Search

(1) Background: Mortality is a major outcome in research on chronic obstructive pulmonary disease (COPD) with various predictors described. However, the dynamic courses of important predictors over time are disregarded. This study evaluates if longitudinal assessment of predictors provides additional information on the mortality risk in COPD when compared with a cross-sectional analysis.; (2) In a longitudinal, prospective, non-interventional cohort study including mild to very severe COPD patients, mortality and its various possible predictors were annually assessed up to seven years.; (3) Results: 297 patients were analysed. Mean (SD) age was 62.5 (7.6) years and 66% males. Mean (SD) FEV1 was 48.8 (21.4)%. A total of 105 events (35.4%) happened with a median (95% CI) survival time of 8.2 (7.2/NA) years. No evidence for a difference between the raw variable and the variable history on the predictive value for all tested variables over each visit was found. There was no evidence for changing effect estimates (coefficients) across the study visits due to the longitudinal assessment; (4) Conclusions: We found no evidence that predictors of mortality in COPD are time dependent. This implies that cross-sectional measured predictors show robust effect estimates over time and multiple assessments seem not to change the predictive value of the measure.

Background: A significant proportion of patients with obstructive lung disease have clinical and functional features of both asthma and chronic obstructive pulmonary disease (COPD), referred to as the asthma-COPD overlap (ACO). The distinction of these phenotypes, however, is not yet well-established due to the lack of defining clinical and/or functional criteria. The aim of our investigations was to assess the discriminating power of various lung function parameters on the assessment of ACO., Methods: From databases of 4 pulmonary centers, a total of 540 patients (231 males, 309 females), including 372 patients with asthma, 77 patients with ACO and 91 patients with COPD, were retrospectively collected, and gradients among combinations of explanatory variables of spirometric (FEV 1 , FEV 1 /FVC, FEF 25-75 ), plethysmographic (sR eff , sG eff , the aerodynamic work of breathing at rest; sWOB), static lung volumes, including trapped gases and measurements of the carbon monoxide transfer (DL CO , K CO ) were explored using multiple factor analysis (MFA). The discriminating power of lung function parameters with respect to ACO was assessed using linear discriminant analysis (LDA)., Results: LDA revealed that parameters of airway dynamics (sWOB, sR eff , sG eff ) combined with parameters of static lung volumes such as functional residual capacity (FRC pleth ) and trapped gas at FRC (V TG FRC ) are valuable and potentially important tools discriminating between asthma, ACO and COPD. Moreover, sWOB significantly contributes to the diagnosis of obstructive airway diseases, independent from the state of pulmonary hyperinflation, whilst the diffusion capacity for carbon monoxide (DL CO ) significantly differentiates between the 3 diagnostic classes., Conclusion: The complexity of COPD with its components of interaction and their heterogeneity, especially in discrimination from ACO, may well be differentiated if patients are explored by a whole set of target parameters evaluating, interactionally, flow limitation, airway dynamics, pulmonary hyperinflation, small airways dysfunction and gas exchange disturbances assessing specific functional deficits., Competing Interests: The authors have no conflicts of interests to declare in this work., (© 2022 Kraemer et al.)

Alpine cold ice caps are sensitive indicators of local climate. The adequate interpretation of this information in an ice core requires detailed in situ glaciological and meteorological records, of which there are few. The Weißseespitze summit ice cap (3499 m) presents an ideal case to compare past and present climate and mass balance, with limited ice flow, but close to 6000 years locked into about 10 m of ice. First-ever meteorological observations at the ice dome have revealed that over 3 years of observation most of the accumulation took place between October and December and from April to June. In the colder winter months, between January and March, wind erosion prevents accumulation. Melt occurred between June and September, ice was only affected during short periods, mainly in August, which caused ice losses of up to 0.6 m (i.e. ~ 5% of the total ice thickness). Historical data points at a loss of of 34.9 ± 10.0 m between 1893 and 2018 and almost balanced conditions between 1893 and 1914. The local evidence of ice loss lays the basis for the interpretation of past gaps in the ice core records as past warm/melt events., (© 2022. The Author(s).)

Background and Objective: Whether immunological biomarkers combined with clinical characteristics measured during an exacerbation-free period are predictive of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) frequency and severity is unknown., Method: We measured immunological biomarkers and clinical characteristics in 271 stable chronic obstructive pulmonary disease (COPD) patients (67% male, mean age 63 years) from "The Obstructive Pulmonary Disease Outcomes Cohort of Switzerland" cohort on a single occasion. One-year follow-up data were available for 178 patients. Variables independently associated with AECOPD frequency and severity were identified by multivariable regression analyses. Receiver operating characteristic analysis was used to obtain optimal cutoff levels and measure the area under the curve (AUC) in order to assess if baseline data can be used to predict future AECOPD., Results: Higher number of COPD medications (adjusted incident rate ratio [aIRR] 1.17) and platelet count (aIRR 1.03), and lower FEV1% predicted (aIRR 0.84) and IgG2 (aIRR 0.84) were independently associated with AECOPD frequency in the year before baseline. Optimal cutoff levels for experiencing frequent (>1) AECOPD were ≥3 COPD medications (AUC = 0.72), FEV1 ≤40% predicted (AUC = 0.72), and IgG2 ≤2.6 g/L (AUC = 0.64). The performance of a model using clinical and biomarker parameters to predict future, frequent AECOPD events in the same patients was fair (AUC = 0.78) but not superior to a model using only clinical parameters (AUC = 0.79). The IFN-lambda rs8099917GG-genotype was more prevalent in patients who had severe AECOPD., Conclusions: Clinical and biomarker parameters assessed at a single point in time correlated with the frequency of AECOPD events during the year before and the year after assessment. However, only clinical parameters had fair discriminatory power in identifying patients likely to experience frequent AECOPD., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Skeletal muscle dysfunction, functional exercise capacity impairment and reduced physical activity are characteristic features in patients with chronic obstructive pulmonary disease (COPD). Assessments addressing muscle strength of the upper limb, such as measurement of handgrip strength (HGS), are rarely performed and reported. We aimed to analyze the course of HGS and possible predictors of changes in HGS over time in COPD. Yearly assessments of various disease markers were performed for a follow-up of up to seven years in a cohort of COPD patients to assess the longitudinal disease process. Data of 194 patients with at least one follow-up measurement were analyzed. HGS decreased significantly by B = -0.86 (95% CI -1.09/-0.62, p  < 0.001) over time. The multivariate mixed effects model showed an independent association between greater annual declines in HGS and lower numbers of steps per day by B  = 0.11 (95% CI 0.03/0.18, p  = 0.006) and an enhanced change in COPD Assessment Test scores by B = -0.01 (95% CI -0.01/-0.00, p  = 0.034). No evidence for an independent association between annual decline in HGS and FEV 1 % pred. by B = -0.01 (95% CI -0.03/0.01, p  = 0.297) was shown. Patients who died during follow-up did not exhibit greater declines in HGS compared to survivors ( p  = 0.884). Although HGS significantly decreased over time, no pathophysiological link with COPD disease progression could be demonstrated. Previous cross-sectional associations between HGS and mortality could not be confirmed in this longitudinal setting. Our data suggests that repeated monitoring of HGS in clinical settings seems not to be helpful to predict COPD specific disease progression.

Objective: To evaluate the clinical implementation of pharmacotherapy recommendations for chronic obstructive pulmonary disease (COPD) based on the Global Initiative for chronic obstructive lung disease (GOLD) guidelines, in a longitudinal setting., Methods: This is a sub-analysis of a prospective, non-interventional cohort study including patients with confirmed mild-to-very-severe COPD from seven pulmonary outpatient clinics in Switzerland. Follow-up visits took place annually for up to 7 years, from October 2010 until December 2016. For each visit, we evaluated the compliance of the prescribed pharmacotherapy with the concurrently valid GOLD guideline. We investigated whether step-ups or step-downs in GOLD stage or risk-group were accompanied by concordant changes in prescribed medication. Groups were compared via ANOVA., Results: Data of 305 patients (62±7 years, 66% men) were analysed. In 59.1% of visits, the prescribed medication conformed to the respective valid GOLD-guideline. Patients with very severe COPD were most likely to receive pharmacotherapy in compliance with guidelines. Step-ups and step-downs in risk group, requiring escalation, or de-escalation of pharmacotherapy, were noticed in 24 and 43 follow-up visits, respectively. Step-ups were adequately implemented in 4 (16.7%) and step-downs in six cases (14.0%)., Conclusion: The compliance of COPD-pharmacotherapy with GOLD-guidelines is suboptimal, especially in lower risk groups. The high rates of missed out treatment-adjustments suggest that the familiarity of physicians with guidelines leaves room for improvement., Competing Interests: Dr. Kohler reports personal fees from Bayer, Astra Zeneca, personal Boehringer Ingelheim, Novartis, Roche, CSL Behring, GSK, and Mundipharma, outside the submitted work, and grants from Lunge Zurich, during the conduct of the study. Dr. Clarenbach reports personal fees from Roche, from Novartis, Boehringer, GSK, Astra Zeneca, Sanofi, Vifor, and Mundipharma, outside the submitted work. All other authors report no conflicts of interest in this work., (© 2020 Grewe et al.)

Background and Objective: Reduced physical capacity (PC) and physical activity (PA) are common in COPD patients and associated with poor outcome. However, they represent different aspects of physical functioning and interventions do not affect them in the same manner. To address this, a new PC-PA quadrant concept was recently generated to identify clinical characteristics of sub-groups of physical functioning. The objective of this study was to I) proof the new concept and to verify their differentiating clinical characteristics, II) evaluate the consistency of the concept over time, III) assess whether patients changed their quadrant affiliation over time, IV) and to test if changes in quadrant affiliations are associated with changes in clinical characteristics., Methods: In a longitudinal, prospective, non-interventional cohort with mild to very severe COPD patients, PC and PA as well as respiratory variables, COPD-specific health status, comorbidities, survival, and exacerbations were yearly assessed., Results: Data from 283 patients were analysed at baseline. Mean (min/max) follow-up time was 2.4 (0.5/6.8) years. The PC-PA quadrants could be characterized as follows: I) "can't do, don't do": most severe and symptomatic, several comorbidities II) "can do, don't do": severe but less symptomatic, several comorbidities III) "can't do, do do": few patients, severe and symptomatic, less comorbidities IV) "can do, do do": mildest and less symptomatic, less comorbidities, lowest exacerbation frequency. Of the 172 patients with at least one follow-up, 58% patients never changed their quadrant affiliation, while 17% declined either PC, PA or both, 11% improved their PC, PA or both, and 14% showed improvement and decline in PC, PA or both during study period. None of the clinical characteristics or their annual changes showed consistent significant and relevant differences between all individual sub-groups., Conclusion: Our findings suggest that there are no clinical characteristics allowing to distinguish between the PC-PA quadrants and the concept seems not able to illustrate disease process. However, the already low PA but preserved PC in the "can do, don't do" quadrant raises the question if regularly assessment of PA in clinical practice would be more sensitive to detect progressive deterioration of COPD compared to the commonly used PC., Clinical Trial Registration: www.ClinicalTrials.gov, NCT01527773.

Pulmonary Rehabilitation Abstract. Pulmonary rehabilitation is a comprehensive therapeutic approach for patients with advanced chronic lung diseases which leads to a decline of dyspnea, an increase of exercise capacity and an increase of quality of life. Further effects are a reduction of frequency of hospitalisations and an increase of physical activity, if a self management education program is integrated. Pulmonary rehabilitation incorporates an individualised training program with focus on endurance, strength and mobility, further a disease specific education with the goal to improve self efficacy and self management of the patients, specially with the goal to improve their daily physical activity. Due to the good evidence of pulmonary rehabilitation, the accredited programs are accepted and paid by the swiss insurances.

Solvent-induced phase separation (SIPS) and thermally-induced phase separation (TIPS) derived poly(acrylonitrile) (PAN) based monoliths with different morphology and specific surface area were prepared and thermally converted into monolithic sulfur-poly(acrylonitrile) (SPAN) materials for use as active cathode materials in lithium-sulfur batteries. During thermal processing, the macroscopic monolithic structure fully prevailed while significant changes in porosity were observed. Both the monomer content in the precursor PAN-based monoliths and the tortuosity of the final monolithic SPAN materials correlate with the electrochemical performance of the SPAN-based cathodes. Overall, percolation issues predominate. In percolating SPAN-based cathode materials, the specific capacity of the SPAN-based cells increases with decreasing tortuosity. All monolithic SPAN materials provided highly reversible and cycle stable cathodes reaching reversible discharge capacities up to 1330 mA h g sulfur -1 @ 0.25C, 900 mA h g sulfur -1 @ 2C and 420 mA h g sulfur -1 @ 8C., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Introduction: COPD exacerbations are associated with a concomitant profound reduction in daily physical activity (PA). Thereby, exacerbation frequency and severity may have an amplifying effect. Whether the reduced level of PA returns to the level prior to exacerbation or has a sustained negative impact on activity behavior over time is unclear., Methods: The number of steps per day over 1 week, as a measure of daily PA, was assessed annually in a cohort of patients with COPD. Exacerbation frequency and severity were documented. Uni- and multivariate mixed effect models were used to investigate associations between change in number of steps per day (dependent variable) and exacerbations. Stratification by possible confounders was performed., Results: One hundred and eighty one COPD patients (median [quartile] age 64 [59/69] years, 65% male, median [quartiles] FEV 1 % pred. 46 [33/65]) suffered a total of 273 exacerbations during the observation period (median [quartiles] follow-up time of 2.1 [1.6/3.1] years). Neither the frequency nor the severity of exacerbations was significantly related to the overall decline in PA over time. Stratification by different possible confounders such as age, sex and disease severity did not yield a subgroup in which exacerbations enhance the decrease in PA over time., Conclusion: The drop in PA during the phase of an acute exacerbation seems not to be a lasting phenomenon leading to a fundamental change in activity behavior., Trial Registration: www.ClinicalTrials.gov, NCT01527773., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background and Objective: Daily physical activity (PA) and exercise capacity are reduced in patients with COPD. Whether the natural longitudinal course of both appears synchronically or one precedes the other is currently unclear. The aim was to assess the longitudinal relationship between exercise capacity and physical activity and their changes over time in patients with COPD., Methods: In a longitudinal observation-study of heterogeneous COPD patients, recruited from pulmonary outpatient clinics or hospital settings, we annually investigated two exercise capacity tests (1-min sit to stand test (STS) and 6 min walking test (6MWT)) and daily physical activity assessed by number of steps per day for minimum one, up to seven years. Univariable and multivariable mixed effect models were used to investigate the annual change in STS, 6MWD and number of steps per day., Results: 202 COPD patients (17% COPD risk group (considers symptoms and future exacerbation risk to grade disease severity) A, 49% B, 4% C and 34% D) with a mean (min/max) follow-up time of 2.4 (0.9/6.8) years were annually assessed. The number of steps per day decreased significantly over time (annual mean (95% CI) of -451.0 (-605.3/-296.6) steps, p < 0.001) while STS and 6MWD remained stable., Conclusion: Our findings suggest that COPD patients are increasingly impaired in their daily PA while exercise capacity remains stable during the study period. Thus, the longitudinal decline in PA seems not to be explained by a concomitant reduction in exercise tolerance., Clinical Trial Registration: www.Clinicaltrials.Gov, NCT01527773., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Evidence from longitudinal studies on the impact of exacerbation symptoms on physical activity in chronic obstructive pulmonary disease (COPD) is lacking. The aim of this first exploratory study was to assess the association between exacerbation symptoms and physical activity, and to quantify the relative influence of specific symptoms., Methods: We recruited COPD patients at high risk for exacerbations from 2 pulmonary rehabilitation clinics and 1 acute care clinic in Switzerland. For 3 months after discharge, patients completed a daily symptom diary on a smartphone application, the EXAcerbations of Chronic pulmonary disease Tool (EXACT), and wore a pedometer to measure daily steps. We used mixed-effects models to determine the association of daily steps with exacerbation symptoms., Results: A total of 21 patients (Global Initiative for Chronic Obstructive Lung Disease grades 2-4) were enrolled for a mean of 94.4 days (standard deviation 4.2). The baseline median number of daily steps was 3,264.6 (interquartile range [IQR]: 1,851.3-4,784.1) and EXACT score was 37.0 (IQR: 30.9-41.4). A 12-point increase in EXACT score (indicating the start of an exacerbation) was statistically significantly associated with a decrease in daily steps of 653.3 (95% CI 969.7-336.9). Chest symptoms (tightness, discomfort and congestion) were more strongly associated with change in steps than breathlessness, and cough and sputum ( z -value -4.5 vs -2.9 and -3.0)., Conclusion: This is the first study to show that, in a small cohort of COPD patients, increases in exacerbation symptoms were associated with a statistically and clinically significant reduction in daily physical activity. These results underscore the importance for symptom control and exacerbation prevention in COPD patients., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The Swiss National Guidelines 2013 for chronic obstructive pulmonary disease have been revised in order to acknowledge recent progress in diagnosis and management of this disease. The resulting new Swiss recommendations are based on best evidence from the literature, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018 report and other published national guidelines. Misdiagnosis of chronic obstructive pulmonary disease is common and means that patients do not always receive optimal treatment. To improve the management of patients with chronic obstructive pulmonary disease in Switzerland, these recommendations encourage a more comprehensive assessment of patients, based on the combined assessment of symptoms, degree of airflow limitation, risk of exacerbation and the presence of comorbidities. Recommendations for evidence-based preventive measures, as well as pharmacological and non-pharmacological strategies for the management of both stable and acute exacerbations of chronic obstructive pulmonary disease are provided in this update., (© 2018 S. Karger AG, Basel.)

The significant increase in traces of human activity in the environment worldwide provides evidence of the beginning of a new geological era, informally named the Anthropocene. The rate and variability of these human modifications at the local and global scale remain largely unknown, but new analytical methods such as high-resolution mass spectrometry (HRMS) can help to characterize chemical contamination. We therefore applied HRMS to investigate the contamination history of two lakes in Central Europe over the preceding 100 years. A hierarchical clustering analysis (HCA) of the collected time series data revealed more than 13 000 profiles of anthropogenic origin in both lakes, defining the beginning of large-scale human impacts during the 1950s. Our results show that the analysis of temporal patterns of nontarget contaminants is an effective method for characterizing the contamination pattern in the Anthropocene and an important step in prioritizing the identification of organic contaminants not yet successfully targeted by environmental regulation and pollution reduction initiatives. As proof of the concept, the success of the method was demonstrated with the identification of the pesticide imazalil, which probably originated from imported fruits. This new approach applicable to palaeoarchives can effectively be used to document the time and rate of change in contamination over time and provide additional information on the onset of the Anthropocene.

Introduction: Smoking is still the most preventable cause of disease and premature death in Switzerland, as elsewhere. We aimed to assess the main determinants of smoking cessation in the population-based cohort of SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults)., Methods: The SAPALDIA study was initiated in 1991 with 9651 participants aged 18 to 60 years from eight areas (S1). Follow-up assessments were conducted in 2002 (S2; 8047 participants) and 2010/11 (S3; 6088 participants). At each survey, detailed information on health and potential health-related factors was collected and lung function measured. Using logistic regression, we assessed predictors of smoking cessation between S1 and S2 and between S2 and S3., Results: In both periods, highest educational level (summary odds ratio [OR] 1.49, 95% confidence interval [CI] 1.08-2.06; ref. lowest level), FEV1/FVC <0.5 (OR 6.19, 95% CI 2.44-15.7, ref. FEV1/FVC ≥0.7), higher age in men (OR 1.02, 95% CI 1.01-1.03, per year) and overweight (OR 1.38, 95% CI 1.16-1.64) were significant predictors of smoking cessation. Nicotine dependence (OR 0.97, 95% CI 0.96-0.98, per cigarette smoked a day) and female sex between age 45 and 60 (e.g., OR 0.74, 95% CI 0.61-0.91, at age 50) were negatively associated with smoking cessation. Moreover, smokers at S2 reporting a diagnosis of depression were less likely to quit smoking by S3 (OR 0.53, 95% CI 0.30-0.93)., Conclusions: Prospective tobacco control policies in Switzerland should be addressed to women, younger persons and persons of lower education.

Background and Objective: Daily physical activity (PA) is reduced in patients with COPD. Previous cross-sectional analyses indicate various predictors for a low level of PA including airway obstruction, exacerbations and co-morbidities. However, information from longitudinal studies evaluating PA in the context of disease progression, survival and co-morbidities is scant., Methods: In a heterogeneous cohort of COPD patients, we annually assessed the number of steps per day over 1 week and potential determinants including lung function, exacerbations and co-morbidities. Univariable and multivariable mixed effect models were used to investigate associations between the change in steps per day (dependent variable) and possible predictors and their annual changes., Results: A total of 177 COPD patients (46% GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 1/2, 38% stage 3 and 16% stage 4) with a mean (min/max) follow-up time of 2.7 (1/5) years were annually assessed. The number of steps per day decreased significantly over time (P < 0.001) with a mean annual change of -508 steps. The decrease in activity was significantly associated with forced expiratory volume in 1 s (FEV 1 ) % predicted (P = 0.020) but not with annual changes in FEV 1 . Hyperinflation, exacerbations, co-morbidities and their annual changes, and survival did not significantly affect change in PA., Conclusion: COPD patients have a substantial decrease of PA over time. This decrease seems to be determined by the degree of airflow limitation. However, patients with a greater annual decline in lung function did not show a greater decrease in PA. The rate of decline in PA did not differ between survivors and non-survivors in this cohort., (© 2017 Asian Pacific Society of Respirology.)

Background and Objective: Physical activity (PA) is an important outcome parameter in patients with COPD regarding hospitalizations and mortality. Both objective assessment by accelerometers and self-evaluation by questionnaires were used in studies investigating PA in COPD. Whether self-reported questionnaires can adequately reflect PA and its changes over time compared to objective assessments has not been thoroughly investigated in COPD. In this COPD cohort study, we evaluated whether PA measured by accelerometer and its annual changes can also be assessed by self-reported questionnaires., Methods: In 178 COPD patients with at least two assessments of PA, the agreement between objectively measured and self-reported activity was analyzed by Bland-Altman plots. Daily PA was assessed by a triaxial activity monitor over 1 week and by the self-reported German PA questionnaire 50+., Results: Comparison between the two methods of measurement revealed no convincing agreement with a mean difference and limits of agreement (±1.96 standard deviation [SD]) of time spent in at least moderate PA (>3 metabolic equivalent of task [MET]) of -77.6 (-340.3/185.2) min/day, indicating a self-reported overestimation of PA by the questionnaire. The mean difference and limits of agreement (±1.96SD) in the annual change of PA was 1.2 min/day (-208.2/282.6 min/day), showing also a poor agreement on an individual level., Conclusion: Evaluation of objectively measured and self-reported PA and their annual changes revealed no agreement in patients with COPD. Therefore, the evaluated questionnaire seems not helpful for measurement of PA and its changes over time., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Our aim was to comprehensively validate the 1-min sit-to-stand (STS) test in chronic obstructive pulmonary disease (COPD) patients and explore the physiological response to the test.We used data from two longitudinal studies of COPD patients who completed inpatient pulmonary rehabilitation programmes. We collected 1-min STS test, 6-min walk test (6MWT), health-related quality of life, dyspnoea and exercise cardiorespiratory data at admission and discharge. We assessed the learning effect, test-retest reliability, construct validity, responsiveness and minimal important difference of the 1-min STS test.In both studies (n=52 and n=203) the 1-min STS test was strongly correlated with the 6MWT at admission (r=0.59 and 0.64, respectively) and discharge (r=0.67 and 0.68, respectively). Intraclass correlation coefficients (95% CI) between 1-min STS tests were 0.93 (0.83-0.97) for learning effect and 0.99 (0.97-1.00) for reliability. Standardised response means (95% CI) were 0.87 (0.58-1.16) and 0.91 (0.78-1.07). The estimated minimal important difference was three repetitions. End-exercise oxygen consumption, carbon dioxide output, ventilation, breathing frequency and heart rate were similar in the 1-min STS test and 6MWT.The 1-min STS test is a reliable, valid and responsive test for measuring functional exercise capacity in COPD patients and elicited a physiological response comparable to that of the 6MWT., (Copyright ©ERS 2017.)

Background: There are few studies comparing diagnostic accuracy of different lung function parameters evaluating dose-response characteristics of methacholine (MCH) challenge tests (MCT) as quantitative outcome of airway hyperreactivity (AHR) in asthmatic patients. The aim of this retrospectively analysis of our database (Clinic Barmelweid, Switzerland) was, to assess diagnostic accuracy of several lung function parameters quantitating AHR by dose-response characteristics., Methods: Changes in effective specific airway conductance (sG eff ) as estimate of the degree of bronchial obstruction were compared with concomitantly measured forced expiratory volume in 1 s (FEV 1 ) and forced expiratory flows at 50% forced vital capacity (FEF 50 ). According to the GINA Guidelines the patients (n = 484) were classified into asthmatic patients (n = 337) and non-asthmatic subjects (n = 147). Whole-body plethysmography (CareFusion, Würzburg, Germany) was performed using ATS-ERS criteria, and for the MCTs a standardised computer controlled protocol with 3 consecutive cumulative provocation doses (PD 1 : 0.2 mg; PD 2 : 1.0 mg; PD 3 : 2.2 mg) was used. Break off criterion for the MCTs were when a decrease in FEV 1 of 20% was reached or respiratory symptoms occurred., Results: In the assessment of AHR, whole-body plethysmography offers in addition to spirometry indices of airways conductance and thoracic lung volumes, which are incorporated in the parameter sG eff , derived from spontaneous tidal breathing. The cumulative percent dose-responses at each provocation step were at the 1 st level step (0.2 mg MCH) 3.7 times, at the 2 nd level step (1 mg MCH) 2.4 times, and at the 3 rd level step (2.2 mg MCH) 2.0 times more pronounced for sG eff , compared to FEV 1 . A much better diagnostic odds ratio of sG eff (7.855) over FEV 1 (6.893) and FEF 50 (4.001) could be found. Moreover, the so-called dysanapsis, and changes of end-expiratory lung volume were found to be important determinants of AHR., Conclusions: Applying plethysmographic tidal breathing analysis in addition to spirometry in MCTs provides relevant advantages. The absence of deep and maximal inhalations and forced expiratory manoeuvres improve the subject's cooperation and coordination, and provide sensitive and differentiated test results, improving diagnostic accuracy. Moreover, by the combined assessment, pulmonary hyperinflation and dysanapsis can be respected in the differentiation between "asthmatics" and "non-asthmatics".

Background: There is limited knowledge on practice patterns in procedural sedation and analgesia (PSA), the use of propofol, and monitoring during flexible bronchoscopy (FB). The purpose of this study was to assess the current practice patterns of FBs and to focus on the use of propofol, the education of the proceduralist, and the involvement of anaesthesiologists during FB., Methods: An anonymous questionnaire was sent to 299 pulmonologists. Only respondents who were active physicians in adult respiratory medicine performing FB were subsequently analysed., Results: The response rate was 78 % and 27,149 FB in the previous 12 months were analysed. The overall sedation-related morbidity rate was 0.02 % and mortality was 7/100'000 FB. Sedation was used in 95 % of bronchoscopies. The main drugs used for PSA were propofol (77 %) and midazolam (46 %). In 84 % of PSAs propofol was used without the attendance of an anaesthesiologist. The use of propofol was associated with high volume bronchoscopists (p < 0.010) and career-young pulmonologists (p < 0.001). While monitoring vital parameters has become standard practice, pulmonologists reported a very low rate of systematic basic education and training in the field of PSA (50 %)., Conclusions: In Switzerland, PSA during FB is mostly performed with propofol without the attendance of an anaesthesiologist and the use of this drug is expected to increase in the future. While monitoring standards are very high there is need for policies to improve education, systematic training, and support for pulmonologists for PSA during FB.

Background and Objective: Both comorbidities and physical inactivity have been shown to impair quality of life and contribute to hospital admissions and mortality in chronic obstructive pulmonary disease (COPD) patients. We hypothesized that the comorbid status predicts the level of daily physical activity (PA) in COPD., Methods: In 228 patients with COPD (76% men; median (quartiles) age: 64 (59/69) years; percentage of predicted forced expiratory volume in 1 s (FEV1 % pred): 44 (31/63)), comorbidities were assessed by medical history, clinical interviews, examination and blood analysis. PA level (PAL) was measured by an activity monitor (SenseWear Pro, Bodymedia Inc., Pittsburgh, PA, USA). The association between PAL and comorbidities was investigated by univariate and multivariate regression analysis., Results: Seventy-nine percent of the COPD patients had at least one additional chronic comorbidity, 56% had two or more comorbidities and 35% had three or more comorbidities. In univariate analysis body mass index, the number of pack years and having at least one additional comorbidity was negatively associated with PAL while there was a positive nonlinear association between FEV1 and PAL. The presence of at least one additional comorbidity was independently associated with PAL irrespective of airflow limitation., Conclusions: In this cohort, almost 80% of COPD patients had at least one additional chronic comorbidity. The level of daily PA seems to be significantly impaired by the presence of comorbidities irrespective of the type of comorbidity and independent of the degree of airflow limitation., Clinical Trial Registration: NCT01527773 at http://www.clinicalTrials.gov., (© 2015 Asian Pacific Society of Respirology.)

Despite the relevance of resting eggs for ecology and evolution of many aquatic organisms and their exposure to contaminants accumulating in sediments, ecotoxicological studies using resting eggs are vastly underrepresented. The authors established a method to perform exposure assays with resting eggs produced by the Daphnia longispina species complex, key species in large lake ecosystems. A mixture of organic contaminants previously detected in sediments of Lake Greifensee was selected to test the potential effect of organic contaminants present in sediments on the hatching process. Resting eggs were exposed to a mix of 10 chemicals, which included corrosion inhibitors, biocides, pesticides, and personal care products, for a period of 15 d. Using an automated counting software, the authors found a significant increase in hatching success in the exposed resting eggs compared with controls. Such an effect has not yet been reported from ecotoxicological assays with resting eggs. Possible mechanistic explanations as well as the potential implications on the ecology and evolution of aquatic species that rely on a resting egg banks are discussed. Observed increased mortality and developmental abnormalities for hatchlings in the exposure treatments can be explained by toxic contaminant concentrations. The results of the present study highlight the need for additional studies assessing the effects of organic contaminants on resting egg banks and aquatic ecosystems., (© 2014 SETAC.)

Biobank sample storage is critical in population health and epidemiology studies. Biobanks bridge two very different worlds: they connect to the participants and patients at an individual level, but they also aggregate information and represent the cutting edge of scientific discovery. In this brief report, we describe how the LifeLines study in the Netherlands manages its resources for communication and services, and how it can serve as a model for the Human Heredity and Health in Africa Initiative (H3Africa Initiative).

Psychological morbidity is common in chronic respiratory diseases. The diagnostic accuracy of the Hospital Anxiety and Depression Scale (HADS) and risk factors for comorbid depression in chronic obstructive pulmonary disease (COPD) are addressed. Consecutive COPD patients (GOLD stage I-IV, 40-75 years old) were enrolled in a multicentre, cross-sectional cohort study. Diagnosis of depression was ascertained through clinical records. Lung function, HADS score, 6-minute walking test (6-MWT), MRC dyspnoea score, and COPD Assessment Test (CAT) were evaluated. Two hundred fifty-nine COPD patients (mean age 62.5 years; 32% female; mean FEV1 48% predicted) were included. Patients diagnosed with depression (29/259; 11.2%) had significantly higher HADS-D and HADS-Total scores than nondepressed patients (median (quartiles) HADS-D 6 [4; 9] versus 4 [2; 7], median HADS-Total 14 [10; 20] versus 8 [5; 14]). Receiver-operating characteristic plots showed moderate accuracy for HADS-D, AUC 0.662 (95%CI 0.601-0.719), and HADS-Total, AUC 0.681 (95%CI 0.620-0.737), with optimal cut-off scores of >5 and >9, respectively. Sensitivity and specificity were 62.1% and 62.6% for HADS-D compared to 75.9% and 55.2% for HADS-Total. Age, comorbidities, sex, and lower airflow limitation predicted depression. The HADS exhibits low diagnostic accuracy for depression in COPD patients. Younger men with comorbidities are at increased risk for depression.

Physical exercise is highly effective to improve exercise capacity and quality of life of patients with COPD and to reduce the risk for hospital admissions in patients with exacerbations.The combination of physical exercise,patient education and pharmacotherapy,as typically performed during pulmonary rehabilitation, has become the modern disease management for COPD patients. Unfortunately, there is still a lack of evidence on effective treatments to increase levels of physical activity. But there are currently major research efforts to evaluate drug and non-drug treatments for increasing levels of physical activity. This raises hopes that effective treatments could,through an increase in physical activity,reduce the risk for hospital admissions and early death in COPD patients.

Background: Around the world, the timing of referral of chronic obstructive pulmonary disease (COPD) patients for pulmonary rehabilitation differs from immediately after exacerbation (early) to later on when patients are in a stable state (late). There are no trials comparing the different time points of referral for pulmonary rehabilitation., Objectives: Our aim was to compare the effects of early and late pulmonary rehabilitation on exacerbation rates and health-related quality of life (HRQOL) in COPD patients with exacerbations., Methods: We randomized COPD patients (Global Initiative for Chronic Obstructive Lung Disease stages II-IV) with a recent exacerbation to early (within 2 weeks) or late pulmonary rehabilitation (starting 6 months after randomization and in a stable state). The primary outcome was the exacerbation rate over 18 months, and secondary outcomes included HRQOL and mortality. We used multivariate analyses and an intention-to-treat analysis approach., Results: We randomized 36 patients to pulmonary rehabilitation. On average, patients with early rehabilitation (n = 19) had 2.61 (SD 2.96) exacerbations requiring systemic corticosteroids and/or antibiotics, compared to 2.77 (SD 3.41) in patients with late rehabilitation (adjusted incidence rate ratio 0.83, 95% confidence interval 0.43-1.63; p = 0.60). Over the 18-month period, patients with late rehabilitation experienced more dyspnea (difference on Chronic Respiratory Questionnaire dyspnea domain 0.74 and on the Medical Research Council dyspnea scale 0.37), but neither these differences nor any difference in HRQOL domains reached statistical significance., Conclusions: We did not find any statistically significant differences between early and late pulmonary rehabilitation. However, our trial indicates that early rehabilitation may lead to faster recovery of HRQOL after exacerbations compared to rehabilitation later on when patients are in a stable state., (Copyright © 2011 S. Karger AG, Basel.)

Background: The BODE index (including body-mass index, airflow obstruction, dyspnoea, and exercise capacity) was an important contribution to the prognostic assessment of patients with chronic obstructive pulmonary disease (COPD). However, no study has assessed whether the risk of mortality predicted by the BODE index matches the observed mortality in different populations. We assessed the calibration of the BODE index, updated it to improve its calibration, and developed and validated a simplified index for use in primary-care settings., Methods: We included 232 patients from the Swiss Barmelweid cohort with longstanding and severe COPD and 342 patients from the Spanish Phenotype and Course of COPD cohort study who had had their first hospital admission due to moderate-to-severe COPD. In both cohorts we compared the observed 3-year risk of all-cause mortality with the risk predicted by the BODE index. We then updated the BODE index and developed a simplified ADO index (including age, dyspnoea, and airflow obstruction) from the Swiss cohort, and validated both in the Spanish cohort., Findings: Calibration of the BODE index was poor, with relative underprediction of 3-year risk of mortality by 36% in the Swiss cohort (median predicted risk 21.7% [IQR 12.7-31.7] vs 34.1% observed risk; p=0.013) and relative overprediction by 39% in the Spanish cohort (16.7% [12.7-31.7] vs 12.0%; p=0.035). The 3-year risk of mortality predicted by both the updated BODE (median 10.7% [8.1-13.8]) and ADO indices (11.8% [9.1-14.3]) matched the observed mortality in the Spanish cohort well (p=0.99 and p=0.98, respectively)., Interpretation: Both the updated BODE and ADO indices could lend support to the prognostic assessment of patients with COPD in specialised and primary-care settings. Such assessment enhances the targeting of treatments to individual patients., Funding: Swiss National Science Foundation; Klinik Barmelweid; Fondo de Investigación Sanitaria Ministry of Health, Spain; Agència d'Avaluació de Tecnologia i Recerca Mèdiques, Catalonia Government; Spanish Society of Pneumology and Thoracic Surgery; Catalan Foundation of Pneumology; Red RESPIRA; Red RCESP; Fondo de Investigación Sanitaria; Fondo de Investigación Sanitaria; Fundació La Marató de TV3; Novartis Farmacèutica, Spain.

Background: The feasibility of randomized trials often depends on successful patient recruitment. Although numerous recruitment barriers have been identified it is unclear which of them complicate recruitment most. Also, most surveys have focused on the patients' perspective of recruitment barriers whereas the perspective of recruiting physicians has received less attention. Therefore, our aim was to conduct a postal survey among recruiting physicians of a multi-center trial to weigh barriers according to their impact on recruitment., Methods: We identified any potential recruitment barriers from the literature and from our own experience with a multi-center trial of respiratory rehabilitation in patients with chronic obstructive pulmonary disease. We developed and pilot-tested a self-administered questionnaire where recruiting physicians were asked to express their agreement with statements about recruitment barriers on a Likert-type scale from 1 (full agreement with statement = very substantial recruitment barrier) to 7 (no agreement with statement = no recruitment barrier)., Results: 38 of 55 recruiting physicians returned questionnaires (69% response rate), of which 35 could be analyzed (64% useable response rate). Recruiting physicians reported that "time constraints" (median agreement of 3, interquartile range 2-5) had the most negative impact on recruitment followed by "difficulties including identified eligible patients" (median agreement of 5, IQR 3-6). Other barriers such as "trial design barriers", "lack of access to treatment", "individual barriers of recruiting physicians" or "insufficient training of recruiting physicians" were perceived to have little or no impact on patient recruitment., Conclusion: Physicians perceived time constraints as the most relevant recruitment barrier in a randomized trial. To overcome recruitment barriers interventions, that are affordable for both industry- and investigator-driven trials, need to be developed and tested in randomized trials., Trial Registration: ISRCTN84612310.

Background: Interpretation of the Hospital Anxiety and Depression Scale (HADS), commonly used to assess anxiety and depression in COPD patients, is unclear. Since its minimal important difference has never been established, our aim was to determine it using several approaches., Methods: 88 COPD patients with FEV1 /= 0.5 we performed linear regression analyses to predict the minimal important difference from the anchors. As distribution-based approach we used the Effect Size approach., Results: Based on CRQ emotional function and mastery domain as well as on total scores, the minimal important difference was 1.41 (95% CI 1.18-1.63) and 1.57 (1.37-1.76) for the HADS anxiety score and 1.68 (1.48-1.87) and 1.60 (1.38-1.82) for the HADS total score. Correlations of the HADS depression score and CRQ domain and Feeling Thermometer scores were < 0.5. Based on the Effect Size approach the MID of the HADS anxiety and depression score was 1.32 and 1.40, respectively., Conclusion: The minimal important difference of the HADS is around 1.5 in COPD patients corresponding to a change from baseline of around 20%. It can be used for the planning and interpretation of trials.

Background: Guidelines recommend high-intensity continuous exercise to reduce peripheral muscle dysfunction in patients with chronic obstructive pulmonary disease but acknowledge that interval exercise might be an equally effective alternative that is better tolerated by patients., Objective: To assess whether interval exercise is no less effective than high-intensity continuous exercise and whether it is tolerated better by patients with severe chronic obstructive pulmonary disease., Design: Randomized, noninferiority trial., Setting: Publicly funded rehabilitation hospital in Switzerland., Patients: 98 patients with severe chronic obstructive pulmonary disease, with or without recent exacerbations., Intervention: 12 to 15 supervised interval or high-intensity continuous exercise sessions (over 3 weeks) followed by exercise at home., Measurements: Health-related quality of life determined by using the Chronic Respiratory Questionnaire (CRQ) (scores from 1 [most severe impairment] to 7 [no impairment]) after 5 weeks and number of unintended breaks during supervised exercise., Results: Both groups experienced large improvements in health-related quality of life (increase of CRQ total scores of 1.00 [SD, 0.98] for the interval exercise group and 1.02 [SD, 1.05] for the continuous exercise group). Adjusted between-group differences between the interval exercise group and the continuous exercise group (-0.05 [95% CI, -0.42 to -0.32] for CRQ and 1.1 meters [CI, -25.4 to 27.6 meters] for 6-minute walking distance) were within the a priori defined boundaries of noninferiority (0.5 for CRQ and 45 meters for 6-minute walking distance). Twenty-one (47.9%) patients using interval exercise and 11 (24.0%) patients using continuous exercise were able to adhere to the protocol (difference, 23.9 percentage points [CI, 5.0 to 42.8 percentage points]; P = 0.014). The median number of unintended breaks lasting 1 minute or more was 2 (interquartile range, 0 to 16) for patients in the interval exercise group and 11 (interquartile range, 2 to 26) for patients in the continuous exercise group (P = 0.023)., Limitations: The study focused on initiation of exercise and not on outpatient or home-based maintenance of exercise., Conclusions: Clinicians and patients can choose either of the 2 exercise plans to initiate physical exercise. International Standard Randomized Controlled Trial number: SRCTN11611768.

Rationale: Exposure to environmental tobacco smoke (ETS) is associated with increased reports of respiratory symptoms and reduced lung function, but the long-term effects of ETS are unclear, notably in healthy individuals with bronchial hyperresponsiveness (BHR)., Objective: To assess the longitudinal effects of ETS exposure on the development of respiratory symptoms and spirometry in subjects with BHR., Methods: The study population included 1,661 never-smokers from the SAPALDIA (Swiss Study on Air Pollution and Lung Diseases in Adults) cohort, assessed in 1991 (baseline) and 11 yr later, who were symptom-free at baseline. Incident reports of respiratory symptoms and results of spirometry were assessed at the follow-up survey., Main Results: Exposure to ETS reported in the two surveys was strongly associated with the development of cough (odds ratio, 2.1; 95% confidence interval, 1.2-3.7; p = 0.01). In subjects with BHR exposed to ETS at both surveys, a trend for strong associations were observed for wheeze, cough, dyspnea, and chronic bronchitis; however, the association reached statistical significance only for the symptom of dyspnea (p < 0.01). Lower FEV1/FVC (mean +/- SD, 72.9 +/- 7.7 vs. 76.8 +/- 6.1%; p < 0.01) and FEF(25-75) (forced expiratory flow, midexpiratory phase)/FVC (mean +/- SD, 56.1 +/- 22.5 vs. 68.1 +/- 21.6%; p < 0.01) were observed in subjects with BHR exposed to ETS compared with nonexposed subjects without BHR. Lower values were found in subjects continuing exposure by the follow-up survey., Conclusion: Exposure to ETS was strongly associated with the development of respiratory symptoms in previously asymptomatic subjects with BHR within 11 yr. Furthermore, subjects with underlying BHR had reduced lung function at follow-up, thus suggesting a higher risk for the development of chronic respiratory disease in this subset of the population.

A novel mechatronic body weight support (BWS) system has been developed to provide precise body weight unloading for patients with neurological or other impairments during treadmill training. The system is composed of a passive elastic spring element to take over the main unloading force and an active closed-loop controlled electric drive to generate the exact desired force. Both force generating units, the passive spring and the active electric drive, act on the patient via a polyester rope connected to a harness worn by the patient. The length of the rope can be adjusted with an electric winch to adapt the system to different patient sizes. The system is fully computer controlled. At unloading loads of up to 60 kg and walking speeds of up to 3.2 km/h, the mean unloading error and the maximum unloading error of the presented BWS system was less than 1 and 3 kg, respectively. The performance was compared with those of two purely passive BWS systems currently being used by most other rehabilitation groups. This comprised counterweight systems and static BWS systems with fixed rope lengths. Counterweight systems reached mean and maximum unloading errors of up to 5.34 and 16.22 kg, respectively. The values for the static BWS were 11.02 kg and 27.67 kg, respectively. The novel mechatronic BWS system presented in this study adjusts desired unloading changes of up to 20 kg within less than 100 ms. Thus, not only constant BWS, but also gait cycle dependent or time variant oscillations of the desired force can be realized with high accuracy. Precise and constant unloading force is believed to be an important prerequisite for BWS gait therapy, where it is important to generate physiologically correct segmental dynamics and ground reaction forces. Thus, the novel BWS system presented in this paper is an important contribution to maximize the therapeutic outcome of human gait rehabilitation.

An analytical, dynamic model of the human knee joint has been developed to simulate the unloaded knee joint behaviour in 6 degrees of freedom. It is based on extensive robot-based measurements of the elastic properties of a human cadaver knee joint. The measured data are compared with data from the literature to ensure that a proper database for modelling is used. The analytical modelling of the passive elastic joint properties is done with Local Linear Model Trees. The deduced knee joint model incorporates passive elastic properties of the internal knee joint structures, passive elastic muscle forces, damping forces, gravitational forces, and external forces. There are two sets of parameters, one simulating the movement of the intact knee joint, and a second simulating the knee joint with ruptured anterior cruciate ligament. The dynamic model can be easily processed in real-time. It is implemented in the haptic display of the Munich Knee Joint Simulator (MKS), which enables a person to move a plastic leg driven by a robot manipulator and feel the simulated knee joint force. Orthopaedic physicians judged the performance of the dynamic knee joint model by executing physical knee joint tests at the MKS.

Background: The aim was to determine if effects from smoking on lung function measured over 11 years differ between men and women., Methods: In a prospective population based cohort study (Swiss Study on Air Pollution and Lung Diseases in Adults) current smokers in 1991 (18-60 yrs) were reassessed in 2002 (n = 1792). Multiple linear regression was used to estimate effects from pack-years of cigarettes smoked to 1991 and mean packs of cigarettes smoked per day between 1991 and 2002 on change in lung volume and flows over the 11 years., Results: In both sexes, packs smoked between assessments were related to lung function decline but pack-years smoked before 1991 were not. Mean annual decline in FEV1 was -10.4 mL(95%CI -15.3, -5.5) per pack per day between assessments in men and -13.8 mL(95%CI-19.5,-8.1) in women. Decline per pack per day between 1991 and 2002 was lower in women who smoked in 1991 but quit before 2002 compared to persistent smokers (-6.4 vs -11.6 mL, p = 0.05) but this was not seen in men (-14.3 vs -8.8 mL p = 0.49). Smoking related decline was accelerated in men and women with airway obstruction, particularly in women where decline in FEV1 was three fold higher in participants with FEV1/FVC<0.70 compared to other women (-39.4 vs -12.2 mL/yr per pack per day, p < 0.002)., Conclusion: There are differences in effects from smoking on lung function between men and women. Lung function recovers faster in women quitters than in men. Women current smokers with airway obstruction experience a greater smoking related decline in lung function than men.

Background: There is a controversy about the additional benefit of various supplemental interventions used in clinical practice to further enhance the effectiveness of respiratory rehabilitation in patients with Chronic obstructive pulmonary disease (COPD). The aim of this research was to assess randomised controlled trials (RCTs) testing the additional benefit of supplemental interventions during respiratory rehabilitation in COPD patients., Methods: Systematic review with literature searches in six electronic databases, extensive hand-searching and contacting of authors. Two reviewers selected independently eligible RCTs, rated the methodological quality and extracted the data, which were analyzed considering the minimal important difference of patient-important outcomes where possible., Findings: We identified 20 RCTs whereof 18 provided sufficient data for analysis. The methodological quality was low and sample sizes were too small for most trials to produce meaningful results (median total sample size = 28). Data from five trials showed that supplemental oxygen during exercise did not have clinically meaningful effects on health-related quality of life while improvements of exercise capacity may be even larger for patients exercising on room air. RCTs of adding assisted ventilation, nutritional supplements or a number of anabolically acting drugs do not provide sufficient evidence for or against the use any of these supplemental interventions., Interpretation: There is insufficient evidence for most supplemental interventions during respiratory rehabilitation to estimate their additional value, partly due to methodological shortcomings of included RCTs. Current data do not suggest benefit from supplemental oxygen during exercise, although the methodological quality of included trials limits conclusions. To appropriately assess any of the various supplemental interventions used in clinical practice, pragmatic trials on respiratory rehabilitation of COPD patients need to consider methodological aspects as well as appropriate sample sizes.

Introduction: To provide optimal care for patients with chronic obstructive pulmonary disease physicians need to understand if their patients benefit from an intervention. The objective of this study was to assess agreement between patients and physicians on health-related quality of life (HRQL) changes in response to respiratory rehabilitation and to explore sources for disagreement., Methods: Sixty-one patients rated their health states on a validated preference-based instrument, the feeling thermometer (FT). In an analogous manner, the eight treating physicians rated the patients' health states on the FT. Patients and physicians were blinded to each other's ratings. We calculated intraclass correlation coefficients (ICC) to assess agreement between patients and physicians and used HRQL instruments and the 6-min walking test to assess the evaluative properties of the FT., Results: We found moderate agreement at baseline (ICC 0.40, P = 0.018) and follow-up (ICC 0.49, P = 0.008) but large disagreement about change scores (ICC 0.02, P = 0.46). Patients' FTchange scores correlated well with change scores of the Chronic Respiratory Questionnaire, SF-36 and the Borg scale for dyspnoea whereas physicians' FT change scores correlated significantly with the change score of the 6- min walking test (r = 0.33). Physicians' ratings showed an inconsistent pattern for correlations with HRQL measures., Conclusions: There is large disagreement between patients and physicians on HRQL changes in response to respiratory rehabilitation. Investigators should assess whether the introduction of HRQL instruments into clinical practice raises the awareness of physicians towards HRQL and improves agreement with their patients.

Background: Physical exercise has become a cornerstone of management of chronic obstructive pulmonary disease (COPD) because it leads to clinically relevant improvements of exercise capacity and health-related quality of life (HRQL). Despite the scarcity of randomised trials directly comparing exercise protocols, current guidelines recommend high intensity continuous exercise for lower extremities as the probably most effective exercise modality. However, for patients admitted to inpatient respiratory rehabilitation programmes, it is often difficult to initiate such an exercise programme because they are severely limited by dyspnoea and leg fatigue and therefore unable to perform continuous exercise at higher intensities and for periods longer than 30 minutes. Interval exercise may be an attractive alternative for these COPD patients because it allows high intensity exercise with recovery periods. The aim of this study is to assess if interval exercise compared to high intensity continuous exercise is not of inferior effectiveness in terms of HRQL and exercise capacity improvements but associated with better exercise tolerance in patients with moderate to severe COPD at the beginning of a respiratory rehabilitation., Methods/design: We will assign patients with moderately severe to severe COPD to either continuous exercise or interval exercise using a stratified randomisation. Patients will follow 12-15 exercise sessions during a comprehensive inpatient respiratory rehabilitation. Primary end point for effectiveness is HRQL as measured by the Chronic Respiratory Questionnaire (CRQ) two weeks after the end of rehabilitation and secondary endpoints include additional clinical outcomes such as functional exercise capacity, other HRQL measures, patients' experience of physical exercise as well as physiological measures of the effects of physical exercise such as cardiopulmonary exercise testing. Including expected drop-outs, we will need 52 patients per group to show differences corresponding to the minimal clinically important difference of the CRQ. Outcome assessors and investigators involved in data analysis will be blinded to group assignment until analyses have been carried out., Discussion: Clinicians and the scientific community need evidence on the benefits and tolerance of exercise protocols available in clinical practice. The proposed trial will provide important and needed data on interval and continuous exercise for decision making in clinical practice.

Simulation environments based on virtual reality technologies can support medical education and training. In this paper, the novel approach of an "interactive phantom" is presented that allows a realistic display of haptic contact information typically generated when touching and moving human organs or segments. The key idea of the haptic interface is to attach passive phantom objects to a mechanical actuator. The phantoms look and feel as real anatomical objects. Additional visualization of internal anatomical and physiological information and sound generated during the interaction with the phantom yield a multimodal approach that can increase performance, didactic value, and immersion into the virtual environment. Compared to classical approaches, this multimodal display is convenient to use, provides realistic tactile properties, and can be partly adjusted to different, e.g., pathological properties. The interactive phantom is exemplified by a virtual human knee joint that can support orthopedic education, especially for the training of clinical knee joint evaluation. It is suggested that the technical principle can be transferred to many other fields of medical education and training such as obstetrics and dentistry.

Background: Assessment of health-related quality of life (HRQL) is important in patients with chronic obstructive pulmonary disease (COPD). Despite the high prevalence of COPD in Germany, Switzerland and Austria there is no validated disease-specific instrument available. The objective of this study was to translate the Chronic Respiratory Questionnaire (CRQ), one of the most widely used respiratory HRQL questionnaires, into German, develop an interviewer- and self-administered version including both standardised and individualised dyspnoea questions, and validate these versions in two randomised studies., Methods: We recruited three groups of patients with COPD in Switzerland, Germany and Austria. The 44 patients of the first group completed the CRQ during pilot testing to adapt the CRQ to German-speaking patients. We then recruited 80 patients participating in pulmonary rehabilitation programs to assess internal consistency reliability and cross-sectional validity of the CRQ. The third group consisted of 38 patients with stable COPD without an intervention to assess test-retest reliability. To compare the interviewer- and self-administered versions, we randomised patients in groups 2 and 3 to the interviewer- or self-administered CRQ. Patients completed both the standardised and individualised dyspnoea questions., Results: For both administration formats and all domains, we found good internal consistency reliability (Crohnbach's alpha between 0.73 and 0.89). Cross-sectional validity tended to be better for the standardised compared to the individualised dyspnoea questions and cross-sectional validity was slightly better for the self-administered format. Test-retest reliability was good for both the interviewer-administered CRQ (intraclass correlation coefficients for different domains between 0.81 and 0.95) and the self-administered format (intraclass correlation coefficients between 0.78 and 0.86). Lower within-person variability was responsible for the higher test-retest reliability of the interviewer-administered format while between person variability was similar for both formats., Conclusions: Investigators in German-speaking countries can choose between valid and reliable self-and interviewer-administered CRQ formats.

Force-torque measuring input devices can significantly enhance the performance of classical simulation environments that are, for example, based on pure passive phantoms. Such devices allow not only the determination of force/torque amplitude and direction but also the contact point on the phantom. The force/torque information can be displayed visually or acoustically, drive a realistic graphical animation environment or it can be saved and compared with a haptic library comprising the force/torque history of any medical specialist. In this paper the technical principle is exemplified by an interactive human torso. A plastic phantom model of a human torso is instrumented with a 6-degree-of-freedom force/torque sensor, thus, allowing an intuitive and interactive use for education of human anatomy.

In this paper, we propose a new interactive simulation system for dental treatment training. The system comprises a virtual reality environment and a force-torque measuring device to enhance the capabilities of a passive phantom of tooth anatomy in dental treatment training processes. The measuring device is connected to the phantom, and provides essential input data for generating the graphic animations of physical behaviors such as drilling and bleeding. The animation methods of those physical behaviors are also presented. This system is not only able to enhance interactivity and accessibility of the training system compared to conventional methods but it also provides possibilities of recording, evaluating, and verifying the training results.

Background: Failure to achieve an adequate heart rate limits the sensitivity of exercise myocardial perfusion imaging (MPI) for the detection of coronary artery disease. In addition, it is often not possible to discontinue medications that may blunt the heart rate response to exercise, because of conditions such as hypertension or angina. However, if pharmacologic stress testing is performed, the ability to assess functional capacity is lost. Accordingly, we developed a protocol that incorporates adenosine stress with symptom-limited exercise., Methods and Results: As part of a multicenter study, 35 patients were enrolled prospectively and underwent both exercise MPI and exercise MPI with a 4-minute adenosine infusion on a separate day. Technetium 99m sestamibi was injected at or near peak exercise (exercise only) and at 2 minutes into the adenosine infusion (combined exercise and adenosine). The perfusion images were interpreted in a blinded fashion. The combined adenosine and exercise protocol was well tolerated. The summed stress scores and summed difference scores were greater in the exercise-plus-adenosine group than in the exercise-only group (10.0 vs 8.5, P =.02, and 4.9 vs 3.3, P =.002, respectively). Exercise time was slightly but significantly less with the exercise-plus-adenosine protocol (8 minutes 46 seconds vs 8 minutes 11 seconds, P =.027)., Conclusion: A protocol combining 4 minutes of adenosine infusion with symptom-limited exercise was safe and well tolerated. Furthermore, this protocol resulted in a greater amount of myocardial ischemia detected on MPI while allowing for the assessment of functional capacity. A combined exercise and adenosine protocol may be a useful test for patients undergoing MPI who are unlikely to achieve an adequate chronotropic response.

This paper presents a new force-torque input device that can be used to navigate within any kind of anatomical atlas. As an example, we demonstrate how it can be used to drive a virtual knee joint. The device is comprised by a realistic phantom shank that is attached to a self-made high-sensitive force-torque sensor. It records forces and moments in six degrees-of-freedom and feeds them into a biomechanical model of the knee. Resulting joint movements and sounds are displayed by a visual and acoustic display, respectively. The entire multi-modal simulation environment can provide a better understanding of joint anatomy, e.g. for the education of medical students. Furthermore, it can be a practical tool for resident orthopaedic physicians in order to enhance the consultation, clarification, and treatment planning together with the patient.

Force-torque measuring input devices can significantly enhance the performance of classical simulation environments that are, for example, based on pure passive phantoms. Such devices allow not only the determination of force/torque amplitude and direction but also the contact point, where a torque-free force is applied to the phantom. The force/torque information can be displayed visually or acoustically, drive a realistic graphical animation environment or it can be saved and compared with a haptic library comprising the force/torque history of any medical specialist.

Background: In comparison with treatment with unfractionated heparin (UFH) and aspirin (ASA), both tirofiban administered with UFH and ASA, and enoxaparin plus ASA have shown superiority in reducing cardiac ischemic events in patients with unstable angina and non-ST-segment elevation myocardial infarction. Replacing UFH with enoxaparin when tirofiban is administered to patients may offer further therapeutic benefit, but could also increase bleeding., Objective: Our objective was to provide estimates of the frequency of bleeding complications, as defined by means of the Thrombolysis In Myocardial Infarction(TIMI) group, and collect data on clinical efficacy of the combination of tirofiban with enoxaparin plus ASA., Methods: Five hundred twenty-five patients with UA/NSTEMI were treated with tirofiban coadministered with ASA and randomized to receive either UFH (n = 210) or enoxaparin (n = 315). Therapy was administered for 24 to 96 hours. Bleeding incidences were assessed until 24 hours after trial therapy was discontinued; other clinical outcomes were assessed for as long as 30 days., Results: The total bleeding rate (TIMI major + minor + loss-no-site) for the UFH group versus the enoxaparin group was 4.8% vs 3.5% (odds ratio [OR] 1.4, CI 0.6-3.4). The TIMI major and minor bleeding rates for the UFH versus the enoxaparin groups were 1.0% versus 0.3% (OR 3.0, CI 0.3-33.8) and 4.3% versus 2.5% (OR 1.7, CI 0.7-4.6). There was an increase in nuisance cutaneous and oral bleeds (<50 mL of blood loss) in the enoxaparin group. Death or myocardial infarction occurred with similar frequency in the 2 groups (9.0% vs 9.2%). However, refractory ischemia requiring urgent revascularization and rehospitalization because of unstable angina occurred more frequently in the UFH group (4.3% vs 0.6% and 7.1% vs 1.6%, respectively)., Conclusions: Combination therapy with tirofiban plus enoxaparin appears safe, relative to therapy with tirofiban plus UFH.