Exhaled breath profiling for diagnosing acute respiratory distress syndrome

BACKGROUND The acute respiratory distress syndrome (ARDS) is a common, devastating complication of critical illness that is characterized by pulmonary injury and inflammation. The clinical diagnosis may be improved by means of objective biological markers. Electronic nose (eNose) technology can rapidly and non-invasively provide breath prints, which are profiles of volatile metabolites in the exhaled breath. We hypothesized that breath prints could facilitate accurate diagnosis of ARDS in intubated and ventilated intensive care unit (ICU) patients. METHODS Prospective single-center cohort study with training and temporal external validation cohort. Breath of newly intubated and mechanically ventilated ICU-patients was analyzed using an electronic nose within 24 hours after admission. ARDS was diagnosed and classified by the Berlin clinical consensus definition. The eNose was trained to recognize ARDS in a training cohort and the diagnostic performance was evaluated in a temporal external validation cohort. RESULTS In the training cohort (40 patients with ARDS versus 66 controls) the diagnostic model for ARDS showed a moderate discrimination, with an area under the receiver-operator characteristic curve (AUC-ROC) of 0.72 (95%-confidence interval (CI): 0.63-0.82). In the external validation cohort (18 patients with ARDS versus 26 controls) the AUC-ROC was 0.71 [95%-CI: 0.54 - 0.87]. Restricting discrimination to patients with moderate or severe ARDS versus controls resulted in an AUC-ROC of 0.80 [95%-CI: 0.70 - 0.90]. The exhaled breath profile from patients with cardiopulmonary edema and pneumonia was different from that of patients with moderate/severe ARDS. CONCLUSIONS An electronic nose can rapidly and non-invasively discriminate between patients with and without ARDS with modest accuracy. Diagnostic accuracy increased when only moderate and severe ARDS patients were considered. This implicates that breath analysis may allow for rapid, bedside detection of ARDS, especially if our findings are reproduced using continuous exhaled breath profiling. TRIAL REGISTRATION NTR2750, registered 11 February 2011.