The presence of excess scar tissue in the lungs is a typical characteristic of pulmonary fibrosis, a disease with a poor prognosis and response to current therapies. The build-up of fibrotic tissue associated with lung injury leads to an irreversible reduction of the elastic properties of the lungs and a gradual decline in lung function.
Experimental research in this area aims to increase knowledge of the underlying pathophysiological mechanisms associated with disease manifestation and progression while attempting to address the challenges of therapeutic intervention and early disease detection.
As a result of the fibrotic tissue accumulation, the lungs become stiffer. In humans, the disease is typically diagnosed using computed tomography (CT) scans and pulmonary function tests, both of which can be performed in small laboratory animals using the flexiVent. The ability of this integrated system to synchronize with micro-CT scanners, to provide static and dynamic measurements of respiratory mechanics, as well as to capture information on specific lung volumes or flows make it an extremely valuable tool to investigate pulmonary fibrosis at the preclinical level. As an example, changes in static compliance, acquired using the sensitive pressure-volume curves, allowed researchers to distinguish between degrees of disease severity or therapeutic efficacy. Furthermore, the flexiVent system’s Negative Pressure Forced Expiration (NPFE) extension offers additional insight by permitting outcomes similar to those commonly used in a clinical setting, such as the forced vital capacity (FVC).
Finally, the longitudinal aspect of the disease or the efficacy of a potential therapeutic approach over time can now be more easily assessed with the flexiVent since the recent publication of simple techniques of non-surgical subject integration to the system. Numerous examples of the use of the flexiVent in pulmonary fibrosis preclinical research can be found in the literature. Learn how a leading pulmonary fibrosis researcher uses the flexiVent in this interview.
The induced changes in lung parenchyma observed in preclinical models of pulmonary fibrosis are likely to result in impaired breathing patterns, which can be captured repeatedly in conscious spontaneously breathing subjects using one of the various plethysmography techniques (e.g. whole body plethysmography, double-chamber plethysmography, head-out plethysmography).
The lung parenchyma, like the airway smooth muscle, possesses contractile properties and can also be studied in vitro in isolated tissue baths. In pulmonary fibrosis, the accumulation of fibrotic tissue can potentially alter the contractility of the lung parenchyma. Studying this tissue in the absence of external influences can offer additional insights when exploring pathophysiological mechanisms, characterizing preclinical disease models, or assessing the efficacy of a potential therapeutic treatment. In response to a constricting agent, increased contractility has been consistently observed in lung parenchymal from a fibrotic model relative to a corresponding control group.
Dr. Karmouty-Quintana is a PI at the University of Texas Health Science Center. His lab studies the mechanisms behind vascular remodeling and fibrosis as well as pulmonary hypertension associated with chronic lung diseases. Learn more about his work and get his thoughts on the current state and future of preclincial pulmonary fibrosis research
Pre-clinical pulmonary fibrosis model selection requires an assessment of the most appropriate model for the recapitulation of the fibrosis form under study, balanced with considerations around the advantages and disadvantages of each particular model. Read more about the advantages, and disadvantages of common small animal fibrosis models.
The flexiVent’s ability to synchronize with micro-CT scanners, provide static & dynamic measurements of respiratory mechanics, & capture information on specific lung volumes or flows make it an extremely valuable tool to investigate pulmonary fibrosis. This short video covers how the flexiVent can advance pulmonary fibrosis research.
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