Die Sarkoidose ist eine chronische Erkrankung, charakterisiert durch das Vorkommen nicht-verkäsender, epitheloidzelliger Granulome, die in jedem Organ gebildet werden können. Bei über 80% der Patienten besteht eine intrathorakale Manifestation.
The aim of the present study was to investigate the efficacy of infliximab for the treatment of extrapulmonary sarcoidosis. A prospective, randomised, double-blind, placebo-controlled trial was conducted, with infliximab at 3 and 5 mg·kg −1 body weight administered over 24 weeks. Extrapulmonary organ severity was determined by a novel severity tool (extrapulmonary physician organ severity tool; ePOST) with an adjustment for the number of organs involved (ePOSTadj). In total, 138 patients enrolled in the trial of infliximab versus placebo for the treatment of chronic corticosteroid-dependent pulmonary sarcoidosis. The baseline severity of extrapulmonary organ involvement, as measured by ePOST, was similar across treatment groups. After 24 weeks of drug-therapy study, the change from baseline to week 24 in ePOST was greater for the combined infliximab group compared with the placebo group. After adjustment for the number of extrapulmonary organs involved, the improvement in ePOSTadj observed in the combined infliximab group was also greater than that observed in placebo-treated patients, after 24 weeks of therapy. The improvements in ePOST and ePOSTadj were not maintained during a subsequent 24-week washout period. Infliximab may be beneficial compared with placebo in the treatment of extrapulmonary sarcoidosis in patients already receiving corticosteroids, as assessed by the severity tool described in the present study.
Introduction: 6-min walk tests (6MWT) are routinely performed in CODP patients. Oxygen (VO2) kinetics during 6MWT can be modeled and indicators of patients9 exercise capacity can be derived. VO2 recovery has not been extensively investigated. A number of nonlinear regression models may be suitable for describing recovery kinetics and the uncertainty in considering several models can be captured by model averaging. We applied model averaging in the context of nonlinear mixed effects regression to better understand the physiological underpinnings of VO2 recovery after 6MWT in COPD. Methods: 61 patients with COPD (GOLD stages 2 to 4) were included in this study. VO2 kinetics were modeled using nonlinear regression. The recovery phase was modeled using 3 distinct equations: one describing a symmetrical sigmoid pattern (log-logistic), and 2 describing asymmetrical patterns with an inflection point either at beginning (Weibul I) or at the end of the recovery (Weibul II). Model averaging was used to estimate the time to half decrease of VO2 (T1/2 VO2). Results: Three models were fitted to the 61 oxygen kinetics. A significant model-averaged difference of 40.39 sec in T1/2 VO2 was found between stage 2 and 4 (p=0.0178). Weibul I model characterized by a steeper decrease at the beginning of the recovery phase showed an improved goodness of fit in stage 2 kinetics in comparison with the 2 other models. Conclusion: Nonlinear mixed models combined with model averaging were successfully applied to model VO2 recovery after 6MWT in patients with COPD. Significant differences in T1/2 VO2 were found between moderate and very severe COPD patients. The pattern of VO2 recovery differed among COPD stages, with a steeper early decline in stage 2 patients.
Evaluating the importance of the different sources of variations is essential in microarray data experiments. Complex experimental designs generally include various factors structuring the data which should be taken into account. The objective of these experiments is the exploration of some given factors while controlling other factors. We present here a family of methods, the analyses with respect to instrumental variables, which can be easily applied to the particular case of microarray data. An illustrative example of analysis with instrumental variables is given in the case of microarray data investigating the effect of beverage intake on peripheral blood gene expression. This approach is compared to an ANOVA-based gene-by-gene statistical method. Instrumental variables analyses provide a simple way to control several sources of variation in a multivariate analysis of microarray data. Due to their flexibility, these methods can be associated with a large range of ordination techniques combined with one or several qualitative and/or quantitative descriptive variables.
Background: Transcutaneous measurement of carbon dioxide (PtCO2) has been suggested as an alternative to invasively obtained PaCO2 for the monitoring of patients with respiratory failure. Current data show conflicting results in patients on the emergency department (ED).
Abstract: Static and dynamic hyperinflation is an important factor of exertional dyspnea in patients with severe COPD. This proof-of-concept intervention trial sought to study whether laughter can reduce hyperinflation through repetitive expiratory efforts in patients with severe COPD. For small groups of patients with severe COPD (n = 19) and healthy controls (n = 10) Pello the clown performed a humor intervention triggering regular laughter. Plethysmography was done before and up to 24 hours after intervention. Laughing and smiling were quantified with video-analysis. Real-time breathing pattern was assessed with the LifeShirt™, and the psychological impact of the intervention was monitored with self-administered questionnaires. The intervention led to a reduction of TLC in COPD (p = 0.04), but not in controls (p = 0.9). TLC reduction was due to a decline of the residual volume. Four (22 [CI 95% 7 to 46] %) patients were ≥10% responders. The frequency of smiling and TLC at baseline were independent predictors of TLC response. The humor intervention improved cheerfulness, but not seriousness nor bad mood. In conclusion, smiling induced by a humor intervention was able to reduce hyperinflation in patients with severe COPD. A smiling-derived breathing technique might complement pursed-lips breathing in patients with symptomatic obstruction. Keywords: bronchodilator, cheerfulness, COPD, dyspnoea, humor, hyperinflation
