Detection and analysis of volatile compounds in exhaled breath represents an attractive tool for monitoring the metabolic status of a patient and disease diagnosis, since it is non-invasive and fast. Numerous studies have already demonstrated the benefit of breath analysis in clinical settings/applications and encouraged multidisciplinary research to reveal new insights regarding the origins, pathways, and pathophysiological roles of breath components. Many breath analysis methods are currently available to help explore these directions, ranging from mass spectrometry to laser-based spectroscopy and sensor arrays. This review presents an update of the current status of optical methods, using near and mid-infrared sources, for clinical breath gas analysis over the last decade and describes recent technological developments and their applications. The review includes: tunable diode laser absorption spectroscopy, cavity ring-down spectroscopy, integrated cavity output spectroscopy, cavity-enhanced absorption spectroscopy, photoacoustic spectroscopy, quartz-enhanced photoacoustic spectroscopy, and optical frequency comb spectroscopy. A SWOT analysis (strengths, weaknesses, opportunities, and threats) is presented that describes the laser-based techniques within the clinical framework of breath research and their appealing features for clinical use.

We present a compact sensor for carbon monoxide (CO) in air and exhaled breath based on a room temperature interband cascade laser (ICL) operating at 4.69 µm, a low-volume circular multipass cell and wavelength modulation absorption spectroscopy. A fringe-limited (1σ) sensitivity of 6.5 × 10⁻⁸ cm⁻¹Hz^-1/2 and a detection limit of 9 ± 5 ppbv at 0.07 s acquisition time are achieved, which constitutes a 25-fold improvement compared to direct absorption spectroscopy. Integration over 10 s increases the precision to 0.6 ppbv. The setup also allows measuring the stable isotope ¹³CO in breath. We demonstrate quantification of indoor air CO and real-time detection of CO expirograms from healthy non-smokers and a healthy smoker before and after smoking. Isotope ratio analysis indicates depletion of ¹³CO in breath compared to natural abundance.

Ammonia concentrations in exhaled breath (eNH3) and skin gas of 20 healthy subjects were measured on-line with a commercial cavity ring-down spectrometer and compared to saliva pH and plasma ammonium ion (NH(+)4), urea and creatinine concentrations. Special attention was given to mouth, nose and skin sampling procedures and the accurate quantification of ammonia in humid gas samples. The obtained median concentrations were 688 parts per billion by volume (ppbv) for mouth-eNH3, 34 ppbv for nose-eNH3, and 21 ppbv for both mouth- and nose-eNH3 after an acidic mouth wash (MW). The median ammonia emission rate from the lower forearm was 0.3 ng cm(-2) min(-1). Statistically significant (p < 0.05) correlations between the breath, skin and plasma ammonia/ammonium concentrations were not found. However, mouth-eNH3 strongly (p < 0.001) correlated with saliva pH. This dependence was also observed in detailed measurements of the diurnal variation and the response of eNH3 to the acidic MW. It is concluded that eNH3 as such does not reflect plasma but saliva and airway mucus NH(+)4 concentrations and is affected by saliva and airway mucus pH. After normalization with saliva pH using the Henderson-Hasselbalch equation, mouth-eNH3 correlated with plasma NH(+)4, which points to saliva and plasma NH(+)4 being linked via hydrolysis of salivary urea.

A calibration-free scanned wavelength modulation spectroscopy scheme requiring minimal laser characterization is presented. Species concentration and temperature are retrieved simultaneously from a single fit to a group of 2f/1f-WMS lineshapes acquired in one laser scan. The fitting algorithm includes a novel method to obtain the phase shift between laser intensity and wavelength modulation, and allows for a wavelength-dependent modulation amplitude. The scheme is demonstrated by detection of H₂O concentration and temperature in atmospheric, premixed CH₄/air flat flames using a sensor operating near 1.4 µm. The detection sensitivity for H₂O at 2000 K was 4 × 10⁻⁵ cm⁻¹ Hz^-1/2, and temperature was determined with a precision of 10 K and absolute accuracy of ~50 K. A parametric study of the dependence of H₂O and temperature on distance to the burner and total fuel mass flow rate shows good agreement with 1D simulations.