Exercise-induced airway obstruction in young asthmatics measured by impulse oscillometry.

Abstract

Impulse oscillometry (IOS) is a good method for measuring airway resistance. It does not require special breathing skills and it can reflect different aspects of airway obstruction to those revealed by spirometry, which is an effort-dependent maneuver.
To evaluate the characteristics of airway obstruction in young asthmatics after an exercise bronchial provocation test (EBPT) using IOS.
Forty-seven young adults were enrolled in the study. All the participants underwent a methacholine bronchial provocation test (MBPT) and an EBPT for the evaluation of their asthma. IOS and spirometric parameters were collected at baseline and at 0, 5, 10, 20, and 30 minutes post-EBPT.The participants were divided into 2 groups according to MBPT positivity: an airway hyperresponsiveness (AHR) group and a no-AHR group.
There were differences in the percent decrease in forced expiratory volume in the first second (FEV1) between the 2 groups at 5, 10, and 20 minutes after exercise. Resistance at 5 Hz (R5) increased in the AHR group but not in the no-AHR group at 5 and 10 minutes after exercise. Integration of reactance from 5 Hz to resonance frequency (area of reactance, AX) was also increased in the AHR group at only 5 and 10 minutes post-EBPT. Delta R5 and delta AX at 5 and 10 minutes post-exercise were well correlated with the percent decrease in FEV1.
IOS parameters, especially delta R5 and delta AX, may be useful for performing objective evaluations and improving our understanding of exercise-induced airway obstruction in young asthmatics.

Full text

Page 1

J Investig Allergol Clin Immunol 2010; Vol. 20(7): 575-581 © 2010 Esmon Publicidad
JH Lee, et al
ORIGINAL ARTICLE
Exercise-Induced Airway Obstruction in
Young Asthmatics Measured by Impulse
Oscillometry
JH Lee, YW Lee, YS Shin, YH Jung, CS Hong, and JW Park
Division of Allergy and Immunology, Department of Internal Medicine, Institute of Allergy, Brain Korea
21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
■ Abstract
Background: Im pulse oscillom etry (IOS) is a good m ethod for m easuring airway resistance. It does not require special breathing skills and
it can refl ect different aspects of airway obstruction to those revealed by spirom etry, which is an effort-dependent m aneuver .
Objective: To evaluate the characteristics of airway obstruction in young asthm atics after an exercise bronchial provocation test (EBPT)
using IOS.
Methods: Forty-seven young adults were enrolled in the study. All the participants underwent a m ethacholine bronchial provocation test
(MBPT) and an EBPT for the evaluation of their asthm a. IOS and spirom etric param eters were collected at baseline and at 0, 5, 10, 20,
and 30 m inutes post-EBPT . The participants were divided into 2 groups according to MBPT positivity: an airway hyperresponsiveness (AHR)
group and a no-AHR group.
Results: There were differences in the percent decrease in forced expiratory volum e in the fi rst second (FEV1) between the 2 groups at 5, 10,
and 20 m inutes after exercise. Resistance at 5 Hz (R5) increased in the AHR group but not in the no-AHR group at 5 and 10 m inutes after
exercise. Integration of reactance from 5 Hz to resonance frequency (area of reactance, AX) was also increased in the AHR group at only
5 and 10 m inutes post-EBPT . ∆R5 and ∆AX at 5 and 10 m inutes post-exercise were well correlated with the percent decrease in FEV1.
Conclusions: IOS param eters, especially ∆R5 and ∆AX, m ay be useful for perform ing objective evaluations and im proving our understanding
of exercise-induced airway obstruction in young asthm atics.
Key words: Im pulse oscillom etry. Exercise-induced bronchoconstriction. Asthm a.
■ Resumen
Antecedentes: La oscilom etría de im pulsos (IOS) es un buen m étodo para determ inar la resistencia de las vías respiratorias. No requiere
una técnica de respiración especial y puede refl ejar aspectos de la obstrucción de las vías respiratorias distintos de los revelados por la
espirom etría, una m aniobra dependiente del esfuerzo.
Objetivo: Evaluar las características de la obstrucción de las vías respiratorias en jóvenes asm áticos tras una prueba de provocación bronquial
con ejercicio físico (PPBE) m ediante IOS.
Métodos: En el estudio participaron cuarenta y siete adultos jóvenes. Todos los participantes se som etieron a una prueba de provocación
bronquial con m etacolina (PPBM) y a una PPBE para evaluar el asm a. Se recopilaron los parám etros espirom étricos y de la IOS al inicio
del estudio y a los 0, 5, 10, 20 y 30 m inutos tras la PPBE. Los participantes se dividieron en dos grupos según la positividad de la PPBM:
un grupo con hiperreactividad de las vías respiratorias (HRVR) y un grupo sin HRVR.
Resultados: Se observaron diferencias en la dism inución porcentual de volum en espiratorio m áxim o en el prim er segundo (VEM1) entre los
dos grupos a los 5, 10 y 20 m inutos tras el ejercicio físico. La resistencia a 5 Hz (R5) aum entó en el grupo con HRVR pero no en el grupo
sin HRVR a los 5 y 10 m inutos tras el ejercicio físico. La integración de la reactancia desde 5 Hz hasta la frecuencia de resonancia (área
de reactancia, AX) tam bién aum entó en el grupo con HRVR a los 5 y 10 m inutos después de la PPBE. Los parám etros ∆R5 y ∆AX a los 5
y 10 m inutos tras el ejercicio físico m ostraron una buena correlación con la dism inución porcentual de VEM
Conclusiones: Los parám etros de la IOS, especialm ente ∆R5 y ∆AX, pueden ser útiles para realizar evaluaciones subjetivas y m ejorar el
conocim iento de la obstrucción de las vías respiratorias inducida por el ejercicio físico en jóvenes asm áticos.
Palabras clave: Oscilom etría de im pulsos. Broncoconstricción inducida por el ejercicio físico. Asm a.
1.

Page 2

IOS in Exercise-induced Asthma

J Investig Allergol Clin Immunol 2010; Vol. 20(7): 575-581© 2010 Esmon Publicidad
Introduction
Exercise is an important exacerbating factor in bronchial
asthma, especially in children and young adults because
of their high level of physical activity [1]. The exercise
bronchial provocation test (EBPT) has been used to confi rm
exercise-induced bronchoconstriction (EIB) [2]. In this test,
serial spirometric data are collected after 5 to 10 minutes of
exercise. A decrement in forced expiratory volume in the fi rst
second (FEV1) from baseline is the most important diagnostic
value, with a decrease of 10% or more indicating a diagnosis
of EIB [3].
In allergic airway diseases such as asthma and allergic
rhinitis, airway hyperresponsiveness (AHR) caused by
nonspecifi c airway irritation is a characteristic fi nding [4].
However, there is controversy regarding whether or not exercise
can induce or increase nonspecifi c AHR [5-7]. Although not
all asthmatics present EIB, the EBPT is a necessary test,
especially in pre-recruitment physical examinations for
military conscription [8].
In many countries, including Korea, Turkey, and
Switzerland, military reinforcement is supplied by obligatory
recruitment [9], and the detection of draft evaders is important.
In many other countries, however, such as the United States,
England, and Japan, military forces are entirely made up of
career soldiers [9]. In these countries, pre- and post-recruitment
physical examinations are important when choosing suitable
young men and women for the physically demanding tasks
required in the military.
Spirometry is used to detect EIB [10] but because it is an
effort-dependent forced maneuver, those undergoing this test
can theoretically manipulate results [11]. Another technique
known as the forced oscillation technique (FOT) offers a
reliable means of measuring airway resistance. The FOT is
useful for evaluating disease status or severity in chronic
obstructive pulmonary disease and bronchial asthma [12] and
is used with children and elderly patients unable to cooperate
with forced expiration [13]. FOT measurements are taken
during tidal breathing and therefore cannot be manipulated
by those undergoing the test.
In this study, we evaluate exercise-induced airway
characteristics measured by impulse oscillometry (IOS),
a commercially-available FOT, in young asthmatics with
nonspecifi c AHR.

Methods
Patients
Forty-seven individuals who visited the Allergy-Asthma
Clinic at our institution between September 2006 and July
2008 were enrolled in the study. They were all male and
wished to have their asthma status evaluated prior to mandatory
military recruitment by the Korean Military Manpower
Administration. The inclusion criterion was defi ned as the
presence of intermittent asthma or mild persistent asthma as
defi ned by the Global Initiative for Asthma guidelines [14].
Individuals on long-acting ß2 agonists and who had taken
rescue medication within 48 hours before the examination, or
who had had an upper respiratory infection in the 4 previous
weeks, were excluded. Those enrolled were divided into 2
groups according to their methacholine bronchial provocation
test (MBPT) results: an AHR group (those with a PC20
[amount of methacholine required to cause a 20% reduction
in FEV1 from baseline] of <25 mg/mL; n=35) and a no-AHR
group (those with a PC20 of ≥25 mg/mL; n=12) (Table 1). The
Institutional Review Board of Yonsei University approved the
study (IRB protocol no. 4-2009-0241) and informed consent
was obtained from all participants.
Exercise Bronchial Provocation Test
The exercise challenge was performed using a free-running
test on a treadmill. The participants ran for 10 minutes or
until 80% to 90% of their estimated maximum heart rate
was achieved. Maximum heart rate was calculated using the
equation (205-(1/2)?age) [15]. Heart rate was assessed using a
heart rate monitor (VIASYS Healthcare, Höchberg, Germany).
IOS and spirometry parameters were obtained at baseline and
at 0, 5, 10, 20, and 30 minutes after the exercise challenge.
Impulse Oscillometry
IOS parameters were collected before conventional
spirometry using the MasterLab IOS System (Erich Jaeger
Co., Würzburg, Germany). Calibration was performed using a
single volume of air (3 L) at different fl ow rates and a reference
resistance device (0.2 kPa/L/s). The individuals wore a nose
clip and a manufacturer-provided oval hard plastic mouthpiece
to prevent expired air from escaping. They were also asked
to support their cheeks with their hands to decrease shunt
compliance. Artifacts caused by coughing, breath-holding,
swallowing, and vocalization were not included. A single,
experienced, respiratory technician performed all the IOS
measurements. The parameters evaluated were resonance
frequency (Rfreq), resistance at 5 Hz (R5), resistance at 10 Hz
(R10), resistance at 20 Hz (R20), difference in resistance between
5 Hz and 20 Hz (R5-R20), reactance at 5 Hz (X5), and area of
reactance (AX; area integrated from 5 Hz to Rfreq). With the
exception of Rfreq, all of the above values were used to calculate
differences from baseline.
Spirometry
Spirometric parameters were measured immediately after
IOS measurements in all individuals. A pneumotachometer
system with a Lilly head (MasterScreen system; Erich Jaeger
Co.) was used to measure maximum expiratory fl ow volume.
The spirometric flow-volume curve was obtained using
international criteria [16]. All the individuals wore a nose clip
and performed standard forced expiratory maneuvers. At least
3 acceptable attempts were included and the best was selected
for the fi nal analysis.
Methacholine Bronchial Provocation Test
The MBPT was also performed in all cases according to
international guidelines [2]. Methacholine powder was distilled
and diluted in isotonic saline and administered using a handheld
576

Page 3

J Investig Allergol Clin Immunol 2010; Vol. 20(7): 575-581 © 2010 Esmon Publicidad
JH Lee, et al
nebulizer (Devilbis 646; Devilbis Health Care Inc, Somerset,
England) connected to a Rosental dosimeter (Devilbis Health
Care Inc). For each dose, each individual inhaled 5 times
from functional residual capacity without holding their breath
after a full inspiration. The fi rst concentration of administered
methacholine was 0.075 mg/mL, and a dose-response
curve was plotted by serial doubling in the concentration of
methacholine up to 25 mg/mL. The PC20 was calculated using
linear interpolation between the last 2 points on the dose-
response curve. When this value was lower than 25 mg/mL,
AHR was considered to be present. The MBPT was conducted
2 weeks before the EBPT.
Statistical Analysis
Data were analyzed using version 12 of the SPSS statistical
software (SPSS Inc, Chicago, Illinois, USA). Nonparametric
statistical methods were used. The Mann-Whitney U test was
used for comparing means and the Spearman rank correlation
test was used for analyzing correlations. The discriminative
properties of the different IOS parameters to identify AHR
patients were evaluated using receiver operating characteristic
(ROC) curves. To compare each variable, areas under the curve
(AUC) with 95% confi dence intervals (CIs) were determined.
Signifi cance was defi ned as P<.05. The data are shown as
means±SEM. Logistic regression analysis was used to compare
IOS parameters with FEV1 values.

Abbreviations: AHR, airway hyperresponsiveness; AX, area of reactance (area integrated from 5 Hz to
Rfreq); FEV1, forced expiratory volum e in the fi rst second; FVC, forced vital capacity; PC20, am ount of
m ethacholine required to cause a 20% decrease in FEV1 from baseline; R5, resistance at 5 Hz; Rfreq,
resonance frequency; X5, reactance at 5 Hz.
aAll data are shown as m eans (SD).
bP<.01.
Table 1. Characteristics of Study Patientsa

AHR (n=12) No-AHR (n=35)
P Value
Age, y
Sex (male:female)
Height, cm
Weight, kg
Body mass index, kg/m2
FVC, L
FEV1, L
FVC, % predicted
FEV1, % predicted
FEV1/FVC ratio, %
Rfreq
R5
R10
R20
R5-R20
X5
AX
PC20, mg/mLb
20.7 (0.9)
12:0
174.2 (6.1)
72.8 (11.5)
23.9 (3.3)
4.68 (0.76)
4.05 (0.72)
92.6 (9.4)
94.5 (13.5)
86.4 (7.2)
10.6 (3.5)
0.27 (0.05)
0.24 (0.05)
0.20 (0.05)
0.07 (0.03)
-0.08 (0.05)
0.18 (0.14)
>25.00
20.3 (1.7)
33:0
174.5 (5.3)
70.4 (10.7)
23.1 (3.1)
4.53 (0.44)
3.84 (0.42)
91.1 (7.9)
91.6 (10.0)
85.0 (7.5)
12.0 (3.3)
0.27 (0.08)
0.23 (0.06)
0.19 (0.05)
0.08 (0.06)
-0.10 (0.06)
0.33 (0.41)
2.78 (2.72)
.129
.625
.575
.584
.843
.337
.843
.342
.433
.143
.723
.669
.462
.722
.704
.209
<.001
Results
Changes in Spirometry and Impulse Oscillometry
Parameters After the Exercise Bronchial
Provocation Test
There were no differences between the AHR group and
the no-AHR group in terms of baseline spirometry results
(forced vital capacity [FVC], FEV1, or FEV1/FVC), or IOS
parameters. Baseline Rfreq and AX values were slightly higher
in the AHR group but the differences were not statistically
signifi cant (Table 1).
Signifi cant differences were found between the groups
in the EBPT, with considerable differences found for time-
related patterns of spirometry and IOS parameters. In the AHR
group, FEV1 fell immediately after the exercise challenge with
a maximum decrement of –9.96±1.74% (0.11±0.97% in the
no-AHR group, P<.001) at 5 minutes and recovery of normal
ranges at 10 to 30 minutes after the exercise challenge. There
were no changes in FEV1 in the no-AHR group (Figure 1A).
Rfreq was signifi cantly higher in the AHR group than in the
no-AHR group at 5 minutes (15.1±0.6 Hz vs 12.8±0.8 Hz,
P=.034), 10 minutes (13.9±0.7 Hz vs 10.7±0.7 Hz, P=.010), 20
minutes (12.6±0.6 Hz vs 9.5±0.6 Hz, P=.025), and 30 minutes
(12.2±0.7 Hz vs 9.1±0.5 Hz, P=.033) after exercise (Figure 1B).
In addition, increments of resistance at 5 Hz (∆R5) were also
much higher in the AHR than in the no-AHR group at 5 minutes
577

Page 4

IOS in Exercise-induced Asthma

J Investig Allergol Clin Immunol 2010; Vol. 20(7): 575-581 © 2010 Esmon Publicidad
0.10
0.8
0.6
0.4
0.2
-0.0
-0.2
-0.4
-0.10
0.08
0.06
0.04
0.02
0.00
-0.02
-0.04
0.06
0.04
0.02
0.00
-0.02
-0.04
-0.06
-0.08
∆R20, kPa/L/s
2
0
-2
-4
-6
-8
-10
-12
FEV1 Fall, % Change
16
15
14
13
12
11
10
9
8
Rfreq, Hz
0.10
0.08
0.06
0.04
0.02
0.00
-0.02
-0.04
R10 , kPa/L/s
0.10
0.08
0.06
0.04
0.02
0.00
-0.02
-0.04
∆, RS-R20, kPa/L/s
0.60
0.50
0.40
0.30
0.20
0.10
0.00
-0.10
∆R20, kPa/L/s
∆XS, kPa/L/s
Baseline 0 m in 5 m in10 m in 20 m in 30 m in
Tim e After Exercise Challenge
∆AX, kPa/L
Baseline 0 m in 5 m in10 m in 20 m in 30 m in
Tim e After Exercise Challenge
Figure 1. Serial changes in fall in forced expiratory volum e in the fi rst second (FEV1) (A); Rfreq (B); R5 (C); R10 (D); R20 (E); (R5-R20) (F); X5 (G); and AX (H)
according to tim e after exercise bronchial provocation test. All data are shown as m eans±SEM. (P<.05 ). Open circles indicate the group without airway
hyperresponsiveness (AHR) and closed circles, the group with AHR. AX indicates area of reactance (area integrated from 5 Hz to Rfreq); R5, resistance at
5 Hz; Rfreq, resonance frequency; X5, reactancy at 5 Hz.
(0.071±0.013 kPa/L/s vs 0.018±0.008 kPa/L/s, P=.027) and
10 minutes (0.055±0.013 kPa/L/s vs –0.007±0.008 kPa/L/s,
P<.001) post-challenge (Figure 1C). Increments of resistance
at 10 Hz (∆R10) at both 5 minutes (0.033±0.008 kPa/L/s vs
–0.003±0.010 kPa/L/s, P=.011) and 10 minutes (0.031±0.008
kPa/L/s vs –0.010±0.011 kPa/L/s, P=.005), in addition to ∆(R5-
R20) values (frequency dependency of airway resistance) at
10 minutes (0.039±0.010 kPa/L/s vs –0.002±0.009 kPa/L/s,
P=.009) were also signifi cantly higher in the AHR group
than in the no-AHR group (Figures 1D, 1F). The decrease
in reactance at 5 Hz (∆X5) at 5 minutes after the exercise
challenge was greater in the AHR group than in the no-AHR
578

Page 5

J Investig Allergol Clin Immunol 2010; Vol. 20(7): 575-581 © 2010 Esmon Publicidad
JH Lee, et al
group (–0.048±0.012 kPa/L/s vs 0.002±0.014 kPa/L/s, P=.040)
(Figure 1G). Finally, AX values in the AHR group compared
to the no-AHR group were also signifi cantly increased at
5 minutes (0.431±0.083 kPa/L vs 0.091±0.060 kPa/L, P=.010)
and 10 minutes (0.298±0.072 kPa/L vs 0.007±0.039 kPa/L,
P=.031) after the exercise (Figure 1H).
25
20
15
10
5
0
-30 -20 -100 10
Resonance Frequency, Hz
0.3
0.2
0.1
0.0
-0.1
-30
-10
10
∆R10, kPa/L/s
0.3
0.2
0.1
0.0
-0.1
-30 -20 -100 10
∆R5, kPa/L/s
0.3
0.2
0.1
0.0
-0.1
-30 -20 -100 10
∆R5-∆R20, kPa/L/s
2.0
1.5
1.0
0.5
-0.5
161616 16 16
∆AX, kPa/L
0.3
0.2
0.1
0.0
-0.1
-30 -20 -10
FEV1 Fall, % Change
01
∆R20, kPa/L/s
0.1
0.0
-0.1
-0.2
-0.3
-30 -20 -10
FEV1 Fall, % Change
0 10
∆X5, kPa/L/s
0.0
FEV1 fall, % Change
FEV1 Fall, % Change
Figure 2. Correlations between fall in forced expiratory volum e in the fi rst second (FEV1) vs. im pulse oscillom etry (IOS) param eters at 5 m inutes after
exercise challenges. RFreq, R5, R5-R20, AX, and X5 were all well correlated with FEV1. The exceptions were R10 and R20. AX indicates area of reactance (area
integrated from 5 Hz to Rfreq); R5, resistance at 5 Hz; Rfreq, resonance frequency; X5, reactance at 5 Hz.
Table 2. Correlation Coeffi cients (ρ) and P values of Fall in FEV1 vs IOS Param eters

IOS
Time After Exercise Bronchial Provocation Test
















Parameters
0 min 5 min 10 min 20 min 30 min
Rfreq

∆R5

∆R10

∆R20

∆(R5-R20)

∆AX

∆X5

ρ
P
ρ
P
ρ
P
ρ
P
ρ
P
ρ
P
ρ
P
0.040
.791
0.156
.296
0.038
.801
0.266
.071
-0.097
.517
-0.025
.867
-0.171
.249
-0.456b
.001
-0.314a
.032
-0.278
.059
-0.104
.487
-0.375b
.009
-0.545b
<.001
0.396b
.006
-0.412b
.004
-0.367a
.011
-0.302a
.039
-0.293a
.046
-0.328a
.024
-0.441b
.002
0.190
.201
-0.346a
.017
-0.323a
.027
-0.296a
.043
-0.145
.330
-0.308a
.035
0.455b
.001
0.138
.355
-0.159
.287
0.030
.839
-0.021
.889
0.064
.669
-0.136
.363
-0.229
.121
0.084
.577
Abbreviations: AX, area of reactance (area integrated from 5 Hz to Rfreq); FEV1, forced expiratory volum e in the fi rst second; IOS, im pulse oscillom etry;
R5, resistance at 5 Hz; Rfreq, resonance frequency; X5, reactance at 5 Hz.
aP<.05.
bP<.01.
Correlation Analysis of Spirometry and Impulse
Oscillometry Parameters
The IOS parameters Rfreq, ∆R5, ∆(R5–R20), ∆AX, and ∆X5
were all well correlated with the decrease in FEV1 at 5 minutes
after exercise (Figure 2). At 10 minutes, ∆R10 but not X5 was
579