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Iranian Society of Pulmonology

Pulmonary Function Tests

Impulse oscillometry (IOS)


Clinical applications & interpretation

Hans-Juergen Smith, Germany


Sr. Product Manager Pneumonology
Ahvaz – Iran
17th February
Indications for IOS examinations
 Assessment of resting conditions
 Only passive co-operation (pediatrics, geriatrics, occupational
medicine, severe diseased…)
 Trend reports
 Excellent intra-individual reproducibility CV% < 10%
 Determination of abnormal Lung function
 Measurement of airways resistance
 Independent determination of peripheral airways
 Classification of abnormality
 Bronchial hyperresponsiveness
 Degree of reversibility
 Non-specific and specific challenge testing
 Prognosis
 Expert reports
Simple clinical interpretation
The major thrust for clinical application of FOT
(oscillometry) derives from a number of European clinical
research centres.

Goldman MD. Review: Clinical Application of Forced Oscillation.


Pulmonary Pharmacology & Therapeutics (2001) 14, 341–350
Reference values for IOS
In comparison to spirometry

IOS reference values are mostly height dependent.


In adults relatively independent on age – extrapolation possible.

FEV1 [L] R5Hz [kPa/(L/s)]


 2 to 12 years 6 0.6

Dencker/Malmberg
 13 to 17 years 4 0.4

Berdel/Lechtenboerger
 18 to 60 years 2 0.2
Vogel/Smidt
Extrapolation > 100 0 0
 45 to 91 years 5 15 25 35 45 55 65 75 85 years
Schulz Spirometry is age and height dependent!

A. Paes Cardoso, R. Ferreira, Portugal 1997


Determination of abnormality
Automated classification

Definition of abnormality:
R5Hz Resistance - if > 140 % of predicted
X5Hz Lung reactance - difference to predicted > 0.15 kPa/(L/s)

Automated classification
Detection of flow limitation at resting breathing – DX5

Classification based on R5Hz and X5Hz and their predicted in 5 levels


Survey of typical resistance spectra
3 characteristic spectra

Abnormal range

a) Normal lung function


b) Central obstruction
c) Peripheral obstruction (Small airways)
d) Restriction
e) Extra thoracic stenosis
Survey of typical reactance spectra
3 characteristic spectra to differentiate

Abnormal area

a) Normal lung function


b) Extra thoracic obstruction
c) Peripheral obstruction
d) Restriction
e) Extra thoracic stenosis
Pre-post assessment
Application of US Goldman chart

Dilatation R5Hz -20% to -25% | Fres -20% | AX -40%


Provocation R5Hz +40% | Fres +35%

Pre Dilatation Post


Fres

Fres

AX AX
R5Hz R5Hz

Post Provocation Pre


A. Marotta et al. “Impulse oscillometry provides an effective measure of lung dysfunction in 4-year-
old children at risk for persistent asthma” J ALLERGY CLIN IMMUNOL, August 2003, 317-322
Evaluation of challenge testing
Differentiated tidal breathing analysis

Provocation dose PD; provocation concentration PC


PD/PC +40 R5Hz PD/PC +35 Fres

Resistance Fres
6
R5Hz 7 1 6

1
7

Reactance

1 Baseline
6 Maximal constriction ! Peripheral obstruction
7 Dilatation step
Bronchial hyperresponsiveness
Contra indication
R5 Airways resistance - abnormal if > 140 % of predicted
X5 Lung reactance - abnormal if (predicted – X5) > 0,15 kPa.s.L-1
Contra indication as soon as R5 and/or X5 in abnormal range

Bronchial hyperresponsiveness
Reversibility R5 Airways resistance - 20-25%
Fres Resonant frequency - 20%
AX Reactance area - 40%
Diff R5-R20 Frequency dependence - 0.04 kPa.s.L-1
FEV1 Forced volume in 1 s +12% + 200mL

Provocation R5 Airways resistance PD/C +40 R5


Fres Resonant frequency PD/C +35 Fres
FEV1 Forced volume in 1 s PD/C -20 FEV1

Small airways obstruction Delta R5-R20% > 30% - 35%


Diff R5-R20 > 0.08 kPa.s.L-1
Restrictions not safely detected
Limited sensitivity of oscillometric method

 Detection of restriction by decrease of lung reactance X5Hz only in


higher degrees of disease
 VC-manoeuvre in oscillometry or in spirometry to proof restriction

Xrs [kPa/(L/s)]
Restriction
0,3 Decrease of VC
0,2 Reactance spectrum
0,1
 VC
0
Fres
-0,1 VC
-0,2 X5Hz
-0,3
0 5 10 20 30 40 f [Hz]

! TLC measurement (body, diffusion) recommended!


Extra thoracic Stenosis
Fixed or functional stenoses in upper, extrathoracic airways generate
a plateau on the usually continuous reactance course. Additional
measurement of forced spirometry recommended.
Xrs [kPa/(L/s)]

0,3

0,2 Reactance Spectrum


0,1

-0,1

-0,2 X5
-0,3

0 5 10 20 30 40 f [Hz]
Clinical studies utilizing IOS
Oscillometry as clinical monitor of response to treatment.

Smith HJ. et al. Forced oscillation technique and impulse


oscillometry. European Respiratory Monograph 31, 2005; 10: 72-105
IOS in pre-school children
First ambulant examination with mouthpiece

Total number
60

40

20 Total

Correctly measured

Examination failed
2 years
3 years
4 years
5 years

W. Kamin. I. Bieber, H. Trübel (1995)


Phenotyping of wheezing

Wheezing phenotypes
in 4 years old children
Never wheezing (144)
Early transient wheeze (127)
Persistent wheeze (54)

Note: Small airways obstruction

E. Oostveen et al. Lung function


and bronchodilator response
in 4-year-old children with different
wheezing phenotypes. Eur Respir J
2010; 35: 865–872
Pro-post assessment
Pre-post assessment
in 4 years old children
baseline
post bronchodilator
* p<0.05
** p<0.01
*** p<0.001
Never wheezing (144)
Early transient wheeze (127)
Persistent wheeze (54)

E. Oostveen et al. Lung function


and bronchodilator response
in 4-year-old children with
different
wheezing phenotypes. Eur Respir J
2010; 35: 865–872
Methacholine challenge in pre-school
8
Rosc

6 21 (of 48) children aged 4-6 Raw


Index

TcO2
4
Rocc
2 FEV1

0
Methacholine
NaCl 0.5 1 2 4 8 16 32 log [mg/ml]

B. Klug, H. Bisgaard. Lung function measurement in awake young children. Eur


Respir J, 1995, 8, 2067–2075
IOS in challenge testing

A: Correlation between Raw and R5 in all subjects after MCh.


B: Corresponding Bland-Altman

Beretta et al. Involvement of the distal lung in response to methacholine


challenge test: comparison between impulse oscillometry and plethysmographic
technique.
Challenge testing – phenotyping
2/3 small airways involvement 1/3 central reaction

Beretta E, et al. Involvement of the distal lung in response to methacholine


challenge test: comparison between impulse
oscillometry and plethysmographic technique.
Deep Inspiration causes dilatation
Deep inspiration (FEV1)
Fres [Hz]
30

Asthmatics
without dilating effect
20 *** Asthmatics
with dilating effect
** ***
10 Healthy volunteers

Challenge: Isocapnic hyperventilation of cold air

-1 1 3 5 7 9 10 11 13 [min]

B. Schmekel, H.J. Smith (1997)


FEV1 and resistance at spasmolysis
Nietzman et al., Erasmus Medical Center, Rotterdam, 2003
FEV1 % pred SDS
1mg Terbutalin 1mg Terbutalin
120 8
n=73 * sign.
7 n=73
100
6
80
5
n=27 * sign. * sign.
60 4
3
40

Post
Post

Post
2

Pre
Pre
Pre
Post
Post

Pre
Pre

20 upper
1
limit
0 0
Healthy COPD Reff R5 Rocc
K. Nietzmann et al.: Comparison of bronchodilator response in COPD as measured by
FEV1 and resistance; European Respiratory Society, 13th Annual Congress 2003,
Vienna, September 27 – October 1, [3618]
Resistance R5 in stages of disease
Nietzman et al., Erasmus Medical Center, Rotterdam, 2003
Impuls-Oscillometry R5 SDS
6
n=11
5
COPD - Classification 4 n=8
following
ERS Consensus 1995 3 n=8

Degree FEV1%Pred 2
n=73
mild > 70 1

Post

Post

Post
moderate 50-69

Pre

Pre
Pre
0 0 -0,3
severe < 50
mild moderate severe healthy

N.M. Siafakas et al.: Optimal assessment and management of chronic obstructive pulmonary
disease (COPD); Eur Respir J 1995, 8, 1398-1420
Intra breath
Phenotyping of obstruction
Respiratory phases
1234 inspiration
5678 expiration

Healthy subjects
average
COPD
average

Peripheral indices
R5, X5, Fres
Central indices
R20

Junichi Ohishi et al. Application of impulse oscillometry for within-breath analysis


in patients with chronic obstructive pulmonary disease:
pilot study. BMJ Open 2011;2
Staging of COPD
Intra breath & average

Staging of COPD
Healthy
Stage I
Stage II
Stage III
Stage IV

Junichi Ohishi et al. Application of impulse oscillometry for within-breath analysis


in patients with chronic obstructive pulmonary disease:
pilot study. BMJ Open 2011;2
IOS for detection of EFL
Methodology according to Dellacà et al.
 Prerequisite is continuous recording of reactance Xrs(t)
 No averaging!
 In case of EFL, impulses don‘t reach the alveolies but are
blocked from „Choke Points“ which has effect on Xrs

Tidal breathing analysis with IOS


 Non-invasive
 Simple and reliable breath-by-breath analysis to determine EFL
 Average parameters for clinical evaluation of degree of impairment

R.L. Dellacà et al.: Detection of expiratory flow limitation in COPD using the forced
oscillation technique. Eur Respir J 2004, 232-240
Clinical evaluation of EFL
Flow limited patient Optimal range Parameter
Flow Volume

Xexp
Average of expiration

Xexp, min
Minimum of Xrs
Poes

In expiration

Mead Whittenberger Method D Xrs


R5

Difference of average
values between in- and
expiration
X5

Xpeak-to-peak
Difference of peak-values
Sensitivity
Specificity
Dellacà et al.: Detection of expiratory flow limitation in COPD using the forced oscillation
technique; ERJ 2004, 232-240
Bronchial dilatation in COPD
Problem: Bronchodilators improve breathing mechanics in
COPD patients WITHOUT large effect on FEV1

 Decrease of hyperinflation 50
24 COPD Patients
 Decrease of peripheral

Improvement [%]
40 sGaw
obstruction 30 Fres

20
R5
Conclusion:
10 FEV1
… Impulse Oscillometry and
0
Bodyplethysmography should 20 50 100 200 400 800

be favoured over spirometry … Dose Salbutamol [mg]

L. Borrill et al.: Measuring bronchodilatation in COPD clinical trials; Br J Clin Pharmacol 2004,
59:4, 379-384
Distal airways function in obesity

Prior bariatric surgery, IOS detected


distal airways dysfunction despite
normal spirometry findings in 342
subjects.

Abnormalities improved significantly


towards normal after weight loss.

--- Threshold to normal

Beno W. Oppenheimer et al. Distal airway


dysfunction in obese subjects corrects after
bariatric surgery. Published by Elsevier Inc. on
behalf of American Society for Metabolic and
Bariatric Surgery; 2011.
Epidemiological studies
Male Non-Smokers - Smokers
( 3.500 each, Pneumobile, Portugal )
Years Years
15 25 35 45 55 65 75 85 15 25 35 45 55 65 75 85

0 0
without
-0.1 -0.1 with
wheezing
-0.2

-0.3
! -0.2

-0.3
cough
c. & w. !
Non-Smokers Smokers
-0.4 -0.4

-0.5 -0.5
Symptoms
X5 [kPa/(L/s)] X5 [kPa/(L/s)]

A. Paes Cardoso, R. Ferreira, Portugal, (1997)


IOS in pharmaceutical studies
Budesonide/Formeterol caused an unexpected worsening of
IOS outcomes (resting breathing). This finding was not
observed with spirometry!

Peter A. Williamson et al. Paradoxical Trough Effects of Triple Therapy With


Budesonide/Formoterol and Tiotropium Bromide on Pulmonary Function
Outcomes in COPD. Chest 2010;138;595-604
Degree of tracheal stenosis
Risk assessment

Non-invasive morphological evaluation of tracheal stenosis.


Threshold of R5 > 0.35 kPa.s.L-1 demands bronchoscopy.

Karl-Josef Franke et al. Removal of the Tracheal Tube after Prolonged Mechanical
Ventilation: Assessment of Risk by Oscillatory Impedance.
Respiration 2011;81 :118-123
Correlation to tracheostenosis
Non-invasive detection and follow
up of airway stenosis.

Determination of flow limitation in


upper airways for improved
interpretation of spirometry!!

Differentiation only with


IOS

Thomas Horan et al. Forced Oscillation Technique to Evaluate Tracheostenosis in


Patients with Neurologic Injury. Chest 2001;120;69-73
Extrathoracic stenosis
Differentiation
Flow dependent resistance as function of
lumen area: pre- post-intervention

Sylvia Verbanck et al. Detecting upper airway obstruction in patients with


tracheal stenosis. J Appl Physiol 109: 47–52, 2010.
Clinical application of IOS
Tidal breathing analyses – complementary to spirometry
 Nearly all patients can be measured
 Important clinical questions concerning breathing mechanics can be
answered
Pre-post assessment - phenotyping
Challenge testing - phenotyping
Phenotyping of obstruction
 Stratification in extra-thoracic, central, small, peripheral airways
 Intra-breath volume- and flow-dependence
 Expiratory flow limitation
Early detection of lung diseases
Pharmaceutical studies
Epidemiological studies
Conclusion
Impulse oscillometry (IOS)

 Quite breathing manoeuvres are more


suitable for a larger patient population
 Results are highly sensitive to
treatment – early diagnosis
 Small airways diagnostics possible

IOS is simple
 Patient is only passively cooperating
 Operator is supported in quality issues
 Physician is supported by various
classification & interpretation strategies

IOS averaging of trials after artefact rejection is a world novelty!

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