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Extended Nitric Oxide Measurements in Exhaled Air of Cystic Fibrosis and Healthy Adults

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Abstract

In cystic fibrosis (CF) lung disease, exhaled nitric oxide (FeNO) is not raised, but rather is normal or even decreased when measured at a single expiratory flow. FeNO measurements at several flow rates allow differentiation between alveolar and bronchial nitric oxide (NO) production. Extended FeNO measurements therefore should be useful to localize the FeNO deficit in CF airways. FeNO was measured in stable CF adults with moderate lung disease and in healthy controls. Bronchial NO fluxes (JNO,Br) and alveolar NO concentrations (CAlv) were calculated from FeNO measurements at flow rates of 100, 150 and 200 ml/s using a method previously described. Thirty-two adults were included in the study, 12 of whom had CF. CF adults had significantly lower FeNO values at all flow rates. The median JNO,Br was significantly lower in CF adults than in healthy controls [0.31 nl/s (range = 0.11–0.63) vs. 0.70 nl/s (0.27–3.52); P < 0.001], while the median CAlv was similar in both groups [1.7 ppb (0.3–3.9) vs. 1.2 (0.1–5.2)]. Pulmonary NO exchange did not differ significantly between subgroups of CF patients with and without chronic Pseudomonas aeruginosa infection. No significant correlation was detectable between FEV1/VC and JNO,Br and CAlv, respectively. Extended FeNO measurements can separate alveolar and bronchial NO outputs in CF adults. The lower FeNO in adults with moderate to severe CF lung disease is likely to be the result of lower bronchial NO output.

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References

  1. Grasemann H, Ratjen F (1999) Cystic fibrosis lung disease: the role of nitric oxide. Pediatr Pulmonol 28(6):442–448

    Article  PubMed  CAS  Google Scholar 

  2. Ricciardolo FL, Sterk PJ, Gaston B, Folkerts G (2004) Nitric oxide in health and disease of the respiratory system. Physiol Rev 84(3):731–765

    Article  PubMed  CAS  Google Scholar 

  3. American Thoracic Society (2005) ATS/ERS Recommendations for standardized procedures for the online, offline measurement of exhaled lower respiratory nitric oxide, nasal nitric oxide, 2005. Am J Respir Crit Care Med 171(8):912–930

    Article  Google Scholar 

  4. Ricciardolo FL, Di Stefano A, Sabatini F, Folkerts G (2006) Reactive nitrogen species in the respiratory tract. Eur J Pharmacol 533(1–3):240–252

    Article  PubMed  CAS  Google Scholar 

  5. Barnes PJ, Belvisi MG (1993) Nitric oxide and lung disease. Thorax 48(10):1034–1043

    Article  PubMed  CAS  Google Scholar 

  6. Kharitonov SA, Wells AU, O’Connor BJ, Cole PJ, Hansell DM, Logan-Sinclair RB, Barnes PJ (1995) Elevated levels of exhaled nitric oxide in bronchiectasis. Am J Respir Crit Care Med 151(6):1889–1893

    PubMed  CAS  Google Scholar 

  7. Lundberg JO, Nordvall SL, Weitzberg E, Kollberg H, Alving K (1996) Exhaled nitric oxide in paediatric asthma and cystic fibrosis. Arch Dis Child 75(4):323–326

    Article  PubMed  CAS  Google Scholar 

  8. Balfour-Lynn IM, Laverty A, Dinwiddie R (1996) Reduced upper airway nitric oxide in cystic fibrosis. Arch Dis Child 75(4):319–322

    Article  PubMed  CAS  Google Scholar 

  9. Grasemann H, Michler E, Wallot M, Ratjen F (1997) Decreased concentration of exhaled nitric oxide (NO) in patients with cystic fibrosis. Pediatr Pulmonol 24(3):173–177

    Article  PubMed  CAS  Google Scholar 

  10. De Winter-de Groot KM, van der Ent CK (2005) Nitric oxide in cystic fibrosis. J Cyst Fibros 4(Suppl 2):25–29

    Article  PubMed  Google Scholar 

  11. Tsoukias NM, George SC (1998) A two-compartment model of pulmonary nitric oxide exchange dynamics. J Appl Physiol 85(2):653–666

    PubMed  CAS  Google Scholar 

  12. Hyde RW, Geigel EJ, Olszowka AJ, Krasney JA, Forster RE 2nd, Utell MJ, Frampton MW (1997) Determination of production of nitric oxide by lower airways of humans—theory. J Appl Physiol 82(4):1290–1296

    PubMed  CAS  Google Scholar 

  13. Pietropaoli AP, Perillo IB, Torres A, Perkins PT, Frasier LM, Utell MJ, Frampton MW, Hyde RW (1999) Simultaneous measurement of nitric oxide production by conducting and alveolar airways of humans. J Appl Physiol 87(4):1532–1542

    PubMed  CAS  Google Scholar 

  14. Lehtimäki L, Turjanmaa V, Kankaanranta H, Saarelainen S, Hahtola P, Moilanen E (2000) Increased bronchial nitric oxide production in patients with asthma measured with a novel method of different exhalation flow rates. Ann Med 32(6):417–423

    Article  PubMed  Google Scholar 

  15. Lehtimäki L, Kankaanranta H, Saarelainen S, Turjanmaa V, Moilanen E (2002) Increased alveolar nitric oxide concentration in asthmatic patients with nocturnal symptoms. Eur Respir J 20(4):841–845

    Article  PubMed  Google Scholar 

  16. George SC, Hogman M, Permutt S, Silkoff PE (2004) Modelling pulmonary nitric oxide exchange. J Appl Physiol 96(3):831–839

    Article  PubMed  CAS  Google Scholar 

  17. Condorelli P, Shin HW, Aledia AS, Silkoff PE, George SC (2007) A simple technique to characterize proximal and peripheral nitric oxide exchange using constant flow exhalations and an axial diffusion model. J Appl Physiol 102(1):417–425

    Article  PubMed  Google Scholar 

  18. Suri R, Paraskakis E, Bush A (2007) Alveolar, but not bronchial nitric oxide production is elevated in cystic fibrosis. Pediatr Pulmonol 42(12):1215–1221

    Article  PubMed  Google Scholar 

  19. Döring G, Conway SP, Heijerman HG, Hodson ME, Høiby N, Smyth A, Touw DJ (2000) Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus. Eur Respir J 16(4):749–767

    Article  PubMed  Google Scholar 

  20. Roca J, Burgos F, Sunyer J, Saez M, Chinn S, Antó JM, Rodríguez-Roisin R, Quanjer PH, Nowak D, Burney P (1998) Reference values for forced spirometry Group of the European Community Respiratory Health Survey. Eur Respir J 11(6):1354–1362

    Article  PubMed  CAS  Google Scholar 

  21. Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC (1993) Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Test, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl 16:5–40

    PubMed  CAS  Google Scholar 

  22. Hofer M, Benden C, Inci I, Schmid C, Irani S, Speich R, Weder W, Boehler A (2009) True survival benefit of lung transplantation for cystic fibrosis patients: the Zurich experience. J Heart Lung Transplant 28(4):334–339

    Article  PubMed  Google Scholar 

  23. Ratjen F, Döring G (2003) Cystic fibrosis. Lancet 361(9358):681–689

    Article  PubMed  CAS  Google Scholar 

  24. Thomas SR, Kharitonov SA, Scott SF, Hodson ME, Barnes PJ (2000) Nasal and exhaled nitric oxide is reduced in adult patients with cystic fibrosis and does not correlate with cystic fibrosis genotype. Chest 117(4):1085–1089

    Article  PubMed  CAS  Google Scholar 

  25. Kelley TJ, Drumm ML (1998) Inducible nitric oxide synthase expression is reduced in cystic fibrosis murine and human airway epithelial cells. J Clin Invest 102(6):1200–1207

    Article  PubMed  CAS  Google Scholar 

  26. Meng QH, Springall DR, Bishop AE, Morgan K, Evans TJ, Habib S, Gruenert DC, Gyi KM, Hodson ME, Yacoub MH, Polak JM (1998) Lack of inducible nitric oxide synthase in bronchial epithelium: a possible mechanism of susceptibility to infection in cystic fibrosis. J Pathol 184(3):323–331

    Article  PubMed  CAS  Google Scholar 

  27. Lane C, Knight D, Burgess S, Franklin P, Horak F, Legg J, Moeller A, Stick S (2004) Epithelial inducible nitric oxide synthase activity is the major determinant of nitric oxide concentration in exhaled breath. Thorax 59(9):757–760

    Article  PubMed  CAS  Google Scholar 

  28. Zheng S, Xu W, Bose S, Banerjee AK, Haque SJ, Erzurum SC (2004) Impaired nitric oxide synthase-2 signalling pathway in cystic fibrosis airway epithelium. Am J Physiol Lung Cell Mol Physiol 287(2):L374–L381

    Article  PubMed  CAS  Google Scholar 

  29. Moeller A, Horak F Jr, Lane C, Knight D, Kicic A, Brennan S, Franklin P, Terpolilli J, Wildhaber JH, Stick SM (2006) Inducible NO synthase expression is low in airway epithelium from young children with cystic fibrosis. Thorax 61(6):514–520

    Article  PubMed  CAS  Google Scholar 

  30. Gaston B, Drazen JM, Loscalzo J, Stamler JS (1994) The biology of nitrogen oxides in the airways. Am J Respir Crit Care Med 149(2 Pt 1):538–551

    PubMed  CAS  Google Scholar 

  31. Grasemann H, Ioannidis I, Tomkiewicz RP, de Groot H, Rubin BK, Ratjen F (1998) Nitric oxide metabolites in cystic fibrosis lung disease. Arch Dis Child 78(1):49–53

    Article  PubMed  CAS  Google Scholar 

  32. Gaston B, Ratjen F, Vaughan JW, Malhotra NR, Canady RG, Snyder AH, Hunt JF, Gaertig S, Goldberg JB (2002) Nitrogen redox balance in the cystic fibrosis airway: effects of antipseudomonal therapy. Am J Respir Crit Care Med 165(3):387–390

    PubMed  Google Scholar 

  33. Gaston B, Singel D, Doctor A, Stamler JS (2006) S-nitrosothiol signalling in respiratory biology. Am J Respir Crit Care Med 173(11):1186–1193

    Article  PubMed  CAS  Google Scholar 

  34. Högman M, Drca N, Ehrstedt C, Meriläinen P (2000) Exhaled nitric oxide partitioned into alveolar, lower airways and nasal contributions. Respir Med 94(10):985–991

    Article  PubMed  Google Scholar 

  35. Grasemann H, Lax H, Treseler JW, Colin AA (2004) Dornase alpha and exhaled NO in cystic fibrosis. Pediatr Pulmonol 38(5):379–385

    Article  PubMed  Google Scholar 

  36. Shin HW, Rose-Gottron CM, Sufi RS, Perez F, Cooper DM, Wilson AF, George SC (2002) Flow-independent nitric oxide exchange parameters in cystic fibrosis. Am J Respir Crit Care Med 165(3):349–357

    PubMed  Google Scholar 

  37. Elizur A, Cannon CL, Ferkol TW (2008) Airway inflammation in cystic fibrosis. Chest 133(2):489–495

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Pulmonary Medicine, University Hospital Zurich, Raemistr 100, 8091, Zurich, Switzerland

    Markus Hofer, Luzia Mueller, Thomas Rechsteiner, Christian Benden & Annette Boehler

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  1. Markus Hofer
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  2. Luzia Mueller
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  3. Thomas Rechsteiner
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  4. Christian Benden
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  5. Annette Boehler
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Correspondence to Annette Boehler.

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Hofer, M., Mueller, L., Rechsteiner, T. et al. Extended Nitric Oxide Measurements in Exhaled Air of Cystic Fibrosis and Healthy Adults. Lung 187, 307–313 (2009). https://doi.org/10.1007/s00408-009-9160-8

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  • DOI: https://doi.org/10.1007/s00408-009-9160-8

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