8-epi-prostaglandin-f2alpha and Cystic-Fibrosis

In the middle of the nineties a new, non-invasive method for investigation of the lung aroused the interest of many researchers: the exhaled breath condensate. It shows the extent of the interest that in the last five years more than 80 original articles have been published in this theme. Many substances are found in the expired breath which are detectable in the liquid that we obtain by cooling (= condensing) the exhaled breath. The advantages of this method are that it is non-invasive, convenient, it could be performed with mechanically ventilated patients as well as with children. The most studied substance is the hydrogen-peroxide, which is the marker of oxidative stress, and its level in condensate is elevated in numerous inflammatory diseases. 8-isoprostane was also studied a lot, which is another marker of oxidative stress. Numerous substances could be even measured in condensate, so the decay-product of nitric-oxide (nitrite, nitrate, nitrotyrosine), further nitrosothiol, adenosine, ammonia, different ions, leukotrienes, cytokines; recently even other feature of condensate is examined, such as its pH. The different mediators could help us to know better the diseases, support the diagnosis, follow the treatment or the disease. In this study the authors attempt to present the most important knowledge till now.

Topics: Asthma; Biomarkers; Breath Tests; Bronchiectasis; Cystic Fibrosis; Dinoprost; F2-Isoprostanes; Humans; Hydrogen Peroxide; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Respiratory Distress Syndrome; Respiratory Tract Diseases; Smoking

Despite supplementation with standard multivitamins and pancreatic enzymes, deficiencies of vitamins D and K and antioxidants are common in cystic fibrosis (CF).. In this non-randomized, open-label study, AquADEKs® softgels were given daily over 12 weeks to 14 CF subjects (mean age 15 years, range 10-23) without a preceding wash-out period. Both pancreatic sufficient and insufficient subjects were enrolled. Plasma vitamin and antioxidant levels, urine 8-isoprostane levels, anthropometric measures, and pulmonary function were determined at baseline, 6 and 12 weeks.. Daily supplementation significantly increased plasma beta(β)-carotene, coenzyme Q10, and γ-tocopherol concentrations, decreased proteins induced in vitamin K absence (PIVKA-II) levels, but did not normalize vitamin D and K status in all subjects. Vitamin A levels did not exceed the normal range for any subject during the entire study period. Modest improvements in weight percentile and pulmonary function were observed. Change in plasma β-carotene concentrations weakly correlated with changes in weight and body mass index percentiles.. In this study, AquADEKs® increased systemic antioxidant levels, while maintaining vitamin A levels in the normal range, and improved but did not completely normalize vitamin D and K status. Increased β-carotene levels were associated with improved growth parameters. These results warrant further clinical evaluation in CF.

Topics: Adolescent; Antioxidants; Biomarkers, Pharmacological; Body Mass Index; Child; Cystic Fibrosis; Dietary Supplements; Dinoprost; Exocrine Pancreatic Insufficiency; Female; Humans; Male; Oxidative Stress; Respiratory Function Tests; Treatment Outcome; Ubiquinone; Vitamin A Deficiency; Vitamin D Deficiency; Vitamin K Deficiency; Vitamins; Young Adult

The sustained imbalance between oxidant and antioxidant species contributes to lung damage in patients with cystic fibrosis (CF). Glutathione (GSH) is an important component of the antioxidant defense in the airways epithelial lining fluid and its transportation out of the cells may be altered in CF. The aim of this study was to assess the oxidants/antioxidants balance in the airways of patients with CF. We measured the concentrations of GSH, the total antioxidant capacity and the concentration of 8-iso-prostaglandin F

Topics: Adolescent; Antioxidants; Biomarkers; Breath Tests; Case-Control Studies; Cystic Fibrosis; Dinoprost; Exhalation; Female; Glutathione; Humans; Lung; Male; Oxidative Stress; Young Adult

The association between oxidative stress and neutrophilic inflammation in cystic fibrosis (CF) lung disease is well recognized. 8-Isoprostane is a product of non-enzymatic oxidation of arachidonic acid. The aim of the present study was to examine the relationship between lung function decline and 8-isoprostane concentrations in exhaled breath condensate (EBC) in CF patients with Burkholderia cenocepacia airway colonization. Concentrations of 8-isoprostane in EBC were measured in 24 stable CF patients with B. cenocepacia airway colonization. The median (interquartile range) age of the cohort was 23.9 (22.0; 26.6) years. All patients underwent clinical examinations and pulmonary function tests at the time of EBC collection and in 1-, 3-, and 5-year intervals. 8-Isoprostane concentrations in EBC correlated to 1- and 3-year declines of forced expiratory volume in 1 s (FEV1) with r(S) values of -0.511 (p = 0.0011) and -0.495 (p = 0.016), respectively. In multiple regression analysis, 8-isoprostane concentrations in EBC were the only independent predictor for 1-year FEV1 decline (p = 0.01). When the median value of 8-isoprostane concentration in EBC (10.0 pg/mL) was used as a cutoff, subgroups of patients with lower and higher level of oxidative stress had significantly different median (interquartile range) FEV1 declines in 1-year interval, -2.4% (-5.3; 0.8) and -7.3% (-10.3; -5.8) predicted (p = 0.009). In conclusion, 8-isoprostane concentrations in EBC correlated to short-term lung function decline in CF patients with B. cenocepacia airway colonization. This correlation reflects the role of oxidative stress in CF lung pathogenesis and contributes to prediction of prognosis in these patients.

Topics: Adult; Burkholderia cenocepacia; Burkholderia Infections; Cystic Fibrosis; Dinoprost; Exhalation; Female; Forced Expiratory Volume; Humans; Male; Opportunistic Infections; Oxidative Stress; Respiratory Function Tests; Time Factors; Young Adult

The aim of the study was to analyse the relationship between the intensity of the respiratory tract inflammation, expressed by oxidative stress markers, and the severity of the disease in patients with bronchiectasis unassociated with cystic fibrosis.. The study included 25 patients with stable bronchiectasis (15 females and 10 males). As determining factors of severity, the following parameters were collected: degree of dyspnoea, number of exacerbations/admissions in the last year, mean daily sputum volume, sputum colour (graduated colour scale), bacterial colonisation, respiratory function tests, quality of life (St. George questionnaire) and radiological extension of the lesions (Bhalla scale). Inflammation was analysed using the measurement of nitric oxide, pH and concentration of nitrites, nitrates and isoprostane in the exhaled air condensate. The C reactive protein and erythrocyte sedimentation rate were also determined in peripheral blood.. There were no significant relationships between the markers in the exhaled air condensate and the clinical, radiological and functional involvement or the quality of life of the patients. Only bacterial colonisation (16 cases) was associated with higher values of nitrates in exhaled air (mean+/-standard deviation: 18+/-4 compared to 7+/-2microM; r(2)=0.6) and a higher number of exacerbations (3.1+/-1.9 compared to 1.7+/-1.9; r(2)=0.3).. In our study, the measurement of inflammation markers in exhaled air is only associated with some parameters of severity in patients with bacterial bronchiectasis.

Topics: Biomarkers; Breath Tests; Bronchiectasis; C-Reactive Protein; Cystic Fibrosis; Dinoprost; Female; Humans; Inflammation; Male; Middle Aged; Nitrates; Nitric Oxide; Nitrites; Oxidative Stress; Severity of Illness Index

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.

Topics: Breath Tests; C-Reactive Protein; Child; Cross-Sectional Studies; Cystic Fibrosis; Dinoprost; Dinoprostone; Female; Humans; Leukocyte Count; Male; Respiratory Function Tests

Chronic airway inflammation is present in cystic fibrosis (CF). Non-invasive inflammometry may be useful in disease management. The aim of the present cross-sectional study was to investigate: (i) the ability of fractional exhaled nitric oxide and inflammatory markers (IM) [exhaled breath condensate (EBC) acidity, nitrite, nitrate, hydrogen peroxide (H(2)O(2)), 8-isoprostane, Th1/Th2 cytokines] to indicate (exacerbations of) CF; and (ii) the ability of these non-invasive IM to indicate CF disease severity. In 98 children (48 CF/50 controls), exhaled nitric oxide was measured using the NIOX, and condensate was collected using a glass condenser. In CF interferon (IFN-gamma) and nitrite concentrations were significantly higher, whereas exhaled nitric oxide levels were significantly lower compared with controls (3.3 +/- 0.3 pg/ml, 2.2 +/- 0.2 microM, 10.0 +/- 1.2 p.p.b. vs. 2.6 +/- 0.2 pg/ml, 1.4 +/- 0.1 microM, 15.4 +/- 1.4 p.p.b. respectively). Using multivariate logistic regression models, the presence of CF was best indicated by 8-isoprostane, nitrite and IFN-gamma [sensitivity 78%, specificity 83%; area under receiver operating characteristic curve (AUC) 0.906, p < 0.001]. An exacerbation of CF was best indicated by 8-isoprostane and nitrite (sensitivity 40%, specificity 97%, AUC curve 0.838, p = 0.009). Most indicative biomarkers of CF severity were exhaled nitric oxide, and condensate acidity (sensitivity 96%, specificity 67%; AUC curve 0.751, p = 0.008). In this cross-sectional study, the combination of different exhaled IM could indicate (exacerbations of) CF, and severity of the disease in children. Longitudinal data are necessary to further confirm the role of these markers for the management of CF in children.

Topics: Adolescent; Biomarkers; Breath Tests; Child; Cross-Sectional Studies; Cystic Fibrosis; Cytokines; Dinoprost; Exhalation; Female; Humans; Hydrogen Peroxide; Logistic Models; Male; Nitrates; Nitric Oxide; Nitrites; Severity of Illness Index

In cystic fibrosis (CF) very few studies have assessed sputum 8-iso-PGF2alpha levels during pulmonary exacerbations as a direct measure of airway oxidative stress. The role of other lipid-derived inflammatory mediators, such as the cysteinyl leukotrienes (cys-LTs) and prostaglandin (PG)-E2, during exacerbations is also poorly defined and the effect of conventional antibiotic therapy on these components of the inflammatory process is unclear.. Sputum 8-iso-PGF2alpha, total cys-LT and PGE2 levels were measured in 17 CF patients experiencing a pulmonary exacerbation and repeated analysis were performed in 15 of these patients after antibiotic treatment. Eight stable CF and nine healthy subjects provided control data.. Sputum 8-iso-PGF2alpha was significantly elevated in acute, but not stable CF patients versus healthy controls (P < 0.001). Similarly, sputum cys-LT and PGE2 levels were increased in acute compared with stable CF patients and healthy controls (P

Topics: Adolescent; Adult; Anti-Bacterial Agents; Biomarkers; Cysteine; Cystic Fibrosis; Dinoprost; Disease Progression; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Immunoenzyme Techniques; Leukotrienes; Male; Oxidative Stress; Prognosis; Sputum

To examine oxidative stress in CF by measuring 8-iso-PGF2alpha and antioxidant defenses, in relation to dietary intake, immune function and clinical status.. We measured total plasma concentrations of 8-iso-PGF2alpha and dietary antioxidants (vitamin E, vitamin C, beta-carotene), erythrocyte antioxidant enzyme activities (glutathione peroxidase and superoxide dismutase), lung function and dietary intake in 21 CF subjects and 21 healthy age- and gender-matched controls.. Total plasma 8-iso-PGF2alpha concentration (median [quartile 1-quartile 3]) was significantly higher in CF subjects compared to controls (214 pg/mL (155-331) vs. 135 pg/mL (101-168), p = 0.001). Neutrophil, monocyte and total white cell counts were elevated in the CF group and these correlated with 8-iso-PGF2alpha concentration. Despite similar dietary intake, lower plasma antioxidant concentrations were observed in the CF group (vitamin E, p < 0.001, vitamin C, p = 0.004, beta-carotene, p = 0.001). 8-iso-PGF2alpha correlated negatively with plasma vitamin E, C and beta-carotene concentrations.. Oxidative stress is increased in CF patients, despite normal dietary antioxidant intake. The immune response appears to be a key factor causing oxidative stress. Antioxidant intervention aimed at reducing oxidative stress in CF needs to be assessed.

Topics: Adolescent; Antioxidants; Case-Control Studies; Cystic Fibrosis; Dinoprost; Erythrocytes; F2-Isoprostanes; Female; Glutathione Peroxidase; Humans; Leukocytes; Male; Oxidative Stress; Respiratory Function Tests; Superoxide Dismutase; Vitamins

Cystic fibrosis is characterised by oxidative stress in the airways. Isoprostanes are prostaglandin isomers formed by free radical catalysed peroxidation of arachidonic acid. 8-Isoprostane is increased in interstitial lung diseases, asthma, chronic obstructive pulmonary disease, and adult respiratory distress syndrome. Exhaled nitric oxide (NO) and carbon monoxide (CO) are biomarkers of inflammation and oxidative stress in the airways, respectively.. Concentrations of 8-isoprostane in the breath condensate of 10 normal subjects and 19 patients with stable cystic fibrosis were measured using an enzyme immunoassay (EIA). Breath condensate is a non-invasive method of collecting airway secretions. Exhaled nitric oxide (NO) and carbon monoxide (CO) levels were measured by a chemiluminescence analyser.. Concentrations of 8-isoprostane in the breath condensate of patients with stable cystic fibrosis were increased about threefold compared with normal subjects (42.7 (4.5) pg/ml vs 15.2 (1.7) pg/ml; p<0.005, 95% CI 14.6 to 40.9). 8-Isoprostane concentrations were negatively correlated with forced expiratory volume in one second in patients with cystic fibrosis (r = -0.61; p<0.005). Exhaled CO was also increased in patients with cystic fibrosis compared with normal subjects (6.7 (1.2) ppm vs 2.9 (0.3) ppm; p<0.05, 95% CI 0.2 to 7.4). 8-Isoprostane concentrations were significantly correlated with CO levels (r = 0.66; p<0.002).. The results of this study show that oxidative stress is increased in cystic fibrosis and may be quantified by measuring 8-isoprostane concentrations in breath condensate.

Topics: Adult; Biomarkers; Breath Tests; Carbon Monoxide; Cystic Fibrosis; Dinoprost; F2-Isoprostanes; Forced Expiratory Volume; Humans; Male; Nitric Oxide; Oxidative Stress; Vital Capacity

F(2)-isoprostanes are bioactive peroxidation products of arachidonic acid whose urinary excretion provides an index of lipid peroxidation in vivo. We tested the hypothesis that formation of F(2)-isoprostanes is altered in patients with cystic fibrosis and contributes to platelet activation and pulmonary dysfunction in this setting. The urinary excretion of immunoreactive 8-iso-prostaglandin F(2alpha) (PGF(2alpha)) was significantly (p = 0.0001) higher in 36 patients with cystic fibrosis than in 36 age-matched healthy subjects: 618 +/- 406 versus 168 +/- 48 pg/mg creatinine. The urinary excretion of immunoreactive 11-dehydro-thromboxane B(2) (TXB(2)), an index of in vivo platelet activation, was also significantly (p = 0.0001) higher in patients than in control subjects: 2,440 +/- 1,453 versus 325 +/- 184 pg/mg creatinine. The excretion rate of 8-iso-PGF(2alpha) was correlated with that of 11-dehydro-TXB(2) (rho = 0.51; p = 0.0026) and inversely related to FEV(1) (rho = -0.40; p = 0.0195). Urinary 8-iso-PGF(2alpha) excretion was largely unaffected during cyclooxygenase inhibition with low-dose aspirin, nimesulide, or ibuprofen, consistent with a noncyclooxygenase mechanism of F(2)-isoprostane formation in cystic fibrosis. Increased vitamin E supplementation (from 200 to 600 mg/d) was associated with statistically significant (p = 0.005) reductions in urinary 8-iso-PGF(2alpha) and 11-dehydro-TXB(2) excretion, by 42% and 29%, respectively. We conclude that enhanced lipid peroxidation is an important feature of cystic fibrosis and may contribute to persistent platelet activation and pulmonary dysfunction via generation of bioactive isoeicosanoids. Our results provide a rationale for reassessing the adequacy of vitamin E supplementation in this setting.

Topics: Adolescent; Adult; Child; Cyclooxygenase Inhibitors; Cystic Fibrosis; Dinoprost; F2-Isoprostanes; Female; Genotype; Humans; Ibuprofen; Lipid Peroxidation; Lung; Male; Platelet Activation; Sulfonamides; Thromboxane B2; Vitamin E

Cystic fibrosis (CF) is associated with chronic lung infection, inflammation, and elevated indices of oxidative stress. Recently, isoprostanes were shown to be a reliable in vivo marker of oxidant injury with 8-iso-PGF2 alpha, shown to cause airflow obstruction and plasma exudation in guinea pig lung. The present study was designed to examine the relationship between 8-iso-PGF2 alpha levels, plasma antioxidants, and clinical status in CF. We hypothesized that plasma 8-iso-PGF2 alpha levels would be higher in subjects with CF compared to healthy controls. Plasma 8-iso-PGF2 alpha levels were prospectively measured in 22 subjects with CF and nine healthy controls using an 8-isoprostane enzyme immunoassay kit along with plasma vitamins A, E, and beta-carotene. Plasma 8-iso-PGF2 alpha levels were shown to be significantly elevated in the CF subjects compared to controls (319.6 +/- 52.6 vs. 145.0 +/- 21.0 pg/mL, P = 0.005). Plasma levels of antioxidants were significantly lower for the CF subjects compared to the controls (vitamin A, P < 0.003; vitamin E, P < 0.001; and beta-carotene, P < 0.01). This study confirms significantly elevated lipid peroxidation in CF using 8-iso-PGF2 alpha levels.

Topics: Adolescent; Adult; Aged; beta Carotene; Case-Control Studies; Child; Cross-Sectional Studies; Cystic Fibrosis; Dinoprost; Erythrocyte Membrane; F2-Isoprostanes; Fatty Acids; Humans; Middle Aged; Vitamin A; Vitamin E