ORLANDO – The presence of certain carbonyl volatile organic compounds in exhaled breath can aid in the detection of early lung cancer, according to Dr. Michael Bousamra.

An analysis of volatile organic compounds (VOCs) in the exhaled breath of 10 lung cancer patients and 88 controls, including 45 smokers and 43 nonsmokers, identified four carbonyl VOCs that occurred significantly more often in the lung cancer patients’ breath samples than in the control samples: 2-butanone, 3-hydroxy-2-butanone, hydroxylacetaldehyde, and 4-hydroxyhexenal.

Further study of 151 patients with suspicious lung nodules found no single VOC marker that was independently predictive of lung cancer, but when the levels of three or more were elevated in a single patient, the sensitivity and specificity for lung cancer were 60% and 95.2%, respectively. When the levels of at least two of the VOCs were elevated, the sensitivity and specificity were 84.7% and 81%, respectively, and when at least one was elevated, the sensitivity and specificity were 93.8% and 45.2%, respectively.

A close-up of the microchip used to detect the VOCs in exhaled breath.

The absence of VOC elevation was predictive of benign disease in 80% of cases, Dr. Bousamra of the University of Louisville, Ky., reported at the annual meeting of the Society of Thoracic Surgeons.

Notably, the concentrations of three of four VOCs in samples from lung cancer patients decreased to the level found in healthy controls after resection, he noted.

This finding "lends credence to the notion that these carbonyl markers really aren’t indicators of something other than cancer," he said.

Of the 151 patients studied, 109 were diagnosed with lung cancer and 42 with benign nodules. Of those with lung cancer, 1 had stage 0 disease, 47 had stage I, 18 had stage II, 26 had stage III, and 17 had stage IV.

The exhaled breath samples were collected using a 1-L Tedlar bag and were analyzed by investigators blinded to the preoperative diagnosis and pathology.

The findings suggest that these specific VOCs in exhaled breath could be used as an adjunct to computed tomography (CT) for the diagnosis of early lung cancer. In this study, the VOCs were also useful for distinguishing benign from malignant nodules, Dr. Bousamra noted. "When three or four carbonyl markers were elevated, the probability of cancer was very high; when no carbonyl markers – or even one – was elevated, associated pulmonary disease was likely benign. I think that clinical decision making could be assisted in these instances," he said.

Dr. Michael Bousamra with Dr. Xiao-An Fu, professor of chemical engineering at the University of Louisville, who developed the device for detecting the VOCs in exhaled breath.

Carbonyl VOC testing, however, is not quite ready for prime time, he noted.

Exhaled breath has long been considered a promising noninvasive tool for the diagnosis of early lung cancer, but studies conducted to date have failed to achieve clinical significance because of a lack of specificity and challenges associated with complex volatile mixtures.

Although the findings of the current study advance the possibility of using exhaled breath in lung cancer diagnosis and clinical decision making, the study was limited by an inadequate control group. In addition, further study is needed in patients with pulmonary nodules and benign pulmonary disease, as well as in patients following resection, Dr. Bousamra said.

The study also lacked a specific look at patients with chronic obstructive pulmonary disease and other interstitial lung disease common in patients with lung cancer, he noted.

He estimated, however, that VOC testing could be in place to help with the diagnosis of lung cancer within 2 years.

The possibilities for this testing are exciting, and the work of Dr. Bousamra and his colleagues represents a window into the future of lung cancer screening and diagnosis, according to the invited discussant, Dr. Tom Varghese Jr. of the University of Washington, Seattle.

Lung cancer is the leading cause of cancer deaths worldwide, with higher mortality than the next three leading causes of cancer death combined, Dr. Varghese said.

A large screening trial showed that using low-dose CT for screening could reduce mortality by 20% – a finding that led to the recent endorsement by the U.S. Preventive Services Task Force of low-dose screening CTs for high-risk patients.

Such screening, if applied using strict criteria, "would avert 12,000 lung cancer deaths today," he said.

Adding measurement of VOCs in exhaled breath to the screening protocol could result in fewer invasive procedures for abnormal screening results, and VOC measurement could thus prove to be a simple, straightforward cost-saving measure, Dr. Varghese added.

Dr. Bousamra reported having no disclosures.

Compounds in exhaled breath could improve high-risk lung cancer screening