In this issue of CHEST (see page 2115), Phillips et al expand on previous work, examining the role of volatile organic compounds and monomethylated alkanes in human breath as biological markers of lung cancer.17
Those entities are produced by lipid peroxidation of polyunsaturated fatty acids in ubiquitous cell membranes, which are measured in the breath as ethanes, pentanes, or methylated alkanes. In this preliminary work, the authors present evidence suggesting that lung cancers are associated with a relatively unique chemical footprint, an observation that may be incorporated into lung cancer screening. In a group of 219 subjects, 178 of whom had undergone bronchoscopy for the evaluation of lung cancer, breath analysis detected lung cancer with a sensitivity of 90% and a specificity of 83%. The negative predictive value was a remarkable 99%, a finding that, if confirmed, could lead to the elimination of most benign false-positive results that are picked up on spiral CT screening, thus obviating the need for further workup and potentially unnecessary surgery. Unfortunately, separation by tumor type or smoking status was not associated with unique patterns on breath analysis. Disappointingly, there did not seem to be a correlation between cancer stage, and therefore tumor mass, and chemical footprint. In addition, the authors observed high rates of false-positive results in those subjects in whom cancer had not been confirmed by CT scanning or bronchoscopy. The authors suggest a role for breath analysis in screening, with CT scanning or bronchoscopy reserved only for those with positive results. If this technology were developed further, however, the optimal sequencing of CT scanning and breath analysis would need to be evaluated. It may be that spiral CT scanning would be the initial test, with breath analysis used subsequently.