Can Pulmonary Hypertension Be Detected in Breath? E-Nose Thinks So

An electronic nose, or “e-nose,” that can detect the presence of pulmonary arterial hypertension (PAH) was created by researchers at the Université Paris-Saclay in partnership with the Technion Israel Institute of Technology. The e-nose device makes use of the fact that PAH has a marked olfactory signature, with a specific profile of volatile compounds, that can be detected in exhaled breath.

A proof-of-concept study for the e-nose in the detection of PAH, “A Proof of Concept for the Detection and Classification of Pulmonary Arterial Hypertension through Breath Analysis with a Sensor Array,” was published by Sylvia Cohen-Kaminsky, PhD, and colleagues in the American Journal of Respiratory and Critical Care Medicine.

“The gold standard for the diagnosis of PAH is right heart catheterism, which can make the right diagnosis, but it is invasive, risky and unsuitable for widespread screening,” said Cohen-Kaminsky in a press release. “The e-nose is a non-invasive and safe detection method that means general screening of PAH could eventually be made available.”

E-nose was tested in small groups of PAH patients, using two different combinations of sensing-feature in two different tests: one for disease detection in a mix of 22 patients with PAH and 23 healthy controls, and the other for distinguishing between idiopathic (no known cause) and heritable (mutation of the BMPR2 gene) forms of PAH among patients (15 versus 7 patients, respectively).

Researchers observed that the e-nose detected with 100% sensitivity, 83% specificity and 92% accuracy those people with PAH from those without the disease, and distinguished between the two forms of PAH with 87% accuracy, showing that the presence of a genetic mutation can translate into a specific breath “fingerprint.”

A clinical trial to validate the device as a non-invasive test for the diagnosis of PAH is now ongoing outside Paris, France, (SNOOPY2 trial, NCT02782026). The trial, which is recruiting PAH patients and healthy participants, intends to confirm if, in a larger population sample, the e-nose can discriminate between controls and PAH patients, as well as to distinguish between idiopathic, heritable (with BMPR2 mutation) and chronic thromboembolic PAH (CTEPH). More information on this study, including recruitment information, is available on its clinical trials.gov website.

The e-nose technology was originally created by Professor Hossam Haick, with Technion, to detect ovarian cancer through the presence of compounds specific to this cancer in breath samples. Given that PH patients also have an altered breath signature, Cohen-Kaminsky proposed a partnership to adapt the device for PH.

The e-nose consists of a small, breath-diagnostic array based on gold nanoparticle sensors coupled with chemical modules to be used as an “electronic nose.” Similar to a human nose, the e-nose will respond to a given odor and generate a pattern, or “smellprint,” which is collected by the sensor arrays within the device, and then analyzed by statistical algorithms.

If proven to work, the e-nose will allow an easier and earlier diagnosis of PH, an important step in the management of the disease.