8-epi-prostaglandin-f2alpha and Bronchiectasis

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

Background: systemic inflammation and oxidative stress are important factors in the pathogenesis of bronchiectasis. Pulmonary rehabilitation (PR) is recommended for bronchiectasis, but there is no data about its effect on the inflammatory and REDOX status of these patients. Aims: to investigate the effect of PR in non-cystic-fibrosis bronchiectasis (NCFB) patients, and to compare it with the effect of PR plus a hyperproteic oral nutritional supplement (PRS) enriched with beta-hydroxy-beta-methylbutyrate (HMB) on serum inflammatory and oxidative biomarkers. Materials and methods: this was an open randomized, controlled trial. Thirty individuals (65 years old or younger with a body mass index over 18.5, older than 65 years with a body mass index over 20) were recruited from September 2013 to September 2014, and randomly assigned to receive PR or PRS. Total neutrophils, and inflammatory and oxidative biomarker levels were measured at baseline, and then at 3 and 6 months. Results: in the PRS group neutrophil levels were decreased from baseline at 6 months. A significantly different fold change was found between the PR and PRS groups. In the PR group, IL-6 and adiponectin were increased by the end of the study while TNFα levels were decreased from baseline at 6 months. REDOX biomarkers remained stable throughout the study except for 8-isoprostane levels, which were increased from baseline at 6 months in both groups of patients. Conclusions: a PR program induced a pro-oxidative effect accompanied by changes in circulating inflammatory cytokine levels in NCFB patients. Our results would also suggest a possible beneficial effect of the HMB enriched supplement on neutrophil level regulation in these patients. The information provided in this study could be useful for choosing the right therapeutic approach in the management of bronchiectasis.. Introducción: la inflamación sistémica y el estrés oxidativo son factores importantes en la patogénesis de la bronquiectasia. La rehabilitación pulmonar (PR) está recomendada en los sujetos con bronquiectasias, pero no hay datos sobre sus posibles efectos sobre el estado inflamatorio y REDOX de estos pacientes. Objetivos: investigar el efecto de la PR en pacientes con bronquiectasias no asociadas a fibrosis quística (NCFB) sobre los biomarcadores oxidativos e inflamatorios, y compararlo con los efectos de la PR junto con la suplementación oral de un suplemento hiperproteico (PRS) enriquecido con beta-hidroxi-beta-metilbutirato (HMB). Material y métodos: ensayo clínico abierto, aleatorizado y controlado. Treinta pacientes (de 65 años o menos con un índice de masa corporal por encima de 18,5, y mayores de 65 años con un índice de masa corporal de más de 20) se aleatorizaron para recibir PR o PRS. Los niveles circulantes de neutrófilos totales y los de biomarcadores de estado inflamatorio y oxidativo se determinaron al inicio del estudio y a los 3 y 6 meses. Resultados: los niveles de neutrófilos en el grupo de PRS se redujeron desde el inicio a los 6 meses, presentando una tasa de cambio significativamente diferente según el tratamiento. En el grupo de PR, la IL-6 y la adiponectina aumentaron al final del estudio, mientras que los niveles de TNFα disminuyeron desde el inicio a los 6 meses. Los biomarcadores de estrés oxidativo se mantuvieron estables durante todo el estudio excepto por los niveles de 8-isoprostano, que aumentaron desde el inicio a los 6 meses en ambos grupos de pacientes. Conclusión: el programa de PR indujo un efecto pro-oxidativo acompañado de cambios en los niveles de citoquinas inflamatorias circulantes en pacientes con NCFB. Nuestros resultados también sugieren un posible efecto beneficioso del suplemento nutricional sobre la regulación de los niveles de neutrófilos de estos pacientes.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Bronchiectasis; C-Reactive Protein; Combined Modality Therapy; Diet, Mediterranean; Dietary Proteins; Dietary Supplements; Dinoprost; Female; Humans; Inflammation; Interleukin-6; Leukocyte Count; Male; Middle Aged; Neutrophils; Nutritional Support; Oxidation-Reduction; Oxidative Stress; Prospective Studies; Respiratory Therapy; Tumor Necrosis Factor-alpha; Valerates; Young Adult

To explore the effect of long-term therapy with azithromycin in regards to airway oxidative stress markers in exhaled breath condensate (EBC) of adult patients with stable non-cystic fibrosis (CF) bronchiectasis.. Open-label prospective study of 30 patients randomized to azithromycin 250 mg three times per week during 3 months (16 patients) or control (14 patients). Primary outcome were changes in nitric oxide, 8-isoprostane, pH, nitrites and nitrates in EBC. Secondary outcomes were changes in exacerbation rates, dyspnoea (Borg scale), sputum volume (cc), sputum colour (15-point scale), bacterial infection, health-related quality of life (St George's Respiratory Questionnaire), lung function and radiological extension.. Azithromycin produced a significant decrease in sputum volume (8.9 (1.8) mL vs 2.1 (3.4) mL) and number of exacerbations (0.1 (0.6) vs 1.2 (0.9)). Dyspnoea (0.4 (0.1) vs 0.1 (0.2)) and health-related quality of life also improved after therapy. However, oxidative stress markers in EBC, systemic inflammatory markers as well as functional respiratory tests did not differ from the control group after therapy. A post-hoc analysis comparing patients infected or not with Pseudomonas aeruginosa revealed that these effects were more pronounced in infected patients. In this subgroup, treatment was followed by a significant reduction in sputum volume, number of exacerbations, dyspnoea and St George's Respiratory Questionnaire total score. Of all airway oxidative stress markers, only nitrates in EBC were reduced after therapy.. Long-term azythromicin treatment has some clinical benefits in patients with non-CF stable bronchiectasis, but it does not affect airway oxidative stress markers.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Biomarkers; Bronchiectasis; Dinoprost; Female; Follow-Up Studies; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Nitrates; Nitric Oxide; Nitrites; Oxidative Stress; Prospective Studies; Treatment Outcome

Induced sputum 8-iso-prostaglandin F(2alpha) (PGF(2alpha)) concentrations may be a useful marker of oxidative stress in airways disease. This study examines oxidative stress (measured by 8-iso-PGF(2alpha)) in airway disease according to disease type (asthma and bronchiectasis), disease activity (stable and acute asthma), and disease pattern (intermittent, mild, moderate, and severe persistent asthma). We compared subjects with stable asthma (n = 71) and bronchiectasis (n = 23) with healthy control subjects (n = 29). Another group of patients with asthma (n = 39) were assessed during and after acute exacerbation. Induced sputum 8-iso-PGF(2alpha) concentrations were validated and found to be elevated in subjects with stable asthma and bronchiectasis versus control subjects (median [interquartile range] 216 [103-389] and 698 [264-1,613] ng/L vs. 123 [41-290] ng/L, p < 0.001) and increased as clinical asthma pattern worsened (intermittent 115 [42-153], mild persistent 116 [89-229] ng/L, moderate persistent 183 [110-317] ng/L, severe persistent 387 [102-587] ng/L; p = 0.010). Sputum 8-iso-PGF(2alpha) concentrations were elevated during acute asthma and decreased with recovery (458 [227-950] ng/L vs. 214 [148-304] ng/L, p = 0.0002). We conclude that 8-iso-PGF(2alpha) is involved in the pathophysiology of inflammatory airway diseases, being related to disease type, pattern, and activity. Analysis of 8-iso-PGF(2alpha) concentrations in induced sputum provides a useful tool for monitoring oxidative stress and investigating strategies aimed at reducing oxidative stress in airways disease.

Topics: Adult; Age Factors; Asthma; Biomarkers; Bronchiectasis; Dinoprost; Eosinophils; Female; Humans; Leukocyte Count; Male; Middle Aged; Multivariate Analysis; Neutrophils; Oxidative Stress; Pneumonia; Respiratory Function Tests; Sex Factors; Sputum

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