Screening for emphysema via exhaled volatile organic compounds.

Chronic obstructive pulmonary disease (COPD)/emphysema risk groups are well defined and screening allows for early identification of disease. The capability of exhaled volatile organic compounds (VOCs) to detect emphysema, as found by computed tomography (CT) in current and former heavy smokers participating in a lung cancer screening trial, was investigated. CT scans, pulmonary function tests and breath sample collections were obtained from 204 subjects. Breath samples were analyzed with a proton-transfer reaction mass spectrometer (PTR-MS) to obtain VOC profiles listed as ions at various mass-to-charge ratios (m/z). Using bootstrapped stepwise forward logistic regression, we identified specific breath profiles as a potential tool for the diagnosis of emphysema, of airflow limitation or gas-exchange impairment. A marker for emphysema was found at m/z 87 (tentatively attributed to 2-methylbutanal). The area under the receiver operating characteristic curve (ROC) of this marker to diagnose emphysema was 0.588 (95% CI 0.453-0.662). Mass-to-charge ratios m/z 52 (most likely chloramine) and m/z 135 (alkyl benzene) were linked to obstructive disease and m/z 122 (most probably alkyl homologs) to an impaired diffusion capacity. ROC areas were 0.646 (95% CI 0.562-0.730) and 0.671 (95% CI 0.524-0.710), respectively. In the screening setting, exhaled VOCs measured by PTR-MS constitute weak markers for emphysema, pulmonary obstruction and impaired diffusion capacity.