Imagine the scene: it’s 2030, you feel unwell, your body hasn’t felt like itself for a few weeks now. You’re worried it could be something concerning. You head to the nearest hospital and they wish to run a few tests. A decade ago, perhaps, you would be worried about whether your insurance covers the series of tests and machines you’re about to be put through. Instead, all that the doctors require are samples of your blood, breath, saliva and some dental and eye images. You sit in a regular chair, no whirring machinery; you simply blow into a breathalyzer; spit in a test tube; feel a prick against your finger and have some images of your eye and teeth taken. Next thing you know, the display in front of you has text and graphics running across the screen, showing all possible areas of concern.
This scenario is a paradigm shift from the way screening and diagnosis happens today: a litany of invasive, expensive tests that detect the disease late in its life cycle, to potentially a painless, quick and convenient set of tests capturing a complete health profile that can detect conditions early.
Healthcare screening today is riddled with problems far beyond just high cost and inconvenience. Most diseases - serious illnesses and chronic ailments alike, lack preventative screening options and require specialists for diagnosis. Some require tests which are invasive and prohibitively expensive. Many of these diseases can be controlled if they’re detected early, improving the patient’s quality of life.
Using novel testing methods involving blood, breath, saliva, eye and dental images, it might be possible to envision a future with non-invasive, affordable tests that can detect these diseases early, all while being patient-friendly.
Some of the new modalities that we envision would become mainstream in the near future are:
Traditional biopsies and other testing methods are invasive, charged with potential complications, sometimes unrepeatable and cannot be performed when clinical conditions have worsened or when a tumor is inaccessible.
Combining liquid biopsy with DNA-sequencing data has shown some promising results for early detection of cancer.
During the past decade, liquid biopsy — the analysis of tumours using biomarkers circulating in fluids such as the blood — has received tremendous attention. The ability to detect and characterize tumours in such a minimally invasive and repeatable way could have considerable clinical implications, and huge progress has been made in the development of methods that can do just that.
Biomarkers can be characteristic biological properties or molecules that can be detected and measured in parts of the body like the blood or tissue. They may indicate either normal or diseased processes in the body and can be specific cells, molecules, or genes.
Recently, circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) in blood plasma have emerged as promising cancer biomarkers. They have been demonstrated to have utility for non-invasive detection of cancer, personalized treatment of late stage cancer, and residual monitoring of cancer during and after treatment.
Measuring the concentration of ctDNA released during cell death can help detect tumours
Grail, (eponymous to its objective of being the holy grail of cancer detection) a United States based company recently released clinical data of its liquid biopsy test that can detect 50 different types of cancer from a single blood draw. While its test isn’t yet FDA approved and serves as a support with other tests, it heralds a change in cancer detection methods.
Identifying and enriching these biomarkers and combining them with a genetic profile of the patient have resulted in encouraging developments towards a multitude of early disease detection tests via blood.
Metabolic diseases such as diabetes and inflammatory diseases such as IBD, Crohn’s disease and fatty liver can be controlled with early diagnosis. New research suggests that the measurement of the volatile organic compounds (VOCs) produced by the body's metabolic activity is a powerful approach for health monitoring and disease detection.
Volatile organic compounds (VOCs) are gaseous molecules that can be sampled quickly and non-invasively from breath. They can originate either from within the body (endogenous VOCs) or from external sources such as diet, prescription drugs and environmental exposure (exogenous VOCs).
Studies have identified over 900 VOCs that can be found on breath and alongside respiratory droplets, they provide a rich source of information regarding overall health and have great potential as indicators of disease onset and progression.
Biomarkers in breath*
Research is ongoing to establish clearer connections between specific VOCs and the biological processes involved in their production. Below are just a few illustrations of the association between VOCs in major diseases:
It is increasingly clear that metabolism in cancer cells vastly differs from that of healthy cells. Metabolic changes can be some of the earliest detectable changes in cancer and become more pronounced as the disease develops. The resulting changes to exhaled VOCs are further enhanced by changes resulting from responses by the immune system. Cancer is notable for its rapid growth driven largely by energy generated by drastically increased glycolytic flux, a phenomenon where more energy is released in cells due to rapid cell growth. Elevated glycolysis leads to altered VOC abundances in exhaled breath.
- VOC Biomarkers in Inflammatory Disease
The metabolic changes caused by inflammation are relevant in a range of diseases and can be detected through VOCs on breath. For example, VOCs such as undecane, 3-methylhexane and 1-pentadecene, reflect airway inflammation in respiratory diseases. Similarly, patients with inflammatory bowel disease (IBD) show elevated levels of ester, indole and short-chain fatty acids. These VOC profiles can be used to detect IBD and to differentiate between the two main forms, Crohn’s disease and those suffering from ulcerative colitis.
Saliva based tests:
Saliva is being looked at more closely than ever for its diagnostic possibilities. In recent times, because of the improved efficiency of genomic and proteomic technologies, the use of salivary diagnostics in a clinical setting is becoming a reality, a trend somewhat driven by discoveries in testing for COVID-19. The wide spectrum of biomarkers present in saliva provides valuable information for clinical diagnostic applications and can be used to detect a wide range of conditions, ranging from oral cancer to autoimmune diseases.
Saliva can be used to detect a host of conditions ranging from tumours to infections
Dental imaging involves taking a number of photographs of the teeth and jaw region. Apart from identifying dental abnormalities such as cavities and malalignment of teeth, new research suggests dental images can also be used to detect a few other health conditions early. Based on the density of the lower jaw bone, it might be possible to detect bone loss, indicative of early signs of osteoporosis**. It might also be an early indication of diabetes. Similarly, dental images can also be used to identify mucosal thickening, a sign of maxillary sinusitis***
Dental images can be used to identify a number of conditions beyond just dental abnormalities
Fundus imaging refers to the process of taking many photographs of the interior of the eye through the pupil. A fundus camera is a specialized low-power microscope attached to a camera used to examine structures such as the optic disc, retina, and lens. It is a non-invasive procedure, only takes a minute or two and provides a bird’s eye view of entire layers on the retina (the interior surface of the eye). This can be used to detect conditions such as glaucoma, diabetic retinopathy and retinoblastoma (tumour in the eye) among others, allowing early and accurate diagnosis, especially changes in the eye of patients with diabetes and blood pressure.
As a window to the brain, the retina provides a unique opportunity to study many ophthalmic and neurodegenerative diseases. A growing body of evidence has indicated that both the brain and the retina are affected in Alzheimer’s disease and these pathologic changes are significantly correlated. Using fundus imaging, it might be possible to diagnose neurodegenerative diseases such as Alzheimer’s early, improving a patient’s quality of life.
Pictured: Left - Retinal image of Alzheimer’s patients vs Right - Normal retinal image****
Future of healthcare screening:
Early detection of neurodegenerative diseases, cancer, metabolic disorders and other conditions can be life-altering for patients. In most cases, detecting a condition early enables a demonstrable treatment plan, leading to higher survival rates and quality of life. Improving patient outcomes can also help in reducing the burden on stressed healthcare systems across the world that are teetering on the brink of collapse. This vision is bolstered by research work that is underway on breath and saliva based tests and recent FDA approvals of multi-cancer liquid biopsies. Correlations are also being established between dental and fundus imaging and various other diseases that are hard to detect today. A future of non-invasive, quick tests to diagnose ailments early may prove to be a reality, paving the way towards a more proactive approach to healthcare.