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. 2003 Jun;58(6):505–509. doi: 10.1136/thorax.58.6.505

Cysteinyl leukotrienes and 8-isoprostane in exhaled breath condensate of children with asthma exacerbations

E Baraldi 1, S Carraro 1, R Alinovi 1, A Pesci 1, L Ghiro 1, A Bodini 1, G Piacentini 1, F Zacchello 1, S Zanconato 1
PMCID: PMC1746712  PMID: 12775861

Abstract

Background: Cysteinyl leukotrienes (Cys-LTs) and isoprostanes are inflammatory metabolites derived from arachidonic acid whose levels are increased in the airways of asthmatic patients. Isoprostanes are relatively stable and specific for lipid peroxidation, which makes them potentially reliable biomarkers for oxidative stress. A study was undertaken to evaluate the effect of a course of oral steroids on Cys-LT and 8-isoprostane levels in exhaled breath condensate of children with an asthma exacerbation.

Methods: Exhaled breath condensate was collected and fractional exhaled nitric oxide (FENO) and spirometric parameters were measured before and after a 5 day course of oral prednisone (1 mg/kg/day) in 15 asthmatic children with an asthma exacerbation. Cys-LT and 8-isoprostane concentrations were measured using an enzyme immunoassay. FENO was measured using a chemiluminescence analyser. Exhaled breath condensate was also collected from 10 healthy children.

Results: Before prednisone treatment both Cys-LT and 8-isoprostane concentrations were higher in asthmatic subjects (Cys-LTs, 12.7 pg/ml (IQR 5.4–15.6); 8-isoprostane, 12.0 pg/ml (9.4–29.5)) than in healthy children (Cys-LTs, 4.3 pg/ml (2.0–5.7), p=0.002; 8-isoprostane, 2.6 pg/ml (2.1–3.0), p<0.001). After prednisone treatment there was a significant decrease in both Cys-LT (5.2 pg/ml (3.9–8.8), p=0.005) and 8-isoprostane (8.4 pg/ml (5.4–11.6), p=0.04) concentrations, but 8-isoprostane levels remained higher than in controls (p<0.001). FENO levels, which fell significantly after prednisone treatment (p<0.001), did not correlate significantly with either Cys-LT or 8-isoprostane concentrations.

Conclusion: After a 5 day course of oral prednisone there is a reduction in Cys-LT and 8-isoprostane levels in EBC of children with an asthma exacerbation, although 8-isoprostane levels remain higher than in controls. This finding suggests that corticosteroids may not be fully effective in reducing oxidative stress in children with an exacerbation of asthma.

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Selected References

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  1. Bisgaard H. Leukotriene modifiers in pediatric asthma management. Pediatrics. 2001 Feb;107(2):381–390. doi: 10.1542/peds.107.2.381. [DOI] [PubMed] [Google Scholar]
  2. Bland J. M., Altman D. G. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986 Feb 8;1(8476):307–310. [PubMed] [Google Scholar]
  3. Crocker I. C., Zhou C. Y., Bewtra A. K., Kreutner W., Townley R. G. Glucocorticosteroids inhibit leukotriene production. Ann Allergy Asthma Immunol. 1997 May;78(5):497–505. doi: 10.1016/S1081-1206(10)63238-3. [DOI] [PubMed] [Google Scholar]
  4. Csoma Zsuzsanna, Kharitonov Sergei A., Balint Beatrix, Bush Andrew, Wilson Nicola M., Barnes Peter J. Increased leukotrienes in exhaled breath condensate in childhood asthma. Am J Respir Crit Care Med. 2002 Sep 5;166(10):1345–1349. doi: 10.1164/rccm.200203-233OC. [DOI] [PubMed] [Google Scholar]
  5. Dworski R., Fitzgerald G. A., Oates J. A., Sheller J. R. Effect of oral prednisone on airway inflammatory mediators in atopic asthma. Am J Respir Crit Care Med. 1994 Apr;149(4 Pt 1):953–959. doi: 10.1164/ajrccm.149.4.8143061. [DOI] [PubMed] [Google Scholar]
  6. Dworski R., Murray J. J., Roberts L. J., 2nd, Oates J. A., Morrow J. D., Fisher L., Sheller J. R. Allergen-induced synthesis of F(2)-isoprostanes in atopic asthmatics. Evidence for oxidant stress. Am J Respir Crit Care Med. 1999 Dec;160(6):1947–1951. doi: 10.1164/ajrccm.160.6.9903064. [DOI] [PubMed] [Google Scholar]
  7. Dworski R. Oxidant stress in asthma. Thorax. 2000 Oct;55 (Suppl 2):S51–S53. doi: 10.1136/thorax.55.suppl_2.S51. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hanazawa T., Kharitonov S. A., Barnes P. J. Increased nitrotyrosine in exhaled breath condensate of patients with asthma. Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1273–1276. doi: 10.1164/ajrccm.162.4.9912064. [DOI] [PubMed] [Google Scholar]
  9. Hood P. P., Cotter T. P., Costello J. F., Sampson A. P. Effect of intravenous corticosteroid on ex vivo leukotriene generation by blood leucocytes of normal and asthmatic patients. Thorax. 1999 Dec;54(12):1075–1082. doi: 10.1136/thx.54.12.1075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hunt J. F., Fang K., Malik R., Snyder A., Malhotra N., Platts-Mills T. A., Gaston B. Endogenous airway acidification. Implications for asthma pathophysiology. Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):694–699. doi: 10.1164/ajrccm.161.3.9911005. [DOI] [PubMed] [Google Scholar]
  11. Hunt John. Exhaled breath condensate: an evolving tool for noninvasive evaluation of lung disease. J Allergy Clin Immunol. 2002 Jul;110(1):28–34. doi: 10.1067/mai.2002.124966. [DOI] [PubMed] [Google Scholar]
  12. Jöbsis Q., Raatgeep H. C., Schellekens S. L., Kroesbergen A., Hop W. C., de Jongste J. C. Hydrogen peroxide and nitric oxide in exhaled air of children with cystic fibrosis during antibiotic treatment. Eur Respir J. 2000 Jul;16(1):95–100. doi: 10.1034/j.1399-3003.2000.16a17.x. [DOI] [PubMed] [Google Scholar]
  13. Kaneko Yasuyuki, Floras John S., Usui Kengo, Plante Julie, Tkacova Ruzena, Kubo Toshihiko, Ando Shin-ichi, Bradley T. Douglas. Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea. N Engl J Med. 2003 Mar 27;348(13):1233–1241. doi: 10.1056/NEJMoa022479. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Kostikas Konstantinos, Papatheodorou Georgios, Ganas Konstantinos, Psathakis Konstantinos, Panagou Panos, Loukides Stelios. pH in expired breath condensate of patients with inflammatory airway diseases. Am J Respir Crit Care Med. 2002 May 15;165(10):1364–1370. doi: 10.1164/rccm.200111-068OC. [DOI] [PubMed] [Google Scholar]
  16. Macfarlane A. J., Dworski R., Sheller J. R., Pavord I. D., Kay A. B., Barnes N. C. Sputum cysteinyl leukotrienes increase 24 hours after allergen inhalation in atopic asthmatics. Am J Respir Crit Care Med. 2000 May;161(5):1553–1558. doi: 10.1164/ajrccm.161.5.9906068. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Oosaki R., Mizushima Y., Kawasaki A., Kashii T., Mita H., Shida T., Akiyama K., Kobayashi M. Urinary excretion of leukotriene E4 and 11-dehydrothromboxane B2 in patients with spontaneous asthma attacks. Int Arch Allergy Immunol. 1997 Dec;114(4):373–378. doi: 10.1159/000237697. [DOI] [PubMed] [Google Scholar]
  20. Pavord I. D., Ward R., Woltmann G., Wardlaw A. J., Sheller J. R., Dworski R. Induced sputum eicosanoid concentrations in asthma. Am J Respir Crit Care Med. 1999 Dec;160(6):1905–1909. doi: 10.1164/ajrccm.160.6.9903114. [DOI] [PubMed] [Google Scholar]
  21. Shindo K., Machida M., Fukumura M., Koide K. Prednisolone inhibits synthesis of 5-H(P)ETE in eosinophils from asthmatic patients during a wheezing attack but not during remission. Prostaglandins Leukot Essent Fatty Acids. 1998 Feb;58(2):111–117. doi: 10.1016/s0952-3278(98)90149-1. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Wenzel S. E., Larsen G. L., Johnston K., Voelkel N. F., Westcott J. Y. Elevated levels of leukotriene C4 in bronchoalveolar lavage fluid from atopic asthmatics after endobronchial allergen challenge. Am Rev Respir Dis. 1990 Jul;142(1):112–119. doi: 10.1164/ajrccm/142.1.112. [DOI] [PubMed] [Google Scholar]
  24. Wood L. G., Fitzgerald D. A., Gibson P. G., Cooper D. M., Garg M. L. Lipid peroxidation as determined by plasma isoprostanes is related to disease severity in mild asthma. Lipids. 2000 Sep;35(9):967–974. doi: 10.1007/s11745-000-0607-x. [DOI] [PubMed] [Google Scholar]

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