Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2014
Abstract Background: The efficacy of inhaled corticosteroids (ICS) in moderately severe COPD pati... more Abstract Background: The efficacy of inhaled corticosteroids (ICS) in moderately severe COPD patients remains unclear. At the same time, the use of extrafine particles in COPD patients is a topic of ongoing research. Objectives: This study assessed the effect of ICS in steroid-naïve mild COPD patients and the effect of reducing the ICS dose in more severe COPD patients previously using ICS when switching to an extrafine particle BDP/F formulation (Foster using Modulite technology, Chiesi Pharmaceutici, Parma, Italy). Methods: Novel functional respiratory imaging (FRI) methods, consisting of multi-slice CT scans and Computational Fluid Dynamics, were used in combination with conventional pulmonary function tests and patient reported outcomes. Results: The study showed that the administration of extrafine BDP/F after 4-6 h led to a significant improvement in lung function parameters and hyperinflation as determined by spirometry, body plethysmography, and functional respiratory imaging. After 6 months of treatment, it was observed that, compared to baseline, the hyperinflation on lobar level at total lung capacity was significantly reduced (-1.19±7.19 %p, p=0.009). In addition, a significant improvement in SGRQ symptom score was noted in the entire patient population. Patients who improved in terms of hyperinflation also improved their MMRC dyspnea score. CFD indicated a difference in regional deposition between extrafine and non-extrafine formulations with -11% extrathoracic deposition and up to +4% lobe deposition for the extrafine formulation. Conclusions: The study showed that the administration of extrafine BDP/F improved lung function parameters and hyperinflation. Patients previously treated with ICS remained stable despite the lower dose, while ICS naïve patients improved in terms of lobar hyperinflation. FRI seems to be a sensitive biomarker to detect clinically relevant changes that are not detected by spirometry. The next step is to confirm these findings in a controlled trial.
... (Street Level), Colorado Convention Center Proposition Of A Method To Measure Lobar Airway Re... more ... (Street Level), Colorado Convention Center Proposition Of A Method To Measure Lobar Airway Resistance And Lobar Tissue Stiffness Using Functional Imaging , W. Vos , S. Vinchurkar , D. Daems , L. De Backer , WA De Backer J. De Backer1 2 3 4 4 5 ...
ABSTRACT To the Editor:Recently, roflumilast has been added as a therapeutic option for chronic o... more ABSTRACT To the Editor:Recently, roflumilast has been added as a therapeutic option for chronic obstructive pulmonary disease (COPD). Roflumilast is a selective phosphodiesterase type 4 (PDE4) inhibitor (1). The main concern of the large-scale studies performed was that they did not assess the effect of roflumilast in addition to a combination product such as long-acting β2-agonists (LABA) or long-acting muscarinic agents (LAMA) combined with inhaled corticosteroids (ICS) (2). A novel technology called functional respiratory imaging (FRI) defines, in great detail, lung geometry and regional changes in airway volume and resistance (3-5). By assessing changes close to the site of action of the intervention, the method is more sensitive (higher effect size) compared with standard pulmonary function tests (PFT) (3). This implies that the mode of action of an intervention can be assessed in a small number of patients, while maintaining sufficient power to have statistically significant results (3-4). We performed a study aimed at investigating the mode of action of roflumilast in COPD patients on top of triple therapy (LABA/LAMA/ICS), using PFT, exercise tolerance tests, patient-reported outcomes (PRO) and FRI. The hypothesis was that roflumilast provides a large benefit to a subset of COPD patients and that FRI can assist in.
B107. OUTCOME MEASURES TO ASSESS PEDIATRIC LUNG HEALTH, 2010
University Hospital Antwerp, Edegem, Belgium, FluidDA nv, Edegem, Belgium, Antwerp University Hos... more University Hospital Antwerp, Edegem, Belgium, FluidDA nv, Edegem, Belgium, Antwerp University Hospital, Edegem, Belgium 1 ... Lung function tests (LFT's) are used traditionally as a reliable measure for monitoring the progression of cystic fibrosis (CF) lung disease. FEV1 has ...
Inhaled formulations using extrafine particles of long-acting β2-agonists and corticosteroids wer... more Inhaled formulations using extrafine particles of long-acting β2-agonists and corticosteroids were developed to optimize asthma treatment. Findings that these combinations reach and treat smaller airways more effectively are predominantly based on general non-specific outcomes with little information on regional characteristics. This study aims to assess long-term effects of extrafine beclomethasone/formoterol on small airways of asthmatic patients using novel functional imaging methods. Twenty-four stable asthma patients were subdivided into three groups (steroid naive, n = 7; partially controlled, n = 6; well controlled, n = 11). Current treatment was switched to a fixed combination of extrafine beclomethasone/formoterol (Foster®; Chiesi Pharmaceuticals, Parma, Italy). Patients underwent lung function evaluation and thorax high-resolution computerized tomography (HRCT) scan. Local airway resistance was obtained from computational fluid dynamics (CFD). After 6 months, the entire population showed improvement in pre-bronchodilation imaging parameters, including small airway volume (p = 0.0007), resistance (p = 0.011), and asthma control score (p = 0.016). Changes in small airway volume correlated with changes in asthma control score (p = 0.004). Forced expiratory volume in 1 s (p = 0.044) and exhaled nitric oxide (p = 0.040) also improved. Functional imaging provided more detail and clinical relevance compared to lung function tests, especially in the well-controlled group where only functional imaging parameters showed significant improvement, while the correlation with asthma control score remained. Extrafine beclomethasone/formoterol results in a significant reduction of small airway obstruction, detectable by functional imaging (HRCT/CFD). Changes in imaging parameters correlated significantly with clinically relevant improvements. This indicates that functional imaging is a useful tool for sensitive assessment of changes in the respiratory system after asthma treatment.
A number of computational fluid dynamics (CFD) studies have explored local deposition patterns of... more A number of computational fluid dynamics (CFD) studies have explored local deposition patterns of inhaled aerosols in the respiratory tract. These studies have highlighted the effects of multiple physiologic, geometric, and particle characteristics on deposition. However, very few studies have reported local or sub-branch quantitative comparisons to in vitro particle deposition data. The objective of this study is to numerically investigate the effects of transition and turbulence on highly localized particle deposition in a respiratory double bifurcation model in order to quantitatively validate CFD results. To perform the validations, local comparisons have been made to a specific in vitro case study of 10 microm particles depositing in a model of respiratory generations G3-G5. To achieve this objective, two geometric cases have been considered. The first case includes only the double bifurcation model. The second case includes a portion of the experimental particle delivery geometry, where transitional flow is expected. To evaluate the effectiveness of two-equation turbulence models in this system, the flow field solutions have been computed using laminar, standard k-omega, and low Reynolds number (LRN) k-omega approximations. Results indicate that even though the Reynolds number remained below the critical limit required for full turbulence, transition and turbulence have a significant impact on the flow field and local particle deposition patterns. For the experimental case considered, turbulence impacted the local deposition of 10 microm particles primarily by influencing the initial velocity and particle profiles. As such, both the laminar and LRN k-omega flow models provided good local quantitative matches to the in vitro deposition data, provided that the correct initial particle profile was specified. Implications of this study include the need for local quantitative validations of particle deposition results, the importance of correct inlet conditions, and the need to consider upstream effects in experimental and computational studies of the respiratory tract. Applications of these results to realistic respiratory geometries will require consideration on upstream flow conditions in the lung, transient flow, and intermittent turbulent structures.
Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2014
Abstract Background: The efficacy of inhaled corticosteroids (ICS) in moderately severe COPD pati... more Abstract Background: The efficacy of inhaled corticosteroids (ICS) in moderately severe COPD patients remains unclear. At the same time, the use of extrafine particles in COPD patients is a topic of ongoing research. Objectives: This study assessed the effect of ICS in steroid-naïve mild COPD patients and the effect of reducing the ICS dose in more severe COPD patients previously using ICS when switching to an extrafine particle BDP/F formulation (Foster using Modulite technology, Chiesi Pharmaceutici, Parma, Italy). Methods: Novel functional respiratory imaging (FRI) methods, consisting of multi-slice CT scans and Computational Fluid Dynamics, were used in combination with conventional pulmonary function tests and patient reported outcomes. Results: The study showed that the administration of extrafine BDP/F after 4-6 h led to a significant improvement in lung function parameters and hyperinflation as determined by spirometry, body plethysmography, and functional respiratory imaging. After 6 months of treatment, it was observed that, compared to baseline, the hyperinflation on lobar level at total lung capacity was significantly reduced (-1.19±7.19 %p, p=0.009). In addition, a significant improvement in SGRQ symptom score was noted in the entire patient population. Patients who improved in terms of hyperinflation also improved their MMRC dyspnea score. CFD indicated a difference in regional deposition between extrafine and non-extrafine formulations with -11% extrathoracic deposition and up to +4% lobe deposition for the extrafine formulation. Conclusions: The study showed that the administration of extrafine BDP/F improved lung function parameters and hyperinflation. Patients previously treated with ICS remained stable despite the lower dose, while ICS naïve patients improved in terms of lobar hyperinflation. FRI seems to be a sensitive biomarker to detect clinically relevant changes that are not detected by spirometry. The next step is to confirm these findings in a controlled trial.
... (Street Level), Colorado Convention Center Proposition Of A Method To Measure Lobar Airway Re... more ... (Street Level), Colorado Convention Center Proposition Of A Method To Measure Lobar Airway Resistance And Lobar Tissue Stiffness Using Functional Imaging , W. Vos , S. Vinchurkar , D. Daems , L. De Backer , WA De Backer J. De Backer1 2 3 4 4 5 ...
ABSTRACT To the Editor:Recently, roflumilast has been added as a therapeutic option for chronic o... more ABSTRACT To the Editor:Recently, roflumilast has been added as a therapeutic option for chronic obstructive pulmonary disease (COPD). Roflumilast is a selective phosphodiesterase type 4 (PDE4) inhibitor (1). The main concern of the large-scale studies performed was that they did not assess the effect of roflumilast in addition to a combination product such as long-acting β2-agonists (LABA) or long-acting muscarinic agents (LAMA) combined with inhaled corticosteroids (ICS) (2). A novel technology called functional respiratory imaging (FRI) defines, in great detail, lung geometry and regional changes in airway volume and resistance (3-5). By assessing changes close to the site of action of the intervention, the method is more sensitive (higher effect size) compared with standard pulmonary function tests (PFT) (3). This implies that the mode of action of an intervention can be assessed in a small number of patients, while maintaining sufficient power to have statistically significant results (3-4). We performed a study aimed at investigating the mode of action of roflumilast in COPD patients on top of triple therapy (LABA/LAMA/ICS), using PFT, exercise tolerance tests, patient-reported outcomes (PRO) and FRI. The hypothesis was that roflumilast provides a large benefit to a subset of COPD patients and that FRI can assist in.
B107. OUTCOME MEASURES TO ASSESS PEDIATRIC LUNG HEALTH, 2010
University Hospital Antwerp, Edegem, Belgium, FluidDA nv, Edegem, Belgium, Antwerp University Hos... more University Hospital Antwerp, Edegem, Belgium, FluidDA nv, Edegem, Belgium, Antwerp University Hospital, Edegem, Belgium 1 ... Lung function tests (LFT's) are used traditionally as a reliable measure for monitoring the progression of cystic fibrosis (CF) lung disease. FEV1 has ...
Inhaled formulations using extrafine particles of long-acting β2-agonists and corticosteroids wer... more Inhaled formulations using extrafine particles of long-acting β2-agonists and corticosteroids were developed to optimize asthma treatment. Findings that these combinations reach and treat smaller airways more effectively are predominantly based on general non-specific outcomes with little information on regional characteristics. This study aims to assess long-term effects of extrafine beclomethasone/formoterol on small airways of asthmatic patients using novel functional imaging methods. Twenty-four stable asthma patients were subdivided into three groups (steroid naive, n = 7; partially controlled, n = 6; well controlled, n = 11). Current treatment was switched to a fixed combination of extrafine beclomethasone/formoterol (Foster®; Chiesi Pharmaceuticals, Parma, Italy). Patients underwent lung function evaluation and thorax high-resolution computerized tomography (HRCT) scan. Local airway resistance was obtained from computational fluid dynamics (CFD). After 6 months, the entire population showed improvement in pre-bronchodilation imaging parameters, including small airway volume (p = 0.0007), resistance (p = 0.011), and asthma control score (p = 0.016). Changes in small airway volume correlated with changes in asthma control score (p = 0.004). Forced expiratory volume in 1 s (p = 0.044) and exhaled nitric oxide (p = 0.040) also improved. Functional imaging provided more detail and clinical relevance compared to lung function tests, especially in the well-controlled group where only functional imaging parameters showed significant improvement, while the correlation with asthma control score remained. Extrafine beclomethasone/formoterol results in a significant reduction of small airway obstruction, detectable by functional imaging (HRCT/CFD). Changes in imaging parameters correlated significantly with clinically relevant improvements. This indicates that functional imaging is a useful tool for sensitive assessment of changes in the respiratory system after asthma treatment.
A number of computational fluid dynamics (CFD) studies have explored local deposition patterns of... more A number of computational fluid dynamics (CFD) studies have explored local deposition patterns of inhaled aerosols in the respiratory tract. These studies have highlighted the effects of multiple physiologic, geometric, and particle characteristics on deposition. However, very few studies have reported local or sub-branch quantitative comparisons to in vitro particle deposition data. The objective of this study is to numerically investigate the effects of transition and turbulence on highly localized particle deposition in a respiratory double bifurcation model in order to quantitatively validate CFD results. To perform the validations, local comparisons have been made to a specific in vitro case study of 10 microm particles depositing in a model of respiratory generations G3-G5. To achieve this objective, two geometric cases have been considered. The first case includes only the double bifurcation model. The second case includes a portion of the experimental particle delivery geometry, where transitional flow is expected. To evaluate the effectiveness of two-equation turbulence models in this system, the flow field solutions have been computed using laminar, standard k-omega, and low Reynolds number (LRN) k-omega approximations. Results indicate that even though the Reynolds number remained below the critical limit required for full turbulence, transition and turbulence have a significant impact on the flow field and local particle deposition patterns. For the experimental case considered, turbulence impacted the local deposition of 10 microm particles primarily by influencing the initial velocity and particle profiles. As such, both the laminar and LRN k-omega flow models provided good local quantitative matches to the in vitro deposition data, provided that the correct initial particle profile was specified. Implications of this study include the need for local quantitative validations of particle deposition results, the importance of correct inlet conditions, and the need to consider upstream effects in experimental and computational studies of the respiratory tract. Applications of these results to realistic respiratory geometries will require consideration on upstream flow conditions in the lung, transient flow, and intermittent turbulent structures.
Uploads
Papers by Samir Vinchurkar