974 Original Research [ 1 4 6 # 4 CHEST OCTOBER 2 0 1 4 ]

Increased Day-to-Day Variability of Forced

Oscillatory Resistance in Poorly Controlled or
Persistent Pediatric Asthma
Paul D. Robinson , MBChB , PhD ; Nathan J. Brown , PhD ; Martin Turner , PhD ; Peter Van Asperen , MD ;
Hiran Selvadurai , PhD ; and Gregory G. King , MBChB , PhD
BACKGROUND: Pediatric asthma lacks sensitive objective measures for asthma monitoring.
Te forced oscillation technique (FOT) ofers strong feasibility across the pediatric age range,
but relationships between FOT parameter day-to-day variability and pediatric asthma severity
and control are unknown.
METHODS: Day-to-day variability in FOT respiratory system resistance (Rrs) and respiratory
system reactance (Xrs) compared with peak expiratory flow (PEF) were defined in 22 chil-
dren with asthma (mean SD age, 10.4 1.1 years) during a 5-day asthma camp. FOT was
performed at 6 Hz in triplicate on each test occasion. Relationships between day-to-day FOT
variability (expressed as within-subject SD [SDW ] and asthma control and severity (defined
according to GINA [Global Initiative for Asthma] recommendations) were explored. For
comparison, normal baseline FOT values and variability, measured on two occasions, were
defned in a separate cohort of 38 healthy children (age, 9.5 1.0 years).
RESULTS: Day-to-day Rrs variability was greater in persistent (n 5 16) vs intermittent (n 5 6)
asthma (mean SDW, 0.69 cm H
2
O/L/s vs 0.39 cm H
2
O/L/s; P .01). Day-to-day Rrs vari-
ability was increased in uncontrolled (n 5 13) vs partly controlled asthma (n 5 9) (mean
SDW, 0.75 cm H
2
O/L/s vs 0.42 cm H
2
O/L/s; P .05). PEF variability did not differentiate
the groups. Day-to-day variability of Rrs and Xrs but not baseline values were increased in
children with asthma vs control children (Rrs mean SDW, 0.61 cm H
2
O/L/s vs 0.33 cm H
2
O/L/s
[ P .05]; Xrs mean SDW, 0.24 cm H
2
O/L/s vs 0.15 cm H
2
O/L/s [ P .05]).
CONCLUSIONS: Increased day-to-day FOT variability exists in school-aged children with
asthma. Day-to-day Rrs variability was associated with asthma severity and asthma control.
FOT may be a useful objective monitoring tool in pediatric asthma and warrants further study .
TRIAL REGISTRY: Australian and New Zealand Clinical Trials Registry; No.:
ACTRN12614000885695; URL: www.anzctr.org.au CHEST 2014; 146(4): 974 - 981
[ Original Research Asthma ]
Manuscript received February 4, 2014 ; revision accepted June 2, 2014;
originally published Online First July 3, 2014.
ABBREVIATIONS: FOT 5 forced oscillation technique; ICC 5 intraclass
correlation coef cient; ICS 5 inhaled corticosteroid; PEF 5 peak expi-
ratory fow; Rrs 5 respiratory system resistance; SDW 5 within-subject
SD; Xrs 5 respiratory system reactance
AFFILIATIONS: From the Woolcock Institute of Medical Research (Drs
Robinson, Brown, Turner, and King), Sydney; Te University of Sydney
(Drs Robinson, Brown, Turner, Van Asperen, Selvadurai, and King),
Sydney; the Department of Respiratory Medicine (Drs Robinson,
Van Asperen, and Selvadurai), Te Childrens Hospital at Westmead,
Westmead; the Cooperative Research Centre for Asthma and Airways
(Drs Robinson, Brown, Turner, and King), Sydney; and the Department
of Respiratory Medicine (Dr King), Royal North Shore Hospital,
St. Leonards, NSW, Australia.
FUNDING/SUPPORT: Tis study was supported by a National Health
and Medical Research Council (NHMRC) Postgraduate Research
Scholarship, an NHMRC Practitioner Fellowship, the Cooperative
Research Centre for Asthma and Airways (Project 2.1), the Australian
Research Council (UPTECH [Ultrafine Particles from Traffic Emis-
sions and Childrens Health] study), and an NHMRC project grant
[512387 ].
CORRESPONDENCE TO: Paul D. Robinson, MBChB, PhD, Department
of Respiratory Medicine, Te Childrens Hospital at Westmead, Locked
Bag 4001, Westmead, NSW 2145, Australia; e-mail: dr.pdrobinson@
gmail.com
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journal.publications.chestnet.org 975
Asthma is the most common chronic respiratory condi-
tion among children in the developed world, and
despite recent advances in treatment, it remains a signif-
icant cause of respiratory morbidity and mortality.
1

Asthma is characterized by variable airfow obstruction.
Increased day-to-day variability of lung function, mea-
sured by peak expiratory fow (PEF), is characteristic of
asthma in adults and a marker of severity and risk of
exacerbations,
2
suggesting that monitoring of lung func-
tion should be an integral component of clinical man-
agement of asthma in adults. However, pediatric asthma
management is primarily symptom based because there
are no suitable objective measurements for monitoring
lung function. Symptom-based management, although
useful,
3
is limited by poor perception and reporting by
both patients and parents.
4
Development of objective
pediatric monitoring tools would improve existing clin-
ical management strategies.
In children, conventional lung function tests such
as FEV
1
and PEF are not well suited to monitoring
day-to-day lung function variability. Both FEV
1
and PEF
are efort dependent and require considerable patient
cooperation. Reduced FEV
1
is associated with an increased
risk of future exacerbations,
5
and increased variability in
FEV
1
occurs in children with chronic respiratory symp-
toms or asthma.
6
However, FEV
1
utility as a monitoring
tool is limited because the majority of patients have nor-
mal FEV
1
, even during acute exacerbations.
7
Although
PEF variability predicts subsequent response to asthma
treatment,
8
written daily PEF diaries are unreliable in
children.
9
Even with electronic PEF meters, correlation
between PEF variability and asthma severity is poor.
10

Te forced oscillation technique (FOT) measures
respiratory system resistance (Rrs) and respiratory
system reactance (Xrs) during tidal breathing. FOT,
therefore, is an efort-independent measure of lung
function and feasible across wide age ranges, including
preschool age.
11
Although diagnostic utility of FOT in
children with asthma is limited,
12,13
it may be suitable as
a monitoring tool. In children, FOT parameters objec-
tively measure bronchodilator response
14,15
and airways
hyperresponsiveness
16,17
and have greater day-to-day
variability than FEV
1
in children with asthma
18
or
chronic respiratory symptoms.
19
However, relationships
between day-to-day variability of FOT parameters and
clinical markers of asthma in children are unknown.
We hypothesized that day-to-day FOT variability in
children would be increased in asthma and would relate
to both asthma severity and asthma control. Te aims of
this study were to determine relationships between FOT
variability and asthma severity and symptom control in
a cohort of school-aged children with asthma and to
compare measures of FOT variability to those in chil-
dren without asthma.
Materials and Methods
Asthma Camp Cohort
Children with asthma were recruited for this study from those aged 8 to
12 years attending a 5-day holiday camp for children with asthma. Te
camp is run by the Asthma Foundation of New South Wales. Attendees
had a physician diagnosis of asthma as reported by their parents, which
was a prerequisite for camp attendance. Parents of all children com-
pleted questionnaires on past and current respiratory health, symp-
toms, and medication use.
Asthma severity and asthma symptom control were determined based
on the questionnaire information and by daily recording of symptoms and
medication use while at camp, as recorded by camp staf. Children were
classifed as having intermittent or persistent asthma.
20
Asthma was also
classifed as being controlled, partly controlled, or uncontrolled
3
based
on GINA (Global Initiative for Asthma) guideline recommendations.
FOT was performed daily during asthma camp at the same time each
day, at least 30 min afer supervised medication administration, and with at
least 10 min rest prior to measurement. Respiratory system impedance
was measured at 6 Hz using an in-house-built FOT device, as described
in detail previously,
21
but modifed to reduce total equipment dead space
2014 AMERICAN COLLEGE OF CHEST PHYSICIANS. Reproduction of
this article is prohibited without written permission from the American
College of Chest Physicians. See online for more details.
DOI: 10.1378/chest.14-0288
to comply with recent pediatric recommendations.
22
Impedance repeat-
ability checks and volume checks were performed at the start and end of
each testing session. At each visit, following a practice test, three tech-
nically acceptable 1-min FOT measurements were performed with the
child sitting upright while wearing a nose clip and with the cheeks and
foor of mouth supported (by the child under instruction). Recordings
were deemed acceptable by the technician if tidal volume and breath-
ing frequency appeared stable, with no obvious leaks or glottic closures
from visual inspection of the volume trace. Breath-by-breath data flter-
ing was used to identify and reject entire breaths in which respiratory
artifact occurred.
23
Rrs and Xrs were recorded for each session as the
mean of all three tests and expressed as raw values because of the lack of
equipment-specifc FOT normative data in this age-group.
Spirometry was also performed on one occasion during the camp afer
FOT measurement. Spirometry was performed using a SpiroCard (QRS
Diagnostic) in accordance with American Toracic Society recommen-
dations
24
and expressed as z scores using recently published normative
data.
25,26
An asthma camp volunteer experienced in the technique super-
vised bid PEF measurement for each child just prior to medication
administration. The highest measurement of three acceptable PEF
attempts was recorded for each test session.
Healthy Control Comparison Cohort
Te healthy control cohort was recruited as part of a separate study, com-
prising a randomly selected cross-section of children aged 8 to 12 years
attending two primary schools in Brisbane, Queensland, Australia.
Tey had been recruited as part of a feasibility study of air pollution
efects on respiratory health. Parents of these children completed detailed
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976 Original Research [ 1 4 6 # 4 CHEST OCTOBER 2 0 1 4 ]
respiratory history questionnaires as part of the recruitment process
and had no history of diagnosis of chronic respiratory disease and no
chronic respiratory symptoms or medication use. As part of the protocol
for the air pollution study, FOT was performed in a designated room
within the school at the same time of day on two occasions 2 weeks apart.
Spirometry was also performed at each visit afer FOT.
Data Handling and Analysis
Data were analyzed using Analyze-it for Microsoft Excel software
(Analyze-it Sofware Ltd). FOT variability was quantifed using the SD,
given that it was unrelated to mean across-the-cohort data sets (data
not shown). Within-session test repeatability was calculated as within-
subject SD (SDW) of three FOT measurements within a single testing
session. Day-to-day repeatability of impedance (termed day-to-day
SDW) was calculated for the asthma camp cohort as SDW of the means
from all testing days (ie, a single mean value used for each day) and for
the healthy cohort, as SDW of the means of the two testing sessions (ie,
days 1 and 14). To adjust for difering test numbers in the SDW calculation
(n 5 5 asthma vs n 5 2 healthy, respectively), additional SDW values
for children with asthma were calculated from frst and last testing ses-
sions alone. Intraclass correlation coef cients (ICCs) were calculated as
recommended by Bland and Altman.
27
PEF variability was expressed
as the lowest PEF value as a percentage of the best PEF value , as rec-
ommended by Brand et al,
28
due to previous correlation with asthma
symptoms. Te t test was used to compare means between groups, and
the x
2
test was used to compare categorical variables. Statistical signif-
cance was defned as P .05. Ethics committee approvals were obtained
for the two studies contributing data to this article. Ethics approval for
the air pollution study (healthy cohort testing) was obtained from the
Queensland University of Technology (Institutional Review Board refer-
ence 1000000703), whereas approval for the asthma camp study was
obtained from Te Childrens Hospital at Westmead (Institutional Review
Board reference 07/CHW/14). Written informed consent to participate
was provided by a parent or guardian of each child.
Results
Twenty-two children (100% of attendees) were recruited
from the asthma camp, and 39 children were eligible for
inclusion from the healthy cohort. All of the asthma
camp cohort provided technically acceptable FOT data
on all days of testing. Of the healthy cohort, two chil-
dren failed to attend both testing sessions, and data
from three children were subsequently excluded
following FOT data analysis (one due to marked tachy-
pnea and two due to presence of frequent upper airway
artifact and variable leak). Tirty-four children, there-
fore, were included in the healthy cohort analysis. Char-
acteristics and baseline lung function of the children
according to asthma status are shown in Table 1 . Te
asthma camp cohort had a higher proportion of boys
(77% vs 47%, P 5 .03) and similar spirometry (% pre-
dicted and z scores) but lower Rrs than the healthy
cohort. Tis fnding likely is due to the diference in
height between the cohorts, with lower Rrs values seen
in the taller children with asthma. Tis relationship
between Rrs and height is shown in e-Figure 1 and is
consistent with published data.
29

Day-to-Day FOT Variability and Asthma Severity
Sixteen children with asthma (68%) were classifed as
having persistent asthma and six as having intermittent
asthma. Baseline characteristics were similar for both
asthma severity groups ( Table 1 ). All children with
TABLE 1 ] Baseline Characteristics and Lung Function of the Asthma Camp (According to Asthma Severity)
and Healthy Control Cohorts
Characteristic
Asthma
Healthy All Intermittent Asthma Persistent Asthma
Male sex 22 (17
a
) 6 (3) 16 (14) 38 (18)
Age, y 10.5 1.2 11.0 0.9 10.3 1.3 9.5 1.0
Height, cm 141.5 10.5 143.3 5.1 141.5 12.0 137.1 6.8
z score 0.12 1.42 0.00 1.08 0.17 1.56 0.62 1.30
FEV
1
% predicted, L 93.6 16.0 94.2 8.0 93.6 18.3 93.6 8.7
z score 2 0.18 1.37 0.09 0.69 2 0.29 1.56 2 0.26 1.29
FVC % predicted, L 103.5 16.2 101.5 8.6 103.5 18.5 93.7 10.0
z score 0.18 1.37 0.18 0.79 0.18 1.56 2 0.25 1.43
FEV
1
/FVC 0.83 0.10 0.86 0.07 0.83 0.11 0.88 0.06
z score 2 0.44 1.20 2 0.15 1.11 2 0.55 1.24 2 0.06 0.93
Rrs, cm H
2
O/L/s 6.04 1.43
a
5.64 1.21 6.19 1.51 7.03 1.25
Xrs, cm H
2
O/L/s 2 1.43 0.64
a
2 1.09 0.28 2 1.55 0.70 2 1.64 0.60
Data are presented as No. (%) and mean SD. Forced oscillation technique and spirometry data were taken from the rst testing session for each
cohort. Rrs 5 respiratory system resistance; Xrs 5 respiratory system reactance.

a
P .05 compared with healthy.
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journal.publications.chestnet.org 977
persistent asthma were prescribed maintenance asthma
preventer medications. Fourteen were managed with
inhaled corticosteroids (ICSs) of which seven used ICS
and a long-acting b
2
-agonist; four used ICS alone; and
three used ICS, long-acting b
2
-agonist, and a leukotriene
receptor antagonist. Te remaining two children were
managed with leukotriene receptor antagonist alone.
Within-session SDW of Rrs and Xrs did not difer
between the intermittent and persistent asthma groups.
Day-to-day variability of Rrs, however, was greater in
the persistent than in the intermittent asthma group
( Fig 1 , Table 2 ). Day-to-day variability of Xrs did not
difer between the two groups ( P 5 .12).
Day-to-Day FOT Variability and Asthma Control
Tirteen children with asthma (59%) were classifed as
having uncontrolled asthma and nine as having partly
controlled asthma. Within-session repeatability of Rrs
in the uncontrolled asthma group was slightly worse
than in the partly controlled asthma group ( P .05).
Day-to-day variability of Rrs was greater in the uncon-
trolled than in the partly controlled asthma group
( P .05) ( Fig 2 , Table 3 ) and greater than the within-
session repeatability seen. Repeatability of Xrs in the
children with uncontrolled asthma was worse than in
the healthy children ( P .05) but did not difer from
the children with partly controlled asthma ( P 5 .21).
Day-to-day variability of Xrs did not difer between the
two groups ( P 5 .11). PEF day-to-day variability did not
difer between the uncontrolled and partly controlled
asthma groups ( Fig 3 ).
Comparison Between the Asthma Camp
and Healthy Control Cohorts
Within-session repeatability for Rrs and Xrs were sim-
ilar between the asthma camp and healthy cohorts. In
healthy children, Rrs and Xrs remained highly repeat-
able between testing sessions, with between-session
ICCs of 0.89 and 0.88, respectively. Corresponding ICCs
in the children with asthma, however, were lower at 0.64
and 0.71, respectively (based on the frst and last testing
session for comparison). Day-to-day variability of Rrs
and Xrs were signifcantly greater than the correspond-
ing within-session repeatability in children with asthma
( P .05) ( Table 2 ). Tis was also found for Rrs among
healthy children ( P .05) but not for Xrs. Day-to-day
variability of Rrs and Xrs in children with asthma was
increased compared with healthy children ( P .05)
( Table 2 ). Increased day-to-day variability compared
with healthy children remained similar in magnitude
and statistical signifcance, using SDW calculated from
the frst and last testing sessions in the children with
asthma (data not shown).
Discussion
In this study, we showed for the frst time in our knowl-
edge that day-to-day Rrs variability is related to both
asthma severity and asthma control, whereas PEF vari-
ability did not diferentiate. Day-to-day variability in
Xrs did not diferentiate. Rrs and Xrs are highly repeat-
able measurements in both healthy children and children
with asthma. Day-to-day Rrs variability was greater in
children with asthma compared with healthy children
and was greater than the variability of the measurement
itself. Tese novel fndings provide evidence that FOT
Rrs may be a suitable objective monitoring tool in pedi-
atric asthma because increased variability in children
with asthma is likely due to the efects of disease.
Potential clinical utility of serial Rrs measurements both
in terms of asthma severity and control are novel fnd-
ings. Tis is reinforced by the single FOT measurements
at baseline being poorly discriminative between children
with asthma and healthy children ( e-Fig 1 , Table 1 ).
Past attempts to investigate the utility of FOT variability
have focused on FOT fuctuations within single record-
ings or across tests within single testing sessions.
23,30-32

Increased within-recording variability (or reduced test
repeatability) has been reported for both adult and pedi-
atric patients with asthma compared with healthy con-
trol subjects. Increased variability of impedance over
a 15-min recording period was originally reported in
adults with asthma.
23
In children, where prolonged
Figure 1 Day-to-day variability, expressed as SD
W
, for children in the
asthma camp cohort classifed according to asthma severity as having
either intermittent ( ) or persistent ( ) asthma. Horizontal bars indi-
cate mean SD
W
values for each group. Rrs
6
5 respiratory system resis-
tance at 6 Hz; SD
W
5 within-subject SD .
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978 Original Research [ 1 4 6 # 4 CHEST OCTOBER 2 0 1 4 ]
TABLE 2 ] Repeatability and Day-to-Day Variability of Rrs and Xrs in Children With Intermittent and Persistent
Asthma Compared With Healthy Control Children
Variable
Asthma
Healthy (n 5 34) All (N 5 22) Intermittent (n 5 6) Persistent (n 5 16)
Repeatability (within-session SDW)
Rrs, cm H
2
O/L/s 0.25 0.29 0.23 0.24
Xrs, cm H
2
O/L/s 0.16 0.18 0.16 0.13
Day-to-day variability (between-session SDW)
Rrs, cm H
2
O/L/s 0.61
a
0.39 0.69
a,b
0.33
Xrs, cm H
2
O/L/s 0.24
c
0.17 0.26
c
0.15
SDW 5 within-subject SD. See Table 1 legend for expansion of other abbreviations.

a
P .01 compared with healthy.

b
P .05 compared with intermittent asthma.

c
P .05 compared with healthy.
recording is more technically dif cult, increased Rrs
variability was described across three 1-min recordings
joined together
31
or across successive Rrs values at
points of zero fow within a single recording of 40 to
45 breaths.
32
However, clinical utility of within-session
variability has not been consistently found in adult
asthma studies.
30
Diba et al,
30
using a shortened 1-min
recording window, compared with Que et al,
23
found no
diference in impedance variability between adults with
asthma and healthy control subjects and no relation-
ships between this measured variability and either diur-
nal variability or airways hyperresponsiveness. In the
current study, within-recording variability was not
examined, and within-session repeatability of Rrs and
Xrs was expressed as the variability across the mean Rrs
and Xrs values from technically acceptable recordings.
Within-session repeatability was similar in the healthy
and asthma camp cohorts but was worse in children
with uncontrolled vs partly controlled asthma. How-
ever, considerable overlap existed between these
groups, which would be expected to limit utility of this
approach.
Day-to-day variability of both Rrs and Xrs was greater
than inherent test variability (within-session SDW),
suggesting that increased day-to-day variability in chil-
dren with asthma compared with healthy children is
due to asthma-related diferences in lung physiology.
Previously, Goldman et al
18
performed daily impulse
oscillometry and spirometry measurements over 3 days
in an asthma camp setting and showed that Rrs
day-to-day variability was greater than that of spirom-
etry. Timonen et al
19
measured FOT in children with
chronic respiratory disease and showed increased Rrs
day-to-day and week-to-week variability compared with
both FEV
1
and FEF, midexpiratory phase. Te fndings of
the current study are consistent with these previous
pediatric studies. In adults with asthma, Timmins et al
33

also reported increased day-to-day variability in Rrs
but not Xrs compared with healthy control subjects.
Relationships to asthma control and severity were not
examined in their study. It is unclear why Rrs is more
variable in poorly controlled and persistent asthma,
whereas Xrs is not. Rrs and Xrs may confer diferent
information in relation to the dynamic behavior of
asthmatic airways. However, the basis of these difer-
ences is unknown, but nevertheless, Rrs may be more
informative than Xrs in children and adults with
asthma. Several possible explanations can be speculated.
Tere may be diferent contributions of airway narrow-
ing and airway closure in asthma to Rrs and Xrs. Inter-
estingly, the volume dependence of Xrs, reflecting
Figure 2 Day-to-day variability, expressed as SD
W
, for children in the
asthma camp cohort classifed according to asthma symptom control as
having either partly controlled ( ) or uncontrolled ( ) asthma. Hori-
zontal bars indicate mean SD
W
values for each group. See Figure 1 legend
for expansion of abbreviations.
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journal.publications.chestnet.org 979
airway closure, relates to asthma control.
34
However, the
simple measure of Xrs at functional residual capacity
may not capture the same clinically important informa-
tion. Rrs and Xrs may refect abnormalities in various
airway compartments, although the nature of the difer-
ences are again uncertain.
Te current study extends these fndings in two impor-
tant ways. First, inclusion of a control group confrms
the increased variability present in children with
asthma by defning normal variability of FOT parame-
ters in school-aged children. Second, FOT variability
was related to test repeatability and measures of
asthma control and severity. Te similar relationship
with both symptom control and severity is not sur-
prising given that both are predominantly symptom
TABLE 3 ] Repeatability and Day-to-Day Variability of Rrs and Xrs in Children With Partly Controlled or
Uncontrolled Asthma Compared With Healthy Control Children
Variable
Asthma
Healthy (n 5 34) Partly Controlled (n 5 9) Uncontrolled (n 5 13)
Repeatability (within-session SDW)
Rrs, cm H
2
O/L/s 0.22 0.28
a,b
0.24
Xrs, cm H
2
O/L/s 0.15 0.18
a
0.13
Day-to-day variability (between-session SDW)
Rrs, cm H
2
O/L/s 0.42 0.75
a,c
0.33
Xrs, cm H
2
O/L/s 0.17 0.28
c
0.15
See Table 1 and 2 legends for expansion of abbreviations.

a
P .05 compared with partly controlled.

b
P .05 compared with healthy.

c
P .01 compared with healthy.

Figure 3 Relationship between asthma control and day-to-day PEF
variability, expressed as the lowest PEF value as a percentage of the best
PEF value, for children with asthma classifed as having either partly
controlled ( ) or uncontrolled ( ) asthma. Horizontal bars indicate
mean values for each group. PEF 5 peak expiratory fow.
based, with preventer treatment being considered in
the severity score. Despite the small numbers, a statis-
tically signifcant diference with relatively small over-
lap was observed ( Figs 1, 2 ) and suggests that repeated
measurements could be clinically useful as an assess-
ment for asthma control. However, larger longitudinal
studies are required to confrm this fnding and deter-
mine whether increased Rrs variability predicts future
loss of control in children, as shown by PEF in adults.
35

Dif culties with PEF in children have already been
discussed, and in the present cohort, PEF variability
did not relate to asthma control.
In measuring between-session repeatability in healthy
children and comparing with an asthma cohort, we
assumed that variability of two measurements per-
formed 14 days apart were representative of test vari-
ability over a few days. We believe that this was a
reasonable assumption for two reasons. First, the
healthy children studied were stable, without evidence
of acute illness, over the period of measurement. Sec-
ond, in the asthma camp cohort, there were no efects
from the environment, particularly in relation to
supervised medication administration. Such efects are
unlikely because no signifcant changes in either Rrs or
Xrs occurred from the start to the end of the camp. In
addition, supervised medication administration might
have actually decreased observed FOT variability;
therefore, fnding increased variability under these
circumstances may underestimate the actual increased
variability present. Finally, although there was a sex
diference between cohorts (more boys in the asthma
cohort), we do not believe that this infuenced the fnd-
ings reported because most pediatric FOT studies con-
ducted to date have not reported a sex efect on FOT
results.
22

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980 Original Research [ 1 4 6 # 4 CHEST OCTOBER 2 0 1 4 ]
Although asthma camps provide a unique opportunity
to conduct well-supervised studies of this nature in
children,
18,31
future studies will need to establish feasibility,
as already demonstrated in adults,
36,37
of FOT monitoring
in children in the unsupervised home setting. Te clinical
relevance of the current fndings is that Rrs variability
difers in relation to asthma control and severity, giving
support for future studies on home monitoring provided
that technological advances will lead to small, practical
FOT devices for this purpose in children and adults.
In conclusion, day-to-day variability of Rrs in school-
aged children with asthma is related to both disease
severity and symptom control and is greater than that
observed in healthy children. Tese fndings, combined
with low variability of Rrs in healthy, school-aged chil-
dren, suggest potential utility of daily FOT measure-
ment in pediatric asthma management. Future studies
are needed to confrm these relationships in the home
setting and the ability of FOT monitoring to predict
future asthma exacerbations and response to treatment.
Acknowledgments
Author contributions: P. D. R. had full access
to all of the data in the study and takes respon-
sibility for the integrity of the data and the
accuracy of the data analysis. P. D. R., N. J. B.,
M. T., P. V. A., H. S., and G. G. K. contributed
to the study concept and design, data analysis
and interpretation, drafing of the manuscript,
review of the manuscript for important intel-
lectual content, and fnal approval of the man-
uscript; and P. D. R. and M. T. contributed to
the data acquisition.
Financial/nonfnancial disclosures: Te
authors have reported to CHEST the
following conficts of interest: Dr King has
received various sponsorships from Boehringer
Ingelheim GmbH; Novartis AG; Pfzer, Inc;
AstraZeneca plc; and GlaxoSmithKline plc
for travel and accommodation to attend inter-
national, local, and interstate meetings that
include pharmaceutical industry-sponsored
meetings and independent society scientifc
meetings. A proportion of Dr Kings research
is conducted at the Woolcock Institute of Med-
ical Research, which receives or has received
unrestricted grants from AstraZeneca plc,
Boehringer Ingelheim GmbH, GlaxoSmithKline
plc, and Pharmaxis Ltd and which also has
current and past consultancy agreements
with AstraZeneca plc; Boehringer Ingelheim
GmbH; GlaxoSmithKline plc; and Pfzer, Inc.
His research group receives a proportion of
the grants and monies that arise from those
companies as part of a general allocation of
funds for research purposes across all research
groups of the Woolcock Institute of Medical
Research. Dr King provides consultancy ser-
vices related to asthma and COPD, which
include sitting on advisory boards and pro-
viding talks at local and national meetings
for AstraZeneca plc, Boehringer-Ingelheim
GmbH, GlaxoSmithKline plc, Mundipharma
International, and Novartis AG, for which
his institution and research group receive
payments. His research group receives sup-
port from competitive grants arising from
local research foundations, the National
Health and Medical Research Council of
Australia, Cooperative Research Centre for
Asthma and Airways, and Lung Founda-
tion Australia. Dr Kings research group is
also supported by grants from Boehringer
Ingelheim GmbH, GlaxoSmithKline plc, and
Mundipharma International. Drs Robinson,
Brown, Turner, Van Asperen, and Selvadurai
have reported that no potential conficts of
interest exist with any companies/organizations
whose products or services may be discussed
in this article .
Role of sponsors: Te sponsors had no role
in the design of the study, the collection and
analysis of the data, or the preparation of the
manuscript.
Other contributions: Te authors thank
Asthma Foundation New South Wales for
its support in facilitating the FOT measure-
ments at its annual asthma camp held in
conjunction with the New South Wales
Department of Sport and Recreation. Tey
also thank the members of the UPTECH
(Ultrafne Particles from Traf c Emissions
and Childrens Health) project, including Guy
Marks, Lidia Morawska, Kerrie Mengersen,
Zoran Ristovski, Godwin Ayoko, Mandana
Mazaheri, Sama Low Choy, Jaime Mejia, Wafaa
Ezz, Gail Williams, Diane Keogh, Adriana
Cortes, and Brett Toelle for their contribu-
tion to this work. Te authors further thank
Matthew Falk for his assistance in the
classifcation of the epidemiologic studies
and his contribution to the discussion of
epidemiologic study design, Folasade Fatokun
(formerly from International Laboratory for
Air Quality and Health, Queensland Univer-
sity of Technology, and currently from the
Department of Employment, Economic
Development and Innovation) for the initial
collection of the literature, and Rachael
Appleby for administrative assistance .
Additional information: Te e-Figure can
be found in the Supplemental Materials
section of the online article.
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