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. 2003 Apr;58(4):294–298. doi: 10.1136/thorax.58.4.294

Increased leukotriene B4 and 8-isoprostane in exhaled breath condensate of patients with exacerbations of COPD

W Biernacki 1, S Kharitonov 1, P Barnes 1
PMCID: PMC1746632  PMID: 12668789

Abstract

Background: Exacerbations are an important feature of chronic obstructive pulmonary disease (COPD), accounting for a large proportion of health care costs. They are associated with increased airway inflammation and oxidative stress.

Methods: Concentrations of leukotriene B4 (LTB4), a marker of inflammation, and 8-isoprostane, a marker of oxidative stress, were measured in the exhaled breath condensate of 21 patients (11 M) with COPD during an exacerbation and 2 weeks after treatment with antibiotics. In 12 patients who had no further exacerbations these markers were also measured after 2 months.

Results: LTB4 concentrations were raised during the COPD exacerbation (mean (SE) 15.8 (1.1) pg/ml and fell after treatment with antibiotics to 9.9 (0.9) pg/ml (p<0.0001). In 12 patients the level of LTB4 fell further from 10.6 (1.1) pg/ml to 8.5 (0.8) pg/ml (p<0.005) after 2 months. In 12 normal age matched subjects the LTB4 levels were 7.7 (0.5) pg/ml. Concentrations of 8-isoprostane were also increased during the exacerbation (13.0 (0.9) pg/ml) and fell after antibiotic treatment to 9.0 (0.6) pg/ml (p<0.0001). In 12 patients there was a further fall from 9.3 (0.7) pg/ml to 6.0 (0.7) pg/ml (p<0.001) after 2 months compared with normal subjects (6.2 (0.4) pg/ml).

Conclusions: Non-invasive markers of inflammation and oxidative stress are increased during an infective exacerbation of COPD and only slowly recover after treatment with antibiotics.

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Selected References

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  1. Aaron S. D., Angel J. B., Lunau M., Wright K., Fex C., Le Saux N., Dales R. E. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001 Feb;163(2):349–355. doi: 10.1164/ajrccm.163.2.2003122. [DOI] [PubMed] [Google Scholar]
  2. Adams S. G., Melo J., Luther M., Anzueto A. Antibiotics are associated with lower relapse rates in outpatients with acute exacerbations of COPD. Chest. 2000 May;117(5):1345–1352. doi: 10.1378/chest.117.5.1345. [DOI] [PubMed] [Google Scholar]
  3. Alexis N. E., Hu S. C., Zeman K., Alter T., Bennett W. D. Induced sputum derives from the central airways: confirmation using a radiolabeled aerosol bolus delivery technique. Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1964–1970. doi: 10.1164/ajrccm.164.10.2104051. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Bhowmik A., Seemungal T. A., Sapsford R. J., Wedzicha J. A. Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations. Thorax. 2000 Feb;55(2):114–120. doi: 10.1136/thorax.55.2.114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bigby T. D., Lee D. M., Meslier N., Gruenert D. C. Leukotriene A4 hydrolase activity of human airway epithelial cells. Biochem Biophys Res Commun. 1989 Oct 16;164(1):1–7. doi: 10.1016/0006-291x(89)91674-4. [DOI] [PubMed] [Google Scholar]
  7. Crooks S. W., Bayley D. L., Hill S. L., Stockley R. A. Bronchial inflammation in acute bacterial exacerbations of chronic bronchitis: the role of leukotriene B4. Eur Respir J. 2000 Feb;15(2):274–280. doi: 10.1034/j.1399-3003.2000.15b09.x. [DOI] [PubMed] [Google Scholar]
  8. Dekhuijzen P. N., Aben K. K., Dekker I., Aarts L. P., Wielders P. L., van Herwaarden C. L., Bast A. Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996 Sep;154(3 Pt 1):813–816. doi: 10.1164/ajrccm.154.3.8810624. [DOI] [PubMed] [Google Scholar]
  9. Fletcher C., Peto R. The natural history of chronic airflow obstruction. Br Med J. 1977 Jun 25;1(6077):1645–1648. doi: 10.1136/bmj.1.6077.1645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Gompertz S., Bayley D. L., Hill S. L., Stockley R. A. Relationship between airway inflammation and the frequency of exacerbations in patients with smoking related COPD. Thorax. 2001 Jan;56(1):36–41. doi: 10.1136/thorax.56.1.36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gompertz S., O'Brien C., Bayley D. L., Hill S. L., Stockley R. A. Changes in bronchial inflammation during acute exacerbations of chronic bronchitis. Eur Respir J. 2001 Jun;17(6):1112–1119. doi: 10.1183/09031936.01.99114901. [DOI] [PubMed] [Google Scholar]
  13. Hill A. T., Campbell E. J., Hill S. L., Bayley D. L., Stockley R. A. Association between airway bacterial load and markers of airway inflammation in patients with stable chronic bronchitis. Am J Med. 2000 Sep;109(4):288–295. doi: 10.1016/s0002-9343(00)00507-6. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Kanner R. E., Anthonisen N. R., Connett J. E., Lung Health Study Research Group Lower respiratory illnesses promote FEV(1) decline in current smokers but not ex-smokers with mild chronic obstructive pulmonary disease: results from the lung health study. Am J Respir Crit Care Med. 2001 Aug 1;164(3):358–364. doi: 10.1164/ajrccm.164.3.2010017. [DOI] [PubMed] [Google Scholar]
  16. Keatings V. M., Barnes P. J. Granulocyte activation markers in induced sputum: comparison between chronic obstructive pulmonary disease, asthma, and normal subjects. Am J Respir Crit Care Med. 1997 Feb;155(2):449–453. doi: 10.1164/ajrccm.155.2.9032177. [DOI] [PubMed] [Google Scholar]
  17. Mahadevia Parthiv J., Fleisher Lee A., Frick Kevin D., Eng John, Goodman Steven N., Powe Neil R. Lung cancer screening with helical computed tomography in older adult smokers: a decision and cost-effectiveness analysis. JAMA. 2003 Jan 15;289(3):313–322. doi: 10.1001/jama.289.3.313. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Montuschi P., Collins J. V., Ciabattoni G., Lazzeri N., Corradi M., Kharitonov S. A., Barnes P. J. Exhaled 8-isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):1175–1177. doi: 10.1164/ajrccm.162.3.2001063. [DOI] [PubMed] [Google Scholar]
  20. Montuschi P., Corradi M., Ciabattoni G., Nightingale J., Kharitonov S. A., Barnes P. J. Increased 8-isoprostane, a marker of oxidative stress, in exhaled condensate of asthma patients. Am J Respir Crit Care Med. 1999 Jul;160(1):216–220. doi: 10.1164/ajrccm.160.1.9809140. [DOI] [PubMed] [Google Scholar]
  21. Paredi P., Kharitonov S. A., Leak D., Ward S., Cramer D., Barnes P. J. Exhaled ethane, a marker of lipid peroxidation, is elevated in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):369–373. doi: 10.1164/ajrccm.162.2.9909025. [DOI] [PubMed] [Google Scholar]
  22. Praticò D., Basili S., Vieri M., Cordova C., Violi F., Fitzgerald G. A. Chronic obstructive pulmonary disease is associated with an increase in urinary levels of isoprostane F2alpha-III, an index of oxidant stress. Am J Respir Crit Care Med. 1998 Dec;158(6):1709–1714. doi: 10.1164/ajrccm.158.6.9709066. [DOI] [PubMed] [Google Scholar]
  23. Rahman I., Morrison D., Donaldson K., MacNee W. Systemic oxidative stress in asthma, COPD, and smokers. Am J Respir Crit Care Med. 1996 Oct;154(4 Pt 1):1055–1060. doi: 10.1164/ajrccm.154.4.8887607. [DOI] [PubMed] [Google Scholar]
  24. Repine J. E., Bast A., Lankhorst I. Oxidative stress in chronic obstructive pulmonary disease. Oxidative Stress Study Group. Am J Respir Crit Care Med. 1997 Aug;156(2 Pt 1):341–357. doi: 10.1164/ajrccm.156.2.9611013. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Roland M., Bhowmik A., Sapsford R. J., Seemungal T. A., Jeffries D. J., Warner T. D., Wedzicha J. A. Sputum and plasma endothelin-1 levels in exacerbations of chronic obstructive pulmonary disease. Thorax. 2001 Jan;56(1):30–35. doi: 10.1136/thorax.56.1.30. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Saetta M., Turato G., Facchini F. M., Corbino L., Lucchini R. E., Casoni G., Maestrelli P., Mapp C. E., Ciaccia A., Fabbri L. M. Inflammatory cells in the bronchial glands of smokers with chronic bronchitis. Am J Respir Crit Care Med. 1997 Nov;156(5):1633–1639. doi: 10.1164/ajrccm.156.5.9701081. [DOI] [PubMed] [Google Scholar]
  28. Seemungal T. A., Donaldson G. C., Bhowmik A., Jeffries D. J., Wedzicha J. A. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000 May;161(5):1608–1613. doi: 10.1164/ajrccm.161.5.9908022. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Woolhouse I. S., Hill S. L., Stockley R. A. Symptom resolution assessed using a patient directed diary card during treatment of acute exacerbations of chronic bronchitis. Thorax. 2001 Dec;56(12):947–953. doi: 10.1136/thorax.56.12.947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yamamoto C., Yoneda T., Yoshikawa M., Fu A., Tokuyama T., Tsukaguchi K., Narita N. Airway inflammation in COPD assessed by sputum levels of interleukin-8. Chest. 1997 Aug;112(2):505–510. doi: 10.1378/chest.112.2.505. [DOI] [PubMed] [Google Scholar]
  32. van Beurden W. J. C., Harff G. A., Dekhuijzen P. N. R., van den Bosch M. J. A., Creemers J. P. H. M., Smeenk F. W. J. M. An efficient and reproducible method for measuring hydrogen peroxide in exhaled breath condensate. Respir Med. 2002 Mar;96(3):197–203. doi: 10.1053/rmed.2001.1240. [DOI] [PubMed] [Google Scholar]

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