Interactive, Visual Simulation of a Spatio-Temporal Model of Gas Exchange in the Human Alveolus.

In interdisciplinary fields such as systems biology, good communication between experimentalists and theorists is crucial for the success of a project. Theoretical modeling in physiology usually describes complex systems with many interdependencies. On one hand, these models have to be grounded on experimental data. On the other hand, experimenters must be able to understand the interdependent complexities of the theoretical model in order to interpret the model's results in the physiological context. We promote interactive, visual simulations as an engaging way to present theoretical models in physiology and to make complex processes tangible. Based on a requirements analysis, we developed a new model for gas exchange in the human alveolus in combination with an interactive simulation software named Alvin. Alvin exceeds the current standard with its spatio-temporal resolution and a combination of visual and quantitative feedback. In Alvin, the course of the simulation can be traced in a three-dimensional rendering of an alveolus and dynamic plots. The user can interact by configuring essential model parameters. Alvin allows to run and compare multiple simulation instances simultaneously. We exemplified the use of Alvin for research by identifying unknown dependencies in published experimental data. Employing a detailed questionnaire, we showed the benefits of Alvin for education. We postulate that interactive, visual simulation of theoretical models, as we have implemented with Alvin on respiratory processes in the alveolus, can be of great help for communication between specialists and thereby advancing research.

Quality of life is associated with physical activity and fitness in cystic fibrosis.

BACKGROUND: Health-related and disease-specific quality of life (HRQoL) has been increasingly valued as relevant clinical parameter in cystic fibrosis (CF) clinical care and clinical trials. HRQoL measures should assess - among other domains - daily functioning from a patient's perspective. However, validation studies for the most frequently used HRQoL questionnaire in CF, the Cystic Fibrosis Questionnaire (CFQ), have not included measures of physical activity or fitness. The objective of this study was, therefore, to determine the cross-sectional and longitudinal relationships between HRQoL, physical activity and fitness in patients with CF. METHODS: Baseline (n = 76) and 6-month follow-up data (n = 70) from patients with CF (age ≥12 years, FEV1 ≥35%) were analysed. Patients participated in two multi-centre exercise intervention studies with identical assessment methodology. Outcome variables included HRQoL (German revised multi-dimensional disease-specific CFQ (CFQ-R)), body composition, pulmonary function, physical activity, short-term muscle power, and aerobic fitness by peak oxygen uptake and aerobic power. RESULTS: Peak oxygen uptake was positively related to 7 of 13 HRQoL scales cross-sectionally (r = 0.30-0.46). Muscle power (r = 0.25-0.32) and peak aerobic power (r = 0.24-0.35) were positively related to 4 scales each, and reported physical activity to 1 scale (r = 0.29). Changes in HRQoL-scores were directly and significantly related to changes in reported activity (r = 0.35-0.39), peak aerobic power (r = 0.31-0.34), and peak oxygen uptake (r = 0.26-0.37) in 3 scales each. Established associates of HRQoL such as FEV1 or body mass index correlated positively with fewer scales (all 0.24 < r < 0.55). CONCLUSIONS: HRQoL was associated with physical fitness, especially aerobic fitness, and to a lesser extent with reported physical activity. These findings underline the importance of physical fitness for HRQoL in CF and provide an additional rationale for exercise testing in this population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00231686.

Predictors for future cystic fibrosis-related diabetes by oral glucose tolerance test.

BACKGROUND: An annual oral glucose tolerance test (OGTT) has become part of standard care in cystic fibrosis (CF) to screen for CF-related diabetes (CFRD). The objective of this study was to determine predictors for future CFRD derived from an OGTT. METHODS: Data were collected from 2001 to 2009 during a longitudinal prospective study on "Early Diagnosis of Diabetes Mellitus in CF Patients, trial number NCT00662714". The 1093 patients included in the analysis had at least two valid OGTTs each and no CFRD at the first glucose challenge. Normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and CFRD were defined using WHO criteria. In a subsample of 521 patients, the NGT group was further divided into patients with a 1-hour glucose level >11.1 mmol/l (indeterminate glucose tolerance -- INDET) and those with a lower level (no-INDET). Logistic regression analysis was used to identify predictors from the first OGTT for future diabetes. RESULTS: Compared with NGT (n = 838), IFG (n = 70; odds ratio [OR], 95% confidence interval: 2.92, 1.60-5.33) and IGT without IFG (n = 155, OR 2.37, 1.48-3.79) were both significant and independent risk factors for future CFRD. Patients with IGT and IFG (n = 30) had the highest risk (OR 5.30, 2.32-12.10). In the subsample analysis, INDET (n = 116) was associated with a significantly increased risk for future CFRD compared with no-INDET (n = 269; OR 2.81, 1.43-5.51). CONCLUSIONS: In this large study, IFT, IGT, and INDET were all predictors of future CFRD. The OGTT in patients with CF should include a 1-hour post-challenge value.