In silico modeling of asthma

Martonen, T. B.; Fleming, John; Schroeter, Jeffrey; Conway, Joy; Hwang, Dongming

doi:10.1016/s0169-409x(03)00080-2

Cited by 56 publications

(33 citation statements)

References 38 publications

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“…The modified airway geometry of asthmatics and COPD patients may influence the fate of the inhaled medication. Martonen et al (2003) have shown that deposition efficiency of the inhaled particles was strongly dependent on the degree of the reduction of airway lumen. The deposited fraction and both regional (Horváth et al, 2011) and local (Farkas et al, 2006; 2007) distribution of the deposited particles changes when the airways are constricted.…”

Section: Resultsmentioning

confidence: 99%

Computer Modelling as a Tool in Characterization and Optimization of Aerosol Drug Delivery

Farkas

Jókay

Füri

et al. 2015

Aerosol Air Qual. Res.

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The number of patients with obstructive airway disease has been increasing worldwide. The delivery of aerosol drugs through the respiratory system has become a central element in the management of asthma and chronic obstructive pulmonary disease (COPD). The aim of this study was to validate and apply a stochastic whole respiratory tract deposition model in order to characterize airway deposition distribution of two different marketed drugs delivered in form of dry powders (Seretide ® Diskus ® and Symbicort ® Turbuhaler, and to analyze the possibility of computerized drug delivery optimization in the future. Spirometry measurements on 17 adult volunteers have been performed. Relationships between breathing parameters measured during diagnostic spirometry and those characterising breathing during drug administration through Diskus ® and Turbuhaler ® inhalers have been derived. The doses deposited in different anatomical regions of the respiratory tract and airway generation number specific deposited doses have been computed for the participating individuals based on both mass median aerodynamic diameter (MMAD) and detailed size distribution of the two drugs. Although regional deposited doses were not very different in the two cases, airway generation number specific deposition distributions were sensitive to this input parameter, indicating the need for the whole size distribution when modelling airway deposition of aerosol drugs. Significant intersubject variability in terms of oropharyngeal, bronchial and acinar deposited doses have been found. The results highlight the necessity for and open the possibility of simulation assisted customized drug selection in the future.

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Section: Resultsmentioning

confidence: 99%

Computer Modelling as a Tool in Characterization and Optimization of Aerosol Drug Delivery

Farkas

Jókay

Füri

et al. 2015

Aerosol Air Qual. Res.

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“…The mathematical calculations and computer simulations performed in this study used the in silico dosimetry model which has evolved through the works of Martonen 7) and Martonen et al 8,9) . The in silico model was tested by comparing its theoretical predictions with in vivo data from the work of Heyder et al 10) .…”

Section: Methodsmentioning

confidence: 99%

Estimation of Particle Deposition in the Airways from Different Inhaler Formulations Using an In Silico Model

Smyth

Martonen²,

Isaacs

et al. 2011

KONA

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“…It eventually leads to modified airflow patterns in the airway lumen, which in turn influence the flight of inhaled particles and their deposition in the different regions of the lungs. Thus, to study the altered behavior of the particles in an asthmatic lung, Martonen et al (105) proposed a mathematical model with the intention of exploring the various factors influencing particle deposition in disease-induced lung model.…”

Section: Application Of In Silico Modeling In Lung Diseasesmentioning

confidence: 99%

“…In this in silico model of particle deposition in asthma, Martonen et al (105) incorporated various changes occurring in human lungs during progression of the disease into a previously developed in silico model of healthy human respiratory system (85,93). In this model, computer codes were developed in such a way that they had immediate applicability to the delivery of inhaled aerosol and could be customized to each patient.…”

Section: Application Of In Silico Modeling In Lung Diseasesmentioning

confidence: 99%

Computational and bioengineered lungs as alternatives to whole animal, isolated organ, and cell-based lung models

Patel

Gauvin

Absar

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Development of lung models for testing a drug substance or delivery system has been an intensive area of research. However, a model that mimics physiological and anatomical features of human lungs is yet to be established. Although in vitro lung models, developed and fine-tuned over the past few decades, were instrumental for the development of many commercially available drugs, they are suboptimal in reproducing the physiological microenvironment and complex anatomy of human lungs. Similarly, intersubject variability and high costs have been major limitations of using animals in the development and discovery of drugs used in the treatment of respiratory disorders. To address the complexity and limitations associated with in vivo and in vitro models, attempts have been made to develop in silico and tissue-engineered lung models that allow incorporation of various mechanical and biological factors that are otherwise difficult to reproduce in conventional cell or organ-based systems. The in silico models utilize the information obtained from in vitro and in vivo models and apply computational algorithms to incorporate multiple physiological parameters that can affect drug deposition, distribution, and disposition upon administration via the lungs. Bioengineered lungs, on the other hand, exhibit significant promise due to recent advances in stem or progenitor cell technologies. However, bioengineered approaches have met with limited success in terms of development of various components of the human respiratory system. In this review, we summarize the approaches used and advancements made toward the development of in silico and tissue-engineered lung models and discuss potential challenges associated with the development and efficacy of these models. bioengineered lung; computational modeling; in silico; lung models; tissue engineering LUNG DISEASES ARE THE THIRD leading cause of deaths in the United States that translate into one in six deaths. More than 400,000 Americans die of lung disease every year and around 35 million are now living with chronic lung problems (1). Therefore, there is an important need to understand as to how a new drug entity or a novel formulation may influence the anatomy, physiology, and pathogenesis of lungs and vice versa.The human lung has an approximate volume of six liters, contains about 300 million alveoli, and provides a total surface area of 100 square meters as blood-air interface, which is packed into an elastic dynamic structure responsible for gas exchange (159). The human airway wall is a connective tissue that includes smooth muscle cells (SMC), mucus glands, blood vessels, and fibroblasts surrounded by a collagen-rich extracellular matrix (ECM). Epithelial cells, responsible for the efficient oxygen and carbon dioxide transfer, are at the interface between air and the connective tissue and are attached to an underlying basement membrane. The respiratory system is the site of a variety of pulmonary diseases such as asthma, bronchitis, pneumonia, cystic fibrosis, emphysema, a...

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In silico modeling of asthma

Cited by 56 publications

References 38 publications

Computer Modelling as a Tool in Characterization and Optimization of Aerosol Drug Delivery

Computer Modelling as a Tool in Characterization and Optimization of Aerosol Drug Delivery

Estimation of Particle Deposition in the Airways from Different Inhaler Formulations Using an In Silico Model

Computational and bioengineered lungs as alternatives to whole animal, isolated organ, and cell-based lung models

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