Techniques & Measurements
This page lists techniques and measurements employed by the flexiVent system and used primarily in the area of measuring respiratory mechanics.
DID YOU KNOW?
The flexiVent was the first commercial device to measure respiratory mechanics using the forced oscillation technique in animals.
FORCED OSCILLATION TECHNIQUE (FOT)
The forced oscillation technique allows for a highly detailed and reproducible assessment of lung function in subjects from neonate mice to humans. This technique consists of applying an oscillatory waveform to the subject’s airways opening and measuring the pressure, flow and volume signals resulting from the subject’s response to the applied waveform. These signals can then be fit to various models in order to gain insight into subject’s lung mechanics.
DID YOU KNOW?
Resistance and compliance are the most commonly reported outcomes when assessing lung function.
SINGLE FREQUENCY FOT (RESISTANCE AND COMPLIANCE)
In a single frequency forced oscillation manoeuvre, the subject’s response to a sinusoidal waveform is studied. The resulting pressure, flow and volume signals are fit to the single compartment model using linear regression and total respiratory system resistance, elastance and compliance are obtained.
Resistance (R): dynamic resistance quantitatively assesses the level of constriction in the lungs.
Elastance (E): elastance captures the elastic stiffness of the respiratory system at the ventilation frequency. If measured under closed-chest conditions, it includes a contribution from the lung, the chest walls, and the airways. Elastance is the reciprocal of compliance and vice versa.
Compliance (C): compliance (also known as dynamic compliance) describes the ease with which the respiratory system can be extended. In a subject with intact chest walls, it provides a characterisation of the overall elastic properties that the respiratory system needs to overcome during tidal breathing to move air in and out of the lungs.
Coefficient of determination (COD): quality control parameter measuring the quality of the single compartment model fit.
DID YOU KNOW?
Although the broadband forced oscillation manoeuvre may look like random noise during execution, it is in fact a precisely constructed signal that contains specific frequencies relevant to the subject being studied.
BROADBAND FOT (PARTITIONED RESPIRATORY MECHANICS)
Also referred to as the low-frequency forced oscillation technique, a broadband forced oscillation manoeuvre measures the subject’s response to a signal containing a wide range of frequencies both below and above the subject’s breathing frequency. The outcome, respiratory system input impedance (Zrs), is the most detailed assessment of respiratory mechanics currently available.
Input impedance can be further analyzed using the Constant Phase Model (CPM), introduced by Hantos et al., to obtain a parametric distinction between airway and tissue mechanics. This distinction is invaluable to obtain an accurate understanding of how diseases affect lungs.
Input Impedance (Zrs): the combined effects of resistance, compliance and inertance as a function of frequency.
Newtonian resistance (Rn): parameter of the CPM which represents the resistance of the central or conducting airways.
Tissue damping (G): parameter of the CPM closely related to tissue resistance and reflects the energy dissipation in the alveoli.
Tissue elastance (H): parameter of the CPM closely related to tissue elastance and reflects the energy conservation in the alveoli.
Coefficient of determination (COD): quality control parameter measuring the quality of the constant phase model fit.
DID YOU KNOW?
There is a progressive loss in lung volume due to airway closure during mechanical ventilation, which can be recovered through Deep Inflation manoeuvers.
RECRUITMENT THROUGH DEEP INFLATION
The deep inflation gradually inflates the subject’s lungs to a total lung capacity state, defined as a pressure of 30 cmH2O, and then holds to allow the alveolar pressure to equilibrate.
The manoeuvre is useful to open closed lung areas, restore airway patency, or normalize the volume in the lung. The initial and end volumes are used in the calculation of the inspiratory capacity (IC).
Estimate of Inspiratory Capacity (IC): amount of air that can be inhaled after the end of a normal expiration.
- The allergic mouse model of asthma: normal smooth muscle in an abnormal lung? – Wagers S, Lundblad LK, Ekman M, Irvin CG, Bates JH. 2004. J Appl Physiol 96: 2019-27.
- Combined forced oscillation and forced expiration measurements in mice for the assessment of airway hyperresponsiveness. – Shalaby KH, Gold LG, Schuessler TF, Martin JG, Robichaud A. 2010. Respir Res 11: 82.
Pressure-volume (PV) loops capture the quasi-static mechanical properties of the respiratory system. The Salazar-Knowles equation (SKE) can be fit to the expiratory branch of the PV loop, and quasi-static elastance and compliance values can be calculated.
A: estimate of inspiratory capacity. The parameter A of the Salazar-Knowles equation is an upper bounds estimate of the difference between total lung capacity and zero volume.
B: the parameter B of the Salazar-Knowles equation is an estimate of the difference between the volume at total lung capacity and the predicted volume at zero pressure.
Note: The volume at zero pressure can only be obtained by extrapolating the SKE model fit, as a measurement at zero pressure is only possible if the lungs are fully degassed. While the SKE describes the upper portion of the PV loop, it deviates significantly at zero pressure, therefore B is a theoretical parameter and should not be interpreted physiologically or reported.
K: curvature of the upper portion of the deflation limb of the PV curve. This shape parameter has been shown to change with different chronic disease models.
Cst: quasi-static compliance is a classic parameter extracted from a PV curve. If measured under closed-chest conditions, it reflects the intrinsic elastic properties of the respiratory system (i.e. lung+chest wall) at rest.
Area: the area enclosed by the pressure volume loop provides an estimate of the amount of atelectasis (airspace closure) that existed before the PV loop manoeuvre.
DID YOU KNOW?
This is just one of the translational outcomes the flexiVent offers to help correlate clinical and preclinical research.
FORCED EXPIRED MANOEUVRE
Forced expirations attempt to mimic clinical spirometry in preclinical research. This is achieved by rapidly exposing the subjects airway opening to a negative pressure and measuring the expired flow.
Forced Expired Volume (FEVx): the volume expired during the first x seconds of a forced expiration, is indicative of obstructive airway disease and increased expiratory flow limitation.
Forced Expired Flow (FEFx): the expiratory flow calculated at a specific time or volume fraction into a forced expiration.
Forced Vital Capacity (FVC): is the total volume expired during a forced expiration, is typically reduced in many lung diseases.
Peak Expiratory Flow (PEF): the highest expiratory flow achieved during a forced expiration.
Learn more on how to obtain these measurements with the FEV extension.
The flexiVent is now capable of providing more measurements of lung volumes. In addition to measuring inspiratory capacity (IC) and forced vital capacity (FVC), the flexiVent now includes measurements of the total and residual lung volumes (TLC/RV). As with other techniques, this is done using a computer-controlled automated manoeuvre for standardization and control of parameters.
The acquisition of these new outcomes does not require the use of a separate device and can easily be preceded by comprehensive respiratory mechanics measurements typically performed with the flexiVent. Lung volume changes are sensitive to physiological or pathophysiological changes.
Please contact SCIREQ technical support should you be interested in obtaining other lung volumes.
DID YOU KNOW?
For the average mouse, only 10% of the generated aerosol gets delivered to its airways.
Dose response challenges delivering a bronchoconstrictor are commonly used for assessing airway hyperresponsiveness. Typically reported against concentration, these dose response curves are greatly influenced by protocol variations. In order to allow for comparable and reproducible results, flexiWare software now generates an estimate of the dose delivered to the subject’s airways during an inhaled challenge. This characterization of the nebulizer offers standardization by taking into account rainout, ventilation patterns, aerosol rates and other variables that can alter the dose delivered. Researchers can now easily and accurately compare results across subjects, groups, studies and even other labs.
In unrestrained whole-body plethysmography (UWP), a spontaneously breathing animal moves freely within a small, closed plethysmograph chamber. Depending on the chamber design, box pressure or flow in and out of the box are measured. Additional temperature and humidity sensors may be used to partly compensate thermodynamic effects in the chamber. UWP analyzers typically provide measurements of respiratory rate (RR) and estimates of tidal volume (Vt) and minute ventilation (RMV), as well as a dimensionless quantity known as enhanced pause (Penh).
On one hand, UWP is an extremely non-invasive technique for testing conscious, unrestrained subjects. However, the quality and detail is limited; only respiratory rate can be measured reliably under a wide range of circumstances, while tidal volume estimates and the controversial Penh parameter are only qualitative and/or valid under a limited range of experimental conditions.
- Measuring lung function in mice: the phenotyping uncertainty principle – Bates JH, Irvin CG. J Appl Physiol 94: 1297-1306, 2003.
- Issues determining direct airways hyperresponsiveness in mice – Lundblad, LK. Front. Physiol., 21 October 2012 | doi: 10.3389/fphys.2012.00408
- SCIREQ APPLICATION NOTE – FLEXIVENT VS. UNRESTRAINED WHOLE-BODY-PLETHYSMOGRAPHY