I have a tendency to assume the worst, and once in a while, this habit plays tricks on me. For example, if I feel unexpected pain in my body that I have not experienced before and that I cannot attribute, then all of a sudden, my mind might turn a tense back into heart disease or calf muscle pain into deep vein thrombosis. But so far, I haven't been diagnosed with any deadly or incurable disease. Sometimes things just hurt for no clear reason.
But not everyone is as lucky as me. Every year, more than 50 million people die worldwide. Especially in high-income economies like ours, a large fraction of deaths is caused by slowly progressing diseases: heart disease, chronic lung disease, cancer, Alzheimer's, diabetes, just to name a few.
Now, humanity has made tremendous progress in diagnosing and treating many of these. But we are at a stage where further advancement in health cannot be achieved only by developing new treatments. And this becomes evident when we look at one aspect that many of these diseases have in common: the probability for successful treatment strongly depends on when treatment is started. But a disease is typically only detected once symptoms occur. The problem here is that, in fact, many diseases can remain asymptomatic, hence undetected, for a long period of time. Because of this, there is a persisting need for new ways of detecting disease at early stage, way before any symptoms occur. In health care, this is called screening. And as defined by the World Health Organization, screening is "the presumptive identification of unrecognized disease in an apparently healthy person, by means of tests...that can be applied rapidly and easily..." That's a long definition, so let me repeat it: identification of unrecognized disease in an apparently healthy person by means of tests that can be applied both rapidly and easily. And I want to put special emphasis on the words "rapidly" and "easily" because many of the existing screening methods are exactly the opposite. And those of you who have undergone colonoscopy as part of a screening program for colorectal cancer will know what I mean.
Obviously, there's a variety of medical tools available to perform screening tests. This ranges from imaging techniques such as radiography or magnetic resonance imaging to the analysis of blood or tissue. We have all had such tests. But there's one medium that for long has been overlooked: a medium that is easily accessible, basically nondepletable, and it holds tremendous promise for medical analysis. And that is our breath.
Human breath is essentially composed of five components: nitrogen, oxygen, carbon dioxide, water and argon. But besides these five, there are hundreds of other components that are present in very low quantity. These are called volatile organic compounds, and we release hundreds, even thousands of them every time we exhale. The analysis of these volatile organic compounds in our breath is called breath analysis. In fact, I believe that many of you have already experienced breath analysis. Imagine: you're driving home late at night, when suddenly, there's a friendly police officer who asks you kindly but firmly to pull over and blow into a device like this one. This is an alcohol breath tester that is used to measure the ethanol concentration in your breath and determine whether driving in your condition is a clever idea. Now, I'd say my driving was pretty good, but let me check.
0.0, so nothing to worry about, all fine.
Now imagine a device like this one, that does not only measure alcohol levels in your breath, but that detects diseases like the ones I've shown you and potentially many more. The concept of correlating the smell of a person's breath with certain medical conditions, in fact, dates back to Ancient Greece. But only recently, research efforts on breath analysis have skyrocketed, and what once was a dream is now becoming reality. And let me pull up this list again that I showed you earlier. For the majority of diseases listed here, there's substantial scientific evidence suggesting that the disease could be detected by breath analysis.
But how does it work, exactly? The essential part is a sensor device that detects the volatile organic compounds in our breath. Simply put: when exposed to a breath sample, the sensor outputs a complex signature that results from the mixture of volatile organic compounds that we exhale. Now, this signature represents a fingerprint of your metabolism, your microbiome and the biochemical processes that occur in your body. If you have a disease, your organism will change, and so will the composition of your exhaled breath. And then the only thing that is left to do is to correlate a certain signature with the presence or absence of certain medical conditions.
The technology promises several undeniable benefits. Firstly, the sensor can be miniaturized and integrated into small, handheld devices like this alcohol breath tester. This would allow the test to be used in many different settings and even at home, so that a visit at the doctor's office is not needed each time a test shall be performed.
Secondly, breath analysis is noninvasive and can be as simple as blowing into an alcohol breath tester. Such simplicity and ease of use would reduce patient burden and provide an incentive for broad adoption of the technology.
And thirdly, the technology is so flexible that the same device could be used to detect a broad range of medical conditions. Breath analysis could be used to screen for multiple diseases at the same time. Nowadays, each disease typically requires a different medical tool to perform a screening test. But this means you can only find what you're looking for.
With all of these features, breath analysis is predestined to deliver what many traditional screening tests are lacking. And most importantly, all of these features should eventually provide us with a platform for medical analysis that can operate at attractively low cost per test. On the contrary, existing medical tools often lead to rather high cost per test. Then, in order to keep costs down, the number of tests needs to be restricted, and this means (a) that the tests can only be performed on a narrow part of the population, for example, the high-risk population; and (b) that the number of tests per person needs to be kept at a minimum. But wouldn't it actually be beneficial if the test was performed on a larger group of people, and more often and over a longer period of time for each individual? Especially the latter would give access to something very valuable that is called longitudinal data.
Longitudinal data is a data set that tracks the same patient over the course of many months or years. Nowadays, medical decisions are often based on a limited data set, where only a glimpse of a patient's medical history is available for decision-making. In such a case, abnormalities are typically detected by comparing a patient's health profile to the average health profile of a reference population. Longitudinal data would open up a new dimension and allow abnormalities to be detected based on a patient's own medical history. This will pave the way for personalized treatment.
Sounds pretty great, right? Now you will certainly have a question that is something like, "If the technology is as great as he says, then why aren't we using it today?" And the only answer I can give you is: not everything is as easy as it sounds. There are technical challenges, for example. There's the need for extremely reliable sensors that can detect mixtures of volatile organic compounds with sufficient reproducibility. And another technical challenge is this: How do you sample a person's breath in a very defined manner so that the sampling process itself does not alter the result of the analysis? And there's the need for data. Breath analysis needs to be validated in clinical trials, and enough data needs to be collected so that individual conditions can be measured against baselines. Breath analysis can only succeed if a large enough data set can be generated and made available for broad use.
If breath analysis holds up to its promises, this is a technology that could truly aid us to transform our health care system—transform it from a reactive system where treatment is triggered by symptoms of disease to a proactive system, where disease detection, diagnosis and treatment can happen at early stage, way before any symptoms occur.
Now this brings me to my last point, and it's a fundamental one. What exactly is a disease? Imagine that breath analysis can be commercialized as I describe it, and early detection becomes routine. A problem that remains is, in fact, a problem that any screening activity has to face because, for many diseases, it is often impossible to predict with sufficient certainty whether the disease would ever cause any symptoms or put a person's life at risk. This is called overdiagnosis, and it leads to a dilemma. If a disease is identified, you could decide not to treat it because there's a certain probability that you would never suffer from it. But how much would you suffer just from knowing that you have a potentially deadly disease? And wouldn't you actually regret that the disease was detected in the first place?
Your second option is to undergo early treatment with the hope for curing it. But often, this would not come without side effects.
To be precise: the bigger problem is not overdiagnosis, it's overtreatment, because not every disease has to be treated immediately just because a treatment is available. The increasing adoption of routine screening will raise the question: What do we call a disease that can rationalize treatment, and what is just an abnormality that should not be a source of concern? My hopes are that routine screening using breath analysis can provide enough data and insight so that at some point, we'll be able to break this dilemma and predict with sufficient certainty whether and when to treat at early stage.
Our breath and the mixture of volatile organic compounds that we exhale hold tremendous amounts of information on our physiological condition. With what we know today, we have only scratched the surface. As we collect more and more data and breath profiles across the population, including all varieties of gender, age, origin and lifestyle, the power of breath analysis should increase. And eventually, breath analysis should provide us with a powerful tool not only to proactively detect specific diseases but to predict and ultimately prevent them. And this should be enough motivation to embrace the opportunities and challenges that breath analysis can provide, even for people that are not part-time hypochondriacs like me.