WO2005104944A1 - Method of assessment of airway variability in airway hyperresponsiveness - Google Patents
Method of assessment of airway variability in airway hyperresponsiveness Download PDFInfo
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- WO2005104944A1 WO2005104944A1 PCT/CA2005/000664 CA2005000664W WO2005104944A1 WO 2005104944 A1 WO2005104944 A1 WO 2005104944A1 CA 2005000664 W CA2005000664 W CA 2005000664W WO 2005104944 A1 WO2005104944 A1 WO 2005104944A1
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- Prior art keywords
- rrs
- xrs
- patient
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/48—Other medical applications
- A61B5/4884—Other medical applications inducing physiological or psychological stress, e.g. applications for stress testing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/08—Detecting, measuring or recording devices for evaluating the respiratory organs
- A61B5/085—Measuring impedance of respiratory organs or lung elasticity
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H40/00—ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices
- G16H40/60—ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices
- G16H40/63—ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for local operation
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
- G16H50/20—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/08—Detecting, measuring or recording devices for evaluating the respiratory organs
- A61B5/087—Measuring breath flow
Definitions
- the invention relates to a method of assessing airway variability in airway responsiveness or asthma by measuring the variation of resistance (Rrs) by a forced oscillation technique utilizing either a single or a plurality of input frequencies during a plurality of respiratory cycles of a patient; calculating the statistical variability of the Rrs for the patient; and, correlating the statistical variability of the Rrs of the patient to a standard curve to quantify the degree of asthma of the patient.
- the invention also enables the effectiveness of a bronchoactive agent to be measured.
- Asthma is a disease affecting 100 - 150 million people worldwide with deaths from asthma reaching 180 000 annually [']. Asthma affects all age groups but often starts in childhood and is the most common chronic childhood disease affecting 6.3 million children worldwide ["]. Asthma is also more prevalent in the developing world with the incidence in children increasing by approximately 75% every 10 years in the United States ['"]. However currently there is no easy accepted non-invasive method of measuring pulmonary function in children under the age of 6. , The standard measure of lung function used in older children and adults is spirometry, a learned manoeuvre that depends on the active cooperation of the subject, therefore it does not produce reliable and reproducible results in young children ( ⁇ 6 yr).
- the forced oscillation technique offers a non invasive method of assessing lung mechanics that requires only passive patient cooperation [ V1 , V11 ].
- FOT can also be applied in adults, and is also useful when spirometry is difficult, unpractical or infeasible, for example in the assessment of the elderly, paralysed and unconscious as well as in sleep studies and with mechanically ventilated patients.
- the forced oscillation technique was first introduced in 1956 by Dubois and colleagues [ v ] as a method of characterizing respiratory mechanics.
- Airway diameters have been shown to be constantly changing within a breathing cycle and over short periods of time [ XX11 ]. This leads to a respiratory system resistance that also varies over a breathing cycle, which can be reduced by deep inhalation [ XX111 ]. Lack of significant bronchodilation or bronchoprotection due to deep inhalation may contribute to the variability in airway calibre that characterizes asthma [ XX1V 5 XXV ].
- a method of assessment of airway variability in airway responsiveness or asthma comprising the steps of measuring the variation of resistance (Rrs) by a forced oscillation technique utilizing either a single or a plurality of input frequencies during a plurality of respiratory cycles of a patient; calculating the statistical variability of the Rrs for the patient; and, correlating the statistical variability of the Rrs of the patient to a standard curve to quantify the degree of airway responsiveness or asthma of the patient.
- Rrs variation of resistance
- the invention also provides a method of determining the effectiveness of a pharmacological agonist or antagonist comprising the steps of: measuring the variation of resistance (Rrs) by a forced oscillation technique utilizing either a single or a plurality of input frequencies during a plurality of respiratory cycles of a patient; measuring the variation of resistance (Rrs) by a forced oscillation technique utilizing a plurality of input frequencies during a plurality of respiratory cycles of a patient having been administered pharmacological agonist or antagonist; calculating the statistical variability of the Rrs for the patient for each of the first two steps; and, comparing the statistical variability of the Rrs to determine the effectiveness of the pharmacological agonist or antagonist.
- the invention provides a method of determining the effectiveness of a pharmacological agonist or antagonist on altering airway diameter variability comprising the steps of: measuring the variation of reactance (Xrs) by a forced oscillation technique utilizing a plurality of input frequencies during a plurality of respiratory cycles of a patient both pre- and post-administration of a pharmacological agonist or antagonist; calculating the Xrs for the patient for each of the pre- and post-administration steps; and, comparing Xrs to determine the effectiveness of the pharmacological agonist or antagonist.
- Xrs variation of reactance
- a method for determining baseline values of variations of resistance (Rrs), variations in reactance (Xrs) and standard deviation of resistance (SDRrs) and the changes in these values in response to bronchoactive agents comprising the steps of: measuring and storing closed impedance (Zc); measuring and storing open impedance (Zo) measuring and compensating baseline subject impedance Zm(t) over several cycles to determine Zrs(t); measuring and comparing Rrs, Xrs and variations in Rrs and Xrs; administering a bronchoactive agent to a patient; measuring post drug impedance Zm p and compensating to determine Zrs p ; calculating post-drug and pre-drug Rrs, Xrs and variation in Rrs and Xrs; comparing post-drug and pre-drug values of Rrs, Xrs and variations in Rrs and Xrs to standard values to determine if the Rrs, Xrs and variation in Xrs and Rr
- Figure 1 is a schematic diagram of a test protocol, where FO is a forced oscillation measurement, and BD is administration of a pharmacological agonist or antagonist
- Figure 2 are two plots with the top panel showing FOT Rrs over time calculated once per second at 4 and 34 Hz in an asthmatic child and the bottom panel showing FOT median Rrs and median Xrs over frequency in an asthmatic child calculated from 180 seconds
- Figure 3 are plots showing percent predicted FEVI vs. median Rrs and FEVI vs.
- Figure 6 is a plot of the simulated effect of noise on Rrs values
- Figure 7 is a plot of median Rrs in asthmatic and control children
- Figure 8 is a plot of the baseline standard deviation of Rrs in asthmatic and control children
- Figure 9 is a plot of the median Rrs in control children before and after administration of bronchrodilator or sham saline dose
- Figure 10 is a plot of the standard deviation of Rrs in control children vs.
- Figure 11 is a plot of coherence calculated between pressure (circles) and flow (crosses) signals from two different representative subjects at the oscillation frequencies;
- Figure 12 is a representative example of magnitudes of fast Fourier transformed pressure and flow signals vs. frequency showing the oscillation frequencies used (4, 10, 14, 22, 26, 34 Hz) and breathing noise at low frequencies;
- Figure 13 is a representative plot of signal to noise ratios computed from data in Figure 12 vs.
- Figure 14 is a plot of percent predicted FEVI versus median Xrs from children with asthma pre (diamonds) and post bronchodilator (squares) at low, mid and high frequencies;
- Figure 15 is a plot of median Xrs pre- and post- bronchodilator in asthmatic children versus frequency;
- Figure 16 is a plot showing a comparison of FEV1%, median Rrs, SDRrs and median Xrs in response to BD, with error bars showing standard error;
- Figure 17 is a plot of the relationship between SDRrs and Xrs before bronchodilator (diamonds) and post bronchodilator (squares) in children with asthma;
- Figure 18 is a plot of the relationship between % change in SDRrs with bronchodilator and change in Xrs with bronchodilator in children with asthma.
- Figure 19 is a flow chart of a method to determine baseline Rrs, Xrs and SDRs and the changes in these values in response to bronchoactive agents; and, Figure 20 is a flow chart of a method to determine baseline values of Rrs, Xrs and SDRs, and changes in these values in response to bronchoactive agents.
- a patient study was performed in order to measure the statistical variation in the respiratory system resistance (Rrs) by a forced oscillation technique (FOT).
- the study provided a measure of baseline bronchial activity and thus airway smooth muscle activity in terms of optimal frequency of measurement, sensitivity in distinguishing between asthmatic and control children and a measure of bronchodilator (BD) effect in asthmatics which also enabled distinguishing between asthmatic and control children.
- Rrs respiratory system resistance
- FOT forced oscillation technique
- the study also measured the reactance of the patient to determine changes in airway stiffness and degree of airway closure caused by changes in airway smooth muscle activity, in terms of optimal frequency of measurement, sensitivity in distinguishing between asthmatic and control children and a measure of bronchodilator (BD) effect in asthmatics, which also enabled distinguishing between asthmatic and control children.
- BD bronchodilator
- the signal driving the pressure oscillations was composed of frequency components at 4, 6, 10, 14, 22, 26 and 34 Hz within a one second oscillation period that was continuously repeated. While different oscillation period durations could be chosen depending on the oscillation frequencies, as long as the oscillation period was an integer multiple of the inverse of all oscillation frequencies, one second was used in all cases.
- Each patient was asked to breathe through the breathing tube for three recording periods of one minute duration with nose clips on and with their cheeks supported. Between each of the one minute recording periods were provided breaks of approximately 10 seconds during which patients could swallow if needed. Pressure and flow data were collected at 700 Hz using a data acquisition system.
- Zrs (2) Zc - Zm Zo + Zc
- P(f) and V(f) are the Fourier transforms of pressure and flow respectively of one or more oscillation periods
- Zc and Zo are calibrated impedances obtained with the FOT device system closed (Zc) and open to the atmosphere (Zo)
- Zm is a time series of the measured impedance. Equation (1) and (2) are applied for each repeated oscillation period, forming a time series of Zm and Zrs with lengths equal to the number of oscillation periods. If multiple oscillation periods of pressure and flow are used in the Fourier transforms of Equation (1), the length of Zm and Zrs correspondingly decreases by that multiple.
- Zc and Zo are typically calculated from recordings of up to 1 minute or until coherences > 0.95 are achieved.
- the correction of Zm by the system impedances compensates for resistive and reactive losses within the measuring device and any filter at the patient attachment as described in "Schuessler TF and Bates JH. A computer- controlled research ventilator for small animals: design and evaluation. IEEE Trans Biomed Eng 42: 860-866, 1995.”
- Successful application of the method required that measurement of Zrs be calculated including compensation for the impedance of the device (including any tubing or filters between the device and the patient).
- the impedance of the device is a significant amount of the measured Zrs and should be removed from Zm to accurately determine Zrs.
- Zrs is thus calculated from Zm, Zc and Zo forming a time series usually up to 180 points in length calculated once per oscillation period (1 second) from the three concatenated one minute recording periods, and cycles with inadequate coherence or signal to noise ratio are removed.
- Rrs and Xrs ( Figure 2) are the real and imaginary parts of Zrs respectively.
- Rrs, Xrs and variation in Rrs were analyzed at different frequencies in asthmatic children and control children before and after a BD performed both pre- and post-spirometry.
- Table 1 Summary of asthmatic patient population
- FIG. 14 shows the percent predicted FEVI versus median Xrs from children pre- (diamonds) and post-bronchodilator (squares) at low, mid and high frequencies.
- Figure 15 shows median reactance pre- and post- bronchodilator in asthmatic children versus frequency.
- Figure 16 is a comparison of FEV1%, median Rrs, standard deviation of resistance
- SDRrs SDRrs
- median Xrs are more sensitive measures of bronchodilator effect than either FEVI or Median Rrs, in children with asthma aged 6-9.
- Figure 17 shows the relationship between SDRrs and Xrs before bronchodilator (diamonds) and post bronchodilator (squares) in children with asthma. Each point represents the Xrs and SDRrs from an individual and shows there is a moderate dependency between Xrs and SDRrs either before or after bronchodilator, such that those with high SDRrs also have low Xrs.
- FIG. 18 shows the relationship between % change in SDRrs with bronchodilator and change in Xrs with bronchodilator in children with asthma. Each point represents the Xrs and SDRrs from an individual. It is apparent that a decrease in SDRrs is usually found with an increase in Xrs (especially at mid frequencies). Thus these measures could be used together to determine the efficacy of a particular bronchodilator.
- Control Data with Placebo The control data with half taking a placebo instead of a bronchodilator was collected.
- the control data with half taking a bronchodilator was collected.
- the controls (Table 2) were all children with no history of respiratory illness.
- Figure 11 is a plot of coherence between pressure (circles) and flow signals (crosses)
- Figure 12 is a plot of the Fourier transformed pressure and flow signals
- Figure 13 is a plot of the signal to noise ratios for pressure (circles) and for flow (crosses) for each oscillation frequency.
- Rrs, Xrs and variations in Rrs and Xrs are measured and if desired are compared (step 10) to standard values to compute % predicted to determine if the Rrs, Xrs and variation in Xrs and Rrs are normal or abnormal.
- a bronchoactive agent may be administered to the patient.
- the post drug impedance Zm p is measured and compensated to determine Zrs p .
- Rrs, Xrs and variation in Rrs and Xrs are calculated.
- post-drug and pre-drug values of Rrs, Xrs and variations in Rrs and Xrs are measured.
- steps 6-8 are repeated.
- an alternate method is described for determining baseline values of Rrs, Xrs and SDRs and the changes in these values in response to bronchoactive agents.
- closed impedance Zc is measured until coherence and signal to noise ratio at each frequency is acceptable and stored.
- open impedance Zo is measured until coherence and signal to noise ratio is acceptable and stored.
- the baseline subject impedance Zm(t) is measure and Zm at each frequency is calculated once per period of the perturbation waveform.
- Zm is compensated with Zo and Zc to compute baseline Zrs.
- periods of Zrs are removed for which coherence and/or signal to noise ratio was low.
- Rrs, Xrs and variation in the Rrs and Xrs are calculated and if desired are compared (step 31) to standard values to compute % predicted to determine if normal or abnormal.
- a bronchoactive agent may be administered.
- post drug impedance Zm p is measured and compensated to determine Zrs p .
- Rrs, Xrs and variations in Rrs and Xrs are calculated.
- baseline values of Rrs, Xrs and variations in Rrs and Xrs are compared to post-drug values.
- the increased drug dose is administered and steps 27-29 are repeated.
Abstract
Description
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Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2007511798A JP2007536026A (en) | 2004-05-04 | 2005-05-03 | A method to assess airway variability in airway hyperresponsiveness |
CA002565625A CA2565625A1 (en) | 2004-05-04 | 2005-05-03 | Method of assessment of airway variability in airway hyperresponsiveness |
EP05740892A EP1742572A4 (en) | 2004-05-04 | 2005-05-03 | Method of assessment of airway variability in airway hyperresponsiveness |
NZ551074A NZ551074A (en) | 2004-05-04 | 2005-05-03 | Method of assessment of airway variability in airway hyperresponsiveness |
CN2005800143269A CN1972631B (en) | 2004-05-04 | 2005-05-03 | Method of assessment of airway variability in airway hyperresponsiveness |
AU2005237191A AU2005237191A1 (en) | 2004-05-04 | 2005-05-03 | Method of assessment of airway variability in airway hyperresponsiveness |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US56744604P | 2004-05-04 | 2004-05-04 | |
US60/567,446 | 2004-05-04 | ||
US63056704P | 2004-11-26 | 2004-11-26 | |
US60/630,567 | 2004-11-26 |
Publications (1)
Publication Number | Publication Date |
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WO2005104944A1 true WO2005104944A1 (en) | 2005-11-10 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/CA2005/000664 WO2005104944A1 (en) | 2004-05-04 | 2005-05-03 | Method of assessment of airway variability in airway hyperresponsiveness |
Country Status (8)
Country | Link |
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US (1) | US8172765B2 (en) |
EP (1) | EP1742572A4 (en) |
JP (1) | JP2007536026A (en) |
CN (1) | CN1972631B (en) |
AU (1) | AU2005237191A1 (en) |
CA (1) | CA2565625A1 (en) |
NZ (1) | NZ551074A (en) |
WO (1) | WO2005104944A1 (en) |
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JP2009240752A (en) * | 2008-03-10 | 2009-10-22 | Chest M I Inc | Respiration impedance measuring device and method, and respiration impedance display method |
JP2010501291A (en) * | 2006-08-30 | 2010-01-21 | レスメド・リミテッド | Discrimination of respiratory airway obstruction and open apnea by complex admittance values |
EP2384697A1 (en) * | 2010-05-05 | 2011-11-09 | Universiteit Gent | Method and device for determining non-linear effects in the respiratory impedance |
ITBG20100049A1 (en) * | 2010-09-10 | 2012-03-11 | Milano Politecnico | SYSTEM FOR THE AUTOMATIC ASSESSMENT OF RESPIRATORY DISEASES AND FOR THE PREDICTION OF ACUTE FUTURE INSTABILITY OF AIRWAYS |
US9649050B2 (en) | 2009-12-03 | 2017-05-16 | Koninklijke Philips N.V. | Method and apparatus for estimating respiratory impedance |
IT201700093172A1 (en) * | 2017-08-11 | 2019-02-11 | Restech S R L | METHOD FOR THE EARLY IDENTIFICATION OF REPUTATION OF CHRONIC OBSTRUCTIVE BRONCOPNEUMOPATHY |
CN109475304A (en) * | 2016-07-14 | 2019-03-15 | 皇家飞利浦有限公司 | System and method for monitoring asthma symptoms |
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EP1895908A4 (en) * | 2005-06-10 | 2009-12-09 | Telethon Inst For Child Health | A method of measuring an acoustic impedance of a respiratory system and diagnosing a respiratory disease or disorder or monitoring treatment of same |
CA2511070A1 (en) * | 2005-06-29 | 2006-12-29 | Scireq Scientific Respiratory Equipment Inc. | Self-actuated cylinder and oscillation spirometer |
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US20120283592A1 (en) * | 2009-11-03 | 2012-11-08 | Scireq Scientific Respiratory Equipment Inc. | System and method for simultaneous lung function assessment in parallel subjects |
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WO2018069198A1 (en) * | 2016-10-13 | 2018-04-19 | Koninklijke Philips N.V. | Auto-adjustment of patient expiratory pressure |
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ITBG20100049A1 (en) * | 2010-09-10 | 2012-03-11 | Milano Politecnico | SYSTEM FOR THE AUTOMATIC ASSESSMENT OF RESPIRATORY DISEASES AND FOR THE PREDICTION OF ACUTE FUTURE INSTABILITY OF AIRWAYS |
CN109475304A (en) * | 2016-07-14 | 2019-03-15 | 皇家飞利浦有限公司 | System and method for monitoring asthma symptoms |
IT201700093172A1 (en) * | 2017-08-11 | 2019-02-11 | Restech S R L | METHOD FOR THE EARLY IDENTIFICATION OF REPUTATION OF CHRONIC OBSTRUCTIVE BRONCOPNEUMOPATHY |
WO2019030632A1 (en) * | 2017-08-11 | 2019-02-14 | Restech S.R.L. | A method for the early identification of recurrences of chronic obstructive pulmonary disease |
Also Published As
Publication number | Publication date |
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JP2007536026A (en) | 2007-12-13 |
CA2565625A1 (en) | 2005-11-10 |
CN1972631A (en) | 2007-05-30 |
AU2005237191A1 (en) | 2005-11-10 |
CN1972631B (en) | 2010-05-05 |
US8172765B2 (en) | 2012-05-08 |
US20050247307A1 (en) | 2005-11-10 |
EP1742572A1 (en) | 2007-01-17 |
EP1742572A4 (en) | 2009-11-25 |
NZ551074A (en) | 2010-08-27 |
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