Scent has been used as a diagnostic tool by physicians for thousands of years. But smell tests are not common in modern medicine—when’s the last time you were smelled by your doctor or received a batch of smell results back from the lab? Now, new research suggests that odors can be used to screen for Parkinson’s disease, which currently is without a definitive diagnostic.
In the animal kingdom, scents emitted from a body often signal information about an individual’s mental or physical state. For example, stressed rodents have been shown to excrete distinctive odors. Human body odors also have this function, emitting a wide array of odor and non-odor related chemicals called volatile organic compounds. These compounds are emitted from different areas of the human body and vary with age, diet, sex and possibly genetic background. Moreover, disease processes can influence our daily odor by changing these compounds.
So, it is perhaps not surprising that physicians have used their sense of smell to diagnose patients. In ancient Greece, Hippocrates—of the eponymous medical oath—recognized the diagnostic usefulness of body odors and reported on several disease-specific smells from urine. In an experiment published in 1776, English doctor Matthew Dobson evaporated a diabetes patient’s urine, yielding a white, granulated powder that smelled and tasted like sugar. More recently, the composition of exhaled breath was shown to be different in patients with lung cancer, inflammatory lung or liver disease, hepatic or renal dysfunction or diabetes. However, there has been little evidence to tie scent to diseases of the nervous system, with the possible exception of schizophrenia—although controversial, it has long been claimed that these patients have a particular peculiar odor.
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Here’s where Joy Milne comes in, a woman who first noticed a "musky" smell on her husband Les, who was diagnosed years later with Parkinson's disease. It turns out that Joy can distinguish the unique Parkinson's odor before clinical symptoms appear in a person’s sebum—the moisturizing, waterproofing wax that protects the skin produced by sebaceous glands. Characterizing the compounds linked to this distinctive odor in sebum could enable rapid, early screening of Parkinson’s disease as well as provide insights into changes that occur as the disease progresses. Which is exactly what researchers were able to do—chemically define the scent in sebum that Milne is picking up on in Parkinson's patients.
In preliminary tests to identify the origin of the scent, Joy inspected T-shirts and medical gauze that had sampled the upper backs of Parkinson’s patients. The odor was not present in the armpits and instead was on the forehead and upper back—not surprisingly, areas of high sebum production. The researchers then tested and compared the sebum samples from the upper backs of 43 Parkinson’s patients and 21 matched healthy subjects to discover volatile organic compounds linked to disease. To investigate the aroma-causing chemicals, the researchers used a sophisticated analytical technology: thermal desorption-gas chromatography-mass spectrometry. With it, the researchers shortened the list of Parkinson’s smell-causing candidates from the hundreds to just 17. Joy confirmed that mixing all 17 identified chemicals, or specific combinations of just nine or four, closely matched the musky fragrance she smelled on Parkinson’s patients, demonstrating that, indeed, these chemicals contribute to the unique smell associated with Parkinson’s.
This study highlights the potential of analyzing the sebum from Parkinson’s patients and raises the possibility that individuals can be screened noninvasively using a diagnostic device with a nose for these odor-based biomarkers. Such a device could allow earlier diagnosis and treatment to prevent the disease from progressing to stages with severe symptoms. However, with samples from just over 60 people, the current study is limited by sample size.The next steps are to study the sebum of more patients for an odor signature to establish a panel of odor-based biomarkers associated with Parkinson’s disease.
Without an objective test, such as a blood test or brain scan, to make a definitive diagnosis of Parkinson's disease, doctors instead look for key neurological symptoms. However, the misdiagnosis rate remains significant because the symptoms are similar to other neurological conditions, and patients cannot be treated until symptoms manifest. As the foundation of a diagnostic medical device, odorous biomarkers for Parkinson’s can open new avenues for facilitating earlier detection of the disease to prevent progressive neurodegeneration and motor symptoms, such as tremor.
However, the concept of using disease-associated odorous biomarkers as the basis for a medical device has been simmering for nearly 40 years but has so far come up empty handed. Since the 1980s, devices called “electronic noses” that mimic the human olfactory system have been developed but have only been used for research purposes. In the future, the development of new sensors with improved sensitivity could make the electronic nose an effective clinical tool for the early detection of Parkinson’s and other health problems such as infections, tumors and exposure to toxic agents. An electronic nose with the accuracy to identify specific volatile organic compounds has the potential to yield a catalog of diagnostic odorous biomarkers for patients with diseases that cannot be diagnosed with traditional clinical tools.