CICM FOT Theories and Reports interpretation slides (1) (1).pptx 5112023.pptx

forced oscillometry

1. Oscillometry The Physiology & Interpretation AND ILLUSTRATIVE CASES BY DR . ANIMESH ARYA SENIOR CONSULTANT CHEST PHYSICIAN SHRI BALAJI MEDICAL INSTITUTE PASCHIM VIHAR NEW DELHI & ASRA CENTRE FOR CHEST DISEASES, ALLERGY AND SLEEP DISORDERS NEW DELHI

2. WHY WE DO LUNG FUNCTION TEST ?

3. SO HOW TODAY’S STANDARD - SPIROMETRY, LIVES UP TO THESE PREREQUISITES…??? Spirometry is difficult to perform IN individuals such as preschool children , handicaps and also many elderly and dyspnoeic patients. Requires cooperation having to perform a forced exhalation from total lung capacity down to residual volume The test is effort dependent and the patient needs to be coached by an experienced technician to guarantee an acceptable maneuver; however, up to 20% of patients cannot perform an acceptable measurement. 40% measurements are not acceptable . Spirometry takes a relatively long time to perform - up to 20minutes Spirometry is not sensitive to alterations in the small airways There are at least 29 contraindications to spirometry due to the high pressures that result when forcibly exhaling, potentially causing injury, the risk of spreading infection from contagious patients, and inability to participate for some patient populations like dementia where COPD can be common. Aerosol Generating Procedure - contraindicated in CoVid Pandemic.

4. SMALL AIRWAYS The small airways are frequently involved early in the course of [lung] diseases, with significant pathologies often demonstrable before the onset of symptoms or changes in spirometry or imaging. McNulty & Usmani, ECRJ 2014 Unlocking “Silent Zone” Oscillometry . In COPD, we call those small airways ‘quiet’ or ‘silent’ – not because they actually are, but because our listening tools haven’t been that sensitive to pick up the noisy disease of COPD

5. Lipworth et al Lancet RM 2014 ;2:497-506 Small airways in asthma: “the quiet zone”

6. SMALL AIRWAYS DISEASE The diagnosis of lung diseases such as Asthma and COPD has traditionally relied on a combination of symptoms and conventional lung function tests using spirometry that primarily identify the large airways and leave problems in the small airways undetected . Surface area of the larger airways approximately equals size of a beach towel, whereas the area of the small airways approaches the size of a standard tennis court. Peripheral airway impairment may be more clinically relevant at all levels of asthma severity and control

7. Assessment of small airways Lipworth et al Lancet RM 2014 ;2:497-506

8. SMALL AIRWAY FUNCTION : IMPORTANCE OF ASSESSMENT Monitoring small airway function can be useful in identifying patients who are at risk for losing asthma control, and in assisting with clinical decisions and treatmen In their 2009 study, Yamaguchi et al. demonstrated that an ultrafine particle formulation improved small airway function in ASTHMA AND COPD patients whereas the same active substance offered in a conventional inhaler failed to produce any effect. Moreover, the benefits of the novel finer particulate inhalers were picked up only with Oscillometry and missed by Spirometry.

9. That,s Why Oscillometry…?

10. AIRWAY OSCILLOMETRY Oscillometry (also known as the forced oscillation technique) Measures the mechanical properties of the respiratory system (upper and intrathoracic airways, lung tissue and chest wall) during quiet tidal breathing, by the application of an oscillating pressure signal (input or forcing signal), most commonly at the mouth. King, Gregory G., et al. "Technical standards for respiratory oscillometry ."  European Respiratory Journal  55.2 (2020).

11. OSCILLOMETRY : FROM PAST TO PRESENT Oscillations were first used to quantify the mechanical behavior of respiratory system by Dubois et al . in 1956 . The approach commonly known as forced oscillation technique (FOT) , in which airway characteristics in the form of impedance were monitored using sound waves of various frequencies . There have been several modifications in FOT over the past 6 decades with regard to configuration, oscillation type, frequencies, and assessment of airway parameters. Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020

12. OSCILLOMETRY : FROM PAST TO PRESENT One such development, known as impulse oscillometry (IOS) , was demonstrated by Michaelson et al . in 1975 using multiple frequencies at one point of time. Oscillometry provides a detailed description of pressure-flow relationships over discrete frequencies. This provides a better insight about resistance and reactance of respiratory system than conventional spirometry. Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020

13. OSCILLOMETRY : CLINICAL APPLICATIONS Provides practically useful information regarding the subtle changes in airways with greater sensitivity, in both children and adults, when compared to spirometry Useful to assess abnormal distal airway function, in case of clinical suspicion with normal spirometry Bronchodilator reversibility can be demonstrated with short-acting β-2 agonists and ipratropium Good potential in diagnosis and monitoring of restrictive lung diseases such as bronchopulmonary dysplasia, cystic fibrosis, and interstitial lung disease PARTICULARL EARLY BOOPPOST LUNG TX Feasible option in children, the elderly , and those with neuromuscular diseases and impaired intellect Potentially useful in patients on mechanical ventilation and during sleep . Karnataka Paediatric Journal • Volume 35 • Issue 2 • October-December 2020 |

14. Principle of Oscillometry In oscillometry testing, a stimulus is applied to the respiratory system at the mouth. The input signal is either the pressure or flow oscillation, and the response (in terms of flow or pressure, respectively) is measured. The ratio of oscillatory pressure to oscillatory flow generated from this oscillatory stimulus is used to calculate input impedance, and represents the total mechanical properties of the respiratory system. Sound waves (green) are superimposed over the normal tidal breath (blue) during respiration. Transducers measure the pressure and flow during exhalation for individual frequency which is utilized to calculate impedance of the respiratory system

15. Oscillometry Principle (continued)… The sound waves, being the mini pressure waves, cause subtle pressure changes in the airway which leads to change in airflow. Smaller frequencies (2–4 Hz) can travel till the depth of lung peripheries, whereas higher frequencies (>20 Hz) reach to proximal conducting airways only. Middle range frequencies (5–20 Hz) are commonly used in clinical practice to determine respiratory characteristics using fast Fourier transform technique. Frequencies less than 5 Hz get easily altered by harmonics of the normal breathing, whereas larger frequencies (>30 Hz) cause subjective discomfort and are affected by shunting properties of upper airways. Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020

16. Principle … The sound wave signals of pressure and flow are separated from the breathing pattern, by signal filtering mechanism, while returning from lungs during exhalation. The complex ratio of sinusoidal pressure (P) and flow (Q) for individual sound wave frequency, as determined by the pressure and flow transducers ( pneumotachograph ) at the mouthpiece, informs about the impedance of various segments of the respiratory system. Impedance is calculated at discrete frequencies by ohm’s law. Where , Z – Impedance, P – Pressure, Q – Flow, ω – oscillation frequency function, f – frequency . Measured impedance (Z) is the sum of opposing forces in the respiratory system, resistance (R), and reactance (X). Z, calculated at individual frequency, informs about the mechanical properties of respective portion of airways Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020

17. NORMAL VALUES Impedance – Several studies have provided reference values for respiratory characteristics till date. The references might vary as per the ethnicity and the oscillation technique used in different machines. The commonly used regression equations, by the machine, for calculating R and X based on height (H) in meters, weight (W) in kilograms, and age (A) in years are as follows: for men – Rmen = –0.2454. H+0.001564. W–0.00055. A+0.5919 Xmen = 0.1479. H–0.000402. W–0.00022. A–0.1721 and for women – Rwomen = –0.4300. H+0.00165. W–0.00070. A+0.9312 Xwomen = 0.2487. H–0.001700. W–0.00053. A–0.2158 Karnataka Paediatric Journal • Volume 35 • Issue 2 • October-December 2020 |

18. Normal Values Normative values from Indian populations need to be devised. Gupta et al. have recently demonstrated a negative correlation between oscillometry parameters with height followed by body mass index in Indian children, while evaluating airway reversibility in asthmatic patients.[16] There was no gender influence observed on any of the parameter. • Resonant frequency – The normal values of Fres varies in between 6 and 12 Hz in healthy adults and it tends to be more in children • Reversibility – The recommended cutoffs for significant bronchodilator response in both adults and children are –40% in R5, +50% in X5, and –80% in Ax. These values might vary with severity of disease and more studies are required before considering them as benchmark • Degree of bronchoconstriction – Cutoffs for X5 have varied from 50 to 80% and more studies are needed to provide reference values for specific populations. Karnataka Paediatric Journal • Volume 35 • Issue 2 • October-December 2020 |

19. INTERPRETATION Resistance (R) – Total, large/central, and small/ peripheral airway resistances are represented as R5, R19/20, and R5–R19/20. R5 is always higher than R19/20. This difference is practically negligible in adults, whereas it increases in younger children due to significant contribution by peripheral airway resistance. In peripheral airway obstruction, R5 will increase with normal R19/20 (and higher R5–R19/20) making frequency dependent airway resistance (R α 1/f). In larger airway obstruction, both R5 and R19/20 will rise equally (with normal R5–R19/20), which will be frequency independent. There will not be any change in restrictive lung diseases. Karnataka Paediatric Journal • Volume 35 • Issue 2 • October-December 2020 |

20. Interpretation… Spiky pattern in inspiration, demonstrated by >2 standard deviation variation in subsequent efforts at 5 Hz, may suggest vocal cord dysfunction.[18] The finding needs to be supported with further research • Reactance (X) – It is usually measured at 5 Hz and becomes more negative in both peripheral airway obstruction and lung parenchymal disease . It is not affected by large airway obstruction • Resonant frequency ( Fres ) – It increases (shift to right) in both restrictive and peripheral airway obstructive diseases.[24] It is not affected by large airway obstruction • Reactance area (Ax) – It increases in both small airway obstruction and restrictive diseases.It is not affected by central airway problems. Karnataka Paediatric Journal • Volume 35 • Issue 2 • October-December 2020 |

21. Respiratory characteristics in health and disease. Respiratory characteristics in health and disease. R – Resistance (in cm H2O.L-1.s-1), X – Reactance (in cm H2O.L-1.s-1). During normal healthy conditions, the resistance and reactance are at baseline (green). Various combinations of changes in these parameters will help in determining the nature and location of pathology. Karnataka Paediatric Journal • Volume 35 • Issue 2 • October-December 2020 |

22. Changes in Oscillometry during pathological conditions Respiratory characteristics in health and disease. R – Resistance (in cm H2O.L-1.s-1), X – Reactance (in cm H2O.L-1.s-1). During normal healthy conditions, the resistance and reactance are at baseline (green). Various combinations of changes in these parameters will help in determining the nature and location of pathology

23. Limitations: A minimum amount of cooperation is still needed from patients even though technique is tidal breath based. Standardization of the available machines with different manufactures is needed. Reference values for different populations are not available. Reference cutoff values for bronchodilator reversibility need to be validated with more studies . Poor cheek support can reduce the resistance values. More research required in restrictive diseases, ventilated, and/ or sedated patients and patients with vocal cord dysfunction. Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020

24. COMPARISON WITH SPIROMETRY Oscillometry is more sensitive for the detection of peripheral airway obstruction and restrictive diseases affecting lung parenchyma. Use of spirometry has been restricted in current COVID-19 pandemic due to reasons of enhanced risk of disease transmission by potential aerosol generation. Forced breathing maneuver causes more aerosol generation due to “airway reopening phenomenon.” Breathing till residual volume will reopen the collapsed alveoli causing increased air turbulence, leading to more production and release of smaller particles. A small volume tidal breath, as used in oscillometry , will not cause much disturbance in the internal milieu and thus safeguarded in situations of active infections (such as influenza and corona). Recent study by Gupta et al . suggests oscillometry procedure being safer than spirometry in viral pandemic situations Karnataka Paediatric Journal • Volume 35 • Issue 2 • October-December 2020 |

25. Spirometry and Oscillometry : Comparative analysis Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020

26.   Spirometry AO Outputs FEV1,FVC ,FEF25-75 R5, R20, X5, AX Signal to noise ratio + + Patient friendly - + Breathing pattern Forced expiratory Tidal Large/small airways +/- + Cost + - Portability + + FDA approved + +   Comparison of Spirometry and AO Lipworth et al, Resp Med 2018; 139 :106–109

27. AOS in a Nutshell – Tickboxes all characterstics of ideal lung function evaluation Airwave Oscillometry (AOS) is a quick, easy pulmonary assessment, effortlessly obtained during regular tidal breathing ,that provides unique insights into small airway function . Classic PFT tremoflo AOS Portable  /   Effortless (Tidal Breathing)   Suitable for Preschoolers   Easy for the Elderly   Captures Small Airways  

28. Approach to a patient with Oscillomatric Assessment Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020

29. TAKE HOME MESSAGE Oscillometry , being a tidal breath-based technique, can be a real privilege to physicians and their patients for monitoring lung functions. It is more sensitive in detecting small airway pathologies than conventional spirometry. Limited aerosol generation could be another reason for its use in viral pandemics for monitoring lung functions. More research is required for identifying regional reference values and standardization of machines.

30. SUMMARY TAKE HOME MESSAGE AO IS AN EFFORT INDEPENDENT RAPID TEST TO MEASURE RESISTANCE (R) AND COMPLIANCE (X) AO (TREMOFLO) IS A MODERN PORTABLE USER FRIENDLY DEVICE TO MEASURE LUNG RESISTANCE AND COMPLIANCE AO IS USEFUL AND SENSITIVE TO DETECT SMALL AIRWAYS DYSFUNCTION (AX AND R5-20) IN ASTHMA PATIENTS WITH PRESERVED FEV1 THAN CONVENTIONAL SPIROMETRY AX AND R5-20 ARE CLOSELY RELATED TO ASTHMA CONTROL AND T2 INFLAMMATION LUNG COMPLIANCE (AX) IS MORE SENSITIVE THAN RESISTANCE (R5) IN COPD OSCILLOMETRY, BEING A TIDAL BREATH-BASED TECHNIQUE, CAN BE A REAL PRIVILEGE TO PHYSICIANS AND THEIR PATIENTS FOR MONITORING LUNG FUNCTIONS. AO SHOULD BE USED IN CONJUNCTION WITH SPIROMETRY TO FULLY CHARACTERIZE THE PHYSIOLOGY OF YOUR PATIENTS WITH ASTHMA AND COPD

31. THANK YOU

32. Airway Oscillometry Oscillometry (also known as the forced oscillation technique) Measures the mechanical properties of the respiratory system (upper and intrathoracic airways, lung tissue and chest wall) during quiet tidal breathing, by the application of an oscillating pressure signal (input or forcing signal), most commonly at the mouth. King, Gregory G., et al. "Technical standards for respiratory oscillometry ."  European Respiratory Journal  55.2 (2020).

33. Oscillometry : Origins & Evolution Dubois et al., JAP 1956 1990 2000 2010 2020 Desktop Handheld …

34. Patient’s Quiet Breathing tremoFlo Oscillation Measured Waveform Breathing Pattern Respiratory Impedance: Resistance and Compliance + = Airway Oscillometry : Measurement Sequence

35. Nomenclature: FOT / IOS / AOS /OSC…..? Confusion Cleared FOT - “forced oscillation technique” IOS or iOS - “impulse oscillometry,” often used interchangeably. Both are oscillation mechanics methodologies They use different stimulations to achieve sound viberation akin to vehicle can be driven by Diesel,Petrol,CNG & now electric. The “forced” of FOT refers the forcing properties of sine waves upon the respiratory system. Unlike the FEV1, the term “forced” has nothing to do with the maneuver performed by the subject It is preferred to the use of the term “oscillometry” or “OSC,” or Airway Oscillometry ( AOS ) which is the only term that correctly applies to all devices and modes of stimulation and avoids the term “forced” that may be confusing to some.

36. Types of Oscillometry Forced Oscillation Technique (FOT) = Oscillometry Pseudo-Impulses IOS Single Frequency e.g. 5 Hz Harmonic Prime AOS Sequential Multiple Frequencies

37. Principle of Oscillometry In oscillometry testing, a stimulus is applied to the respiratory system at the mouth. The input signal is either the pressure or flow oscillation, and the response (in terms of flow or pressure, respectively) is measured. The ratio of oscillatory pressure to oscillatory flow generated from this oscillatory stimulus is used to calculate input impedance, and represents the total mechanical properties of the respiratory system. Sound waves (green) are superimposed over the normal tidal breath (blue) during respiration. Transducers measure the pressure and flow during exhalation for individual frequency which is utilized to calculate impedance of the respiratory system

38. Oscillometry Principle (continued)… The sound waves, being the mini pressure waves, cause subtle pressure changes in the airway which leads to change in airflow. Smaller frequencies (2–4 Hz) can travel till the depth of lung peripheries, whereas higher frequencies (>20 Hz) reach to proximal conducting airways only. Middle range frequencies (5–20 Hz) are commonly used in clinical practice to determine respiratory characteristics using fast Fourier transform technique. Frequencies less than 5 Hz get easily altered by harmonics of the normal breathing, whereas larger frequencies (>30 Hz) cause subjective discomfort and are affected by shunting properties of upper airways. Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020

39. Principle … The sound wave signals of pressure and flow are separated from the breathing pattern, by signal filtering mechanism, while returning from lungs during exhalation. The complex ratio of sinusoidal pressure (P) and flow (Q) for individual sound wave frequency, as determined by the pressure and flow transducers ( pneumotachograph ) at the mouthpiece, informs about the impedance of various segments of the respiratory system. Impedance is calculated at discrete frequencies by ohm’s law. Where , Z – Impedance, P – Pressure, Q – Flow, ω – oscillation frequency function, f – frequency . Measured impedance (Z) is the sum of opposing forces in the respiratory system, resistance (R), and reactance (X). Z, calculated at individual frequency, informs about the mechanical properties of respective portion of airways Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020

40. Patient’s Quiet Breathing tremoflo Oscillation Measured Waveform Breathing Pattern Respiratory Mechanics Resistance (R) Reactance (X) + = Click! Measurement Sequence

41. Real life practicality of Tremoflo Portable Easy Maintenance Easy Calibration U ser friendly for patient and clinician PC friendly – Easy exportable data

42. OSC Asthma : Bronchodlation & Provocation Test > Spirometry Oscillometry parameters are more sensitive to identify patients with asthma and to exclude those without asthma than the parameters of spirometry . OSC is useful in the follow-up of asthma patients and may detect airway obstruction earlier than spirometry Several studies have shown that a BDR based on oscillometric parameters is better than one based on forced expiratory volume in 1 s (FEV1) at differentiating asthmatic from healthy children Several studies found that OSC may be more sensitive than spirometry in detecting bronchoconstriction induced by methacholine or allergens, as the increase in resistance values preceded the fall in FEV1.

43. So why not Oscillometry ……? Reflects lung mechanics that provides a more “real-world” assessment of respiratory function. Lung Function assessment done in normal breathing. Humans do not use forced maneuvers in daily activity- hence obviates the need of patient’s cooperation. Reproducible over time,quick,more sensitive & correctly assesses small airway function Can be done in pre school children,elderly,cognitive dysfuction & even physically challanged patients. Anyone who can breath can do ….!

44. Oscillometry : Challenges Normograms are Specific to individual make of devices Few Indian Normograms , more in children than adults No uniform standardization ( Spirometry took 26 yr from 1979-2005 ) Cost : Oscillometry Devices > Spirometry , Portable > Fixed Need for structured teaching module for learning oscillometry/interpretations .

45. AGENDA Overview of small airways physiology Airway oscillometry (AO) outcomes Asthma: Asthma severity and AO AO in relation to asthma control, exacerbations and type 2 inflammation COPD: Discordance between resistance and reactance GOLD 1-4 Bronchoconstriction/dilatation and lung compliance Summary

46. AOS vs IOS: Calibration

47. Airway oscillometry outcomes Shi et al. JACI 2012;129(3):671-678 . Figure.

48. Reversibility: R5 = 48% R20=23% R5-20 =75% AX=79% X5=58% FEV1=16% FEF25-75=15% R/X [ Kpa /L.s] AO reversibility to salbutamol in severe asthma Galant et al Ann Allergy Immunol 2017;118:664-71

49. Comparison of FEV1 and R5 response to methacholine in asthmatic adults Short et al , Ann Allergy Asthma Immunol 2015 ;115:17-20 R5: 43.5% change (95%CI 29.4 - 57.5) FEV1: 23.3% change (95%CI 18.7 - 27.9)

50. Kuo et al ,Lung 2019 ; 197: 473–481 65% difference AOS>IOS 10% difference IOS>AOS

51. % Reversibility to salbutamol 400ug: FEV1: Asthma 8% vs COPD 8% AX : Asthma 40% vs COPD 24% Reversibility in asthma and COPD Kuo et al ,Lung 2019 ; 197: 473–481

52. AO and asthma severity Except for central resistance, all AO parameters showed increased abnormality with increased asthma severity and airflow obstruction Williamson PA, et al. Lung 2011;189(2):121-129. Total resistance (R5) Central resistance (R20) Peripheral resistance (R5–R20) Peripheral Reactance (X5) Median kPa lˉ 1 sˉ 1

53. Peripheral airway resistance R5-R20 (n=378) across BTS steps 2,3 and 4 Abnormal values (>0.03kPa/L/s) are those above upper 95%CI for healthy controls S teps 2, 3 & 4 : 64.6%, 63.5% and 69.9% were abnormal FEV1=84% FEV1=90% FEV1=86% Anderson et al, Ann Allergy Asthma Immunol 2012; 109(3):185-189

54. Relationship of R5 to height in children Galant Ann Allergy Asthma Immunol 2017;118:664-71

55. Using AO to predict subsequent loss of control in asthmatic children AX >0.7kPa/L = 91% correctly classified R5-R20 >0.1kPa/L/s = 83% correctly classified Shi et al JACI 2013 ;131:718-23. .

56. Small airways dysfunction (SAD) in pts with preserved FEV1 in mild to mod asthma n= 302/442 (68%) of mild to mod asthma pts in BTS steps 2-4 had preserved FEV1>80% (mean FEV1 97%) In such pts with preserved FEV1 ,n=135/302 (45%) had impaired AO as R5-20 >0.07 kPa/L/s Pts with impaired R5-20 45% more likely to require OCS (p=0.02) and and 47% more likely to require SABA (p=0.01) Manoharan et al ERJ 2014 ;44:1353-5

57. Kuo et al Ann Allergy 2018;121:631-2 AO in relation to type 2 inflammation in mild to mod asthma

58. AO in relation to asthma control in mild-mod asthma Kuo et al ,Annals Allergy 2020 ; 124: 288-290

59. Relationship of AO and Spiro to disease control in mod- sev asthma Jabbal et al JACI 2016 ;138:601-3

60. Determinants of disease control and exacerbations in mod- sev asthma Combining spiro and AO Chan & Lipworth ,JACI IP 2022 ;10:2758–2760

61. Combining low frequency oscillometry (R5/X5) with FEV1 in relation to disease control and exacerbations in mod- sev asthma Chan & Lipworth JACI IP 2022 ;10:1910–1912

62. Impaired resistance and compliance are associated with bronchial wall thickening in persistent asthma Chan et al JACI IP 2022

63. Summary: AO in asthma Resistance (R) and compliance (X) are concordant in asthma Small airways dysfunction is common across all asthma severities SAD is related to poor asthma control and T2 inflammation Combining AO and Spiro provides the best predictor of poor control and exacerbations

64. Relationship of Resistance (R) and Compliance (X) to COPD severity Crim et al Respir Med 2011;105:1069-78 % Difference GOLD 4 vs 2 AX = 136% R5-20= 60%

65. Discordance between compliance (X) and resistance (R) after methacholine challenge at PC20 in COPD Walker Respir Med 2009 ;103:535-41

66. Relative discordance between resistance and compliance after carvedilol challenge and LABA withdrawal in severe COPD Jabbal & Lipworth ,Lung 2018; 196:15-18 ICS/LABA

67. Abe et al Pulm Pharmacol Ther 2011;24:617–624 Effect of LAMA and LABA on small but not large airways in COPD

68. Summary : AO in COPD Compliance (X) and resistance (R) are relatively discordant in COPD Lung compliance is more sensitive than resistance in COPD

69. NORMAL VALUES Impedance – Several studies have provided reference values for respiratory characteristics till date. The references might vary as per the ethnicity and the oscillation technique used in different machines. The commonly used regression equations, by the machine, for calculating R and X based on height (H) in meters, weight (W) in kilograms, and age (A) in years are as follows: for men – Rmen = –0.2454. H+0.001564. W–0.00055. A+0.5919 Xmen = 0.1479. H–0.000402. W–0.00022. A–0.1721 and for women – Rwomen = –0.4300. H+0.00165. W–0.00070. A+0.9312 Xwomen = 0.2487. H–0.001700. W–0.00053. A–0.2158 Karnataka Paediatric Journal • Volume 35 • Issue 2 • October-December 2020 |

70. Normal Values Normative values from Indian populations need to be devised. Gupta et al. have recently demonstrated a negative correlation between oscillometry parameters with height followed by body mass index in Indian children, while evaluating airway reversibility in asthmatic patients.[16] There was no gender influence observed on any of the parameter. • Resonant frequency – The normal values of Fres varies in between 6 and 12 Hz in healthy adults and it tends to be more in children • Reversibility – The recommended cutoffs for significant bronchodilator response in both adults and children are –40% in R5, +50% in X5, and –80% in Ax. These values might vary with severity of disease and more studies are required before considering them as benchmark • Degree of bronchoconstriction – Cutoffs for X5 have varied from 50 to 80% and more studies are needed to provide reference values for specific populations. Karnataka Paediatric Journal • Volume 35 • Issue 2 • October-December 2020 |

71. INTERPRETATION Resistance (R) – Total, large/central, and small/ peripheral airway resistances are represented as R5, R19/20, and R5–R19/20. R5 is always higher than R19/20. This difference is practically negligible in adults, whereas it increases in younger children due to significant contribution by peripheral airway resistance. In peripheral airway obstruction, R5 will increase with normal R19/20 (and higher R5–R19/20) making frequency dependent airway resistance (R α 1/f). In larger airway obstruction, both R5 and R19/20 will rise equally (with normal R5–R19/20), which will be frequency independent. There will not be any change in restrictive lung diseases. Karnataka Paediatric Journal • Volume 35 • Issue 2 • October-December 2020 |

72. Respiratory characteristics in health and disease. Respiratory characteristics in health and disease. R – Resistance (in cm H2O.L-1.s-1), X – Reactance (in cm H2O.L-1.s-1). During normal healthy conditions, the resistance and reactance are at baseline (green). Various combinations of changes in these parameters will help in determining the nature and location of pathology. Karnataka Paediatric Journal • Volume 35 • Issue 2 • October-December 2020 |

73. INTERPRETATION Resistance (R) – Total, large/central, and small/ peripheral airway resistances are represented as R5, R19/20, and R5–R19/20. R5 is always higher than R19/20. This difference is practically negligible in adults, whereas it increases in younger children due to significant contribution by peripheral airway resistance. In peripheral airway obstruction, R5 will increase with normal R19/20 (and higher R5–R19/20) making frequency dependent airway resistance (R α 1/f). In larger airway obstruction, both R5 and R19/20 will rise equally (with normal R5–R19/20), which will be frequency independent. There will not be any change in restrictive lung diseases. Karnataka Paediatric Journal • Volume 35 • Issue 2 • October-December 2020 |

74. INTERPRETATION… Spiky pattern in inspiration, demonstrated by >2 standard deviation variation in subsequent efforts at 5 Hz, may suggest vocal cord dysfunction.[18] The finding needs to be supported with further research • Reactance (X) – It is usually measured at 5 Hz and becomes more negative in both peripheral airway obstruction and lung parenchymal disease . It is not affected by large airway obstruction • Resonant frequency ( Fres ) – It increases (shift to right) in both restrictive and peripheral airway obstructive diseases.[24] It is not affected by large airway obstruction • Reactance area (Ax) – It increases in both small airway obstruction and restrictive diseases.It is not affected by central airway problems. Karnataka Paediatric Journal • Volume 35 • Issue 2 • October-December 2020 |

75. Changes in Oscillometry during pathological conditions Respiratory characteristics in health and disease. R – Resistance (in cm H2O.L-1.s-1), X – Reactance (in cm H2O.L-1.s-1). During normal healthy conditions, the resistance and reactance are at baseline (green). Various combinations of changes in these parameters will help in determining the nature and location of pathology

76. COMPARISON WITH SPIROMETRY Oscillometry is more sensitive for the detection of peripheral airway obstruction and restrictive diseases affecting lung parenchyma. Use of spirometry has been restricted in current COVID-19 pandemic due to reasons of enhanced risk of disease transmission by potential aerosol generation. Forced breathing maneuver causes more aerosol generation due to “airway reopening phenomenon.” Breathing till residual volume will reopen the collapsed alveoli causing increased air turbulence, leading to more production and release of smaller particles. A small volume tidal breath, as used in oscillometry , will not cause much disturbance in the internal milieu and thus safeguarded in situations of active infections (such as influenza and corona). Recent study by Gupta et al . suggests oscillometry procedure being safer than spirometry in viral pandemic situations Karnataka Paediatric Journal • Volume 35 • Issue 2 • October-December 2020 |

77. Spirometry and Oscillometry : Comparative analysis Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020

78. OSCILLOMETRY : CLINICAL APPLICATIONS Provides practically useful information regarding the subtle changes in airways with greater sensitivity, in both children and adults, when compared to spirometry Useful to assess abnormal distal airway function, in case of clinical suspicion with normal spirometry Bronchodilator reversibility can be demonstrated with short-acting β-2 agonists and ipratropium Good potential in diagnosis and monitoring of restrictive lung diseases such as bronchopulmonary dysplasia, cystic fibrosis, and interstitial lung disease Feasible option in children, the elderly , and those with neuromuscular diseases and impaired intellect Potentially useful in patients on mechanical ventilation and during sleep . Safer than spirometry during viral pandemic situations (e.g., influenza and corona) due to less aerosol generation. Oscillometry can be used to reliably diagnose and monitor patients with asthma and COVID-19 pneumonia. Karnataka Paediatric Journal • Volume 35 • Issue 2 • October-December 2020 |

79. Approach to a patient with Oscillomatric Assessment Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020

80. Approach to a patient with Oscillomatric Assessment Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020 FOT: Forced oscillation technique, IOS: Impulse oscillometry , SABA: Short-acting β2 agonist, LABA: Long-acting β2 agonist, R: Resistance (in cm H 2 O.L -1 .s- 1 ), X: Reactance (in cm H 2 O.L -1 .s -1 ), Fres : Resonant frequency (in Hz), Ax: Reactance area

81. Approach to a patient with Oscillomatric Assessment Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020 FOT: Forced oscillation technique, IOS: Impulse oscillometry , SABA: Short-acting β2 agonist, LABA: Long-acting β2 agonist, R: Resistance (in cm H 2 O.L -1 .s- 1 ), X: Reactance (in cm H 2 O.L -1 .s -1 ), Fres : Resonant frequency (in Hz), Ax: Reactance area

82. APPROACH TO A PATIENT WITH OSCILLOMATRIC ASSESSMENT Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020

83. Limitations: A minimum amount of cooperation is still needed from patients even though technique is tidal breath based. Standardization of the available machines with different manufactures is needed. Reference values for different populations are not available. Reference cutoff values for bronchodilator reversibility need to be validated with more studies . Poor cheek support can reduce the resistance values. More research required in restrictive diseases, ventilated, and/ or sedated patients and patients with vocal cord dysfunction. Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020

84. Cho et al. ARJCCM 2020 Lung Transplants Monitoring : Oscillometry > Spirometry AOS in Acute Cell Rejection SAD in all 16 episodes 100% success Spirometry unaltered in 15 /16 episodes Acute cell rejection picked up in all case earlier than spirometry obviating need of biopsy. OSCILLOMETRY HAS REPLACED SPIROMETRY HERE.

85. THANK YOU  

86. Technique He/she is asked to hold the mouth piece with his/her teeth and to make a tight seal around it with lips to prevent any air leak during the FOT maneuver. A nose clip is applied to occlude both the nostrils and he/she is asked to breathe through mouth piece. Height of sitting stool/chair and/or mouth piece is adjusted to achieve a comfortable position for the patient with slight neck extension. As FOT is based on small pressure oscillations and a little change in resistance or air leak can affect the interpretations significantly, it is important to ensure adequate seal around nose and mouth piece. The cheeks, most compliant part of respiratory system in children, should be supported firmly either by patient him/herself or attendant to minimize wobbling. After appropriate positioning, patient is asked to perform normal tidal breathing in a relaxed manner. Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020

87. Technique Calibration of the machine, at least once a day, is desired with the external resistor or as per the manufacturer’s specifications. Bronchodilator medications (short-acting β-2 agonist for 4 h and long-acting β-2 agonist for 24 h) should be stopped before the procedure. After explaining the procedure (preferably by recorded video demonstration) to patient and attendants, anthropometric measurements (weight, height, and body mass index) are documented. Demographic (name, age, gender, area of residence, and identification number) and anthropometric parameters are entered in the machine after calibration. Patient is asked to sit on an examination stool/chair, with uncrossed legs to reduce the influence of extrathoracic pressure with straight back . Image taken from Karnataka Paediatric Journal • Volume 35 • Issue 2 • October-December 2020 Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020

88. An average of 10 respiratory efforts or 1 min, whichever is earlier, is required to assess the respiratory characteristics during any maneuver. Acquisitions of minimum 30 s for adults and 16 s for children (<12 years of age) with at least three acceptable breaths are recommended. Respiratory efforts meeting acceptability criteria are considered valid, whereas maneuvers with artifacts such as airflow obstruction by tongue or glottic closure, irregular breathing, coughing, crying, swallowing, and improper technique will be discarded by the machine. A maximum of three acceptable maneuvers are recorded and checked for coherence or CoV . Mean respiratory impedance (resistance and reactance), resonant frequency, and reactance area are documented. The procedure is repeated 15 min after inhaled short-acting β-2 agonist to identify any post-bronchodilator reversibility. Technique Acceptability criterias – All are required Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020

89. Approach to a patient with Oscillomatric Assessment Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020

90. Approach to a patient with Oscillomatric Assessment Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020 FOT: Forced oscillation technique, IOS: Impulse oscillometry , SABA: Short-acting β2 agonist, LABA: Long-acting β2 agonist, R: Resistance (in cm H 2 O.L -1 .s- 1 ), X: Reactance (in cm H 2 O.L -1 .s -1 ), Fres : Resonant frequency (in Hz), Ax: Reactance area

91. Approach to a patient with Oscillomatric Assessment Gupta, et al.: Oscillometry – The future PFT. Karnataka Pediatric Journal • Volume 35 • Issue 2 • October-December 2020 FOT: Forced oscillation technique, IOS: Impulse oscillometry , SABA: Short-acting β2 agonist, LABA: Long-acting β2 agonist, R: Resistance (in cm H 2 O.L -1 .s- 1 ), X: Reactance (in cm H 2 O.L -1 .s -1 ), Fres : Resonant frequency (in Hz), Ax: Reactance area