Flow analyses in the lower airways: Patient-specific model and boundary conditions

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, p¼0.009). 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.

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“…More details on the segmentation and CFD principles can be found in previously published studies. (7)(8)(9)(10)19) …”

Section: Image Post-processingmentioning

confidence: 99%

“…CFD yields total pressure drops and airflow, the resistance is ratio between the two. More information can be found in De Backer et al (19) Lobar volumes at functional residual capacity (iVlobes_ FRC). Lobar volumes at total lung capacity (iVlobes_TLC).…”

Section: Assessmentsmentioning

confidence: 99%

The Effects of Extrafine Beclometasone/Formoterol (BDP/F) on Lung Function, Dyspnea, Hyperinflation, and Airway Geometry in COPD Patients: Novel Insight Using Functional Respiratory Imaging

Backer

Vos²,

Vinchurkar³

et al. 2015

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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“…The challenge is to develop mathematical models that realistically reflect the respiratory physiology of the animal by accurately simulating its fluid flow conditions. These models comprise of accurate geometrical representations of the airway structures and realistic boundary conditions which drive the flow (De Backer et al, 2007b). The CFD method and these models can assist in the development of new inhalation therapies and the optimization of inhaler devices (Coates et al, 2007;Kleinstreuer et al, 2007).…”

mentioning

confidence: 99%

Study of the Variability in Upper and Lower Airway Morphology in Sprague–Dawley Rats Using Modern Micro‐CT Scan‐Based Segmentation Techniques

Backer

Vos

Burnell

et al. 2009

The Anatomical Record

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Animal models are being used extensively in pre-clinical and safety assessment studies to assess the effectiveness and safety of new chemical entities and delivery systems. Although never entirely replacing the need for animal testing, the use of computer simulations could eventually reduce the amount of animals needed for research purposes and refine the data acquired from the animal studies. Computational fluid dynamics is a powerful tool that makes it possible to simulate flow and particle behavior in animal or patient-specific respiratory models, for purposes of inhaled delivery. This tool requires an accurate representation of the respiratory system, respiration and dose delivery attributes. The aim of this study is to develop a representative airway model of the Sprague-Dawley rat using static and dynamic micro-CT scans. The entire respiratory tract was modeled, from the snout and nares down to the central airways at the point where no distinction could be made between intraluminal air and the surrounding tissue. For the selection of the representative model, variables such as upper airway movement, segmentation length, airway volume and size are taken into account. Dynamic scans of the nostril region were used to illustrate the characteristic morphology of this region in anaesthetized animals. It could be concluded from this study that it was possible to construct a highly detailed representative model of a Sprague-Dawley rat based on imaging modalities such as micro-CT scans.

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“…Functional respiratory imaging (FRI) has added functionality to CT data by means of computational fluid dynamics (CFD) airflow calculations [9,10]. FRI has been used in different settings and populations [11][12][13].…”

Section: Estimation Of Post-operative Forced Expiratory Volume By Funmentioning

confidence: 99%

Estimation of post-operative forced expiratory volume by functional respiratory imaging

et al. 2014

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Flow analyses in the lower airways: Patient-specific model and boundary conditions

Cited by 94 publications

References 28 publications

The Effects of Extrafine Beclometasone/Formoterol (BDP/F) on Lung Function, Dyspnea, Hyperinflation, and Airway Geometry in COPD Patients: Novel Insight Using Functional Respiratory Imaging

The Effects of Extrafine Beclometasone/Formoterol (BDP/F) on Lung Function, Dyspnea, Hyperinflation, and Airway Geometry in COPD Patients: Novel Insight Using Functional Respiratory Imaging

Study of the Variability in Upper and Lower Airway Morphology in Sprague–Dawley Rats Using Modern Micro‐CT Scan‐Based Segmentation Techniques

Estimation of post-operative forced expiratory volume by functional respiratory imaging

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