Exhaled 8-isoprostane and prostaglandin E(2) in patients with stable and unstable cystic fibrosis.

We measured 8-isoprostane, a biomarker of oxidative stress, and prostaglandin (PG) E(2) in exhaled breath condensate in 36 stable and 14 unstable cystic fibrosis (CF) patients, and in 15 healthy age-matched controls. We studied the relationships of these eicosanoids with clinical, radiological, and systemic inflammatory parameters. Compared with controls [15.5 (11.5-17.0) pg/ml] exhaled 8-isoprostane was increased in stable CF patients [30.5 (25.3-36.0) pg/ml, P<0.001]. Unstable CF patients had higher exhaled 8-isoprostane levels [47.5 (44.0-50.0) pg/ml, P<0.001] than stable CF patients. Unlike PGE(2), exhaled 8-isoprostane was negatively correlated with FEV(1) (r=-0.67; P<0.0001; r=-0.63; P<0.02) and Shwachman score (r=-0.43, P=0.012; r=-0.58, P=0.031) and positively correlated with Chrispin-Norman score (r=0.51, P<0.002; r=0.56, P=0.039) in stable and unstable CF patients, respectively. No correlation was observed with C-reactive protein. Compared with controls [41.0 (29.0-50.0) pg/ml], exhaled PGE(2) was also elevated in stable [72.0 (64.3-81.8) pg/ml, P<0.001) and, to a greater extent, in unstable CF patients [83.0 (74.3-91.3) pg/ml, P<0.001). In patients with CF, exhaled 8-isoprostane and PGE(2) could be a useful marker of disease severity.

[1]  R. Crystal,et al.  Neutrophil elastase in respiratory epithelial lining fluid of individuals with cystic fibrosis induces interleukin-8 gene expression in a human bronchial epithelial cell line. , 1992, The Journal of clinical investigation.

[2]  J. Lötvall,et al.  8-Epi-PGF2alpha induces airflow obstruction and airway plasma exudation in vivo. , 1997, American journal of respiratory and critical care medicine.

[3]  C. Delacourt,et al.  Neutrophil-derived long-lived oxidants in cystic fibrosis sputum. , 1995, American journal of respiratory and critical care medicine.

[4]  A. Chrispin,et al.  The systematic evaluation of the chest radiograph in cystic fibrosis , 2005, Pediatric Radiology.

[5]  G. FitzGerald,et al.  Immunological characterization of urinary 8-epi-prostaglandin F2 alpha excretion in man. , 1995, The Journal of pharmacology and experimental therapeutics.

[6]  M. Konstan,et al.  Leukotriene B4 markedly elevated in the epithelial lining fluid of patients with cystic fibrosis. , 1993, The American review of respiratory disease.

[7]  J. Morrow The isoprostanes - unique products of arachidonate peroxidation: their role as mediators of oxidant stress. , 2006, Current pharmaceutical design.

[8]  H. Forman,et al.  Antioxidants in cystic fibrosis. Conclusions from the CF antioxidant workshop, Bethesda, Maryland, November 11-12, 2003. , 2007, Free radical biology & medicine.

[9]  P. Montuschi Review: Analysis of exhaled breath condensate in respiratory medicine: methodological aspects and potential clinical applications , 2007, Therapeutic advances in respiratory disease.

[10]  C. Vancheri,et al.  The lung as a privileged site for the beneficial actions of PGE2. , 2004, Trends in immunology.

[11]  P. Montuschi,et al.  Validation of 8-isoprostane and prostaglandin E2 measurements in exhaled breath condensate , 2003, Inflammation Research.

[12]  D. Spitz,et al.  Pseudomonas aeruginosa pyocyanin directly oxidizes glutathione and decreases its levels in airway epithelial cells. , 2004, American journal of physiology. Lung cellular and molecular physiology.

[13]  N. Vij,et al.  CHOP transcription factor mediates IL-8 signaling in cystic fibrosis bronchial epithelial cells. , 2008, American journal of respiratory cell and molecular biology.

[14]  B. Strandvik,et al.  Prostanoid biosynthesis in patients with cystic fibrosis. , 1996, Prostaglandins, leukotrienes, and essential fatty acids.

[15]  H. Shwachman,et al.  Long-term study of one hundred five patients with cystic fibrosis; studies made over a five- to fourteen-year period. , 1958, A.M.A. journal of diseases of children.

[16]  Massimo Corradi,et al.  Exhaled 8-isoprostane as a new non-invasive biomarker of oxidative stress in cystic fibrosis , 2000, Thorax.

[17]  F. Kelly,et al.  Evidence for Increased oxidative Damage in Patients with Cystic Fibrosis , 1994, Pediatric Research.

[18]  E. Rietschel,et al.  Oxidative changes of bronchoalveolar proteins in cystic fibrosis. , 2006, Chest.

[19]  L. Wood,et al.  Increased plasma fatty acid concentrations after respiratory exacerbations are associated with elevated oxidative stress in cystic fibrosis patients. , 2002, The American journal of clinical nutrition.

[20]  R. Stern,et al.  The diagnosis of cystic fibrosis. , 1997, The New England journal of medicine.

[21]  M S Pepe,et al.  Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group. , 1999, The New England journal of medicine.

[22]  P. Montuschi,et al.  Insights into oxidative stress: the isoprostanes. , 2007, Current medicinal chemistry.

[23]  R. Huber,et al.  Inhaled glutathione decreases PGE2 and increases lymphocytes in cystic fibrosis lungs. , 2005, Free radical biology & medicine.

[24]  J. Morrow,et al.  A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[25]  Paolo Montuschi,et al.  Analysis of exhaled breath condensate for monitoring airway inflammation. , 2002, Trends in pharmacological sciences.

[26]  Q. Jöbsis,et al.  Free radicals in exhaled breath condensate in cystic fibrosis and healthy subjects , 2006, Free radical research.

[27]  G. Downey,et al.  Enhancement of pulmonary inflammation by PGE2: evidence for a vasodilator effect. , 1988, Journal of applied physiology.

[28]  J. Morrow,et al.  Airway and vascular effects of 8-epi-prostaglandin F2 alpha in isolated perfused rat lung. , 1993, Journal of applied physiology.

[29]  P. Montuschi,et al.  Exhaled leukotrienes and prostaglandins in asthma. , 2002, The Journal of allergy and clinical immunology.

[30]  L. Wood,et al.  Oxidative Stress in Cystic Fibrosis: Dietary and Metabolic Factors , 2001, Journal of the American College of Nutrition.

[31]  N. Misso,et al.  Oxidative stress and lipid‐derived inflammatory mediators during acute exacerbations of cystic fibrosis , 2007, Respirology.

[32]  B. Raymond,et al.  Impact of CFTR ∆ F508 mutation on prostaglandin E 2 production and type IIA phospholipase A 2 expression by pulmonary epithelial cells , 2020 .

[33]  L. Wood,et al.  Elevated plasma levels of F2α isoprostane in cystic fibrosis , 1999, Lipids.

[34]  Paolo Montuschi,et al.  Indirect monitoring of lung inflammation , 2002, Nature Reviews Drug Discovery.

[35]  P. Montuschi,et al.  Isoprostanes: markers and mediators of oxidative stress , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[36]  G. Davı̀,et al.  In vivo lipid peroxidation and platelet activation in cystic fibrosis. , 2000, American journal of respiratory and critical care medicine.

[37]  K. S. Prabhu,et al.  Nuclear factor-kappaB mediates over-expression of cyclooxygenase-2 during activation of RAW 264.7 macrophages in selenium deficiency. , 2002, Free radical biology & medicine.