Abstract
Background: Leukotriene-like immunoreactivity has been detected in exhaled breath condensate (EBC), but definitive evidence for the presence of leukotrienes (LTs) in this biological fluid is not available. A study was undertaken to determine whether LTC4, LTD4, LTE4, and LTB4 are measurable in EBC by gas chromatography/mass spectrometry and to quantify exhaled LTs in adults and children with asthma and in control subjects.
Methods: Twenty eight adults and 33 children with mild to moderate persistent asthma treated with inhaled corticosteroids and age matched healthy controls (50 adults and 50 children) were studied. LTB4, LTC4, LTD4, and LTE4 in EBC were measured by gas chromatography/mass spectrometry.
Results: LTD4, LTE4, and LTB4 were detectable in all samples. Concentrations of LTC4 in EBC were either close to or below the detection limit of 1 pg/ml. Median exhaled LTD4, LTE4, and LTB4 concentrations in asthmatic adults were increased 4.1-fold (p<0.001), 1.8-fold (p<0.01), and 2.6-fold (p<0.001), respectively, compared with values in healthy adults. Median exhaled LTD4, LTE4, and LTB4 concentrations in asthmatic children were increased 2.8-fold (p<0.001), 1.3-fold (p<0.001), and 1.6-fold (p<0.001), respectively, compared with those in healthy children. In patients with asthma there was a correlation between exhaled LTD4 and LTE4 in both adults (r = 0.87, p<0.0001) and children (r = 0.78, p<0.0001).
Conclusions: Gas chromatography/mass spectrometry can be used to accurately quantify exhaled LTs which are increased in asthmatic adults and children compared with controls.
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Selected References
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- Antczak Adam, Montuschi Paolo, Kharitonov Sergei, Gorski Pawel, Barnes Peter J. Increased exhaled cysteinyl-leukotrienes and 8-isoprostane in aspirin-induced asthma. Am J Respir Crit Care Med. 2002 Aug 1;166(3):301–306. doi: 10.1164/rccm.2101021. [DOI] [PubMed] [Google Scholar]
- 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]
- Barnes P. J., Chung K. F., Page C. P. Inflammatory mediators of asthma: an update. Pharmacol Rev. 1998 Dec;50(4):515–596. [PubMed] [Google Scholar]
- Busse WW. Leukotrienes and inflammation . Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):S210–S213. [PubMed] [Google Scholar]
- Chavis C., van Vyve T., Chanez P., Farce M., Bousquet J., Michel F. B., Godard P. Leukotriene E4 plasma levels in adult asthmatic patients with variable disease severity. Allergy. 1997 May;52(5):589–592. doi: 10.1111/j.1398-9995.1997.tb02606.x. [DOI] [PubMed] [Google Scholar]
- 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]
- Drazen J. M., Israel E., O'Byrne P. M. Treatment of asthma with drugs modifying the leukotriene pathway. N Engl J Med. 1999 Jan 21;340(3):197–206. doi: 10.1056/NEJM199901213400306. [DOI] [PubMed] [Google Scholar]
- Effros Richard M., Biller Julie, Foss Bradley, Hoagland Kelly, Dunning Marshall B., Castillo Daniel, Bosbous Mark, Sun Feng, Shaker Reza. A simple method for estimating respiratory solute dilution in exhaled breath condensates. Am J Respir Crit Care Med. 2003 Sep 25;168(12):1500–1505. doi: 10.1164/rccm.200307-920OC. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Husek P. Amino acid derivatization and analysis in five minutes. FEBS Lett. 1991 Mar 25;280(2):354–356. doi: 10.1016/0014-5793(91)80330-6. [DOI] [PubMed] [Google Scholar]
- Husek P. Chloroformates in gas chromatography as general purpose derivatizing agents. J Chromatogr B Biomed Sci Appl. 1998 Oct 9;717(1-2):57–91. [PubMed] [Google Scholar]
- Husek P. Long-chain fatty acids esterified by action of alkyl chloroformates and analysed by capillary gas chromatography. J Chromatogr. 1993 Jun 2;615(2):334–338. [PubMed] [Google Scholar]
- Kumlin M. Measurement of leukotrienes in humans. Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 2):S102–S106. doi: 10.1164/ajrccm.161.supplement_1.ltta-20. [DOI] [PubMed] [Google Scholar]
- Leff A. R. Role of leukotrienes in bronchial hyperresponsiveness and cellular responses in airways. Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 2):S125–S132. doi: 10.1164/ajrccm.161.supplement_1.ltta-25. [DOI] [PubMed] [Google Scholar]
- 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]
- Montuschi P., Kharitonov S. A., Ciabattoni G., Barnes P. J. Exhaled leukotrienes and prostaglandins in COPD. Thorax. 2003 Jul;58(7):585–588. doi: 10.1136/thorax.58.7.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Montuschi Paolo, Barnes Peter J. Analysis of exhaled breath condensate for monitoring airway inflammation. Trends Pharmacol Sci. 2002 May;23(5):232–237. doi: 10.1016/s0165-6147(02)02020-5. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- 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]
- Wenzel S. E., Trudeau J. B., Kaminsky D. A., Cohn J., Martin R. J., Westcott J. Y. Effect of 5-lipoxygenase inhibition on bronchoconstriction and airway inflammation in nocturnal asthma. Am J Respir Crit Care Med. 1995 Sep;152(3):897–905. doi: 10.1164/ajrccm.152.3.7663802. [DOI] [PubMed] [Google Scholar]
