Oxidative and nitrosative stress in the diaphragm of patients with COPD

COPD is associated with an increased load on the diaphragm. Since chronic muscle loading results in changes in antioxidant capacity and formation of reactive oxygen and reactive nitrogen species, we hypothesized that COPD has a similar effect on the diaphragm, which is related to the severity of COPD. Catalase activity was determined spectrophotometrically. Levels of 4-hydroxy-2-nonenal (HNE)-protein adducts and 3-nitrotyrosine (NT) formation were measured using western blotting. Levels of malondialdehyde (MDA) were assessed by high-performance liquid chromatography. We found that catalase activity was ~89% higher in the diaphragm of severe COPD patients (FEV1 37 ± 5% predicted) compared with non-COPD patients. MDA levels, a marker for lipid peroxidation, were significantly lower in the diaphragm of COPD patients compared with non-COPD patients, whereas the level of HNE-protein adducts was equal in both groups. NT formation was not different between groups. However, increasing hyperinflation and NT formation were inversely correlated. These results indicate that in COPD the diaphragm adapts to a higher work load by increasing catalase activity, resulting in a reduction in oxidative damage to lipids and tyrosine nitration of proteins

Plasma from septic shock patients induces loss of muscle protein

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Evaluation of inhaler technique and achievement and maintenance of mastery of budesonide/formoterol Spiromax® compared with budesonide/formoterol Turbuhaler® in adult patients with asthma: the Easy Low Instruction Over Time (ELIOT) study

Background: Incorrect inhaler technique is a common cause of poor asthma control. This two-phase pragmatic study evaluated inhaler technique mastery and maintenance of mastery with DuoResp® (budesonide-formoterol [BF]) Spiromax® compared with Symbicort® (BF) Turbuhaler® in patients with asthma who were receiving inhaled corticosteroids/long-acting β2-agonists. Methods: In the initial cross-sectional phase, patients were randomized to a 6-step training protocol with empty Spiromax and Turbuhaler devices. Patients initially demonstrating ≥1 error with their current device, and then achieving mastery with both Spiromax and Turbuhaler (absence of healthcare professional [HCP]-observed errors), were eligible for the longitudinal phase. In the longitudinal phase, patients were randomized to BF Spiromax or BF Turbuhaler. Co-primary endpoints were the proportions of patients achieving device mastery after three training steps and maintaining device mastery (defined as the absence of HCP-observed errors after 12 weeks of use). Secondary endpoints included device preference, handling error frequency, asthma control, and safety. Exploratory endpoints included assessment of device mastery by an independent external expert reviewing video recordings of a subset of patients. Results: Four hundred ninety-three patients participated in the cross-sectional phase, and 395 patients in the longitudinal phase. In the cross-sectional phase, more patients achieved device mastery after three training steps with Spiromax (94%) versus Turbuhaler (87%) (odds ratio [OR] 3.77 [95% confidence interval (CI) 2.05–6.95], p < 0.001). Longitudinal phase data indicated that the odds of maintaining inhaler mastery at 12 weeks were not statistically significantly different (OR 1.26 [95% CI 0.80–1.98], p = 0.316). Asthma control improved in both groups with no significant difference between groups (OR 0.11 [95% CI -0.09–0.30]). An exploratory analysis indicated that the odds of maintaining independent expert-verified device mastery were significantly higher for patients using Spiromax versus Turbuhaler (OR 2.11 [95% CI 1.25–3.54]). Conclusions: In the cross-sectional phase, a significantly greater proportion of patients using Spiromax versus Turbuhaler achieved device mastery; in the longitudinal phase, the proportion of patients maintaining device mastery with Spiromax versus Turbuhaler was similar. An exploratory independent expert-verified analysis found Spiromax was associated with higher levels of device mastery after 12 weeks. Asthma control was improved by treatment with both BF Spiromax and BF Turbuhaler

Random variation of inspiratory lung function parameters in patients with COPD: A diagnostic accuracy study.

Contains fulltext : 89500.pdf (publisher's version ) (Open Access)BACKGROUND: In chronic obstructive pulmonary disease (COPD), the response of the forced expiratory volume in 1 second (FEV1) after bronchodilator application is weak. Inspiratory parameters like the forced inspiratory volume in 1 second (FIV1) and inspiratory capacity (IC) can be responsive to bronchodilators. In an individual patient with COPD, a significant bronchodilator response must at least exceed the random variation for that parameter. Therefore, it is important that the type of scatter is homoscedastic, as the chance of underestimating or overestimating the random variation for low or high parameter values is minimized. The aim of this study is to investigate the random variation (type and quantity) of inspiratory parameters. METHODS: In 79 stable COPD patients, spirometry was performed. The forced inspiratory volume in 1 second (FIV1), inspiratory capacity (IC), maximal inspiratory flow at 50% (MIF50) and peak inspiratory flow (PIF) were measured five times in one day and again within two weeks of the first measurement. The values of these parameters, taken within one hour, within one day and between two different days, were compared. The coefficient of repeatability (CR) was calculated, and, in addition, linear regression was performed to investigate the type of scatter (homo- or heteroscedastic) of the measured parameters. RESULTS: The type of scatter was heteroscedastic for all of the parameters when the differences were expressed as absolute values; however, when the differences were expressed as the percent change from the initial values, we found a more homoscedastic scatter. The CR within one hour of each parameter expressed as the percent change from the initial value was: IC, 19%; FIV1, 14%; PIF, 18%; MEF50, 21%. CONCLUSIONS: To obtain a more homoscedastic scatter, percentage changes in FIV1, IC and MIF50 are more appropriate than absolute changes. In an individual patient with COPD, a significant improvement for a particular parameter must at least exceed the above-mentioned CR.9 p