ReviewPathologies currently identified by exhaled biomarkers☆
Highlights
► Volatile breath markers distinguish health from disease. ► Multiple chemical sensitivity (MCS) syndrome underlies chronic fatigue. ► Electronic nose identifies ‘smellprint’ characteristic of lung cancer. ► Volatile organic compounds (VOCs) change in exhaled breath during cognitive tasks.
Introduction
Biophysical, biochemical, and molecular biological methods have mainly been developed for blood and urine analysis in medical monitoring equipments and diagnostics. Comparatively, diagnostics based on breath analysis, which are among the least invasive methods for monitoring person's health, are less developed and not yet regularly used in clinical practice. The applications of breath tests are valuable in diagnosis of disease, including aging and neurodegenerative pathology, and in the assessment of exposure to environmental pollutants or drugs (Risby and Sehnert, 1999, Cao and Duan, 2006).
Gas exchange at the alveolar-blood capillary membrane of the respiratory tract is essential to life. This mechanism is a passive diffusion driven by the carbon dioxide and oxygen unbalanced concentration gradients. Following these vital gasses, molecules present either in the blood or in inhaled air can also diffuse passively into the breath or blood, respectively. Interestingly, exhaled breath could be characterized by a distinctive smell. These unique stenches have been used, since the time of Hippocrates, as indicators of several diseases: diabetes, lung, liver or renal pathology, sepsis, or periodontal infections (Phillips, 1992). These intuitive observations have later been proven by using classical analytical methods. The molecular profile of breath has been characterized in concentrations and identities of the compounds in healthy and pathological conditions (for review see Miekisch et al., 2004). Principal components up to 99% are few compounds: nitrogen, oxygen, carbon dioxide, water vapor, and the inert gases. The residue consists of a mixture of many molecules with concentrations in the range of parts per million (ppm) to parts per trillion (ppt) by volume (Chen et al., 1970, Pauling et al., 1971, Riely et al., 1974, Dannecker et al., 1981, Solga and Risby, 2010). In normal subjects, more than 3400 different volatile organic compounds (VOCs) can be detected in the exhaled breath; however, only a small fraction of these VOCs are present in all subjects. These are principally isoprene, alkanes, methylalkane, and benzene derivatives (Phillips et al., 1999). Intuitively, this residual part is the most interesting for searching biomarkers of pathological conditions (Risby, 2002). However, given the minute concentration of these molecules, it is essential to investigate breath by the application of new generation of analytical instruments capable of high resolution detection (Risby and Solga, 2006, Solga and Risby, 2010). This review is intended to describe the broad range of applications of breath analysis, including a new sensor generation and its potential for clinical diagnosis of new diseases and a real time monitoring during cognitive performance tests.
Section snippets
Breath analysis techniques, limitations and future perspectives
Capnography is a classic monitoring system of the concentration or partial pressure of carbon dioxide (CO2) in the respiratory gases. It provides information about CO2 production, lung perfusion, alveolar ventilation, respiratory patterns, indirect metabolism measurement, and elimination of CO2 after anesthesia from the breathing circuit and ventilator. It is usually represented as a graph, the capnogram, of expiratory CO2 plotted against time or expired volume. The capnogram is a direct
Clinical application of breath analysis
Breath analysis has been applied both in cross-sectional and longitudinal studies (Miekisch et al., 2004). In cross-sectional studies, a control group is compared with a disease group, and breath biomarkers are analyzed to identify qualitative or quantitative differences between the two groups. In longitudinal studies, breath biomarkers are observed during the course of a disease or monitoring of pharmacologic interventions. As a result of these studies, several breath biomarkers have been
Future perspective in breath analysis
Clinical usefulness of breath analysis has been well demonstrated in several diagnostic applications; however, a new future in breath analysis is upcoming at an accelerating pace. We have investigated and quantified exhaled VOCs while performing cognitive tasks, consisting of solving the Sudoku puzzles, in patients suffering from diabetes type 2 and in control subjects, using a MOS sensor. The rationale for that was that the brain target areas for insulin are particularly located in the
Conflicts of interest
The authors declare no conflicts of interest in relation to this article.
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This paper is part of a special issue entitled “Immunopathology of the Respiratory System”, guest-edited by Professor Mieczyslaw Pokorski.