allopurinol and Pulmonary-Disease--Chronic-Obstructive

Oxidative stress (OS) has been implicated in the development of pulmonary hypertension (PH) and ventricular hypertrophy. Xanthine oxidase is a well-recognised source of reactive oxygen species, which lead to OS. The aim of this proof of concept study was to assess whether allopurinol (xanthine oxidase inhibitor) would reduce right ventricular mass (RVM) in patients with PH-associated chronic lung disease (PH-CLD).. We conducted a randomised, double-blind, parallel-group, placebo-controlled trial in patients with PH-CLD (93% COPD, 7% IPF) who were randomly assigned to receive allopurinol or placebo for 12 months. The primary outcome was the mean change in RVM, as assessed by cardiac magnetic resonance imaging (CMRI). Secondary outcomes included quality of life (QOL), spirometry and six-minute walk test (6MWT).. Seventy-one patients were recruited: mean age 71 years, mean pulmonary arterial pressure 30 mm Hg, FEV. Allopurinol had no overall impact on patients with PH-CLD but had potential benefit in COPD patients with more severe airflow limitation.

Topics: Aged; Allopurinol; Double-Blind Method; Humans; Hypertension, Pulmonary; Pulmonary Disease, Chronic Obstructive; Quality of Life; Walk Test

The aim of this study was to determine the implication of xanthine oxidase (XO) in the exercise-induced muscle oxidative stress and muscle dysfunction of these patients.. A randomized, crossover and double-blind study was conducted in nine severe COPD patients, who performed a localized quadriceps endurance test after oral treatment with allopurinol, a XO inhibitor or placebo. Redox status was studied in arterial and venous femoral blood before and after the endurance test.. In placebo condition, muscle exercise resulted in a significant increase in AOPP and isoprostanes, with a significant increase in the venoarterial difference (v-a) in isoprostanes after exercise as compared with before (p<0.05). In contrast, allopurinol treatment prevented the elevation in AOPP levels and v-a isoprostanes after exercise. However, no significant improvement in quadriceps muscle endurance was observed, but allopurinol treatment seemed to preserve muscle strength properties.. This study demonstrates that XO is implicated in the exercise-induced muscle oxidative stress of COPD patients. Allopurinol administration seemed to improve only some muscle properties. Therefore other sources of muscle oxidative stress should be implicated in muscle dysfunction observed in these patients.

Topics: Administration, Oral; Aged; Allopurinol; Cross-Over Studies; Double-Blind Method; Enzyme Inhibitors; Female; Humans; Male; Middle Aged; Muscles; Oxidative Stress; Placebos; Pulmonary Disease, Chronic Obstructive; Quadriceps Muscle; Xanthine Oxidase

In Japan, patients with chronic airway disease are administered bakumondo-to (TJ-29), a mixture of six herbal components. We have assessed the effects of TJ-29 on the activities of cytochrome P450 (CYP) 1A2, xanthine oxidase and N-acetyltransferase 2 in 26 healthy subjects under a double-blind, randomized, placebo-controlled cross-over study design. The baseline activities of the three enzymes were assessed by the respective urinary metabolic ratios of an 8-h urine sample after an oral 150-mg dose of caffeine. Thereafter, the subjects received a thrice-daily 3.0-g dose of TJ-29 or placebo for seven days, and underwent the same caffeine test on the post-dose days 1 and 7. No statistically significant difference was observed in the activity of the three enzymes between those at baseline, and on day 1 after dosing with TJ-29 or placebo. The mean activity of CYP1A2, xanthine oxidase and N-acetyltransferase 2 tended to be lower on day 7 after dosing with TJ-29 compared with those at baseline and on day 7 after dosing with placebo. However, these changes were not statistically significant in CYP1A2 (P = 0.120), xanthine oxidase (P = 0.123) or N-acetyltransferase 2 (P = 0.056). In conclusion, TJ-29 did not appear to substantially affect the activity of CYP1A2, xanthine oxidase or N-acetyltransferase 2 in man.

Topics: Adult; Analysis of Variance; Arylamine N-Acetyltransferase; Cross-Over Studies; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP1A2 Inhibitors; Double-Blind Method; Drugs, Chinese Herbal; Enzyme Inhibitors; Female; Humans; Japan; Male; Medicine, East Asian Traditional; Plant Extracts; Pulmonary Disease, Chronic Obstructive; Xanthine Oxidase

The aim of this study was to evaluate factors of digoxin use and its relation to mortality in ED patients with atrial fibrillation (AF).. The Chinese AF registry enrolled 2016 AF patients from 20 representative EDs, and the period of study was one year. Predictors of digoxin use and its relation to mortality were assessed by logistic and Cox regression analyses.. Digoxin was assigned in 609 patients (30.6%), and younger age, lower body mass index values, and existence of permanent AF, heart failure (HF), chronic obstructive pulmonary disease, and valvular heart disease were identified to be factors associated with digoxin use. During the follow-up, compared to patients without digoxin therapy, digoxin-treated patients had significantly higher risk of all-cause death (17.2% vs. 13.0%, P=0.012) and cardiovascular death (15.1% vs. 6.7%, P<0.001), but similar risk of sudden cardiac death (1.1% vs. 0.7%, P=0.341). However, after adjustment for related covariates, digoxin use was no longer notably associated with increased all-cause mortality (hazards ratio [HR] 0.973, 95% confidence interval [CI] 0.718-1.318) and cardiovascular death (HR 1.313, 95% CI 0.905-1.906). Besides, neutral associations of digoxin treatment to mortality were obtained in relevant subgroups, with no interactions observed between digoxin and gender, HF, valvular heart disease, or concomitant warfarin treatment in mortality risk.. In ED patients with AF, digoxin was more frequently assigned to vulnerable patients with concomitant HF or valvular heart disease, and digoxin use was not related to a significantly increased risk of mortality.

Topics: Age Factors; Aged; Aged, 80 and over; Allopurinol; Anti-Arrhythmia Agents; Atrial Fibrillation; Body Mass Index; Cardiovascular Diseases; Cause of Death; China; Comorbidity; Death, Sudden, Cardiac; Digoxin; Emergency Service, Hospital; Female; Heart Failure; Heart Valve Diseases; Humans; Male; Middle Aged; Mortality; Proportional Hazards Models; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Registries; Risk Factors

Topics: Animals; Asthma; Coordination Complexes; Enzyme Inhibitors; Gene Expression Regulation; Gold; Humans; Macrophages, Alveolar; Mice; Osteopontin; Pulmonary Disease, Chronic Obstructive; RANK Ligand; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; Xanthine Oxidase

Reactive oxygen species have been reported to be involved in the airway inflammatory process of chronic obstructive pulmonary disease (COPD). The aim of this study was to quantify the activity of xanthine oxidase (XO), which generates a potent radical superoxide anion in COPD airways. Thirteen stable COPD patients and 10 healthy subjects participated in this study. We collected the epithelial lining fluid using a newly developed microsampling technique, and quantified of cytokines responsible for the XO gene upregulation. The XO activity was significantly increased in COPD patients compared with that in healthy subjects. A significant negative correlation was found between the XO activity and the %FEV1 values. The level of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma in COPD patients was significantly higher than that in healthy subjects. Both the amount of tumor necrosis factor-alpha and interleukin-1beta were significantly correlated with the degree of XO activity. These results suggest that the XO activity is increased in COPD airways, possibly due to its gene upregulation by proinflammatory cytokines. Because the XO activity was significantly correlated with the degree of airway obstruction, these cytokine-XO production pathways may play a key role in the inflammation of COPD.

Topics: Aged; Bronchoalveolar Lavage Fluid; Bronchoscopy; Cytokines; Female; Forced Expiratory Volume; Humans; Inflammation Mediators; Interleukin-1; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Respiratory System; Tumor Necrosis Factor-alpha; Up-Regulation; Xanthine Oxidase; Xanthopterin

Reactive nitrogen species, formed via the reaction of nitric oxide (NO) with superoxide anion and via (myelo)peroxidase-dependent oxidation of NO(2)(-), have potent proinflammatory and oxidizing actions. Reactive nitrogen species formation and nitrosative stress are potentially involved in chronic obstructive pulmonary disease (COPD) pathogenesis.. To investigate the expression of markers of nitrosative stress, including nitrotyrosine (NT), inducible NO synthase (iNOS), endothelial NO synthase (eNOS), myeloperoxidase (MPO), and xanthine oxidase (XO) in bronchial biopsies and bronchoalveolar lavage from patients with mild to severe stable COPD compared with control groups (smokers with normal lung function and nonsmokers).. The expression of NT, iNOS, eNOS, MPO and XO in the bronchial mucosa and bronchoalveolar lavage of patients was measured by using immunohistochemistry, Western blotting, and ELISA and correlated with the inflammatory cell profile.. Patients with severe COPD in stable phase had higher numbers of NT(+) and MPO(+) cells in their bronchial submucosa compared with mild/moderate COPD, smokers with normal lung function, and nonsmokers (P < .01). iNOS(+) and eNOS(+) but not XO(+) cells were significantly increased in smokers with COPD or normal lung function compared with nonsmokers (P < .05 and P < .01, respectively). In patients with COPD, the number of MPO(+) cells was significantly correlated with the number of neutrophils (r = +0.61; P < .0025) in the bronchial submucosa. Furthermore, the number of NT(+) and MPO(+) cells was negatively correlated with postbronchodilator FEV(1).. These data suggest that nitrosative stress, mainly mediated by MPO and neutrophilic inflammation, may contribute to the pathogenesis of severe COPD.

Topics: Aged; Bronchi; Bronchitis; Case-Control Studies; Cell Count; Epithelium; Female; Forced Expiratory Volume; Humans; Immunohistochemistry; Male; Middle Aged; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Oxidative Stress; Peroxidase; Pulmonary Disease, Chronic Obstructive; Reactive Nitrogen Species; Respiratory Mucosa; Smoking; Tyrosine; Vital Capacity; Xanthine Oxidase

Topics: Humans; Lung; Nitric Oxide; Oxidation-Reduction; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Superoxides; Tyrosine; Xanthine Oxidase

Reactive nitrogen species (RNS) have been reported to be involved in the inflammatory process in chronic obstructive pulmonary disease (COPD). However, there are no studies on the modulation of RNS in COPD. It was hypothesised that inhibition of xanthine oxidase (XO) might decrease RNS production in COPD airways through the suppression of superoxide anion production. Ten COPD and six healthy subjects participated in the study. The XO inhibitor allopurinol (300 mg x day(-1) p.o. for 4 weeks) was administered to COPD patients. RNS production in the airway was assessed by 3-nitrotyrosine immunoreactivity and enzymic activity of XO in induced sputum as well as by exhaled nitric oxide (eNO) concentration. XO activity in the airway was significantly elevated in COPD compared with healthy subjects. Allopurinol administration to COPD subjects significantly decreased XO activity and nitrotyrosine formation. In contrast, eNO concentration was significantly increased by allopurinol administration. These results suggest that oral administration of the xanthine oxidase inhibitor allopurinol reduces airway reactive nitrogen species production in chronic obstructive pulmonary disease subjects. This intervention may be useful in the future management of chronic obstructive pulmonary disease.

Topics: Aged; Allopurinol; Breath Tests; Enzyme Inhibitors; Female; Humans; Lung; Male; Middle Aged; Nitric Oxide; Pulmonary Disease, Chronic Obstructive; Reactive Nitrogen Species; Sputum; Tyrosine; Xanthine Oxidase