Office of Research & Development

VA research on

Respiratory Health


Introduction

According to the United States Environmental Protection Agency, the average person takes between around 17,000 to 23,000 breaths a day. For the healthy, this is a simple process. But for millions of people with respiratory problems, breathing is not easy.

Two specific types of respiratory diseases that can restrict breathing are asthma and chronic obstructive pulmonary disease (COPD). Asthma is a chronic inflammatory disorder of the airways characterized by episodes of breathing problems. While it cannot be cured, its symptoms can be controlled.

COPD is characterized by airflow limitation. The limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, such as those in cigarette smoke.

The term COPD includes two main conditions: emphysema (in which the air sacs of the lung are damaged and enlarged), and chronic bronchitis (a long-lasting cough caused by chronic inflammation of the bronchi). Most people with COPD have both conditions.

Veterans may suffer from other respiratory problems due to exposure to respiratory hazards such as infectious agents and other environmental exposures. Examples of respiratory diseases that may be caused by infectious agents are tuberculosis, lung cancer, and pneumonia. Environmental hazards found in war theaters, such as Agent Orange, may put Veterans at additional risk of respiratory problems.

Veterans who develop respiratory cancer (cancer of the lung, bronchus, larynx, or trachea) and were exposed to Agent Orange or other herbicides during military service do not have to prove a connection between their disease and their service to be eligible to receive VA health care and disability compensation.

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Selected Major Accomplishments

  • 1946: Developed and tested effective therapies for tuberculosis through multicenter clinical trials that led to the development of the VA Cooperative Studies Program
  • 1950: Concluded there is "strong circumstantial evidence" linking cigarette smoking with respiratory tract cancers
  • 2013: Found that sleep apnea and poor sleep quality predicted diabetes, independent of other diabetes risk factors or mental health status.
  • 2014: Learned that treatment for pneumonia that included the antibiotic azithromycin (Zithromax) was associated with a significantly lower risk of death and a slightly increased risk of heart attack
  • 2016: Developed a blood test to determine the causes of upper respiratory illness, to help ensure antibiotics are used appropriately

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New, Ongoing, and Published Research

VA researchers are advancing the understanding, prevention, and treatment of numerous respiratory illnesses, ranging from the common cold and pneumonia to major public health threats such as tuberculosis and lung cancer. The department's Office of Public Health (OPH) works with all levels of government to prepare for possible pandemic influenza (flu) outbreaks.

Respiratory problems are the leading cause of death in Veterans and others who have spinal cord injury (SCI). VA's Center of Excellence on the Medical Consequences of Spinal Cord Injury (SCI), located in the Bronx, New York, is studying ways to treat complications of SCI, including those that affect breathing. Other secondary disabilities related to SCI are problems with muscular function, bowel movements, and cardiovascular health.

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➤ Tuberculosis

The VA research program began in 1925, just four years after VA was established. (The organization was then called the Veterans' Bureau.) Forty percent of VA's first patients had tuberculosis (TB), a contagious bacterial infection that involves the lungs and may spread to other organs.

The first head of VA research was a TB specialist, and in the 1920s and 1930s, VA researchers published a number of scientific papers on the subject. After World War II, VA and the Department of Defense conducted a major study to test the effectiveness of the antibiotic streptomycin to treat TB. While initial results were very favorable, researchers soon learned that the antibiotic could cause inner ear damage, and that many patients developed resistance to the drug.

In 1947, however, VA researchers determined in a follow-up study that a lower dose of streptomycin could achieve similar good results with fewer side effects and less risk of drug resistance. These studies, conducted at a number of VA facilities, were among VA's first-ever large-scale clinical trials. They eventually led (in 1972) to the development of VA's Cooperative Studies Program, which plans and conducts large multicenter clinical trials and epidemiological studies for VA.

Although TB rates in the United States have fallen to all-time lows, largely thanks to antibiotics such as streptomycin and its successors, 11 million Americans are infected with the TB germ, 5 to 10 percent of whom will develop the disease if they are not treated, according to the Centers for Disease Control and Prevention. Accordingly, VA researchers have continued to study the disease.

New drug combination—In 2011, an international study that included six VA sites found that patients with latent tuberculosis (those who are infected but have no symptoms and are not contagious) could keep the disease from developing by taking a combination of drugs (rifapentine and isoniazid) once a week for three months.

The combination appears to work just as well as the previous standard of care, which called for taking isoniazid every day for nine months. Nearly 8,000 people at high risk of developing TB from Brazil, Canada, Spain, and the United States took part in the study.

More effective treatment—In 2016, researchers with the VA Tennessee Valley Health Care System and Vanderbilt University found that a small chemical change to floroquinolone, an antibacterial drug used to treat TB, results in a compound that is more effective against tuberculosis enzymes.

The new compound, a modified version of the drug moxifloaxin, also maintains its activity against drug-resistance forms of the enzyme, and could lead to a more effective treatment for tuberculosis.

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➤ Lung cancer

Early associations of lung cancer to smoking—In 1932, the Hines VA hospital established a Tumor Research Laboratory to complement the work of its cancer treatment center—VA's first laboratory to receive funds specifically for research work.

The laboratory's first success came through the work of Dr. Robert Schrek, who did pioneering studies on the effects of cigarette smoking on cancers of the lung, larynx, and pharynx.

Schrek's work was followed up by the work of Dr. Oscar Auerbach, of VA's East Orange hospital, now the East Orange campus of the VA New Jersey Health Care System. Auerbach's landmark animal research study found that smoking for three years caused major changes in the lungs of animals who were taught to inhale cigarettes—and that many developed cancer.

Auerbach was later a participant in the first Surgeon General's report, published in 1964, which explained the harmful effects of smoking to America and the world.

Risks of e-cigarettes—In 2015, a team of researchers at the VA San Diego Healthcare System looked at the possible health risks of electronic cigarettes, and found they damaged cells in ways that could lead to cancer. The damage occurred even with nicotine-free versions of the products. On the other hand, the experiments also showed that the e-cigarette vapor was not as harmful to cells as regular cigarette smoke.

The team concluded that further research is needed to better understand the long-term health effects of e-cigarettes in humans.

A 2016 study by a different team of researchers in San Diego reported that e-cigarettes can kill human airway cells. At high doses, they also suppress users' immune defenses, inflame the lungs, and promote the growth of bacteria in the lungs that can cause pneumonia and other diseases.

The team found these issues in the airways and blood of mice that inhaled e-cigarettes for one hour a day, five days a week, for four weeks. According to team member Dr. Laura Crotty Alexander, the study demonstrates that the vapor from e-cigarettes is not benign. She described the findings as "frightening" for those who use the products.

Genomics and lung cancer—In 2015, VA's New England Healthcare System and the Massachusetts Veterans Epidemiology Research and Information Center instituted a clinical program to help Veterans who have been newly diagnosed with non-small cell lung center.

As Veterans are diagnosed, VA physicians take a specimen of their tumor and send it to qualified laboratories for targeted genomic sequencing, a process that determines the DNA sequence of genes that are considered important in lung cancer.

The sequencing will identify specific mutations, or changes, that are causing the Veterans' lung cancers to grow, allowing them to benefit from drugs that are targeted to those mutations, and to take part in clinical trials of new drugs targeted toward their specific mutations.

The program is now expanding nationwide in VA and will receive funding from the Cooperative Studies Program to conduct precision oncology trials.

Limitations of PET scans—Positron emission tomography (PET) is a medical imaging technique that produces 3-D images showing differences between healthy and diseased tissue. PET commonly uses a radioactive tracer called FDG (fluorodeoxyglucose), so the test is sometimes called an FDG-PET scan.

FDG-PET scans are often used in combination with computed tomography (CT) scans to diagnose lung cancer. In 2014, a team from VA's Tennessee Valley Health Care System and Vanderbilt University Medical Center in Nashville found that FDG-PET scans combined with CT are not as good at detecting lung cancer in regions where there is endemic infectious lung disease, compared with regions where such disease is not widespread.

The researchers reviewed 70 previous studies on FDG-PET. In patients who had pulmonary nodules but not lung cancer, FDG-PET was 16 percent more likely to give a false-positive result when the patients lived in regions where infectious lung disease is prevalent. This suggests that the lung diseases common in those regions may sometimes be mistaken for cancer on imaging tests.

Examples of regional lung diseases include histoplasmosis and blastomycosis, which are caused by inhaling airborne fungal spores. TB is also much more common in some regions of the United States than in others.

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➤ Helping smokers quit

Development of the nicotine patch—In 1984, VA Research made a major contribution toward helping Veterans and others quit smoking through the development of the nicotine transdermal patch. The patch was developed by Drs. Jed Rose, Daniel Rose, and Murray Jarvik, The patch transfers nicotine into the bloodstream to reduce cravings for the substance.

Successful counseling method—In 2016, a team led by researchers from the VA New York Harbor Healthcare System and the New York University School of Medicine found that specialized counseling delivered by telephone may be more effective than state quit lines to help smokers in mental health care to kick the habit.

The study looked at 522 Veterans with mental health issues, 270 of whom received specialized counseling that incorporated motivational interviewing, problem-solving therapy and cognitive behavioral therapy. The other 307 Veterans were referred to their local quit lines.

The team found that the specialized counseling yielded a quit rate of 26 percent at six months, versus 18 percent for the state quit lines.

Varenicline and buproprion do not appear to increase neuropsychiatric risk—Varenicline (sold as Chantix) and buproprion (sold as Wellbutrin and Zyban) are prescription medications used to treat nicotine addiction.

A 2016 study by VA researchers in Hines, Illinois; Bedford, Massachusetts; and Pittsburgh, along with researchers from the U.S. Food and Drug Administration and two universities, found that these medications do not appear to increase the incidence of serious neuropsychiatric illnesses such as depression, schizophrenia ,or bipolar disorder, when compared with placebo.

Participants in the study were more than 8,000 adults aged 18-75 who smoked more than 10 cigarettes a day and were motivated to stop smoking. About half (4,116) had a history of a past or current stable psychiatric condition. For 9 to 12 weeks, some received varenicline, some buproprion, some a nicotine patch, and others a placebo.

The participants were assessed to see whether they had any moderate to severe neuropsychiatric events during their treatment, and at a follow-up visit 9 to24 weeks after the treatment ended. These events included agitation, aggression, panic, anxiety, and suicidal ideation.

While there were more adverse events reported in the group that previously had psychiatric disorders, there was no significant increase in the incidence of such events in the groups receiving any of the four kinds of treatment.

Varenicline was more effective in helping people stop smoking than bupropion, nicotine patches, or placebo. Bupropion was about as effective as nicotine patches, and both were more effective than placebo.

QuitNet study—In a four-year study, researchers at the Durham VA Medical Center are looking at Web-based methods of quitting smoking as an alternative to clinic-based programs, which are often poorly attended. They are examining QuitNet, a website launched 10 years ago, which offers chat rooms, advice from experts, medication tips, buddy match-ups, and other tools to support smokers in their quest to stop smoking.

The researchers are providing half of the 400 Veterans involved in the study with premium memberships in QuitNet, and comparing their quit rates over a four-year period with those of Veterans enrolled in a clinic at the Durham VA geared toward helping returning Veterans quit smoking.

VA also offers Veterans hoping to quit smoking a smoker's quitline (1-855-QUIT-VET), and a smoking cessation texting program called SmokefreeVet.

Lung cancer screening issues—A 2015 study by researchers with the VA Puget Sound Health Care System and the University of Seattle found that lung cancer screening can lower smokers' motivation to quit smoking.

The team studied 37 current smokers offered lung cancer screening by their primary care physician during 2014. After the screening, the smokers were interviewed by the research team. The team found nearly half of those interviewed found some reason to believe that just being screened meant that they did not need to stop smoking.

Some told the researchers that undergoing the test had the same benefit as stopping smoking, even when precancerous lung nodules were found. Others felt that being able to return for additional screenings would protect them, and still others felt that a cancer-free screening test indicated that they were among the lucky ones who would avoid the harms of smoking.

All of these assumptions are false—as is the assumption many study participants had that lung cancer was the only potentially lethal effect of smoking. The team suggested that counseling for smokers should target these and other rationalizations some people use to avoid quitting.

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➤ Marijuana use and respiratory disease

Marijuana and lung disease—Marijuana, a preparation of the hemp plant that is used both as a recreational drug and as medicine, is commonly smoked to get a "high." However, some sick people, especially cancer patients, can use it to relieve their pain.

In 2014, researchers from the Central Arkansas Veterans Healthcare System in Little Rock and the University of Arkansas reviewed recent studies on the controversial drug and its ties to lung diseases. They found that smoking marijuana is not as bad as smoking cigarettes when it comes to lung disease.

They found a clear linkage between marijuana use and chronic bronchitis and large airway inflammation, conditions that make breathing difficult. However, they found no links to emphysema, a chronic disease in which the air sacs in the lungs are gradually damaged, and only weak, if any, links to lung cancer.

The researchers concluded, however, that there is unequivocal evidence that habitual or regular marijuana use is not harmless, and that doctors should caution patients about possible lung damage from regular heavy marijuana use.

A previous study, conducted in 2012 by researchers at the Birmingham, Alabama, VA Medical Center, the University of Alabama at Birmingham, and the University of San Francisco, found that marijuana does not impair lung function, at least not in the doses inhaled by the majority of users. The team even found that some marijuana smokers could blow air in and out slightly better than those who did not smoke at all.

The investigators tested the lung function of 5,115 young adults over the course of 20 years, starting in 1985. They found that marijuana use was almost as common as cigarette smoking in the sample, and that the average user smoked marijuana about two to three times a month, while the average cigarette smoker smoked eight cigarettes a day.

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➤ Influenza

The flu is a contagious respiratory illness caused by influenza viruses that infect the nose, throat and lungs. It can cause mild to severe illness, and at times can lead to death. Experts say the best way to prevent the flu is by getting a flu vaccine each year.

According to VA's Office of Public Health, flu shots are both safe and effective. Most people have no serious side effects or allergic reactions. A very small number of people may get minor body aches, headache or a low-grade fever that lasts a day or two. People cannot get the flu from a flu shot, because it only contains strains of non-living flu viruses.

Other things people can do to slow the spread of flu include avoiding contact with people who are sick; washing their hands often; keeping their hands away from their face; covering coughs and sneezes; and staying home when they are sick.

Flu vaccines for the elderly—In 2015, researchers at the Philadelphia VA Medical Center and the University of Pennsylvania attempted to determine whether the standard dose version of flu vaccine or a higher dose were better for Americans over 65.

The study, which looked at more than 165,000 VA patients, found that for those between the ages of 65 and 84, the standard dose worked just as well. However, for Veterans 85 or older, the higher dose was better in terms of avoiding hospitalization for the flu or pneumonia.

Determining flu outbreaks—Another 2015 study, by researchers with VA and other health care institutions throughout the nation, described a new algorithm to help hospitals and public health officials determine the earliest stages of flu season. Having this information could help them preserve resources while combatting the virus.

The algorithm, which researchers call the Above Local Elevated Respiratory Illness Threshold (ALERT), uses routine information, such as the number of influenza cases confirmed per week in a region, to determine where and when the flu needs to be combated.

The tool takes a region's flu history into account and allows users to identify the number of cases per week they believe would signal the start of the season in their area. It also identifies the length of time influenza outbreaks are likely to last.

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➤ Pneumonia

Pneumonia is common among older Americans, and sends hundreds of thousands of seniors to the hospital each year.

Best method of treatment for the elderly—A 2015 study by researchers with VA and the University of Michigan Medical School found that many seniors with pneumonia had a better chance of surviving if they went to an intensive care unit instead of a general hospital bed—and that despite ICUs' reputation as a high-cost place to care for patients, the costs to Medicare and hospitals were the same for both groups.

Researchers looked at data from 1.1 million hospital stays at nearly 3,000 hospitals between 2010 and 2012. They focused on patients "on the bubble"—those whom doctors could send to either an ICU bed or a general bed, depending on their judgment.

The team is now evaluating if the ICU is beneficial for other conditions, including chronic obstructive pulmonary disease, congestive heart failure and heart attack.

Pneumonia and heart disease—Older men hospitalized with pneumonia may also be at risk of heart problems. In 2011, researchers at the South Texas Veterans Health Care System completed a national study of the records of more than 50,000 patients admitted to VA hospitals with pneumonia aged 65 or older.

They found that about 10 percent of these Veterans experienced congestive heart failure within 90 days of their admission to the hospital. Virtually the same percentage experienced an arrhythmia (a problem with the rate or rhythm of the heartbeat.) Another 1.5 percent had a heart attack. Most of these events occurred while patients were in the hospital.

The study's authors suggested that cardiovascular events may be a principal reason for death following the onset of pneumonia in older people, and recommend further studies to determine whether interventions can reduce the frequency of these events.

Efficacy of Zithromax—In a study published in 2014, researchers from the VA North Texas Health Care System and the University of Texas looked at the records of 65,000 older patients hospitalized with pneumonia. They found that treatment that included the antibiotic azithromycin (Zithromax) compared with other antibiotics was associated with a significantly lower risk of death and a slightly increased risk of heart attack. The researchers concluded there is a net benefit associated with azithromycin use in patients hospitalized for pneumonia.

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➤ Environmental hazards and Iraq and Afghanistan Veterans

For many of the more than 2.6 million service members who have served in Iraq and Afghanistan, respiratory health after deployment has become a major concern. One reason for problems such as persistent cough or shortness of breath may be burn pits—large open-air ditches in which the military disposed of trash ranging from human waste to compact discs and plastics.

Additional reasons for respiratory problems among Iraq and Afghanistan Veterans may include other airborne hazards including sand and dust storms and general air quality. Many also smoked.

Respiratory issues and long-term health—A 2015 review of 19 studies on this issue appeared to confirm higher rates of respiratory problems for service members during deployment and immediately afterward, but was inconclusive on whether those problems would affect the long- term health of these Veterans. The research team, from VA's War-Related Illness and Injury Study Center in New Jersey, suggested that additional studies were needed.

This study follows a 2011 report from the Institutes of Medicine (IOM), which was also inconclusive about the long-term health effects of burn pits, and recommended further study. The IOM report also drew attention to other deployment risks that may harm respiratory health.

Iraq and Afghanistan Veterans are encouraged to visit the website of VA's Airborne Hazards and Open Burn Pit Registry, where they can enroll in the registry to learn about and help researchers learn more about potential health effects. Veterans concerned about their exposure to burn pits are encouraged to talk to their health care provider or local VA environmental health coordinator. A directory of these coordinators is found here.

Risk of developing respiratory illnesses—A 2014 study by researchers at the South Texas Veterans Health Care System found that Iraq and Afghanistan Veterans are at an increased risk of developing respiratory illnesses, compared with non-deployed troops.

The investigators found that 6 percent of more than 768,000 Veterans who served in Iraq and Afghanistan and received VA care between 2002 and 2011 met the criteria for one or more chronic pulmonary conditions, such as asthma, bronchitis, or emphysema.

Another 10.5 percent met the criteria for chronic wheezing or coughing. The researchers found the rate of illness increased over the 10-year period they examined.

The researchers noted that Veterans found to have respiratory symptoms, asthma, and COPD were more likely to smoke, and smoking may have had a role in these high rates of illness.

New Generation study results—Another study, conducted by VA OPH researchers, resulted in somewhat different findings. This investigation, part of VA's National Health Study for a New Generation of U.S. Veterans, found that Veterans deployed to Iraq and Afghanistan were 29 percent more likely to have been diagnosed with sinusitis (inflammation of the sinus, the airspaces within the bones of the face) compared to Veterans who were deployed elsewhere at the same time.

Some 6.9 percent of all Iraq and Afghanistan Veterans who were part of the study developed sinusitis, compared to 5.6 percent of those who served elsewhere.

Researchers conducting this study also found, however, that only 3.3 percent of Iraq and Afghanistan Veterans had developed asthma, compared to 3.4 percent of those who were elsewhere. The researchers also found that 5.9 percent of Iraq and Afghanistan developed bronchitis, compared to 5.3 percent of others. The differences in the percentages of asthma and bronchitis cases were not considered statistically significant.

The National Health Study for a New Generation of U.S. Veterans is a long-term study of the health of 30,000 Veterans who served in Iraq and Afghanistan, and

30,000 Veterans from the same era who were not deployed to those countries.

Millennium Cohort Study results—A 2012 study by VA and DoD researchers involved with the Millennium Cohort Study found little evidence of increased respiratory risk for those who had served close to burn pits in Iraq. (The Millennium Cohort Study is a study designed to evaluate the long-term health effects of military service in Iraq and Afghanistan, with 200,000 enrolled Veterans.)

Burn pit registry study results—A 2016 study by a team of VA researchers from the department's Office of Post Deployment Health Services, the War Related Illness and Injury Study Center, and other programs examined the association between burn pit emissions exposure and respiratory and cardiovascular conditions in Iraq and Afghanistan Veterans registered in VA's Airborne Hazards and Open Burn Pit registry.

The team looked at the records of 4,343 registry participants and found an association between higher levels exposure to burn pit emissions and higher risks of some respiratory and cardiovascular conditions, including emphysema, chronic bronchitis or COPD, and hypertension. They suggested, however, that these findings should be interpreted with caution because the measurements they used of potential exposure to burn pits may not reflect the actual exposure of individuals in the study.

They hope to conduct future analyses after longer periods of time have elapsed so that they can study the relationship of burn pit exposure with diseases that take longer to develop, like cancer. They also hope to better understand explain the relationship between burn pit exposure and respiratory disease.

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➤ Environmental hazards and Veterans of previous wars

IOM report—The Institute of Medicine (IOM) of the National Academy of Sciences concluded in its 1994 report "Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam" that there is limited or suggestive evidence of an association between exposure to herbicides such as Agent Orange, and respiratory cancers.

In updates to this report, IOM noted that associations linking development of respiratory cancers and exposure to dioxin were found consistently only when herbicide exposures appeared to be high and prolonged.

Army Chemical Corps health study—OPH is currently conducting the Army Chemical Corps Vietnam-Era Veterans Health Study to learn if high blood pressure and COPD, including emphysema and chronic bronchitis, is related to Agent Orange exposure during the Vietnam War.

The study is looking at the health status of approximately 4,000 Veterans who served in the U.S. Army Chemical Corps between 1965 and 1973. Army Chemical Corps personnel were responsible for the maintenance and distribution of application of chemicals for military operations.

OPH researchers have conducted telephone interviews, collected medical records, and measured the blood pressure and lung function of participating Veterans. They are currently analyzing the data.

Chronic multisymptom illness—Some 1990-91 Gulf War Veterans are affected by a debilitating cluster of medically unexplained chronic symptoms that can include respiratory disorders. (More information on Gulf War Veterans' medically unexplained illnesses can be found here.) Researchers recently found that 96 percent of Gulf War Veterans with chronic multisymptom illness experienced breathing problems while they slept, compared to only 36 percent of Gulf War Veterans without multi-symptom illness.

The research team also found that CPAP therapy can ease breathing and sleep problems. Some Veterans receiving CPAP therapy also reported less pain and fatigue and improved thinking, sleep quality, and general health.

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➤ COPD

COPD is a progressive disease that makes it hard to breathe. COPD can cause coughing that produces large amounts of mucus, wheezing, shortness of breath, chest tightness, and other symptoms.

COPD and bacterial colonization—Doctors have long known that patients with COPD have a variety of bacterial pathogens in their lungs, because the disease compromises the lungs' defenses against bacteria, allowing bacteria to persist. Though this is abnormal and potentially damaging, physicians have long believed these bacteria were not harmful as long as the patient was not having a flare-up of his or her respiratory problems.

A recent study by researchers at the VA Western New York Healthcare System and the University of Buffalo demonstrated that COPD patients experience significant respiratory symptoms when their lungs are colonized by bacteria, even when they are not having acute respiratory problems.

They found bacterial colonization is sufficient to trigger clinically significant increases in shortness of breath, coughing and sputum (a mixture of saliva and mucus coughed up from the respiratory tract). It can also cause increased inflammation of a patient's airways.

Treating these infections, the study concluded, should help improve the quality of life for patients with COPD.

Airway changes and bacteria—For many people, problems with COPD are a result of their smoking history. However, stopping smoking often does not halt the progression of the disease.

A 2016 study by researchers with the VA Tennessee Valley Healthcare System and Vanderbilt University found that in mice, changes in the airways resulting from cigarette smoke exposure are what make the lungs more susceptible to bacterial invasion over time.

These changes, according to the research team, allow airway bacteria to invade deeper into the lung, and may explain why COPD persists in many people even after they stop smoking. The team also found that treatment with the anti-inflammatory drug roflumilast halted the progress of these changes, and may prove to be a possible future therapy for COPD patients.

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➤ Sleep apnea

Sleep apnea (pauses that occur in breathing at night) can cause excessive daytime sleepiness, trouble thinking and concentrating, high blood pressure, cardiac and pulmonary disease, and motor vehicle accidents.

Predictor of diabetes—A 2013 study by researchers at the VA Puget Sound Health Care System, conducted as part of the joint VA-Department of Defense Millennium Cohort Study on the health of service members and Veterans, found that sleep apnea and poor sleep quality predicted diabetes, independent of other diabetes risk factors or mental health status.

Sleep apnea increased the risk of diabetes by 78 percent, and simply having trouble sleeping increased the risk of diabetes by 21 percent. The study included more than 47,000 service members and Veterans who were an average age of about 49.

Sleep apnea was associated with a greater risk of kidney disease in a 2015 database study of more than 3 million VA patients. In obstructive sleep apnea, the airway becomes narrowed or blocked during sleep.

Other complications of sleep apnea—Researchers from the Memphis VA Medical Center, the University of Tennessee Health Science Center, and the University of California, Irvine, also found that Veterans with sleep apnea were at greater risk of coronary heart disease, strokes, and death from any cause. The researchers did not show that sleep apnea caused kidney disease and the other outcomes—only that there was a strong relationship between them.

Relationship with PTSD—In 2016, researchers at the VA San Diego Healthcare System and the University of California found that the risk of obstructive sleep apnea among Iraq and Afghanistan Veterans increased with the severity of their PTSD symptoms.

The investigators looked at 195 Iraq and Afghanistan Veterans, more than 93 percent men, who had visited a VA outpatient PTSD clinic for evaluation of their symptoms.

Using clinical questionnaires to evaluate both their levels of PTSD and their likelihood of developing sleep apnea, the researchers found that nearly 70 percent of these Veterans were at high risk of developing sleep apnea, and that the risk increased with the severity of their PTSD symptoms. This was despite the fact that many of them did not have a high body mass index or high blood pressure, considered classic predictors of sleep apnea.

Weight loss and sleep apnea—In another study related to sleep breathing problems, researchers at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia and the University of Pennsylvania found that losing weight does far more to reduce cardiovascular risk factors in people with sleep apnea, which is strongly linked to obesity, than a therapy called continuous positive airway pressure (CPAP).

The researchers treated some of the 181 Veterans in the study, each of whom were both obese and had moderate to severe sleep apnea, with CPAP therapy. Others received interventions to lose weight, and some in the study group received both CPAP and weight loss help. They found that, while CPAP therapy was helpful in reducing high blood pressure, weight loss was the most important factor in improving cardiovascular health in patients with sleep apnea. They also found that weight loss and CPAP therapy together will result in larger reductions in blood pressure than either therapy alone. .

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➤ Spinal cord injury and respiratory issues

Reduced lung function and SCI patients—VA researchers with the VA Boston Healthcare System and Harvard Medical School have found that reduced lung function in Veterans with SCI is associated with high levels of two proteins that indicate systemic inflammation of the body. The research team studied 59 Veterans and found that levels of IL 6 and C-reactive protein were highest in Veterans with the poorest results on tests of lung function.

The results suggest that lung problems after SCI are related not only to the physical injury itself, but also to bodywide inflammation.

Breathing during sleep—A 2014 study by researchers at the John D. Dingell VA Medical Center in Detroit and Wayne State University looked at breathing during sleep in 16 patients with SCIs. The study included eight patients with thoracic SCI, which paralyzed their legs, and eight with cervical SCI, which paralyzed their torsos and all four limbs.

Each study participant was tested at the VA sleep research laboratory in Detroit to assess various factors, including breathing during sleep. The researchers found that 63 percent of patients with cervical SCI had sleep apnea, compared with only 13 percent of patients with thoracic SCI. They also found cervical SCI individuals' respiratory systems were less efficient and their breathing was shallower during sleep, compared with patients who had thoracic SCI.

The findings suggest that the level of SCI can affect the likelihood and type of sleep breathing problems, and the study offers new insight to help guide care for those with SCI.

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➤ Viral and bacterial upper respiratory infections

New blood test developed—An acute upper respiratory infection (URI) is a contagious infection of the upper respiratory tract, which includes the nose, throat, pharynx, larynx, and bronchi. The common cold is the most well-known URI, but other types include sinusitis, pharyngitis, epiglottitis, and tracheobronchitis.

Both viruses and bacteria can cause acute URIs, and the condition is one of the most common reasons for seeking medical care. However, it is difficult to determine whether a URI is viral or whether it is caused by a bacterial pathogen—thereby leading to many instances of inappropriate prescribing of antibiotics, which fight only bacteria and not viruses. This is one of the chief reasons new strains of bacteria are developing that are resistant to antibiotics.

Scientists with the Durham VA Medical Center and Duke University are developing a blood test that can determine the source of a URI, whether viral or bacterial. In 2016, they published a study in which they took blood samples from 273 people with acute respiratory infection or non-infectious illnesses, and 44 healthy people.

By looking at the genetic expression associated with the illness, in the blood samples, they were able to determine with 87 percent accuracy whether the illness was bacterial or viral, or the result of a noninfectious cause .

Currently, it takes 8 to 10 hours to obtain results from the test. The team is working to shorten the time frame so that the correct treatment can be prescribed while the patient is still at the health care facility .

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More on Our Website

Selected Scientific Articles by Our Researchers

Tobacco smoking as an etiologic factor in disease; cancer. Schrek R, Baker LA, et al. VA's first major study linking smoking to cancer. Cancer Res. 1950 Jan; 10(1):49-58.

The effect of direct cigarette smoke inhalation on the respiratory tree of dogs. Auerbach O, Hammond, EC, Kirman D, Garfinkel L, Stout AP. Auerbach's seminal paper on the effects of smoking. Natl Cancer Inst Monogr 1968 Jun;28:65-67

Transdermal administration of nicotine. Rose JE, Javik ME, Rose KD. A paper describing the value of the nicotine patch. Drug Alcohol Depend. 1984 May;13(3):209-13

Three months of rifapentine and isoniazid for latent tuberculosis infection. Sterling TR, Villarino ME, Borisov AS, Shang N, Gordin F, Bliven-Sizemore E, Hackman J, Hamilton CD, Menzies D, Kerrigan A, Weis SE, Weiner M, Wing D, Conde MB, Bozemen L, Horsburgh CR Jr, Chaisson RE; TB Trials Consortium PREVENT TB Study Team. The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate. N Engl J Med. 2011 Dec 8;365(23):2155-66.

Association between marijuana exposure and pulmonary function over 20 years. Pletcher MJ, Vittinghoff E, Kalhan R, Richman J, Safford M, Skiney S, Lin F, Kertesz S. Occasional and low cumulative marijuana use was not associated with adverse effects on pulmonary function. JAMA. 2012 Jan 11;307(2):173-91.

The effects of exposure to documented open-air burn pits on respiratory health among deployers of the Millennium Cohort Study. Smith B, Wong CA, Boyko EJ, Phillips CJ, Gackstetter GD, Ryan MA, Smith TC, Millennium Cohort Study Team. Findings do not support an elevated risk for respiratory outcomes among personnel deployed within proximity of documented burn pits in Iraq. J Occup Environ Med. 2012 Jun;54(6):708-16.

Sleep characteristics, mental health, and diabetes risk: a prospective study of U.S. military service members in the Millennium Cohort Study. Boyko EJ, Seelig AD, Jacobson IG, Hooper TI, Smith B, Smith TC, Crum-Cianflone NF; Millennium Cohort Study Team. Trouble sleeping and sleep apnea predict diabetes risk independent of mental health conditions and other diabetes risk factors. Diabetes Care. 2013 Oct;36(10):3154-61.

Tetraplegia is a risk factor for central sleep apnea. Sankari A, Bascom AT, Chowdhuri S, Badr MS. Sleep-related hypoventilation may play a significant role in the mechanism of sleep-disordered breathing in higher SCI levels. J Appl Physiol (1985). 2014 Feb 1;116(3):345-53.

Marijuana and lung disease. Joshi M, Joshi A, Bartler T. There is unequivocal evidence that habitual or regular marijuana smoking is not harmless. A caution against regular heavy marijuana usage is prudent. The medicinal use of marijuana is likely not harmful to lungs in low cumulative doses, but the dose limit needs to be defined. Recreational use is not the same as medicinal use and should be discouraged. Curr Opin Pulm Med. 2014 Mar;20(2): 173-9.

Bacterial colonization increases daily symptoms in patients with chronic obstructive pulmonary disease. Desai H, Eschberger K, Wrona C, Grove L, Agarwal A, Grant B, Yin J, Parameswaran GI, Murphy T, Sethi S. Even in the absence of clinical exacerbation, colonization by bacterial pathogens in COPD was associated with a clinically significant moderate increase in daily symptoms, likely mediated by increased airway inflammation. Ann Am Thorac Soc. 2014 Mar;11(3):303-9.

CPAP, weight loss, or both for obstructive sleep apnea. Chirinos JA, Gurubhagavatula I, Teff K, Rader DJ, Wadden TA, Townsend R, Foster GD, Maislin G, Saif H, Broderick P, Chittams J, Hanlon AL, Pack AI. In adults with obesity and obstructive sleep apnea, CPAP combined with a weight-loss intervention did not reduce C-reactive protein levels more than either intervention alone. N Engl J Med. 2014 Jun 12;370(24):2265-75.

Association of azithromycin with mortality and cardiovascular events among older patients hospitalized with pneumonia. Mortensen EM, Halm EA, Pugh MJ, Copeland LA, Metersky M, Fine MJ, Johnson CS, Alvarez CA, Frei CR, Good C, Restrepo MI, Downs JR, Anzueto A. Among older patients hospitalized with pneumonia, treatment that included azithromycin compared with other antibiotics was associated with a lower risk of 90-day mortality and a smaller increased risk of myocardial infarction. JAMA. 2014 Jun 4; 311(21):2199-208.

Accuracy of FDG-PET to diagnose lung cancer in areas with infectious lung disease: a meta-analysis. Deppen SA, Blume JD, Kensinger CD, Morgan AM, Aldrich MC, Masssion PP, Walker RC, McPheeters ML, Putnam JB Jr, Grogan EL. FDG-PET scans combined with CT are not as good at detecting lung cancer in regions where there is endemic infectious lung disease, compared with regions where such disease is not widespread. JAMA. 2014 Sep 24:312(12):1227-36.

Triggering interventions for influenza: the ALERT algorithm. Reich NG, Cummings DA, Laurer SA, Zorn M, Robinson C, Nyquist AC, Price CS, Simberkoff M, Radonovich LJ, Perl TM. The ALERT algorithm provides a simple, robust, and accurate metric for determining the onset of elevated influenza activity at the community level. Clin Infect Dis. 2015 Feb 15;60(4):499-504.

Obstructive sleep apnea and posttraumatic stress disorder among OEF/OIF/OND Veterans. Colvonen PJ, Masino T, Drummond SP, Myers US, Angkaw AC, Norman SB. Iraq and Afghanistan Veterans with PTSD screen as high risk for obstructive sleep apnea at much higher rates than those seen in community studies. J Clin Sleep Med. 2015 Apr 15;11(5):513-8.

Comparative effectiveness of high-dose versus standard-dose influenza vaccination in community-dwelling Veterans. Richardson DM, Medvedeva EL, Roberts CB, Linkin DR; Centers for Disease Control and Prevention Epicenter Program. High-dose flu vaccine was not found to be effective than small dose vaccine in protecting against hospitalization for influenza and pneumonia among older patients, except for having a protective effect in the oldest group of patients. Clin Infect Dis. 2015 Jul 15;61(2):171-6.

Attitudes and perceptions about smoking cessation in the context of lung cancer screening. Zeliadt SB, Heffner JL, Sayre G, Klein DE, Simons C, Williams J, Reinke LF, Au DH. Health care professionals should be aware that the opportunity for early detection of lung cancer may be interpreted as a way of avoiding the harms of smoking. JAMA Intern Med. 2015 Sep;175(9):1530-7. 12;370(24):2265-75

Association of incident obstructive sleep apnoea with outcomes in a large cohort of US Veterans. Molnar MZ, Mucsi I, Novak M, Szabo Z, Freire AX, Huch KM, Arah OA, Ma JZ, Lu JL, Sim JJ, Streja E, Kalantar-Zadeh K, Kovesdy CP. A diagnosis of obstructive sleep apnea is associated with higher mortality, incident coronary heart disease, stroke, and CHD, and with faster kidney function decline. Thorax. 2015 Sep:70(9):888-95.

Association of intensive care unit admission with mortality among older patients with pneumonia. Valley TS, Sjoding MW, Ryan AM, Iwashyna TJ, Cooke CR. Among Medicare beneficiaries hospitalized with pneumonia, Intensive Care Unit admission of patients for whom the decision appeared to be discretionary was associated with improved survival and no significant difference in costs. JAMA. 2015 Sep 22-29;314(12):1272-9.

Host gene expression classifiers diagnose acute respiratory illness etiology. Tsalik EL, Henao R, Nichols M, Burke T, Ko ER, McClain MT, Hudson LL, Mazur A, Freeman DH, Veldman T, Langley RJ, Quackenbush EB, Glickman SW, Cairns CB, Jaehne AK, Rivers EP, Otero RM, Zaas AK, Kingsmore SF, Lucas J, Fowler VG Jr., Carin L, Ginsburg GS, Woods CW. Host gene expression classifiers can be used as diagnostic platforms to combat inappropriate antibiotic use and emerging antibiotic resistance. Sci Transl Med. 2016 Jan 20;8(322):322ra11.

Electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines. Yu V, Rahimy M, Korrapati A, Xuan Y, Zou AE, Krishnan AR, Tsui T, Aguilera JA, Advani S, Crotty Alexander LE, Brumund KT, Wang-Rodriguez J, Ongkeko WM. E-cigarette vapor, both with or without nicotine, is cytotoxic to epithelial cell lines and is a DNA strand break-inducing agent. Further assessment of the potential carcinogenic effects of e-cigarette vapor is urgently needed. Oral Oncol. 2016 Jan;52:58-65.

Electronic cigarette inhalation alters innate immunity and airway cytokines while increasing the virulence of colonizing bacteria. Hwang JH, Lyes M, Sladewski K, Enany S, McEachern E, Mathew DP, Dae S, Moshensky A, Bapat S, Pride DT, Ongkeko WM, Crotty Alexander LE. E-cigarettes may be toxic to airway cells, suppress host defenses, and promote inflammation over time, while also promoting virulence of colonizing bacteria. J Mol Med (Berl). 2016 Jan 25. (Epub ahead of print.)

A comparison of neuropsychiatric adverse events during early treatment with varenicline or a nicotine patch. Cunningham FE, Hur K, Dong D, Miller DR, Zhang R, Wei X, McCarren M, Mosholder AD, Graham DJ, Aspinall SL, Good CB. Use of varenicline for smoking cessation was not associated with a detectable increase compared with nicotine patches in hospitalization for any mental health outcomes. Adiction. 2016 Jan 30. (Epub ahead of print.)

Fluoroquinolone interactions with mycobacterium tuberculosis gyrase: enhancing drug activity against wild-type and resistant gyrase. Aldred KJ, Blower TR, Kerns RJ, Berger JM, Osheroff N. A new approach to defining drug-enzyme interactions with the potential to identify novel drugs with improved activity against tuberculosis. Proc Natl Acad Sci USA, 2016 Feb 16:113(7):E839-46.

Telephone smoking-cessation counseling for smokers in mental health clinics: a patient-randomized controlled trial. Rogers ES, Smelson DA, Gillespie CC, Elbel B, Poole S, Hagedorn HJ, Kalman D, Krebs P, Fang Y, Wang B, Sherman SE. A specialized counseling intervention was more effective at helping patients quit than transfer to a state quit-line. Am J Prev Med. 2016 April;50(4):518-27.

Airway bacteria drive a progressive COPD-like phenotype in mice with polymeric immunoglobulin receptor deficiency. Richmond BW, Brucker RM, Han W, Du RH, Zhang Y, Cheng DS, Gleaves L, Abdolrasulnia R, Polosukhina D, Clark PE, Bordenstein SR, Blackwell TS, Polosukhin VV. In mice, persistent inflammation in COPD may result from a defect in the immune system that allows airway bacteria to invade deeper into the lung. Nat Commun. 2016 Apr 5;7:11240.

Burn pit emissions exposure and respiratory and cardiovascular conditions among airborne hazards and open burn pit registry participants. Liu J, Lezana N, Gasper J, Kawata J, Morley S, Helmer D, Ciminaro P. there is an association between burn pit emissions exposure and higher incidences of postdeployment self-reported respiratory and cardiovascular conditions. JOEM 2016 Jul;58(7):e249-55.

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