Exhaled Breath Condensate Eicosanoid Levels Associate with Asthma and Its Severity

Overview

Journal J Allergy Clin Immunol

Specialty Allergy & Immunology

Date 2013 Apr 24

PMID 23608729

Citations 41

Authors

Shamsah Kazani

Anna Planaguma

Emiko Ono

Matteo Bonini

Muhammad Zahid

Gautham Marigowda

Michael E Wechsler

Bruce D Levy

Elliot Israel

Affiliations

Soon will be listed here.

Abstract

Background: The relationship between anti-inflammatory lipoxins and proinflammatory leukotrienes might be important in the pathobiology and severity of asthma.

Objective: We sought to investigate whether exhaled breath condensate (EBC) lipoxin and leukotriene measurements can noninvasively characterize the asthmatic diathesis and its severity.

Methods: We measured lipoxin A4 (LXA4) and leukotriene B4 (LTB4) levels in EBC collected from patients with asthma of different severities and from healthy control subjects.

Results: EBC LXA4 and LTB4 levels are increased in asthmatic patients compared with those seen in healthy control subjects (LXA4: 31.40 vs 2.41 pg/mL EBC, respectively [P < .001]; LTB4: 45.62 vs 3.82 pg/mL EBC, respectively [P < .001]). Although levels of both eicosanoids are increased in asthmatic patients, the LXA4/LTB4 ratio decreases with increasing asthma severity. It is 41% lower in patients with severe versus moderate asthma (0.52 vs 0.88, P = .034). EBC LXA4 levels correlate with the degree of airflow obstruction measured by using FEV1 (r = 0.28, P = .018). An LXA4 cutoff value of 7 pg/mL EBC provides 90% sensitivity and 92% specificity for the diagnosis of asthma (area under the curve, 0.96; P < .001). An LTB4 cutoff value of 11 pg/mL EBC provides 100% sensitivity and 100% specificity for the diagnosis of asthma (area under the curve, 1; P < .001).

Conclusions: Proresolving and proinflammatory eicosanoids are generated in the airways of all asthmatic patients. The proportion of proresolving compounds decreases with asthma severity. These findings support the role for EBC eicosanoid measurements in the noninvasive diagnosis of asthma and suggest that proresolving eicosanoid pathways are dysregulated in patients with severe asthma.

Citing Articles

The Role of Exhaled Breath Condensate in Chronic Inflammatory and Neoplastic Diseases of the Respiratory Tract.

Kita K, Gawinowska M, Chelminska M, Niedoszytko M Int J Mol Sci. 2024; 25(13).

PMID: 39000502 PMC: 11242091. DOI: 10.3390/ijms25137395.

Bronchial Asthma, Airway Remodeling and Lung Fibrosis as Successive Steps of One Process.

Savin I, Zenkova M, Senkova A Int J Mol Sci. 2023; 24(22).

PMID: 38003234 PMC: 10671561. DOI: 10.3390/ijms242216042.

Endogenous inhibitory mechanisms in asthma.

Chiarella S, Barnes P J Allergy Clin Immunol Glob. 2023; 2(4):100135.

PMID: 37781649 PMC: 10509980. DOI: 10.1016/j.jacig.2023.100135.

Editorial: Particles and Health 2021: An international conference addressing issues in science and regulation.

McCunney R, Borm P, Driscoll K, Krueger N, Levy L Front Public Health. 2022; 10:1062221.

PMID: 36582379 PMC: 9793851. DOI: 10.3389/fpubh.2022.1062221.

Immune Metabolism in TH2 Responses: New Opportunities to Improve Allergy Treatment - Disease-Specific Findings (Part 1).

Goretzki A, Zimmermann J, Rainer H, Lin Y, Schulke S Curr Allergy Asthma Rep. 2022; 23(1):29-40.

PMID: 36441389 PMC: 9832111. DOI: 10.1007/s11882-022-01057-8.

References

Gronert K, Ravasi S, Chiang N, Serhan C . Selectivity of recombinant human leukotriene D(4), leukotriene B(4), and lipoxin A(4) receptors with aspirin-triggered 15-epi-LXA(4) and regulation of vascular and inflammatory responses. Am J Pathol. 2001; 158(1):3-9. PMC: 1850279. DOI: 10.1016/S0002-9440(10)63937-5. View

Kowal-Bielecka O, Kowal K, Distler O, Rojewska J, Bodzenta-Lukaszyk A, Michel B . Cyclooxygenase- and lipoxygenase-derived eicosanoids in bronchoalveolar lavage fluid from patients with scleroderma lung disease: an imbalance between proinflammatory and antiinflammatory lipid mediators. Arthritis Rheum. 2005; 52(12):3783-91. DOI: 10.1002/art.21432. View

Levy B, Kohli P, Gotlinger K, Haworth O, Hong S, Kazani S . Protectin D1 is generated in asthma and dampens airway inflammation and hyperresponsiveness. J Immunol. 2006; 178(1):496-502. PMC: 3005704. DOI: 10.4049/jimmunol.178.1.496. View

Szefler S, Wenzel S, Brown R, Erzurum S, Fahy J, Hamilton R . Asthma outcomes: biomarkers. J Allergy Clin Immunol. 2012; 129(3 Suppl):S9-23. PMC: 3390196. DOI: 10.1016/j.jaci.2011.12.979. View

Bozinovski S, Uddin M, Vlahos R, Thompson M, McQualter J, Merritt A . Serum amyloid A opposes lipoxin A₄ to mediate glucocorticoid refractory lung inflammation in chronic obstructive pulmonary disease. Proc Natl Acad Sci U S A. 2012; 109(3):935-40. PMC: 3271884. DOI: 10.1073/pnas.1109382109. View

Bonnans C, Vachier I, Chavis C, Godard P, Bousquet J, Chanez P . Lipoxins are potential endogenous antiinflammatory mediators in asthma. Am J Respir Crit Care Med. 2002; 165(11):1531-5. DOI: 10.1164/rccm.200201-053OC. View

Kazani S, Israel E . Exhaled breath condensates in asthma: diagnostic and therapeutic implications. J Breath Res. 2011; 4(4):047001. DOI: 10.1088/1752-7155/4/4/047001. View

Yang J, Eiserich J, Cross C, Morrissey B, Hammock B . Metabolomic profiling of regulatory lipid mediators in sputum from adult cystic fibrosis patients. Free Radic Biol Med. 2012; 53(1):160-71. PMC: 3412514. DOI: 10.1016/j.freeradbiomed.2012.05.001. View

Christie P, Spur B, Lee T . The effects of lipoxin A4 on airway responses in asthmatic subjects. Am Rev Respir Dis. 1992; 145(6):1281-4. DOI: 10.1164/ajrccm/145.6.1281. View

10.

Borish L . The role of leukotrienes in upper and lower airway inflammation and the implications for treatment. Ann Allergy Asthma Immunol. 2002; 88(4 Suppl 1):16-22. DOI: 10.1016/s1081-1206(10)62024-8. View

11.

Drazen J, Israel E, OByrne P . Treatment of asthma with drugs modifying the leukotriene pathway. N Engl J Med. 1999; 340(3):197-206. DOI: 10.1056/NEJM199901213400306. View

12.

Csoma Z, Kharitonov S, Balint B, Bush A, Wilson N, Barnes P . Increased leukotrienes in exhaled breath condensate in childhood asthma. Am J Respir Crit Care Med. 2002; 166(10):1345-9. DOI: 10.1164/rccm.200203-233OC. View

13.

Bandeira-Melo C, Diaz B, Cordeiro R, Jose P, Serhan C, Martins M . Inhibition of allergen-induced eosinophil migration by lipoxin (LX)A4 and aspirin-triggered 15-epi-LXA4. Adv Exp Med Biol. 2003; 507:211-6. DOI: 10.1007/978-1-4615-0193-0_32. View

14.

Levy B, Bonnans C, Silverman E, Palmer L, Marigowda G, Israel E . Diminished lipoxin biosynthesis in severe asthma. Am J Respir Crit Care Med. 2005; 172(7):824-30. PMC: 2718403. DOI: 10.1164/rccm.200410-1413OC. View

15.

Mondino C, Ciabattoni G, Koch P, Pistelli R, Trove A, Barnes P . Effects of inhaled corticosteroids on exhaled leukotrienes and prostanoids in asthmatic children. J Allergy Clin Immunol. 2004; 114(4):761-7. DOI: 10.1016/j.jaci.2004.06.054. View

16.

Badr K, DeBoer D, Schwartzberg M, Serhan C . Lipoxin A4 antagonizes cellular and in vivo actions of leukotriene D4 in rat glomerular mesangial cells: evidence for competition at a common receptor. Proc Natl Acad Sci U S A. 1989; 86(9):3438-42. PMC: 287148. DOI: 10.1073/pnas.86.9.3438. View

17.

Moore W, Bleecker E, Curran-Everett D, Erzurum S, Ameredes B, Bacharier L . Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program. J Allergy Clin Immunol. 2007; 119(2):405-13. PMC: 2837934. DOI: 10.1016/j.jaci.2006.11.639. View

18.

Levy B, De Sanctis G, Devchand P, Kim E, Ackerman K, Schmidt B . Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A(4). Nat Med. 2002; 8(9):1018-23. DOI: 10.1038/nm748. View

19.

Claesson H, Odlander B, Jakobsson P . Leukotriene B4 in the immune system. Int J Immunopharmacol. 1992; 14(3):441-9. DOI: 10.1016/0192-0561(92)90174-j. View

20.

Serhan C . Lipoxins and aspirin-triggered 15-epi-lipoxin biosynthesis: an update and role in anti-inflammation and pro-resolution. Prostaglandins Other Lipid Mediat. 2002; 68-69:433-55. DOI: 10.1016/s0090-6980(02)00047-3. View