Skip to main content
NCBI home page
Thorax logoLink to Thorax
. 2001 May;56(5):366–372. doi: 10.1136/thorax.56.5.366

Assessment of airway neutrophils by sputum colour: correlation with airways inflammation

R Stockley 1, D Bayley 1, S Hill 1, A Hill 1, S Crooks 1, E Campbell 1
PMCID: PMC1746057  PMID: 11312405

Abstract

BACKGROUND—Airway inflammation, with recruitment of neutrophils to the airway lumen, results in purulent secretions and a variety of potential adverse consequences for patients with chronic bronchitis and bronchiectasis. We hypothesised that gradations of sputum colour would correlate directly with the myeloperoxidase content of sputum and with various other indicators of the activity and consequences of bronchial diseases.
METHODS—To test this hypothesis, we quantified sputum colour by reference to a sensitive nine point colour chart and correlated this assessment with indices of a number of inflammatory mediators in sputum.
RESULTS—The results indicate that standardised visual measurements of sputum colour correlated strongly with myeloperoxidase, interleukin 8, leucocyte elastase (both activity and total quantity), sputum volume, protein leak, and secretory leucocyte proteinase inhibitor (p<0.001 for all). In addition, there was a strong direct correlation between leucocyte elastase and both myeloperoxidase (p<0.003) and sputum volume (p<0.001), but a strong negative correlation with secretory leucocyte proteinase inhibitor (p<0.001).
CONCLUSIONS—These results indicate that sputum colour graded visually relates to the activity of the underlying markers of bronchial inflammation. The results of this simple visual analysis of sputum provides guidance concerning underlying inflammation and its damaging potential. It also provides a useful scientific tool for improving the monitoring of chronic airways diseases and response to treatment.



Full Text

The Full Text of this article is available as a PDF (159.1 KB).

Selected References

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

  1. Afford S. C., Burnett D., Campbell E. J., Cury J. D., Stockley R. A. The assessment of alpha 1 proteinase inhibitor form and function in lung lavage fluid from healthy subjects. Biol Chem Hoppe Seyler. 1988 Sep;369(9):1065–1074. doi: 10.1515/bchm3.1988.369.2.1065. [DOI] [PubMed] [Google Scholar]
  2. Amitani R., Wilson R., Rutman A., Read R., Ward C., Burnett D., Stockley R. A., Cole P. J. Effects of human neutrophil elastase and Pseudomonas aeruginosa proteinases on human respiratory epithelium. Am J Respir Cell Mol Biol. 1991 Jan;4(1):26–32. doi: 10.1165/ajrcmb/4.1.26. [DOI] [PubMed] [Google Scholar]
  3. Anthonisen N. R., Manfreda J., Warren C. P., Hershfield E. S., Harding G. K., Nelson N. A. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 1987 Feb;106(2):196–204. doi: 10.7326/0003-4819-106-2-196. [DOI] [PubMed] [Google Scholar]
  4. Buttle D. J., Abrahamson M., Burnett D., Mort J. S., Barrett A. J., Dando P. M., Hill S. L. Human sputum cathepsin B degrades proteoglycan, is inhibited by alpha 2-macroglobulin and is modulated by neutrophil elastase cleavage of cathepsin B precursor and cystatin C. Biochem J. 1991 Jun 1;276(Pt 2):325–331. doi: 10.1042/bj2760325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bédard M., McClure C. D., Schiller N. L., Francoeur C., Cantin A., Denis M. Release of interleukin-8, interleukin-6, and colony-stimulating factors by upper airway epithelial cells: implications for cystic fibrosis. Am J Respir Cell Mol Biol. 1993 Oct;9(4):455–462. doi: 10.1165/ajrcmb/9.4.455. [DOI] [PubMed] [Google Scholar]
  6. Campbell E. J., Silverman E. K., Campbell M. A. Elastase and cathepsin G of human monocytes. Quantification of cellular content, release in response to stimuli, and heterogeneity in elastase-mediated proteolytic activity. J Immunol. 1989 Nov 1;143(9):2961–2968. [PubMed] [Google Scholar]
  7. Cardozo C., Padilla M. L., Choi H. S., Lesser M. Goblet cell hyperplasia in large intrapulmonary airways after intratracheal injection of cathepsin B into hamsters. Am Rev Respir Dis. 1992 Mar;145(3):675–679. doi: 10.1164/ajrccm/145.3.675. [DOI] [PubMed] [Google Scholar]
  8. Ford-Hutchinson A. W., Bray M. A., Doig M. V., Shipley M. E., Smith M. J. Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature. 1980 Jul 17;286(5770):264–265. doi: 10.1038/286264a0. [DOI] [PubMed] [Google Scholar]
  9. Hill A. T., Campbell E. J., Bayley D. L., Hill S. L., Stockley R. A. Evidence for excessive bronchial inflammation during an acute exacerbation of chronic obstructive pulmonary disease in patients with alpha(1)-antitrypsin deficiency (PiZ). Am J Respir Crit Care Med. 1999 Dec;160(6):1968–1975. doi: 10.1164/ajrccm.160.6.9904097. [DOI] [PubMed] [Google Scholar]
  10. Hill S. L., Morrison H. M., Burnett D., Stockley R. A. Short term response of patients with bronchiectasis to treatment with amoxycillin given in standard or high doses orally or by inhalation. Thorax. 1986 Jul;41(7):559–565. doi: 10.1136/thx.41.7.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hubbard R. C., Fells G., Gadek J., Pacholok S., Humes J., Crystal R. G. Neutrophil accumulation in the lung in alpha 1-antitrypsin deficiency. Spontaneous release of leukotriene B4 by alveolar macrophages. J Clin Invest. 1991 Sep;88(3):891–897. doi: 10.1172/JCI115391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Janoff A., Sloan B., Weinbaum G., Damiano V., Sandhaus R. A., Elias J., Kimbel P. Experimental emphysema induced with purified human neutrophil elastase: tissue localization of the instilled protease. Am Rev Respir Dis. 1977 Mar;115(3):461–478. doi: 10.1164/arrd.1977.115.3.461. [DOI] [PubMed] [Google Scholar]
  13. Kargi H. A., Campbell E. J., Kuhn C., 3rd Elastase and cathepsin G of human monocytes: heterogeneity and subcellular localization to peroxidase-positive granules. J Histochem Cytochem. 1990 Aug;38(8):1179–1186. doi: 10.1177/38.8.2164060. [DOI] [PubMed] [Google Scholar]
  14. Kramps J. A., Rudolphus A., Stolk J., Willems L. N., Dijkman J. H. Role of antileukoprotease in the human lung. Ann N Y Acad Sci. 1991;624:97–108. doi: 10.1111/j.1749-6632.1991.tb17010.x. [DOI] [PubMed] [Google Scholar]
  15. Lucey E. C., Stone P. J., Breuer R., Christensen T. G., Calore J. D., Catanese A., Franzblau C., Snider G. L. Effect of combined human neutrophil cathepsin G and elastase on induction of secretory cell metaplasia and emphysema in hamsters, with in vitro observations on elastolysis by these enzymes. Am Rev Respir Dis. 1985 Aug;132(2):362–366. doi: 10.1164/arrd.1985.132.2.362. [DOI] [PubMed] [Google Scholar]
  16. McElvaney N. G., Nakamura H., Birrer P., Hébert C. A., Wong W. L., Alphonso M., Baker J. B., Catalano M. A., Crystal R. G. Modulation of airway inflammation in cystic fibrosis. In vivo suppression of interleukin-8 levels on the respiratory epithelial surface by aerosolization of recombinant secretory leukoprotease inhibitor. J Clin Invest. 1992 Oct;90(4):1296–1301. doi: 10.1172/JCI115994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mikami M., Llewellyn-Jones C. G., Bayley D., Hill S. L., Stockley R. A. The chemotactic activity of sputum from patients with bronchiectasis. Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):723–728. doi: 10.1164/ajrccm.157.3.9606120. [DOI] [PubMed] [Google Scholar]
  18. Morihara K., Tsuzuki H., Oda K. Protease and elastase of Pseudomonas aeruginosa: inactivation of human plasma alpha 1-proteinase inhibitor. Infect Immun. 1979 Apr;24(1):188–193. doi: 10.1128/iai.24.1.188-193.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nakamura H., Yoshimura K., McElvaney N. G., Crystal R. G. Neutrophil elastase in respiratory epithelial lining fluid of individuals with cystic fibrosis induces interleukin-8 gene expression in a human bronchial epithelial cell line. J Clin Invest. 1992 May;89(5):1478–1484. doi: 10.1172/JCI115738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Owen C. A., Campbell M. A., Boukedes S. S., Stockley R. A., Campbell E. J. A discrete subpopulation of human monocytes expresses a neutrophil-like proinflammatory (P) phenotype. Am J Physiol. 1994 Dec;267(6 Pt 1):L775–L785. doi: 10.1152/ajplung.1994.267.6.L775. [DOI] [PubMed] [Google Scholar]
  21. Owen C. A., Campbell M. A., Sannes P. L., Boukedes S. S., Campbell E. J. Cell surface-bound elastase and cathepsin G on human neutrophils: a novel, non-oxidative mechanism by which neutrophils focus and preserve catalytic activity of serine proteinases. J Cell Biol. 1995 Nov;131(3):775–789. doi: 10.1083/jcb.131.3.775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Powers J. C., Gupton B. F. Reaction of serine proteases with aza-amino acid and aza-peptide derivatives. Methods Enzymol. 1977;46:208–216. doi: 10.1016/s0076-6879(77)46021-x. [DOI] [PubMed] [Google Scholar]
  23. Rice W. G., Weiss S. J. Regulation of proteolysis at the neutrophil-substrate interface by secretory leukoprotease inhibitor. Science. 1990 Jul 13;249(4965):178–181. doi: 10.1126/science.2371565. [DOI] [PubMed] [Google Scholar]
  24. Riise G. C., Ahlstedt S., Larsson S., Enander I., Jones I., Larsson P., Andersson B. Bronchial inflammation in chronic bronchitis assessed by measurement of cell products in bronchial lavage fluid. Thorax. 1995 Apr;50(4):360–365. doi: 10.1136/thx.50.4.360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sallenave J. M., Shulmann J., Crossley J., Jordana M., Gauldie J. Regulation of secretory leukocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor (ESI/elafin) in human airway epithelial cells by cytokines and neutrophilic enzymes. Am J Respir Cell Mol Biol. 1994 Dec;11(6):733–741. doi: 10.1165/ajrcmb.11.6.7946401. [DOI] [PubMed] [Google Scholar]
  26. Senior R. M., Tegner H., Kuhn C., Ohlsson K., Starcher B. C., Pierce J. A. The induction of pulmonary emphysema with human leukocyte elastase. Am Rev Respir Dis. 1977 Sep;116(3):469–475. doi: 10.1164/arrd.1977.116.3.469. [DOI] [PubMed] [Google Scholar]
  27. Smallman L. A., Hill S. L., Stockley R. A. Reduction of ciliary beat frequency in vitro by sputum from patients with bronchiectasis: a serine proteinase effect. Thorax. 1984 Sep;39(9):663–667. doi: 10.1136/thx.39.9.663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Smith I. E., Jurriaans E., Diederich S., Ali N., Shneerson J. M., Flower C. D. Chronic sputum production: correlations between clinical features and findings on high resolution computed tomographic scanning of the chest. Thorax. 1996 Sep;51(9):914–918. doi: 10.1136/thx.51.9.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Stockley R. A., Afford S. C. Qualitative studies of lung lavage alpha 1-proteinase inhibitor. Hoppe Seylers Z Physiol Chem. 1984 Apr;365(4):503–510. doi: 10.1515/bchm2.1984.365.1.503. [DOI] [PubMed] [Google Scholar]
  30. Stockley R. A. Bronchiectasis--new therapeutic approaches based on pathogenesis. Clin Chest Med. 1987 Sep;8(3):481–494. [PubMed] [Google Scholar]
  31. Stockley R. A., Burnett D. Alpha,-antitrypsin and leukocyte elastase in infected and noninfected sputum. Am Rev Respir Dis. 1979 Nov;120(5):1081–1086. doi: 10.1164/arrd.1979.120.5.1081. [DOI] [PubMed] [Google Scholar]
  32. Stockley R. A., Hill S. L., Morrison H. M., Starkie C. M. Elastolytic activity of sputum and its relation to purulence and to lung function in patients with bronchiectasis. Thorax. 1984 Jun;39(6):408–413. doi: 10.1136/thx.39.6.408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Stockley R. A., O'Brien C., Pye A., Hill S. L. Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD. Chest. 2000 Jun;117(6):1638–1645. doi: 10.1378/chest.117.6.1638. [DOI] [PubMed] [Google Scholar]
  34. Takahashi G. W., Andrews D. F., 3rd, Lilly M. B., Singer J. W., Alderson M. R. Effect of granulocyte-macrophage colony-stimulating factor and interleukin-3 on interleukin-8 production by human neutrophils and monocytes. Blood. 1993 Jan 15;81(2):357–364. [PubMed] [Google Scholar]
  35. Tosi M. F., Zakem H., Berger M. Neutrophil elastase cleaves C3bi on opsonized pseudomonas as well as CR1 on neutrophils to create a functionally important opsonin receptor mismatch. J Clin Invest. 1990 Jul;86(1):300–308. doi: 10.1172/JCI114699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wewers M. Pathogenesis of emphysema. Assessment of basic science concepts through clinical investigation. Chest. 1989 Jan;95(1):190–195. doi: 10.1378/chest.95.1.190. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES