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Learn more about preclinical fEV in Drug Discovery

Spirometry

Respiratory diseases pose substantial challenges to global public health, necessitating a comprehensive understanding of their underlying mechanisms and potential therapeutic interventions. As researchers strive to bridge the gap between preclinical investigations and clinical outcomes, the accurate assessment of Forced Expired Volume (FEV) and Forced Vital Capacity (FVC) emerges as a cornerstone for establishing translational relevance.

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About the FEV Extension

The forced expiration extension (FEV) extension is a hardware add-on that allows the study of expiratory flow limitations, analogous to spirometry, a widely known clinical pulmonary test measuring volumes and flows expired by patients that is used to confirm a diagnostic of respiratory disease or follow treatment. The FEV extension permits the generation of flow-volume loops and its associated parameters by rapidly exposing the subject’s airway opening to negative pressure, referred to as Negative Pressure Forced Expirations (NPFE). The NPFEs can be interspersed with all other flexiVent measurements, uniquely combining the forced expiratory and forced oscillation measurements into a single platform.

NPFE Manoeuvre

During the NPFE manoeuvre, the subject is inflated to total lung capacity (TLC) state and then rapidly switched to a negative pressure reservoir to essentially draw the air out of its lungs. The FEV extension’s outcomes include flow-volume loops, peak expiratory flow (PEF), forced vital capacity (FVC), forced expired volumes (FEVx) and flows (FEFx) at user-defined times are automatically displayed/ calculated by the software.

Available for Mice, rats and ferrets

The FEV extension readily connects to most existing flexiVent systems for use in mice, rats and ferrets. It includes a plethysmograph chamber with an integrated sensor to measure chest flow, a negative pressure reservoir with its controller, and two additional valves. Upon completion of the NPFE, the flexiWare software immediately displays flow-volume loops and automatically calculates all pertinent volume and flow parameters (FEVx, FEFx, FVC, PEF).

Towards Clinical Studies

The addition of FEV offers a means to more directly assess expiratory flow limitation. Although NPFE manoeuvres are obtained under conditions that differ substantially from clinical spirometry, they may provide a useful cross-species correlation for drug development studies. A recent publication by Devos et al, characterized forced expiration measurements in some well-established mouse models of lung diseases, which specific phenotypes were confirmed by a concomitant respiratory mechanics assessment. The researchers observed that disease-induced changes in forced expiration-related charts and parameters were generally similar to what was observed in the clinic. For example, when compared to a control group of healthy mice.

  • Mice with fibrosis exhibited a typical restrictive profile, with a reduced PEF & FVC and a normal FEV0.1/FVC ratio.
  • Mice with emphysema displayed a decrease in PEF characteristic of an obstructive phenotype.
  • Mice presenting an acute lung injury had significantly reduced PEF.
  • Mice with features of asthma showed a decrease in FEV0.1 following methacholine challenges.

Resources

Publications

Asthma
Pulmonary Fibrosis
Emphysema
Pollutant Exposure
Cigarette, E-cigarette & IQOS
Cystic Fibrosis
Infectious Disease
Bronchopulmonary Dysplasia
Other

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