Breathomics is a noninvasive method that could help to improve the detection and diagnosis of esophageal cancer, according to a study published in JAMA Network Open.

Most patients with esophageal cancer are diagnosed at a late stage. Endoscopy is not suitable for population-based screening, as it is invasive, expensive, and not sensitive among patients without symptoms. Therefore, a better-suited tool is urgently needed for detecting esophageal cancer at an early stage of disease.

Breathomics, which focuses on metabolites in exhaled breath, offers the possibility of noninvasive disease diagnosis and therapeutic monitoring. Researchers in China investigated whether breathomics can detect esophageal cancer among patients without a previous diagnosis of cancer using high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS).

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This study included participants who planned to receive an upper endoscopy or esophageal surgery at a single center.  Patients were randomly divided into a discovery data set and a validation data set. A total of 1000 mL of exhaled breaths were collected via air bags for each patient and tested with HPPI-TOFMS. Sensitivity, specificity, accuracy, positive and negative predictive values, and area under the receiver operating curves (AUC) were analyzed to determine the diagnostic accuracy of breathomics.

Out of the exhaled breath samples obtained from 675 patients, 31% were women; mean participant age was 64.0 years. In total, 216 [32%] patients had esophageal cancer and 459 [68%] had noncancer diseases.

In the discovery set, esophageal cancer was successfully detected with a sensitivity of 97.55%, a specificity of 86.13%, an accuracy of 93.89%, a positive predictive value of 94.30%, a negative predictive value of 93.72%, and an AUC of 0.97.

The researchers found that in the validation data set, esophageal cancer was detected with a sensitivity of 97.83%, a specificity of 83.72%, an accuracy of 93.33%, a positive predictive value of 94.74%, a negative predictive value of 92.78%, and an AUC of 0.89. Additionally, for 16 patients with high-grade intraepithelial neoplasia, 12 (75%) were predicted to have esophageal cancer.

Investigators noted they were unable to characterize exact molecules of specific features, as the chemistry involved would be beyond the scope of their research. 

The authors concluded, “In this diagnostic study, we demonstrated as a proof of concept that testing breathomics is feasible and highly acceptable among patients receiving upper endoscopy.”


Huang Q, Wang S, Li Q, at al. Assessment of breathomics testing using high-pressure photon ionization time-of-flight mass spectrometry to detect esophageal cancer. JAMA Netw Open. 2021;4(10):e2127042. doi: 10.1001/jamanetworkopen.2021.27042