Pathology of COPD and Asthma

Baraldo, Simonetta; Cazzuffi, Riccardo; Bazzan, Erica; Luppi, Fabrizio; Turato, Graziella; Saetta, Marina

doi:10.1007/978-88-470-5647-3_3

Cited by 2 publications

(2 citation statements)

References 68 publications

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“…Asthma is a chronic inflammatory disease of the airways in which many different innate and adaptive cells of the immune system act together with epithelial cells to promote excessive mucus production, airway wall remodeling, smooth muscle thickening and lumen narrowing (Lambrecht and Hammad, 2015), in addition to bronchial hyperresponsiveness, characterized as an increase in airway smooth muscle sensitivity and responsiveness to bronchoconstrictors (Baraldo et al, 2014) as well as a decrease in response to bronchodilator stimuli (Brehm et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

A Guinea Pig Model of Airway Smooth Muscle Hyperreactivity Induced by Chronic Allergic Lung Inflammation: Contribution of Epithelium and Oxidative Stress

Lhc

Mdcc

et al. 2019

Front. Pharmacol.

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Asthma is a heterogeneous disease of the airways characterized by chronic inflammation associated with bronchial and smooth muscle hyperresponsiveness. Currently, different murine models for the study of asthma show poor bronchial hyperresponsiveness due to a scarcity of smooth muscle and large airways, resulting in a failure to reproduce smooth muscle hyperreactivity. Thus, we aimed to standardize a guinea pig model of chronic allergic lung inflammation mimicking airway smooth muscle hyperreactivity observed in asthmatics (Asth). Animals were randomly divided into a control group (Ctrl), which received saline (0.9% NaCl), and the Asth group, subjected to in vivo sensitization with ovalbumin (OVA) nebulization. Morphological analysis was performed by hematoxylin-eosin staining. Bronchial hyperresponsiveness was evaluated by nebulization time in the fifth, sixth, and seventh inhalations (NT5-7) and tracheal isometric contractions were assessed by force transducer. Total antioxidant capacity was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method and protein expression by Western blot. Histologically, the Asth group developed peribronchial cellular infiltrate, epithelial hyperplasia and smooth muscle thickening. After the fourth nebulization, the Asth group developed bronchial hyperreactivity. The trachea from the Asth group contracted after in vitro stimulation with OVA, differing from the Ctrl group, which showed no response. Additionally, airway smooth muscle hyperreactivity to carbachol and histamine was observed in the Asth group only in intact epithelium preparations, but not to KCl, and this effect was associated with an augmented production of reactive oxygen species. Moreover, lung inflammation impaired the relaxant potency of isoproterenol only in intact epithelium preparations, without interfering with nifedipine, and it was found to be produced by transforming growth factor-β negative modulation of β adrenergic receptors and, furthermore, big-conductance Ca 2+ -sensitive K + channels. These effects were also associated with increased levels of phosphatidylinositol 3-kinases but not extracellular signal-regulated kinases 1/2 or phosphorylation, and augmented α-actin content as well, explaining the increased smooth muscle mass. Furthermore, pulmonary antioxidant capacity was impaired in the Asth group. Therefore, we developed a standardized and easy-to-use, reproducible guinea pig model of lung inflammation that mimics airway smooth muscle hypercontractility, facilitating the investigation of the mechanisms of bronchial hyperresponsiveness in asthma and new therapeutic alternatives.

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Section: Introductionmentioning

confidence: 99%

A Guinea Pig Model of Airway Smooth Muscle Hyperreactivity Induced by Chronic Allergic Lung Inflammation: Contribution of Epithelium and Oxidative Stress

Lhc

Mdcc

et al. 2019

Front. Pharmacol.

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“…This model is widely used in textbooks to describe lung physiology but neglects critical spatial and temporal variation in lung function, which in many cases may be drivers for disease response. [44][45][46] In most cases, this simple description of the lung is considered too simple to adequately describe physiology (see Hahn and Farmery 43 for a critical review of this approach), and so, lung modellers have increasingly focussed on adding more physiological and anatomical complexities. In this review, we do not aim to describe all models of respiratory function that exist, rather we will focus on examples which illustrate the evolution of modelling in the field and which have moved or attempted to move towards increasing clinical applicability.…”

Section: Functional Models Of the Respiratory Systemmentioning

confidence: 99%

Capturing complexity in pulmonary system modelling

Clark

Kumar

Burrowes

2017

Proc Inst Mech Eng H

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Respiratory disease is a significant problem worldwide, and it is a problem with increasing prevalence. Pathology in the upper airways and lung is very difficult to diagnose and treat, as response to disease is often heterogeneous across patients. Computational models have long been used to help understand respiratory function, and these models have evolved alongside increases in the resolution of medical imaging and increased capability of functional imaging, advances in biological knowledge, mathematical techniques and computational power. The benefits of increasingly complex and realistic geometric and biophysical models of the respiratory system are that they are able to capture heterogeneity in patient response to disease and predict emergent function across spatial scales from the delicate alveolar structures to the whole organ level. However, with increasing complexity, models become harder to solve and in some cases harder to validate, which can reduce their impact clinically. Here, we review the evolution of complexity in computational models of the respiratory system, including successes in translation of models into the clinical arena. We also highlight major challenges in modelling the respiratory system, while making use of the evolving functional data that are available for model parameterisation and testing.

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Pathology of COPD and Asthma

Cited by 2 publications

References 68 publications

A Guinea Pig Model of Airway Smooth Muscle Hyperreactivity Induced by Chronic Allergic Lung Inflammation: Contribution of Epithelium and Oxidative Stress

A Guinea Pig Model of Airway Smooth Muscle Hyperreactivity Induced by Chronic Allergic Lung Inflammation: Contribution of Epithelium and Oxidative Stress

Capturing complexity in pulmonary system modelling

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