Skip to main content
NCBI home page
Thorax logoLink to Thorax
. 1999 Jul;54(7):576–580. doi: 10.1136/thx.54.7.576

Markers of nitric oxide metabolism in sputum and exhaled air are not increased in chronic obstructive pulmonary disease

S Rutgers 1, T W van der Mark 1, W Coers 1, H Moshage 1, W Timens 1, H Kauffman 1, G Koeter 1, D Postma 1
PMCID: PMC1745531  PMID: 10377200

Abstract

BACKGROUND—Nitric oxide (NO) is involved in inflammation and host defence of the lung. It has been found in increased concentrations in the airways in asthmatic subjects but its levels in patients with chronic obstructive pulmonary disease (COPD) have not been investigated. A study was undertaken to determine whether markers of NO metabolism (NO in exhaled air, iNOS expression in sputum cells, and nitrite + nitrate (NO2-/NO3-) in sputum supernatant) are increased in subjects with COPD, and whether they correlate with inflammatory indices in induced sputum. The associations of these markers with smoking were also assessed.
METHODS—Sixteen subjects with COPD (median age 66 years, median forced expiratory volume in one second (FEV1) 63% predicted, eight current smokers) and 16 healthy subjects (median age 63 years, median FEV1 113% predicted, eight current smokers) participated in the study. NO was measured during tidal breathing and sputum was induced by inhalation of hypertonic saline.
RESULTS—No differences were observed between subjects with COPD and healthy controls in exhaled NO excretion rate (median 5.15 and 6.25 nmol/min), sputum macrophage iNOS expression (14% and 12%), and sputum supernatant NO2-/NO3- (46 and 73 µM). NO in exhaled air correlated with the percentage of sputum eosinophils in patients with COPD (rho = 0.65, p = 0.009) but not in healthy individuals. Exhaled NO and supernatant NO2-/NO3- levels were lower in healthy smokers than in healthy non/ex-smokers.
CONCLUSIONS—Our findings indicate that NO metabolism is not increased in patients with stable COPD. The close association between exhaled NO levels and sputum eosinophils suggests a role for NO in airway inflammation in COPD. Studies performed during exacerbations may clarify this role.



Full Text

The Full Text of this article is available as a PDF (133.5 KB).

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. Beauvais F., Michel L., Dubertret L. The nitric oxide donors, azide and hydroxylamine, inhibit the programmed cell death of cytokine-deprived human eosinophils. FEBS Lett. 1995 Mar 20;361(2-3):229–232. doi: 10.1016/0014-5793(95)00188-f. [DOI] [PubMed] [Google Scholar]
  3. Ferreira H. H., Medeiros M. V., Lima C. S., Flores C. A., Sannomiya P., Autunes E., De Nucci G. Inhibition of eosinophil chemotaxis by chronic blockade of nitric oxide biosynthesis. Eur J Pharmacol. 1996 Aug 29;310(2-3):201–207. doi: 10.1016/0014-2999(96)00379-2. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Jeffery P. K. Comparative morphology of the airways in asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1994 Nov;150(5 Pt 2):S6–13. doi: 10.1164/ajrccm/150.5_Pt_2.S6. [DOI] [PubMed] [Google Scholar]
  7. Juniper E. F., Frith P. A., Dunnett C., Cockcroft D. W., Hargreave F. E. Reproducibility and comparison of responses to inhaled histamine and methacholine. Thorax. 1978 Dec;33(6):705–710. doi: 10.1136/thx.33.6.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kanazawa H., Shoji S., Yamada M., Fujii T., Kawaguchi T., Kudoh S., Hirata K., Yoshikawa J. Increased levels of nitric oxide derivatives in induced sputum in patients with asthma. J Allergy Clin Immunol. 1997 May;99(5):624–629. doi: 10.1016/s0091-6749(97)70024-1. [DOI] [PubMed] [Google Scholar]
  9. Keatings V. M., Collins P. D., Scott D. M., Barnes P. J. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med. 1996 Feb;153(2):530–534. doi: 10.1164/ajrccm.153.2.8564092. [DOI] [PubMed] [Google Scholar]
  10. Kharitonov S. A., Robbins R. A., Yates D., Keatings V., Barnes P. J. Acute and chronic effects of cigarette smoking on exhaled nitric oxide. Am J Respir Crit Care Med. 1995 Aug;152(2):609–612. doi: 10.1164/ajrccm.152.2.7543345. [DOI] [PubMed] [Google Scholar]
  11. Maziak W., Loukides S., Culpitt S., Sullivan P., Kharitonov S. A., Barnes P. J. Exhaled nitric oxide in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):998–1002. doi: 10.1164/ajrccm.157.3.97-05009. [DOI] [PubMed] [Google Scholar]
  12. Moshage H., Kok B., Huizenga J. R., Jansen P. L. Nitrite and nitrate determinations in plasma: a critical evaluation. Clin Chem. 1995 Jun;41(6 Pt 1):892–896. [PubMed] [Google Scholar]
  13. Quanjer P. H., Tammeling G. J., Cotes J. E., Pedersen O. F., Peslin R., Yernault J. C. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993 Mar;16:5–40. [PubMed] [Google Scholar]
  14. Robbins R. A., Floreani A. A., Von Essen S. G., Sisson J. H., Hill G. E., Rubinstein I., Townley R. G. Measurement of exhaled nitric oxide by three different techniques. Am J Respir Crit Care Med. 1996 May;153(5):1631–1635. doi: 10.1164/ajrccm.153.5.8630613. [DOI] [PubMed] [Google Scholar]
  15. Ronchi M. C., Piragino C., Rosi E., Amendola M., Duranti R., Scano G. Role of sputum differential cell count in detecting airway inflammation in patients with chronic bronchial asthma or COPD. Thorax. 1996 Oct;51(10):1000–1004. doi: 10.1136/thx.51.10.1000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rutgers S. R., Meijer R. J., Kerstjens H. A., van der Mark T. W., Koëter G. H., Postma D. S. Nitric oxide measured with single-breath and tidal-breathing methods in asthma and COPD. Eur Respir J. 1998 Oct;12(4):816–819. doi: 10.1183/09031936.98.12040816. [DOI] [PubMed] [Google Scholar]
  17. Turato G., Di Stefano A., Maestrelli P., Mapp C. E., Ruggieri M. P., Roggeri A., Fabbri L. M., Saetta M. Effect of smoking cessation on airway inflammation in chronic bronchitis. Am J Respir Crit Care Med. 1995 Oct;152(4 Pt 1):1262–1267. doi: 10.1164/ajrccm.152.4.7551380. [DOI] [PubMed] [Google Scholar]
  18. Vagaggini B., Paggiaro P. L., Giannini D., Franco A. D., Cianchetti S., Carnevali S., Taccola M., Bacci E., Bancalari L., Dente F. L. Effect of short-term NO2 exposure on induced sputum in normal, asthmatic and COPD subjects. Eur Respir J. 1996 Sep;9(9):1852–1857. doi: 10.1183/09031936.96.09091852. [DOI] [PubMed] [Google Scholar]
  19. del Pozo V., de Arruda-Chaves E., de Andrés B., Cárdaba B., López-Farré A., Gallardo S., Cortegano I., Vidarte L., Jurado A., Sastre J. Eosinophils transcribe and translate messenger RNA for inducible nitric oxide synthase. J Immunol. 1997 Jan 15;158(2):859–864. [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES