Online monitoring of exhaled breath using mid-infrared laser spectroscopy

NATO Science for Peace and Security Series B: Physics and Biophysics

Volumn , Issue , 2008, Pages 535-555

  Mürtz, Manfred ^a   Hering, Peter ^a  

^a HEINRICH HEINE UNIVERSITY   (Germany)

Author keywords

Cavity ring down; Exhaled breath; Laser absorption spectroscopy; Trace gas monitoring

Indexed keywords

EID: 77949480740     PISSN: 18746500     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-4020-6463-0_18     Document Type: Article

References (99)

1. Andreoni K. A., Kazui M., Cameron D. E., Nyhan D., Sehnert S. S., Rohde C. A., Bulkley G. B., and Risby T. H., 1999, Ethane: a marker of lipid peroxidation during cardiopulmonary bypass in humans, Free Radic. Biol. Med. 26:439-445.
2. Bakhirkin Y. A., Kosterev A. A., Roller C., Curl R. F., and Tittel F. K., 2004, Mid-infrared quantum cascade laser based off-axis integrated cavity output spectroscopy for biogenic nitric oxide detection, Applied Optics 43:2257-2266.
3. Bakhirkin Y. A., Kosterev A. A., Curl R. F., Tittel F. K., Yarekha D. A., Hvozdara L., Giovanni M., and Faist J., 2006, Sub-ppbv nitric oxide concentration measurements using cw thermoelectrically cooled quantum cascade laser-based integrated cavity output spectroscopy, Applied Physics B-Lasers and Optics 82:149-154.
4. Chen W., Mouret G., and Boucher D., 1998, Difference-frequency laser spectroscopy detection of acetylene trace constituent, Applied Physics B-Lasers and Optics 67:375-378.
5. Dahnke H., Kahl J., Schüler G., Boland W., Urban W., and Kühnemann F., 2000, On-line monitoring of biogenic isoprene emissions using photoacoustic spectroscopy, Appl. Phys. B 70:275-280.
6. Dahnke H., Kleine D., Hering P., and Mürtz M., 2001, Real-time monitoring of ethane in human breath using mid-infrared cavity leak-out spectroscopy, Applied Physics B-Lasers and Optics 72:971-975.
7. Elia A., Lugara P. M., and Giancaspro C., 2005, Photoacoustic detection of nitric oxide by use of a quantum-cascade laser, Opt. Lett. 30:988-990.
8. Fink T., Büscher S., Gäbler R., Yu Q., Dax A., and Urban W., 1996, An improved CO2 laser intracavity photoacoustic spectrometer for trace analysis, Rev. Sci. Instrum. 67:4000-4004.
9. Fischer C., Sigrist M. W., Yu Q., and Seiter M., 2001, Photoacoustic monitoring of trace gases by use of a diode-based difference frequency laser source, Opt. Lett. 26:1609-1611.
10. Fischer C., and Sigrist M. W., 2002, Trace-gas sensing in the 3.3-μm region using a diode-based difference-frequency laser photoacoustic system, Applied Physics B-Lasers and Optics 75:305-310.
11. Ganser H., Urban W., and Brown J. M., 2003, The sensitive detection of NO by Faraday modulation spectroscopy with a quantum cascade laser, Mol. Phys. 101:545-550.
12. Ganser H., Horstjann M., Suschek C. V., Hering P., and Mürtz M., 2004, On-line monitoring of biogenic nitric oxide with a QC-laser based Faraday modulation technique, Applied Physics B-Lasers and Optics 78:513-517.
13. Ghoos Y., Geypens B., and Rutgeerts P., 2002, Stable isotopes and 13CO2 breath tests for investigating gastrointestinal functions, Food Nutr. Bull. 23:166-168.
14. Giubileo G., Fantoni R., De Dominicis L., Giorgi M., Pulvirenti R., and Snels M., 2001, A TDLAS system for the diagnosis of Helicobacter pylori infection in humans, Laser Physics 11:154-157.
15. Gustafsson L. E., Leone A. M., Persson M. G., Wiklund N. P., and Moncada S., 1991, Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs, and humans, Biochem. Biophys. Res. Commun. 181:852-867.
16. Halmer D., von Basum G., Horstjann M., Hering P., and Mürtz M., 2005, Time resolved simultaneous detection of 14NO and 15NO via mid-infrared cavity leak-out spectroscopy, Isotopes in Environmental and Health Studies 41:303-311.
17. Harren F. J. M., Oomens J., Persijn S., Veltman R. H., de-Vries H. S. M., and Parker D., 1998, Multi-component trace gas analysis with a CO laser based photoacoustic detector; emission of ethanol, acetaldehyde, ethane and ethylene from fruit, Proc. SPIE 3405:556-562.
18. Harren F. J. M., Berkelmans R., Kuiper K., Hekkert S. T., Scheepers P., Dekhuijzen R., Hollander P., and Parker D. H., 1999, On-line laser photoacoustic detection of ethene in exhaled air as biomarker of ultraviolet radiation damage of the human skin, Applied Physics Letters 74:1761-1763.
19. Hekkert S. T., Staal M. J., Nabben R. H. M., Zuckermann H., Persijn S., Stal L. J., Voesenek L. A. C. J., Harren F. J. M., Reuss J., and Parker D. H., 1998, Laser photoacoustic trace gas detection, an extremely sensitive technique applied in biological research, Instrumentation Science & Technology 26:157-175.
20. Heller H., Brandt S., Gäbler R., and Schuster K. D., 2002, The use of 15N-labeled nitric oxide in lung function tests, Nitric. Oxide. 6:98-100.
21. Heller H., Korbmacher N., Gäbler R., Brandt S., Breitbach T., Juergens U., Grohe C., and Schuster K. D., 2004, Pulmonary 15NO uptake in interstitial lung disease, Nitric. Oxide. 10:229-232.
22. Heller H., Gäbler R., and Schuster K. D., 2005, Real-time detection of nitric oxide isotopes in lung function tests, Methods Enzymol. 396:592-597.
23. Hofstetter D., Beck M., Faist J., Nägele M., and Sigrist M. W., 2001, Photoacoustic spectroscopy with quantum cascade distributed-feedback lasers, Opt. Lett. 26:887-889.
24. Horstjann M., Bakhirkin Y. A., Kosterev A. A., Curl R. F., Tittel F. K., Wong C. M., Hill C. J., and Yang Q., 2004, Formaldehyde sensor using interband cascade laser based quartz-enhanced photoacoustic spectroscopy, Applied Physics B-Lasers and Optics 79:799-803.
25. Kharitonov S. A., 1999, Exhaled nitric oxide and carbon monoxide in asthma, Europ. Respir. J. 9:212-218.
26. Kharitonov S. A., and Barnes P. J., 2001, Exhaled markers of pulmonary disease, Am. J. Respir. Crit. Care Med. 163:1693-1722.
27. Knutson M. D., Lim A. K., and Viteri F. E., 1999, A practical and reliable method for measuring ethane and pentane in expired air from humans, Free Radic. Biol. Med. 27:560-571.
28. Kosterev A. A., Malinovsky A. L., Tittel F. K., Gmachl C., Capasso F., Sivco D. L., Baillargeon J. N., Hutchinson A. L., and Cho A. Y., 2001, Cavity ringdown spectroscopic detection of nitric oxide with a continuous-wave quantum-cascade laser, Appl Opt 40:5522-5529.
29. Kosterev A. A., Tittel F. K., Kohler R., Gmachl C., Capasso F., Sivco D. L., Cho A. Y., Wehe S., and Allen M. G., 2002a, Thermoelectrically cooled quantum-cascade-laser-based sensor for the continuous monitoring of ambient atmospheric carbon monoxide, Applied Optics 41:1169-1173.
30. Kosterev A. A., Bakhirkin Y. A., Curl R. F., and Tittel F. K., 2002b, Quartz-enhanced photoacoustic spectroscopy, Opt. Lett. 27:1902-1904.
31. Kosterev A. A., Tittel F. K., Durante W., Allen M., Gmachl C., Capasso F., Sivco D. L., and Cho A. Y., 2002c, Detection of biogenic CO production above vascular cell cultures using a near-room-temperature QC-DFB laser, Appl Phys B 74:95-99.
32. Kosterev A. A., Bakhirkin Y. A., and Tittel F. K., 2005, Ultrasensitive gas detection by quartz-enhanced photoacoustic spectroscopy in the fundamental molecular absorption bands region, Applied Physics B-Lasers and Optics 80:133-138.
33. Kühnemann F., Schneider K., Hecker A., Martis A. A. E., Urban W., Schiller S., and Mlynek J., 1998, Photoacoustic trace-gas detection using a cw single-frequency parametric oscillator, Applied Physics B-Lasers and Optics 66:741-745.
34. Lancaster D. G., Richter D., Curl R. F., and Tittel F. K., 1998, Real-time measurements of trace gases using a compact difference frequency based sensor operating at 3.5 μm, Appl. Phys. B 67:339.
35. Lancaster D. G., Richter D., and Tittel F. K., 1999, Portable fiber-coupled diode-laser-based sensor for multiple trace gas detection, Applied Physics B-Lasers and Optics 69:459-465.
36. Lancaster D. G., Weidner R., Richter D., Tittel F. K., and Limpert J., 2000, Compact CH4 sensor based on difference frequency mixing of diode lasers in quasi-phasematched LiNbO3, Optics Communications 175:461-468.
37. Lee P. S., Majkowski R. F., and Perry T. A., 1991, Tunable diode-laser spectroscopy for isotope analysis - detection of isotopic carbon-monoxide in exhaled breath, Ieee Transactions on Biomedical Engineering 38:966-973.
38. Lee P. S., Schreck R. M., Hare B. A., and McGrath J. J., 1994, Biomedical applications of tunable diode laser spectrometry: correlation between breath carbon monoxide and low level blood carboxyhemoglobin saturation, Ann Biomed Eng 22:120-125.
39. Malara P., Maddaloni P., Gagliardi G., and De Natale P., 2006, Combining a difference-frequency source with an off-axis high-finesse cavity for trace-gas monitoring around 3 μm, Optics Express 14:1304-1313.
40. Mansfield C. D., Mantsch H. H., and Rutt H. N., 2002, Application of infrared spectroscopy in the measurement of breath trace compounds: A review, Canadian Journal of Analytical Sciences and Spectroscopy 47:14-28.
41. Martis A., Büscher S., Kühnemann F., and Urban W., 1998, Simultaneous ethane and ethylene detection using a CO Overtone laser PA spectrometer: A new tool for stress/damage studies, Instr. Sci. Technol. 26:177-187.
42. Menzel L., Kosterev A. A., Curl R. F., Tittel F. K., Gmachl C., Capasso F., Sivco D. L., Baillargeon J. N., Huchinson A. L., Cho A. Y., and Urban W., 2001, Spectroscopic detection of biological NO with a quantum cascade laser, Appl Phys B 72:859-863.
43. Menzel L., Hess A., Bloch W., Michel O., Schuster K. D., Gäbler R., and Urban W., 2005, Temporal nitric oxide dynamics in the paranasal sinuses during humming, J Appl Physiol 98:2064-2071.
44. Miekisch W., Schubert J. K., and Noeldge-Schomburg G. F. E., 2004, Diagnostic potential of breath analysis - focus on volatile organic compounds, Clinica Chimica Acta 347:25-39.
45. Miklos A., Lim C. H., Hsiang W. W., Liang G. C., Kung A. H., Schmohl A., and Hess P., 2002, Photoacoustic measurement of methane concentrations with a compact pulsed optical parametric oscillator, Applied Optics 41:2985-2993.
46. Moeskops B. W. M., Cristescu S. M., and Harren F. J. M., 2006a, Sub-part-per-billion monitoring of nitric oxide by use of wavelength modulation spectroscopy in combination with a thermoelectrically cooled, continuous-wave quantum cascade laser, Opt. Lett. 31:823-825.
47. Moeskops B. W. M., Naus H., Cristescu S. M., and Harren F. J. M., 2006b, Quantum cascade laser-based carbon monoxide detection on a second time scale from human breath, Applied Physics B-Lasers and Optics 82:649-654.
48. Morimoto Y., Durante W., Lancaster D. G., Klattenhoff J., and Tittel F. K., 2001, Real-time measurements of endogenous CO production from vascular cells using an ultrasensitive laser sensor, American Journal of Physiology-Heart and Circulatory Physiology 280: H483-H488.
49. Moskalenko K., Nadezhdinskii A., and Adamovskaya I. A., 1996, Human breath trace gas content study by tunable diode laser spectroscopy technique, Infrared Phys Technol 37:181-192.
50. Müller F., Popp A., Kühnemann F., and Schiller S., 2003, Transportable, highly sensitive photoacoustic spectrometer based on a continuous-wave dual-cavity optical parametric oscillator, Optics Express 11:2820-2825.
51. Mürtz M., Frech B., and Urban W., 1999a, High-resolution cavity leak-out absorption spectroscopy in the 10-μm region, Applied Physics B-Lasers and Optics 68:243-249.
52. Mürtz P., Menzel L., Bloch W., Hess A., Michel O., and Urban W., 1999b, LMR spectroscopy: a new sensitive method for on-line recording of nitric oxide in breath, J Appl Physiol 86:1075-1080.
53. Nägele M., and Sigrist M. W., 2000, Mobile laser spectrometer with novel resonant multipass photoacoustic cell for trace-gas sensing, Applied Physics B-Lasers and Optics 70:895-901.
54. Nägele M., Hofstetter D., Faist J., and Sigrist M. W., 2001, Low power quantum-cascade laser photoacoustic spectrometer for trace-gas monitoring, Analytical Sciences 17:S497-S499.
55. Paldus B. A., Spence T. G., Zare R. N., Oomens J., Harren F. J. M., Parker D. H., Gmachl C., Capasso F., Sivco D. L., Baillargeon J. N., Hutchinson A. L., and Cho A. Y., 1999, Photoacoustic spectroscopy using quantum cascade lasers, Opt. Lett. 24:178-180.
56. Paldus B. A., Harb C. C., Spence T. G., Zare R. N., Gmachl C., Capasso F., Sivco D. L., Baillargeon J. N., Hutchinson A. L., and Cho A. Y., 2000, Cavity Ring-down Spectroscopy using Mid-Infrared Quantum Cascade Lasers, Opt. Lett. 25:668.
57. Paredi P., Invernizzi G., Biernacki W., Kharitonov S. A., and Barnes P. J., 1999, Exhaled carbon monoxide levels are elevated in diabetes and correlate with glycemia, American Journal of Respiratory and Critical Care Medicine 159:A887.
58. Paredi P., Kharitonov S. A., Leak D., Shah P. L., Cramer D., Hodson M. E., and Barnes P. J., 2000, Exhaled ethane is elevated in cystic fibrosis and correlates with carbon monoxide levels and airway obstruction, Am. J. Respir. Crit. Care Med. 161:1247-1251.
59. Paunel A. N., Dejam A., Thelen S., Kirsch M., Horstjann M., Gharini P., Mürtz M., Kelm M., de Groot H., Kolb-Bachofen V., and Suschek C. V., 2005, Enzyme-independent nitric oxide formation during UVA challenge of human skin: characterization, molecular sources, and mechanism, Free Radic. Biol. Med. 38:606-615.
60. Persijn S. T., Harren F. J. M., Wijkamp I., and Mitrayana L., 2006, Study of gas exchange in insects by sensitive laser photoacoustic spectroscopy, Instrumentation Science & Technology 34:85-97.
61. Pesce G., Rusciano G., and Sasso A., 2003, High sensitivity spectrometer at 3 μm based on difference frequency generation for N2O detection, Ieee Sensors Journal 3:206-211.
62. Petrov K. P., Curl R. F., and Tittel F. K., 1998, Compact laser difference-frequency spectrometer for multicomponent trace gas detection, Applied Physics B-Lasers and Optics 66:531-538.
63. Phillips M., 1992, Breath tests in medicine, Scientific American 267:74-79.
64. Phillips M., Gleeson K., Hughes J. M. B., Greenberg J., Cataneo R. N., Baker L., and Mcvay W. P., 1999, Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study, Lancet 353:1930-1933.
65. Phillips M., Cataneo R. N., Cummin A. R. C., Gagliardi A. J., Gleeson K., Greenberg J., Maxfield R. A., and Rom W. N., 2003, Detection of lung cancer with volatile markers in the breath, Chest 123:2115-2123.
66. Popp A., Müller F., Kühnemann F., Schiller S., von Basum G., Dahnke H., Hering P., and Mürtz M., 2002, Ultra-sensitive mid-infrared cavity leak-out spectroscopy using a cw optical parametric oscillator, Applied Physics B-Lasers and Optics 75:751-754.
67. Provencal R., Gupta M., Owano T. G., Baer D. S., Ricci K. N., O'Keefe A., and Podolske J. R., 2005, Cavity-enhanced quantum-cascade laser-based instrument for carbon monoxide measurements, Applied Optics 44:6712-6717.
68. Pryor W. A., and Godber S. S., 1991, Noninvasive measures of oxidative stress status in humans, Free Radic. Biol. Med. 10:177-184.
69. Puiu A., Giubileo G., and Bangrazi C., 2005, Laser sensors for trace gases in human breath, International Journal of Environmental Analytical Chemistry 85:1001-1012.
70. Richter D., Fried A., Wert B. P., Walega J. G., and Tittel F. K., 2002, Development of a tunable mid-IR difference frequency laser source for highly sensitive airborne trace gas detection, Applied Physics B-Lasers and Optics 75:281-288.
71. Richter D., and Weibring P., 2006, Ultra-high precision mid-IR spectrometer I: Design and analysis of an optical fiber pumped difference-frequency generation source, Applied Physics B-Lasers and Optics 82:479-486.
72. Risby T. H., and Sehnert S. S., 1999, Clinical application of breath biomarkers of oxidative stress status, Free Radic. Biol. Med. 27:1182-1192.
73. Risby, T.H., 2005, Current status of clinical breath analysis, in: Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring, A. Amann and D. Smith, eds., World Scientific, Singapore, pp. 251-266.
74. Roller C., Namjou K., Jeffers J., Potter W., McCann P. J., and Grego J., 2002, Simultaneous NO and CO2 measurement in human breath with a single IV-VI mid-infrared laser, Opt. Lett. 27:107-109.
75. Roller C. B., Namjou K., Jeffers J. D., Camp M., McCann P. J., and Grego J., 2002, Nitric Oxide Breath Testing Using Tunable Diode Laser Absorption Spectroscopy: Application in Respiratory Inflammation Monitoring, Applied Optics 41:6018-6029.
76. Romanini D., Kachanov A. A., Sadeghi N., and Stoeckel F., 1997, CW cavity ring down spectroscopy, Chemical Physics Letters 264:316-322.
77. Rusciano G., Pesce G., Pignatiello F., and Sasso A., 2003, Difference-frequency-generator-based spectrometer at 3 μm for high-sensitivity C2H2 and H2O detection, Optics Express 11:3010-3021.
78. Santosa I. E., Laarhoven L. J. J., Harbinson J., Driscoll S., and Harren F. J. M., 2003, Laser-based trace gas detection of ethane as a result of photooxidative damage in chilled cucumber leaves (invited), Review of Scientific Instruments 74:680-683.
79. Sies H., 1997, Oxidative stress: oxidants and antioxidants, Exp. Physiol. 82:291-295.
80. Sigrist M. W., Bohren A., von Lerber T., Nägele M., and Romann A., 2001, Environmental applications of laser-based photoacoustic spectroscopy, Analytical Sciences 17:S511-S514.
81. Silva M. L., Sonnenfroh D. M., Rosen D. I., Allen M. G., and O'Keefe A., 2005, Integrated cavity output spectroscopy measurements of NO levels in breath with a pulsed room-temperature QCL, Applied Physics B-Lasers and Optics 81:705-710.
82. Skeldon K. D., Patterson C., Wyse C. A., Gibson G. M., Padgett M. J., Longbottom C., and McMillan L. C., 2005a, The potential offered by real-time, high-sensitivity monitoring of ethane in breath and some pilot studies using optical spectroscopy, Journal of Optics A-Pure and Applied Optics 7:S376-S384.
83. Skeldon K. D., Gibson G. M., Wyse C. A., McMillan L. C., Monk S. D., Longbottom C., and Padgett M. J., 2005b, Development of high-resolution real-time sub-ppb ethane spectroscopy and some pilot studies in life science, Applied Optics 44:4712-4721.
84. Skeldon K. D., McMillan L. C., Wyse C. A., Monk S. D., Gibson G., Patterson C., France T., Longbottom C., and Padgett M. J., 2006, Application of laser spectroscopy for measurement of exhaled ethane in patients with lung cancer, Respiratory Medicine 100:300-306.
85. Stepanov E. V., and Moskalenko K. L., 1993, Gas analysis of human exhalation by tunable diode laser spectroscopy, Opt Eng 32:361-367.
86. Stry S., Hering P., and Mürtz M., 2002, Portable difference-frequency laser-based cavity leak-out spectrometer for trace-gas analysis, Applied Physics B-Lasers and Optics 75:297-303.
87. Suschek C. V., Schroeder P., Aust O., Sies H., Mahotka C., Horstjann M., Ganser H., Mürtz M., Hering P., Schnorr O., Kröncke K. D., and Kolb-Bachofen V., 2003, The presence of nitrite during uva irradiation protects from apoptosis, FASEB J. 17:2342-2344.
88. Urban, W., 2004, Detection of nitric oxide in human exhalation using laser magnetic resonance, in: Lasers in Environmental and Life Sciences, P. Hering, J. P. Lay, and S. Stry, eds., Springer, Berlin, pp. 269-282.
89. van Herpen M. M. J. W., Li S. C., Bisson S. E., and Harren F. J. M., 2002, Photoacoustic trace gas detection of ethane using a continuously tunable, continuous-wave optical parametric oscillator based on periodically poled lithium niobate, Applied Physics Letters 81:1157-1159.
90. van Herpen M. M. J. W., Ngai A. K. Y., Bisson S. E., Hackstein J. H. P., Woltering E. J., and Harren F. J. M., 2006, Optical parametric oscillator-based photoacoustic detection of CO2 at 4.23 mu m allows real-time monitoring of the respiration of small insects, Applied Physics B-Lasers and Optics 82:665-669.
91. von Basum G., Dahnke H., Halmer D., Hering P., and Mürtz M., 2003, On-line recording of ethane traces in breath via infrared laser spectroscopy, J Appl Physiol 95:2583-2590.
92. von Basum G., Halmer D., Hering P., Mürtz M., Schiller S., Müller F., Popp A., and Kühnemann F., 2004, Parts per trillion sensitivity for ethane in air with an optical parametric oscillator cavity leak-out spectrometer, Opt. Lett. 29:797-799.
93. von Basum, G., Halmer, D., Hering, P., and Mürtz, M., 2005, Laserspectroscopic online monitoring of exhaled trace gases, in: Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring, A. Amann and D. Smith, eds., World Scientific, Singapore, pp. 67-74.
94. Weidmann D., Kosterev A. A., Roller C., Curl R. F., Fraser M. P., and Tittel F. K., 2004a, Monitoring of ethylene by a pulsed quantum cascadelaser, Applied Optics 43:3329-3334.
95. Weidmann D., Tittel F. K., Aellen T., Beck M., Hofstetter D., Faist J., and Blaser S., 2004b, Mid-infrared trace-gas sensing with a quasi-continuous- wave Peltier-cooled distributed feedback quantum cascade laser, Applied Physics B-Lasers and Optics 79:907-913.
96. Wyse C. A., Preston T., Yam P. S., Sutton D. G., Christley R. M., Hotchkiss J. W., Mills C. A., Glidle A., Cumming D. R., Cooper J. M., and Love S., 2004, Current and future uses of breath analysis as a diagnostic tool, Vet. Rec. 154:353-360.
97. Wyse C. A., Skeldon K., Hotchkiss J. W., Gibson G., Yam P. S., Christley R. M., Preston T., Cumming D. R., Padgett M., Cooper J. C., and Love S., 2005, Effects of changes to the stable environment on the exhalation of ethane, carbon monoxide and hydrogen peroxide by horses with respiratory inflammation, Vet. Rec. 157:408-412.
98. Wysocki G., McCurdy M., So S., Weidmann D., Roller C., Curl R. F., and Tittel F. K., 2004, Pulsed quantum-cascade laser-based sensor for trace-gas detection of carbonyl sulfide, Applied Optics 43:6040-6046.
99. Zayasu K., Sekizawa K., Okinaga S., Yamaya M., Ohrui T., and Sasaki H., 1997, Increased carbon monoxide in exhaled air of asthmatic patients, American Journal of Respiratory and Critical Care Medicine 156:1140-1143.