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Cancer Breath Test

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CLEVELAND, Ohio (Ivanhoe Newswire) - Each person breathes in and out about 14 times a minute. That adds up to 21,000 breaths a day, ten and a half million breaths a year. Each one says a lot about you, and not just if you need a mint. We explain how our breath could revolutionize disease diagnosis.

Failing a particular breath test could mean jail. Failing this one could mean cancer.

Doctors at Cleveland Clinic are working on a breath test that can detect liver, kidney, and heart disease.

"The way I look at breath testing, it's the new frontier of medical testing," Raed A. Dweik, M.D., Professor of Medicine, Director of the Pulmonary Vascular Program at the Cleveland Clinic told Ivanhoe.

That's because a lot of things, good or bad, make their way from your tissues to your blood and go through your lungs.

"Our breath works kind of like an exhaust system for the body. Depending on how the different body parts are working, the chemicals in the breath might be different," Peter Mazzone, M.D., a Lung Specialist at the Cleveland Clinic said.

Hi-tech sensors can detect differences up to a part per billion in a person's chemistry.

"To give you a concept, if you have baseball field filled with white ping pong balls, and only one red one. That's a part per billion. That's how sensitive these devices are," Dr. Dweik said.

Studies show the breath test to be 80 percent accurate in not only detecting lung cancer, but also the type, the stage, and how aggressive the cancer is.

Doctors hope the breath test will one day detect all types of cancer.

"That's the holy grail of breath testing," Dr. Dweik said.

Proving medicine's next big thing could be just a breath away.

Doctors at the Cleveland Clinic hope to have this in general practitioners' offices within five years. Soon after, they hope to develop a test that would work through your smart phone.

RESEARCH SUMMARY

BACKGROUND:

  • Liver disease: Liver problems include a wide range of diseases and conditions that can affect your liver. Your liver is an organ about the size of a football that sits just under your rib cage on the right side of your abdomen. Without your liver, you couldn't digest food and absorb nutrients, get rid of toxic substances from your body or stay alive. Liver problems can be inherited, or liver problems can occur in response to viruses and chemicals. Some liver problems are temporary and go away on their own, while other liver problems can last for a long time and lead to serious complications.
  • Kidney disease: Most kidney diseases attack the nephrons. This damage may leave kidneys unable to remove wastes. Causes can include genetic problems, injuries, or medicines. You are at greater risk for kidney disease if you have diabetes, high blood pressure, or a close family member with kidney disease.
  • Heart disease: Heart disease is a broad term used to describe a range of diseases that affect your heart. The various diseases that fall under the umbrella of heart disease include diseases of your blood vessels, such as coronary artery disease; heart rhythm problems (arrhythmias); heart infections; and heart defects you're born with (congenital heart defects). (Source: MayoClinic)

DIAGNOSIS:

  • Liver disease: Tests and procedures used to diagnose liver problems include blood tests, imaging tests, and tests of liver tissue.
  • Kidney disease: BUN (Blood Urea Nitrogen) is a blood test which assesses kidney function. Urea is a by-product of protein metabolism and is formed in the liver. Urea is filtered from the blood by the kidneys and excreted in the urine.
  • Heart disease: Blood tests, chest x-ray, electrocardiogram, holter monitoring, echocardiogram, cardiac catheterization, heart biopsy, cardiac computerized tomography (CT) scan, and cardiac magnetic resonance imaging (MRI) (Source: MayoClinic)

NEW TECHNOLOGY: Doctors at Cleveland Clinic are working on a breath test that can detect liver disease, kidney disease, and heart disease, among other things. When a person breathes into the "electronic nose" machine, it activates a sensor and changes its color based on chemicals in the breath. A miniature camera inside the machine takes pictures of the sensor and sends them to a computer, which stores the images and analyzes color changes to determine the type of cells present and diagnose patients while they're still in the office. A study in which breath samples were taken from 229 patients at the Clinic (92 with untreated lung cancer, the rest cancer-free but with a history of smoking) was 81 percent accurate for detecting lung cancer. The study also showed accuracy of between 83 percent and 89 percent for the kind of lung cancer a patient has and about 79 percent accuracy in distinguishing early-stage cancer from late stage, according to Metabolomx. (Source: Cleveland Clinic)

INTERVIEW

 

Raed Dweik, M.D., a Staff Physician at the Respiratory Institute, discusses a new breath test that could help to detect liver disease, cancer and possibly other diseases.

Can you talk about the breath test?

Dr. Dweik: Yes, we're using the breath test as a tool to look at a variety of diseases. We've looked at things all the way from lung cancer, to liver disease, to kidney failure, to heart failure even, and other lung diseases like asthma and pulmonary hypertension. It seemed like the more we look the more we find. Some diseases we were expecting to find to be different, like patients with liver disease or kidney disease, even when you are interacting with them you know the breath smell is different. They know there's something going on with them, but even patients that to the normal nose don't smell any differently we are finding differences in their breath. That can tell us that they are different from people who do not have a specific disease, which is exciting for us.

Can you tell these differences when someone is in the beginning stages of heart disease?

Dr. Dweik: That's correct. You see it differently in stages of the disease. Sometimes early on. When we start testing things, we like to look at the extreme. So we try to see the sickest people compared to control groups, but even when you look at people who are less sick, we are still finding the breath signature of the disease in many of those as well.

It's all different signatures, correct?

Dr. Dweik: That's correct. It's different molecules in different diseases, yes.

Could it be one day we just all go to our general practitioner and blow into a sensor and find if we have anything going on?

Dr. Dweik: I think so, that's definitely the Holy Grail of breath testing. When you go to a physician now, you are used to getting either a blood test or a urine test or an x-ray. The way I look at breath testing is it's really the new frontier of medical testing, that in the future you'll go in your physician's office and blow into the device and tell if you have a certain disease or not. We're not there yet, but definitely we're building a lot of that scientific basis and the proof of concepts to get there. In some diseases we are already there, like in asthma for example we have a test already FDA approved to look at that. For looking at carbon dioxide in exhaled breath there are several tests that are approved for use in the medical ICU and operating room. So these are some existing breath tests that we don't even think of them as breath tests, because there are so commonly used in clinical practice, but they are breath tests. The kind of testing that we're talking about now is even far beyond that. We will look at diseases that traditionally we don't think of them as ones that we can detect in the breath.

Why is it that the breath is the key?

Dr. Dweik: If you think about it, your whole blood goes through your lungsand the air in the lungs is the headspace of that blood. So anything in your blood that is potentially volatile has a vapor pressure basically and it can be detected in the breath. The problem historically was of course that we did not have the technology to detect these things. We knew for a long time that we consume oxygen and produce carbon dioxide as part of normal breathing. We thought that's all the lungs did, but as we get new technology like mass spec and laser devices, different types of technologies now reveal that we are able to detect these compounds in the breath because they are present in very small amounts. For example, with nitric oxide, the FDA approved test, we are detecting things at the level of parts per billion. A part per billion is a very small amount. Just to give you a concept of it, it is like you have a baseball field filled with white ping pong balls and only one red ping pong ball in all these ping pong balls is a part per billion. This is how sensitive these devices are. 20 or 30 years ago we could not do that kind of stuff so it's really an interface between technology and medicine that's helping this become a reality. So it's a relatively new field but is moving very fast because of improvements in technology and acceptance in the medical field that this is a reality and something that can be done.

Is the breath test more accurate than the fluids of your eyes?

Dr. Dweik: I'm not familiar with the details of that research, but I can see how they can be complementary. Maybe some things we can detect by an eye test that you cannot detect with a breath test and the same thing for the blood. I'm not saying that the breath will replace the blood, but maybe some things are better tested in the blood, some things are better tested in the breath depending on the compound and on the need. Even the breathalyzer tests you can do as a blood test, but it's not practical to do that on the side of the road to see if somebody has a high level of alcohol. This is why the breath in a way is better and more practical than the blood test. I think for some medical applications that would also be the case as we get more tests tested and verified.

What wouldn't the breath test be good at?

DR. Dweik: We're focusing on what diseases that I call low hanging fruit diseases. The ones we're focusing on as you mentioned are liver disease and kidney disease. We have a lot of data showing that you can tell not only liver disease from not liver disease, but also different types of liver disease and even the specific diagnosis of liver disease. That's kind of exciting because liver disease is not just one thing, you have different known types and different diseases.

What can it tell the difference between just in the liver?

Dr. Dweik: Like if we have acute liver disease versus chronic liver disease. Somebody whose liver is just failing versus it has been failing for a while. In patients with kidney disease, for example, it can detect whether you've had dialysis or not. So it may not only be useful as a diagnostic test but maybe be more useful as monitoring how much dialysis somebody needs or does not need. When people think of the test they always think it is for making a diagnosis, but that's not the only reason we use tests in medicine. Sometimes we use them to either predict a prognosis, how well the patient's going to do or their response to treatment. So there are a lot of applications that the breath can fill a gap for that doesn't existing in current tests.

It seems like it would be super cost-effective for catching early kinds of disease.

Dr. Dweik: Yes, we call it screening in medicine, like to screen for something. I think that does make a lot of sense because it's an easy thing to do, we can do it quickly, and it may not be the definitive test but we can tell if there's a risk. We have 10 patients with suspicion of a disease, you screen a bunch of them, and then you find out two or three of them need more testing. The other 7 you say are fine, don't need any more testing, their breath is clean, and move on. That maybe one way where the breath can be used as a screening tool because as you said, it's easy to do and can be more practical in the physician's office than doing something that takes longer or is more sophisticated.

For liver disease and kidney disease, how would you normally test that?

Dr. Dweik: Blood tests, most of these things are blood test.

Do you have any numbers on how more cost effective the breath test is?

Dr. Dweik: We are not there yet, so I think this is going to be maybe a few years down the line. Where we are now is what you call proof of concept studies where we know that this can be done, but it has not been done in large scale clinical trials. We have access to a large number of patients here at the clinic, but the stage that we're in now is early, we first have to discover that there's a problem and then you can do more studies to confirm it and verify it. That needs probably larger studies that are multicenter and we have not done that yet, but I think that that needs to be done.

What has been the main result of the study?

Dr. Dweik: The main result from the studies for the liver is that we can tell liver disease from controls, people that don't have liver disease.

How efficient is the test in detecting liver disease from the controls?

Dr. Dweik: In our hands we can now tell in the high 90s percent of the time. Of course when you take that to a more general population the tests may not work as well, but definitely it's very promising when it works this well to start with. In patients with kidney disease we focused on the effect of dialysis. It seems like the breath of these patients after dialysis is much cleaner than the patient before dialysis which tells us it's a potential use to monitor the effects of dialysis in these patients.

Is the key to your sensors much smaller than the other sensors?

Dr. Dweik: Yes.. We are collaborating with NASA. NASA is good at making things smaller, miniaturize everything, and to send it in space it has to be lightweight and low-energy consuming. So we are working in collaboration with them and a group at Ohio State. You need large equipment to discover the molecule, like mass spectrometry type devices, but once you know what molecule you're looking at you can build smaller sensors that can detect that molecule and then miniaturize them even further. That can be used in a handheld device or a portable device. A few years ago we called it a dream to have a breath test in your smart phone or something that small, but I think that we're even closer to this than we would have thought five years ago. The devices that could be available now are the size of a small bottle of water, for example. I can see how something like that will end up with technology getting better and being put into cell phones and other devices like that. We're not there yet, but I think that's coming soon.

How long until this is a reality?

Dr. Dweik: I'm thinking a few years, maybe in three or four years, but to be that small it probably needs both verification of the testing so the miniaturization will be in more like the five to ten years kind of range.

If you would like more information, please contact:

Raed A. Dweik, M.D.
Office (Pulmonary): (216) 445-5763
Breath Analysis Program: (216) 445-4365
dweikr@ccf.org

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