The present invention relates to an installation for determining twitch mouth pressure of a patient.

Respiratory failure is a main cause of death with neuromuscular diseases. The supervision of patients with such diseases requires regular monitoring of respiratory function and tests of the respiratory muscles to prevent acute respiratory decompensation. These tests also help to evaluate new and promising therapies in the field of neuromuscular diseases

The monitoring of the respiratory muscles is generally based on either non-invasive volitional or relatively invasive procedures.

Furthermore, there is a non-volitional and non-invasive procedure which involves measuring the pressure at the mouth when the two phrenic nerves are stimulated by a magnetic stimulator and the patient is connected to an occluded inspiratory circuit. During the stimulation, the measurement of pressure variations at the mouth reflects changes in esophageal pressure provided that the glottis and the upper airways remain open. To avoid closure of the glottis or upper airway, it was proposed to ensure a minimum expiratory or inspiratory effort when the phrenic nerves are stimulated.

In this respect, the article "Use of twitch mouth pressure to assess diaphragm strength in patients with chronic obstructive pulmonary disease" from Hua et al, published in Respiratory Physiology & Neurobiology in 2013, discloses a non-invasive and non- volitional method based on measuring twitch mouth pressure (TwPmo). Twitch mouth pressure is measured using a mouthpiece connected to a fully automatic trigger device. The phrenic nerve is stimulated using a stimulator.

In the article "Influence of different trigger techniques on twitch mouth pressure during bilateral anterior magnetic phrenic nerve stimulation", published in July 2005, in CHEST, volume 128, Kabitz et al have determined that the correlation between twitch mouth pressure and twitch esophageal pressure is excellent when a controlled inspiratory trigger is used. Twitch mouth pressure is measured using a flanged mouthpiece connected to cylinder with a shutter at its distal end that functions as a magnetic catch piston to completely occlude the external airway for 2 seconds. The cylinder is connected to a pressure transducer and pneumotachograph interfaced with a computer system. This allows visualization of the pressure-time curves and displaying of the flow signal to the patient.

However, such installations are quite complex and require experimented teams to be operated. A goal of the present invention is to propose a simpler and easier-to-use installation in order to determine twitch mouth pressure of a patient.

To this end, the invention relates to an installation for determining twitch mouth pressure of a patient, said installation comprising:

- a mouth pressure sensor,

- a magnetic phrenic nerve stimulation device for stimulating the phrenic nerve of the patient,

- a controller for controlling the phrenic nerve stimulation device, said controller being connected to the magnetic phrenic nerve stimulation device,

wherein the controller includes an input terminal for receiving an input electric signal provided by the mouth pressure sensor, an output terminal, and at least an electronic board, said electronic board comprising:

+ a comparison stage for comparing the input signal with at least one reference value,

+ a generating stage for generating an output electric control signal to the phrenic nerve stimulation device via the output terminal, said output signal being generated on the basis of a comparison performed by the comparison stage, the generating stage being distinct from the comparison stage.

Thanks to the invention, the controller allows to compare directly a variable external voltage obtained from the pressure sensor, with an adjustable reference voltage to determine when the external voltage just gets bigger or smaller than the reference. The controller then emits a signal adapted to control the magnetic phrenic nerve stimulation device. The controller is ready-to-use as it is dedicated to the installation for determining twitch mouth pressure, also very easy-to-use in comparison with a computer system where specific software needs to be installed and then launched, and also easy to move where the patient has to be examined.

According to other advantageous aspects of the invention, the installation comprises one or more of the following features taken alone or according to all technically possible combinations:

- the comparison stage includes a hysteresis comparator;

- the comparison stage is an analogic stage including several electric components;

- the generating stage is an analogic stage including several electric components;

- the controller further includes first selection means for selecting a generating mode among two modes, a first mode wherein the output control signal is generated for each true comparison and a second mode wherein the output control signal is generated once for a first true comparison and only under condition after said first generation; - the controller further includes second selection means for selecting a comparison mode among four modes, a first mode wherein the comparison stage is adapted for comparing if the input signal is greater or equal than a negative reference value, a second mode wherein the comparison stage is adapted for comparing if the input signal is greater or equal than a positive reference value, a third mode wherein the comparison stage is adapted for comparing if the input signal is smaller or equal than a positive reference value and a fourth mode wherein the comparison stage is adapted for comparing if the input signal is smaller or equal than a negative reference value;

- the output signal is a pulse signal, preferably a TTL signal;

- the controller further includes adjusting means for adjusting the duration of the pulse signal;

- the controller further includes setting means for setting a predetermined value of the or each reference value;

- the controller further includes disabling means for disabling the generation of the output control signal;

- the controller further includes an input stage connected between the input terminal and the comparison stage, said input stage including overvoltage protection means; and

- the installation further comprises a pneumotachograph for recording different values of an air flow issued from the mouth.

The invention will be better understood upon reading of the following description, which is given solely by way of example and with reference to the appended drawings, in which:

- Figure 1 is a schematic view of an installation for determining twitch mouth pressure of a patient, said installation comprising a mouth pressure sensor, a magnetic phrenic nerve stimulation device for stimulating the phrenic nerve of the patient, and a controller for controlling the phrenic nerve stimulation device;

- Figure 2 is a schematic view of the controller of Figure 1 , said controller including an input stage for receiving an input signal, a reference value stage for determining a reference value, a comparison stage for comparing the input signal with the reference value, and a generating stage for generating an output control signal to the phrenic nerve stimulation device, said output signal being generated on the basis of the comparison performed by the comparison stage;

- Figure 3 is a schematic view of a front panel of the controller;

- Figure 4 is a circuit diagram of the input stage of Figure 2;

- Figure 5 is a circuit diagram of the reference value stage of Figure 2;

- Figure 6 is a circuit diagram of the comparison stage of Figure 2; - Figure 7 is a circuit diagram of the generating stage of Figure 2;

- Figure 8 is a set of curves representing the input signal, the result of the comparison and the output control signal according to a first comparison mode;

- Figure 9 is a view similar to that of Figure 8 according to another comparison mode;

- Figure 10 is a view similar to that of Figure 8 according to a particular generating mode wherein the output control signal is generated once for a first true comparison and only under condition after said first generation; and

- Figure 1 1 is a set of points illustrating comparisons of twitch mouth pressure (TwPmo) tests with twitch esophageal pressure (TwPeso) tests, said tests being carried out on patients with neuromuscular disorder and selective respiratory muscle disorder.

In the following, the expression "substantially equal to" defines an equality relation to more or less 5%.

In Figure 1 , an installation 10 for determining twitch mouth pressure TwPmo of a patient, not shown, comprises a mouth pressure sensor 12, a magnetic phrenic nerve stimulation device 14 for stimulating the phrenic nerve of the patient, and a controller 16 for controlling the phrenic nerve stimulation device 14, the controller 16 being connected between the mouth pressure sensor 12 and the stimulation device 14.

In addition, the installation 10 includes a pneumotachograph 17A for recording different values of an air flow issued from the mouth. The pneumotachograph 17 A is connected to a differential pressure transducer 17B in order to measure flow.

The installation 10 includes for example a mouth piece 18 adapted to be placed inside the mouth and connected to the pneumotachograph 17A which is itself connected to a pipe 19 for circulation of air going to and issued from the mouth. The pipe 19 is for example equipped with two two-ways valves 20A and a solenoid valve 20B under manual control and connected to a pressure sensor 12. The two-ways valves 20A are adapted to close a volume inside the pipe 19 and the mouth pressure sensor 12 is adapted to measure the pressure inside this closed volume.

In addition also, the installation 10 comprises a recorder 21 for recording the result of a comparison between a signal issued from the mouth pressure sensor 12 and a reference signal, said comparison being done by the controller 16, the recorder 21 being connected to the controller 16. The recorder 21 is connected to the mouth pressure sensor 12 to record the pressure values measured by said mouth pressure sensor. The recorder 21 is also connected to the differential pressure transducer 17B to record the flow values measured by said pneumotachograph. The mouth pressure sensor 12 is known per se and is adapted to measure the mouth pressure and to issue an electric signal representative of the mouth pressure, for example to the controller 16.

The magnetic phrenic nerve stimulation device 14 is also known per se and includes a magnetic stimulator, not shown, to stimulate the phrenic nerve of the patient. The stimulation device 14 is controllable by an electric signal, for example by a TTL (Transistor-Transistor Logic) signal.

The controller 16 includes an input terminal 22 for receiving an input electric signal provided by the mouth pressure sensor 12, an output terminal 24 for issuing an output electric control signal to the phrenic nerve stimulation device 14, and a recorder output terminal 26 for connecting the recorder 21 .

The controller 16 includes at least an electronic board, not shown, connected between the input terminal 22 and the output terminal 24. The electronic board comprises an input stage 30 for receiving the input signal, a reference value stage 32 for determining a reference value, a comparison stage 34 for comparing the input signal with the reference value, and a generating stage 36 for generating the output signal to the stimulation device 14 via the output terminal 24, said output signal being generated on the basis of the comparison performed by the comparison stage 34, as shown in Figure 2.

The controller 16 also includes a housing 38, which has for example a parallelepiped shape and comprises a front panel 40, as shown in Figure 3.

The controller 16 includes first selection means 42 for selecting a generating mode among two modes, a first mode M1 wherein the output control signal is generated for each true comparison and a second mode M2 wherein the output control signal is generated once for a first true comparison and only under condition after said first generation. The first selection means 42 comprise a first two-position selector 43A with a first lever 43B for switching from one mode M1 , M2 to the other mode M2, M1 .

The controller 16 includes second selection means 44 for selecting a comparison mode among four modes, a first mode wherein the comparison stage 34 is adapted for comparing if the input signal is greater or equal than a negative reference value, a second mode wherein the comparison stage 34 is adapted for comparing if the input signal is greater or equal than a positive reference value, a third mode wherein the comparison stage 34 is adapted for comparing if the input signal is smaller or equal than a positive reference value and a fourth mode wherein the comparison stage 34 is adapted for comparing if the input signal is smaller or equal than a negative reference value. The second selection means 44 comprise a first knob 45 movable between four positions around an axis perpendicular to the front panel 40. The four positions are respectively labeled "Increasing negative" for the first comparison mode, "Increasing positive" for the second comparison mode, "Decreasing positive" for the third comparison mode and "Decreasing negative" for the fourth comparison mode.

In addition, the controller 16 includes adjusting means 46 for adjusting the duration of the pulse signal, for example from 10 milliseconds (ms) to 100 ms. The adjusting means 46 comprise a second knob 48 movable, around an axis perpendicular to the front panel 40, between extreme positions which correspond for example to durations of 10 ms, respectively 100 ms.

In addition, the controller 16 further includes setting means 50 for setting a predetermined value of the reference value. The setting means 50 comprise a third knob 52 movable around an axis perpendicular to the front panel 40.

In addition, the controller 16 further includes disabling means 54 for disabling the generation of the output control signal. The disabling means 54 comprise a second two- position selector 56 with a second lever 57 for switching from an ON position corresponding to enabling the generation of the output control signal to an OFF position corresponding to disabling said generation and vice versa.

In addition, the controller 16 includes third selection means 58 for selecting a caliber relative to a voltage of the input electric signal, for example between a 1 V capacity and a 10V capacity. The third selection means 58 comprise a third two-position selector 60 with a third lever 61 for switching between the 1 V capacity and the 10V capacity.

In addition, the controller 16 comprises three indicator lamps 62, 64, 66: a first indicator lamp 62 for indicating that the controller 16 is switched on and electrically powered, a second indicator lamp 64 for indicating a true comparison done by the comparison stage 34, and a third indicator lamp 66 for indicating that the controller is ready to issue the pulse output signal. On the front panel 40, the first indicator lamp 62 is labeled "Powered", the second indicator lamp 64 is labeled "Comparison OK" and the third indicator lamp 66 is labeled "Ready".

In addition, the controller 16 includes enabling means 68 for enabling the generation of the output control signal in the second mode M2. Accordingly, the output control signal is generated only after activation of said enabling means 68. The enabling means 68 comprise for example a push button 70 and the generation of the output signal in the second mode M2 is enabled after a push on said button 70.

The input stage 30, shown in Figure 4, includes an adjusting section 80 for adjusting the voltage value of the input signal received by the input terminal 22 according to the third selection means 58. The adjusting section 80 comprises a voltage divider 82 and a first switch 84, the first switch 84 being coupled to the third lever 61 of the third selection means for switching between the 1 V capacity and the 10V capacity. In the 1 V capacity position, the voltage value of the input signal is unchanged, and in the 10V capacity position, the voltage value of the input signal is divided by 10 approximately by the voltage divider 82. The voltage divider 82 is made of passive components, for example of resistances R1 , R2 and of a potentiometer P1 .

The input stage 30 includes an overvoltage protection section 86 for protecting the other stages of the controller 16 against an overvoltage. In the example of Figure 4, the voltage is limited between -12V and +12V by the overvoltage protection section 86. The overvoltage protection section 86 is made of passive components, for example of resistances R3, R4 R5, R6, R7 and of diodes D1 , D2. The overvoltage protection section 86 is connected to -12V and +12V power supplies.

The input stage 30 includes a first amplification section 88 for amplifying the input signal received by the input terminal 22. The first amplification section 88 is connected to the adjusting section 80, the overvoltage protection section 86 being connected in derivation between the connection of the first amplification section 88 to the adjusting section 80 and a ground GND. The first amplification section 88 comprises a first operational amplifier 90 connected in a non-inverting mode. The first amplification section 88 is for example made of the first operational amplifier 90, of resistances R8, R9, R10 and of a potentiometer P2. The first amplification section 88 has a gain substantially equal to 3. In the example of Figure 4, the gain depends on the value of the resistances R8, R10 and the potentiometer P2. The resistance R9 is connected between an intermediate terminal OF1 and the inverting input of the first operational amplifier 90, the intermediate terminal OF1 being adapted to receive an offset voltage. The offset of the first amplification section 88 is substantially equal to zero. The output of the first amplification section 88, which corresponds to the output of the first operational amplifier 90, is connected to an intermediate terminal E Dir and to a first inverting section 92.

The input stage 30 includes the first inverting section 92 for inverting the amplified signal issued by the first amplification section 88, the first inverting section 92 being connected to the output of the first amplification section 88. The first inverting section 92 comprises a second operational amplifier 94 connected in an inverting mode. The first inverting section 92 is for example made of the second operational amplifier 94 and of resistances R1 1 , R12, R13. The resistance R12 is connected between an intermediate terminal OF2 and the inverting input of the second operational amplifier 94, the intermediate terminal OF2 being adapted to receive an offset voltage. The output of the first inverting section 92, which corresponds to the output of the second operational amplifier 94, is connected to an intermediate terminal E lnv. Therefore, a voltage relative to the input voltage is issued to the intermediate terminal E Dir and a voltage relative to the opposite of the input voltage is issued to the intermediate terminal EJnv by the input stage 30.

The reference value stage 32, shown in Figure 5, includes a reference voltage section 100 for issuing a stabilized reference voltage, for example a voltage substantially equal to +2.5V. The reference voltage section 100 is connected to +12V power supply. The reference voltage section 100 is made of passive components, for example of resistance R14, potentiometer P3, Zener diode ZD1 and diodes D3, D4.

The reference value stage 32 includes a second amplification section 102 connected to the output of the reference voltage section 100, the second amplification section 102 being adapted for amplifying the reference voltage delivered by the reference voltage section 100. The second amplification section 102 comprises a third operational amplifier 104 connected in a non-inverting mode. The second amplification section 102 is for example made of the third operational amplifier 104, of resistances R15, R16 and of a potentiometer P4. The second amplification section 102 has an adjustable gain according to the setting of the potentiometer P4. In the example of Figure 5, the gain depends on the value of resistance R15 and of the potentiometer P4. The output of the second amplification section 102, which corresponds to the output of the third operational amplifier 104, is connected to an intermediate terminal Ref+3V and to a second inverting section 106.

The reference value stage 32 includes the second inverting section 106 for inverting the amplified signal issued by the second amplification section 102, the second inverting section 106 being connected to the output of the second amplification section 102. The second inverting section 106 comprises a fourth operational amplifier 108 connected in an inverting mode. The second inverting section 106 is for example made of the fourth operational amplifier 108 and of resistances R17, R18, R19. The resistance R18 is connected between an intermediate terminal OF3 and the inverting input of the fourth operational amplifier 108, the intermediate terminal OF3 being adapted to receive an offset voltage. The output of the second inverting section 106, which corresponds to the output of the fourth operational amplifier 108, is connected to an intermediate terminal Ref-3V.

Therefore, a reference voltage is issued by the reference value stage 32 to the intermediate terminal Ref+3V, said reference voltage being preferably equal to +3V to more or less 0.15%, and the opposite of the reference voltage is issued by the reference value stage 32 to the intermediate terminal Ref-3V, said opposite reference voltage being preferably equal to -3V to more or less 0.15%. The intermediate terminals EJnv, E Dir, Ref+3V, Ref-3V are connected to the input of a four-position switch 1 10 which belongs to the second selection means 44. The four- position switch 1 10 has two outputs respectively connected to an intermediate terminal E Comp and to a third amplification section 1 12. The four positions of the four-position switch 1 10 are a first position labeled "1 ", a second position labeled "2", a third position labeled "3" and a fourth position labeled "4", as shown in Figure 5.

The intermediate terminal E Comp is connected to the intermediate terminal E Dir in the first and second positions of the four-position switch 1 10 and to the intermediate terminal EJnv in the third and fourth positions of the four-position switch 1 10. The input of the third amplification section 1 12 is connected to the intermediate terminal Ref+3V in the first and fourth positions of the four-position switch 1 10 and to the intermediate terminal Ref-3V in the second and third positions of the four-position switch 1 10. The four-position switch 1 10 is linked to the first knob 45 and the four positions labeled "1 ", "2", "3" and "4" respectively correspond to the four comparison modes "Increasing negative", "Increasing positive", "Decreasing positive" and "Decreasing negative".

The reference value stage 32 includes the third amplification section 1 12 for amplifying the reference voltage or the opposite reference voltage received from the sections 102, 106 via the four-position switch 1 10. The third amplification section 1 12 is connected to the output of the second amplification section 102 or to the output of the second inverting section 106 according to the selected position of the four-position switch 1 10. The third amplification section 1 12 comprises a potentiometer P5 for setting the value of a comparison voltage, a low-pass filter 1 14 for filtering noise during setting of the comparison voltage and a fifth operational amplifier 1 16 connected in a non-inverting mode. The third amplification section 1 12 is for example made of the potentiometer P5, the low-pass filter 1 14, the fifth operational amplifier 1 14, of resistance R21 and of a potentiometer P6. The third amplification section 1 12 has a gain substantially equal to 1 . In the example of Figure 5, the offset of the third amplification section 1 12 is substantially equal to zero due to the potentiometer P6 and the resistance R21 which is connected to +12V power supply. The output of the third amplification section 1 12, which corresponds to the output of the fifth operational amplifier 1 16, is connected to an intermediate terminal Ref_Comp. The low-pass filter 1 14 made of passive components, and comprises for example a resistance R20 and a capacitor C1 .

The reference value stage 32 is adapted to deliver to the intermediate terminal Ref_Comp a reference comparison voltage comprised between 0 and -3V in the second and third positions of the four-position switch 1 10 or between 0 and +3V in the first and fourth positions of the four-position switch 1 10. The comparison stage 34, shown in Figure 6, includes a summation section 120 for operating a difference between the voltages delivered respectively to intermediate terminals E Comp and Ref_Comp. The summation section 120 comprises a sixth operational amplifier 122 connected in a summation mode. The summation section 120 is adapted to receive to the inverting input of the sixth operational amplifier 122 the voltages respectively delivered to intermediate terminals E Comp and Ref_Comp and to operate a difference between said voltages so that a voltage passing by zero is issued to a comparison section 124. The summation section 120 is for example made of the sixth operational amplifier 122, of resistances R22, R23, R24, R25, of a capacitor C2 and of a Zener diode ZD2. The resistance R22 is connected between the inverting input of the sixth operational amplifier 122 and the intermediate terminal Ref_Comp, the resistance R23 is connected between said inverting input and the intermediate terminal E Comp and the resistance R24 is connected between said inverting input and an intermediate terminal OF4. The resistance R25, the capacitor C2 and the Zener diode ZD2 are connected in parallel between the output and the inverting input of the sixth operational amplifier 122. The capacitor C2 is adapted to limit the bandwidth of the summation section 120. The Zener diode ZD2 is adapted to limit between +0.7V and -4.7V the voltage delivered to the output of the summation section 120, which corresponds to the output of the sixth operational amplifier 122.

The comparison stage 34 includes the comparison section 124 which is connected to the output of the summation section 120. The comparison section 124 comprises a seventh operational amplifier 126 connected in a comparison mode. The comparison section 124 is adapted to compare the output of the summation section 120 with a null voltage, said output being connected to the inverting input of the seventh operational amplifier 126 and the non-inverting input of the seventh operational amplifier 126 being linked to the ground GND. The comparison section 124 is for example made of the seventh operational amplifier 126, of resistances R26, R27, R28, R29, R30 of diodes D5, D6 and of a Zener diode ZD3. The resistance R26 is connected between the inverting input of the seventh operational amplifier 126 and the output of the summation section 120, the resistances R27 and R28 are connected between the non-inverting input of said amplifier and the ground GND. The Zener diode ZD3 is connected between the output and the inverting input of the seventh operational amplifier 126 in order to limit to +4.7V or to -0.7V the voltage delivered to the output of the comparison section 124, which corresponds to the output of the seventh operational amplifier 126.

The comparison section 124 forms an hysteresis comparator, the output of said hysteresis comparator being for example stabilized to +4.7V when the comparison is true, i.e. when the voltage delivered by the summation section 120 and received by the inverting input of the seventh operational amplifier 126 becomes negative, or otherwise to -0.7V when the comparison is false. The output of the comparison section 124, which corresponds to the output of the comparison stage 34, is connected to an intermediate terminal Comp Out.

The comparison stage 34 is an analogic stage including several electric components, for example the operational amplifiers 122, 126, the resistances R22 to R30, the capacitor C2, the Zener diodes ZD2, ZD3 and the diodes D5, D6, as previously described in view of Figure 6.

The generating stage 36, shown in Figure 7, is connected to the output of the comparison stage 34 via the intermediate terminal Comp Out. The generating stage 36 includes a formatting section 130 for formatting the comparison signal issued by the comparison stage via the intermediate terminal Comp Out before the generation of a TTL signal. The formatting section 130 comprises NAND gates NG1 , NG2, NG3, NG4 connected between the intermediate terminal Comp Out and a generating and adjusting section 132. The NAND gates NG1 , NG2 are adapted to format the comparison signal and the NAND gates NG3, NG4 are adapted to memorize the result of the last comparison. This memorization via the NAND gates NG3, NG4 avoids the risk of multiple triggers of the magnetic phrenic nerve stimulation device 14.

The generating stage 36 includes the generating and adjusting section 132 which comprises a first integrated circuit IC1 for generating the output electric control signal, for example a pulse output signal, and preferably a TTL output signal, based on the formatted comparison signal received from the formatting section 130. The output electric control signal is quasi-synchronous with the comparison stage 34 for the first time of the comparison. The generating and adjusting section 132 comprises a potentiometer P7 for adjusting the duration of the pulse signal, for example from 10 ms to 100 ms. The potentiometer P7 is linked to the second knob 48 for adjusting said duration. The first integrated circuit IC1 , the potentiometer P7 and the second knob 48 form the adjusting means 46. The generating and adjusting section 132 is for example made of the first integrated circuit IC1 , the potentiometer P7, capacitors C3, C4, C5 and resistances R31 , R32, R33, R34. The generating and adjusting section 132 is connected to the output terminal 24 of the controller 16. The resistance R34 is a resistance for protecting the output terminal 24 of the controller.

The generating stage 36 also includes a display and record section 134 connected to the output of the formatting section 130. The display and record section 134 comprises two light-emitting diodes LED1 , LED2 forming respectively the second indicator lamp 64 for indicating a true comparison done by the comparison stage 34, and the third indicator lamp 66 for indicating that the controller 16 is ready to issue the pulse output signal. The anodes of the two light-emitting diodes LED1 , LED2 are connected to +5V power supply via resistances R35, R36 and the cathodes of the two light-emitting diodes LED1 , LED2 are linked to the ground GND via controllable interrupters SW1 , SW2, such as transistors.

In the example of Figure 7, the controllable interrupters SW1 , SW2 are bipolar transistors and the base electrodes of said bipolar transistors are respectively connected to the output of the NAND gate NG2 via a resistance R37 and to the output of the NAND gate NG4 via a resistance R38. When the controllable interrupters SW1 , SW2 are closed, the two light-emitting diodes LED1 , LED2 emit some light and inversely when the controllable interrupters SW1 , SW2 are open, the two light-emitting diodes LED1 , LED2 are off. The display and record section 134 also comprises resistances R39 and R40 for connecting the output of the NAND gate NG2 to the recorder output terminal 26.

The generating stage 36 includes a generating mode section 136 connected to the input of the formatting section 130. The generating mode section 136 is adapted for operating the generating mode among the two aforementioned modes: the first mode M1 wherein the output control signal is generated for each true comparison and the second mode M2 wherein the output control signal is generated once for a first true comparison and only under condition after said first generation. The generating mode section 136 comprises two NAND gates NG5, NG6 connected in series, the output of the NAND gate NG6 being connected to one input of the NAND gate NG4 of the formatting section 130, the other input of said NAND gate NG4 being connected to the output of the NAND gate NG3.

The generating mode section 136 comprises a second switch 138 connected to a first input of the NAND gate NG5, the second switch 138 being coupled to the first lever 43B of the first selection means for switching between a first position 139A corresponding to the first mode M1 and a second position 139B corresponding to the second mode M2. In the first position 139A of the second switch 138, the first input of the NAND gate NG5 is connected to a release section 140 for releasing the memorization of the comparison done by the NAND gates NG3, NG4. In the second position 139B of the second switch 138, the first input of the NAND gate NG5 is connected to +5V power supply via a resistance R41 , so that said input is powered by the +5V voltage when the second switch 138 is in its second position 139B.

The generating mode section 136 comprises a third switch 142 connected to the second input of the NAND gate NG5, the third switch 142 being coupled to the second lever 57 for switching between an ON position corresponding to enabling the generation of the output control signal and an OFF position corresponding to disabling said generation. In the OFF position of the third switch 142, the second input of the NAND gate NG5 is connected to the ground GND.

The generating mode section 136 comprises a fourth switch 144 connected to the second input of the NAND gate NG5, similarly to the third switch 142, the fourth switch 144 being coupled to the push button 70 and closed when the push button 70 is pressed. The generation of the output signal in the second mode M2 is enabled after a push on said button 70, i.e. after a commutation of the fourth switch 144 from its open position to its closed position. In the closed position of the fourth switch 144, the second input of the NAND gate NG5 is connected to the ground GND. The second input of the NAND gate NG5 is connected to +5V power supply via a resistance R42, so that said input is powered by the +5V voltage when the third switch 142 is in its ON position, i.e. with the second lever 57 in ON position, or when the fourth switch 144 in its open position, i.e. with the push button 70 released, the second input of the NAND gate NG5 being linked to the ground GND otherwise.

The generating stage 36 includes the release section 140 which comprises a second integrated circuit IC2 for generating a release signal after a delay comprised between 25 ms and 50 ms, and a NAND gate NG7 for formatting the release signal issued by the second integrated circuit IC2 towards the second switch 138. The second integrated circuit IC2 is connected to the output of the NAND gate NG2 via a capacitor C6 and the release section 140 also comprises resistances R43, R44, R45 and capacitors C7, C8.

The operation of the installation 10 according to the invention will now be described in view of Figures 8 to 10. The mouth pressure sensor 12 measures the mouth pressure of a patient and delivers an electric signal representative of the mouth pressure to the controller 16. The controller 16 receives said electric signal representative of the mouth pressure via its input terminal 22 and the received signal is formatted by the input stage 30. A voltage corresponding to the received signal, eventually divided by 10 if the third lever 61 is in its 10V capacity position, and the opposite of said voltage are issued by the input stage 30 to the comparison stage 34. The comparison stage 34 also receives a reference comparison voltage and the opposite of said reference comparison voltage from the reference value stage 32, the value of said reference comparison voltage depending on the setting of the third knob 52.

The comparison stage 34 then compares the voltage corresponding to the received signal with the reference comparison voltage and according to the position of the first knob 45 among the four positions corresponding to the four comparison modes "Increasing negative", "Increasing positive", "Decreasing positive" and "Decreasing negative".

In the first mode also called "Increasing negative" mode, the comparison stage 34 compares if the input signal is greater or equal than a negative reference value, as shown in Figure 8. In Figure 8, a curve 200 represents the voltage corresponding to the received signal and a curve 202 represents the negative reference value to be compared with the input signal. The result of the comparison is represented by the curve 204 wherein a null level corresponds to a false comparison and a 1 level corresponds to a true comparison. Therefore, in the first mode, the comparison is true when the value of the curve 200 is greater than the value of the curve 202 and a pulse output signal, represented by the curve 206, is generated simultaneously with the change in the comparison output from false to true. In the example of Figure 8, the selected mode among the two generating modes is the first mode M1 wherein the output control signal is generated for each true comparison.

In the second mode also called "Increasing positive", the comparison stage 34 compares if the input signal is greater or equal than a positive reference value, as shown in Figure 9. In Figure 9, a curve 210 represents the voltage corresponding to the received signal and a curve 212 represents the positive reference value to be compared with the input signal. The result of the comparison is represented by the curve 214 wherein a null level corresponds to a false comparison and a 1 level corresponds to a true comparison. In the second mode, the comparison is true when the value of the curve 210 is greater than the value of the curve 212 and a pulse output signal, represented by the curve 216, is generated simultaneously with the change in the comparison output from false to true, similarly to the first mode. In the example of Figure 9, the selected mode among the two generating modes is also the first mode M1 .

In the third mode also called "Decreasing positive", the comparison stage 34 compares if the input signal is smaller or equal than a positive reference value.

In the fourth mode also called "Decreasing negative", the comparison stage 34 compares if the input signal is smaller or equal than a negative reference value, as shown in Figure 10. In Figure 10, a curve 220 represents the voltage corresponding to the received signal and a curve 222 represents the negative reference value to be compared with the input signal. The result of the comparison is represented by the curve 224 wherein a null level corresponds to a false comparison and a "1 " level corresponds to a true comparison. In the fourth mode, the comparison is true when the value of the curve 220 is smaller or equal than the value of the curve 222. In the example of Figure 10, the selected mode among the two generating modes is the second mode M2 wherein the output control signal is generated once for a first true comparison and only under condition after said first generation, said condition being for example the activation of the enabling means 68. The pressure on the push button 70, corresponding to the activation of the enabling means 68 in the described embodiment, is represented by the curve 226 where the change from null level to 1 level corresponds to said activation.

In the example of Figure 10, the pulse output signal, represented by the curve 216, is generated each time after an activation of the enabling means 68 when the comparison is true. It should be noted that after the true comparison shown on left in Figure 10 no pulse is generated as a first pulse, not shown, was already generated in the second mode M2 for the first true comparison and as the condition (pressure on push button 70) was not fulfilled for this true comparison on left of Figure 10.

Thus, the controller 16 allows to compare a variable external voltage, obtained for example from the pressure sensor 12, with an adjustable reference voltage to determine when the external voltage just gets bigger or smaller than the reference, according to the choice of the user via the first knob 45. The reference value is also easy to adjust via the third knob 52.

The controller 16 then emits a signal adapted to synchronize another device, such as the magnetic phrenic nerve stimulation device 14. The controller 16 allows a comparison in the four quadrants of the input voltage through the second selection means 44 for selecting a comparison mode among the four modes M1 to M4.

In addition, the hysteresis avoids oscillating the comparator with a noisy input. The hysteresis comparator 124 therefore improves stability of the comparison.

The controller 16 is much easier-to-use in comparison with a computer system where specific software needs to be installed and then launched. In addition, the controller 16 according to the invention is dedicated to the installation for determining twitch mouth pressure and easy to move where the patient has to be examined.

The installation 10 according to the invention is therefore a simple and easy-to-use installation which allows determining twitch mouth pressure of a patient.

The installation 10 according to the invention allows a very good detection of inspiratory muscle weakness as it will be described hereinafter in view of Figure 1 1 .

Figure 1 1 illustrate comparisons results of twitch mouth pressure (TwPmo) tests using a pressure trigger technique on one hand, with twitch esophageal pressure (TwPeso) tests after magnetic stimulation on the other hand, said tests being carried out on patients with neuromuscular disorder and selective respiratory muscle disorder. The aim was to validate TwPmo test on patients with neuromuscular disorder and selective respiratory muscle disorder by comparing it to TwPeso test after magnetic stimulation. The aim was also to determine whether TwPmo test reduces the number of patients mistakenly diagnosed with muscle weakness when using only sniff nasal pressure (SNIP).

Seventy-two patients were tested were evaluated non-invasively with SNIP test on one hand and with TwPmo test on the other hand. Among said seventy- two patients; sixty patients were suspect of neuromuscular disorder and twelve patients were suspect of isolated diaphragmatic dysfunction. Among them, 42 patients received an invasive diaphragmatic exploration allowing TwPeso measurements. Magnetic stimulation for TwPmo and TwPeso measurements was triggered by inspiratory pressure of -5 cm H ₂ 0 and -1 cm H ₂ 0.

Overall, in the 42 patients with invasive exploration of the diaphragm (22 males; 44.9 ±18.7 years old), the best correlation between TwPmo and TwPeso was obtained when using an inspiratory pressure trigger of -5 cm H ₂ 0 (R°= 0.93; P < 0.0001 ), as shown in Figure 1 1 .

With non-invasive exploration techniques, SNIP was below normal value (< -50 cm H ₂ 0 for males and < - 45 cm H ₂ 0 for females) in 48 patients among 72 patients. However, when combining SNIP with TwPmo, at a -5 cm H ₂ 0 inspiratory pressure trigger, the number of patients with suspected inspiratory muscle weakness (abnormal SNIP and abnormal TwPmo (< -1 1 cm H ₂ 0)) was reduced to 37 patients. Accordingly, when analyzing etiologies in the 1 1 patients with abnormal SNIP and normal TwPmo, 7 patients presented a non-muscular cause of restrictive syndrome (3 patients with pulmonary fibrosis and 4 patients with parietal disease).

Thus, TwPmo measurement using an inspiratory pressure trigger adjusted at -5 cm

H ₂ 0 is a simple and non-invasive technique correlated to TwPeso for patients with neuromuscular disorder and selective respiratory muscle disorder. Moreover, it allows reducing the number of erroneous diagnosis of muscle weakness determined by SNIP and therefore reducing the indication of invasive exploration of inspiratory muscles.