Clinical Investigations

Received: January 19, 2010

Accepted after revision: July 15, 2010
Published online: November 5, 2010

Respiration 2011;81:461468
DOI: 10.1159/000319580

Multidetector Row Computed

Tomography to Assess Changes in
Airways Linked to Asthma Control
Pierre-Y.Brillet a ValrieAttali b GalleNachbaur e AndrCapderou c,f
Marie-H.Becquemin c CatherineBeigelman-Aubry d CatalinI.Fetita g
ThomasSimilowski b MarcZelter c PhilippeA.Grenier d

UPRES EA 2363, Service de radiologie, Hpital Avicenne, Assistance Publique Hpitaux de Paris, Universit
Paris 13, Bobigny, b Service de pneumologie, c UPRES 2397, Service dexplorations fonctionnelles respiratoires,
d
Institut National de la Sant et de la Recherche mdicale U678, Service de radiologie, Hpital Piti-Salptrire,
Assistance Publique Hpitaux de Paris, Universit Pierre et Marie Curie Paris 6, e Clinical research
department Respirology, GlaxoSmithKline, Paris, f Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson,
g
ARTEMIS Department, CNRS UMR8145, TELECOM Sud Paris, Evry, France

Abstract
Background: In asthma, multidetector row computed tomography (MDCT) detects abnormalities that are related to
disease severity, including increased bronchial wall thickness. However, whether these abnormalities could be related to asthma control has not been investigated yet. Objective: Our goal was to determine which changes in airways
could be linked to disease control. Methods: Twelve patients
with poor asthma control were included and received a salmeterol/fluticasone propionate combination daily for 12
weeks. Patients underwent clinical, functional, and MDCT
examinations before and after the treatment period. MDCT
examinations were performed using a low-dose protocol at
a controlled lung volume (65% TLC). Bronchial lumen (LA)

2010 S. Karger AG, Basel

00257931/11/08160461$38.00/0
Fax +41 61 306 12 34
E-Mail [email protected]
www.karger.com

Accessible online at:

www.karger.com/res

and wall areas (WA) were evaluated at a segmental and subsegmental level using BronCare software. Lung density was
measured at the base of the lung. Baseline and end-of-treatment data were compared using the Wilcoxon signed-rank
test. Results: After the 12-week treatment period, asthma
control was achieved. Airflow obstruction and air trapping
decreased as assessed by the changes in FEV1 (p ! 0.01) and
expiratory reserve volume (p ! 0.01). Conversely, LA and WA
did not vary significantly. However, a median decrease in LA
of 110% was observed in half of the patients with a wide intra- and intersubject response heterogeneity. This was concomitant with a decrease in lung density (p ! 0.02 in the anteroinferior areas). Conclusions: MDCT is insensitive for
demonstrating any decrease in bronchial wall thickness. This
is mainly due to changes in bronchial caliber which may be
linked to modifications of the elastic properties of the bronchopulmonary system under treatment.
Copyright 2010 S. Karger AG, Basel

Dr. P.Y. Brillet

Service de radiologie, Hpital Avicenne
125 rue de Stalingrad
FR93009 Bobigny (France)
Tel. +33 1 4895 5852, Fax +33 1 4895 5554, E-Mail [email protected]

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Key Words
Asthma control Respiratory mechanics, physiology
Inhaled treatment Quantitative evaluation Multidetector
row computed tomography

Material and Methods

One of the goals of asthma treatment is to achieve disease control and reduce chronic airway inflammation
[1]. Indeed, inflammation, which is essentially characterized by edema, leads to airway remodeling, which is
essentially characterized by subepithelial fibrosis [2]. Finally, these structural modifications are likely to contribute to the decline of lung function and can lead to
chronic respiratory insufficiency [3]. Clinically, it has
been demonstrated that inflammation is associated with
symptoms and poor asthma control [1]. However, detecting persisting inflammation remains challenging [47].
Therefore, treatment efficacy remains based on the clinical features of the disease, including lung function abnormalities.
In asthmatic patients, computed tomography (CT)
detects abnormalities that are related to airway inflammation and remodeling [8, 9]. Using CT, authors have
noted an increase in lung density that may reflect inflammation in the lung and distal airways [10]. Others
have observed an increase in the wall area (WA) of bronchi that is related to the duration and/or severity of the
disease and correlated to the intensity of structural [11,
12] and functional [9, 13] changes. Recently, Niimi et al.
[13] showed that in a population including a majority of
moderate and severe asthma patients, the increase in WA
responds partially to treatment by an inhaled corticosteroid [14]. However, whether patients in that group had
uncontrolled disease was not mentioned and could be a
confounding bias. Based on these results, the present
study was designed to see whether modifications in airway geometry and lung density could be observed in a
group of patients with poor asthma control but a homogeneous severity level.
Image acquisition was performed using multidetector
row CT (MDCT), and analysis of bronchial dimensions
was performed using a dedicated software (BronCare)
[15]. This software makes it possible to create 3-dimensional reconstructions of the airway tree with quantification of the lumen area (LA) and WA orthogonal to the
central axis of the bronchi and evaluation of the length
(Lg) of the bronchi. Herein, we evaluated changes in airways using MDCT after the achievement of asthma control under inhaled treatment. The objective was to determine which changes in bronchial dimensions could be
observed after disease control.

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Respiration 2011;81:461468

This was a pilot, open-label, one-arm, 12-week study evaluating changes in airways before and after treatment with a salmeterol/fluticasone propionate combination (SFC; Seretide or Advair) of 50/250 g [16, 17]. This treatment is a combination of an
inhaled corticosteroid which aims to target inflammation and a
long-acting 2-agonist which aims to target smooth muscle relaxation. The achievement of asthma control after 12 weeks with such
a treatment has been proved [18]. The protocol, including the irradiation dose, was approved by the local Ethics Committee (Comit Consultatif de Protection des Personnes dans la Recherche
Biomdicale). All patients gave their written informed consent.
Patients
Twelve patients with poor asthma control i.e. not fulfilling
the criteria of asthma control defined by the GINA [1] were recruited through a contracted research organizations database for
voluntary asthmatics trials. Patients who were 1840 years old
and has a prebronchodilator forced expiratory volume in 1 s
(FEV1) 170% of the predicted value were included. Active smokers or previous smokers with a smoking history of 610 pack-years
and patients suffering from any respiratory pathology that could
also interfere with radiologic examination were not included.
Treatment with corticosteroids (inhaled or systemic) within the 3
months prior to inclusion and treatment with long-acting inhaled
2-agonists, oral 2-agonists, or oral theophylline within 4 weeks
prior to inclusion were not allowed.
Study Design
Patients entered a 12-week treatment period and received 1
inhalation of SFC twice daily. The treatment administration was
performed within 2 weeks after inclusion (delay necessary to perform all baseline evaluations including the CT scan). Short-acting
2-agonists or any other bronchodilator therapy used as rescue
were allowed. Seven visits were scheduled during the study. Clinical assessments were performed at the inclusion visit and at each
following visit. A diary record card was filled out daily by patients
who recorded their morning and evening peak expiratory flow
rates, occurrence of asthma symptoms, and the number of puffs
of rescue short-acting 2-agonist, allowing comparisons between
baseline and the 12-week treatment period. Asthma control was
assessed using the Asthma Control Questionnaire (ACQ) [19] at
the inclusion visit, twice during follow-up visits, and at the endof-the-study visit. MDCT acquisitions and lung function tests
were performed before starting the study treatment and at the end
of the treatment period.
Pulmonary Function Tests
Lung function measurements were performed at baseline and
at the end of the treatment period, at least 6 h from short-acting
bronchodilator use and 12 h after the last dose of treatment. FEV1,
maximal expiratory flow between 25 and 75% (MEF2575%), and
forced vital capacity (FVC) were measured by a flow-volume loop.
Lung volumes, including residual volume (RV), expiratory reserve volume (ERV), functional residual capacity (FRC), and total
lung capacity (TLC), were evaluated by helium diffusion in the
sitting position and by body plethysmography. The absence of significant air trapping was assessed by comparing the results obtained by helium diffusion to those obtained by plethysmography

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Introduction

d
Before treatment

Before
treatment

After treatment

Fig. 1. MDCT evaluation of the variations in bronchial dimensions (WA, LA, and Lg) before (bd) and after (eg) treatment at

a subsegmental level using BronCare software. Three-dimensional automated segmentation of the lumen (a) and automatic 3-dimensional computation of the central axis of the airway tree (b,
e) with selection of the bronchus under study [red arrows indicate

[20]. Helium diffusion was also performed in the supine position

at baseline in order to measure FRC in the position of MDCT acquisitions and to calculate the 65% TLC value used for these acquisitions. FEV1 was measured before and after 400 g salbutamol, permitting the calculation of the reversibility of FEV1 (percentage of variation before and after salbutamol).
MDCT Protocol
Low-dose acquisitions were performed on a 16-channel detector row CT (GE LightSpeed 16; General Electric, Buc, France) at
a controlled lung volume using a pneumotachograph (V2000;
Sensormedic, Yorba Linda, Calif., USA). To ensure a comparable
wash-out of the bronchodilator, CT examinations were performed
at least 6 h from short-acting bronchodilator use and, for the second CT examination, at least 12 h after the last dose of treatment.
Patients were instructed to perform a full inhalation followed by
a slow exhalation. Acquisitions were made after interruption of
the slow expiratory phase at 65% TLC according to a previously
described protocol [10]. In order to limit the radiation dose delivered to patients, acquisitions were performed at the base of the
lung with a slice thickness of 0.6 mm and low-dose irradiation
parameters ranging from 100 kVp and 50100 mAs according to
the patients morphotype, with a gantry rotation time of 0.5 s and
a pitch of 1.3. This corresponded to a range of CT dose indexes of
2.546.36 mGy with a dose length product from 26 mGycm (an
estimated effective radiation dose of 0.4 mSv) to 65 mGycm (estimated effective radiation dose of 1 mSv). Reconstruction was
centered on the right middle and lower lobes using a lung kernel.
The field of view was 1820 cm with a 512 ! 512 pixel matrix.
Slice thickness was 0.6 mm with a reconstruction interval of 0.3

Changes in Airways Linked to Asthma

Control

basilar subsegmental bronchus of the lateral bronchus of the inferior lobe (B9b)]. Cross-section image reformation of the bronchus
perpendicular to the central axis (c, f) with automatic segmentation of the lumen (green area) and wall contour (red line) (d, g).
Results show a decrease in LA on the second MDCT acquisition
(after treatment) compared to the first one (before treatment).

mm, corresponding to an extrapolated voxel size of 0.35 ! 0.35

! 0.3 mm. The bronchi of the left lower lobe were not assessed
because of cardiac motion artifacts.
Analysis of Airway Geometry and Lung Density
The evaluation of bronchial dimensions [LA, WA, WA% (defined as the ratio of WA to the total area of the bronchus), and Lg]
was performed using BronCare software [15] for segmental and
subsegmental bronchi of the middle and right lower lobe that fulfilled the validation criteria defined by Brillet et al. [15], including
an LA 1 4 mm. The different steps of the procedure are presented
in figure 1. These validation criteria permitted limitation of the
inaccuracy of bronchial segmentation with an overestimation of
WA that could be observed when the bronchus was surrounded
by vascular structures. For the evaluation of variations in bronchial dimensions, interactive selection of a given bronchial pair
(before and after treatment) was performed on the 3-dimensional computation of the central axis by the same radiologist (P.Y.B.).
This was based on anatomic landmarks, mainly the shape of the
bronchus and the relationship between the bronchus and the adjacent vessels. The results of the segmentation as well as the location of the measurements were validated by 2 observers (P.Y.B.
and C.I.F.).
Evaluation of the lung densities (Hounsfield Units; HU) was
performed according to previously described methodology [10].
Regions of interest consisted of squares measuring 1215 ! 1215
mm positioned in the periphery of the right lung in vessel-free
areas. These regions included mainly alveolar units and distal
conducting airways. Six areas were drawn in the anterior, lateral,
and posterior part of the lung at 2 levels.

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After
treatment

the 12-week treatment period (end of treatment)

Baseline
median
(minmax)

End treatment
median
(minmax)

Peak expiratory flow rate, l/min

Morning
454 (370636)
504 (394697)
Evening
458 (385649)
509 (398692)
Absence of symptoms, %
Days
60 (088)
99 (25100)
Nights
100 (80100)
100 (90100)
Absence of short-acting bronchodilator use, %
Days
70 (0100)
99 (94100)
Nights
95 (0100)
99 (87100)

p value

<0.001*
<0.001*
<0.001*
0.156
<0.001*
0.039*

* p < 0.05 calculated using Wilcoxon signed-rank test was considered as significant.

Table 2. Results of the pulmonary function tests measured by a

flow-volume loop (FEV1, MEF2575%, FVC, FEV1/VC, and FEV1
reversibility) and body plethysmography (RV, ERV, FRC, and
TLC) at baseline and at the end of the 12-week treatment period

FEV1
MEF2575%
FVC
FEV1/VC
RV
ERV
FRC
TLC

Baseline,
median %
predicted
(minmax)

End of treatment,
median %
predicted
(minmax)

p value

92 (66109)
58 (4294)
101 (81126)
94 (8199)
109 (83145)
89 (53123)
105 (67130)
99 (84116)

98 (78113)
79 (53106)
100 (81126)
101 (84118)
100 (72147)
99 (81122)
107 (76140)
93 (81114)

0.007*
0.007*
0.131
0.007*
0.006*
0.006*
0.252
0.33

* p < 0.05 calculated using the Wilcoxon signed-rank test was

considered statistically significant.

Statistical Analysis
The statistical analysis was performed using SAS version 8.02
(SAS Institute, Cary, N.C., USA). No data evaluating the effect of
SFC on airways using CT was available in the literature, therefore
no hypothesis was formulated for this exploratory pilot study. It
was scheduled to include a total of 12 subjects in the study in order
to obtain 8 patients with evaluable MDCT sets of data in the whole
treatment period. Baseline and end-of-treatment bronchial dimensions, lung densities, and clinical and functional results were
compared to the null hypothesis using a Wilcoxon signed-rank
test (except when otherwise stated). For the selected bronchial
pairs (before and after treatment), comparisons were also per-

464

Respiration 2011;81:461468

formed for subgroups of bronchi: (i) segmental or subsegmental

bronchi and (ii) LA on initial examination normalized to body
surface (BS; mm2/m2) or !7. This cutoff was determined empirically, permitting the separation of bronchi into 2 groups equal in
number. Data were therefore presented as medians and ranges
(minimummaximum values). p ! 0.05 was considered statistically significant, taking into account that the variation of bronchial dimensions between values at baseline and at the end of
treatment should exceed the 95% interscan variability of measurements. This variability was established using the Bland and
Altman approach according to the methodology defined by Brillet et al. [21], giving thresholds of 1.6 mm2, 2.71 mm2, and 2 mm
for LA, WA, and Lg, respectively.
Due to the design of the study, the type I error spending rate
was not addressed.

Results

Patient Characteristics
The study population included 8 males and 4 females
with a median age of 25.5 years (range 1937). The median time between inclusion and SFC administration was
10 days (range 814). The patient population had poor
asthma control with a median percentage of days without
symptoms of 60% and a median percentage of days without short-acting 2-agonist use of 70%. The flow-volume
curve analysis demonstrated a decrease in MEF2575%
(58% predicted). Conversely, the FEV1 value remained in
the normal range. Body plethysmography and helium diffusion showed that FRC was in the normal range, although
ERV (median of 89.5% predicted) was on the lower side
and RV (median 109.5% predicted) on the higher side.
Clinical and Functional Response to Treatment
After the 12-week treatment period, the results of the
diary record cards indicated that the asthma was controlled (table1) with a change in the ACQ from 1.57 at
baseline to 0.43 under treatment (p ! 0.001). This was
associated to a significant increase in FEV1, MEF2575%,
and ERV (p ^ 0.007; table2) and to a significant decrease in RV (p = 0.018 compared to baseline). Conversely, no significant change in TLC or FRC was observed. Finally, a median (min, max) reduction of the
reversibility of FEV1 from 5.9% (0.9, 13.9) to 1.0% (3.2,
4.5) was noted (p ^ 0.007).
Changes in Bronchial Geometry under Treatment
Among the 12 patients included in this study, 10 fulfilled the complete MDCT protocol. The numbers of
bronchi which matched the validation criteria and were
included for statistical analysis are presented in table3. No
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Table 1. Results of the diary record cards at baseline and during

60

780

40

800

After

820

20

HU

Percentage variation of LA (%)

Treatment
Before

0
20

840
860
880

40

900

60

920

p = 0.016
Sup/Post
Inf/Post

Sup/Lat
Inf/Lat

Sup/Ant
Inf/Ant

Fig. 2. Percentage variation of the LA before and after treatment

Fig.3. Median pulmonary density changes (HU) before and after

for each bronchus (diamonds). Results are presented for each of

the 10 patients that completed the MDCT protocol and the median variation per patient is presented as a horizontal bar.

treatment in regions of interest drawn in the anterior, lateral, and

posterior areas at the superior and inferior levels. Error bars represent the upper quartile limit. The difference was significant in
the anterior areas of the lower level (p = 0.016). Ant = Anterior;
Lat = lateral; Post = posterior; Sup = superior; Inf = inferior.

Table 3. Bronchial dimensions of segmental and subsegmental bronchi at baseline and at the end of the 12-week treatment period.
LA, mm2

All bronchi
Segmental
Subsegmental
LA/BS >7
LA/BS 7

WA, mm2

Length, mm2

WA%, %

baseline

end of
treatment

p
value

baseline

end
treatment

p
value

baseline

end of
p
treatment value

baseline

end of
treatment

p
value

12.7
(9.619.8)
18.9
(11.229.5)
10.5
(6.414.9)
18.5
(13.325.1)
8.8
(7.811)

13.5
(8.117.1)
19.1
(10.325.2)
10.1
(7.314.5)
19.4
(12.422.2)
9.1
(6.310.9)

0.62

13.7
(11.215.3)
17.7
(12.820.2)
12.7
(9.514.8)
17
(13.919)
12.2
(9.614.2)

13.3
(10.614.7)
15.1
(11.718.7)
12.6
(10.614.6)
16.1
(12.922)
11.6
(1013.6)

0.37

55
(5059)
51
(5056)
56
(5360)
48
(4650)
58
(5561)

56
(5160)
55
(5260)
55
(5260)
46
(5260)
55
(5160)

14.1
(11.315.9)
14.5
(1015.8)
13.7
(11.116.9)
13.9
(11.316.5)
14.8
(10.719.4)

13.6
(10.815.4)
13.8
(10.815.6)
13.3
(10.816)
13.8
(1115.6)
13.9
(1018.4)

0.049*

0.85
0.32
0.62
0.77

0.47
0.85
0.85
0.16

1
0.16
0.19
0.92
0.62

0.43
0.06
0.38
0.02*

Data are presented as the median (minmax) values obtained for each patient for all bronchi (n = 112 for Lg and LA and n = 74 for WA and WA%)
and for categories of bronchi.
* p < 0.05 was calculated using the Wilcoxon signed-rank test, but the variations under treatment were inferior to the interscan variability of measurements between successive acquisitions [personal data; 20, 34] so that results could not be considered significant.

statistically significant difference in bronchial dimensions (LA, WA, WA%, and Lg) was observed after treatment (table3) in the whole population or in the different
subgroups of bronchi compared to baseline measures.
The change in bronchial caliber under treatment was
very heterogeneous for each patient (intrasubject) and between patients (intersubjects) (fig.2). Indeed, 5 patients
(50%) had at least a 10% decrease in LA, whereas 2 pa-

tients (20%) tended to dilate their bronchi. For WA, the

median variations were inferior to 5%, except for bronchi
with an LA/BS ratio ^7 (5.4%, p = 0.16; fig.1).

Changes in Airways Linked to Asthma

Control

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Changes in Lung Density under Treatment

The median change in pulmonary density decreased
in all areas (fig.3) and was significant in the anterior areas of the lower level (p = 0.016).

MDCT evaluation of bronchial dimensions is gaining

interest in bronchial diseases. It provides an accurate
evaluation of the bronchial caliber, as confirmed by comparisons with quantitative videobronchoscopy [22]. In
recent studies, airway dimensions were obtained using
volumetric CT, which allows measurement in a plane orthogonal to the long axis of the airways. Such an approach
associates a 3-dimensional computation of the central
axis of the tracheobronchial tree (leading to skeletonization of the airway tree) and a 2-dimensional segmentation of bronchial boundaries (leading to the quantification of LA and WA) [11, 15]. The bronchial segmentation
is performed using an energy-driven contour estimation
method which has proved to be as accurate as the full
width at half maximum principle but induces less overestimation of LA for the smallest bronchi [21].
Our study is one of the very few to focus on the effect
of asthma control on airway geometry and lung density.
We focused on a homogeneous group of patients and applied inclusion criteria ensuring the exclusion of patients
with a long history of asthma and severe disease and with
nonreversible bronchial wall remodeling. Our results
show that MDCT evaluation of bronchial dimensions at
65% TLC permitted the detection of some changes in
bronchial caliber after treatment by SFC but not in bronchial wall thickness. This was associated with an improvement in clinical symptoms and pulmonary function tests and implied that the mechanical properties of
the bronchopulmonary system had changed.
In our protocol, the MDCT acquisition pairs (before/
after treatment) were performed at 65% TLC [10], a
known volume predetermined experimentally by helium
dilution in the supine position prior to the acquisition.
The rationale of this protocol was based on the relation
between lung volume and transbronchial pressure. Bronchi distend as the lungs are inflated, secondary to the
transmission of pleural pressure to the lung and peribronchial space [23, 24]. At 65% TLC, the transbronchial
pressure is minimized compared to full inspiration.
Based on this assumption we would have expected to observe identical bronchial calibers before and after treatment. Surprisingly, this was not the case in our study as
most bronchi changed caliber under treatment. In light
of the clinical and functional results, we hypothesize that
the change in LA values may be due to a change in bronchial hysteresis [25]. Based on the decrease in lung density and functional results evaluating distal lung function, our results suggest that the changes in the mechan466

Respiration 2011;81:461468

ical properties of the bronchopulmonary system may be

linked to a decrease in lung inflammation in the lung and
distal airways. This conclusion can also be drawn in light
of the histological findings using transbronchial biopsy
techniques supporting the role of inflammation in distal
regions of the lungs [26, 27] and evaluating the effect of
inhaled treatment [6].
In comparison to the results of Niimi et al. [14], we did
not observe any significant difference in WA between results obtained before and after treatment. Their study included a majority of moderate and severe asthma patients
and did not take into account asthma control. The authors noted an 11% decrease in WA under treatment leading from 28.3 to 21.5 mm2 (p ! 0.001) for the apical bronchus of the right upper lobe. However, values remained
higher than in the controls (17.6 mm2). Therefore, the authors hypothesized that the reversible part of bronchial
wall thickening may reflect a decrease in bronchial inflammation [14] and that the thickened remaining part is
linked to remodeling. Herein, patients were younger and
had a less severe disease ensuring the existence of reversible inflammatory lesions. These 2 conditions may explain why the variation in WA under treatment measured
using MDCT was mild, i.e. around 5%. Therefore, we
conclude that the evaluation of WA lacks sensitivity for
the direct detection of structural changes linked to bronchial inflammation and remodeling in our population of
patients and, more generally, in patients with a recent history of asthma. This last point is also corroborated by the
study of Siddiqui et al. [28] who observed no change in
WA on CT performed at full inspiration in patients with
mild-to-moderate asthma after 2 weeks of oral prednisolone. We hypothesize that longer treatment and follow-up
periods as well as a large cohort of patient should be required for that kind of study in early stages of the disease.
Conversely to WA, the quantification of LA at 65%
TLC may be an important endpoint in clinical studies,
giving indirect information on airway inflammation and
demonstrating the heterogeneity of airway response to
treatment [29, 30]. Indeed, LA evaluation of proximal
bronchi makes it possible to observe intrasubject i.e.
from one bronchus to another and intersubject i.e.
between patients variations between both MDCT acquisitions. Moreover, we could observe more prevailing
changes in the smallest airways under study, whether
they were subsegmental bronchi or bronchi with an LA/
BS ratio ^7, and noted a high intra- and intersubject variability in LA variations (fig.2) under SFC. Therefore, it
would be interesting to determine in future studies how
heterogeneity could be quantified and whether or not it
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Discussion

References

Changes in Airways Linked to Asthma

Control

contrast with the report by Mitsunobu et al. [37] who observed low values of mean lung density in asthmatics.
One explanation for this apparent paradox is overinflation associated with an evaluation of lung density at full
inspiration in their study. Moreover, their population
study is also different as it includes older patients with
more severe disease. Therefore, we hypothesize that only
the analysis at 65% TLC may demonstrate mechanicalproperty changes in the bronchopulmonary system as
a consequence of the decrease in inflammation under
treatment [10]. Finally, our results outline the great dependency of measurements to bronchial caliber using the
combined 3-dimensional/2-dimensional approach applied here. We hypothesize that a fully 3-dimensional approach leading to an extraction and quantification of the
bronchial wall volume should improve the sensitivity of
measurements of bronchial remodeling [38]. Moreover,
our results suggest that other parameters aside from WA
should be considered for the evaluation of asthma control. These parameters would have to take into account
the heterogeneity of bronchial geometry from one bronchus to another or along the bronchial axis [21]. Another
interesting approach would be to compute fluid dynamics from the realistic 3-dimensional reconstructions of
the lumen. Using this technique, De Backer et al. [39]
demonstrated that measuring change in airway volume
and airflow resistance was possible and correlated well
with clinical improvement under treatment.
In conclusion, asthma control was associated with significant changes in pulmonary function tests and lung
density at MDCT. However, even though no significant
change was noted for bronchial dimensions, this technique seems to be an informative tool to demonstrate
changes in airway caliber and is relevant for evaluating
disease heterogeneity.

Acknowledgement
This study was supported by GlaxoSmithKline, France.

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3 Lange P, Parner J, Vestbo J, Schnohr P, Jensen

G: A 15-year follow-up study of ventilatory
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could be considered as a biomarker of asthma control.

Indeed, we may hypothesize that asthma control should
be associated to a more homogeneous distribution of
bronchial calibers.
The main limitation of our study is the small number
of patients, impairing the significance of the results obtained with MDCT and the power of the statistical analysis. For example, we could not conclude with regard to
the significance of the changes in bronchial length (table1; p ^ 0.05). Indeed, this result was inferior to our
evaluation of the interscan variability of measurements
of this parameter (personal data). However, as MDCT
have few indications in asthma [31], limiting the irradiation in research settings is relevant [32, 33]. This was performed by limiting the number of patients involved and
by decreasing the irradiation dose during acquisition. Using this low-dose protocol, thus minimizing any hypothetical risk of carcinogenesis due to repeated CT, we
showed that the quantification of bronchial dimensions
was feasible. However, in future clinical trials inclusion of
a larger number of patients than in the present study will
be required. Secondly, we could not demonstrate the respective roles of salmeterol and fluticasone propionate in
the clinical improvement, and the changes in bronchial
caliber could not be determined. In the light of our results, we hypothesized that the changes in the mechanical
properties of the bronchopulmonary system through
changes in the lung parenchyma-airway interdependence
and pulmonary elastic recoil seemed the most prevailing
factors responsible for the changes in LA under treatment
[34, 35]. However, bronchial wall stiffness, bronchial hyperresponsiveness [29], and bronchial smooth muscle
tone through the individual sensibility of patients to the
inhaled 2-agonist [36] may also be involved. Therefore,
it could be interesting to compare SFC to inhaled corticosteroids alone in order to distinguish the specific additional effect of salmeterol in patients naive to inhaled
corticosteroids. This study should conclude on how the
combination works and whether the 2 drugs have synergic effects. Third, the variations in lung density seem to

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