Original Article
Correlation between impulse
oscillometry and spirometry
parameters in Indian patients
with cystic fibrosis
Chronic Respiratory Disease
2014, Vol. 11(3) 139–145
ª The Author(s) 2014
Reprints and permission:
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DOI: 10.1177/1479972314539980
crd.sagepub.com
Dinesh Raj, Ganesh Kumar Sharma, Rakesh Lodha
and Sushil Kumar Kabra
Abstract
Impulse oscillometry (IOS) is an emerging tool to assess lung function in chronic respiratory diseases, more
often in preschool children and patients who are unable to perform spirometry. We conducted a prospective
cross-sectional study on patients with cystic fibrosis (CF). Primary objective was to evaluate correlation between
IOS and spirometry parameters. Secondary objective was to evaluate the ability of IOS parameters to discriminate patients with airflow limitation at various forced expiratory volume in 1 second (FEV1) cutoffs. Patients with
CF above 6 years of age, who were following up on a routine visit, were enrolled in the study. Patients underwent
IOS and spirometry as per guidelines. A total of 39 patients (34 children and 5 adults) were enrolled in the study.
There was a significant moderate negative correlation between spirometry parameters (FEV1, forced vital capacity, and peak expiratory flow rate) and IOS parameters, that is, impedance at 5 Hz (Z5), resistance at 5 Hz (R5),
and reactance area, both between raw values and percent predicted values. Of the various IOS parameters,
Z5 percent predicted had the maximum area under the curve (AUC) of 0.8152 and 0.8448 for identifying
children with FEV1 <60% and <80%, respectively. R5 percent predicted had an AUC of 0.8185 for identifying
children with FEV1 <40%. IOS can be used as an alternative pulmonary function test in patients with CF more
so in patients who are unable to perform spirometry.
Keywords
Impulse oscillometry, spirometry, cystic fibrosis, pulmonary function tests, chronic respiratory disease
Introduction
Cystic fibrosis (CF) is a chronic respiratory disease
with progressive deterioration of lung function. Spirometry is considered to be the gold standard of lung
function measurements in children above 6 years of
age and adults. Spirometry is routinely used to assess
lung function in children with CF. However, spirometry may not be possible in acute exacerbation settings
and children with deteriorating lung function may not
be able to perform spirometry as per standard guidelines as it requires forced expiratory maneuvers. It has
also been shown that spirometry may not be very sensitive in detecting mild to moderate lung damage in
children with CF.1 Hence, there is need of a lung function test that is sensitive enough to pick up early
changes and that can also be performed easily in
preschool children and children with advanced disease, which are unable to perform using spirometry.
Impulse oscillation technique or forced oscillation
technique (FOT) utilizes tidal breathing to assess airway limitation and has been used in preschool children
and other situations in which forced exhalation is not
possible.2,3 Lung clearance index (LCI) is another sensitive evolving tool to assess lung function in children
Division of Pulmonology, Department of Pediatrics, All India
Institute of Medical Sciences, New Delhi, India
Corresponding author:
Dinesh Raj, Division of Pulmonology, Department of Pediatrics,
All India Institute of Medical Sciences, Ansari Nagar, New Delhi
110029, India.
Email: [email protected]
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140
Chronic Respiratory Disease
with CF. However, as compared to impulse oscillometry (IOS), which is now available as a portable device,
LCI that is derived from multiple-breath washout
(MBW) test is not available at most centers.
IOS superimposes brief air pressure impulses on
the tidal breathing of the patient and assesses the
mechanical properties of the lung. The respiratory
impedance (Z) consists of respiratory resistance (R)
and respiratory reactance (X). These measurements
depend on frequency of the applied pressure signal
(5–35 Hz). Resonant frequency (RF) is the point at
which the magnitude of capacitative and inertive reactance are equal. Area of reactance (AX) is a quantitative index of total respiratory reactance at all
frequencies between 5 Hz and RF.4 IOS is different
from classical FOT as the impulse applied by the
loudspeaker has a rectangular waveform as compared
to a pseudorandom noise signal in classical FOT.
Moreover, there are differences in data processing
techniques. IOS has been evaluated in childhood
asthma in assessing therapeutic response, bronchodilator response, methacholine challenge testing, and
long-term follow-up.5–11 IOS has hence a potential
place in routine evaluation of children with CF.
Correlation between IOS parameters and spirometry parameters has been observed in asthmatic children and found to be significant. However, little
data are available in CF patients. Moreau et al.
assessed the relationship between IOS parameters and
spirometry parameters in a retrospective study and
found significant but poor correlation.12 Studies have
evaluated the feasibility of these techniques, correlated with spirometric indices and inflammatory
parameters, and assessed the therapeutic response in
patients with CF.12–15 We planned to evaluate the
utility of IOS in our patients with CF in terms of its
correlation with spirometry and ability to predict airway obstruction.
Materials and methods
Study design
The study design applied in the present work is a prospective cross-sectional study.
Study setting and population
This study was conducted at the Pediatric Chest Clinic
of the All India Institute of Medical Sciences, New
Delhi, India, which is a tertiary care referral center.
Patients with CF above 6 years of age who were
following up on a routine visit were enrolled in the
study. CF was diagnosed on the basis of suggestive
clinical features, sweat chloride measurements, and/
or genetic studies. Eligibility criteria were children
who were able to perform spirometry as per American
Thoracic Society (ATS) standards.16 Thirty-nine
children were prospectively enrolled to participate
in the study after informed consent. The subjects at
the time of recruitment were not in acute exacerbation.
The patients were part of an ongoing randomized controlled trial assessing the role of zinc supplementation
on use of systemic antibiotics in CF patients. The study
was approved by the institutional review board.
Impulse oscillometry
IOS was performed using MasterScreen (Carefusion,
Hoechberg, Germany). The equipment was calibrated
through multiple full strokes of a single volume (3 L)
of air at various flow rates as recommended by the
manufacturer. The measurements were performed
by one of the authors (DR, GKS), who received training in pulmonary function tests. The child was
explained the procedure beforehand and was made
familiar with the instrument. Child’s nose was
occluded using a noseclip and asked to breathe quietly
through the mouthpiece. Cheeks and chin were supported with hands to prevent dissipation of the impulse.
The measurement was taken for 60 seconds. In case of
artifacts like swallowing, hyperventilation, and mouth
opening, the measurements were repeated. The results
were expressed as raw values and percent predicted.
The methodology of measurement was in accordance
with European Respiratory society standardization
group17 with a slight modification of the duration and
number of measurements. We performed one measurement in 60 seconds, instead of three to five measurements in 15–30 seconds. Predicted values for IOS
were based on height and gender according to the
equipment’s default normal reference values.18,19
Spirometry
Spirometry was performed using MasterScreen as per
ATS standards.16 Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and peak
expiratory flow rate (PEFR) were calculated and
expressed in raw values as well as percent predicted
values. Reference values for spirometry were based
on predicted normal European reference values.20
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Raj et al.
141
Table 1. Baseline characteristics of CF patients.
Characteristics
Age (years)
Height (cm)
Weight (kg)
BMI z score
FEV1 (% predicted)
FVC (% predicted)
Mean (SD)
11.8
134.0
27.3
1.93
57.7
65.2
+ 3.8
+ 16.2
+ 10.3
+ 1.38
+ 23.7
+ 18.6
CF: cystic fibrosis; BMI: body mass index; FEV1: forced expiratory
volume in 1 second; FVC: forced vital capacity.
Statistical analysis
Data were entered using Microsoft Access. Statistical
analysis was performed using Stata 9.0 statistical software (Stata Corp., College Station, Texas, USA).
Results were expressed as mean + SD. Correlation
between IOS and spirometry parameters was analyzed
using Spearman’s rank correlation test. Raw values of
spirometry (FEV1, FVC, and PEFR) were correlated
with raw values of IOS (Z at 5 Hz (Z5), R at 5 Hz
(R5), R at 20 Hz (R20), X at 5 Hz (X5), RF, and
AX). Percent predicted spirometry parameters
(FEV1%, FVC%, and PEFR%) were correlated with
percent predicted IOS parameters (Z5%, R5%,
R20%, and X5%). Receiver operating characteristics
(ROC) curves were constructed at various levels of
airway obstruction (FEV1 40%, FEV1 60%, and
FEV1 80%) to identify the ability of IOS parameter
to predict airway obstruction. The value of p < 0.05
was considered significant.
Results
Of the 39 patients (34 children and 5 adults) enrolled
in the study, 23 were males. Mean age was 11.8 + 3.8
years, mean height was 134.0 + 16.2 cm, and mean
weight was 27.3 + 10.3 kg. The baseline characteristics are given in Table 1.
The correlation between percent predicted spirometry parameters and percent predicted IOS
parameters are given in Table 2. FEV1% was significantly negatively correlated with Z5%, R5%, and R20%
(r ¼ 0.6535, 0.6276, and 0.3251, respectively).
FVC% was significantly negatively correlated with
Z5%, R5%, and R20% (r ¼ 0.5946, 0.5767, and
0.3229, respectively). PEFR% was significantly negatively correlated with Z5% and R5% (r ¼ 0.5328 and
0.5188, respectively). X5% did not have any significant correlation with any of the spirometry parameters
(FEV1%, FVC%, and PEFR%). Figure 1 shows the
scatter plots depicting the correlation between percent
predicted values of spirometry and IOS.
The correlation between actual observed values of
spirometry and IOS is given in Table 3. The actual
observed values of FEV1 had a significant negative correlation with Z5, R5, R20, RF, and AX (r ¼ 0.6607,
0.6186, 0.3722, 0.4473, and 0.6656, respectively). It had a significant positive correlation with
X5 (r ¼ 0.3871). The actual observed values of FVC
had a significant negative correlation with Z5, R5,
R20, RF, and AX (r ¼ 0.6443, 0.6631, 0.4967,
0.3395, and 0.5680, respectively). It had a significant positive correlation with X5 (r ¼ 0.3294).
The actual observed values of PEFR had a significant
negative correlation with Z5, R5, R20, and AX
(r ¼ 0.5314, 0.5346, 0.3465, and 0.4760,
respectively). It did not have significant correlations with X5 and RF.
ROC curves were constructed at various FEV1 cutoffs of 40%, 60%, and 80% to assess the discriminatory power of IOS parameters to identify children
with lung function impairment. The area under the
curve (AUC) for IOS parameters to identify patients
with lung function impairment at FEV1 cutoffs of
40%, 60%, and 80% are given in Table 4. Of the various IOS parameters, Z5% had the maximum AUC
of 0.8152 and 0.8448 for identifying children with
FEV1 < 60% and FEV1 < 80%, respectively. R5% had
a maximum AUC of 0.8185 for identifying children
with FEV1 < 40%. Z5% of 96.1% had a sensitivity
of 82.8% and a specificity of 80.0% to predict an
FEV1 of <80%. R5% of 95% had a sensitivity of
75.9% and a specificity of 80.0% to predict an FEV1
of <80%. Z5% of 144% had a sensitivity of 60.9% and
specificity of 93.8% to predict an FEV1 of <60%.
R5% of 134.8% had a sensitivity of 56.5% and specificity of 93.8% to predict an FEV1 of <60%. For identifying patients with an FEV1 of <40%, both Z5% and
R5% had a sensitivity of 77.8% and specificity of
83.3%.
Discussion
This prospective study on patients with CF suggests
that there is a significant moderate negative correlation between spirometry parameters (FEV1, FVC,
and PEFR) and IOS parameters (Z5 and R5). X5 had
significant but poor positive correlation with FEV1
and FVC when raw values were considered. RF had
significant but poor negative correlation with FEV1
and FVC.
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Chronic Respiratory Disease
Table 2. Correlation between percent predicted values of spirometry and percent predicted IOS parameters.
FEV1% predicted
FVC% predicted
PEFR% predicted
r
p
r
p
r
p
Z5 % predicted
R5 % predicted
R20 % predicted
X5 % predicted
0.6535
<0.0001
0.5946
0.0001
0.5328
0.0006
0.6276
<0.0001
0.5767
0.0001
0.5188
0.0008
0.3251
0.0434
0.3229
0.0450
0.2242
0.1759
0.2161
0.1863
0.2158
0.1870
0.1496
0.3701
IOS: impulse oscillometry; FEV1: forced expiratory volume in 1 second; FVC: forced vital capacity; PEFR: peak expiratory flow rate; Z5:
impedance at 5 Hz; R5: resistance at 5 Hz; X5: reactance at 5 Hz; R20: resistance at 20 Hz.
Figure 1. Correlation of percent predicted values of spirometry with percent predicted values of IOS. IOS: impulse
oscillometry.
Table 3. Correlation of actual observed values of spirometry with observed values of IOS.
FEV1
FVC
PEFR
r
p
r
p
r
p
Z5
R5
R20
X5
RF
AX
0.6607
<0.0001
0.6443
<0.0001
0.5314
0.0006
0.6186
<0.0001
0.6631
<0.0001
0.5346
0.0005
0.3722
0.0196
0.4967
0.0013
0.3465
0.0331
0.3871
0.0149
0.3294
0.0406
0.2446
0.1389
0.4473
0.0043
0.3395
0.0345
0.2869
0.0807
0.6656
<0.0001
0.5680
0.0002
0.4760
0.0029
IOS: impulse oscillometry; FEV1: forced expiratory volume in 1 second; FVC: forced vital capacity; PEFR: peak expiratory flow rate;
RF: resonant frequency; AX: area of reactance; Z5: impedance at 5 Hz; R5: resistance at 5 Hz; X5: reactance at 5 Hz; R20: resistance
at 20 Hz.
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Raj et al.
143
Table 4. Ability of IOS parameters to discriminate patients with airflow limitation at various FEV1 cutoffs.
AUC (95% CI) for various FEV1 cutoffs
IOS parameters
FEV1 < 80%, n ¼ 29
FEV1 80%, n ¼ 10
FEV1 < 60%, n ¼ 23
FEV1 60%, n ¼ 16
FEV1 < 40%, n ¼ 9
FEV1 40%, n ¼ 30
Z5%
R5%
X5%
R20%
0.845
0.804
0.731
0.643
0.815
0.804
0.707
0.673
0.815
0.819
0.429
0.693
(0.716–0.973)
(0.659–0.951)
(0.574–0.888)
(0.463–0.824)
(0.682–0.948)
(0.667–0.941)
(0.537–0.876)
(0.499–0.845)
(0.631–0.998)
(0.632–1.000)
(0.152–0.707)
(0.463–0.922)
IOS: impulse oscillometry; FEV1: forced expiratory volume in 1 second; Z5: impedance at 5 Hz percent predicted; R5: resistance at 5 Hz
percent predicted; X5: reactance at 5 Hz percent predicted; R20: resistance at 20 Hz percent predicted; AUC: area under the curve; CI:
confidence interval.
Just as spirometry measures airflow limitation during forced exhalation, IOS measures airway resistance
and reactance during tidal breathing. Patients with CF
are known to have decreased lung compliance due to
parenchymal lung disease apart from airflow limitation. IOS measures both R and X, thereby allowing
us to evaluate the mechanical properties of the airways and lung parenchyma.3 Although both these
techniques are measuring different pathophysiological aspects of the respiratory tract during different
types of breathing maneuvers, both are likely to be
deranged in airflow obstruction. IOS, therefore, theoretically should be of good use in monitoring and
following up patients with CF. There is limited data on
comparison of spirometry and IOS in children with CF.
Moreau et al. evaluated the relationship between
IOS parameters and spirometric tests in 30 children
with CF.12 They found significant but poor negative
correlation between raw values of IOS (R5, Z, and
RF) and spirometry parameters. X5 correlated positively with spirometric indices. The correlations were
nonsignificant and poor when percent predicted values were considered. In our study, there was a significant moderate negative correlation between IOS
parameters (raw as well as percent predicted) and
spirometry parameters. X5 and R20 were poorly correlated with spirometric parameters.
We attempted to identify IOS cutoffs to identify
patients with lung function impairment at FEV1 < 40%,
60%, and 80%. The discriminatory power for Z5%
and R5% was good at all FEV1 cutoffs (<40%, <60%,
and <80%) as suggested by AUC ranging from 0.804
to 0.845. R5% and Z5% of 95% and 96.1%, respectively, had a reasonable combination of sensitivity
and specificity to identify lung function impairment of
<80%. Moreau et al. also constructed ROC curves to
identify cutoff values for IOS parameters to discriminate
between children according to predefined FEV1
thresholds.12 However, no acceptable cutoffs were
identified.
Some of the earlier works on CF patients have been
performed using FOT. Gangell et al. evaluated 56 CF
children using FOT and demonstrated that lung function
was reduced in CF group compared to a healthy reference
group.13 Furthermore, they showed that children with CF
with current symptoms show reduced lung function compared to children with CF who are asymptomatic.
Utility of IOS in CF patients is likely to be in evaluating treatment response especially in young children,
patients with advanced lung disease, and serial monitoring during follow-up. Ren et al. evaluated CF children hospitalized for respiratory tract exacerbations
using spirometry and FOT.14 They demonstrated significant relationship between changes in FEV1 and
X5 (p ¼ 0.003, r2 ¼ 0.54) pre- and posttreatment.
As with any other pulmonary function test, IOS has
been associated with issues of repeatability. IOS has
been observed to be having higher coefficient of
variability (COV) as compared to spirometry.21 We
did not evaluate COV in our report. Having said that,
this is one issue with IOS that should be kept in mind.
The need of tidal breathing tests like IOS could be justified in the young age group and advanced disease
patients despite these demerits given its feasibility.
Certain studies evaluating FOT have been carried out
in patients with CF highlighting the limitations of this
technique.22–24 Lebecque et al. assessed the ability of
FOT to detect airway obstruction in asthmatic children and patients with CF.22 They demonstrated that
FEV1 and R10 yielded concordant information in
asthmatic children much more often (38 out of 45)
than in CF patients (16 out of 45; p < 0.001). They
observed that the total respiratory resistance was not
suitable to detect airway obstruction in patients with
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Chronic Respiratory Disease
CF. It should be noted however that they measured
resistance only at 10 Hz. Higher frequencies like
R10 and R20 represent the resistance of proximal airways, whereas R5 will provide information of the
entire pulmonary system.3 It is possible that assessment of resistance at a lower frequency like 5 Hz
might provide more information about the peripheral
airway. CF, being a disease of pulmonary parenchyma
with early involvement of distal airways, is likely to
show an abnormality on lower frequencies like 5 Hz.
From our study, it appears that most IOS parameters correlate significantly with the much validated
spirometry parameters. Of the IOS parameters, Z5%
and R5% had a reasonable combination of sensitivity
and specificity to identify children with airway
obstruction. However, a larger adequately powered
study should be conducted to address this question.
To conclude, IOS can be used as an alternative pulmonary function test in patients with CF more so in
children who are unable to perform spirometry.
8.
9.
10.
11.
12.
Funding
This research received no specific grant from any funding
agency in the public, commercial, or not-for-profit sectors.
13.
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