Increased amount of nitric oxide in exhaled air of asthmatics

The presence of nitric oxide (NO) in the exhaled air of humans has recently been described. We wanted to assess at what level exhaled NO originates in normal airways, and to determine whether airway inflammation induces changes in the levels of exhaled NO. Exhaled NO was continuously measured by chemiluminescence technique during normal tidal breathing through the nose or mouth, with a detection limit of 1 part per billion (ppb). Twelve control subjects were compared to eight patients with mild atopic asthma and rhinitis caused by occupational allergen. In control subjects, the major part of NO in exhaled air (up to 30 ppb) seemed to originate in the nasal airways, with only minor contribution from the lower airways and the oral cavity. However, in mild asthmatics, the level of exhaled NO during oral breathing, indicating the involvement of the lower airways, was increased 2-3 fold. Since increased production of NO in the lower airways may involve activated macrophages or neutrophils, we suggest that exhaled NO may be used to instantly monitor ongoing bronchial inflammation, at least when involving inducible NO synthase.

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				H.-W. Shin, P. Condorelli, and S. C. George Examining axial diffusion of nitric oxide in the lungs using heliox and breath hold J Appl Physiol, February 1, 2006; 100(2): 623 - 630. [Abstract] [Full Text] [PDF]

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				N Berkman, A Avital, R Breuer, E Bardach, C Springer, and S Godfrey Exhaled nitric oxide in the diagnosis of asthma: comparison with bronchial provocation tests Thorax, May 1, 2005; 60(5): 383 - 388. [Abstract] [Full Text] [PDF]

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				C. M. Prado, E. A. Leick-Maldonado, V. Arata, D. I. Kasahara, M. A. Martins, and I. F. L. C. Tiberio Neurokinins and inflammatory cell iNOS expression in guinea pigs with chronic allergic airway inflammation Am J Physiol Lung Cell Mol Physiol, April 1, 2005; 288(4): L741 - L748. [Abstract] [Full Text] [PDF]

				H Marteus, D C Tornberg, E Weitzberg, U Schedin, and K Alving Origin of nitrite and nitrate in nasal and exhaled breath condensate and relation to nitric oxide formation Thorax, March 1, 2005; 60(3): 219 - 225. [Abstract] [Full Text] [PDF]

				D. C. Tornberg, M. Angdin, G. Settergen, J. Liska, J. O. Lundberg, and E. Weitzberg Exhaled nitric oxide before and after cardiac surgery with cardiopulmonary bypass--response to acetylcholine and nitroglycerin Br. J. Anaesth., February 1, 2005; 94(2): 174 - 180. [Abstract] [Full Text] [PDF]

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				J C Ojoo, S A Mulrennan, J A Kastelik, A H Morice, and A E Redington Exhaled breath condensate pH and exhaled nitric oxide in allergic asthma and in cystic fibrosis Thorax, January 1, 2005; 60(1): 22 - 26. [Abstract] [Full Text] [PDF]

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				F. L. M. Ricciardolo, P. J. Sterk, B. Gaston, and G. Folkerts Nitric Oxide in Health and Disease of the Respiratory System Physiol Rev, July 1, 2004; 84(3): 731 - 765. [Abstract] [Full Text] [PDF]

				P. Condorelli, H.-W. Shin, and S. C. George Characterizing airway and alveolar nitric oxide exchange during tidal breathing using a three-compartment model J Appl Physiol, May 1, 2004; 96(5): 1832 - 1842. [Abstract] [Full Text] [PDF]

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				A. D. Smith, J. O. Cowan, S. Filsell, C. McLachlan, G. Monti-Sheehan, P. Jackson, and D. R. Taylor Diagnosing Asthma: Comparisons between Exhaled Nitric Oxide Measurements and Conventional Tests Am. J. Respir. Crit. Care Med., February 15, 2004; 169(4): 473 - 478. [Abstract] [Full Text] [PDF]

				H.-W. Shin, C. M. Rose-Gottron, D. M. Cooper, R. L. Newcomb, and S. C. George Airway diffusing capacity of nitric oxide and steroid therapy in asthma J Appl Physiol, January 1, 2004; 96(1): 65 - 75. [Abstract] [Full Text] [PDF]

				S. Galijasevic, G. M. Saed, M. P. Diamond, and H. M. Abu-Soud Myeloperoxidase up-regulates the catalytic activity of inducible nitric oxide synthase by preventing nitric oxide feedback inhibition PNAS, December 9, 2003; 100(25): 14766 - 14771. [Abstract] [Full Text] [PDF]

				P J Franklin, S W Turner, P N Le Souef, and S M Stick Exhaled nitric oxide and asthma: complex interactions between atopy, airway responsiveness, and symptoms in a community population of children Thorax, December 1, 2003; 58(12): 1048 - 1052. [Abstract] [Full Text] [PDF]

				D. C. Tornberg, H. Bjorne, J. O. Lundberg, and E. Weitzberg Multiple Single-breath Measurements of Nitric Oxide in the Intubated Patient Am. J. Respir. Crit. Care Med., November 15, 2003; 168(10): 1210 - 1215. [Abstract] [Full Text] [PDF]

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				L. Prieto, L. Bruno, V. Gutierrez, S. Uixera, C. Perez-Frances, A. Lanuza, and A. Ferrer Airway Responsiveness to Adenosine 5'-Monophosphate and Exhaled Nitric Oxide Measurements: Predictive Value as Markers for Reducing the Dose of Inhaled Corticosteroids in Asthmatic Subjects Chest, October 1, 2003; 124(4): 1325 - 1333. [Abstract] [Full Text] [PDF]

				M. Maniscalco, E. Weitzberg, J. Sundberg, M. Sofia, and J.O. Lundberg Assessment of nasal and sinus nitric oxide output using single-breath humming exhalations Eur. Respir. J., August 1, 2003; 22(2): 323 - 329. [Abstract] [Full Text] [PDF]

				M. Deja, T. Busch, S. Bachmann, K. Riskowski, V. Campean, B. Wiedmann, M. Schwabe, B. Hell, J. Pfeilschifter, K. J. Falke, et al. Reduced Nitric Oxide in Sinus Epithelium of Patients with Radiologic Maxillary Sinusitis and Sepsis Am. J. Respir. Crit. Care Med., August 1, 2003; 168(3): 281 - 286. [Abstract] [Full Text] [PDF]

				J. Agorreta, M. Garayoa, L. M. Montuenga, and J. J. Zulueta Effects of Acute Hypoxia and Lipopolysaccharide on Nitric Oxide Synthase-2 Expression in Acute Lung Injury Am. J. Respir. Crit. Care Med., August 1, 2003; 168(3): 287 - 296. [Abstract] [Full Text] [PDF]

				K. S. van's Gravesande, M. E. Wechsler, H. Grasemann, E. S. Silverman, L. Le, L. J. Palmer, and J. M. Drazen Association of a Missense Mutation in the NOS3 Gene with Exhaled Nitric Oxide Levels Am. J. Respir. Crit. Care Med., July 15, 2003; 168(2): 228 - 231. [Abstract] [Full Text] [PDF]

				A. Soop, A. Sollevi, E. Weitzberg, J.O.N. Lundberg, J. Palm, and J. Albert Exhaled NO and plasma cGMP increase after endotoxin infusion in healthy volunteers Eur. Respir. J., April 1, 2003; 21(4): 594 - 599. [Abstract] [Full Text] [PDF]

				P A Steerenberg, N A H Janssen, G de Meer, P H Fischer, S Nierkens, H van Loveren, A Opperhuizen, B Brunekreef, and J G C van Amsterdam Relationship between exhaled NO, respiratory symptoms, lung function, bronchial hyperresponsiveness, and blood eosinophilia in school children Thorax, March 1, 2003; 58(3): 242 - 245. [Abstract] [Full Text] [PDF]

				F L M Ricciardolo Multiple roles of nitric oxide in the airways Thorax, February 1, 2003; 58(2): 175 - 182. [Abstract] [Full Text] [PDF]

				L.G. Wood, P.G. Gibson, and M.L. Garg Biomarkers of lipid peroxidation, airway inflammation and asthma Eur. Respir. J., January 1, 2003; 21(1): 177 - 186. [Abstract] [Full Text] [PDF]

P. Paredi, S. A. Kharitonov, and P. J. Barnes Analysis of Expired Air for Oxidation Products Am. J. Respir. Crit. Care Med., December 15, 2002; 166(12): S31 - 37. [Abstract] [Full Text] [PDF]