Lukas Kern

Management of Parapneumonic Effusion and Empyema: Medical Thoracoscopy and Surgical Approach

Parapneumonic effusions or empyemas are frequently seen in patients with lower respiratory tract infections. The condition is associated with significant morbidity and mortality. Since Gram stains and bacterial cultures are usually negative, treatment focuses on empiric antibiotic treatment and chest tube drainage. The role of intrapleural fibrinolytics is still a matter of debate. Medical thoracoscopy is a simple and effective therapeutic alternative associated with better outcome and fewer complications than conservative treatment. Furthermore, it can be performed in analgo-sedation in a bronchoscopy suite. Video-assisted thoracic surgery carries the advantage of providing optimal visibility of the pleural cavity, thus allowing better debridement. Thoracotomy is the treatment of choice when thoracoscopic cleaning is not satisfactory.

Oxygen kinetics during 6-minute walk tests in patients with cardiovascular and pulmonary disease

BackgroundThe 6-Minute Walk Test (6MWT) is representative of daily-life activities and reflects the functional capacity of patients. The change of oxygen uptake (VO2) in the initial phase of low-intensity exercise (VO2 kinetics) can be used to assess submaximal exercise performance of patients.The objective of the following study was to analyse VO2 kinetics in patients with different pulmonary and cardiovascular diseases. In addition, we investigated the extent to which VO2 kinetics at the onset of the 6MWT were associated with exercise capacity, morbidity and mortality.MethodsVO2 kinetics of 204 patients and 16 healthy controls were obtained using mobile telemetric cardiopulmonary monitoring during a 6MWT. A new mean response time (MRT) index (wMRT) was developed to quantify VO2 kinetics by correcting MRT for work rate. The differences in wMRT between disease categories as well as the association between wMRT and patients’ exercise capacity and outcome - time to hospitalization/death- were tested.ResultsThe assessment of a robust wMRT was feasible in 86% (244/284) patients. wMRT was increased in patients compared to healthy controls (p <0.001). wMRT was largest in patients with pulmonary arterial hypertension (PAH). There were significant associations between wMRT and exercise capacity in all patients. High wMRT was found to be associated with a high rate of death and re-hospitalization in patients with CHF (p = 0.024). In patients with pulmonary diseases and pulmonary hypertension wMRT was not associated with outcome (p = 0.952).ConclusionsSubmaximal exercise performance of patients is reduced. O2 kinetics at the onset of exercise are associated with exercise capacity in all patients. wMRT was found to be an important prognostic factor in patients with congestive heart failure (CHF), but not with pulmonary diseases.

Exploring the transcription factor activity in high-throughput gene expression data using RLQ analysis

BackgroundInterpretation of gene expression microarray data in the light of external information on both columns and rows (experimental variables and gene annotations) facilitates the extraction of pertinent information hidden in these complex data. Biologists classically interpret genes of interest after retrieving functional information from a subset of genes of interest. Transcription factors play an important role in orchestrating the regulation of gene expression. Their activity can be deduced by examining the presence of putative transcription factors binding sites in the gene promoter regions.ResultsIn this paper we present the multivariate statistical method RLQ which aims to analyze microarray data where additional information is available on both genes and samples. As an illustrative example, we applied RLQ methodology to analyze transcription factor activity associated with the time-course effect of steroids on the growth of primary human lung fibroblasts. RLQ could successfully predict transcription factor activity, and could integrate various other sources of external information in the main frame of the analysis. The approach was validated by means of alternative statistical methods and biological validation.ConclusionsRLQ provides an efficient way of extracting and visualizing structures present in a gene expression dataset by directly modeling the link between experimental variables and gene annotations.

Oxygen Uptake Recovery Kinetics after the 6-Minute Walk Test in Patients with Chronic Obstructive Pulmonary Disease.

Background: There is a growing interest in exercise parameters capable of objectively evaluating the functional capacity of patients with chronic obstructive pulmonary disease (COPD). Objectives: The purpose of the present study was to analyze breath-by-breath cardiopulmonary and gas exchange recovery responses of patients with COPD after a 6-minute walk test (6MWT). Methods: Oxygen uptake (VO2) kinetics of patients were obtained using mobile telemetric cardiopulmonary monitoring during and after a 6MWT. Recovery kinetics were modelled using a 4-parameter nonlinear logistic model. Multiple linear regression was performed to assess the association between the half-time of recovery of oxygen consumption (T1/2 VO2) and exercise capacity (6-minute walking distance, 6MWD). Results: Sixty-nine patients with COPD (28 females) with a mean age of 65 ± 10 years took part in the study. After adjustment for covariates (body mass index, forced expiratory volume in 1 s, forced vital capacity, and age), T1/2 VO2 was significantly associated with 6MWD (p = 0.002). Conclusions: T1/2 VO2 can be used to reflect exercise capacity in patients with COPD. As T1/2 VO2 mostly depends on the rate of increase in pulmonary blood flow, the results of the present study underline the importance of cardiocirculatory impairment for exercise intolerance in patients with COPD.

Multimodel inference applied to oxygen recovery kinetics after 6-min walk tests in patients with chronic obstructive pulmonary disease

6-min walk tests (6MWT) are routinely performed in patients with chronic obstructive pulmonary disease (COPD). Oxygen uptake (V˙O2) kinetics during 6MWT can be modeled and derived parameters provide indicators of patients’ exercise capacity. Post-exercise V˙O2 recovery also provides important parameters of patients’ fitness which has not been extensively investigated in COPD. Several nonlinear regression models with different underlying biological assumptions may be suitable for describing recovery kinetics. Multimodel inference (model averaging) can then be used to capture the uncertainty in considering several models. Our aim was to apply multimodel inference in order to better understand the physiological underpinnings of V˙O2 recovery after 6MWT in patients with COPD. 61 patients with COPD (stages 2 to 4) were included in this study. Oxygen kinetics during 6MWT were modeled using nonlinear regression. Three statistical approaches (mixed-effects, meta-analysis and weighted regression) were compared in order to summarize estimates obtained from multiple kinetics. The recovery phase was modeled using 3 distinct equations (log-logistic, Weibull 1 and Weibull 2). Three models were fitted to the set of 61 kinetics. A significant model-averaged difference of 40.39 sec (SE = 17.1) in the time to half decrease of V˙O2 level (T1/2V˙O2) was found between stage 2 and 4 (p = 0.0178). In addition, the Weibull 1 model characterized by a steeper decrease at the beginning of the recovery phase showed some improvement of goodness of fit when fitted to the kinetics of patients with stage 2 COPD in comparison with the 2 other models. Multimodel inference was successfully used to model V˙O2 recovery after 6MWT in patients with COPD. Significant model-averaged differences in T1/2V˙O2 were found between moderate and very severe COPD patients. Furthermore, specific patterns of V˙O2 recovery could be identified across COPD stages.

Contents Vol. 92, 2016

P.J. Barnes, London X. Basagana Flores, Barcelona (Statistical Consultant) S. Bilaceroglu, Izmir E. Brambilla, Grenoble P. Camus, Dijon M. Cazzola, Rome P.N. Chhajed, Mumbai U. Costabel, Essen H. Dutau, Marseille S. Fernandez-Bussy, Santiago de Chile A. Foresi, Sesto San Giovanni M.E. Froudarakis, Alexandroupolis G. Hoheisel, Leipzig M. Humbert, Clamart G. Izbicki, Jerusalem M. Kneussl, Vienna M. Kreuter, Heidelberg N. Künzli, Basel S. Li, Guangzhou W. Li, Chengdu P.N. Mathur, Indianapolis, Ind. A.R.L. Medford, Bristol A. Mehta, Boston, Mass. T. Nakajima, Chiba V. Poletti, Forlì H.-B. Ris, Lausanne F. Rodriguez-Panadero, Sevilla I. Rubinstein, Chicago, Ill. T. Schaberg, Rotenburg F.C. Sciurba, Pittsburgh, Pa. M. Solèr, Basel S. Spiro, London A. Valipour, Vienna A. Warth, Heidelberg H. Wirtz, Leipzig E.F.M. Wouters, Maastricht European Association for Bronchology and Interventional Pulmonology EABIP

First experience with a biodegradable endobronchial stent in a case of bronchomalcia

Introduction: Stents are widely used to preserve airways from obstruction. Complications include migration, formation of granuloma and obstruction due to trapped secretions. In this context the use of biodegradable stents might be an alternative. Methods: A 72 years old patient suffering from dyspnea especially on exercise was refered to our Department. The patient9s history included a liver-transplantation related to a cryptogenic cirrhosis in 1994, an oropharyngial carcinoma in 2003 treated with radiation (cervical & supraclavicular) followed by laryngectomy. The patient also suffered from normofrequent atrial fibrillation. Endoscopically there was a breath dependent subtotal stenosis of the left main bronchus (under conscious sedation & awake). The right main bronchus showed a small narrowing. The FEV1 was 0.94 l (37%) and VC 2.17 l (67%). Results: The patient had a history of granulomas in the area of larynectomie. He also had a tracheostomy, therefore a silicon stent was difficult to implant. As a consequence, in this case of benign stenosis we decided to implant a 14 x 30 mm biodegradable polydioxanone stent. The wall tension seemed to be less than with silicon or nitinol stent. In situ the stent did not expand fully and was longer than calculated spaning from the main carina to the partially open ostium of the left upper lob. Fifty days later, the stent was partially bioabsorbed and the in- and expiratory functionality the left main bronchus was open. There were no problem of mucus. The lung functions improved regarding FEV1 1.40 l (55%) and VC 2.79 l (87%). Conclusion: Biodegradable stents are a promising alternative option for the maintainance of the endobronchial lumen.