Exhaled breath analysis using laser absorption spectroscopy
Trace gas sensing is a rapidly developing field, with many applications in breath diagnostics and therapeutic monitoring. For this thesis, laser spectroscopic techniques were employed to measure exhaled nitric oxide (NO), carbonyl sulfide (OCS) and carbon dioxide (CO2). A pulsed quantum cascade laser operating at 4.86 microns was coupled to a 36-m optical path length Herriott cell for simultaneous measurement of exhaled OCS and CO2. Exhaled OCS was evaluated as a marker of acute rejection in lung transplant recipients. A continuous wave thermoelectrically cooled quantum cascade laser at 5.47 microns coupled with off-axis integrated cavity output spectroscopy (ICOS) was developed to simultaneously measure exhaled NO and CO2. Using the Bland-Altman method, the ICOS platform was found to be in good agreement with two commercial gas sensors---a chemiluminescent analyzer for NO and a non-dispersive infrared capnograph for CO2. The ICOS NO sensor was used to measure exhaled NO in patients with moderate to severe COPD. Four flow-independent NO exchange parameters were determined by measuring exhaled NO at six exhalation flow rates. Large airway NO flux (J'awNO) was reduced in current smokers compared to former smokers (p &lt; 0.05). Alveolar NO (CANO) was correlated with declining functional capacity (r = -0.63, p &lt; 0.05) and was unaffected by smoking status, indicating its potential use as a marker specific to peripheral lung inflammation in COPD. This thesis demonstrates the merits of mid-infrared laser-based trace gas sensing of multiple target gas species. This technology can be used for rapid human breath analysis and has diagnostic and therapeutic applications.
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