Asthma and COPD have a number of similarities and differences.
Purpose - To compare lobar lung ventilation computed from expiratory and inspiratory computed tomographic (CT) data with direct measurements of ventilation at hyperpolarized helium 3 (3He) magnetic resonance (MR) imaging by using same-breath hydrogen 1 (1H) MR imaging examinations to coregister the multimodality images.
Modern medicine therapies tend to generate and rely on an immense amount of data that are usually produced by CT, MRI and other imaging techniques as well as genetic data coming from NGS sequencing. In order to plan a patientspecific therapy these data need to be efficiently analyzed and interpreted per individual subject. The EU-founded AirPROM project (Airway Disease Predicting Outcomes through Patient Specific Computational Modeling) is a prime example of joint cooperation that aims to develop tools to predict the progression of selected diseases and response to treatment in the area of respiratory medicine. This would not be possible without support of computer science methods. In particular, a lot of effort has been spent to integrate different software tools and present them to specialists in a form of one unified system that may be used without in depth ICT knowledge. This paper presents selected tools and techniques used to achieve this goal.
Gaining an understanding of a system as complex as the respiratory system is difficult if not impossible via experimental methods alone. Computational models offer a powerful complementary method to unravel the structure-function relationships occurring within a multi-scale, multi-physics system such as this.
In previous work we have demonstrated that functional respiratory imaging (FRI) is more sensitive than the classic pulmonary function tests (PFT) with regards to the evaluation of treatment of respiratory diseases [De Backer et al, ERJ 2012;40:298-305; Vos et al, ERS 2010].
We sought to investigate the bronchial submucosal DP2 expression in asthmatic patients and healthy control subjects and to explore its functional role in epithelial cells.
The analysis of high-resolution computed tomography (CT) images of the lung is dependent on inter-subject differences in airway geometry. The application of computational models in understanding the significance of these differences has previously been shown to be a useful tool in biomedical research. Studies using image-based geometries alone are limited to the analysis of the central airways, down to generation 6–10, as other airways are not visible on high-resolution CT. However, airways distal to this, often termed the small airways, are known to play a crucial role in common airway diseases such as asthma and chronic obstructive pulmonary disease (COPD).
Complex flow patterns exist within the asymmetric branching airway network in the lungs. These flow patterns are known to become increasingly heterogeneous during disease as a result of various mechanisms such as bronchoconstriction or alterations in lung tissue compliance. Here, we present a coupled model of tissue deformation and network airflow enabling predictions of dynamic flow properties, including temporal flow rate, pressure distribution, and the occurrence of reverse flows. We created two patient-specific airway geometries, one for a healthy subject and one for a severe asthmatic subject, derived using a combination of high-resolution CT data and a volume-filling branching algorithm. In addition, we created virtually constricted airway geometry by reducing the airway radii of the healthy subject model.
The chronic lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are common affecting over 500 million people worldwide and causing substantial morbidity and mortality. Asthma is typically associated with Th2-mediated eosinophilic airway inflammation, in contrast to neutrophilic inflammation observed commonly in COPD. However, there is increasing evidence that the eosinophil might play an important role in 10-40% of patients with COPD. Consistently in both asthma and COPD a sputum eosinophilia is associated with a good response to corticosteroid therapy and tailored strategies aimed to normalize sputum eosinophils reduce exacerbation frequency and severity. Advances in our understanding of the multistep paradigm of eosinophil recruitment to the airway, and the consequence of eosinophilic inflammation, has led to the development of new therapies to target these molecular pathways. In this article we discuss the mechanisms of eosinophilic trafficking, the tools to assess eosinophilic airway inflammation in asthma and COPD during stable disease and exacerbations and review current and novel anti-eosinophilic treatments.
Direct, non-invasive measurement of airflow distribution in the airways could help in understanding airflow in obstructive lung diseases and in predicting the particle and aerosol deposition process in inhaled therapy research.
There is a paucity of studies comparing asthma and chronic obstructive pulmonary disease (COPD) based on thoracic quantitative computed tomographic (QCT) parameters. We sought to compare QCT parameters of airway remodeling, air trapping, and emphysema between asthmatic patients and patients with COPD and explore their relationship with airflow limitation.
Human airway smooth muscle (HASM) contraction plays a central role in regulating airway resistance in both healthy and asthmatic bronchioles. In vitro studies that investigate the intricate mechanisms that regulate this contractile process are predominantly conducted on tissue culture plastic, a rigid, 2D geometry, unlike the 3D microenvironment smooth muscle cells are exposed to in situ. It is increasingly apparent that cellular characteristics and responses are altered between cells cultured on 2D substrates compared with 3D topographies. Electrospinning is an attractive method to produce 3D topographies for cell culturing as the fibers produced have dimensions within the nanometer range, similar to cells' natural environment. We have developed an electrospun scaffold using the nondegradable, nontoxic, polymer polyethylene terephthalate (PET) composed of uniaxially orientated nanofibers and have evaluated this topography's effect on HASM cell adhesion, alignment, and morphology. The fibers orientation provided contact guidance enabling the formation of fully aligned sheets of smooth muscle. Moreover, smooth muscle cells cultured on the scaffold present an elongated cell phenotype with altered contractile protein levels and distribution. HASM cells cultured on this scaffold responded to the bronchoconstrictor bradykinin. The platform presented provides a novel in vitro model that promotes airway smooth muscle cell development toward a more in vivo-like phenotype while providing topological cues to ensure full cell alignment.
Multiple breath inert gas washout (MBW) is a technique for detecting abnormal ventilation distribution in patients with asthma and other airway diseases.
