Increased 8-isoprostane, a marker of oxidative stress, in exhaled condensate of asthma patients.

Oxidative stress has an important role in the pathogenesis of asthma. 8-Isoprostane is a prostaglandin (PG)-F2-like compound belonging to the F2 isoprostane class that is produced in vivo by the free radical-catalyzed peroxidation of arachidonic acid. 8-Isoprostane is a biomarker of oxidative stress, and its concentration is increased in the bronchoalveolar lavage fluid of patients with interstitial lung diseases. We measured 8-isoprostane concentrations in exhaled breath condensate in healthy subjects and in patients with mild (steroid naive, n = 12), moderate (inhaled steroid treatment, n = 17), and severe asthma (oral steroid treatment, n = 15). We also measured exhaled carbon monoxide (CO) and nitric oxide (NO), which may also reflect oxidative stress in the airways. 8-Isoprostane was detectable in breath condensate of normal subjects (15.8 +/- 1.6 pg/ml), and was increased in the breath condensate of patients with mild (33.7 +/- 2.8, p < 0.001), moderate (38.3 +/- 3.7 pg/ml, p < 0. 001), and severe asthma (48.9 +/- 5.0 pg/ml, p < 0.001). There was a positive correlation (r = 0.68, p < 0.05) of 8-isoprostane with NO, but not with CO, in the exhaled air of patients with mild asthma, but not in that of patients with moderate or severe asthma. There was no correlation between 8-isoprostane and lung function tests in any group of patients. Our study shows that oxidative stress is increased in asthmatic subjects as reflected by 8-isoprostane concentrations in breath condensate.

[1]  G. FitzGerald,et al.  Generation of 8-epiprostaglandin F2alpha by human monocytes. Discriminate production by reactive oxygen species and prostaglandin endoperoxide synthase-2. , 1996, The Journal of biological chemistry.

[2]  D. Yates,et al.  Endogenous nitric oxide is decreased in asthmatic patients by an inhibitor of inducible nitric oxide synthase. , 1996, American journal of respiratory and critical care medicine.

[3]  J. Morrow,et al.  Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers. Smoking as a cause of oxidative damage. , 1995, The New England journal of medicine.

[4]  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.

[5]  G. FitzGerald,et al.  Chronic obstructive pulmonary disease is associated with an increase in urinary levels of isoprostane F2alpha-III, an index of oxidant stress. , 1998, American journal of respiratory and critical care medicine.

[6]  Phillips Yy,et al.  Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, November 1986. , 1987, The American review of respiratory disease.

[7]  J. Morrow,et al.  The generation and actions of isoprostanes. , 1997, Biochimica et biophysica acta.

[8]  T. Evans,et al.  Release of isoprostanes by human pulmonary artery in organ culture: a cyclo-oxygenase and nitric oxide dependent pathway. , 1997, Biochemical and biophysical research communications.

[9]  P. Barnes,et al.  Reactive oxygen species and airway inflammation. , 1990, Free radical biology & medicine.

[10]  W. MacNee,et al.  Prognostic significance of plasma D-dimer levels in patients with lung cancer. , 1997, Thorax.

[11]  A. Choi,et al.  Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury. , 1996, American journal of respiratory cell and molecular biology.

[12]  J. Morrow,et al.  Marked overproduction of non-cyclooxygenase derived prostanoids (F2-isoprostanes) in the hepatorenal syndrome. , 1993, Journal of lipid mediators.

[13]  D. Yates,et al.  Inhaled glucocorticoids decrease nitric oxide in exhaled air of asthmatic patients. , 1996, American journal of respiratory and critical care medicine.

[14]  W. Busse,et al.  Superoxide generation by hypodense eosinophils from patients with asthma. , 1990, The American review of respiratory disease.

[15]  H. Seyberth,et al.  Generation of the isoprostane 8-epi-prostaglandin F2alpha in vitro and in vivo via the cyclooxygenases. , 1997, The Journal of pharmacology and experimental therapeutics.

[16]  P. Barnes,et al.  Increased formation of the potent oxidant peroxynitrite in the airways of asthmatic patients is associated with induction of nitric oxide synthase: effect of inhaled glucocorticoid , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[17]  H Sasaki,et al.  Increased carbon monoxide in exhaled air of asthmatic patients. , 1997, American journal of respiratory and critical care medicine.

[18]  C. Olopade,et al.  Exhaled pentane levels in acute asthma. , 1997, Chest.

[19]  B. Make,et al.  Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. American Thoracic Society. , 1995, American journal of respiratory and critical care medicine.

[20]  P. Barnes,et al.  Raised levels of exhaled carbon monoxide are associated with an increased expression of heme oxygenase-1 in airway macrophages in asthma: a new marker of oxidative stress , 1998, Thorax.

[21]  W. Busse,et al.  Enhanced production of oxygen radicals in nocturnal asthma. , 1992, The American review of respiratory disease.

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

[23]  G. FitzGerald,et al.  Cylooxygenase-dependent Formation of the Isoprostane, 8-Epi Prostaglandin F2α(*) , 1995, The Journal of Biological Chemistry.

[24]  Alfred O. Berg,et al.  Clinical Guidelines And Primary Care Guidelines For The Diagnosis And Management Of Asthma , 2012 .

[25]  K. Chung,et al.  Increased exhaled nitric oxide in asthma is mainly derived from the lower respiratory tract. , 1996, American journal of respiratory and critical care medicine.

[26]  K. Gyurkovits,et al.  Examination of the role of oxygen free radicals in bronchial asthma in childhood. , 1991, Clinica chimica acta; international journal of clinical chemistry.

[27]  P. Montuschi,et al.  8-Isoprostane as a biomarker of oxidative stress in interstitial lung diseases. , 1998, American journal of respiratory and critical care medicine.

[28]  J. Morrow,et al.  The isoprostanes. Current knowledge and directions for future research. , 1996, Biochemical pharmacology.

[29]  I. Horváth,et al.  Elevated levels of expired breath hydrogen peroxide in bronchiectasis. , 1998, American journal of respiratory and critical care medicine.

[30]  J. Morrow,et al.  Evidence of free radical-mediated injury (isoprostane overproduction) in scleroderma. , 1996, Arthritis and rheumatism.

[31]  J. Morrow,et al.  Non-cyclooxygenase-derived prostanoids (F2-isoprostanes) are formed in situ on phospholipids. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[32]  K. Hirata,et al.  The role of free radicals in airway obstruction in asthmatic patients. , 1991, Chest.

[33]  W. MacNee,et al.  Systemic oxidative stress in asthma, COPD, and smokers. , 1996, American journal of respiratory and critical care medicine.

[34]  A. Woodcock,et al.  Evidence of free-radical activity in asthma. , 1991, The New England journal of medicine.