Method of assessment of airway variability in airway hyperresponsiveness

• US 8,172,765 B2
• Filed: 05/04/2005
• Issued: 05/08/2012
• Est. Priority Date: 05/04/2004
• Status: Active Grant

• Current Assignee: THORASYS Thoracic Medical Systems Inc.
• Original Assignee: Dalhousie University
• Inventors: Maksym, Geoffrey N., Lall, Carolyn A.
• Primary Examiner(s): Mallari, Patricia
• Assistant Examiner(s): JANG, CHRISTIAN YONGKYUN
• Application Number:
  US11/121,031
• Publication Number:
  US 20050247307A1
• Time in Patent Office: 2,561 Days
• Field of Search: 600529-543
• US Class Current: 600/529
• CPC Class Codes: A61B 5/085 Measuring impedance of respiratory organs or lung elasticity
• CPC Class Codes: A61B 5/087 Measuring breath flow
• CPC Class Codes: A61B 5/4884 inducing physiological or psychological stress, e.g. applications for stress testing
• CPC Class Codes: G16H 40/63 for local operation
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems

Abstract

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.

Claims

1. A method of assessment of airway variability in airway responsiveness or asthma comprising the steps of:

a) measuring airway resistance by a forced oscillation technique utilizing a pressure signal and a flow signal at each of a plurality of input frequencies during a plurality of respiratory cycles of a patient;

b) collecting and processing airway resistance data measured in step a) using a data acquisition system;

c) calculating a standard deviation of the airway resistance for the patient with the airway resistance data from step b) using a computer; and

d) correlating the standard deviation of the airway resistance from step c) of the patient to a standard curve obtained from a population of asthmatics and non-asthmatics to quantify a degree of asthma of the patient.

2. A method as in claim 1 further comprising the steps of determining a noise level and a signal to noise ratio contributing to airway resistance for each input frequency, including:

obtaining the pressure signal and the flow signal;

obtaining a coherence of the pressure signal and flow signals;

obtaining a Fourier transform of multiple cycles of pressure and a Fourier transform of multiple cycles of flow;

obtaining an absolute value of the pressure and flow signals at each input frequency;

obtaining an average of the absolute values of the pressure and flow signals for a region of frequencies adjacent to input frequencies not including any input frequencies that the signal to noise ratio for either pressure or flow is a ratio of the signal, determined as a magnitude of the pressure or flow at the input frequency, divided by the noise level, determined as a magnitude of the pressure or flow in a region of frequencies adjacent to the input frequency not including any input frequency.

3. A method as in claim 1 wherein the airway resistance of a patient is measured over 1 minute using pressure oscillations having input frequencies ranging from 4 Hz to 34 Hz.

4. A method as in claim 1 wherein the airway resistance of a patient is measured over 1 minute using pressure oscillations having input frequencies ranging from 10 Hz to 34 Hz.

6. A method as in claim 3 wherein the pharmacological agonist or antagonist is a bronchodilator.

5. A method of determining a pharmacological agonist or antagonist'"'"'s effectiveness on altering airway diameter variability comprising the steps of:

a) measuring a patient'"'"'s airway resistance by a forced oscillation technique utilizing a plurality of input frequencies during a plurality of respiratory cycles;

b) measuring the patient'"'"'s airway resistance by the forced oscillation technique utilizing the plurality of input frequencies of step a) during a plurality of respiratory cycles of the patient having been administered a pharmacological agonist or antagonist;

c) collecting and processing airway resistance data measured in steps a) and b) using a data acquisition system;

d) calculating a standard deviation of the airway resistance for the patient for each of steps a) and b) using a computer; and

,

e) comparing the standard deviation of the airway resistance to determine the effectiveness of the pharmacological agonist or antagonist.

7. A method as in claim 5 wherein the pharmacological agonist or antagonist is a bronchoconstrictor.

8. A method of determining a pharmacological agonist or antagonist'"'"'s effectiveness on altering airway diameter variability comprising the steps of:

a) measuring airway reactance (Xrs) by a forced oscillation technique using a forced oscillation measuring device in a patient prior to administration of a pharmacological agonist or antagonist utilizing a plurality of input frequencies during a plurality of respiratory cycles;

b) measuring airway reactance (Xrs) by a forced oscillation technique using the measuring device in the patient post administration of the pharmacological agonist or antagonist utilizing the plurality of input frequencies of step a) during a plurality of respiratory cycles;

c) collecting and processing airway reactance data measured in steps a) and b) using a data acquisition system;

d) calculating a standard deviation of the airway reactance data from step c) for the patient for each of the pre- and post-administration airway reactance data using a computer; and

,

e) comparing the standard deviation of the pre- and post-administration airway reactance data to determine the effectiveness of the pharmacological agonist or antagonist.

9. A method as in claim 8 wherein the pharmacological agonist or antagonist is a bronchodilator.

10. A method as in claim 8 wherein the pharmacological agonist or antagonist is a bronchoconstrictor.

11. A method as in claim 8 where impedance of the measuring device is removed by a compensation algorithm.

12. A method for determining baseline values of resistance, reactance and standard deviation of resistance and the changes in these values in response to bronchoactive agents comprising the steps of:

a, measuring and storing closed impedance (Zc) in a data acquisition system;

b. measuring and storing open impedance (Zo) in a data acquisition system;

c. measuring and compensating baseline subject impedance Zm(t) over several cycles to determine a subject'"'"'s respiratory impedance (Zrs(t));

d. measuring and comparing resistance and reactance and variations in resistance and reactance;

e. administering a bronchoactive agent to a patient;

f. measuring post-drug impedance Zm_p and compensating to determine a subject'"'"'s post-drug respiratory impedance Zrs_p;

g. calculating post-drug and pre-drug resistance and reactance and variation in resistance and reactance using a computer;

h. comparing post-drug and pre-drug values of resistance and reactance and variations in resistance and reactance to standard values to determine if the resistance and reactance and variation in resistance and reactance are normal or abnormal.

13. A method of assessment of airway variability in airway responsiveness or asthma comprising the steps of:

a) measuring airway resistance by a forced oscillation technique utilizing either a single or a plurality of input frequencies during a plurality of respiratory cycles of a patient over a number of sampling periods to obtain airway resistance data sufficient to quantify a standard deviation of any underlying airway resistance of the patient;

b) collecting and processing airway resistance data measured in step a) using a data acquisition system;

c) calculating the standard deviation of airway resistance for the patient with the airway resistance data from step b) using a computer; and

,

d) correlating the standard deviation of the airway resistance from step c) of the patient to a standard curve obtained from a population of asthmatics or non-asthmatics to quantify a degree of asthma of the patient.

14. A method of assessment of airway variability in airway responsiveness or asthma comprising the steps of:

a) measuring airway resistance by a forced oscillation technique utilizing either a single or a plurality of input frequencies during a plurality of respiratory cycles of a patient over a number of sampling periods to obtain airway resistance data sufficient to statistically quantify a standard deviation underlying differences in airway resistance of the patient between sampling periods;

b) collecting and processing the airway resistance data measured in step a) using a data acquisition system;

c) calculating the standard deviation of the airway resistance for the patient with the airway resistance data from step b) using a computer; and

,

d) correlating the standard deviation of the airway resistance from step c) of the patient to a standard curve obtained from a population of asthmatics and non-asthmatics to quantify a degree of asthma of the patient.

15. A method of determining a pharmacological agonist or antagonist'"'"'s effectiveness on altering airway diameter variability comprising the steps of:

a) measuring a patient'"'"'s airway resistance by a forced oscillation technique utilizing a plurality of input frequencies during a plurality of respiratory cycles of the patient over a number of sampling periods to obtain airway resistance data sufficient to statistically quantify a standard deviation underlying differences in airway resistance of the patient between sampling periods;

b) measuring the patient'"'"'s airway resistance by a forced oscillation technique utilizing the plurality of input frequencies of step a) during a plurality of respiratory cycles of the patient having been administered a pharmacological agonist or antagonist over a number of sampling periods to obtain airway resistance data sufficient to statistically quantify a standard deviation underlying differences in airway resistance of the patient between sampling periods;

c) collecting and processing the patient'"'"'s airway resistance data measured in steps a) and b) using a data acquisition system;

d) calculating the standard deviation of the patient'"'"'s airway resistance for each of steps a) and b) using a computer; and

,

e) comparing the standard deviation of the patient'"'"'s airway resistance to determine the effectiveness of the pharmacological agonist or antagonist.

16. A method of determining a pharmacological agonist or antagonist'"'"'s effectiveness on altering airway diameter variability comprising the steps of:

a) measuring a patient'"'"'s airway reactance (Xrs) by a forced oscillation technique utilizing a plurality of input frequencies during a plurality of respiratory cycles of the patient over a number of sampling periods prior to administration of the pharmacological agonist or antagonist;

b) measuring the patient'"'"'s airway reactance (Xrs) by a forced oscillation technique utilizing the plurality of input frequencies of step a) during a plurality of respiratory cycles over a number of sampling periods after administration of the pharmacological agonist or antagonist to obtain pre- and post-administration airway reactance data sufficient to statistically quantify a standard deviation underlying differences in the patient'"'"'s airway reactance between sampling periods;

c) collecting and processing the pre and post-administration airway reactance data measured in step a) using a data acquisition system;

d) calculating the standard deviation of the airway reactance data from step a) for the patient for each of the pre- and post-administration airway reactance data using a computer; and

,

e) comparing the standard deviation of the pre- and post-administration airway reactance data to determine the effectiveness of the pharmacological agonist or antagonist.

17. A method of assessment of airway variability in airway responsiveness or asthma comprising the steps of

a) measuring airway resistance by a forced oscillation technique utilizing a plurality of input frequencies during a plurality of respiratory cycles of a patient;

b) collecting and processing airway resistance data measured in step a) using a computer;

c) calculating a standard deviation of the airway resistance for the patient with the airway resistance data from step b) using a computer; and

d) correlating the standard deviation of the airway resistance from step c) of the patient to a standard curve obtained from a population of asthmatics and non-asthmatics to quantify a degree of asthma of the patient.

18. A method of determining a pharmacological agonist or antagonist'"'"'s effectiveness on altering airway diameter variability comprising the steps of:

a) measuring a patient'"'"'s airway resistance by a forced oscillation technique utilizing a plurality of input frequencies during a plurality of respiratory cycles;

b) measuring the patient'"'"'s airway resistance by a forced oscillation technique utilizing the plurality of input frequencies from step a) during a plurality of respiratory cycles having been administered a pharmacological agonist or antagonist;

c) collecting and processing airway resistance data measured in steps a) and b) using a computer;

d) calculating a standard deviation of the patient'"'"'s airway resistance for each of steps a) and b) using a computer; and

e) comparing the standard deviation of the patient'"'"'s airway resistance pre- and post-administration of the pharmacological agonist or antagonist to determine the pharmacological agonist or antagonist'"'"'s effectiveness on altering airway diameter variability.

19. A method as in claim 18 wherein the pharmacological agonist or antagonist is a bronchodilator.

20. A method as in claim 18 wherein the pharmacological agonist or antagonist is a bronchoconstrictor.

21. A method of determining a pharmacological agonist or antagonist'"'"'s effectiveness on altering airway diameter variability comprising the steps of:

a) measuring a patient'"'"'s airway reactance (Xrs) prior to administration of a pharmacological agonist or antagonist by a forced oscillation technique utilizing a plurality of input frequencies during a plurality of respiratory cycles;

b) measuring the patient'"'"'s airway reactance (Xrs) post administration of the pharmacological agonist or antagonist by the forced oscillation technique utilizing the plurality of input frequencies of step a) during a plurality of respiratory cycles;

c) collecting and processing airway reactance data measured pre- and post-administration of a pharmacological agonist or antagonist in step a) using a computer;

d) calculating a standard deviation of the airway reactance data from step b) for the patient for each of the pre- and post-administration airway reactance data using a computer; and

e) comparing the standard deviation of the pre- and post-administration airway reactance data to determine the pharmacological agonist or antagonist'"'"'s effectiveness on altering airway diameter variability.

22. A method as in claim 21 wherein the pharmacological agonist or antagonist is a bronchodilator.

23. A method as in claim 21 wherein the pharmacological agonist or antagonist is a bronchoconstrictor.

24. A method as in claim 21 further comprising removing impedance of a measuring device by a compensation algorithm.

25. A method for assessment of airway variability in airway responsiveness or asthma comprising:

a) providing a forced oscillation generating device, said oscillation generating device comprising a low-amplitude pressure generator;

b) measuring airway resistance by a forced oscillation technique utilizing pressure oscillations having a plurality of input frequencies generated by said forced oscillation generating device during a plurality of respiratory cycles of a patient;

c) collecting and processing airway resistance data using a data acquisition system;

d) calculating a standard deviation of the airway resistance for the patient using the airway resistance data from step c); and

e) correlating the standard deviation of the airway resistance from step d) of the patient to a standard curve obtained from a population of at least one of asthmatics and non-asthmatics to quantify a degree of asthma of the patient.

26. The method as in claim 25, wherein the plurality of input frequencies range from 4 Hz to 34 Hz.

27. The method as in claim 25, wherein the airway resistance of the patient is measured over 1 minute using pressure oscillations having input frequencies ranging from 10 Hz to 34 Hz.