W. Vos

Functional imaging using computer methods to compare the effect of salbutamol and ipratropium bromide in patient-specific airway models of COPD

Background Salbutamol and ipratropium bromide improve lung function in patients with chronic obstructive pulmonary disease (COPD). However, their bronchodilating effect has not yet been compared in the central and distal airways. Functional imaging using computational fluid dynamics offers the possibility of making such a comparison. The objective of this study was to assess the effects of salbutamol and ipratropium bromide on the geometry and computational fluid dynamics-based resistance of the central and distal airways. Methods Five patients with Global Initiative for Chronic Obstructive Lung Disease Stage III COPD were randomized to a single dose of salbutamol or ipratropium bromide in a crossover manner with a 1-week interval between treatments. Patients underwent lung function testing and a multislice computed tomography scan of the thorax that was used for functional imaging. Two hours after dosing, the patients again underwent lung function tests and repeat computed tomography. Results Lung function parameters, including forced expiratory volume in 1 second, vital capacity, overall airway resistance, and specific airway resistance, changed significantly after administration of each product. On functional imaging, the bronchodilating effect was greater in the distal airways, with a corresponding drop in airway resistance, compared with the central airways. Salbutamol and ipratropium bromide were equally effective at first glance when looking at lung function tests, but when viewed in more detail with functional imaging, hyporesponsiveness could be shown for salbutamol in one patient. Salbutamol was more effective in the other patients. Conclusion This pilot study gives an innovative insight into the modes of action of salbutamol and ipratropium bromide in patients with COPD, using the new techniques of functional imaging and computational fluid dynamics.

Functional respiratory imaging as a tool to assess upper airway patency in children with obstructive sleep apnea.

OBJECTIVEnWe aim to investigate if anatomical and functional properties of the upper airway using computerized 3D models derived from computed tomography (CT) scans better predict obstructive sleep apnea (OSA) severity than standard clinical markers.nnnMETHODSnConsecutive children with suspected OSA underwent polysomnography, clinical assessment of upper airway patency, and a CT scan while awake. A three-dimensional (3D) reconstruction of the pharyngeal airway was built from these images, and computational fluid dynamics modeling of low inspiratory flow was performed using open-source software.nnnRESULTSnThirty-three children were included (23 boys; mean age, was 6.0±3.2y). OSA was diagnosed in 23 patients. Children with OSA had a significantly lower volume of the overlap region between tonsils and the adenoids (median volume, 1408 mm compared to 2173 mm; p=0.04), a lower mean cross-sectional area at this location (median volume, 69.3mm(2) compared to 114.3mm2; p=0.04), and a lower minimal cross-sectional area (median volume, 17.9 mm2 compared to 25.9 mm2; p=0.05). Various significant correlations were found between several imaging parameters and the severity of OSA, most pronounced for upper airway conductance (r=-0.46) (p<0.01) for correlation between upper airway conductance and the apnea-hypopnea index. No differences or significant correlations were observed with clinical parameters of upper airway patency. Preliminary data after treatment showed that none of the patients with residual OSA had their smallest cross-sectional area located in segment 3, and this frequency was significantly lower than in their peers whose sleep study normalized (64%; p=0.05).nnnCONCLUSIONnFunctional imaging parameters are highly correlated with OSA severity and are a more powerful correlate than clinical scores of upper airway patency. Preliminary data also showed that we could identify differences in the upper airway of those subjects who did not benefit from a local upper airway treatment.

Assessment of lung deposition and analysis of the effect of fluticasone/salmeterol hydrofluoroalkane (HFA) pressurized metered dose inhaler (pMDI) in stable persistent asthma patients using functional respiratory imaging

ABSTRACT Background: Unambiguously for inhaled products, PK measures are best suited for ensuring that the total systemic exposure is equivalent for two products but cannot provide regional information about lung deposition and structural changes. Functional respiratory imaging (FRI) has been demonstrated to be sensitive for distinguishing small but imperative differences related to a single treatment. Methods: In this study FRI is used in 16 asthmatic patients to assess equivalence in regional deposition for two products (fluticasone/salmeterol, test and reference) by directly measuring regional functional and structural changes within the lungs following its administration. Results: No differences were observed between the lung deposition patterns and the effects on lung structure and function of two products, having the same formulation and manufactured by different organizations using FRI. Conclusions: Results using FRI complement PK assessments. The added value of this approach to the conventional clinical methods could be significant.

196 Airway surface liquid concentrations of aztreonam lysine for inhalation in children with cystic fibrosis: A modelling study

Introduction nnThe mechanics of inhaled antibiotics in obstructed airways are not well known. It is possible that local areas with concentration below the minimal inhibitory concentration (10xMIC90, 128µg/ml for P. Aeruginosa) exist, causing undertreated parts of the lung. To optimize inhaled therapy, knowledge about antibiotic concentrations throughout the lung should be known. Local deposition characteristics of inhaled Aztreonam lysine (AZLI) were simulated using Functional Respiratory Imaging.nnMethods nnAirways and lungs were segmented from a retrospective dataset of 40 in- and expiratory CT-scans of children with cystic fibrosis (CF) between 5 and 17 years. FRI simulations were performed that simulated the nebulisation of 75mg AZLI through PARI eFlow® with minimal/median/maximal reported aerodynamic diameters (MMAD) and different thicknesses of airway surface liquid (ASL). Figure 1 shows local concentrations in the central airways and lung.nn![Figure][1] nnnnResults nnIn Figure 2, it is shown how many lobes are being undertreated.nn![Figure][1] nnnnConclusion nnParts of the CF-lung receive concentrations < 10xMIC90 with inhaled antibiotics, such as AZLI.nn [1]: pending:yes

Functional respiratory imaging, regional strain, and expiratory time constants at three levels of positive end expiratory pressure in an ex vivo pig model

Heterogeneity in regional end expiratory lung volume (EELV) may lead to variations in regional strain (ε). High ε levels have been associated with ventilator‐associated lung injury (VALI). While both whole lung and regional EELV may be affected by changes in positive end‐expiratory pressure (PEEP), regional variations are not revealed by conventional respiratory system measurements. Differential rates of deflation of adjacent lung units due to regional variation in expiratory time constants (τE) may create localized regions of ε that are significantly greater than implied by whole lung measures. We used functional respiratory imaging (FRI) in an ex vivo porcine lung model to: (i) demonstrate that computed tomography (CT)‐based imaging studies can be used to assess global and regional values of ε and τE and, (ii) demonstrate that the manipulation of PEEP will cause measurable changes in total and regional ε and τE values. Our study provides three insights into lung mechanics. First, image‐based measurements reveal egional variation that cannot be detected by traditional methods such as spirometry. Second, the manipulation of PEEP causes global and regional changes in R, E, ε and τE values. Finally, regional ε and τE were correlated in several lobes, suggesting the possibility that regional τE could be used as a surrogate marker for regional ε.

179* Analysis of local flow and resistance in the lower airways in five children suffering from cystic fibrosis using computational fluid dynamics

179* Analysis of local flow and resistance in the lower airways in five children suffering from cystic fibrosis using computational fluid dynamics W. Vos1, J. De Backer1, S. Verhulst3, K. Desager2, W. De Backer1. 1Pulmonology, University Hospital Antwerp, Antwerp, Belgium; 2CF clinic, Pediatrics, University Hospital Antwerp, Antwerp, Belgium; 3Pediatrics, University Hospital Antwerp, Antwerp, Belgium Five children (13±3.6 y) suffering from CF are being studied using a novel functional imaging method. The aim is to understand the consequences of bronchiectasies on the airflow mechanics in the lower airways. High resolution low radiation dose CT scans of all 5 patients at total lung capacity have been taken to visualize the amount of airway deformation. Through 3D reconstruction, a better idea of the actual extent, impact and location of these deformations could be obtained. The 3D models could be made functional by means of computational fluid dynamics (CFD) techniques. CFD simulates flow behavior throughout the airways based on the Navier-Stokes equations. Very local flow characteristics such as intraluminal pressure and velocities could be obtained. From these it is possible to calculate airway resistance (RAW). RAW provides an indication of the dynamic capabilities of the respiratory system. First analyses showed that bronchiectasies increase RAW, thereby affecting the lung function. Regions with high RAW in the table correspond with inflamated regions in the 3D model. The technique is believed to provide a deeper insight in the CF problematic towards respiratory effort. Future work will investigate local changes (structural and functional) after treatment.