Thoracic Jud W. Gurney, MD #{149}Karen K. Jones, MSN #{149} Richard Kenneth J. Nelson, BS #{149}David Daughton, MS #{149}John

A. Robbins, R. Spurzem,

MD MD

Radiology

Gail L. Gossman, Steven I. Rennard,

BA MD

#{149} #{149}

Regional Distribution of Emphysema: Correlation ofHlgh-Resolutlon CT with Pulmonary Function Tests in Unselected Smokers’ High-resolution computed tomography (CT) was correlated with pulmonary function tests in the evaluation of regional emphysema in 59 smokers. The lung was divided into upper (above the carina tracheae) and lower (below the carina tracheae) zones, and the degree of emphysema was graded with a subjective and an objective measurement. Functional emphysema was defined as a diffusion capacity less than 75% of predicted and forced expiratory volume in 1 second less than 80% of predicted. Three of 15 (20%) subjects with functional emphysema had no subjective evidence of emphysema at high-resolution CT, and 10 of 25 (40%) with emphysema at high-resolution CT had no functional abnormalities consistent with emphysema. Even though the upper lung zones were more severely affected by emphysema, the degree of emphysema in the lower zones had a stronger correlation with pulmonary function abnormalities. The upper lung zones are a relatively silent region where extensive destruction may occur before functional abnormalities become known. Index

terms:

Computed tomography (CT), #{149}Emphysema, pulmonary, #{149} Lung,CT,60.1211

high-resolution 60.751

Radiology

1992;

183:457-463

From the Departments and Internal Medicine, I

of Radiology (J.W.C.) Pulmonary Section

(K.K.J., R.A.R., C.L.G., K.J.N., D.D.,J.R.S.,

SIR.),

University of Nebraska Medical Center, 600S 42nd St. Omaha, NE 68198. From the 1991 RSNA scientific assembly. Received October 1, 1991; revision requested November 22; revision meceived December 26; accepted January 6, 1992. Address reprint requests to J.W.C. t. RSNA, 1992 See also the editorial by Croskin (pp 319-320) in this issue.

C

smoking

ICARE1TE

is the

major

factor associated with the developmcnt of emphysema, the severity of emphysema increasing with the number of cigarettes smoked (1,2). Because 25% of the population in the United States smoke cigarettes, the numben at risk for the development of emphysema is a serious health problem. Emphysema is defined anatomically as the permanent enlargement of air spaces distal to the terminal bronchiole, destruction of their walls, and no obvious fibrosis (3,4). Two main types of emphysema arc recognized, each having a characteristic location within the acinus and a characteristic distribution within the lung (4,5).

The

most

common

type

is centri-

lobular emphysema, which characteristically destroys the proximal portion of the acinus. Centrilobular emphysema is more frequent in the upper lung zones and is the most common type of emphysema among cigarette smokers. The next most common type, panlobular, destroys the entire lobule. Panlobular emphysema is more common in the lower lung zones and is the predominant type of emphysema in patients with a1-antiprotease deficiency (4,5). Emphysema is common, some form being found in at least one-half of adults at autopsy (6). Chest radiographs arc poor in diagnosing cmphyscma (7,8). The loss of lung tissue in the acinus is nearly impossible to detect on chest radiographs (9). The diagnosis of emphysema with this modality is limited to patients with severe emphysema when secondary signs

of hypeninflation

or vascular

pruning become evident (7). The loss of lung tissue impairs pulmonary function, but pulmonary function tests arc limited in diagnosis of emphysema

(10).

It has

Radiologic-pathologic correlation has demonstrated that computed tomognaphy (CT) (more specific, highresolution CT) is superior in the diagnosis of emphysema, even the milder or asymptomatic forms (12-20). This increased diagnostic ability with CT is due to both increased contrast sensitivity and spatial resolution, which can separate the low-density areas of normal

lung

from

lower-density

areas

of emphysematous lung tissue. To further study the role of high-resolution CT in the diagnosis of emphysema, we performed a prospective study of a population of unselected smokers, correlating the severity of emphysema at high-resolution CT

with pulmonary function tests. We also specifically characterized the pulmonary function test abnormalities according to the regional distribution of emphysema. MATERIALS Subject Sixty

AND

METHODS

Recruitment volunteers

were

elicited

through

a

local newspaper advertisement. To be eligible, they had to meet the following mequirements: (b) at least

(a) age greater one and one-half

than 50 years, packs of cigarettes smoked per day, and (c) a smoking history of at least 30 pack-years. All gave

informed consent, approved by the hospital Institutional Review Board, to panticipate in the study. Each filled out questionnames that detailed smoking history and daily activity levels. Pulmonary

Function

Spinometnic volume

Tests

tests-forced

in 1 second

capacity (FVC), and rate (FEF,..75)-were

expimatony

(FEV1),

forced

midexpinatomy performed,

vital

flow and total

been

estimated that 30% of the lung must be destroyed by emphysema before symptoms or pulmonary function abnormalities become evident (11).

Abbreviations:

the lungs expiratory

Dk()

for carbon

=

diffusing

monoxide,

capacity FEF7c

of mid-

flow mate, FEV1 = forced expiratory volume in 1 second, FVC = forced vital capacity, TLC = total lung capacity.

457

lung ity

capacity of the

(DL0)

(TLC),

lungs

were

according (21).

the nitrogen was

was

were by

expressed

using

Graphics,

the

using

and

pulmonary

prediction

tech-

function

test

of predicted of

equations

rived for the whole lung and for the upper and lower lung zones. The upper lung zone was defined as those CT sections located above the carina tracheae, and the lower lung zone was defined as those CT sections located below the canna tracheae. Each

DL0

single-breath

as percentage

the

Minneby

technique,

with

nique (21-24). Values for each

Thoracic

measured

washout

measured

a spinometen

to American (Med

TLC

capac-

monoxide

with

standards

apolis)

and diffusing carbon

measured

calibrated Society

for

Crapo et al for spinometric values and lung volumes (22,23) and the predictive equations of Ayers et al for DLI, (24).

examination

U.W.G.)

to the smoking

history

9800

CT scanner

with

(GE Medical

a GE

Systems,

Milwaukee) and the high-resolution CT technique (1.5-mm section thickness, bone algorithm) at 10-mm intervals from apex to diaphragm. All subjects underwent scanning in the supine position at full inspination.

None

underwent

administration Images were

intravenous

of contrast material. photographed at levels

(-690 HU) and window widths HU) appropriate for lung detail. data were archived on magnetic later

quantitative

as DL0

less

was scored

for emmeth-

subjectively

by

method matous

of Goddard destruction

et al (25). Emphysewas defined as areas

(12,25).

to identify lobular,

the

the

scoring

hypovascular

regions

No attempt

was made

type

of emphysema

panlobular,

lam [26]).

using

was

judged

in the lung

(centri-

panaseptal,

By using

on innegu-

a five-point

scale,

the

percentage of lung involved by emphysema was determined for each level (0, no emphysema; 1, 1 %-25% emphysema; 2, 26%-50%

emphysema;

3, 51%-75%

was

from

attenuation

the

an objective

the CT scanner. cupied

was

by

derived

program

The area of each

voxels

calculated

score

mask of less

for each

DL0

greater

than

75%

than

of low-attenuation

than

-910

(16). The

voxels

oc-

and

lower

lung

was then

zones

area

di-

(defined

be-

low) were used for attenuation mapping. The -910 HU value was a threshold previously

found

logically tissue

separate from normal

For both

by Muller

the

subjective

emphysema scores, of emphysematous 458

#{149} Radiology

et al (16) to patho-

emphysematous lung tissue.

and

SD

Range

Dk0 TLC

78.8

15.3

30-120

114.8

16.4

76-162

FEy1

81.1

FEF75 FVC

92.3

16.5 28.5 13.1

47-117 16-145 67-128

=

standard

deviation.

The

results

56.6

of predicted

of predicted

and

resemble

that

Thoracic

These suggested

Society

(DLC()


120% of predicted) (3). The subjects were also divided into three groups on the basis of the total subjective emphysema score: no emphysema (total subjective CT score, 0), minimal emphyscma

(total

subjective

and emphysema > 10).

CT score,

1-9),

(total subjective CT scone, into these three groups

Separation

has been

shown

late with

the pathologic

by Morrison

physema

(28).

et al to come-

severity

of em-

smoking.

P < .001) score.

tests

CT scones of emphysema with results of pulmonary by

using

cal software package Concepts, Berkeley, ysis

tests

of variance

were

mean

and

used

Results

or minus

statisti-

Student-Neuman-Keuls

to derive

groups. plus

a standard

(Statview II; Abacus Calif). One-way analthe significance

are shown

1 standard

as the

deviation.

pulmo-

and

The

the

the

total

total

subjective

subjective

objective scores

CT

for

both

the total lung and the upper or lower lung zones, however, exceeded the values of the respective objective CT scores

in all cases

(Figure).

There was a weak positive comrelation between both the subjective and objective CT scones and the packyears of cigarette smoking, (r = .323.439, P < .01). A weak but statistically significant

correlation

emphysema ings

between

CT scones

of pulmonary

and

the

the

function

find-

tests

is

shown in Table 3. For the whole lung, the best correlation was between the FEF25-75 and the overall subjective emphysema score (r = - .482, P < .0001). There was no significant difference between the correlation

tive

The various were correlated function

between

CT score

coefficients sema scores

Statistics

of the

nary function tests are summarized in Table 1, and the results of CT scores are summarized in Table 2. There was good correlation (r = .82,

for the subjective and those for

emphysema

1.5-cm segment

emphyobjec-

scores.

of the

important resolution

the

volunteers

findings CT. One cavitary of the

had

identified patient

other

at highhad a

mass in the superior left lower lobe that

proved to be a squamous cell carcinoma of the lung. The second patient had a 4 x 5-cm pleural lipoma of the right chest wall.

HU

vided by the total area of the lung at that level to obtain the percentage of emphysematous lung. The middle images from the upper

75%

80% of predicted.

closely

between

on

lung

level

Mean

Two

em-

physcma; 4, 76%-100% emphysema). A percentage emphysema scone was calculated by adding the emphysema score for each level and dividing by the total possible maximal score for each individual (12). The second method of quantifying cmphysema

than

and FEV1 less than 80% of predicted, and nonfunctional emphysema was defined as

80%

examination

of low-attenuation

having pulmoCT.

nary The combination of decreased DL0 and airway obstruction are the functional abnonmalities characteristic of emphysema (10). We used pulmonary function tests to define two groups of subjects: those with functional and those with nonfunctional emphysema. Functional emphysema was

by the American

Score

physema by means of two different ods. First, the degree of emphysema

Parameter

of pul-

were grouped as those by findings of either function tests on high-resolution

definitions

Each

on findings

Subjects emphysema

FEV1 greaten

analysis.

Emphysema

by

was blinded

Groups

defined

(1,500 Image tape for

of

Predicted

monary function tests. Although only one radiologist interpreted the studies, previous reports have shown good intra- and interobsenven correlations for the subjective estimate of emphysema (12,16,27). Study

was performed

interpreted

who

Tests

Percentage

Note-SD

CT Scanning CT scanning

was

one radiologist

Table 1 Results of Pulmonary Function in 59 Unselected Smokers

lung

objective

the percentage of area destruction was de-

RESULTS One of the 60 volunteers was eliminated from the study because the archived CT magnetic tape used to determine the objective CT score was faulty. This left 59 subjects in the study group. There were 28 men and 31 women whose average age was 58 (range, 50-74) years. They smoked a mean of 39.3 (range, 30-80) cigarettes per day and had accumulated a mean of 60 (range, 32-113) pack-years of

Emphysema Pulmonary When according tests,

Classified Function emphysema to pulmonary

functional

with Tests was

emphysema

classified function was

di-

agnosed in 15 of the 59 subjects. Twenty-five subjects did not have functional evidence of emphysema. Nineteen had either a low DL0 value and normal FEy1 value or normal DL0 value and low FEy1 value; these subjects were excluded from this anal-

May 1992

1.

.

,,

_L.

.

..

.

,..

/

b.

r

C.

(a-e) Five consecutive

p

sections tive

emphysema

score

jective

emphysema

(c)

23.3%.

was

neous ied,

S.

process.

smoking ...

e.

d.

emphysema

in 59 Unselected

Smokers

Area zone zone

Overall

Mean

SD

Range

20.4 6.8

27.2 13.1

12.5

18.7

1 standard

Mean

SD

Range

0-100

7.6

12.5

0-65

0-75

5.3

7.2

0-48

0-84

6.4

8.9

0-41.6

deviation.

(P of the

data

for

non-

functional and functional emphysema are shown in Table 4. Theme was no significant difference between these two groups for age, pack-years, on TLC. A significant difference between was

shown

for

tests

of DL0

and airway obstruction. Subjects with functional evidence of emphysema had a significantly higher percentage of lung involved by emphysema than those with emphysema jects with

no

functional evidence of (P < .002). Of the subfunctional emphysema,

three (20%) of 15 had no subjective evidence of emphysema at high-resolution CT. Of the 25 subjects with nonfunctional emphysema, 10 (40%) had subjective total scores for cmphysema greater 13.3 ± 7.7; mange,

than

6%

6-32). The correlation between and results of pulmonary Volume

183

Number

#{149}

level

lung

is not stud-

occur.

2

(mean,

CT scores function

tests

is summarized

subjects

with

in Table

functional

5. For

emphysema,

correlation between the total subjectivc emphysema scores and DL0 and FVC was good. For the subjects with nonfunctional emphysema, the only statistically

significant

correlation

between the emphysema the FEF25-75 (Table 5). Emphysema High-Resolution In Table jects

are

6, the to the

There

were

was

score

Classified CT

divided

according scones.

and

with

data

for the 59 sub-

into

three

no

and

significant

CT emphysema 23 subjects

significant

difference

with

in age

of FEy1,

those

with

of

those with more se(P < .01). difference in TLC or

FEF.75,

and

three differfor meaDL0.

By


10), 10 had functional emphysema and six had nonfunctional emphysema. Regional

groups

CT score of 0, 14 subjects with minimal emphysema (CT score, 1-9; mean score, 5.9 ± 2.8), and 22 subjects with more severe emphysema (CT score, > 10; mean scone, 29.8 ± 21.1). There was

between

using the Student-Neuman-Keuls test to analyze variance between groups, a significant difference in the FEy1 was found only between those with a CT score of 0 and those with a CT score greater than 10 (P < .01). A significant difference in DL0 was observed only between those with a CT score of 1-9 and a CT score greater than 10

Lung

groups

ob-

inhomoge-

CT evidence

emphysema

sures Objective

Subjective

Comparison

the

is an

FVC was evident among the groups. There was a significant ence among the three groups

CT Score

ysis.

but

three groups. There was increase in pack-year

history

No

=

may

no high-resolution vere

Note-SD

If the entire errors

50%,

for the middle

a

iilI

Upper Lower

was

score

Emphysema

sampling

among the a significant

Table 2 CT Scores

high-resolution CT the upper lung. The subjec-

through

Emphysema

Thirty-four subjects (58%) had subjective emphysema in the upper lung zone (Table 2). Twenty-three (39%) had subjective emphysema in the lower lung zone. For the subjective emphysema score, the difference between the scores for upper and lower lung zones was significant Radiology

#{149} 459

Table 3 Correlation

of CT Scores

with

Findings

of

Function

Pulmonary

in 59 Unselected

Tests

Correlation Pulmonary Function Test Parameter

(r) by CT Score

Coefficient

Subjective

Overall

Dk0 FEy1 FEF

-.482

Lower Zone

(.003)

-.280

NS

Table 4 Clinical Data and Pulmonary

not significant

=

Function

(.0002)

-.390 -.465

NS

(.002) (.0002)

Emphysema*

-.347 -.436

(.007) (.0006)

-.460(0002) .403(002) -.359 (.005) -.394 (.002)

NS

NS

at .05 leveL

Test Results

Age (y)t (n

(n

Note-Values

=

25)

56.3 58.6

15)

=

are expressed

Nineteen

(.002) NS

NS

for Nonfunctional

versus

Functional

Emphysema

Percentage

*

-.394

of Predicted

Value

of

Type

Nonfunctional Functional

Lower Zone

.339 (.009)

(.03) (.003)

-.376

NS

are in parentheses.

-.461

.421 (.0009)

-.449 (.0004) -.507(.0001)

Upper Zone

Overall

-.402(.002)

.312 (.02)

NS

values

Zone

-.383

(.0001)

FVC

Objective

Upper

-.404 (.002) .335 (.009) -.420 (.0009)

mc

Note-P

Smokers

of the

59 subjects

±

5.2

±

4.8

as the mean had

PackYearst

either

54.1 66.9 ±

I standard

a low

Dk0

± ±

Dk0

20.3 24.0

TLCt

87.0

±

8.8

114.8

±

64.9

±

11.0

117.6

±

FEV1t 15.6 21.3

93.4 62.2

± ±

FEF75t

FVC

9.8 7.4

98.4 82.7

±

10.3

76.4

±

±

11.4

29.7

±

25.0 11.5

deviation.

value

and

normal

FEy1

value

or normal

DL,

value

and

low

FEy1

value.

These

subjects

were

excluded

from this analysis. f Difference

between between

Difference

Table

groups groups

was not significant at the .05 level (analysis of variance). was significant (P < .0001; analysis of variance).

5

Correlation

of CT Scores

with

Findings

of Pulmonary

Function

Tests

for Nonfunctional Correlation

Coefficient

Test Parameter Emphysema Type and CT Score Type and Area Nonfunctional (n

CT Score*

and Functional

Emphysema

by Pulmonary Function (Percentage of Predicted) (r)

TLC

FVC

FEF75

FEV1

emphysema =

25)

Subjective

Overall Upper lung zone Lower lung zone Objective Overall

Upper Lower

lung zone lung zone

Functional (n Subjective

5.5 10.4 2.5

±

8 13.8 4.8

NS NS NS

NS NS NS

NS NS NS

-.488 -.480

(.01)

NS

(.02)

NS

-.478

(.02)

NS

2.8

±

2.8

±

NS NS NS

NS NS NS

NS NS NS

-.472

(.02)

±

2.9 4.1 2.3

NS NS NS

2.6

25.3

±

27.4

-.627

(.01)

NS

NS

NS

±

-.546

(.04)

NS

NS

-.752

(.04) (.001)

NS

±

36.4 20.5

-.641 -.534

(.01)

37.8 13.8

.537 (.04)

-.676

(.006)

NS

NS

12.3

±

13.8

-.646

(.009)

(.02)

NS

NS

±

19.5 12.1

NS -.833 (.0001)

.549 (.03) NS .671 (.006)

-.589

15.4

(.02)

NS NS

NS NS

± ±

NS -.558

(.004)

emphysema =

15)

Overall

Upper

lung zone

Lower lung zone Objective

Overall

Note-P *

Upper

lung

zone

Lower

lung

zone

values

are in parentheses.

Values are expressed

as the mean

9.4 NS ±

460

#{149} Radiology

-.589

not significant at the .05 leveL standard deviation. =

1

< .0001). In the upper lung zones, there was a significant difference between the objective and subjective emphysema scores (P < .001). The subjective and objective lower lung zone scores were not significantly different. The subjective scores in the lower lung zone correlated better with DL0

(P

±

NS

and lung volumes than did those in the upper lung zone (Table 3). Conversely, the subjective scores in the upper lung zone showed better comelation with tests of airway obstruction. Similar regional relationships for objective CT scores and pulmonary function tests were present. Statistically, there was no difference for the

correlations

between

lower lung zones function tests.

the

and

upper

the

and

pulmonary

Emphysema classified by means of pulmonaryfunction tests-Of the 15 subjects with functional emphysema

(Table

5), 11 (73%)

physema

in the

with

a mean

had

upper

score

subjective lung

cm-

zone,

of 37.8 (range, May 1992

0-100), and emphysema with a mean

0-75).

The

scores upper (P
10), all 22
10), 29.8 ± 21.1 did from their ob11.6, but was

significantly

from

different

our

objecIn

tive score of 12.3 ± 12.2 (P < .02). both of these groups, our objective

pathologic

correlation

on

our CT scanner, it is difficult to determine the optimal threshold for emphysematous lung at CT. We agree with Kuwano et al (20) that subjective estimates, which are quick and easy

to perform,

evaluate

should

the extent

As shown

be used

to

of emphysema.

in previous

studies,

the

dis-

advantage of intra- and interobserver variability for subjective scoring appears to be negligible (12,16,27). A second affects

sema

methodologic

the extent is the

use

factor

of observed of thin

(1-5

that

emphymm)

on conventional collimation (8-13 mm) (12-14,17,28-33). Since emphysema demonstrates regional inhomogeneity, even within the same lobe, errors will occur if the lung is not adequately sampled. This is important if only a few levels are chosen to evaluate the entire lung or if the collimation is narrowed, limiting the volume of sampled lung. A second reason for the disparity between our objective and subjective upper lung zone scores may have been due to sampling error. The regional distribu(20,27)

Radiology

461

#{149}

tion of emphysema was inhomogcneous, which was apparent in our subjects (Figure). By sampling only one level in the upper lung zone, we underestimated the severity of emphysema with the objective method (Table 2). It is presumed that, if we had calculated the objective score for each level, the discrepancy would have been smaller between the subjective and objective score in the upper lung zone. Our decision, however, to use one level from the upper and one level for the lower lung zone to calculate the objective CT score was a practical one. Attenuation mapping is a tedious and time-consuming process

(19,20).

For

complete

CT of the

chest, mapping of all levels took us approximately 4 hours per patient. Our problem with sampling error points out the difficulty in accurately estimating the extent of emphysema, particularly in those studies in which only a few levels in the lung are sampled (13,14,20,29,32,33). Various subjective scoring systems have been used to estimate the degree of emphysema (12,25,31). The most widely used system (ie, the one we used) is based on the percentage of lung occupied by emphysematous spaces (12,17,25,27,31). Other techniques that have been used include a comparison

with

anatomic

standards,

originally designed for use in pathologic grading of emphysema (19,20). Miller et al used another technique, which involved placing a grid over the CT image and analyzing the cxtent and severity of emphysema in each square centimeter (18). Whether these different visual subjective techniques are equivalent is unknown. Since we have no pathologic confirmation of the extent of emphysema, the accuracy of our subjective scoring method in estimating the extent of emphysema should be questioned. We can compare our results with those of Morrison et al, who obtained pathologic correlation (27). In our study and theirs, the same subjective scoring method and the same highresolution CT technique were used to sample the entire lung. The study populations were similar, with no significant difference in mean Dk0, TLC, FEy1, and FEF.s.7s. An overall emphysema score that was slightly higher in our study (mean, 12.5 ± 18.7; range, 0-84) than in the study of Morrison et al (mean, 8.5 ± 12.1; range, 0-40) is not statistically different. The agreement between our subjective score and their subjective score suggests we were accurate in estimating the extent of emphysema. 462

#{149} Radiology

Many patients with emphysema have no symptoms and normal function, and many patients with functional abnormalities characteristic of emphysema have no evidence of cmphyscma at high-resolution CT (5,10,17). These opposing statements were evident in our study; 20% (three of 15) of our subjects with functional emphysema had no subjective cvidence of emphysema at high-resolution CT and 40% (10 of 25) of our subjects with emphysema at highresolution CT had no functional abnormalities characteristic of emphysema. Without pathologic examination, we cannot exclude the possibility that in the subjects with functional abnormalities,

the

normal

results

of

high-resolution CT were due to observer or technical failure to detect emphysema. Miller ct al (18) and Kinsella et al (30) have shown, by using CT-pathologic correlation, that mild degrees of emphysema may be underestimated or missed with CT. While this fact may account for normal findings of high-resolution CT in some subjects with abnormal function, we think that, in general, the minimal amounts of emphysema missed at high-resolution CT would be unlikely to cause abnormal function. Many subjects with normal function will have extensive emphysema (eg, up to 40% of subjects in our series and 69% in the series of Sanders et al [17]), suggesting that other factors such as airway size and morphology are important in causing decreased function. The distribution of emphysema within the lung may also affect pulmonary function, a factor not taken into account previously. Many prior studies

were

performed

in patients

undergoing lung resection and comelated pulmonary function with the extent of emphysema in one lobe (1214,20,27,28,30). One lobe, however, may not accurately reflect the overall extent of emphysema. Other studies have ignored the lower lung zones, examining only the upper lung zones at CT (13,14,29,33). Thus, these studies provide no insight into how the regional distribution of emphysema contributes to functional abnormali-

ties. The preponderance of emphysema in the upper lung zones in our study, 20% versus 7% in the lower lung zones, suggests that the primary type of emphysema in our subjects is centnilobular

emphysema.

ular emphysema involve the upper known,

bly reflects

but

the

the

Why

centrilob-

has a propensity to lung zone is unphenomenon

normal

proba-

gravitational

gradients in the physiologic teristics of the lung (35,36). physiologic characteristics sessed such

with pulmonary tests too should

characSince arc as-

function depend on

tests, gray-

itational differences in the lung. Since we separately examined the extent of emphysema between the upper and lower lung zones, we tried to examine how the regional distribution of emphysema correlates with overall function. In the subjects with diminished pulmonary function, the degree of emphysema in the lower lung zones had stronger correlation with pulmonary function tests than did the degree of emphysema in the upper lung zones. This trend seems unusual, considering that the extent of emphysema of the upper lung zones far cxceeded the degree of emphysema of the lower lung zones. The importance of the lower lung zones in maintaining function is also evident in the group of patients with nonfunctional emphysema. Of the 10 subjects with nonfunctional emphysema, all 10 had emphysema in the upper lung zones (mean, 10.4; range, 0-50) as compared with five subjects with emphysema in the lower lung zones (mean, 2.5; range, 0-18.7) (Table 5). In the group with normal function, the average degree of destruction of the lower lung zones was only 2.5% as compared with subjects with functional emphysema, in whom the extent of lower zone destruction averaged 14% (Table 5). The regional findings of the present study

are

consistent

with

observa-

tions made by Nairn et al (37) and Martclli et al (38). In radiographically selected patients with either upperzone emphysema or lower-zone emphysema, they found that pulmonary function tests and symptoms were worse in patients whose radiologic evidence of disease was in the lower lung zones (37,38). They emphasized that if the lower lung zones were nonmal, then overall function would be preserved. Both groups found a significant difference between patients with upper-lung-zone emphysema and patients with lower-lung-zone emphysema in tests of airways obstnuction (FEy1) and arterial oxygenation, with the most pronounced impairment occurring in patients with lower-zone disease (37,38). These studies suggest that the upper lung zones arc a relatively silent region where extensive destruction of the lung may occur before functional abnormalities on symptoms become manifest. The concept of a silent mcgion of the lung has been used to May

1992

the small airways (23-mm diameter) (6). Hogg and coworkers demonstrated that these small respiratory bronchioles, because of their large total cross-sectional area, account for only a small proportion of total airways resistance (39). Thus, considerable loss and destruction of these airways are necessary before respiratory function becomes impaired. We suggest that a similar silent zone is present on a large scale in the upper lung zone. Because the contribution of the upper lung zones to total lung function is small compared with the contribution of lower lung zones, considerable loss or destruction may occur before respiratory function becomes impaired. This makes centrilobular, or smoker, emphysema a sinister process. The proclivity of this emphysema to destroy much of the upper lung zone removes valuable pulmonary reserve before symptoms or functional abnormalitics of emphysema become known. The diagnosis of this disease will thus depend on a sensitive screening test before the development characterize

of functional

abnormalities.

This

5.

6.

7.

8.

ture of the lung in smokers. 9.

11.

12.

13.

14.

17.

history

of pulmonary

by computerised

tomography.

of

16.

this disease, especially the onset of emphysema observable at high-resolution CT and the rate of emphysematous destruction. The longitudinal follow-up of subjects with emphysema will be important in further defining the natural history of this dis-

18.

case.

19.

U

K, Itoh

H, Todo

of the lung: demonstration

tion

tests

Radiol Miller NJ,

References Auerbach Benante

0, C.

Hammond Relationship

age to emphysema: 2.

3.

4.

EC, Gamfinkel of smoking

whole-lung

L, and

section

study. N EnglJ Med 1972; 286:853-857. Niewoehner DE. Cigarette smoking, lung inflammation, and the development of emphysema. J Lab Clin Med 1988; 111:15-27. Snider GL, Kleinerman J, Thurlbeck WM, Bengali ZH. The definition of emphysema: report of a National Heart, Lung, and Blood Institute, Division of Lung Diseases Workshop. Am Rev Respir Dis 1985; 132: 182-185.

Thurlbeck Bates ease.

WM, Henderson

DV. Chronic obstructive Medicine 1970; 49:82-145.

JA, Fraser lung

20.

21.

183

Number

#{149}

2

chest

RR, Muller

NL,

CA.

Vedal

28.

29.

30.

31.

23.

34.

Standardization

of spirometry:

1298. Crapo erence

RO, Morris spirometnic

dations. 664. Crapo

1987

that meet

38.

et al.

in em141 :53-

KF, Flenley gas ex-

of emphysema

97:315-321. Kondoh Y, Taniguchi

H, Yokoyama

change

as

5, et al.

in chronic

asthma

in relation to cigarette smoking: assessment by computed tomography. Chest 1990; 97: 845-849. Sakai F, Gamsu C, Im JG, Ray CS. Pulmonary function abnormalities in patients with CT-determined emphysema. J Com-

1987; 11:%3-968.

Knudson RJ, Standen JR, Kaltenborn WT, et al. Expiratory computed tomography

of suspected pulmonary Chest 1991; 99:1357-1366.

Adams H, Bernard MS. McConnochie K. An appraisal of CT pulmonary density mapping in normal subjects. Clin Radiol 1991; 43:238-242. Gurney JW, Schroeder BA. Upper lobe lung disease: physiologic correlates (meGurney

Radiology

1988; 167:359-366.

JW.

Cross-sectional physiology the lung. Radiology 1991; 178:1-10. Naimn JR. Prime FJ, Simon G. Association between radiological findings and total

Martelli NA, Radiological

Hutchison distribution

in emphysema.

or lower

zones

of lungs.

of

Tho-

DC, Barter CE. of pulmonary

physema: clinical and physiological tures of patients with emphysema Thorax

em-

feaof upper 1974;

29:

81-89.

39.

up-

RM. Reftechniques

Am

40.

Hogg JC, Macklem VF, Thurlbeck Site and nature of airway obstruction chronic obstructive lung disease. Med 1968; 278:1355-1360. Sanders C. Radiologic diagnosis physema. Curr Opin Radiol 1989;

WM. in N Engl of em1:16-20.

ATS recommen-

Am Rev

Respir

Dis

RO, Morris

MI,

Nixon

in healthy

and the severity

and regional function max 1969; 24:218-227.

Dis 1987; 136:1285-

MI, Gardner values using

emphysema. 139:1179-1 187. RT, MUller NL,

assessed by quantitative CT scan in chronic bronchitis and emphysema. Am Rev Respir Dis 1989; 139:1509-1515. Kinsella M, Muller NL, Abboud RT, Morn-

view).

tomogra-

phy of inflation-fixed lungs: pathologicradiologic correlation of centrilobular emphysema. Am Rev Respir Dis 1987; 136: 935-940. Kuwano K, Matsuba K, Ikeda T, et al. The diagnosis of mild emphysema: correlation of computed tomography and pathology scores. Am Rev Respir Dis 1990; 141:169178.

and equipment

RG, dis-

EA, et

F, et al.

carbon monpressure-vol-

capillary blood volume Am Rev Respir Dis 1990;

for assessment emphysema.

37.

Zerhouni

in detecting

put Assist Tomogr 33.

of computed

MA,

date. Am Rev Respir 22.

32.

35.

5, Morrison

computed

Ramadan

son NJ, DyBuncio A. Quantitation of emphysema by computed tomography using a “density mask”: program and correlation with pulmonary function tests. Chest 1990;

983. Hruban

resolution

RT,

61. Biemnacki W, Gould GA, Whyte DC. Pulmonary hemodynamics,

change,

36.

RH, Meziane

Abboud

Rev Respir Dis 1989; Morrison NJ, Abboud

Pulmonary physema.

tomography in the assessment of emphysema. Am Rev Respir Dis 1989; 139:980-

High

NJ,

ume curves

Invest

Limitations

of diffusion

Morrison

func-

radiography.

interpretation

27.

Centni-

pulmonary

and

26.

1988; 23:262-266.

Staples

volumes

Volume

and

with

Ayers LN, Ginsberg ML, Fein J, Wasserman K. Diffusing capacity, specific diffusing

Emphysematous

by high-resolution CT and pathologic correlation. Radiology 1986; 161:641-645. Muller NL, Staples CA, Miller RR, Abboud RT. “Density mask”: an objective method to quantitate emphysema using computed tomography. Chest 1988; 94:782-787. Sanders C, Nath PH, Bailey WC. Detection of emphysema with computed tomog-

18:419-

nary emphysema. Clin Radiol 1982; 33:379387. Bergin CJ, Muller NL, Miller RR. CT in the qualitative assessment of emphysema. Thorac Imaging 1986; 1:94-103.

1984;

lesions

al. 1.

Lancet

lobular

correlation

1981;

Comparison of single breath oxide diffusing capacity and

Mumata

raphy:

Respir

25.

emphysema

G, et al.

Physiopathol

defects. West J Med 1975; 123:255-264. Goddard PR, Nicholson EM, Laszlo G, Watt I. Computed tomography in pulmo-

Med 1983; 4:433-442.

Diagnosis

Eur

capacity,

2:320-322.

will

is known

natural

24.

of emphy-

GeIb AF, Gold WM, Bruch HR. NadeiJA. Physiologic diagnosis of subclinical emphysema. Am Rev Respir Dis 1973; 107:5062. Pratt PC, Kilbumn KH. A modern concept of the emphysemas based on correlations of structure and function. Hum Pathol 1970; 1:443-463. Bergin C, Muller N, Nichols DM, et al. The diagnosis of emphysema: a computed tomographic-pathologic correlation. Am Rev Respir Dis 1986; 133:541-546. Gould GA, MacNee W, McLean A, et al. CT measurements of lung density in life can quantitate distal air space enlargement: an essential defining feature of human emphysema. Am Rev Respir Dis 1988; 137: 380-392. Hayhurst MD, MacNee W, Flenley DC, et

al.

15.

the

Clin Chest

Bull 425.

Am Rev Respir

Dis 1979; 119:695-705. Pugatch RD. The radiology

sema. 10.

be especially important if new methods to treat emphysema are introduced. High-resolution CT may be an ideal screening test to detect emphysema before functional impairment occurs (40). It is unfortunate that little about

Thurlbeck WM, Angus GE. The relationship between emphysema and chronic bronchitis as assessed morphologically. Am Rev Respir Dis 1963; 187:815-819. Fraser RG. The radiologist and obstructive airway disease: Caldwell Lecture, 1973. AJR 1974; 120:737-775. Thurlbeck WM, Simon G. Radiographic appearance of the chest in emphysema. AJR 1978; 130:429-440. Bemend N, Woolcock AJ, Marlin GE. Correlation between the function and struc-

1981;

nonsmoking

ER.

123:659Lung

adults.

Radiology

463

#{149}