System and methods for the measurement of lung volumes

A system and method for determining FRC, TGV, TLC and RV includes a hand-held unit with a shutter assembly designed to minimize measured air displacement due to shuttering. Measurements of flow and pressure are used to derive the lung parameters.

FIELD OF THE INVENTION

The present invention relates to measurement of respiratory parameters and, more particularly to measurement of FRC, TGV, TLC and RV.

BACKGROUND OF THE INVENTION

Absolute lung volume is a key parameter in pulmonary physiology and diagnosis but is not easy to measure in the live individual. It is relatively straightforward to measure the volume of air which is exhaled from a subject's mouth but at the end of complete exhalation, a significant amount of air is always left in the lungs because the mechanical properties of the lungs and chest wall, including the ribs, do not allow the lungs to collapse completely. The gas left in the lungs at the end of a complete exhalation is termed the Residual Volume (RV) which may be significantly increased in disease. The total volume of gas in the lungs at the end of a maximal inspiration is termed the Total Lung Capacity (TLC) which includes the RV plus the maximum amount of gas which can be inhaled or exhaled and which is termed the Vital Capacity (VC). However, during normal breathing the subject does not empty the lungs down to RV nor inflate them to TLC. The amount of gas in the lungs at the end of a normal breath, as distinct from a complete exhalation, is termed the Functional Residual Capacity (FRC) or Thoracic Gas Volume (TGV), depending upon the manner in which it is measured. For simplicity when this volume is measured by inert gas dilution techniques it will be termed FRC and when measured by barometric techniques involving gas compression as in this application it will be termed TGV.

In order to determine the total volumes of gas in the lungs at TLC, TGV or RV, indirect methods must be used since it is impossible to completely exhale all the gas from the lungs. There are two basic techniques currently available, gas dilution and whole body plethysmography (a barometric method). Gas dilution involves the dilution of a known concentration and volume of inert gas by the gas in the lungs of the subjects and is critically dependent on complete mixing of the marker gas and lung gas. In subjects with poor gas mixing due to disease, this technique is very inaccurate and generally underestimates the true FRC. In the whole body plethysmograph, the subject makes respiratory efforts against an obstruction within a gas tight chamber and the changes in pressure on the lung side of the obstruction can be related to the changes in pressure in the chamber through Boyle's law to calculate TGV. This method accurately measures TGV even in sick subjects but requires complicated and expensive equipment and is difficult to perform.

Once FRC (gas dilution), or TGV (whole body plethysmograph), is calculated, the measurement by spirometry of the extra volume of gas which can be exhaled from the end of a normal exhalation (Expiratory Reserve Volume, ERV) and the extra volume which can be inhaled from the end of a normal exhalation (Inspiratory Capacity, IC) allows the calculation of TLC and RV.

These three important indicators (TLC, RV and FRC or TGV) are mutually connected through the following formulas: RV=FRC−ERV and TLC=FRC+IC and, TLC=RV+ERV+IC=RV+VC.

If FRC is determined by gas dilution and TGV by a barometric method, then the difference between them (TGV minus FRC) is a measure, albeit approximate, of the volume of poorly ventilated or ‘trapped gas’ in the lungs.

In healthy subjects TGV and FRC should be virtually identical as there is little or no trapped gas, hence, for all practical matters, the term TGV shall apply for FRC as well. In summary, determination of TLC, TGV and RV is central to the complete evaluation of lung function.

At the present time, FRC is measured by two gas-based techniques: the rebreathing of an inert gas, such as helium, in a closed circuit or the wash in or out of an inert marker gas, which can be the nitrogen, normally present in the lung. Both techniques have been used for several decades and are known to have several shortcomings, e.g., they are complex, hard to operate, moderately expensive, unreliable for the measurement of FRC in patients with poor gas mixing due to disease, and the tests are lengthy and uncomfortable for the subjects.

Body plethysmograph devices for determination of TGV are disclosed, for example, in U.S. Pat. No. 6,113,550 to Wilson, and have been known and used since at least 1955. Other devices, which include the use of impedance belts have been disclosed as well, for example, in U.S. Pat. No. 5,857,459. In both types of devices, the plethysmograph chamber or the impedance belts are designed so that the volume in the lungs can be calculated directly, so as to provide reliable measurement parameters for calculation of TGV. However, these methods for measuring TGV are all less than optimal, requiring a sealed chamber in which the subject sits, or external belts which have been shown not to provide reliable results and which may be bulky, expensive and inconvenient to operate, and require full cooperation of the subject during the measurement maneuvers to obtain meaningful results.

Hand held devices for measurement of certain lung parameters, such as spirometers, are known in the art. However, spirometers are not designed to measure internal volume. Other hand held devices known in the art include devices which have been used to determine airway resistance. Such devices use a shutter mechanism for blocking and opening of airways. For example, U.S. Pat. No. 5,233,998 to Chowienczyk discloses an apparatus with an interrupting valve for interrupting the flow of air through a bore. However, since this device is designed to measure resistance to air flow rather than lung volume, the shutter speeds may be relatively slow, and relative air displacement may occur.

The importance and need for a new, accurate, and easy to use method and device to measure TGV have been clearly stated in the ATS (American Thoracic Society)/NHLBI (U.S. National Heart, Lung and Blood Institute) Consensus Statement of Measurement of Lung Volumes in Humans, Clausen and Wagner et al., Nov. 12, 2003 (the Consensus Statement), page 6: “Systems will be available in the future which through new technology will offer potential advantages (e.g., ease of use, rapidity of testing, improved accuracy) over the methodology recommended in this document (i.e., nitrogen wash-out, helium gas dilution and body plethysmography). The ATS and the ERS (European Respiratory Society) encourage such innovation. However, it is the responsibility of the manufacturers to demonstrate that the lung volumes reported by new technology do not differ substantially from those obtained by the standard techniques; such comparisons must be made using subjects with varying severities of obstructive and restrictive lung disease as well as healthy subjects.”

It is thus an object of the present invention to provide systems and methods for measurement of TGV without the need for external belts or chambers and which can provide accurate measurements which are up to the standards of the currently used systems.

SUMMARY OF THE INVENTION

In accordance with embodiments of the present invention, there is provided a method of calculating lung parameters. The method includes providing a system for measuring volume changes in the lungs, the system including a respiration module for inhalation or exhalation, commanding the system to occlude air flow within the respiration module during an inhalation or exhalation, obtaining a flow curve and a pressure curve during the occlusion, calculating an instantaneous volume in the lungs during the occlusion based on parameters of the flow curve and the pressure curve, and calculating a lung volume parameter based on the calculated volume.

In some embodiments, the occlusion of air flow may occur for less than 0.25 seconds and more preferably, for less than 5 ms and even more preferably for less than 2 ms. Calculating the instantaneous volume in the lungs may include determining a first pressure at a first point along the pressure curve, determining a second pressure at a second point along the pressure curve, calculating a pressure change by calculating a difference between the first pressure and the second pressure, determining a first flow point along the flow curve, determining a second flow point along the flow curve, calculating a volume change by integrating the flow curve from the first flow point to the second flow point, and calculating the instantaneous volume from the pressure change and the volume change. In some embodiments, the first point along the pressure curve is approximately at a start of the occlusion of air flow and the second point along the pressure curve is approximately at an end of the occlusion of air flow. In some embodiments, the first flow point is a first point which reaches a baseline flow value following the occlusion of air flow and the second flow point is a second point which reaches the baseline flow value following the first flow point. In other embodiments, the first flow point is a first point which reaches a baseline flow value following the occlusion of air flow and the second flow point is substantially equivalent in time to a point along the pressure curve of a local minimum of pressure.

In some embodiments, calculating the instantaneous volume in the lungs includes calculating a rate of pressure change, determining a baseline flow prior to shutter occlusion, and calculating the instantaneous volume based on the rate of pressure change and the baseline flow.

Embodiments of the present invention further include calculating TGV, FRC, RV and/or TLC based on the calculated instantaneous volume.

There is provided, in accordance with additional embodiments of the present invention, a system for determining respiratory parameters. The system includes a respiration module having a housing with a first end, a second end, and a body connecting the first end and the second end, the body forming a cavity for air flow in a first direction, a shutter assembly having a movable portion positioned within the cavity, the movable portion movable in a second direction which is substantially orthogonal to the first direction. The movable portion is configured to block and allow air flow. The system further includes a pressure measurement component positioned within the cavity for measuring pressure, and an air flow measurement component positioned within the cavity for measuring air flow in said cavity, and a control unit configured to receive pressure data from the pressure measurement component and flow data from the air flow measurement component.

There is provided, in accordance with additional embodiments of the present invention, a system for determining respiratory parameters. The system includes a respiration module having a housing with a first end, a second end, and a body connecting the first end and the second end, the body forming a cavity for air flow in a first direction, the cavity having a pre-shutter cavity component and a post-shutter cavity component, and a shutter assembly with a movable portion positioned within the cavity. The movable portion is configured to move in a second direction such that an opening is created for movement of air flow through the post-shutter cavity component of the cavity, the post-shutter cavity component having a flow area for movement of air flow past said movable portion, wherein a cross-sectional surface area of the movable portion in the second direction is smaller than the flow area of the post-shutter cavity component. The respiration module further includes a pressure measurement component positioned within the cavity for measuring pressure in the cavity, and an air flow measurement component positioned within the cavity for measuring air flow in the cavity. The system further includes a control unit configured to receive pressure data from the pressure measurement component and air flow data from the air flow measurement component.

There is provided, in accordance with yet additional embodiments of the present invention, a hand-held device for measurement of respiratory parameters. The device includes a housing having a first end, a second end, and a body connecting the first end and second end, the body forming a cavity for air flow. The device further includes a shutter assembly with a movable portion positioned within the cavity, wherein a cycle is defined as a single closing and a single opening of the cavity to air flow via the movable portion, and wherein the movable portion is configured to move at a speed of at least 5 ms per cycle. The device further includes a pressure measurement component positioned within the cavity for measurement of pressure within the cavity; and an air flow measurement component positioned within the cavity for measurement of a flow parameter within the cavity.

In accordance with further features, the respiration module may be a hand-held device that is positionable at a mouth of a user.

In some embodiments, the shutter assembly includes a housing having at least one wall defining a chamber, and an air outlet in the wall, wherein the movable portion includes a sealing portion. In a first configuration, the sealing portion abuts a portion of the chamber thereby blocking air flow through the chamber, and in a second configuration the sealing portion does not abut the portion of the chamber, thereby allowing air flow through the chamber and out through the air outlet.

In other embodiments, the shutter assembly includes a housing defining a chamber which is substantially cylindrical, a disk having edges and at least one opening, the disk positioned within the chamber such that air is prevented from flowing around its edges, wherein the movable portion is a rotatable shutter for opening and closing of the one opening. The disk may be movable in a direction opposite to a direction of movement of the rotatable shutter.

In yet additional embodiments, the shutter mechanism includes an outer cylinder with an outer slit along at least a portion of a length of thereof, and the movable portion includes an inner rotatable cylinder having an inner slit along at least a portion of a length thereof. The inner rotatable cylinder is positioned within the outer cylinder such that air is prevented from flowing between the outer cylinder and the inner rotatable cylinder, and wherein when the outer slit and the inner slit are aligned, the opening for said movement of air flow is created. The outer cylinder may be movable in a direction which is opposite to a direction of movement of said inner rotatable cylinder.

It will be appreciated that for simplicity and clarity of illustration, elements shown in the drawings have not necessarily been drawn accurately or to scale. For example, the dimensions of some of the elements may be exaggerated relative to other elements for clarity or several physical components may be included in one functional block or element. Further, where considered appropriate, reference numerals may be repeated among the drawings to indicate corresponding or analogous elements. Moreover, some of the blocks depicted in the drawings may be combined into a single function.

DETAILED DESCRIPTION

The present invention is directed to a system and methods for determination of lung parameters, and more particularly, determination of Functional Residual Capacity (FRC) Thoracic Gas Volume (TGV), Total Lung Capacity (TLC) and Residual Volume (RV). The system and methods of the present application are designed to directly measure volume in the lungs with a handheld device, without the use of external chambers or belts. The principles and operation of a system and methods according to the present invention may be better understood with reference to the drawings and accompanying descriptions.

Reference is now made toFIG. 1, which is a schematic illustration of a system10for measurement of respiration parameters, in accordance with embodiments of the present invention. System10includes a respiration module12and a control unit14. Respiration module12is typically a hand-held device that is positionable at a mouth of a user, and is used for inhalation and/or exhalation of air for the purposes of measuring respiration parameters of the user. Respiration module12includes a housing16having a first end18and a second end20, and a housing body22extending from first end18to second end20and defining a cavity24therethrough. Respiration module12includes a shutter assembly32which can open or close to allow or prevent air flow therethrough and which is controlled by a motor34. Respiration module may be designed to introduce air flow resistance of less than 1.5 cm H2O/Liter/sec, in accordance with ATS (American Thoracic Society) guidelines for respiratory devices.

Housing16may further include at least one pressure measurement component26and at least one air flow measurement component28. Pressure measurement component26may be any suitable manometer or sensor for the measurement of absolute pressure with a data rate of at least 500 Hz; and preferably at a data rate of at least 1000 Hz. Such pressure sensors are readily available and may be acquired, for example, from Honeywell Catalog #40PC001B1A. Air flow measurement component28may be fabricated for example from an air flow resistive means and a differential pressure manometer, or alternatively from a Pitot tube and a differential pressure manometer. The differential pressure manometer may be any suitable sensor with a data rate of at least 500 Hz; and preferably at a data rate of at least 1000 Hz. Such differential pressure manometers are readily available and may be acquired (for example, from Honeywell Catalog #DC002NDR4. Control unit14is in electrical communication with pressure measurement component26, air flow measurement component28, and motor34, which is used for opening and closing of a shutter mechanism, as will be described further hereinbelow.

Reference is now made toFIG. 2, which is a block diagram illustration of control unit14. Control unit14may include a converter17which converts analog data received from pressure measurement component26and air flow measurement component28into digital format at a rate of at least once every 2 milliseconds (ms), and preferably at a rate at least once every 1 ms. Converter17converts digital signals into commands to motor34for shutter assembly32to close and to open. Control unit14further includes a microprocessor19which is programmed to: (a) read digital data of pressure and flow received from the converter17in accordance with real-time recording, at a rate commensurate with the converter rate for each data channel and translate this digital data into pressure and flow appropriate units and store them; (b) generate signals which are sent through converter17to motor34to command the shutter to close or to open, and (c) process above mentioned flow and pressure data in accordance with real time recording, to calculate lung volume and specifically calculate TGV, TLC and RV. Microprocessor19also manages a Man-Machine Interface (MMI) that accepts operation commands from an operator and displays results. Control unit14may further include a display15for displaying the resulting values. Control unit14may further include a keyboard to enter subject's personal and medical information and to select desired operational modes such as shuttering duration, timing, manual versus automatic operation, calibration procedures, etc.

Reference is now made toFIG. 3, which is a perspective view illustration of respiration module12in accordance with one embodiment of the present invention. Respiration module12includes a mouthpiece30for placement into a mouth of a user, a shutter assembly32attached to (but which may be removable from) mouthpiece30, a motor34for controlling movements of shutter assembly32, and a flow meter tube36, which is the air flow resistive means used to calculate air flow parameters. Mouthpiece30may be any suitable mouthpiece such as, for example, those available from A-M Systems, Inc. catalog number 156300. Shutter assembly32may have several different configurations, some of which will be described in greater detail. Shutter assembly32is designed specifically to minimize air displacement during opening and closing thereof. Motor34may be any suitable motor such as, for example, a standard solenoid. Alternatively, motor34may be any electronically, pneumatically, hydraulically or otherwise operated motor. Finally, flow meter tube36is a section of respiration module12which is distal to shutter assembly32. In the present embodiment, flow meter tube36is distal to shutter assembly32so that measurement of air flow can be taken downstream of the open or closed shutter. However, flow meter tube36may also be positioned adjacent to pressure measurement component26. Flow meter tube36may be calibrated in accordance with known methods so as to account for variations in density due to differences in room temperature and body temperature.

Reference is now made toFIG. 4which is a schematic illustration showing the respiration module12ofFIG. 3with the addition of electronic components. An electronics module38may be positioned on or next to shutter assembly32. Electronics module38is configured to receive data from pressure and flow measurements and to send the received data to control unit14for processing. In some embodiments, control unit14is attached to respiration module12(and more particularly, to electronics module38) via wires. In other embodiments, wireless connections may be employed. In the embodiment shown inFIG. 4, pressure measurement component26is a pressure sensor positioned in close proximity to mouthpiece30and shutter assembly32and is within or in direct contact with electronics module38, and air flow measurement component28is a flow meter tube36connected via tubes42to a differential pressure sensor positioned on or within electronics module38. Thus, the pressure sensor receives an air pressure signal through an air pipe from shutter assembly32from a point between mouthpiece30and shutter assembly32. The pressure sensor outputs an electrical signal proportional to the air pressure in the pipe (relative to the surrounding atmospheric pressure). The differential pressure sensor accepts two air pipes from flow meter tube36. The differential pressure sensor outputs an electronic signal proportional to the difference in pressure between the two pipes, which may be converted into a flow signal. It should be readily apparent that the invention is not limited to the embodiment shown herein and that in some embodiments, electronics module38may be positioned in a different location.

Shutter assembly32is used for breaking a stream of inhaled or exhaled air, located within cavity24. Shutter assembly32is configured to operate quietly so as not to create any reflexes or undesired responses by the subject, thereby avoiding inaccuracies of measurement. More importantly, shutter assembly32is configured to operate quickly, both in terms of its shutting speed (i.e., the time it takes for the shutter to go from an open state to a closed state) and in terms of its shutting duration (i.e., the period of time for which the shutter is closed). The shutting speed is in some embodiments less than 10 ms, preferably less than 5 ms, and more preferably less than 2 ms. The shutting duration is in some embodiments less than 2 seconds and preferably less than 100 ms. This fast paced shutting speed and shutting duration are key features in the present invention to provide the accuracy and reliability of the measurement of TGV, TLC and RV. The need for high speed operation of shutter assembly32and high rate of data acquisition (as described above with reference to control unit14) results from the typical response time of the lungs to abrupt occlusion of the airways while breathing. The response time of the lungs of a human being is in the order of ms to tens of ms, and accurate recording of the details of the response of the lungs to such abrupt occlusion is essential for accurate calculation of the internal volume of the lungs.

In addition to high speed, shutter assembly32is also configured to perform occlusion of cavity24with minimum, and preferably without any, displacement of air that may be recorded by the pressure sensor or the flow sensor. In order to provide rapid shutter movement with minimal air displacement, shutter assembly32, as well as other embodiments of shutter assembly in accordance with the present invention, is designed so that the open/close movement of the shutter is substantially orthogonal to the direction of air flow being measured. Thus, in one embodiment, as shown inFIGS. 5A and 5B, a movable portion44is positioned within shutter assembly32and is configured to move back and forth in a first direction, as shown by arrow48. A fixed portion64may be present as well, wherein when movable portion44is in an open position, movable portion44does not contact fixed portion64so as to allow for air flow, and when movable portion is in a closed position, movable portion44is in contact with fixed portion64so as to seal any air flow pathways. Air flow which enters shutter assembly32is configured to move in a direction which is substantially orthogonal to the movement of movable portion44, as shown by arrow46. InFIG. 5A, shutter assembly32is shown in an open configuration, wherein air flow is possible; inFIG. 5B, shutter assembly32is shown in a closed configuration, wherein air flow is stopped due to the movement of movable portion44and contact of movable portion44with fixed portion64. A more detailed example of this type of configuration will be described hereinbelow.

Reference is now made toFIG. 6, which is a perspective illustration of an internal view of a portion of shutter assembly32, in accordance with embodiments of the present invention. Shutter assembly32includes a shutter assembly housing33defining a chamber35. Chamber35is a portion of cavity24of respiration module12, described above with reference toFIG. 1. However, chamber35refers to the portion of cavity24which is part of shutter assembly32. Chamber35has a proximal end37, which is the end closest to mouthpiece30when mouthpiece is present and which is proximal to movable portion44of shutter assembly32, and a distal end39, which is distal to movable portion44and which is closed to air flow. Thus, air flows from proximal end37to distal end39, but is configured to exit chamber35via an outlet56positioned along a wall of chamber35. A fixed portion64is positioned at proximal end37of chamber35. Movable portion44includes a flat surface47, a sealing portion60(not shown) and a connecting portion54connecting flat surface47to sealing portion. Movable portion44is positioned adjacent to and is movable with respect to fixed portion64via leading pins50and springs52positioned there between.

Reference is now made toFIG. 7AandFIG. 7B, which are partially cut-away perspective illustrations of shutter assembly32in a sealed configuration and an open configuration, respectively. As shown inFIG. 7A, sealing portion60of movable portion44includes a circular compartment61within which may be positioned a set of O-rings62. One of O-rings62may be positioned against a chamber floor and the other one of O-rings62may be positioned against a stair63of fixed portion64. When movable portion44is pushed towards fixed portion64(via motor34such as a solenoid, for example) as shown inFIG. 7A, circular compartment61fully encloses O-rings62, thus preventing air flow. When movable portion44is released, springs52push movable portion44away from fixed portion64, resulting in air space between O-rings62and the chamber floor. Thus, air can flow into chamber35, and out through outlet56located on a wall of chamber35. It is a feature of the present invention that the shutter assembly allows for minimal air displacement. This may be accomplished, for example, by providing a small area of movement which can be used to displace a large amount of air and which has available a large “flow area”, defined as an area available for air flow. In the present example, this feature can be seen as follows. The area through which air flows is the area of sealing in the vicinity of the O-rings, and is substantially proportional to the circumference of the O-rings. Moreover, since flat surface47is full of openings58, movement of movable portion44has a relatively small surface area. Thus, movements are contained to a small surface area, while allowing for a relatively large flow area in a post-shutter component of cavity24.

Reference is now made toFIG. 8A, which is a cross sectional illustration of chamber35of shutter assembly32. Fixed portion64is fixed to chamber35via screws65or other fixation means. Flat portion47, connecting portion54and sealing portion60of movable portion44are all visible in cross section. Springs52positioned on pins50allow for movement of movable portion44with respect to fixed portion64. Reference is now made toFIG. 8B, which is a cross sectional illustration showing sealing portion60in greater detail. Sealing portion60includes circular compartment61with O-rings62positioned therein. O-rings62are positioned on fixed portion64and on the floor of chamber35.

Reference is now made toFIG. 9A, which is a perspective illustration of a shutter assembly132in accordance with additional embodiments of the present invention. Shutter assembly132includes a chamber135for air flow wherein chamber135is substantially cylindrical in shape. A motor134is positioned at a first end of chamber135and is attached to a rotatable shaft150running through a center of chamber135. Motor134is configured to provide rotational movements to rotatable shaft150. Rotatable shaft150includes a proximal end151and a distal end153. Motor134may be attached to distal end153, although other locations are possible as well. Motor134may be any motor suitable for providing such movements, such as a step motor, for example. At proximal end151of rotatable shaft150, there is positioned a disk152having openings154for air flow. Disk152fits within chamber135such that air cannot flow around the sides of disk152, but can only flow through openings154. A movable portion144comprises a rotating shutter156attached to proximal end151of rotatable shaft152and is configured to rotate upon activation of motor134. Rotation of rotating shutter156causes openings154to be closed, thus blocking air flow. A direction of air flow, shown by arrows146is substantially orthogonal to a direction of rotation of rotating shutter156, depicted by arrow148. Moreover, a cross-sectional surface area of movable portion144in the direction of movement of movable portion144is equivalent to the thickness of the rotating disk, since movement occurs in the rotational plane. This surface area is much smaller than the flow area just past rotating shutter156. In one embodiment, disk152may be rotatable in a direction opposite to the rotation of rotating shutter156. This provides faster shuttering speeds than one moving part.

Reference is now made toFIG. 9B, which is a partially cut away view of disk152, openings154, and movable portion144—which is rotating shutter156.

Reference is now made toFIG. 10, which is a perspective illustration of a shutter assembly180, in accordance with yet additional embodiments of the present invention. Shutter assembly180includes an outer cylinder182with an outer slit184along at least a portion of a length thereof. Outer slit184is preferably long and narrow. A movable portion186includes an inner rotatable cylinder188having an inner slit190along at least a portion of a length thereof. Inner rotatable cylinder188is positioned within said outer cylinder182such that air is prevented from flowing between outer cylinder182and inner rotatable cylinder188. When outer slit184and inner slit190are aligned, an opening is created for movement of air flow in a direction of arrows192and arrows194. Inner rotatable cylinder188rotates in one direction. In some embodiments, outer cylinder182may rotate as well, in an opposite direction of inner rotatable cylinder188. This provides faster shuttering speeds than one moving part.

In addition, the shape of inner slit190and outer slit184may be configured so as to minimize shuttering time while maximizing air flow. For this reason, a rectangular shape may be used, wherein a narrow width allows for rapid opening and closing, while the length provides a relatively large flow area.

Methods of Calculation:

The basic concept of the methods of the present invention is that estimation of RV, TLC and TGV may be done based on measurements of the change of volume of gas in the lungs, ΔV, and the accompanying pressure change in the lungs, ΔP, during a short interruption to the breathing of the patient. The interruption is achieved by a quick shutter that shuts the mouth of the patient for a short period of time, either during exhalation or during inhalation. Devices which may be used for quick shuttering with minimal air displacement which may be used in the methods of the present invention are described above with reference toFIGS. 1-10. Quick shuttering is critical in order to obtain resolution necessary to discern parameters which may be measured to obtain volume values.

The first parameter which must be obtained is V0, the instantaneous volume of gas in the lungs at a given point in time. For the purposes of the present invention, V0is taken as the volume of gas within the lungs upon the shutter event. V0may be obtained in many different ways. Two different methods for obtaining V0are described hereinbelow as Method A and Method B. Once V0is obtained, the following method may be used to obtain TGV.

Reference is now made toFIG. 11, which is a graphical illustration showing a volume curve701over the course of a series of inspirations and expirations, which are not necessarily tidal respirations. Inspirations702are shown on the curve going from top to bottom, and expirations704are shown going from bottom to top. TLC is determined by a first full inspiration706and a second full inspiration708taken to full capacity. Thus, a patient is asked to fully inhale at least twice in each session in order to determine TLC level710, preferably at the beginning and at the end of each measurement session, to account for potential drifting of volume along the series of inspirations and expirations exercised by the subject. TLC level710is obtained directly from these two full inspirations. Following second full inspiration708, the patient is asked to exhale fully in order to obtain a full expiration712. RV level714is obtained directly from full expiration712, and in parallel to TLC level710. The amplitude from RV level714to TLC level710equals VC713.

At several points along the volume curve701, a shutter event is initiated, and V0is calculated by one of methods A or B. Shutter events are shown inFIG. 11as points716. Each of the shutter events may take place at different points along either an inspiration702or expiration704cycle. The difference in volume between V0measured at a shutter event716and RV level714, is RVADJ718, as computed at that specific timing. RVADJ718stands for all of the volume of air that a subject would have maximally expired during a cycle should the subject have been asked to maximally expire. Thus, once V0is calculated by one of methods A or B per a single shutter event716, RV is obtained as follows:
RV=V0−RVADJ
RVADJ718may be large or small depending on when the shutter event is initiated. However, it is necessarily smaller than VC713, which equals the difference between TLC level710and RV level714. Once RV has been calculated, TLC can be obtained as follows:
TLC=RV+VC
and TGV can be obtained by:
TGV=RV+ERV
where ERV (Expiratory Reserve Volume), is obtained by a standard spirometry measurement.

Methods A and B for determination of V0will now be described.

Starting from the ideal gas law
PV=nkT
where P is the pressure, V the volume, n the number of gas molecules and T the gas temperature, we obtain for the gas in the lungs which is maintained at a fixed temperature (also known as Boyle's Law)
P0V0=Const.
If the lungs contract by some volume ΔV, then the pressure in the lungs rises by an amount ΔP, so that
P0V0=(V0−ΔV)(P0+ΔP)
which yields,
V0=ΔV/ΔP(P0+ΔP)
If the changes in volume and pressure are small compared to the absolute values V0and P0,

V0=P0⁢Δ⁢⁢VΔ⁢⁢P
Hence, by measuring the change in lung volume and the change in the pressure inside the lungs, and knowing the base pressure—which approximates the atmospheric pressure—the internal volume of the lungs at the moment of shutting, V0, may be extracted.

Reference is now made toFIG. 12, which is a graphical illustration of flow and pressure curves over time obtained during exhalation with a shutter closing episode. It should be readily apparent that the scale ofFIG. 12is much smaller than the scale ofFIG. 11, asFIG. 12is a depiction of one single shutter event716as it relates toFIG. 11. A pre-shutter period210is followed by a shutter event212, which is followed by a post-shutter period214. Pressure is shown on the upper curve202and flow is shown on lower curve204. Flow decreases to zero during shutter event212, then rises again, and forms an “overshoot” which relaxes back to the normal flow rate, as the extra volume of gas that was compressed in the lungs during the shutter event is exhaled. The pressure rises sharply when the shutter is closed and then may rise further to a peak just before the shutter opens. Also apparent inFIG. 12is that during shutter event212, a small amount of air (compared to ΔV) may escape through the shutter because of less than ideal shutting. This amount of air, referred to as the Escaped Volume and denoted as ΔVEscis readily calculated by integrating the flow over shutter event212. The correction that the escaped volume introduces into the formula for calculating V0

A method for determining V0, in accordance with an embodiment of the present invention is described. According to this method, referred to herein as method A, the change in pressure (ΔP=P2−P1) is measured during the shutter event (i.e. during the time the shutter is closed), and the change in volume (ΔV) is measured after the shutter is opened. According to this method, the accumulated gas which generates the pressure rise during the shutting is released and measured after the shutter opens. Thus, it is important to quantify the volume which is released due to the shutter event only, and to distinguish this released volume from the volume changes which occur due to regular expiration.

Reference is now made toFIG. 13, which is a flow chart diagram illustration of a method400of calculating TGV, in accordance with embodiments of the present invention. First, a system for measuring volume changes in the lungs is provided (step402). The system includes a respiratory module with means to occlude air flow. Next, a command is given (step404) to the system to occlude air flow within the respiratory module of the system at various stages of inspiration and/or expiration. The command may be given manually or automatically, or as a combination of both. For a given occlusion event, change in pressure (ΔP) during the occlusion event is calculated (step406) and change in volume (ΔV) due to released volume due to the occlusion event is calculated (step408).

Calculation of ΔP can be done as follows. First, a first pressure P1is determined (step410), wherein P1represents the pressure at the beginning of the occlusion event. P1is generally determined at a point at which the pressure curve has finished its initial sharp slope and begins a more moderate slope following closing of the shutter, also referred hereinafter the “knee region”, as to reflect the general shape of the curve at P1. Next, a second pressure P2is determined (step412), wherein P2represents the pressure at the moment at which the shutter starts to open. Next, the difference between second pressure P2and first pressure P1is calculated (step414), resulting in a value for ΔP.

Calculation of ΔV can be done as follows. First, f0is determined (step416), wherein f0represents the flow just prior to the occlusion event. This can be done by determining an average of flow measurement data over a range of up to 20 ms prior to closing of the shutter or may be measured via one appropriate data point in the flow measurement raw data. Next, the portion of the flow curve which exceeds f0is determined (step420). A baseline, referred to as the f0baseline, is shown inFIG. 12, stretching between f1and f2. Finally, the integral of the portion of the flow curve determined in step420is calculated (step422), resulting in ΔV, as illustrated inFIG. 12by the darkened area208.

In an alternative embodiment, calculation of ΔV is done by performing (step424) a best fit of a function, for example, of the form A+B*exp(−C*t), to the flow curve, over the range that starts at least 5 ms after the shutter opens and the flow curve starts to rise, and ends at most 100 ms after the shutter opens, where t is the time measured at the point in time when the shutter opens and the flow curve starts to rise, and A, B and C are the fit parameters. Then ΔV=B/C is calculated (step426). It should be noted that the time period over which measurements are taken may vary depending on shutter event duration or other parameters. It will be appreciated that the invention is not limited to the methods described herein, and that any method which calculates an excess of air which is exhaled immediately following the opening of the shutter is included within the scope of the present invention. Moreover, the methods of present invention are not dependent on specific shutter event duration parameters. Any parameters which allow for the calculation of the values in accordance with the methods presented herein are within the scope of the present invention.

Once ΔV and ΔP are obtained, V0is calculated (step428) from ΔV and ΔP, in accordance with the equation V0=(P0+ΔP)ΔV/ΔP. Finally, RV, TLC and TGV are calculated (step430) based on V0, as described above with reference toFIG. 11.

Determination of P1is critical. However, its exact location may be obscured by oscillations on the pressure signal immediately following shutter closing for as long as 30 ms. In one embodiment, determination of P1is done by performing an extrapolation of the smooth portion of the pressure signal, backwards to the “knee region”, hence overcoming the problem of the oscillations in the immediate vicinity of P1.

Reference is now made toFIG. 14, which is a graphical illustration showing an alternative measurement of ΔV. According to this method, ΔV is obtained by integrating the flow curve above the f0baseline, as described above inFIG. 12. However, the integration is done from the point where the flow crosses f0when the shutter opens until an identifiable point t4, which is typically different from the point in time when the flow crosses again the level of f0on its decrease.

The point t4is identified on the pressure curve, as the point where exponential decrease of the pressure, associated with the relief of excess of air from the lungs, has stopped. This point may be identified by viewing the pressure curve on a logarithmic scale as inFIG. 14, and identifying a knee-shaped pattern on the curve, marked on the graph as t4. InFIG. 14, the pressure curve is shown on a linear scale203and on a logarithmic scale205. The point t4is marked as the end of the linear decrease of the logarithmic scale205. It should be noted that the baseline can be varied by assuming that the normal motion of the lungs accelerates linearly from an initial flow rate proportional to f0to the flow rate at t4.

Example Using Method A:

An example of a measurement taken by measuring ΔP and ΔV wherein ΔP is measured during the time the shutter is closed, and ΔV is measured during the time the shutter is open, in accordance with method A is now given. In the current example, a patient was requested to inhale fully to the TLC level, and then to immediately exhale fully to the RV level, once at the beginning of the measurement and once at the end of the measurement.

In this example, RVADJ718(FIG. 11)=0.81 L. On pressure curve202(FIG. 12) a smooth function is fitted to the curve along the first 50 ms and extrapolated backwards to the point it crosses the pressure curve, P1. P2is noted at the instant just prior to the opening of the shutter and the sharp decrease of the pressure signal. In this example P1=3.99 mmHg and P2=15.20 mmHg, hence ΔP=11.21 mmHg. The excess volume which is released after the shutter opening ΔV, is the area under the flow curve and above f0baseline, which in this example stands for ΔV=0.042 L.

From here V0according to Method A is readily calculated as

V0⁡[A]=P0⁢Δ⁢⁢VΔ⁢⁢P=760⁢0.04211.21=2.84⁢⁢L
Accordingly, RV is found to be
RV[A]=V0[A]−RVADJ=2.84−0.81=2.03L
Method B:

The basic theory behind method B is as follows: Starting from
P0V0=Const.,
assuming P and V are homogeneous and quasi steady, differentiation over time provides:

P0⁢d⁢⁢Vd⁢⁢t+V0⁢d⁢⁢Pd⁢⁢t=0
where P0and V0are the pressure and volume of the system at any given moment. Now dV/dt is the rate of contraction of the lungs' volume, and if we assume continuity of motion over the short period of time of the shutter closing, we conclude that it is equal to the flow rate from the mouth just prior to the closing of the shutter. Hence rearranging the last equation gives

V0=-P0⁢d⁢⁢Vd⁢⁢td⁢⁢Pd⁢⁢t=P0·f0d⁢⁢Pd⁢⁢t
where V0is the lungs' volume, P0approximates the atmospheric pressure, f0is the flow rate just prior to the shutter closing and dP/dt is the slope of pressure rise (as a function of time) just after the shutter closing.

The rate of change of the volume of the lungs is equal to f0, the flow just prior to the closing of the shutter, and the rate of change of the pressure is measured right after the shutter closes. Assuming continuity in the physical movement of body tissues during breathing, the lungs, which contract at a roughly constant pace during breathing, will continue to contract at the same pace for a short time interval after the shutter closes, and hence contribute to the rise in pressure.

Reference is now made toFIG. 15, which is a graphical illustration of a flow curve204and a pressure curve202over time obtained during exhalation with a shutter closing episode. According to this method, referred to herein as method B, the rate of change in pressure (dP/dt) is determined during the shutter event (i.e. during the time the shutter is closed), and the instantaneous volume (V0) is calculated rather than obtained by directly measuring a change of volume, ΔV.

Reference is now made toFIG. 16, which is a flow chart diagram illustration of a method500of calculating TGV, RV and TLC in accordance with embodiments of the present invention. First, a system for measuring volume changes in the lungs is provided (step502). The system includes a respiratory module with means to occlude air flow. Next, a command is given (step504) to the system to occlude air flow within the respiratory module of the system at various stages of inspiration and/or expiration. The command may be given manually or automatically, or as a combination of both. For a given occlusion event, rate of pressure change (dP/dt) during the occlusion event is calculated (step506). dP/dt is determined within the first 100 ms following shutter occlusion. During that lapse of time, intrapulmonary pressure generally climbs in comparison to pre-shutter closure level. Rate of volume change (dV/dt) is flow (f0), which is determined (step508) as described above with reference to Method A. Volume V0is calculated (step510) from the equation above, plugging in the values for dP/dt and f0. Finally, TGV, RV and TLC are calculated (step512) as described above with reference toFIG. 11.

The flow rate f0is easily determined just prior to the shutter occlusion. However there are a few alternatives for finding the correct slope in the pressure (dP/dt) immediately following the closing of the shutter, without being affected by noise or other disturbances caused by shutter operation. Some of the options are as follows:1. Measure the slope of the pressure curve (dP/dt) at the very beginning of the pressure rise following shutter occlusion;2. Measure the slope (dP/dt) after an identifiable point on the pressure curve, which may represent the point of equating the pressure in the lungs to pressure at the mouth;3. Ignore the first oscillation in the pressure curve and extrapolate backwards the main body of the pressure curve to the beginning of the pressure rise. This extrapolation results in the calculation of the pressure curve slope (dP/dt).

As shown inFIG. 15, the flow rate just prior to the shutting event is determined by the average of the flow rate over approximately 20 ms prior to the shutting event, depicted by line300. This type of averaging is quite powerful, and even in cases of low flow rates, (around 0.2 L/sec, for example), when the noise may be as high as ±0.05 L/sec, averaging may take the uncertainty down by a factor of ˜4.5, namely bring it to around ±5%, which is tolerable.

The slope of the pressure curve (dP/dt) is estimated by fitting a curved smooth function to the pressure curve along the first 30 ms starting at the “knee region”. In this way the exact starting point, and any other specific point in this region, does not have a crucial effect on the final result. Hence, the result is relatively unaffected by the exact selection of the fitting range by the operator, or by the existence of the typical oscillation at the “knee region”, as long as it is not too large.

As to the fit function, an exponential of the form A−B exp(−C·t) (where A, B and C are the fit parameters) can be used. This function has been found by trial and error as a function that fits to the various shapes that the pressure curve presents in this region. The slope is calculated at the starting point of the curve (namely at t=0) as B·C.

Variations to method B may include, for example, the fitting of any general smooth function to the pressure curve, and estimating the slope at any given point t>t0. For example, the fit function may be of the form:
ƒ=A−B·exp(−C·t)+D·t
As one example, the fit range may be changed from 30 ms to 50 ms, and the evaluation of the slope may be done at t=5 ms. The slope is thus given in this example by
ƒ=B·C·exp(−C·t)+D|t=5

Another variation of Method B may be the fitting of a sinusoidal component to the oscillations, which could help difficulties in fitting a smooth function to the pressure curve when the oscillations on the pressure curve following the shutter closing are large. Thus, the fit function may be of the form
ƒ=A−B·exp(−C·t)+D·t+E·sin(F·t+G)
The sinusoidal component then fits to the oscillations, and the smooth component emulates the net slope of the pressure curve. The slope of the smooth portion of the fit function at any point t may be again evaluated by
ƒ=B·C·exp(−C·t)+D|t.
Example Using Method B:

Referring again toFIG. 16, to calculate V0according to Method B we find f0to be f0=1.22 L/sec. The slope of the interpolated smooth function, estimated 10 ms after the shutter closing (namely after point) to minimize the effects of the oscillations following the shutter closing, is 333 mmHg/sec. According to method B we thus find

To summarize, the examples provided in Method A and Method B provide substantially the same result, which is also in agreement with the measured RV for this individual, which is approximately 2.0 L, measured by body plethysmography. Small differences between the results of the two methods as well as the difference with respect to results using body plethysmography are associated with measurement noise and may be reduced through averaging.

Example with Results

The tables below detail typical results obtained from measurement of a human volunteer. During measurement, the volunteer would breathe normally through the device which was attached to his mouth through a mouthpiece, so as to ensure that there is absolutely no escape of air between the lips and the mouthpiece. A nose clip ensures there is no escape of air through the nose. While breathing, the volunteer holds his hands on his cheeks, to prevent sudden blowing of the cheeks when the shutter closes. The device recorded flow and pressure data continuously.

Each measurement consisted of a series of breathing cycles, while in each exhale portion the shutter was shut momentarily and opened again. In the last breathing cycle the volunteer was asked to exhale forcefully and fully, so that by the end of the last breathing cycle it is assumed the volume of the lungs reaches the volunteer's RV level. During the shutter event the flow signal drops abruptly to zero and the pressure rises sharply as the pressure in the lungs grows.

Table 1 presents results of 6 measurements taken over a period of two weeks. The table compares RV results that were calculated using Method A (presented as RV[A]) and RV results that were calculated using Method B (presented as RV[B]). The average of all six measurements is compared to the body plethysmograph RV results of the same individual, obtained in accordance with ATS guidelines. VC results measured were in agreement with VC results calculated by a body plethysmograph, and thus, TLC results were in agreement with body plethysmograph's results as well.

The results shown in the tables above show that there is agreement between the results obtained by the industry standard (ie, body plethysmograph), and the results obtained by the device and method of the present invention. These results show that the device and method of the present invention adequately measure a person's RV, TGV and TLC.