Analysis of volatile organic compounds (VOCs) in breath holds great promise for noninvasive diagnostic applications. However, concentrations of VOCs in breath may change quickly, and actual and previous uptakes of exogenous substances, especially in the clinical environment, represent crucial issues. We therefore adapted proton-transfer-reaction-time-of-flight-mass spectrometry for real time breath analysis in the clinical environment. For reasons of medical safety, a 6 m long heated silcosteel transfer line connected to a sterile mouth piece was used for breath sampling from spontaneously breathing volunteers and mechanically ventilated patients. A time resolution of 200 ms was applied. Breath from mechanically ventilated patients was analyzed immediately after cardiac surgery. Breath from 32 members of staff was analyzed in the post anesthetic care unit (PACU). In parallel, room air was measured continuously over 7 days. Detection limits for breath-resolved real time measurements were in the high pptV/low ppbV range. Assignment of signals to alveolar or inspiratory phases was done automatically by a matlab-based algorithm. Quickly and abruptly occurring changes of patients' clinical status could be monitored in terms of breath-to-breath variations of VOC (e.g. isoprene) concentrations. In the PACU, room air concentrations mirrored occupancy. Exhaled concentrations of sevoflurane strongly depended on background concentrations in all participants. In combination with an optimized inlet system, the high time and mass resolution of PTR-ToF-MS provides optimal conditions to trace quick changes of breath VOC profiles and to assess effects from the clinical environment.

Influenza is one of the most common causes of virus diseases worldwide. Virus detection requires determination of Influenza RNA in the upper respiratory tract. Efficient screening is not possible in this way. Analysis of volatile organic compounds (VOCs) in breath holds promise for non-invasive and fast monitoring of disease progression. Breath VOC profiles of 14 (3 controls and 11 infected animals) swine were repeatedly analyzed during a complete infection cycle of Influenza A under high safety conditions. Breath VOCs were pre-concentrated by means of needle trap micro-extraction and analysed by gas chromatography mass spectrometry before infection, during virus presence in the nasal cavity, and after recovery. Six VOCs could be related to disease progression: acetaldehyde, propanal, n-propyl acetate, methyl methacrylate, styrene and 1,1-dipropoxypropane. As early as on day four after inoculation, when animals were tested positive for Influenza A, differentiation between control and infected animals was possible. VOC based information on virus infection could enable early detection of Influenza A. As VOC analysis is completely non-invasive it has potential for large scale screening purposes. In a perspective, breath analysis may offer a novel tool for Influenza monitoring in human medicine, animal health control or border protection.

Analysis of exhaled VOCs can provide information on physiology, metabolic processes, oxidative stress and lung diseases. In critically ill patients, VOC analysis may be used to gain complimentary information beyond global clinical parameters. This seems especially attractive in mechanically ventilated patients frequently suffering from impairment of gas exchange. This study was intended to assess (a) the effects of recruitment maneuvers onto VOC profiles, (b) the correlations between electrical impedance tomography (EIT) data and VOC profiles and (c) the effects of recruitment onto distribution of ventilation. Eleven mechanically ventilated patients were investigated during lung recruitment after cardiac surgery. Continuous breath gas analysis by means of PTR-ToF-MS, EIT and blood gas analyses were performed simultaneously. More than 300 mass traces could be detected and monitored continuously by means of PTR-ToF-MS in every patient. Exhaled VOC concentrations varied with recruitment induced changes in minute ventilation and cardiac output. Ammonia exhalation depended on blood pH. The improvement in dorsal lung ventilation during recruitment ranged from 9% to 110%. Correlations between exhaled concentrations of acetone, isoprene, benzene sevoflurane and improvement in regional ventilation during recruitment were observed. Extent and quality of these correlations depended on physico-chemical properties of the VOCs. Combination of continuous real-time breath analysis and EIT revealed correlations between exhaled VOC concentrations and distribution of ventilation. This setup enabled immediate recognition of physiological and therapeutic effects in ICU patients. In a perspective, VOC analysis could be used for non-invasive control and optimization of ventilation strategies.

Direct time resolved mass spectrometric monitoring of reactive exhaled nitrogen- and sulfur-containing volatile organic compounds (VOCs) related to metabolic processes, diseases and bacterial activity.