A breath test based on detecting volatile organic compounds accurately detected colorectal cancer in a prospective diagnostic study.
The technique, which is also being developed to detect cancers of the esophagus, stomach and pancreas, could be used as a triage tool due to its high negative predictive value.
Wearable biosensors may accelerate the translation of breath analysis, but further development is needed.
A breath test based on detecting volatile organic compounds (VOCs) accurately detected colorectal cancer (CRC) in a prospective diagnostic trial, called COBRA1, with results published in Gastroenterology. The researchers suggest that the technique, which they are developing to detect gastrointestinal cancers, including those of the esophagus, stomach, pancreas and colon, may be used as a triage tool.
“The breath test is non-invasive, easy to complete and universally acceptable to patients,” explained study lead George B. Hanna, PhD, in a news release. “If the breath test is successfully developed, it has great potential to influence clinical practice.”
The 5-year survival rate of CRC, which is the third most common cancer globally, is 92% when diagnosed early. If CRC is diagnosed at an advanced stage, the 5-year survival rate is 10%.
Unlike colonoscopy, a VOC-based breath test is noninvasive, simple to undertake, and acceptable to most patients, making it an ideal intermediate triage tool for CRC, as noted by the Gastroenterology authors.
The aim of the COBRA1 trial was to develop a breath test to detect CRC. Between June 2017 and February 2020, the study recruited patients attending seven UK hospitals for a CRC screening program colonoscopy. Of the patients, 664 had a positive fecal occult blood test, 123 needed surgical colorectal adenocarcinoma resection, and 645 required colonoscopies for other indications. Breath was collected from the patients immediately before colonoscopy and surgery. Machine learning was used to identify VOCs and clinical metadata to develop an analysis model.
A total of 1,432 patients (male, 58%; median age, 66.5 years) were included in the analysis. Of these patients, 619 had low-, intermediate- or high-risk polyps; 357 had a normal colonoscopy; 188 had benign pathology, including hemorrhoids or diverticular disease; 106 had inflammatory bowel disease; and 162 had CRC, of which 64.2% were T3 or T4.
High negative predictive value
A diagnostic model comparing the 162 patients with CRC and the 1,270 patients without CRC based on 14 endogenous VOCs and body mass index predicted CRC with area under the receiver-operating characteristic (ROC) curve of 0.87, sensitivity of 79%, specificity of 86%, and negative predictive value of 97%. A model using data from the 855 patients who reported at least one symptom at the time of breath sampling (CRC, 146; non-CRC, 709), predicted CRC with an area under the ROC curve of 0.91, sensitivity of 83%, specificity of 88%, and negative predictive value of 96%.
If a physician “is presented with a patient with recent gastrointestinal symptoms that may be benign or indicate cancer, they would not need to watch and wait to see if symptoms worsen but could offer the breath test immediately,” Dr. Hanna said. “A positive test would warrant an urgent referral for specialized tests, whereas a negative test would enable the physician to reassure the patient and offer retesting if symptoms persist.”
Application of breath testing
To date, more than 3,000 VOCs have been identified in breath, which could potentially help monitor several health parameters, according to authors of an article in Nature Reviews Bioengineering.
For example, breath tests for lactulose and glucose substrates are widely used to diagnose bacterial overgrowth in the small intestine.
The tests can be carried out at home but they are prone to inaccurate results, including false-negative and false-positive results. Aside from breath analyzers to measure alcohol levels, diagnostic tools that analyze VOCs have been mainly limited to laboratory tests.
Transitioning from the lab
“The transition from laboratory-based measurement techniques to wearable biosensors is necessary to accelerate the translation of breath analysis,” said the Nature authors.
Laboratory-based measurement techniques rely on the collection of an exhaled breath condensate, which is analyzed by chromatography and/or spectroscopy. A lack of workflow standardization, long turnaround times, high costs, and complex sample preparation limit such methods. Meanwhile, wearable sensors provide simultaneous sample collection and analysis, and allow for breath collection over a long period of time, providing real-time sampling and analysis.
Wearables in development
Wearables designed as face masks have been tested for the detection of hydrogen peroxide, which is a biomarker for respiratory illnesses, including asthma, chronic obstructive pulmonary disease, and lung cancer, by electrochemical sensing.
The use of pressure sensors has been studied in breath-condition monitoring, such as respiration rate, cough, and breath holding. Meanwhile, face masks comprising a lyophilized CRISPR sensor can help detect SARS-CoV-2 nucleic acids, and an optical sensor array has been shown to help analyze COVID-19 severity.
While several technological and ethical challenges of wearable breath analysis need to be addressed, it “could become a complementary tool for distributed, preventive healthcare monitoring and transform our understanding of diagnostics,” the Nature authors concluded.
What this means for you
Trials for cancer breath tests are in the final stages. These noninvasive, simple tests could potentially help detect cancer of the esophagus, stomach, pancreas, and colon. Wearable devices may enhance breath analysis, but further development is needed. For information on an open trial of the breath test, click here.