Patent Application
20180325421
The present invention is concerned with a method and device for the measurement of the temperature of selected portions of exhaled breath, such as may find application in medicine.
More specifically, the present invention is concerned with an apparatus useful in the performance of different medical investigations, including diagnostics and prevention and treatment of inflammatory lung and airway illnesses, such as diseases and allergies, in which analysis of the temperature of the exhaled breath may prove useful for the purpose of diagnosis and monitoring of the effect of anti-inflammatory treatments.
A common non-communicable disease, asthma, is linked with allergic inflammation of the airways. Evidence to this end has been collected by means of invasive methods of investigation: bronchoscopy with broncho-alveolar lavage and biopsies. Studies have established a quantitative relationship between the degree of inflammation of the airways and asthma severity, and also between a dose of an anti-inflammatory treatment and an ensuing clinical effect.
Bronchoscopy may be an uncomfortable experience for patients and also bears some risk, both during and after the investigation. Consequently, bronchoscopy is not applied routinely for the evaluation of airway inflammatory processes so as to tailor a therapy for an individual patient.
Noninvasive methods have been introduced as an alternative, for example, using measurement of nitric oxide in exhaled air, whose levels are higher in asthmatics, is complex, expensive and only suitable for use in specialized clinics.
Inflammation is a universal pathophysiological process and increased temperature is one of its five prominent features. In a patient with an inflamed airway, the inflamed airway mucosa acts to warm adjacent air to a higher level compared with the air adjacent to a comparative uninflamed mucosa. The extent of this warming of adjacent air depends upon the spread of an inflammatory region and on the level of inflammation.
The deep structures of the lung typically have temperatures representative of the body core. It is determined by the blood flowing along the rich vascular network of the alveoli, imparting its thermal energy to the alveolar gas content. The temperature of the inhaled air is tempered during its flow in and out of the branching airways, which have a separate system of blood supply deriving from the left ventricle of the heart through the bronchial arteries. As blood is the main carrier of thermal energy, processes that would modify its flow within the airway walls might be reflected in the temperature of the outgoing air, i.e. Exhaled Breath Temperature (EBT). High-precision gauging devices may pick up this signal and provide a basis for clinical inferences. As a breath is exhaled, the first part of the exhaled gas comes from the dead space of the throat and the airways, and later parts of the gas come from the alveoli themselves. Therefore accurate measurement of the temperature of different portions of an exhaled breath can give some indication of inflammation of different parts of the bronchial tree, starting from one central airway (trachea), two main bronchi, and along 17 to 23 generations of branched airways and related lung structures.
Because the thermal capacity of exhaled gas is relatively low, many devices for measurement of temperature will not reach thermal equilibrium with the gas temperature within the length of a single exhaled breath. Prior art devices have relied on collecting multiple breaths until temperature readings are stabilized, which can be referred to as “integral” EBT measurement.
Devices for the measurement of the exhaled breath temperature are described in (1) Piacentini G L, Bodini A, Zerman L, et al. ‘Relationship between exhaled air temperature and exhaled nitric oxide in childhood asthma’, Eur Respir J 2002; 20: 108-111; and (2) Paredi P, Kharitonov S A, Barnes P J. ‘Faster rise of exhaled breath temperature in asthma: a novel marker of airway inflammation?’, Am J Respir Crit Care Med 2001; 165: 181-184.
International Patent publication No. 2007/012930 discloses an EBT monitor which provides measurement of the temperature of exhaled breath as a surrogate marker of the inflammation in the intrathoracic airways, aggregated over a number of separate breaths.
U.S. Pat. No. 3,613,665 describes an air monitor with a valve chamber and temperature sensor for single-breath sampling.
European Patent EP2506757 discloses an exhaled respiratory gas temperature measurement device requiring multiple breaths, with a synchronous two-door shutter, whereby the shutter passes a portion of exhaled gas direct to atmosphere with no measurement of temperature, and a second portion of exhaled gas to a chamber for measurement of temperature, where each subsequent exhalation increase the temperature until an equilibrium is reached.
The present invention provides a system for measuring exhaled respiratory gas temperature during a single exhalation, the system comprising:
The present invention also provides a system for measuring exhaled respiratory gas temperature during a single exhalation, the system comprising:
The system may include any one or more of the following features:
The term “thermal characteristics” includes any one or more of the following parameters being thermal mass, thermal capacity, thermal conductivity, thermal resistance.
The present invention also provides a method of measuring exhaled respiratory gas temperature during a single exhalation, the method comprising:
The present invention also provides a method of measuring exhaled respiratory gas temperature during a single exhalation, the method comprising:
The present invention also provides a method of operating an EBT monitor for measuring exhaled respiratory gas temperature during a single exhalation, the method comprising:
The method may include the following:
In this way, the appropriate fraction of air corresponding to a section of the airways and lungs may be selected by the operator, regardless of the lung capacity of the subject or the breathing rate.
In one embodiment, the flow measurement device is a pressure sensor, and the control unit is operable to use algorithms to estimate the volume passing through the air channel by measuring the pressure difference along one section of the air channel. The pressure sensor provides an accurate indication of flow rate to partition the exhaled breath into portions as required for this application, and is simple and easy to clean. The pressure sensor may be positioned in the air inlet channel in a position where it will sense pressure differences corresponding to the direction and volumetric flow rate of the inhaled or exhaled gas.
Alternative embodiments of the invention may use thermistor temperature sensors or thermocouples.
Preferably, the measurement chambers are identical and constructed of a low thermal capacity material, in order to minimize the heat absorbed by the measurement chamber during the temperature measurement cycle.
In an embodiment of the invention, the valves are pneumatically operated. The valves may comprise an inflatable membrane within the inlet of each measurement chamber.
In one embodiment, the control unit and valves are arranged so that one or more portions of the exhaled gas are discharged without measurement.
Advantageously, the monitor may further comprise an electronic processor for processing signals from the temperature sensors and a display for displaying signals from the processor.
In one embodiment, the monitor may also provide visual and/or audible prompts to the patient to instruct them to inhale and exhale at appropriate times, and to repeat the single-exhalation process as required for a consistent measurement.
According to another aspect of the present invention, there is provided a measurement unit for analyzing portions of a stream of gas, the unit comprising an analysis block having:
In this way, the readings recorded at the respective chambers may be directly compared.
With particular reference to the specific application of the present invention, there is provided a measurement unit for a system for measuring exhaled respiratory gas temperature during a single exhalation, the unit comprising:
This aspect of the present invention may comprise three or four measurement chamber/valve sets.
This aspect of the present invention also provides a method for analyzing portions of a stream of gas, the method comprising:
With particular reference to the specific application of the present invention, this aspect of the present invention also provides a method for measuring exhaled respiratory gas temperature during a single exhalation, the method comprising:
In this aspect of the invention, the measurement chambers may have the same thermal characteristics.
The present invention is directed to an EBT monitor which allows the rapid measurement of temperature of one or more particular localized sections of the airway. The EBT monitor of the present invention is able to selectively measure one or more sections of the total airway from the lung, for example the central region and the peripheral region.
The present invention can be incorporated into an EBT monitor which provides temperature readings for the overall lung airway system, allowing comparison of EBT values measured by standard protocols (EBTst) with the EBT measured by a fractional protocol of the present invention (EBTfr), optionally for multiple regions of the airway system.
The present invention allows a ready, quick and easy temperature measurement of a variety of sections of the airway system, such sectional measurement and analysis not having been previously possible by conventional EBT monitors. The measurement can be carried out during a single exhaled breath, which is of great advantage to the patient, who previously may have been asked to monitor breath temperatures for an extended period of time.
By collecting multiple temperature readings in separate similar measurement chambers, each reading has the same or similar errors or bias, making a reliable comparison of readings possible.
In prior art exhaled breath temperature monitors, multiple breaths were directed over the sensor in order to overcome thermal inertia of the sensor, and the measurement regime had to be repeated with different timings in order to analyse different segments of the exhaled breath. This would mean that an analysis of the early part of exhalation compared with the later alveolar breath required two sets of recordings, introducing potential errors as the patient may have changed their breathing pattern or their metabolic rate in between measurements.
The pneumatic valves that may be used do not generate heat during operation, unlike solenoid or other electronically-operated valves which would add heat to the exhaled breath and affect the recorded temperature.
The pressure type flow sensor used in some embodiments of the present invention can determine the volume of air passing accurately enough to portion the exhaled breath according to the required measurement regime, while still permitting the device to be sterilized after use.
Furthermore, an operator of the EBT monitor, during the measurement procedure of an individual patient, can readily adjust the monitor settings to pinpoint particular regions of the airway for measurement and analysis.
The ability for a medical practitioner, skilled patient or other skilled user to determine small changes in exhaled breath temperature attributable to particular sections of the airways is seen to be potentially beneficial as a means of offering early monitoring and/or control of inflammatory respiratory illness, which illnesses may be observed first by small but significant changes in exhaled breath temperatures which occur before the patient is observed to suffer acute symptoms of the illness.
In order to accurately measure the temperature of portions of the exhaled gas, a means of measurement is provided that can sample portions of the exhaled gas without introducing errors in the temperature measurement that would confound the diagnostic value. The present invention may address this issue.
In order that the invention may be more readily understood, a description is now given, by way of example only, reference being made to various embodiments of the present invention, in which:
Referring now to
Control unit 190 comprises electronic circuitry configured to operate the valves V1 to V4 and to record the values of the temperature sensors t1 to t3 and the flow sensor 150. Control unit 190 may optionally comprise a compressed air supply 230 to operate pneumatic valves. The control unit may also include digital circuitry to convert the temperature readings into digital values and transmit them to a processor.
Control unit 190 is connected to measurement unit 100 by data cables 170, to transmit the temperature and flow sensor readings, and in this example flexible tubing 180 to operate pneumatic valves. If another type of valve is used, then appropriate connections would be required.
Temperature sensor t1 is positioned in measurement chamber 131, sensor t2 is located in air inlet channel 110 and sensor t3 is located in measurement chamber 133. Additional sensors could be installed in additional measurement chambers if required.
The valves V1 to V4 are positioned between the air inlet channel 110 and the measurement chambers 130 to 133. Valve V2 is shown open in this example while V1, V3 and V4 are shown as closed. When a valve is open, air can pass between the inlet channel and the respective measurement chamber.
In a preferred embodiment, the valves may be pneumatically operated, such as an inflatable membrane that can expand to close the top of the measurement chamber. Compressed air connectors such as 160 are shown connected to each valve. A pneumatic valve operated by compressed air at ambient temperature will cause negligible heat gain or loss in the measurement chamber and will produce no electrical interference with the temperature sensors.
In
In this exemplary embodiment, measurement chambers 130 and 132 are positioned at other locations and connected to the air inlet channel. In this embodiment measurement channels 130 and 132 do not contain temperature sensors, but are constructed with the same material and diameters as measurement channels 131 and 133 in order to ensure that the path travelled by the exhaled gas during inhalation and exhalation meets a similar flow resistance, so that determination of the volume of each portion of exhaled gas are not significantly affected by changes in pressure drop along the flow path.
Preferably, the measurement unit is constructed from a biomaterial with low thermal conductivity in order to minimize the heat transfer from the measurement chambers.
During measurement, a patient may inhale and exhale through a replaceable mouthpiece (not shown) connected to air inlet channel 110. The software in processor 200 will signal to control unit 190 when to open or close each valve, and will also record temperatures and flow from the sensors.
To reduce errors in the temperature measurements caused by thermal inertia of the sensors themselves and the measurement chambers, preferably the volumes requiring measurement are selected to be equal.
The start of exhalation may be automatically detected by monitoring a change of direction indicated by the flow sensor, or the patient may be prompted when to exhale by visual and/or audible prompts.
Thus, presently the air volume is measured during a deep inspiration and the processor 200 computer drives the valve system to slice the exhaled flow into relative portions from the upper and lower airways (typically 10 to 33% of the total volume is assigned for the upper airways, and 33 to 70% of the volume for the peripheral airways).
In a variant, the air volume from the upper airways is set as an absolute value (in the range 250-350 mL), while the volume of the peripheral airways is still a proportion of the total volume to be exhaled (e.g. 70%). This may provide measurements closer to reality, to more accurately reflect the anatomic relationships in the human respiratory system: while the volume of the peripheral airways can vary widely between individuals depending on age, height, gender, respiratory morbidities (900-4000 mL), the volume of the upper airways remains relatively constant somewhere between 250 and 350 mL, the measurements closer to the anatomical peculiarities of the large and small airways. In respiratory pathology, the volume of the upper and large airways is more or less constant, while there is a lot of variability in the remainder of the bronchial tree.
The present invention in its various aspects is as set out in the appended claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| 1520496.9 | Nov 2015 | GB | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2016/077953 | 11/17/2016 | WO | 00 |
