WO2008143506A1

WO2008143506A1 - Test and calibration device

Info

Publication number: WO2008143506A1
Application number: PCT/NL2008/050298
Authority: WO
Inventors: Robert Schot; Peter Jan Sterk; Dirk Teunis Van Der Plas; Annelies Margaretha Slats
Original assignee: Publiekrechteiijke Rechtspersoon Academisch Ziekenhuis Leiden H.O.D.N. Leids Universitair Medisch Centrum
Priority date: 2007-05-21
Filing date: 2008-05-21
Publication date: 2008-11-27

Abstract

The invention pertains to a device for testing the lung function in a subject, comprising a pump for providing a gas flow, an actuator for driving said pump, a sensor for determining a flow parameter of said gas flow, and a control unit, operationally coupled to said sensor for receiving at least one flow parameter from said sensor and operationally coupled to said actuator for controlling said actuator, said control unit having a processor and software for calculating a passive inspiration manoeuvre following an active inspiration manoeuvre using said flow parameters.

Description

Test and calibration device

Background

The present invention relates to a device for testing and determining lung function parameters, a device for calibrating lung function apparatus, a method for treating lung patients, a method for determining lung function parameters, and a computer software product for such a device or method. Lung function apparatus are known. These apparatus provide full forced artificial respiration. Some of these apparatus even provide the possibility to assist a patient in breathing. All these apparatus operate in a continuous mode. Most of these devices produce or reproduce pre-recorded flow patterns.

For calibration and testing (for quality control, for instance) of lung function apparatus and lung function measuring apparatus, it is known to use motorised syringes. These devices, however, are only able to reproduce programmed flow curves.

Summary of the invention

The invention aims to provide a versatile device for testing lung function parameters, as well as computer software to provide such a device.

According to a first aspect of the invention this is realized with a device for testing or measuring the lung function in a subject, comprising a pump for providing a gas flow, an actuator for driving said pump, a sensor for determining a flow parameter of said gas flow, and a control unit, operationally coupled to said sensor for receiving at least one flow parameter from said sensor and operationally coupled to said actuator for controlling said actuator, said control unit having a processor and software for calculating a passive inspiration manoeuvre following an active inspiration manoeuvre using said flow parameters. This provides the possibility of providing objective measurements of lung functioning of a patient, yet adapt its functioning to the specific breathing pattern of an individual patient. It is even possible to use the same device for calibration and testing of lung function equipment.

Research has shown that the measurements of many lung function parameters depend on the voluntary manoeuvres of an object, thus introducing errors in the measurements. Forced flow, however, is very uncomfortable to a patient. This will again lead to errors. A device was developed with software which allows an object to breath freely, and which adapts to the breading pattern. At an inspiration of the object, the device provided an additional flow which naturally follows the normal breading pattern of an object, but forces an additional amount of air into the lungs of an object. The device can adapt its operation to an individual object having its specific lung volume and breathing frequency. Using this device, it has proven possible to measure lung parameters in a reproducible and comparable way, making it possible not only to measure parameters of a single object, but to produce parameters which made it possible to compare various objects. This also made it possible to use the device for calibration and quality control purposes.

Furthermore, the passive inflation using the device of the invention even allows a widening of the airways more and better than possible with active maximum inspiration by an object. In for instance Asthma patients, this also showed a beneficial effect.

The invention further relates to a device for calibrating a lung function apparatus or respirator, said device comprising a pump for providing a gas flow, an actuator for driving said pump, a sensor for determining a flow parameter of said gas flow, and a control unit, operationally coupled to said sensor for receiving at least one flow parameter from said sensor and operationally coupled to said actuator for controlling said actuator, said control unit having a processor and software for simulating a passive inspiration manoeuvre, said pump having an outlet which is operationally couplable to an outlet of said apparatus or respirator.

The invention further relates to a method for treating a lung patient, in particular an asthma patient, using the device described above, comprising determining the vital capacity, expiratory reserve volume and inspiratory capacity of the patient, entering said parameters into the control unit of the device, and said software determining the functional residual volume level, the expiratory reserve volume and calculating the specific inspiratory capacity from this value, determining inspiration time and breathing frequency, said control unit controlling said actuator to follow the breathing of the patient during at least several breathings, and after these breathings to provide a machine assisted deep inspiration, said software calculating the required flow of said pump during breathing.

In an embodiment of the device, said software calculates from said flow parameters the volume displacement of said pump during active breathing for following said active inspiration, and provides instructions to said actuator for said driving said pump.

In an embodiment, said software calculates several volume displacement parameters during active inspiration. In an embodiment, said software calculates an FRC level during a first active breathing phase, an inspiratory volume during another active breathing phase, and an inspiration time during yet another breathing phase.

In an embodiment, said software calculates the flow of said passive inflation based on the calculated FRC level, and inspiratory volume and inspiration time. In an embodiment, said software calculates the flow of said passive inflation as a continuation of an active inspiration.

In an embodiment of said device, it further comprises a breathing attachment for allowing a subject to breath through, an inlet for air, coupled to said breathing attachment and provided with a valve which is operable by said control unit, a duct provided with a further valve which is operable by said control unit, said duct coupling said pump to said breathing attachment, and a further inlet for air, coupled to said pump and provided with yet another valve which is operable by said control unit, and wherein said sensor is positioned to provide flow parameters of a flow through said breathing attachment. In an embodiment, said device is further coupled to an FOT-unit via control valves which are operationally coupled to said control unit, for selectively operationally coupling said FOT device to said breathing attachment.

The invention further relates to a method for measuring the lung condition in a subject using the device of the invention, wherein said device further comprising a breathing attachment for allowing a subject to breath through, an inlet for air, coupled to said breathing attachment and provided with a first valve which is operable by said control unit, a duct provided with a second valve which is operable by said control unit, said duct coupling said pump to said breathing attachment, and a further inlet for air, coupled to said pump and provided with a third valve which is operable by said control unit, and said sensor is positioned to provide flow parameters of a flow through said breathing attachment, and said method comprising the subsequent steps of:

-said control unit opening said first and third valve and closing said second valve; -said software determining subject-specific parameters of functional residual volume level, the expiratory reserve volume and calculating the specific inspiratory capacity from this value, and determining inspiration time and breathing frequency using measurement values of said sensor;

-said control unit opening said second valve and closing said first and second valve;

-said software calculating said passive inspiration manoeuvre from said determined parameters;

-said control unit controls said actuator to perform said passive inspiration manoeuvre using said calculated passive inspiration manoeuvre. The invention further relates to a computer software product for calculating a passive inspiration manoeuvre following an active inspiration manoeuvre in a device described above and using said flow parameters, said computer software comprising instructions for calculation a flow pattern using measured flow parameters.

Further details of the invention are elucidated in the description of embodiments and in de dependent claims.

The various aspects discussed in this patent can be combined in order to provide additional advantages. Several of the disclosed features may be the subject of one or more divisional patent applications.

Description of the drawings

The invention will be further elucidated referring to various embodiments shown in the drawing wherein shown in:

Fig. 1 a graph showing an example of several phases of breathing using in the device of the invention; fig. 2 a schematic layout of the coupling of a device of the invention coupled to an FOT device; fig. 3 a more detailed schematic layout of a device of the invention; fig. 4 a drawing of a device of the invention; fig. 5 a functional layout of a calibration and testing setup using a device of the invention; fig. 6 an alternative layout of a calibration and testing setup using a device of the invention; fig. 7 another alternative layout of a calibration and testing setup using a device of the invention; fig. 8 a schematic and functional layout of the motion control and motor for driving the pump; fig. 9 a schedule showing the screening an selection of test objects in a test of a device according to the invention; fig. 10 a time lime of measurements during a test; fig. 11 resulting measurements of an intact response group of test objects; fig. 12 resulting measurements of an impaired response group of test objects; fig. 13 a schematic layout of a device for measuring lung function of an object.

Detailed description of embodiments

We developed a motorized syringe system and software program to perform a passive deep inspiration manoeuvre (Machine Assisted Deep Inspiration). The motorized syringe system was built up from two 3 [L] syringes (Jaeger Manual

Calibration Syringe), driven by a linear servomotor (Copley linear actuator TB2508, with Renishaw Optical encoder RGH24), controlled by a motion controller (Galil

Motion Controller DMC 1810) and powered by a digital servo amplifier (Elmo CORNET-9/230). Figure 4 shows a picture of this device.

The function of a cosine during half a period (period of π radians) was used to simulate the passive deep inspiration manoeuvre, which most naturally followed an active deep inspiration manoeuvre. Second, to make the function specific for each patient, we used a calculated inspiration time as signal period time, and a calculated inspiration capacity as the amplitude of the cosine. How these values are calculated is specified in the next paragraph. Equation 1 shows the formula used to calculate the volume displacement. The points for volume displacement were recalculated to motor counts, where one motor count equals 1 [μm] motor displacement, and 0,0157 [ml] volume displacement. These volume displacements were realized with an interval of 8 [ms].

Equation 1 Calculation deep inspiration volume displacement

Jj J- V_DISPL {n - 1)

Where: n : Index of volume displacement point

V_DISPL(Π) : Volume displacement for index n

ICcLc ■' Calculated inspiratory capacity Ti : Average deep inspiration time * 1,5 tn ■' Time displace point n

Assumption: V_DISPL(O) = 0

Machine assisted deep inspiration measurement

Before starting the measurement with Machine Assisted Deep Inspiration (MADI), vital capacity (VC), expiratory reserve volume (ERV), and inspiratory capacity (IC) of the patient had to be entered into the software program. These parameters were measured beforehand using Jaeger software (v4.67) and spirometer (MasterScreen FRC). The MADI measurement contained four phases. Phase Pl (see fig. 1) was used to determine the functional residual volume (FRC) level. The patient was asked to take five tidal in- and expirations. The software calculated the average FRC level from these five measured end-expiratory levels. This value was then considered as 'zero value' for volume. Note that the calculated FRC level is not the actual FRC level, because it was not possible to measure residual volume (RV).

In phase P2 (see fig. 1) ERV, was measured, by a complete expiration until a plateau was reached, followed by tidal breathing. The ERV was calculated from the volume difference between last end-expiratory value and the plateau of the ERV manoeuvre. Using this ERV, the specific inspiratory capacity was calculated by subtracting the ERV value from the previously measured VC. As safety precaution we used ninety percent of this volume as the volume for the passive deep inspiration. During phase P3 (see fig. 1) both inspiration time as well as breathing frequency were determined. This was done, to calculate the inspiration time for the passive deep inspiration, which was the mean inspiration time of five tidal inspirations multiplied by 1.5. Phase P4 (see fig. 1) is the Start of the passive deep inspiration. At the plateau (zero flow) of a tidal expiration, the actual passive deep inspiration was started. This was done to minimize active participation of the patient to the deep inspiration. Following the passive deep inspiration manoeuvre the actual performed IC was calculated by measuring the difference between the maximal volume point and the starting volume point of the passive deep inspiration manoeuvre.

Valves

We measured the resistance of the respiratory system (respiratory resistance) continuously during the complete measurement using a forced oscillation technique (FOT)-device connected to the motor drive syringe system. To be able to measure respiratory resistance before and after the passive deep inspiration, four balloon valves were integrated in the system. During MADI phases Pl to P3, measurements were performed in valves state A (Valve 1, 2, and 4 open, figure 2). In this state it was possible to measure respiratory resistance and let the patient breath room air through a pneumotach. By using a pneumotach, with a 0,1 [kPa/L/s] impedance, there was no loss of the FOT signal. During the passive deep inspiration manoeuvre, valves state B was used (figure 2), so that only air could move from the motorized syringe into the patient. The speaker inside the FOT-device, which produces sinus waves for the resistance measurements, may damage during the passive deep inspiration manoeuvre, due to the volume forced by the motorized syringe. Therefore, we closed the air passage to the speaker during the passive deep inspiration manoeuvre, prohibiting respiratory resistance data measurements during the passive deep inspiration. However, directly after the passive deep inspiration manoeuvre the valves changed back to state A, enabling respiratory resistance measurements already during the expiration following the manoeuvre. Valves were switched on and off by digital output channels of the motion controller board. During the MADI measurement data of flow and pressure were collected with a sample rate of 100 [Hz] (100 samples per second per channel), and a resolution of 16 bits, using a National Instruments 6014 PCI data acquisition board. The volume signal was calculated from the measured flow signal and corrected with a BTPS (Body Temperature Pressure Saturated) factor for the inspiratory and expiratory part of the flow. All raw data and measurement results were stored in ASCII character based files.

Test of the device for machine assisted inflation in Asthma patients.

Deep inspirations can reverse induced bronchoconstriction in healthy subjects. In patients with asthma this bronchodilatory effect of deep inspirations is impaired. Decreased strain transmission from the parenchyma to the airways during lung inflation, either by airway wall thickening or loss of alveolar attachments, could be a reason for this observation. Another possibility is that the airways are stretched by the deep breath, but that the components of the airway wall respond differently to the stretch imposed on it, for example as a result of airway wall remodelling or altered airway smooth muscle properties or function. Machine assisted passive inflation of the lungs may overcome these impairments by providing adequate stretch of the airways from the inside, and therefore improve the subsequent bronchodilation. We developed a motor-controlled syringe system connected to a forced oscillation device to inflate the lungs to TLC and continuously measure resistance (Rrs) and reactance (Xrs) of the respiratory system before, during and after the passive inflation. This was compared to the response of the airways to an active deep inspiration to TLC in randomized order. A schedule of this device is shown in figure 3.

Hypothesis

Passive inflation of the lungs to TLC reduces Rrs to a greater extent than active deep inspiration in patients with asthma.

Aim:

To measure Rrs and Xrs before, during and after active deep inspiration and passive inflation to TLC in patients with asthma with

• an impaired bronchodilatory response to deep inspiration, or • an intact bronchodilatory response to deep inspiration

Subjects (n = 24)

• Mild to moderate persistent asthma (GINA) • Episodic wheezing, cough, chest tightness

• Atopic

• PC50 Rrs methacholine < 8 mg/ml FEVl > 70% pred

• Non-smoking or ex-smoking (< 5 PY) • β- Agonist on demand and/or inhaled corticosteroids

The study design is shown in fig. 9.

Methacholine challenge (see fig. 10)

• Rrs measurements during 30s of tidal breathing

• Doubling concentrations of methacholine (0.15 - 80 μmol/ml) by tidal breathing at 5 min intervals

PC50Rrs = provocative concentration of methacholine (mg/ml) increasing Rrs by 50% • At 50% increase in Rrs: stop challenge + Rrs measurement with DI manoeuvre to calculate DI response (see below)

• FEVl measurement at baseline and post challenge

Forced Oscillation Device (Woolcock institute of medical research, Sydney, Australia) • 50mm Fleisch Pneumotachograph Vitalograph Ltd, Maids Moreton, UK)

• Pressure transducer (Surense DCAL4, Honeywell Sensing and Control, Milpitas, CA, USA)

• Flow and pressure signals are low pass filtered at 25 Hz, sampled at 300Hz (16- bit A/D converter) • Signals are bandpass filtered using a bandwith of 2 Hz around 8 Hz, divided in segments of 1/8 s, impedance calculated via division in the frequency domain

• Flow signal low-pass filtered at 2 Hz to obtain breathing signal Resistance (Rrs) and Reactance (Xrs) of the respiratory system • Measurement of Rrs and Xrs at 8 Hz: 30 sec tidal breathing, 1 inhalation to TLC, passive expiration, 60 sec tidal breathing.

• Calculation of the mean all data points of Rrs and Xrs during 3 tidal expirations before deep inspiration (RrsExp preDI, Xrsexp preDI ), and after deep inspiration (RrsExp postDI and Xrsexp postDI)

• Calculation DI response: Rrsexp postDI - Rrsexp preDI):

• Intact DI response (Fig. 11): reduction Rrsexp > 2SD of mean Rrs Exp pre DI • Impaired DI response (Fig. 12): reduction Rrsexp < 2SD of mean Rrs Exp pre DI

Machine Assisted passive inflation (fig. 13):

• Two 3 [L] syringes (Jaeger Manual Calibration Syringe) • Linear servomotor (Copley linear actuator TB2508, with Renishaw Optical encoder RGH24)

• Controlled by a motion controller (Galil Motion Controller DMC 1810)

• Powered by a digital servo amplifier (Elmo CORNET-9/230)

• Function of a cosine during half a period (period of π radians) to simulate DI, with

• calculated inspiration time as signal period time

• calculated inspiration capacity as the amplitude of the cosine.

• Points for volume displacement were recalculated to motor counts; 1 motor count equals 1 [μm] motor displacement, and 0,0157 [ml] volume displacement, with an interval of 8 [ms]

• The measurement consisted of 4 phases (see fig. 1) Pl: FRC level was determined and set as zero volume

P2: ERV manoeuvre to calculate the inspiratory volume (=VC - ERV) P3: measurement of inspiration time (DI = multiplied by 1.5) P4: passive inflation

• These phases were also completed when the active deep inspiration was performed

Data are expressed as mean ± SD, geometric mean ± SD in DD for PC50Rrs. * p < 0.05 between groups.

Data are expressed as mean ± SEM for Rrs and Xrs data. * p < 0.05 between groups, # p < 0.05 within groups (passive inflation vs. active DI).

Mean ± SEM for RrsExp (figure 1) and XrsExp (figure 2). Before methacholine inhalation (pre mch), after methacholine inhalation (post mch) and following deep inspiration (post DI). RrsExp significantly increased and XrsExp decreased by methacholine at both visits (* p < 0.01) in both groups. RrsExp was significantly decreased by both the active deep inspiration and passive inflation in the intact DI response group (# p < 0.05). In the impaired DI response group RrsExp was significantly reduced only by passive inflation($ p < 0.05). XrsExp was significantly increased by both active DI and passive inflation in both groups.

Conclusion

• Passive inflation of the lungs to TLC reduces Rrs to a greater extent that active deep inspiration in patients with asthma, who demonstrate an impaired bronchodilatory response to deep inspiration. • Impaired reduction in Rrs following DI is not preceded by impaired reduction in Rrs during DI, nor paralleled by impaired changes in Xrs.

Passive inflation of the lungs may restore the beneficial bronchodilatory effects of deep inspiration in patients with asthma, most likely providing adequate stretch to the airways leading to an altered response of the airways following the DI.

In figures 5, 6 and 7, several setups are shown for using the device of the invention for calibrating or for quality control of measuring devices for lung function measurement, such as for instance a spirometer and for instance ventilators..

In fig. 5, the device of the invention functions as a mechanical lung and provides an input flow to for instance a spirometer. The PC compares the applied flow curve of the device (VBS) with the measured graph of the spirometer.

In fig. 6, the device sends its data of the applied flow curve of the VBS to a PC which is coupled to a network. The spirometer is operationally coupled to another PC which is also coupled to a network. Measured results are placed in databases which can be compared.

Figure 7 shows an embodiment in which the device (VBS) again produces a flow to the spirometer (S. M.) via a tube (" slang"). In this embodiment, an analyst compares the applied flow and the resulting flow.

The device and above-described method can also be used for administering drugs in aerosol, liquid or gas form deep into the lungs of an object or a patient. Using this method and device, it is possible to reach deep areas in the lungs without any uncomfortable procedures. It will be clear that the above description and drawings are included to illustrate some embodiments of the invention, and not to limit the scope of protection. Starting from this disclosure, many more embodiments will be evident to a skilled person which are within the scope of protection and the essence of this invention and which are obvious combinations of prior art techniques and the disclosure of this patent.

Claims

1. Device for testing or measuring the lung function in a subject, comprising a pump for providing a gas flow, an actuator for driving said pump, a sensor for determining a flow parameter of said gas flow, and a control unit, operationally coupled to said sensor for receiving at least one flow parameter from said sensor and operationally coupled to said actuator for controlling said actuator, said control unit having a processor and software for calculating a passive inspiration manoeuvre following an active inspiration manoeuvre using said flow parameters.

2. Device according to claim 1, wherein said software uses said flow parameters for calculating the volume displacement of said pump during active breathing for following said active inspiration, and provides instructions for said actuator for said driving said pump.

3. Device according to claims 1 or 2, wherein said software calculates several volume displacement parameters during active inspiration.

4. Device according to any one of the preceding claims, wherein said software calculates an FRC level during a first active breathing phase, an inspiratory volume during another active breathing phase, and an inspiration time during yet another breathing phase.

5. Device according to claim 4, wherein said software calculates the flow of said passive inflation based on the calculated FRC level, and inspiratory volume and inspiration time.

6. Device according to claim 5, wherein said software calculates the flow of said passive inflation as a continuation of an active inspiration.

7. Device according to any one of the preceding claims, comprising a breathing attachment for allowing a subject to breath through, an inlet for air, coupled to said breathing attachment and provided with a valve which is operable by said control unit, a duct provided with a further valve which is operable by said control unit, said duct coupling said pump to said breathing attachment, and a further inlet for air, coupled to said pump and provided with yet another valve which is operable by said control unit, and wherein said sensor is positioned to provide flow parameters of a flow through said breathing attachment.

8. Device according to claim 7, wherein said device is further coupled to an FOT-unit via control valves which are operationally coupled to said control unit, for selectively operationally coupling said FOT device to said breathing attachment.

9. Device for calibrating a lung function apparatus or respirator, said device comprising a pump for providing a gas flow, an actuator for driving said pump, a sensor for determining a flow parameter of said gas flow, and a control unit, operationally coupled to said sensor for receiving at least one flow parameter from said sensor and operationally coupled to said actuator for controlling said actuator, said control unit having a processor and software for simulating a passive inspiration manoeuvre, said pump having an outlet which is operationally couplable to an outlet of said apparatus or respirator.

10. Method for treating a lung patient, in particular an asthma patient, using the device of claim 1, comprising determining the vital capacity, expiratory reserve volume and inspiratory capacity of the patient, entering said parameters into the control unit of the device, and said software determining the functional residual volume level, the expiratory reserve volume and calculating the specific inspiratory capacity from this value, determining inspiration time and breathing frequency, said control unit controlling said actuator to follow the breathing of the patient during at least several breathings, and after these breathings to provide a machine assisted deep inspiration, said software calculating the required flow of said pump during breathing.

11. Method according to claim 10, wherein said patient is instructed to perform, during said breathings, at least one complete expiration.

12. Method for measuring the lung condition in a subject using the device of claim 1, wherein said device further comprising a breathing attachment for allowing a subject to breath through, an inlet for air, coupled to said breathing attachment and provided with a first valve which is operable by said control unit, a duct provided with a second valve which is operable by said control unit, said duct coupling said pump to said breathing attachment, and a further inlet for air, coupled to said pump and provided with a third valve which is operable by said control unit, and said sensor is positioned to provide flow parameters of a flow through said breathing attachment, and said method comprising the subsequent steps of: -said control unit opening said first and third valve and closing said second valve;

-said software determining subject-specific parameters of functional residual volume level, the expiratory reserve volume and calculating the specific inspiratory capacity from this value, and determining inspiration time and breathing frequency using measurement values of said sensor; -said control unit opening said second valve and closing said first and second valve;

-said control unit controls said actuator to perform said passive inspiration manoeuvre using said calculated passive inspiration manoeuvre.

13. Computer software product for calculating a passive inspiration manoeuvre following an active inspiration manoeuvre in a device according to claim 1 using said flow parameters, said computer software comprising instructions for calculation a flow pattern using measured flow parameters.

14. Device comprising one or more of the characterising features described in the description and/or shown in the attached drawings.

15. Method comprising one or more of the characterising features described in the description and/or shown in the attached drawings.

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