Assessment of Breathomics Testing Using High-Pressure Photon Ionization Time-of-Flight Mass Spectrometry to Detect Esophageal Cancer

Abstract

IMPORTANCE A triage test is needed to increase the detection rate for esophageal cancer. OBJECTIVE To investigate 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). DESIGN, SETTING, AND PARTICIPANTS This diagnostic study included participants who planned to receive an upper endoscopy or surgery of the esophagus at a single center in China. Exhaled breath was collected with a self-designed collector and air bags before participants underwent these procedures. Sample collection and analyses were performed by trained researchers following a standardized protocol. Participants were randomly divided into a discovery data set and a validation data set. Data were collected from December 2020 to March 2021. EXPOSURES Breath samples were analyzed by HPPI-TOFMS, and the support vector machine algorithm was used to construct a detection model. MAIN OUTCOMES AND MEASURESThe accuracy of breathomics was measured by the sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve. RESULTSExhaled breath samples were obtained from 675 patients (216 [32%] with esophageal cancer; 459 [68%] with noncancer diseases). Of all patients, 206 (31%) were women, and the mean (SD) age was 64.0 (11.9) years. In the validation data set, esophageal cancer was detected with an accuracy of 93.33%, sensitivity of 97.83%, specificity of 83.72%, positive predictive value of 94.74%, negative predictive value of 92.78%, and area under the receiver operating characteristic curve of 0.89. Notably, for 16 patients with high-grade intraepithelial neoplasia, 12 (75%) were predicted to have esophageal cancer. CONCLUSIONS AND RELEVANCEIn this diagnostic study, testing breathomics using HPPI-TOFMS was feasible for esophageal cancer detection and totally noninvasive, which could help to improve the diagnosis of esophageal cancer.

Identification of lung cancer breath biomarkers based on perioperative breathomics testing: A prospective observational study

“… 16 , 17 , 18 , 19 , 20 Our pilot studies have confirmed the application of HPPI-TOFMS in exhaled breath testing for lung cancer and esophageal cancer detection based on spectrum characteristics. 21 , 22 This study further confirmed the property of HPPI-TOFMS in cancer screening through identifying specific VOCs.…”

“…The breath collection protocol has been thoroughly reported. 21 , 22 Briefly, all exhaled breath samples were collected by trained investigators using prepared Tedlar (DuPont de Nemours) air bags. On the night before breath collection, the Tedlar bags were baked at 60 °C for 3 h to fully release possible contaminants and continuously purged with high-purity nitrogen four times.…”

“… 20 We have preliminarily confirmed the application of HPPI-TOFMS in exhaled breath testing for lung cancer and esophageal cancer detection in cross-sectional studies. 21 , 22 …”

A feasibility study of Covid-19 detection using breath analysis by high-pressure photon ionization time-of-flight mass spectrometry

“…It does not require preprocessing of exhaled air but with a low detection limit of 0.015 ppbv. It has been employed for lung cancer and esophageal cancer detection and achieved good performances with SEN and SPE >90 [18][19][20]. As the first rapid VOCs based diagnostic test for COVID-19 in China, we found that COVID-19 patients could be easily distinguished from controls using VOCs with HPPI-TOFMS.…”

“…Recently, different online mass spectrometry technologies have been developed to analyze exhaled breath, such as proton transfer reaction MS (PTR-MS) [14], secondary electrospray ionization MS (SESI-MS) [15,16], and high-pressure photon ionization time-offlight mass spectrometry (HPPI-TOFMS) [17]. The HPPI-TOFMS platform has been used for lung cancer and esophageal cancer detection [18][19][20] and achieved good performances with sensitivity (SEN) and specificity (SPE) > 90%.…”