Skip to main content
PMC home page
Archives of Disease in Childhood logoLink to Archives of Disease in Childhood
. 1996 Oct;75(4):319–322. doi: 10.1136/adc.75.4.319

Reduced upper airway nitric oxide in cystic fibrosis.

I M Balfour-Lynn 1, A Laverty 1, R Dinwiddie 1
PMCID: PMC1511723  PMID: 8984918

Abstract

Nitric oxide (NO) produced within the respiratory tract is detectable in exhaled and nasal air. Its synthesis may be induced by inflammatory cytokines and reduced by glucocorticoids. Increased concentrations have been found in asthma and bronchiectasis. In this study, NO concentrations were determined in 63 children with cystic fibrosis, of whom 13 were on inhaled steroids (mean age 13.3 years) and 50 were not (mean age 12.3 years); 57 normal children (mean age 12.2 years) were also studied. NO was measured by chemiluminescence analyser, exhaled NO following a relaxed vital capacity manoeuvre, and nasal NO with the breath held following a full inspiration. Mean concentration of exhaled NO in cystic fibrosis patients (no steroids) was 4.7 parts per billion (ppb) (95% confidence interval (CI) 4.0 to 5.3); this did not differ from values in normal children (mean 4.8 ppb, 95% CI 3.8 to 5.8) or in cystic fibrosis patients on inhaled steroids (mean 3.6 ppb, 95% CI 2.5 to 4.8). Nasal concentrations were significantly lower in cystic fibrosis patients, with or without inhaled steroids, than in normal children (cystic fibrosis, no inhaled steroids: 460 ppb, 95% CI 399 to 520; cystic fibrosis, inhaled steroids: 522 ppb, 95% CI 313 to 730, v normal children: 1024 ppb, 95% CI 896 to 1152, p < 0.0001). Considering the inflammatory nature of cystic fibrosis, it is surprising exhaled NO levels were not increased, but this may have been due to alteration in NO diffusion through thick mucus. The low nasal NO concentrations, which are probably the result of impaired flow from the paranasal sinuses, may contribute to the recurrent respiratory infections typical of cystic fibrosis.

Full text

PDF
319

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alving K., Weitzberg E., Lundberg J. M. Increased amount of nitric oxide in exhaled air of asthmatics. Eur Respir J. 1993 Oct;6(9):1368–1370. [PubMed] [Google Scholar]
  2. Balfour-Lynn I. M., Dinwiddie R. Role of corticosteroids in cystic fibrosis lung disease. J R Soc Med. 1996;89 (Suppl 27):8–13. [PMC free article] [PubMed] [Google Scholar]
  3. Balough K., McCubbin M., Weinberger M., Smits W., Ahrens R., Fick R. The relationship between infection and inflammation in the early stages of lung disease from cystic fibrosis. Pediatr Pulmonol. 1995 Aug;20(2):63–70. doi: 10.1002/ppul.1950200203. [DOI] [PubMed] [Google Scholar]
  4. Barnes P. J., Belvisi M. G. Nitric oxide and lung disease. Thorax. 1993 Oct;48(10):1034–1043. doi: 10.1136/thx.48.10.1034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Belvisi M., Barnes P. J., Larkin S., Yacoub M., Tadjkarimi S., Williams T. J., Mitchell J. A. Nitric oxide synthase activity is elevated in inflammatory lung disease in humans. Eur J Pharmacol. 1995 Sep 5;283(1-3):255–258. doi: 10.1016/0014-2999(95)00421-g. [DOI] [PubMed] [Google Scholar]
  6. Croen K. D. Evidence for antiviral effect of nitric oxide. Inhibition of herpes simplex virus type 1 replication. J Clin Invest. 1993 Jun;91(6):2446–2452. doi: 10.1172/JCI116479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Eigen H., Rosenstein B. J., FitzSimmons S., Schidlow D. V. A multicenter study of alternate-day prednisone therapy in patients with cystic fibrosis. Cystic Fibrosis Foundation Prednisone Trial Group. J Pediatr. 1995 Apr;126(4):515–523. doi: 10.1016/s0022-3476(95)70343-8. [DOI] [PubMed] [Google Scholar]
  8. Gaston B., Drazen J. M., Loscalzo J., Stamler J. S. The biology of nitrogen oxides in the airways. Am J Respir Crit Care Med. 1994 Feb;149(2 Pt 1):538–551. doi: 10.1164/ajrccm.149.2.7508323. [DOI] [PubMed] [Google Scholar]
  9. Greally P., Hussein M. J., Cook A. J., Sampson A. P., Piper P. J., Price J. F. Sputum tumour necrosis factor-alpha and leukotriene concentrations in cystic fibrosis. Arch Dis Child. 1993 Mar;68(3):389–392. doi: 10.1136/adc.68.3.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gustafsson L. E., Leone A. M., Persson M. G., Wiklund N. P., Moncada S. Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans. Biochem Biophys Res Commun. 1991 Dec 16;181(2):852–857. doi: 10.1016/0006-291x(91)91268-h. [DOI] [PubMed] [Google Scholar]
  11. Hamid Q., Springall D. R., Riveros-Moreno V., Chanez P., Howarth P., Redington A., Bousquet J., Godard P., Holgate S., Polak J. M. Induction of nitric oxide synthase in asthma. Lancet. 1993 Dec 18;342(8886-8887):1510–1513. doi: 10.1016/s0140-6736(05)80083-2. [DOI] [PubMed] [Google Scholar]
  12. Jain B., Rubinstein I., Robbins R. A., Leise K. L., Sisson J. H. Modulation of airway epithelial cell ciliary beat frequency by nitric oxide. Biochem Biophys Res Commun. 1993 Feb 26;191(1):83–88. doi: 10.1006/bbrc.1993.1187. [DOI] [PubMed] [Google Scholar]
  13. Karupiah G., Xie Q. W., Buller R. M., Nathan C., Duarte C., MacMicking J. D. Inhibition of viral replication by interferon-gamma-induced nitric oxide synthase. Science. 1993 Sep 10;261(5127):1445–1448. doi: 10.1126/science.7690156. [DOI] [PubMed] [Google Scholar]
  14. Kharitonov S. A., Wells A. U., O'Connor B. J., Cole P. J., Hansell D. M., Logan-Sinclair R. B., Barnes P. J. Elevated levels of exhaled nitric oxide in bronchiectasis. Am J Respir Crit Care Med. 1995 Jun;151(6):1889–1893. doi: 10.1164/ajrccm.151.6.7767536. [DOI] [PubMed] [Google Scholar]
  15. Kharitonov S. A., Yates D. H., Barnes P. J. Inhaled glucocorticoids decrease nitric oxide in exhaled air of asthmatic patients. Am J Respir Crit Care Med. 1996 Jan;153(1):454–457. doi: 10.1164/ajrccm.153.1.8542158. [DOI] [PubMed] [Google Scholar]
  16. Kharitonov S. A., Yates D., Robbins R. A., Logan-Sinclair R., Shinebourne E. A., Barnes P. J. Increased nitric oxide in exhaled air of asthmatic patients. Lancet. 1994 Jan 15;343(8890):133–135. doi: 10.1016/s0140-6736(94)90931-8. [DOI] [PubMed] [Google Scholar]
  17. Konstan M. W., Byard P. J., Hoppel C. L., Davis P. B. Effect of high-dose ibuprofen in patients with cystic fibrosis. N Engl J Med. 1995 Mar 30;332(13):848–854. doi: 10.1056/NEJM199503303321303. [DOI] [PubMed] [Google Scholar]
  18. Leone A. M., Gustafsson L. E., Francis P. L., Persson M. G., Wiklund N. P., Moncada S. Nitric oxide is present in exhaled breath in humans: direct GC-MS confirmation. Biochem Biophys Res Commun. 1994 Jun 15;201(2):883–887. doi: 10.1006/bbrc.1994.1784. [DOI] [PubMed] [Google Scholar]
  19. Lundberg J. O., Farkas-Szallasi T., Weitzberg E., Rinder J., Lidholm J., Anggåard A., Hökfelt T., Lundberg J. M., Alving K. High nitric oxide production in human paranasal sinuses. Nat Med. 1995 Apr;1(4):370–373. doi: 10.1038/nm0495-370. [DOI] [PubMed] [Google Scholar]
  20. Lundberg J. O., Weitzberg E., Nordvall S. L., Kuylenstierna R., Lundberg J. M., Alving K. Primarily nasal origin of exhaled nitric oxide and absence in Kartagener's syndrome. Eur Respir J. 1994 Aug;7(8):1501–1504. doi: 10.1183/09031936.94.07081501. [DOI] [PubMed] [Google Scholar]
  21. Mancinelli R. L., McKay C. P. Effects of nitric oxide and nitrogen dioxide on bacterial growth. Appl Environ Microbiol. 1983 Jul;46(1):198–202. doi: 10.1128/aem.46.1.198-202.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  23. Ramsey B. W., Boat T. F. Outcome measures for clinical trials in cystic fibrosis. Summary of a Cystic Fibrosis Foundation consensus conference. J Pediatr. 1994 Feb;124(2):177–192. doi: 10.1016/s0022-3476(94)70301-9. [DOI] [PubMed] [Google Scholar]
  24. Ramsey B., Richardson M. A. Impact of sinusitis in cystic fibrosis. J Allergy Clin Immunol. 1992 Sep;90(3 Pt 2):547–552. doi: 10.1016/0091-6749(92)90183-3. [DOI] [PubMed] [Google Scholar]
  25. Rosenthal M., Bain S. H., Cramer D., Helms P., Denison D., Bush A., Warner J. O. Lung function in white children aged 4 to 19 years: I--Spirometry. Thorax. 1993 Aug;48(8):794–802. doi: 10.1136/thx.48.8.794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Warren J. B., Loi R., Rendell N. B., Taylor G. W. Nitric oxide is inactivated by the bacterial pigment pyocyanin. Biochem J. 1990 Mar 15;266(3):921–923. [PMC free article] [PubMed] [Google Scholar]

Articles from Archives of Disease in Childhood are provided here courtesy of BMJ Publishing Group

RESOURCES