Exhaled nitric oxide is not elevated in the inflammatory airways diseases of cystic fibrosis and bronchiectasis

Airways inflammation has been associated with increased nitric oxide (NO) in the exhaled breath. It was, therefore, questioned whether exhaled NO could act as an indicator of the severity of airways inflammation in the chronic suppurative lung diseases cystic fibrosis (CF) and bronchiectasis. NO levels in a single exhalation were measured using a chemiluminescence analyser. Thirty-six patients with CF and 16 with bronchiectasis were studied and compared with 22 normal subjects and 35 asthmatic patients. All subjects were nonsmokers and all measurements were made when patients were clinically stable. In addition, exhaled NO was measured in 10 CF patients at the time of onset of an acute infective exacerbation and followed for 7 days during the treatment of the exacerbation in eight of the 10 patients. No significant differences were found in NO levels in patients with CF or bronchiectasis compared with normals (median 4.0, 5.5 and 4.4 parts per billion (ppb), respectively), but all were lower than in asthma patients (10.4 ppb). The NO levels in the CF patients at time of exacerbation were not increased and did not change during treatment. These data show that nitric oxide levels in the exhaled breath of patients with chronic suppurative lung diseases, in contrast to asthma, are not elevated, despite the presence of substantial airways inflammation. Possible explanations include poor diffusion of nitric oxide across increased and viscous airway secretions, removal of nitric oxide by reaction with reactive oxygen species in the inflamed environment and failure of upregulation of epithelial inducible nitric oxide synthase in chronic suppurative conditions.

This article has been cited by other articles:

				R. D. Gray, G. MacGregor, D. Noble, M. Imrie, M. Dewar, A. C. Boyd, J. A. Innes, D. J. Porteous, and A. P. Greening Sputum Proteomics in Inflammatory and Suppurative Respiratory Diseases Am. J. Respir. Crit. Care Med., September 1, 2008; 178(5): 444 - 452. [Abstract] [Full Text] [PDF]

				K. G. Lim and C. Mottram The Use of Fraction of Exhaled Nitric Oxide in Pulmonary Practice Chest, May 1, 2008; 133(5): 1232 - 1242. [Abstract] [Full Text] [PDF]

				C. Grasemann, F. Ratjen, D. Schnabel, E. Reutershahn, U. Vester, and H. Grasemann Effect of growth hormone therapy on nitric oxide formation in cystic fibrosis patients Eur. Respir. J., April 1, 2008; 31(4): 815 - 821. [Abstract] [Full Text] [PDF]

				A. Elizur, C. L. Cannon, and T. W. Ferkol Airway Inflammation in Cystic Fibrosis* Chest, February 1, 2008; 133(2): 489 - 495. [Abstract] [Full Text] [PDF]

				D R Taylor, M W Pijnenburg, A D Smith, and J C D Jongste Exhaled nitric oxide measurements: clinical application and interpretation Thorax, September 1, 2006; 61(9): 817 - 827. [Abstract] [Full Text] [PDF]

				H. Grasemann, F. Kurtz, and F. Ratjen Inhaled L-Arginine Improves Exhaled Nitric Oxide and Pulmonary Function in Patients with Cystic Fibrosis Am. J. Respir. Crit. Care Med., July 15, 2006; 174(2): 208 - 212. [Abstract] [Full Text] [PDF]

				P. J. Franklin, G. L. Hall, A. Moeller, F. Horak, S. Brennan, and S. M. Stick Exhaled nitric oxide is not reduced in infants with cystic fibrosis Eur. Respir. J., February 1, 2006; 27(2): 350 - 354. [Abstract] [Full Text] [PDF]

				H. Grasemann, R. Schwiertz, S. Matthiesen, K. Racke, and F. Ratjen Increased Arginase Activity in Cystic Fibrosis Airways Am. J. Respir. Crit. Care Med., December 15, 2005; 172(12): 1523 - 1528. [Abstract] [Full Text] [PDF]

				ATS/ERS Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide, 2005 Am. J. Respir. Crit. Care Med., April 15, 2005; 171(8): 912 - 930. [Full Text] [PDF]

				H. Grasemann, C. Grasemann, F. Kurtz, G. Tietze-Schillings, U. Vester, and F. Ratjen Oral L-arginine supplementation in cystic fibrosis patients: a placebo-controlled study Eur. Respir. J., January 1, 2005; 25(1): 62 - 68. [Abstract] [Full Text] [PDF]

				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]

				A. J. Kettle, T. Chan, I. Osberg, R. Senthilmohan, A. L. P. Chapman, T. J. Mocatta, and J. S. Wagener Myeloperoxidase and Protein Oxidation in the Airways of Young Children with Cystic Fibrosis Am. J. Respir. Crit. Care Med., December 15, 2004; 170(12): 1317 - 1323. [Abstract] [Full Text] [PDF]

				T. Martinez, A. Weist, T. Williams, C. Clem, P. Silkoff, and R. S. Tepper Assessment of exhaled nitric oxide kinetics in healthy infants J Appl Physiol, June 1, 2003; 94(6): 2384 - 2390. [Abstract] [Full Text] [PDF]

				H. Grasemann, K. S. van's Gravesande, R. Buscher, N. Knauer, E. S. Silverman, L. J. Palmer, J. M. Drazen, and F. Ratjen Endothelial Nitric Oxide Synthase Variants in Cystic Fibrosis Lung Disease Am. J. Respir. Crit. Care Med., February 1, 2003; 167(3): 390 - 394. [Abstract] [Full Text] [PDF]

				I Horvath, S Loukides, T Wodehouse, E Csiszer, P J Cole, S A Kharitonov, and P J Barnes Comparison of exhaled and nasal nitric oxide and exhaled carbon monoxide levels in bronchiectatic patients with and without primary ciliary dyskinesia Thorax, January 1, 2003; 58(1): 68 - 72. [Abstract] [Full Text] [PDF]

				W. Zetterquist, H. Marteus, M. Johannesson, S.L. Nordvall, E. Ihre, J.O.N. Lundberg, and K. Alving Exhaled carbon monoxide is not elevated in patients with asthma or cystic fibrosis Eur. Respir. J., July 1, 2002; 20(1): 92 - 99. [Abstract] [Full Text] [PDF]

				Members of the Task Force:, E. Baraldi, J.C. de Jongste, B. Gaston, K. Alving, P.J. Barnes, H. Bisgaard, A. Bush, C. Gaultier, H. Grasemann, et al. Measurement of exhaled nitric oxide in children, 2001: E. Baraldi and J.C. de Jongste on behalf of the Task Force Eur. Respir. J., July 1, 2002; 20(1): 223 - 237. [Abstract] [Full Text] [PDF]

				K. Kostikas, G. Papatheodorou, K. Ganas, K. Psathakis, P. Panagou, and S. Loukides pH in Expired Breath Condensate of Patients with Inflammatory Airway Diseases Am. J. Respir. Crit. Care Med., May 15, 2002; 165(10): 1364 - 1370. [Abstract] [Full Text] [PDF]

				H.-W. SHIN, C. M. ROSE-GOTTRON, R. S. SUFI, F. PEREZ, D. M. COOPER, A. F. WILSON, and S. C. GEORGE Flow-independent Nitric Oxide Exchange Parameters in Cystic Fibrosis Am. J. Respir. Crit. Care Med., February 1, 2002; 165(3): 349 - 357. [Abstract] [Full Text] [PDF]

				K. W. Tsang, R. Leung, P. Chin-wan Fung, S. L. Chan, G. L. Tipoe, G. C. Ooi, and W. K. Lam Exhaled and Sputum Nitric Oxide in Bronchiectasis : Correlation With Clinical Parameters Chest, January 1, 2002; 121(1): 88 - 94. [Abstract] [Full Text] [PDF]

				H.-W. Shin, C. M. Rose-Gottron, F. Perez, D. M. Cooper, A. F. Wilson, and S. C. George Flow-independent nitric oxide exchange parameters in healthy adults J Appl Physiol, November 1, 2001; 91(5): 2173 - 2181. [Abstract] [Full Text] [PDF]

				S. A. KHARITONOV and P. J. BARNES Exhaled Markers of Pulmonary Disease Am. J. Respir. Crit. Care Med., June 1, 2001; 163(7): 1693 - 1722. [Full Text] [PDF]

				C. ADRIE, M. MONCHI, A. TUAN DINH-XUAN, J. DALL'AVA-SANTUCCI, J.-F. DHAINAUT, and M. R. PINSKY Exhaled and Nasal Nitric Oxide as a Marker of Pneumonia in Ventilated Patients Am. J. Respir. Crit. Care Med., April 1, 2001; 163(5): 1143 - 1149. [Abstract] [Full Text]

				H. GRASEMANN, N. KNAUER, R. BÜSCHER, K. HÜBNER, J. M. DRAZEN, and F. RATJEN Airway Nitric Oxide Levels in Cystic Fibrosis Patients Are Related to a Polymorphism in the Neuronal Nitric Oxide Synthase Gene Am. J. Respir. Crit. Care Med., December 1, 2000; 162(6): 2172 - 2176. [Abstract] [Full Text]

				L.-P. Ho, F. T. Wood, A. Robson, J. A. Innes, and A. P. Greening Atopy Influences Exhaled Nitric Oxide Levels in Adult Asthmatics Chest, November 1, 2000; 118(5): 1327 - 1331. [Abstract] [Full Text] [PDF]

				J. D Antuni, S. A Kharitonov, D. Hughes, M. E Hodson, and P. J Barnes Increase in exhaled carbon monoxide during exacerbations of cystic fibrosis Thorax, February 1, 2000; 55(2): 138 - 142. [Abstract] [Full Text]

				P. Silkoff Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide in Adults and Children---1999 . THIS OFFICIAL STATEMENT OF THE AMERICAN THORACIC SOCIETY WAS ADOPTED BY THE ATS BOARD OF DIRECTORS, JULY 1999 Am. J. Respir. Crit. Care Med., December 1, 1999; 160(6): 2104 - 2117. [Full Text]