Quantum cascade laser-based integrated cavity output spectroscopy of exhaled nitric oxide

A nitric oxide (NO) sensor employing a thermoelectrically cooled, continuous-wave, distributed feedback quantum cascade laser operating at 5.47 μm (1828 cm-1) and off-axis integrated cavity output spectroscopy was used to measure NO concentrations in exhaled breath. A minimum measurable concentration (3σ) of 3.6 parts-per-billion by volume (ppbv) of NO with a data-acquisition time of 4 s was demonstrated. Five prepared gas mixtures and 15 exhaled breath samples were measured with both the NO sensor and for intercomparison with a chemiluminescence-based NO analyzer and were found to be in agreement within 0.6 ppbv. Exhaled NO flow-independent parameters, which may provide diagnostic and therapeutic information in respiratory diseases where single-breath measurements are equivocal, were estimated from end-tidal NO concentration measurements collected at various flow rates. The results of this work indicate that a laser-based exhaled NO sensor can be used to measure exhaled nitric oxide at a range of exhalation flow rates to determine flow-independent parameters in human clinical trials.

[1]  P. Hering,et al.  Online monitoring of biogenic nitric oxide with a QC laser-based Faraday modulation technique , 2004 .

[2]  Douglas G. Altman,et al.  Practical statistics for medical research , 1990 .

[3]  D. Altman,et al.  Measuring agreement in method comparison studies , 1999, Statistical methods in medical research.

[4]  Arthur S Slutsky,et al.  Marked flow-dependence of exhaled nitric oxide using a new technique to exclude nasal nitric oxide. , 1997, American journal of respiratory and critical care medicine.

[5]  F. Tittel,et al.  Exhaled human breath analysis with quantum cascade laser-based gas sensors , 2005 .

[6]  A. Cho,et al.  Spectroscopic detection of biological NO with a quantum cascade laser , 2001, Applied physics. B, Lasers and optics.

[7]  David I. Rosen,et al.  Integrated cavity output spectroscopy measurements of NO levels in breath with a pulsed room-temperature QCL , 2005 .

[8]  Marcella Giovannini,et al.  Characterization of a near-room-temperature, continuous-wave quantum cascade laser for long-term, unattended monitoring of nitric oxide in the atmosphere. , 2006, Optics letters.

[9]  Laurence S. Rothman,et al.  The HITRAN molecular spectroscopic database: edition of 2000 including updates through 2001 , 2003 .

[10]  P. Meriläinen,et al.  Extended NO analysis applied to patients with COPD, allergic asthma and allergic rhinitis. , 2002, Respiratory medicine.

[11]  J G Anderson,et al.  Ultrasensitive absorption spectroscopy with a high-finesse optical cavity and off-axis alignment. , 2001, Applied optics.

[12]  S. Permutt,et al.  Modeling pulmonary nitric oxide exchange. , 2004, Journal of applied physiology.

[13]  N. Tsoukias,et al.  A two-compartment model of pulmonary nitric oxide exchange dynamics. , 1998, Journal of applied physiology.

[14]  F. Capasso,et al.  Cavity ringdown spectroscopic detection of nitric oxide with a continuous-wave quantum-cascade laser. , 2001, Applied optics.

[15]  N. Binding,et al.  NO chemiluminescence in exhaled air: interference of compounds from endogenous or exogenous sources. , 2000, The European respiratory journal.

[16]  M. Zitt Clinical applications of exhaled nitric oxide for the diagnosis and management of asthma: a consensus report. , 2005, Clinical therapeutics.

[17]  Frank K. Tittel,et al.  Sub-ppbv nitric oxide concentration measurements using cw thermoelectrically cooled quantum cascade laser-based integrated cavity output spectroscopy , 2006 .

[18]  H. Magnussen,et al.  Comparison of exhaled nitric oxide analysers. , 2005, Respiratory medicine.

[19]  N. Pride,et al.  Exhaled nitric oxide from lung periphery is increased in COPD , 2005, European Respiratory Journal.

[20]  Khosrow Namjou,et al.  Nitric oxide breath testing by tunable-diode laser absorption spectroscopy: application in monitoring respiratory inflammation. , 2002, Applied optics.

[21]  D. Linnarsson,et al.  Novel hand-held device for exhaled nitric oxide-analysis in research and clinical applications , 2004, Journal of Clinical Monitoring and Computing.

[22]  Dave Singh,et al.  A comparison of exhaled nitric oxide measurements performed using three different analysers. , 2006, Respiratory medicine.

[23]  Yargo Bonetti,et al.  Room-temperature, continuous-wave, single-mode quantum-cascade lasers at λ≃5.4μm , 2005 .

[24]  T. W. van der Mark,et al.  Water vapour and carbon dioxide decrease nitric oxide readings. , 1997, The European respiratory journal.

[25]  Frank K Tittel,et al.  Mid-infrared quantum cascade laser based off-axis integrated cavity output spectroscopy for biogenic nitric oxide detection. , 2004, Applied optics.

[26]  J. Cowan,et al.  Use of exhaled nitric oxide measurements to guide treatment in chronic asthma. , 2005, The New England journal of medicine.