950 HD

29
Influence of smoking on LAA in asthma
Correlation between pulmonary function and
low attenuation area (LAA) on HRCT III
patients with asthma in relation to smoking
Fumihiro Mitsunobu, Takashi Mifune, Yasuhiro
Hosaki, Kozo Ashida, Hirofumi Tsugeno, Makoto
Okamoto, Shingo Takata, Tadashi Yokoi, and
Yoshiro Tanizaki
Department of Medicine, Misasa Medical Branch,
Okayama University Medical School
Abstract : The influence of smoking on pulmonary function and emphysematous
changes of the lung (percentage of attenuation area
<
-950 HU (96LAA) on high
resolution computed tomography (HRCT) was examined in 49 patients with bronchial
asthma.
1. In patients with asthma, the 96 residual volume (RV) in many nonsmokers
was less than 12996, in contrast, the 96RV in many smokers was between 13096 and
18996 , which was higher than that in nonsmokers. 2. Significant correlations between
96RV and 96LAA value, and between 96RV and CT number were observed both in
nonsmokers and smokers with asthma, in which as 96RV more increased, 96LAA value
was larger, and CT number was lower. 3. 960Lco value was lower in smoking patients
with asthma, whose 96RV was between 13096 and 18996 and larger than 19096, however,
the 960Lco value did not change in nonsmoking patients despite of higher valure in
96RV.
4. A significant correlation was also observed between %FEV1.0 value and
96RV both in smoking and nonsmoking patients with asthma; as 96RV value more
increased, %FEV1.0 value was lower.
96RV was not observed.
5. Any correlation between 96FVC value and
These results suggest that smoking affects the %LAA of the
lung on HRCT and 960Lco in patients with asthma.
Key words: asthma, smoking, 96LAA of the lungs, FEV1.0, OLco
Influence of smoking on LAA in asthma
Introduction
Asthma IS characterized by transient or
sometimes persistent narrowing of the airways. The disease sometimes shows emphysematous changes of the lung evaluated by
%low attenuation area (%LAA) <-950 HD
on high resolution computed tomography
(HRCT) I). In contrast, it has been suggested
that the diagnosis of emphysema by pathologic examination is correlated with high
resolution computed tomography (HRCT) scan
findings 2. 3). The low attenuation area (LAA)
< -950 Housfield Unit (HD) of the lungs on
HRCT scans at full inspiration is an objective measure of the extent of pulmonary
emphysema 4. 5). However, the influences of
hyperinflation and of nonemphysematous expiratory airflow limitation on the CT quantification of pulmonary emphysema are still unclear 6 ).
High resolution CT has been also used to
study asthmatic patients. It has been observed that asthmatic patients manifest more
abnormalities related to permanent airways
remodelling, such as bronchial dilatation, and
bronchiectasis, than do healthy subjects 7. 8).
Furthermore, emphysematous changes of the
lung on HRCT have been observed in patients
with asthma in relation to smoking and
severity of the disease!. 9.10).
In this study, influences of smoking on the
percent of low attenuation area (%LAA)
< -950 HD of the lungs by HRCT and on
pulmonary function particularly %DLco, residual volume (RV), and FEV1.0.
Subjects and Methods
The subjects in this study were 49 patients
(21 females and 28 males) with asthma.
Twenty patients were previous and current
30
smokers with an average smoking history of
49.1 ±32.5 pack-year. The remaining 29 pa. tients were nonsmokers. Seven (35.0%) of
the 20 smoking patients had severe intractable asthma with lomg-term glucocorticoid
therapy. In contrast, 9 (31.0%) of the 29
nonsmoking patients had severe asthma being
treated with glucocorticoids. Asthma was
evaluated according to the criteria of the
International Consensus of Diagnosis and Management of Asthmall). All patients revealed
reversible airway response with a difference
between prebronchodilator and postbronch"
odilator values of FEV1 exceeding 15%. An
informed consent for study protocol was
obtained from all study patients.
CT scans were performed on a TOSHIBA
Xpeed scanner (2.7s, 200 mAs, 120 kVp) without infusion of contrast medium, using 2-mm
collimation (HRCT) in patients breathholding
at full inspiration. The lungs were scanned
as preselected three anatomic levels; (l) top
of the aortic arch, (2) origin of the lower
lobe bronchus, (3) three. cm above the top of
the diaphragm, as reported by Miniati M, et
al. 12). Inspiratory HRCT scans were evaluated qunantitatively by measuring the percentage of lung area with CT number < -950
HD (%LAA) and the mean CT number in
HD. In this study, the mean %LAA between
the two anatomic levels of the lung: origin
of the lower lobe bronchus and three cm
above the top of the diaphragm, was expressed as representative %LAA in -each
patient with asthma. The LAA on HRCT can
be evaluated by two aspects: severity and
extent. The severity is graded on a 4-point
scale; O. no emphysema, 1. low attenuation
areas <5 mm in diameter, 2. circumscribed
low attenuation areas>5 mm in diameter,
3. diffuse low attenuation areas without
Influence of smoking on LAA in asthma
31
intervening normal lung. However, in this
study, LAA of the lung < -950HU was evaluated
refardless of the severity. The CT number
was calculated from the CT numbers of the
three anatomic levels.
Pulmonary function tests, %forced vital
capacity (FVC) , %forced expiratory volume
in one second (FEV1, %predicted), %residual
volume (RV, %predicted) and %DLco (%predicted), were carried out in all patients using
a CHESTAC 33 (Chest Co) linked to a Computer, when they were attack-free. The subjects were classified into three groups by the
degree of %RV: < 129%, 130-189%, and
190%<.
IgE antibodies against house dust mite
(HDm) , cockroach, and Candida were estimated by radioallergosorbent test (RAST)
and serum level of total IgE was measured by
radioimmunosorbent test (RIST).
statistically significant differences of the
mean were estimated using the unpaired
Student't test. A p value of <0.05 was regarded as significant.
Results
Table 1 represents the characteristics of
smoking' and nonsmoking patients with asthma. Mean age was higher in smokers than in
nonsmokers with asthma. The level of serum
IgE was higher in smoking patients than in
nonsmoking patients. However, the difference
was not significant.
The positive rate of RAST scores for HDm
was not different between smokers and nonsmokers with asthma (Table 1).
Nonsmoking patients with asthma showed
the %RVless than 129% most frequently
(65.6%), in contrast, the %RV between 130
and 189% was most often observed in smoking subjects with asthma (Fig. 1).
Table 1 . Characterristics of patients with
asthma studied
Subjects
Smoker
No of
patients
Mean age
(years)
20
SerumlfE
(IU/ml
RAST score
(HD2+<)
474
68.1
9/20
(45.0%)
(19-2562)
Nonsmoker
29
12/29
(41.4%)
355
61.0
(2()"1124)
60 -
....c
'.'
'.'
50
:::
.'.
40-
:=:
:::
:::
G1
~
G1
0.
-::=
'.'
r,:::
~.:
...•.
:::::
.....
.
~:::
.....
.....
.....
•....
.....
.....
...•.
.....
~.:.
~:::
:::::
....•
30 -
.:::::
....
~.:.
20 -
100
11: :::::
~;::
~:.:
::: l!!ll
<129
~
.... ~:§:::::
.... .:::::.........
~:::
:::::
•....
.....
.....
.:.~
~j ~~~~~ j ~ ..•...•...
.....
:::~
:::::
130-189
190<
Residual volume (%predicted)
Fig.1. Frequency of asthmatics with three
different degrees of residual volume
inrelation to smoking; smoker ( ~ )
and non smoker (&:;I )
A significant correlation between %RV and
%LAA on HRCT was observed both in nonsmoking and smoking patients with asthma.
In nonsmokers with asthma, the mean of %LAA
was 10.2± 7.7% (mean ± SD) in subjects
with %RV less than 129%, 29.5± 11.4% in
those with %RV between 130 and 189%, and
37.0±4.7% in those with %RV more than
190%. The %LAA was larger as the %RV
increased, and the %LAA was significantly
Influence of smoking on LAA in asthma
lower in the subjects with %RV<129% than
in those with %RV of 130-189% (p<O.OOl),
and 190%< (p<O.OOl). Smoking patients with
asthma showed a same tendency as nonsmoking subjects. The mean %LAA was significantly lower in patients with %RV<129%
than in subjects with %RV of 130-189%
(p<O.Ol) and 190%< (p<O.Ol) (Fig. 2).
-950
-940
•
40
«
«
-l
30
·0
•
0
00
b
b
It.
E -890
:s
•
•
..0
c -880
0
•
0
0
ab
ed
-870
0
0
-860
-850
-840
o
•
•
-920
-910
'GI -900
.Q
o
50
..
-930
lU
32
-830
d
-820
0
0
0
I
<129
130-1 !:I9
0
It
Fig.3. Correlation between residual volume
(RV) and CT number in patients with
asthma : smoker (0 ) and nonsmoker
(
.
).
a and b ; p<0,02, c and d ; p<O,OOl.
<129
130-189
..
190<
Fig.2. Correlation between residual volume
(RV) and %LAA on HRCT in patients
with asthma: smoker ( • ) and nonsmoker ( 0 ).
a and b ; p<O.OOI, c and d ; p<O.Ol.
100
--r~
1
••
90
0
80
0
U
...I
Q
at
A significant correlation was also found
between mean CT number and %RV both in
nonsmoking and smoking patients with asthma, as shown in Fig. 3. The %DLco value
was to a certain extent correlated with %RV
in smokers with asthma. A marked decrease
in %DLco was found in smoking patients of
%RV between 130 and 489%, and those of
%RV more than 190%, however, decrease in
%DLco was not found in the patients of
%RV less than 129% (Fig 4).
•
1
Residual volume (%predicted)
~o
0
.0
0
8
•~
70
0
60
0
•
0
!L.
.·0
8
50
8
40
0
0
oT
<129
130-189
190<
Residual volume (%predicted)
Fig.4. Correlation between residual volume
(RV) and %DLco In patients with
asthma : smoker ( 0 ) and nonsmoker
(
.
).
33
Influence of smoking on LAA in asthma
Regarding ventilatory function, any significant correlation was not observed between
%FVC and %RV both in nonsmoking and
smoking patients with asthma (Fig. 5). In
contrast, %FEVl.O value was significantly
correlated with the degree of %RV both in
patients with and without smoking. In nonsmokers with asthma, the %FEVl.O in patients with %RV less than 129% was significantly higher than the values in subjects with
%RV between 130 and 189% (p<O.OOl), and
more than 190% (p<O.Ol). Regarding smokers with asthma, the %FEVl.O value was
significantly larger in subjects with %RV
<129% than in those with %RV 190%<
(p<O.01) (Fig. 6).
:8
--
..
•
c
I""""
0
0
0
0
ab'
I
.-
8
•
•
J
- •
.-8
_
c
0
a"• 8
•
•
0
0
=
<129
0
.0
130-189
b_· 00
••
•
0
190<
Residual volume (%predicted)
••
o
100
90
U
80
>
LL.
Iill!
•
70
60
•
•
,0
•
o0
•
·8
•
•
•
8
Discussion
o
It is generally agreed that CT scanning is a
sensitive technique of detecting emphysematous lesions in patients with chronic obstructive pulmonary disease (COPD). It has been
shown that the relative lung area with low
attenuation values < -950 HU on HRCT scans
at full inspiration is a sensitive imaging
method to measure the extent of pulmonary
emphysema 4. 5). However, the influences of
50
40
<129
130-189
Fig.6. Correlation between residual volume
(RV) and %FEVl.O in patients with
asthma : smoker ( 0 ) and nonsmoker ( • ).
a ; p<O.OOl, band c ; p<O.Ol.
190<
Residual volume (%predicted)
Fig.5. Correlation between residual volume
(RV) and %FVC m patients with
asthma : smoker ( 0 ) and nonsmoker ( • ).
hyperinflation and of nonemphysematous expiratory airflow limitation on HRCT has not
been investigated in pulmonary emphysema 6).
Regarding the. percentage of low attenuation area (%LAA) of the lung, Newman KB,
et al. have reported that there was no significant difference between asthmatic patients
and control subjects for the inspiratory
Influence of smoking on LAA in asthma
HRCT scans obtained in the lower lung areas
« -900 HD), whereas difference was significant for the upper lung areas I3). They concluded that hyperinflation and airflow obstruction without emphysematous lung destruction would not influence densitometric
measurements obtained from inspiratory scans.
A close correlation between pulmonary
emphysema and smoking has been extensively
suggested. Smoking patients with asthma
have significantly more emphysema than
nonsmoking patientsl4• 15). In this study, to
clarify the influence of smoking on %LAA of
the lungs, and %RV in patients with asthma.
A significant correlation was found between
%RV and %LAA, between %RV and mean
CT number, and between %RV and %FEV1.0
both in nonsmoking and smoking patients
with asthma; as %RV increased, %LAA
showed a tendency to increase, and mean CT
number and %FEV1.0 value decreased in the
two groups (nonsmoking and smoking group).
However, marked differences were observed in
patients with asthma between nonsmokers
and smokers. The %RV was less than 129%
in many of nonsmokers with asthma (65.6%),
in contrast, the %RV was between 130 and
189% in many of smokers with asthma
(60.0%). A marked decrease in %DLco was
found in smoking patients with asthma with
%RVlarger than 130%, however, not found
in nonsmoking patients with asthma. These
results suggest that smoking influences an
increase in %RV, relating to an increase in
%LAA of the lungs, and also shows that
smoking leads to a marled decrease in %Dlco
in patients with asthma.
References
1. Ashida K, Mitsunobu F, Mifune T, et al. :
Clinical effects of spa therapy on patients
34
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Clim 63; 113-119, 2000.
2. Hruban RH, Meziane MA, Zerhouni EA, et
al. : High resolution computed tomography
of inflation-fixed lung. Pathologic-radiologic
correlation of centrilobular emphysema.
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3. Kuwano K, Matsuba K, Ikeda T, et al. :
The diagnosis of mild emphysema. Comparison of computed tomography and pathology scores. Am Rev Respir Dis 141 :
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4. Gevenois PA, deMaertelaer V, DeVuyst P,
et al. : Comparison of computed density
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5. Gevenois PA, DeVuyst P, deMaertelaer V,
et al. : Comparison of computed density
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6. Morgan MDL : Detection and quantification of pulmonary emphysema by computed
tomography: a window of opportunity.
Tho-rax 47 : 1001-1004, 1992.
7. Paganin F, Trussard V, Seneterre E, et al. :
Chest radiography and high resolution
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8. Angus R, Davies M, Cowan M, et al. :
Computed tomographic scanning of the
lungs in patients with allergic bronchopulmonary aspergillosis and in asthmatic
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gillus fumigatus. Thorax 49 : 586 - 589,
1994.
9. Gevenois PA, Scillia P, deMaertelaer V, et
al.: The effects of age, sex, lung size, and
3
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気管支嘱息患者 における肺機能 と HRCT 上の
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%)｡非喫煙例および喫煙例いずれ において も､
2.%RV と %LAA､%RV と CT numbe
r問 に
有意の相関が見 られた :%RVが上昇す るにつれ
光延文裕､御船尚志､保崎泰弘､芦田耕三､
て､%LAA値 は増加 し､CT n
umbe
rは低下す る
柘野浩史､岡本 誠､高田真吾､横井
傾向が見 られた｡ 3.喫煙例 で は､%RVが 1
3
0
-
正､
谷崎勝朗
9
0
% 以上 の症例 で､ %DLc
o値
1
8
9% あるいは 1
が明かに低値を示す症例が見 られたが､非喫煙症
岡山大学医学部三朝分院
例では%RVが高 い値 を示 して も %DLc
oの低下
はみ られなか った｡ 4.喫煙例､非喫煙例 いずれ
9例 を対象 に､肺機能 および Hi
g
h気管支瑞息4
において も､%FEV1
.
0倍 と %RV値の問には有
r
e
s
o
l
ut
i
onc
omput
e
dt
omo
gr
a
phy (
HRCT) 上
の Low at
t
e
nuat
i
o
nar
e(
LAA)<-9
5
0HUで
意の相関が見 られ､ %RV値 が上昇 す るにつれ
示 され る肺気腫様変化に及ぼす喫煙の影響 につい
%FVCと %RVの問には相関 は見 られなか った｡
て検討 した｡ 1.気管支噴息患者の うち､非喫煙
以上 の結 果 よ り､ 喫煙 は気 管支 噂 息 患 者 の
て､%FEV1
.
0値 は低下す る傾向が見 られた｡5.
例では%残気量 (
%RV) は多 くの症例 (
6
5.
6%)
HRCT上の %LAAおよび %DLc
oに影響 を与 え
で1
2
9
%以下であったが､一方喫煙症例では1
3
0%
ることが示唆された｡
か ら1
8
9
%を示す症例が最 も多 く見 られた (
6
0.
0