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Changes in ventilation-perfusion during and after an COPD exacerbation: an assessment using fluid dynamic modeling.

ABSTRACT: Severe exacerbations associated with chronic obstructive pulmonary disease (COPD) that require hospitalization significantly contribute to morbidity and mortality. Definitions for exacerbations are very broad, and it is unclear whether there is one predominant underlying mechanism that leads to them. Functional respiratory imaging (FRI) with modeling provides detailed information about airway resistance, hyperinflation, and ventilation-perfusion (V/Q) mismatch during and following an acute exacerbation.Forty-two patients with COPD participating in a multicenter study were assessed by FRI, pulmonary function tests, and self-reported outcome measures during an acute exacerbation and following resolution. Arterial blood gasses and lung function parameters were measured.A significant correlation was found between alveolar-arterial gradient and image-based V/Q (iV/Q), suggesting that iV/Q represents V/Q mismatch during an exacerbation (p<0.05).Recovery of an exacerbation is due to decreased (mainly distal) airway resistance (p<0.05). Improvement in patient-reported outcomes were also associated with decreased distal airway resistance (p<0.05), but not with forced expiratory volume. FRI is, therefore, a sensitive tool to describe changes in airway caliber, ventilation, and perfusion during and after exacerbation. On the basis of the fact that FRI increased distal airway resistance seems to be the main cause of an exacerbation, therapy should mainly focus on decreasing it during and after the acute event.

SUBMITTER: Hajian B

PROVIDER: S-EPMC5846311 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Changes in ventilation-perfusion during and after an COPD exacerbation: an assessment using fluid dynamic modeling.

Hajian Bita B De Backer Jan J Vos Wim W van Geffen Wouter H WH De Winter Paul P Usmani Omar O Cahn Tony T Kerstjens Huib Am HA Pistolesi Massimo M De Backer Wilfried W

International journal of chronic obstructive pulmonary disease 20180306

<h4>Introduction</h4>Severe exacerbations associated with chronic obstructive pulmonary disease (COPD) that require hospitalization significantly contribute to morbidity and mortality. Definitions for exacerbations are very broad, and it is unclear whether there is one predominant underlying mechanism that leads to them. Functional respiratory imaging (FRI) with modeling provides detailed information about airway resistance, hyperinflation, and ventilation-perfusion (V/Q) mismatch during and fol ...[more]

PMID: 29563783

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Project description:BACKGROUND:Assessment of fluid responsiveness is problematic in intensive care unit (ICU) patients, in particular for those undergoing modes of partial support, such as pressure support ventilation (PSV). We propose a new test, based on application of a ventilator-generated sigh, to predict fluid responsiveness in ICU patients undergoing PSV. METHODS:This was a prospective bi-centric interventional study conducted in two general ICUs. In 40 critically ill patients with a stable ventilatory PSV pattern and requiring volume expansion (VE), we assessed the variations in arterial systolic pressure (SAP), pulse pressure (PP) and stroke volume index (SVI) consequent to random application of 4-s sighs at three different inspiratory pressures. A radial arterial signal was directed to the MOSTCARE™ pulse contour hemodynamic monitoring system for hemodynamic measurements. Data obtained during sigh tests were recorded beat by beat, while all the hemodynamic parameters were averaged over 30?s for the remaining period of the study protocol. VE consisted of 500?mL of crystalloids over 10?min. A patient was considered a responder if a VE-induced increase in cardiac index (CI)???15% was observed. RESULTS:The slopes for SAP, SVI and PP of were all significantly different between responders and non-responders (p?<?0.0001, p?=?0.0004 and p?<?0.0001, respectively). The AUC of the slope of SAP (0.99; sensitivity 100.0% (79.4-100.0%) and specificity 95.8% (78.8-99.9%) was significantly greater than the AUC for PP (0.91) and SVI (0.83) (p?=?0.04 and 0.009, respectively). The SAP slope best threshold value of the ROC curve was -?4.4° from baseline. The only parameter found to be independently associated with fluid responsiveness among those included in the logistic regression was the slope for SAP (p?=?0.009; odds ratio 0.27 (95% confidence interval (CI95) 0.10-0.70)). The effects produced by the sigh at 35 cmH20 (Sigh35) are significantly different between responders and non-responders. For a 35% reduction in PP from baseline, the AUC was 0.91 (CI95 0.82-0.99), with sensitivity 75.0% and specificity 91.6%. CONCLUSIONS:In a selected ICU population undergoing PSV, analysis of the slope for SAP after the application of three successive sighs and the nadir of PP after Sigh35 reliably predict fluid responsiveness. TRIAL REGISTRATION:Australian New Zealand Clinical Trials Registry, ACTRN12615001232527 . Registered on 10 November 2015.

Project description:BackgroundDemographic and disease characteristics have been associated with the risk of chronic obstructive pulmonary disease (COPD) exacerbations. Using previously collected multinational clinical trial data, we developed models that use baseline risk factors to predict an individual's rate of moderate/severe exacerbations in the next year on various pharmacological treatments for COPD.MethodsExacerbation data from 20,054 patients in the ETHOS, KRONOS, TELOS, SOPHOS, and PINNACLE-1, PINNACLE-2, and PINNACLE-4 studies were pooled. Machine learning was used to identify predictors of moderate/severe exacerbation rates. Important factors were selected for generalized linear modeling, further informed by backward variable selection. An independent test set was held back for validation.ResultsPrior exacerbations, eosinophil count, forced expiratory volume in 1 s percent predicted, prior maintenance treatments, reliever medication use, sex, COPD Assessment Test score, smoking status, and region were significant predictors of exacerbation risk, with response to inhaled corticosteroids (ICSs) increasing with higher eosinophil counts, more prior exacerbations, or additional prior treatments. Model fit was similar in the training and test set. Prediction metrics were ~10% better in the full model than in a simplified model based only on eosinophil count, prior exacerbations, and ICS use.ConclusionThese models predicting rates of moderate/severe exacerbations can be applied to a broad range of patients with COPD in terms of airway obstruction, eosinophil counts, exacerbation history, symptoms, and treatment history. Understanding the relative and absolute risks related to these factors may be useful for clinicians in evaluating the benefit: risk ratio of various treatment decisions for individual patients.Clinical trials registered with www.clinicaltrials.gov (NCT02465567, NCT02497001, NCT02766608, NCT02727660, NCT01854645, NCT01854658, NCT02343458, NCT03262012, NCT02536508, and NCT01970878).

Project description:Global brain states are frequently placed within a unidimensional continuum by correlational studies, ranging from states of deep unconsciousness to ordinary wakefulness. An alternative is their multidimensional and mechanistic characterization in terms of different cognitive capacities, using computational models to reproduce the underlying neural dynamics. We explore this alternative by introducing a semi-empirical model linking regional activation and long-range functional connectivity in the different brain states visited during the natural wake-sleep cycle. Our model combines functional magnetic resonance imaging (fMRI) data, in vivo estimates of structural connectivity, and anatomically-informed priors to constrain the independent variation of regional activation. The best fit to empirical data was achieved using priors based on functionally coherent networks, with the resulting model parameters dividing the cortex into regions presenting opposite dynamical behavior. Frontoparietal regions approached a bifurcation from dynamics at a fixed point governed by noise, while sensorimotor regions approached a bifurcation from oscillatory dynamics. In agreement with human electrophysiological experiments, sleep onset induced subcortical deactivation with low correlation, which was subsequently reversed for deeper stages. Finally, we introduced periodic forcing of variable intensity to simulate external perturbations, and identified the key regions relevant for the recovery of wakefulness from deep sleep. Our model represents sleep as a state with diminished perceptual gating and the latent capacity for global accessibility that is required for rapid arousals. To the extent that the qualitative characterization of local dynamics is exhausted by the dichotomy between unstable and stable behavior, our work highlights how expanding the model parameter space can describe states of consciousness in terms of multiple dimensions with interpretations given by the choice of anatomically-informed priors.

Dataset Information

Changes in ventilation-perfusion during and after an COPD exacerbation: an assessment using fluid dynamic modeling.

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Changes in ventilation-perfusion during and after an COPD exacerbation: an assessment using fluid dynamic modeling.

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