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preclinical COPD research

Chronic Obstructive Pulmonary Disease​

Chronic obstructive pulmonary disease (COPD) is a term used to refer to a set of chronic lung diseases with pulmonary manifestations (e.g. emphysema, chronic bronchitis, or a combination of both) resulting from exposure to inhaled irritants such as cigarette smoke and environmental pollutants. The pulmonary aspects of COPD typically include characteristic lesions, chronic inflammation, excessive mucus production, and a degree of fixed airflow limitation associated with disease severity. This disease is one of the major causes of morbidity and mortality worldwide. In the clinical setting, physicians rely heavily on spirometry and its outcome parameters (e.g. FEV1 and FVC) for diagnosis and monitoring as well as for the assessment of disease severity, as defined by the GOLD scale. Other lung function measurements, such as pressure-volume curves, forced oscillations, or thoracic imaging, are used in addition to bronchoprovocation tests to establish a diagnosis or evaluate disease progression.

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Comprehensive & integrated assessment

In preclinical COPD research, the challenge is often to link structural changes (e.g. cigarette-smoke induced alveolar destruction) to altered lung function measurements, such as resistance, compliance or spirometry outcomes. The flexiVent is a comprehensive tool allowing an integrated assessment of various disease determinants (e.g. extent and pattern of induced damage) on lung function decline. It measures the mechanical properties of the lungs with high sensitivity and reproducibility. In addition, it reliably evaluates COPD-diseased lungs through pressure-volume curves, changes in lung volume (e.g. inspiratory or forced vital capacities), or forced expiration outcomes, providing clinically relevant information.

References & Publications

Lung fibroblast-derived extracellular vesicles and soluble factors alleviate elastase-induced lung injury. (2024). Van der Koog, L., et al. European Journal of Pharmacology, 974, 176612

Loss of p73 Expression Contributes to Chronic Obstructive Pulmonary Disease. (2024). Richmond, B., et al. AJRCCM, 209(2): https://doi.org/10.1164/rccm.202303-0503OC

Understanding the modulations of glycero-lysophospholipids in an elastase-induced murine emphysema model. (2024). Isago, H., et al. biochemical and Biophysical Research Communications 694: 149419

Identification and experimental validation of PYCARD as a crucial PANoptosis-related gene for immune response and inflammation in COPD. (2024). Shi, R., et al. Apoptosis, https://doi.org/10.1007/s10495-024-01961-6

Ferroptosis-related genes MDM2 and CDKN1A as reliable biomarkers for COPD. (2024). Shi, R., et al. https://doi.org/10.21203/rs.3.rs-4242155/v1

Nebulized platelet-derived extracellular vesicles attenuate chronic cigarette smoke-induced murine emphysema. (2024). Xuan, W., et al. Translational Research, 269: 76-93

A Comparative Study of the Effects of Electronic Cigarette and Traditional Cigarette on the Pulmonary Functions of C57BL/6 Male Mice. (2024). Zhao, H.Z., et al. Nicotine & Tobacco Research, 26(4): 474-483

Inhibition of oxidative stress by apocynin attenuated chronic obstructive pulmonary disease progression and vascular injury by cigarette smoke exposure. (2023). Chan, S.M.H., et al. BJP, 180(5): 2018-2034

Regorafenib prevents the development of emphysema in a murine elastase model. (2023). Oh, K., et al. BMB Reports, 56(8): 439-444

Characterization of a spontaneous mouse model of mild, accelerated aging via ECM degradation in emphysematous lungs. (2023). Tanino, R., et al. Scientific Reports, 13: 10740

Therapeutic effect of two strategies directed at disruption of pathogenic neutrophil extracellular vesicles in a murine emphysema model. (2023). Genschmer, K.R., et al. Lung Cellular & Molecular Physiology, 325(5): 694-699

Respiratory mechanics following chronic cigarette smoke exposure in the Apoe mouse model. (2023). Matz, J., et al. Biomechanics and Modeling in Mechanobiology, 22: 233-252

RIPK1 kinase-dependent inflammation and cell death contribute to the pathogenesis of COPD. (2023). Van Eeckhoutte, H.P.V. et al. ERJ, 61(4) 2201506; DOI: 10.1183/13993003.01506-20

Compact, reproducible, automated

The inExpose is a compact, computer-controlled system and can integrate with several smoke generation devices and adapters to suit a wide range of specific smoke applications. Its low internal volume allows desired concentrations to be reached with minimal tobacco/cannabis/e-liquid quantities. The pumps are specifically designed to deliver standard and customized puff profiles. Industry standards such as the commonly used ISO standard or the Canadian puffing profiles are often used to generate COPD models.

Smoke composition will be influenced by a number of technical factors. For example, the constituents of smoke will differ whether the smoke is drawn from side-stream, main-stream, or environmental tobacco smoke. Different brands of cigarettes, water filtered smoke (hookah), cigars, or e-cigarette constituents and flavourings will result in different smoke compositions. In addition, the choice of the puff profile will influence cigarette yields. It is therefore important, when studying the impacts of smoke, to consistently and reproducibly be able to introduce the same smoke composition at each experimental session.

To date, this versatility and programmability of the inExpose system has been employed in a variety of exposure studies, both in vivo and in vitro, to evaluate the effects of smoke.

References & Publications

Novel DNA methylation changes in mouse lungs associated with chronic smoking. (2024). Onuzulu, C.D., et al. Epigenetics, 19(1), https://doi.org/10.1080/15592294.2024.2322386

Vaping-Dependent Pulmonary Inflammation Is Ca2+ Mediated and Potentially Sex Specific. (2024). Shipman, J.G., et al. Int j Mol Sci, 25(3), 1785; https://doi.org/10.3390/ijms25031785

Respiratory mechanics following chronic cigarette smoke exposure in the Apoe mouse model. (2023). Matz, J., et al. Biomechanics and Modeling in Mechanobiology, 22: 233-252

Involvement of Parkin-mediated mitophagy in the pathogenesis of chronic obstructive pulmonary disease-related sarcopenia. (2022). Ito, A., et al. Journal of Cachexia, Sarcopenia and Muscle, 13(3): 1864-1882

Impaired TRIM16-Mediated Lysophagy in Chronic Obstructive Pulmonary Disease Pathogenesis. (2021). Araya, J., et al. Journal of Immunology, 207(1): 65-67

Electronic Cigarette Exposure Enhances Lung Inflammatory and Fibrotic Responses in COPD Mice. (2021). Han, H., et al. Front Pharmacol, https://doi.org/10.3389/fphar.2021.726586

Angiotensin-converting enzyme 2 expression in COPD and IPF fibroblasts: the forgotten cell in COVID-19. (2021). Aloufi, N., et al. Lung Cellular and Molecular Physiology, 320(1): 152-157

Interventional low-dose azithromycin attenuates cigarette smoke-induced emphysema and lung inflammation in mice. (2020). Macowan, M.G., et al. Physiological Reports, 8(13): e14419

Protective effect of selegiline on cigarette smoke-induced oxidative stress and inflammation in rat lungs in vivo. (2020). Cui, Y., et al. Ann Transl Med, 8(21): 1418

Endothelial HIF-2α as a Key Endogenous Mediator Preventing Emphysema. (2020). Pasupneti, S., et al. American Journal of Respiratory and Critical Care Medicine, 202(7): 32515984

Symptom screening

Symptoms of COPD include dyspnea, chronic cough, and chronic sputum production. Plethysmography, as a non-invasive technique, offers a powerful means of rapidly screening subjects based on changes in ventilatory parameters (e.g. breathing frequency, tidal volume, peak inspiratory or expiratory flows). Events such as coughing can also be detected and monitored.

References & Publications

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