Progress in the Development of Volatile Exhaled Breath Signatures of XXXX .

@entity5 @entity1 @entity2031 @entity2
RATIONALE: Volatile organic compounds present in the exhaled breath have shown promise as biomarkers of @entity2 . Advances in colorimetric sensor array technology, breath collection methods, and clinical phenotyping may lead to the development of a more accurate breath biomarker. OBJECTIVES: Perform a discovery-level assessment of the accuracy of a colorimetric sensor array-based volatile breath biomarker. METHODS: Subjects with biopsy-confirmed untreated @entity2 , and others at risk for developing @entity2 , performed tidal breathing into a breath collection instrument designed to expose a colorimetric sensor array to the alveolar portion of the breath. Random forest models were built from the sensor output of 70% of the study subjects and were tested against the remaining 30%. Models were developed to separate @entity5 and subgroups from control, and to characterize the @entity5 . Additional models were developed after matching the clinical phenotypes of @entity5 and control subjects. MEASUREMENTS AND MAIN RESULTS: Ninety-seven subjects with @entity2 and 182 control subjects participated. The accuracies, reported @entity2031 -statistics, for models of @entity5 and subgroups versus control ranged from 0.794 to 0.861. The accuracy was improved by developing models for @entity5 and control groups selected through propensity matching for clinical variables. A model built using only subjects from the largest available clinical subgroup (49 subjects) had a C-statistic of 0.982. Models developed and tested to characterize @entity5 histology, and to compare early- with late-stage @entity5 , had C-statistics of 0.881-0.960. CONCLUSIONS: The colorimetric sensor array signature of exhaled breath volatile organic compounds was capable of distinguishing @entity1 with @entity2 from clinically relevant control subjects in a discovery level trial. The incorporation of clinical phenotypes into the further development of this biomarker may optimize its accuracy.
