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. 2003 Jul;58(7):585–588. doi: 10.1136/thorax.58.7.585

Exhaled leukotrienes and prostaglandins in COPD

P Montuschi 1, S Kharitonov 1, G Ciabattoni 1, P Barnes 1
PMCID: PMC1746732  PMID: 12832671

Abstract

Background: The role of eicosanoids, including leukotrienes (LTs) and prostaglandins (PGs), in chronic obstructive pulmonary disease (COPD) is uncertain. The aim of this study was to investigate whether eicosanoids are measurable in exhaled breath condensate (EBC), a non-invasive method of collecting airway secretions, in patients with stable mild to moderate COPD, and to show possible differences in their concentrations compared with control subjects.

Methods: LTB4, LTE4, PGE2, PGD2-methoxime, PGF, and thromboxane B2 (TxB2) were measured in EBC in 15 healthy ex-smokers, 20 steroid naïve patients with COPD who were ex-smokers, and in 25 patients with COPD who were ex-smokers and who were treated with inhaled corticosteroids. The study was of cross sectional design and all subjects were matched for age and smoking habit.

Results: LTB4 and PGE2 concentrations were increased in steroid naïve (LTB4: median 100.6 (range 73.5–145.0) pg/ml, p<0.001; PGE2: 98.0 (range 57.0–128.4) pg/ml, p<0.001) and steroid treated patients with COPD (LTB4: 99.0 (range 57.9–170.5) pg/ml, p<0.001; PGE2: 93.6 (range 52.8–157.0) pg/ml, p<0.001) compared with control subjects (LTB4: 38.1 (range 31.2–53.6) pg/ml; PGE2: 44.3 (range 30.2–52.1) pg/ml). Both groups of patients had similar concentrations of exhaled LTB4 (p=0.43) and PGE2 (p=0.59). When measurable, LTE4 and PGD2-methoxime concentrations were similar in COPD patients and controls, whereas PGF concentrations were increased in the former. TxB2-LI was undetectable in any of the subjects.

Conclusions: There is a selective increase in exhaled LTB4 and PGE2 in patients with COPD which may be relatively resistant to inhaled corticosteroid therapy.

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Selected References

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  1. Asano K., Lilly C. M., O'Donnell W. J., Israel E., Fischer A., Ransil B. J., Drazen J. M. Diurnal variation of urinary leukotriene E4 and histamine excretion rates in normal subjects and patients with mild-to-moderate asthma. J Allergy Clin Immunol. 1995 Nov;96(5 Pt 1):643–651. doi: 10.1016/s0091-6749(95)70263-6. [DOI] [PubMed] [Google Scholar]
  2. Chinn S. Statistics in respiratory medicine. 2. Repeatability and method comparison. Thorax. 1991 Jun;46(6):454–456. doi: 10.1136/thx.46.6.454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ciabattoni G., Pugliese F., Spaldi M., Cinotti G. A., Patrono C. Radioimmunoassay measurement of prostaglandins E2 and F2alpha in human urine. J Endocrinol Invest. 1979 Apr-Jun;2(2):173–182. doi: 10.1007/BF03349310. [DOI] [PubMed] [Google Scholar]
  4. Effros Richard M., Hoagland Kelly W., Bosbous Mark, Castillo Daniel, Foss Bradley, Dunning Marshall, Gare Meir, Lin Wen, Sun Feng. Dilution of respiratory solutes in exhaled condensates. Am J Respir Crit Care Med. 2002 Mar 1;165(5):663–669. doi: 10.1164/ajrccm.165.5.2101018. [DOI] [PubMed] [Google Scholar]
  5. Gauvreau G. M., Watson R. M., O'Byrne P. M. Protective effects of inhaled PGE2 on allergen-induced airway responses and airway inflammation. Am J Respir Crit Care Med. 1999 Jan;159(1):31–36. doi: 10.1164/ajrccm.159.1.9804030. [DOI] [PubMed] [Google Scholar]
  6. Gompertz Simon, Stockley Robert A. A randomized, placebo-controlled trial of a leukotriene synthesis inhibitor in patients with COPD. Chest. 2002 Jul;122(1):289–294. doi: 10.1378/chest.122.1.289. [DOI] [PubMed] [Google Scholar]
  7. Hill A. T., Bayley D., Stockley R. A. The interrelationship of sputum inflammatory markers in patients with chronic bronchitis. Am J Respir Crit Care Med. 1999 Sep;160(3):893–898. doi: 10.1164/ajrccm.160.3.9901091. [DOI] [PubMed] [Google Scholar]
  8. 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]
  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., Barnes P. J. Exhaled markers of pulmonary disease. Am J Respir Crit Care Med. 2001 Jun;163(7):1693–1722. doi: 10.1164/ajrccm.163.7.2009041. [DOI] [PubMed] [Google Scholar]
  11. Maskell N. A., Gleeson F. V., Davies R. J. O. Standard pleural biopsy versus CT-guided cutting-needle biopsy for diagnosis of malignant disease in pleural effusions: a randomised controlled trial. Lancet. 2003 Apr 19;361(9366):1326–1330. doi: 10.1016/s0140-6736(03)13079-6. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Montuschi P., Ragazzoni E., Valente S., Corbo G., Mondino C., Ciappi G., Barnes P. J., Ciabattoni G. Validation of leukotriene B4 measurements in exhaled breath condensate. Inflamm Res. 2003 Feb;52(2):69–73. doi: 10.1007/s000110300003. [DOI] [PubMed] [Google Scholar]
  14. Montuschi Paolo, Barnes Peter J. Exhaled leukotrienes and prostaglandins in asthma. J Allergy Clin Immunol. 2002 Apr;109(4):615–620. doi: 10.1067/mai.2002.122461. [DOI] [PubMed] [Google Scholar]
  15. Montuschi Paolo. Indirect monitoring of lung inflammation. Nat Rev Drug Discov. 2002 Mar;1(3):238–242. doi: 10.1038/nrd751. [DOI] [PubMed] [Google Scholar]
  16. Mutlu G. M., Garey K. W., Robbins R. A., Danziger L. H., Rubinstein I. Collection and analysis of exhaled breath condensate in humans. Am J Respir Crit Care Med. 2001 Sep 1;164(5):731–737. doi: 10.1164/ajrccm.164.5.2101032. [DOI] [PubMed] [Google Scholar]
  17. Pavord I. D., Tattersfield A. E. Bronchoprotective role for endogenous prostaglandin E2. Lancet. 1995 Feb 18;345(8947):436–438. doi: 10.1016/s0140-6736(95)90409-3. [DOI] [PubMed] [Google Scholar]
  18. Peleman R. A., Rytilä P. H., Kips J. C., Joos G. F., Pauwels R. A. The cellular composition of induced sputum in chronic obstructive pulmonary disease. Eur Respir J. 1999 Apr;13(4):839–843. doi: 10.1034/j.1399-3003.1999.13d24.x. [DOI] [PubMed] [Google Scholar]
  19. Seggev J. S., Thornton W. H., Jr, Edes T. E. Serum leukotriene B4 levels in patients with obstructive pulmonary disease. Chest. 1991 Feb;99(2):289–291. doi: 10.1378/chest.99.2.289. [DOI] [PubMed] [Google Scholar]
  20. Verhoeven G. T., Garrelds I. M., Hoogsteden H. C., Zijlstra F. J. Effects of fluticasone propionate inhalation on levels of arachidonic acid metabolites in patients with chronic obstructive pulmonary disease. Mediators Inflamm. 2001 Feb;10(1):21–26. doi: 10.1080/09629350123056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wardlaw A. J., Hay H., Cromwell O., Collins J. V., Kay A. B. Leukotrienes, LTC4 and LTB4, in bronchoalveolar lavage in bronchial asthma and other respiratory diseases. J Allergy Clin Immunol. 1989 Jul;84(1):19–26. doi: 10.1016/0091-6749(89)90173-5. [DOI] [PubMed] [Google Scholar]
  22. Zakrzewski J. T., Barnes N. C., Costello J. F., Piper P. J. Lipid mediators in cystic fibrosis and chronic obstructive pulmonary disease. Am Rev Respir Dis. 1987 Sep;136(3):779–782. doi: 10.1164/ajrccm/136.3.779. [DOI] [PubMed] [Google Scholar]

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