WO2012058767A1

WO2012058767A1 - Apparatus for lung function assessment in conscious subjects

Info

Publication number: WO2012058767A1
Application number: PCT/CA2011/001237
Authority: WO
Inventors: Thomas Florian Schuessler; Anette Robichaud; Liah Anahita Fereydoonzad; Ilan Benjamin Urovitch
Original assignee: Scireq Scientific Respiratory Equipment Inc.
Priority date: 2010-11-02
Filing date: 2011-11-02
Publication date: 2012-05-10

Abstract

Apparatus for the measurement of lung function in laboratory animals as used in pre¬ clinical medical and pharmacological research. The apparatus comprises a conduit, at least one controllable flow generator generating a combination of a net flow of gas through the conduit and an oscillatory flow, at least one subject site being adapted to accommodate the at least one laboratory animal, the subject site comprising a breathing zone with an inlet and an outlet, the inlet being connected to the conduit to allow gas from the at least one flow generator to be delivered to the laboratory animal and a chest wall displacement measurement system connected to the at least one subject site to measure chest wall displacement of the at least one laboratory animal. Also disclosed is a sealing assembly for isolation at least one of a front subject chamber and a rear subject chamber.

Description

APPARATUS FOR LUNG FUNCTION

ASSESSMENT IN CONSCIOUS SUBJECTS

FIELD OF THE INVENTION

The present invention relates to a scientific apparatus for the measurement of lung function in laboratory animals as used in pre-clinical medical and pharmacological research. The present invention also relates to a sealing assembly for isolation of at least one of a front subject chamber and a rear subject chamber.

BACKGROUND OF THE INVENTION

There is currently a variety of documented apparatuses and methods to assess lung function in conscious laboratory animals including, without limitation, mice, rats, guinea pigs, rabbits and primates. Most of these techniques rely on passive observation of a subject, e.g. by placing the subject in a plethysmograph chamber and recording and analyzing the pressure waveform within the chamber that ensues as a result of the subject's breathing. Such measurements are obtained under comparatively non-invasive circumstances, but they commonly lack measurement detail and suffer from poor sensitivity, specificity and signal-to-noise ratios.

One published technique that goes beyond passive observation places the subject in a double chamber plethysmograph with a neck or nose seal, such that the animal breathes from a first chamber while its thorax and lower body are located in the second chamber. A loudspeaker is used to impose a high-frequency forced oscillatory pressure on the subject's chest wall, and the resulting flow is measured at the mouth. In this context, high-frequency means that the frequencies of oscillation exceed the range of frequencies contained in the power spectrum of the subject's spontaneous breathing, so that the imposed oscillation components of the recorded signals can be readily separated from spontaneous breathing components by means of Fourier analysis. Transfer impedance is calculated from the oscillation data as the ratio of pressure at the chest wall and flow at the airway opening, and a variety of parametric models may be fit to the transfer impedance for further analysis and interpretation.

Measurements of transfer impedance as described above suffer from several limitations. First, they require separate oscillators for each subject, resulting in comparatively high equipment cost and potentially introducing variability between the subjects and/or limiting study design. Second, experimental conditions such as the mean inflation pressure of the lungs throughout the measurement, cannot be controlled, standardized or modulated. Third, the frequencies of measurement are limited to high frequencies, therefore the measurement does not include the scientifically and diagnostically pertinent range around the subject's typical breathing frequency. Experiments in anaesthetized, mechanically ventilated animals using the Low-frequency Forced Oscillation Technique (LFOT) have shown i) that the control and modulation of mean inflation pressure is critical to providing reproducible measurements and gaining additional insights into lung function, and ii) that measurements of respiratory system input impedance spanning low to high frequencies permit a reliable and highly useful separation of respiratory mechanics into airway and tissue compartments. Unfortunately, high-frequency transfer impedance measurements do not possess sufficient information to reliably and quantitatively evaluate the tissue compartment. Consequently, there is a need for an improved system and method for lung function assessment that i) facilitates the acquisition of high-frequency transfer impedance data in laboratory animals, ii) permits controlled modulation of the mean airway opening pressure during the measurements, and iii) combines the measurement advantages of the LFOT with the non-invasiveness of transfer impedance measurements to improve pre-clinical lung function assessment in conscious subjects.

SUMMARY OF THE INVENTION

An object of the present invention is to propose a system and method that satisfies at least one of the above-mentioned needs. According to the present invention, that object is accomplished with a setup that overcomes the limitations described above, permitting lung function assessment in conscious subjects over an extended frequency range with controlled mean airway opening pressure and requiring only one single oscillatory flow generator for multiple parallel subjects.

According to the present invention, there is provided an apparatus for lung function assessment of at least one conscious laboratory animal comprising:

- a conduit;

- at least one controllable flow generator generating a combination of a net flow of gas through the conduit and an oscillatory flow;

- at least one subject site being adapted to accommodate the at least one laboratory animal, the subject site comprising a breathing zone with an inlet and an outlet, the inlet being connected to the conduit to allow gas from the at least one flow generator to be delivered to the at least one laboratory animal; and

- at least one chest wall displacement measurement system connected to the at least one subject site to measure chest wall displacement of the at least one laboratory animal.

Preferably, in one embodiment of the present invention, the at least one flow generator comprises first and second flow generators, the second flow generator inducing net flow through the conduit and the at least one subject site, and the first flow generator applying only oscillatory flow components to the breathing zone.

Preferably, in one embodiment of the present invention, the at least one flow generator comprises:

-a cylinder having a cylinder outlet;

-a piston positioned within said cylinder; and

-an actuator for displacing the piston within the cylinder.

Preferably, in one embodiment of the present invention, the at least one flow generator further comprises:

-a gas intake port connected in parallel with the cylinder outlet to the conduit; and -a gas intake valve for controlling flow from the gas intake port.

Preferably, in one embodiment of the present invention, the at least one flow source further comprises a conduit valve downstream of the parallel connection between the gas intake port and the cylinder outlet, for controlling flow through the conduit.

Preferably, in one embodiment of the present invention, the conduit valve and the gas intake valve are configurable to open the conduit valve and to close the gas intake valve during a forward stroke of the piston and to close the conduit valve and to open the gas intake valve during a retraction of the piston to fill the cylinder with gas from a gas intake source.

Preferably, in one embodiment of the present invention, the actuator is configurable to displace the piston through an oscillatory motion. Preferably, in another embodiment of the present invention, the apparatus comprises at least two subject sites connected in parallel to the conduit.

Preferably, in one embodiment of the present invention, each subject site further comprises:

-a front chamber connected to the inlet and the outlet; and

-at least one rear subject chamber; and

-at least one sealing assembly connecting the front chamber to the at least one rear subject chamber.

Preferably, in one embodiment of the present invention, the outlet of each subject site is fitted with an exhaust conduit having an impedance sufficiently high to prevent shunting of the oscillatory flow and sufficiently low to avoid excessive pressurization of the subject site.

Preferably, in one embodiment of the present invention, the outlet of each subject site is fitted with an exhaust conduit having an exhaust conduit control valve to control flow therethrough, wherein the conduit valve, the gas intake valve and the exhaust conduit control valve are configurable to open the conduit valve, to close the gas intake valve and to close the exhaust conduit control valve during an oscillatory motion of the piston. Preferably, in one embodiment of the present invention, the outlet of each subject site comprises a proportional valve that may be controlled to maintain each subject site at a pressure other than atmospheric pressure.

Preferably, the sealing assembly comprises a viscous gel layer having at least one adhesive exposed surface.

Preferably, the sealing assembly further comprises an elastic base membrane applied to the viscous gel layer.

Preferably, in another embodiment of the present invention, the sealing assembly is a rigid cone comprising a viscous liner on an inside surface of the cone, and having an adhesive material on an exposed surface of the liner.

Preferably, in another embodiment of the present invention, the sealing assembly comprises a sealing element receiving structure for receiving a sealing element applicable and moldable onto a subject, the sealing element comprising a viscous gel layer having an adhesive exposed surface.

Preferably, the sealing element further comprises an elastic base membrane applied to the viscous gel layer.

Preferably, in one embodiment of the present invention, the apparatus further comprises a pressure transducer for measuring pressure in the front chamber and the chest wall displacement measurement system comprises:

-a port to atmosphere fitted on the rear subject chamber; and

-a flow measurement device to measure flow through the port to atmosphere. Preferably, in another embodiment of the present invention, the apparatus further comprises a first pressure transducer for measuring pressure in the front chamber and the chest wall displacement measurement system comprises a second pressure transducer for measuring pressure in the rear subject chamber.

According to the present invention, there is also provided a sealing assembly for isolation of at least one of a front subject chamber and a rear subject chamber, the sealing assembly comprising a viscous gel layer having at least one adhesive exposed surface.

According to the present invention, there is also provided a sealing assembly for isolation of at least one of a front subject chamber and a rear subject chamber, the sealing assembly comprising a rigid cone comprising a viscous liner on an inside surface of the cone, and having an adhesive material on an exposed surface of the liner.

According to the present invention, there is also provided a sealing assembly for isolation of at least one of a front subject chamber and a rear subject chamber, the sealing assembly comprising a sealing element receiving structure for receiving a sealing element applicable and moldable onto a subject, the sealing element comprising a viscous gel layer having at least one adhesive exposed surface.

Preferably, the sealing element further comprises an elastic base membrane applied to the viscous gel layer. A non-restrictive description of a preferred embodiment of the invention will now be given with reference to the appended drawings.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a schematic view of an apparatus according to a preferred embodiment of the present invention; Figure 2 is a schematic view of an apparatus according to another preferred embodiment of the present invention;

Figure 3 is a schematic view of an apparatus according to another preferred embodiment of the present invention;

Figure 4 is a schematic view of an apparatus according to another preferred embodiment of the present invention; Figure 5 is a graph of high-frequency transfer impedance measurements of subjects studied with the apparatus illustrated in Figure 2;

Figure 6 is a graph of low-frequency transfer impedance measurements of subjects studied with the apparatus illustrated in Figure 1 ;

Figure 7 is a schematic view of a sealing assembly according to a preferred embodiment of the present invention;

Figure 8 is a schematic view of a sealing assembly according to another preferred embodiment of the present invention;

Figure 9 is a schematic view of a sealing assembly according to another preferred embodiment of the present invention. PREFERRED EMBODIMENT OF THE PRESENT INVENTION

In the preferred embodiment of the apparatus shown in Figure 1 , the subject is restrained in a subject site 100 having a breathing zone, preferably a double chamber plethysmograph (40) fitted with a sealing assembly (41), so that the subject's airway opening protrudes into one chamber (42) while the thorax and lower body of the subject is placed in the second chamber (43). The first chamber (42) herein is commonly referred to as the front chamber, while the second chamber (43) is referred to as the rear subject chamber, respectively. The plethysmograph is fitted with an adjustable restraining mechanism (44) that permits users to position and restrain the subject such that an adequate seal and separation of the two chambers can be ensured. The rear subject chamber of the plethysmograph has a port to atmosphere (60) that is fitted with a device to measure flow (61). The front chamber has two ports (30 and 31) to permit a bias flow through the front chamber that provides fresh gas to the subject and exhausts expired gases. The inlet or bias flow intake port (30) is connected through a conduit (102) to a flow generator or source (10) that can be controlled to provide a combination of a suitable net bias flow and an oscillatory flow, wherein the two flows may be superimposed upon one another or applied alternatingly so as to both provide sufficient fresh air to the subject and obtain regular oscillation measurements.. An optional nebulizer or other device (80) can enrich the bias flow with substances such as aerosols of bronchially active agents, bronchoconstrictors or bronchodilators. The bias flow is exhausted through port 31.

In one preferred embodiment of the device, the flow source (10) consists of a linear actuator (11) connected to a piston (12) inside a cylinder (13). One valve (20) separates the cylinder from a gas intake port (21) while a second valve (22) connects the cylinder to the bias flow intake port of the front chamber (30). Coordinated control of the piston position and the valves permits a pulsatile bias flow as follows: During a slow forward stroke of the piston, valve 22 is open and valve 20 is closed so that the air displaced by the piston is pushed towards the front chamber. Once the piston reaches the end of its stroke, the valves switch and the piston is rapidly retracted to refill the cylinder with fresh gas from the air intake. The linear actuator can furthermore be controlled to produce high, low or mixed-frequency oscillations that may be superimposed on or interspersed with the bias flow. Throughout the oscillations, a pressure transducer (50) records the pressure in the front chamber and the flow meter (60) records the flow in and out of the rear subject chamber, with both channels being phase-matched. In our preferred embodiment, the volume of the rear subject chamber and the resistance of the flow measurement port are such that the time constant of the rear subject chamber is much shorter than the period of the highest frequency of interest, so that the flow measured at the rear subject chamber port can be considered a true representation of the chest wall displacement due to respiratory motion.

In one embodiment of the technique, high frequency oscillations are superimposed continuously on the bias flow during the forward stroke of the piston. In this case, the outlet or exhaust port (31) must be fitted with an exhaust conduit (71) possessing an impedance that is adequate to ensure that a sufficient portion of the oscillatory flows enters the airway opening, but low enough to ensure that the bias flow does not excessively pressurize the front chamber. However, this approach typically suffers from a reduced signal-to-noise ratio because only part of the oscillation reaches the subject's lungs.

In a second embodiment of the technique, the bias flow is briefly interrupted while an oscillation is applied. In this approach, valve 22 remains open throughout the oscillations while valve 20 closes the intake port and an additional valve (70) seals the bias flow exhaust port. For a limited time, the subject rebreathes_^ from the front chamber while the oscillator superimposes a high-frequency oscillation. The bias flow is resumed once the measurement manoeuvre is complete. This approach offers a better signal-to-noise ratio than the previous approach because there are no ports open to atmosphere while the oscillation is applied. A third embodiment of the technique is similar to the previous approach in that the bias flow is briefly interrupted, valve 22 is opened and valves 20 and 70 are closed. In this embodiment, however, the manoeuvre starts by increasing the pressure in the front chamber and hence inflating the lungs to a super-atmospheric pressure that is sufficiently high to trigger the Hering-Breuer reflex and temporarily suppress the subject's respiratory drive for several seconds. During this brief apneic period, an oscillatory signal containing both low and high frequencies is applied to obtain a measurement of pulmonary transfer impedance over the same frequency range as used in the LFOT, hence providing information about the airway and the tissue compartments. The pressure in the front chamber is reduced and bias flow is resumed once the measurement manoeuvre is complete. The data collected in this approach can also be used to assess the quality of the seal around the subject. If, for example, the piston pump oscillates around a fixed position once the desired inflation pressure has been set, the drop in mean pressure throughout the remainder of the manoeuvre provides a measure of the leak in the system, thereby permitting detection of an inadequate nose or neck seal. Alternatively, the piston can be controlled to maintain a constant mean pressure throughout the oscillation; in this case, the presence of a leak would require the piston to move forward to compensate for lost gas, and excessive forward movement of the piston would reflect an inadequate seal. The latter approach is preferable because it assures a constant mean pressure in the presence of a small, tolerable leak.

In a fourth embodiment of the technique, the valve in the bias flow exhaust port (70) is a proportional valve that is controlled such that the front chamber is continuously maintained at a pressure other than atmospheric pressure in order to modulate the mean lung volume of the subject. This allows additional information about the subject's lung function to be obtained by collecting multiple consecutive measurements at different mean inflation pressures, or one extended dataset wherein the mean inflation pressure is slowly modulated throughout the measurement. In the third and fourth embodiments described above or any other configuration where the mean pressures of the two chambers differ significantly, it is important to maintain a good the seal around the animal while preventing excessive restraining force or direct compression on the chest wall, the neck or the glottis. In our preferred embodiment shown in Figure 7, one employs a sealing assembly (41) comprised of a viscous gel layer (90) with an adhesive surface (91) facing the subject attached to an elastic base membrane (92). This sealing assembly is attached to the inside of the plethysmograph (40) such that as the subject is inserted into the plethysmograph, the seal adapts its shape to the animal's snout. The base membrane provides sufficient elasticity to gently press the seal against the subject while the gel layer molds to the finer details of the subject's snout. The adhesive surface connects the seal to the surface of the subject such that small movements of the subject's head are possible without breaking the seal. The subject's airway opening protrudes through a hole in the sealing assembly into the head chamber. In an alternate embodiment of the sealing assembly shown in Figure 8, a rigid cone, preferably a nose cone (93), is attached to the inside of the plethysmographs (40). The cone is lined with a viscous gel or other soft material (90) with an adhesive exposed surface (91) so that the gel can mold to the shape of the subject's head and the surface can attach to the surface of the subject. The subject is inserted and held in the plethysmograph such that its head is pressed gently against and adheres to the sealing assembly, forming a seal against the cone. The subject's airway opening protrudes through the opening in the cone into the front chamber.

In an alternate embodiment of the sealing assembly shown in Figure 9, a sealing element or sleeve (94) produced of a viscous gel or other soft material (90) with an adhesive inner surface (91) is attached to or wrapped around the subject before it is inserted into the plethysmograph (40). The outside layer (95) of the sleeve may include an elastic membrane and may be adhesive. The sleeve is placed around at least one of the subject's snout, head and neck such that it adheres and molds to the shape of the subject. The subject is then inserted into the plethysmograph and gently pushed up against suitably shaped sealing element receiving structure, such as a dividing member (96) separating the front and rear subject chambers. The contact between the sleeve and the dividing member creates a seal separating the subjects' airway opening and lower body.

In an extension to the preferred embodiment of the device described above shown in Figure 2, a single flow source (10) is used to provide bias flow and apply oscillation manoeuvres to two or more subjects simultaneously. In this embodiment, an additional manifold (32) with symmetrically branched tubes (33) is placed between the nebulizer (80) and the bias flow intake ports (30) of the individual front chambers (42). Additional valves (34) may be placed in each branch (33) to permit selective exclusion of individual subjects and measurement sites. In a similar embodiment, a single pressure transducer located at or near manifold 32 could be used instead of the individual pressure transducers 50, provided that the pressure drop across the tubes 33 can be confirmed to be negligible. In a similar embodiment, individual nebulizers could be placed in each tube 33 or directly integrated in each front chamber 42, replacing the common nebulizer 80. In the alternate embodiment of the invention shown in Figure 3, the flow generator comprises a first flow source (14) applying only oscillatory flow components and a second flow source (15) providing the bias flow component. In this case, the nebulizer (80) can be placed in the bias flow branch (as shown) or in the connecting branch closer to the manifold (32).

In an alternate embodiment of the invention shown in Figure 4, the subjects are positioned such that their airway openings protrude into one single, communal front chamber (45) while their thorax and lower bodies remain in individual rear subject chambers (43). The communal front chamber must be constructed in such a way that each subject is equally exposed to bias flow, aerosol and oscillations.

In an alternate embodiment of the invention, the flow generator applies the bias flow by means of suction on the bias flow exhaust port. In an alternate embodiment of the invention where the time constant of the rear subject chamber is too long for the measured flow to accurately represent chest wall displacement, the dynamics of the rear subject chamber are characterized and corrected for to obtain an estimate of chest wall displacement due to respiratory motion. In an alternate embodiment of the invention, the front chamber is minimized to reduce the shunt compliance due to gas compression and deliver the greatest possible amount of the volume provided by the flow source to the subject's lungs.

In an alternate embodiment of the invention, the port 60 is omitted so that the rear subject chamber is sealed, and the flow measurement device 61 is replaced by a pressure sensor. The dynamics of the rear subject chamber are characterized so that an estimate of chest wall displacement due to respiratory motion can be obtained from the pressure measurement in the rear subject chamber. However, this approach is disadvantageous for two reasons. First, gas compression and thermodynamics in the rear subject chamber may be sufficiently complex that the chamber dynamics may not readily be deconvoluted to estimate chest flow. Second, it is likely difficult to trigger the Hering-Breuer reflex with this approach because even a small leak in the seal around the subject would lead to pressurization of the rear subject chamber, reducing the pressure gradient that triggers the reflex and creating circumstances that are physiologically disadvantageous.

In an alternate embodiment of the invention, the rear subject chamber and flow measurement device are replaced by other means of quantitatively measuring chest wall displacement due to respiratory motion, including, without limitation, inductance plethysmography.

Experimental Data

In a first set of experiments, measurements of high-frequency respiratory transfer impedance were obtained from three groups of two subjects, where each group of two subjects was studied simultaneously in a setup as shown in Figure 2. All subjects had spontaneous respiratory rates close to 240 breaths per minute (4 Hz). Each group of two subjects received a bias flow of 30 ml/min. Bias flow was briefly interrupted to perform 16 second measurement manoeuvres during which the subjects were rebreathing from the front chamber while an oscillation waveform containing mutually prime frequencies was applied to their airway opening. Power spectra of the raw data signals showed that above 12 Hz, the frequencies of oscillation were clearly delimited from the harmonics of spontaneous breathing. The means and standard deviations of the resistance (R) and reactance (X) components of the resulting high-frequency transfer impedances in the range from 15 to 65 Hz are shown as in Figure 5.

In a second set of experiments, measurements of low-frequency respiratory transfer impedance were obtained from two subjects studied individually in a setup as shown in Figure 1. Each subject received a bias flow of 30 ml/min that was briefly interrupted to perform measurement manoeuvres. Prior to measurement manoeuvres, the subjects were conditioned by a few slow, deep inflations to 30 cmH20 without oscillation, which was found to reduce drive and extend the apneic period for the measurement manoeuvres. Each measurement manoeuvre consisted of a rapid inflation to 30 cmH20, followed by a 0.5 second hold, followed by a 3 second oscillation designed to maintain the inflation pressure and containing mutually prime frequencies from 0.5 to 18.5 Hz. Representative resistance (R) and reactance (X) components of a low-frequency transfer impedance are shown in Figure 6.

Although preferred embodiments of the present invention have been described in detailed herein and illustrated in the accompanying drawings, it is to be understood that the invention is not limited to these precise embodiments and that various changes and modifications may be effected therein without departing from the scope of the present invention.

Claims

1. An apparatus for lung function assessment of at least one conscious laboratory animal comprising:

- a conduit;

2. The apparatus according to claim 1 , wherein the at least one flow generator comprises first and second flow generators, the second flow generator inducing net flow through the conduit and the at least one subject site, and the first flow generator applying only oscillatory flow components to the breathing zone.

3. The apparatus according to claim 1 or 2, wherein the at least one flow generator comprises:

-a cylinder having a cylinder outlet;

-a piston positioned within said cylinder; and

-an actuator for displacing the piston within the cylinder.

4. The apparatus according to claim 3, wherein the at least one flow generator further comprises:

5. The apparatus according to claim 4, wherein the at least one flow source further comprises a conduit valve downstream of the parallel connection between the gas intake port and the cylinder outlet, for controlling flow through the conduit.

6. The apparatus according to claim 5, wherein the conduit valve and the gas intake valve are configurable to open the conduit valve and to close the gas intake valve during a forward stroke of the piston and to close the conduit valve and to open the gas intake valve during a retraction of the piston to fill the cylinder with gas from a gas intake source.

7. The apparatus according to any one of claims 2 to 6, wherein the actuator is configurable to displace the piston through an oscillatory motion.

8. The apparatus according to any one of claims 1 to 7, comprising at least two subject sites connected in parallel to the conduit.

9. The apparatus according to any one of claims 1 to 8, wherein each subject site further comprises:

-a front chamber connected to the inlet and the outlet; and

-at least one rear subject chamber; and

10. The apparatus according to any one of claims 1 to 9, wherein the outlet of each subject site is fitted with an exhaust conduit having an impedance sufficiently high to prevent shunting of the oscillatory flow and sufficiently low to avoid excessive pressurization of the subject site.

11. The apparatus according to claim 5, wherein the outlet of each subject site is fitted with an exhaust conduit having an exhaust conduit control valve to control flow therethrough, wherein the conduit valve, the gas intake valve and the exhaust conduit control valve are configurable to open the conduit valve, to close the gas intake valve and to close the exhaust conduit control valve during an oscillatory motion of the piston.

12. The apparatus according to any one of claims 1 to 11 , wherein the outlet of each subject site comprises a proportional valve that may be controlled to maintain each subject site at a pressure other than atmospheric pressure.

13. The apparatus according to claim 9, wherein the sealing assembly comprises a viscous gel layer having at least one adhesive exposed surface.

14. The apparatus according to claim 13, wherein the sealing assembly further comprises an elastic base membrane applied to the viscous gel layer.

15. The apparatus according to claim 9, wherein the sealing assembly is a rigid cone comprising a viscous liner on an inside surface of the cone, and having an adhesive material on an exposed surface of the liner.

16. The apparatus according to claim 9, wherein the sealing assembly comprises a sealing element receiving structure for receiving a sealing element applicable and moldable onto a subject, the sealing element comprising a viscous gel layer having an adhesive exposed surface.

17. The apparatus according to claim 16, wherein the sealing element further comprises an elastic base membrane applied to the viscous gel layer.

18. The apparatus according to claim 9, wherein the apparatus further comprises a pressure transducer for measuring pressure in the front chamber and the chest wall displacement measurement system comprises:

-a port to atmosphere fitted on the rear subject chamber; and

-a flow measurement device to measure flow through the port to atmosphere.

19. The apparatus according to claim 9, wherein the apparatus further comprises a first pressure transducer for measuring pressure in the front chamber and the chest wall displacement measurement system comprises a second pressure transducer for measuring pressure in the rear subject chamber.

20. A sealing assembly for isolation of at least one of a front subject chamber and a rear subject chamber, the sealing assembly comprising a viscous gel layer having at least one adhesive exposed surface.

21. The sealing assembly according to claim 20, further comprising an elastic base membrane applied to the viscous gel layer.

22. A sealing assembly for isolation of at least one of a front subject chamber and a rear subject chamber, the sealing assembly comprising a rigid cone comprising a viscous liner on an inside surface of the cone, and having an adhesive material on an exposed surface of the liner.

23. A sealing assembly for isolation of at least one of a front subject chamber and a rear subject chamber, the sealing assembly comprising a sealing element receiving structure for receiving a sealing element applicable and moldable onto a subject, the sealing element comprising a viscous gel layer having at least one adhesive exposed surface.

24. The sealing assembly according to claim 23, wherein the sealing element further comprises an elastic base membrane applied to the viscous gel layer.