma), a serious lung disease, had more chronic cough and a lower maximum distance walked in 6 minutes than HIV-positive people without emphysema in a US study. (1) The link to cough and slower walking held true even in HIV-positive people with milder emphysema. But emphysema did not affect breathing symptoms and walk distance in a comparison group of people without HIV.

Emphysema is a type of chronic obstructive pulmonary disease (COPD); it is an incurable lung disease marked by shortness of breath and increasingly difficult breathing. (2) This serious but manageable illness involves destruction of air sacs in the lung (Figure 1). It can cause shortness of breath as well as daily or almost daily coughing and phlegm (mucus) production.

Smoking is the major cause of emphysema, and smoking is twice as frequent in US people with HIV as in those without HIV. (3) More than 40% of HIV-positive people in the United States smoke. Researchers who conducted the new emphysema study (1) noted that emphysema is more common and occurs at an earlier age in people with than without HIV, even in analyses that account for the higher smoking rate in HIV-positive people.

But little is known about how emphysema affects health in people with HIV. To learn more about the health impact of emphysema in people with versus without HIV, researchers conducted this comparative study.

* How the study worked. The analysis focused on a group of US veterans in the Examinations of HIV-Associated Emphysema (EXHALE) study, a substudy of the larger Veterans Aging Cohort Study (VACS). The EXHALE study enrolled HIV-positive and negative veterans. Each HIV-positive veteran was matched to an HIV-negative veteran according to whether they smoked. Over a study period from 2009 through 2012, researchers collected detailed lung-related data. No one who entered the substudy had chronic obstructive lung diseases other than asthma or COPD, and no one had acute lung symptoms within the last month.

All study participants had a chest CT (a scan similar to an x-ray) read by a single CT expert to determine whether each person had emphysema. The CT expert rated each scan on a scale from 0 (no emphysema) to 5 (more than 75% emphysema). Researchers split participants into two groups: (1) no emphysema or trace emphysema (10% or less emphysema on the CT), and (2) mild or worse emphysema (more than 10% emphysema on the CT).

The researchers used medical records and a questionnaire to collect other health data on study participants, including a detailed smoking history. Participants reported whether they had chronic cough and/ or phlegm and whether they had shortness of breath upon exertion. They also had a spirometry test, a simple way to measure inhaling and exhaling ability. Finally, researchers measured how far each participant could walk in 6 minutes. (This is a standard test used to see whether lung disease limits walking.) Participants completed all these tests within about 2 weeks of entering the study.

The researchers used an accepted statistical method to determine whether HIV could be linked to emphysema independent of other risk factors including smoking. They used a similar test to explore links between CT-confirmed emphysema and shortness of breath on exertion, chronic cough and/or phlegm, and 6-minute walk distance.

* What the study found. The study involved 170 veterans with HIV and 153 without HIV. Large majorities of both groups were men, and most participants were in their early to mid-50s. Most veterans were black (72% with HIV, 63% without HIV). According to the study plan, similar high proportions of participants currently smoked (63% with HIV, 58% without HIV). The HIV group had significantly higher proportions with a history of lung diseases like tuberculosis (7.1% versus 1.3%), Pneumocystis pneumonia (1.8% versus 0), and bacterial pneumonia (17% versus 3.9%). (In this review "significant" means a statistical test determined that the difference cannot be explained by chance.)

Compared with the HIV-negative group, veterans with HIV had significantly worse lung function measured as ability to transfer gas from inhaled air to red blood cells in the lung. And a significantly higher proportion of HIV-positive veterans reported chronic cough and/or phlegm (66% versus 55% without HIV). Overall, the groups were similar in proportions reporting shortness of breath on exertion (about 40%) and in their 6-minute walk distance (about 425 meters, or 465 yards). Three quarters of veterans with HIV were taking antiretroviral therapy, * and two thirds had an undetectable viral load.

About half of veterans with or without HIV had no evidence of emphysema on their CT scan. But the HIV group had a significantly higher proportion with greater than 10% emphysema on their CT scan (31% versus 16%). Statistical analysis determined that HIV-positive veterans had a 2 times higher chance of worse than 10% emphysema than HIV-negative veterans, regardless of whatever other emphysema risk factors these veterans had (Figure 2). In other words, HIV alone--separately from smoking and other risk factors--doubled the odds of emphysema. Other factors that, by themselves, raised chances of emphysema were older age, more smoking, using inhaled drugs, and injecting illegal drugs.

The researchers compared HIV-positive people with worse than 10% emphysema to HIV-positive people without emphysema. Those with emphysema had 2.6 times higher chances of cough and/or phlegm (Figure 2), and those with emphysema walked 35 meters (38 yards) less on the 6-minute walk test. These outcomes were independent of other risk factors like amount of smoking, age, race, sex, drug use, and certain major illnesses. In the same analysis, HIV-negative people with emphysema did not differ from HIV-negative people without emphysema in chronic cough and/or phlegm or in 6-minute walk distance.

Next the researchers limited these analyses to people without evidence of COPD or obstructive lung disease detected by the spirometry test. HIV-positive people with worse than 10% emphysema had 4.2 times higher chances of chronic cough and/or phlegm than HIV-positive people without emphysema (Figure 2). And HIV-positive people with emphysema walked 60 meters (66 yards) less on the 6-minute walk test. In the same analysis, HIV-negative people with emphysema (but without COPD) did not differ from HIV-negative people without emphysema in chronic cough and/or phlegm or in 6-minute walk distance.

Finally the researchers performed a statistical analysis to determine the impact of worsening emphysema on the 0 to 5 scale (with 0 meaning no emphysema and 5 meaning the worst emphysema). In veterans with HIV, every 1-point higher (worse) emphysema score meant a 40% higher chance of cough and/or phlegm, a 40% higher chance of shortness of breath on exertion, and 9.5 fewer meters (10 yards) walked on the 6-minute walk test. In veterans without HIV, worse emphysema scores did not affect 6-minute walk distance or chances of cough or shortness of breath.

* What the results mean for you. This careful comparison of veterans with HIV and a similar group of veterans without HIV made several important findings. First, HIV-positive veterans had a twice higher chance of having emphysema than HIV-negative veterans--regardless of whatever other emphysema risk factors a person had (like smoking). Second, HIV-positive veterans with emphysema had a higher chance of cough or phlegm and could not walk as far in 6 minutes as HIV-positive veterans without emphysema. Third, those findings held true for HIV-positive veterans with milder emphysema and without evidence of COPD measured by the spirometry test. And fourth, in people with HIV worse emphysema measured by CT scan meant worse coughing, worse shortness of breath, and a shorter distance on the 6-minute walk test.

These findings in HIV-positive veterans did not apply to veterans without HIV. That result adds to the evidence that something about HIV makes certain non-HIV diseases more frequent or worse. Since most of these veterans had good control of their HIV with antiretroviral therapy, it is possible that ongoing inflammation despite good HIV control plays a role in making non-HIV diseases more frequent or worse. In people with emphysema, that inflammation probably involves the airways.

These findings are important because emphysema can usually be prevented by avoiding smoking or quitting smoking. And someone who already has emphysema should try hard to quit because smoking will make emphysema worse. This study confirmed earlier research linking more smoking to a higher risk of emphysema. If you smoke, your HIV provider can help you make a plan to quit. That plan may involve nicotine-replacement therapy, a smoke-ending medicine, or an online individual smoke-ending program designed for people with HIV (see the link at reference 4). About 20% of HIV-positive people in the United States are people who successfully quit smoking. (3)

Uncontrolled emphysema can lead to large holes in the lungs, collapsed lung, respiratory failure, (5) and ultimately death. The Centers for Disease Control and Prevention (CDC) estimates that 3.4 million new cases of emphysema developed in the United States in the past year and almost 7500 people died of emphysema. COPD, which includes emphysema, is the third leading cause of death in the United States 6 Don't add yourself to those numbers. Stop smoking to avoid emphysema and COPD.


(1.) Triplette M, Attia E, Akgun K, et al. The differential impact of emphysema on respiratory symptoms and 6-minute walk distance in HIV infection./Acquir Immune Defic Syndr. 2017; 74:e23-e29.

(2.) American Lung Association. Lung health and diseases. Emphysema.

(3.) Mdodo R, Frazier EL, Dube SR, et al. Cigarette smoking prevalence among adults with HIV compared with the general adult population in the LTnited States: cross-sectional surveys. Ann Intern Med. 2015; 162:335-344.

(4.) Positively Smoke Free. Created by experts, refined by real users like you.

(5.) Mayo Clinic. Emphysema. Complications.

(6.) Centers for Disease Control and Prevention (CDC). National Center for Health Statistics. Chronic obstructive pulmonary disease (COPD) includes: chronic bronchitis and emphysema,

* Words in bold are defined in the Technical Word List at the end of this issue of HIV Treatment Alerts.

Caption: Figure 1. In a person with emphysema, walls of air sacs in the lung (also called alveoli) begin to collapse. As a result, breathing becomes harder. (Illustrations from Servier PowerPoint Image Bank,
Figure 2. Three separate analyses determined the impact of HIV on
chances of emphysema (left bar) or the impact of emphysema with HIV
on chances of cough and/or phlegm (two right bars). The bar at the
far right shows chances of cough and/or phlegm in HIV-positive
people with emphysema but without evidence of chronic obstructive
pulmonary disease (COPD) detected by the spirometry test.

HIV and emphysema impacts on cough/phlegm symptoms

                           Chances of   Chances of     Chances of
                           emphysema    cough/phlegm   cough/phlegm

HIV+ vs HIV-               2.1
HIV+ with vs without                    2.6
HIV+ with vs without                                   4.2
  emphysema without COPD

Note: Table made from bar graph.
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Publication:HIV Treatment: ALERTS!
Date:Mar 1, 2017
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