Value of the ventilation / perfusion scan in acute pulmonary ...

t' ,
~. ..Original Contributions (\"f§;) 1fJ- \
JI
,
Value of the Ventilation/Perfusion Scan
in Acute Pulmonary Embolism
Results of the Prospective Investigation of
Pulmonary Embolism Diagnosis (PIOPED)
The PIOPED Investigators
To determine the sensitivities and specificities of ventilation/perfusion lung nosis (PIOPED) investigators have asscans
for acute pulmonary embolism, a random sample of 933 of 1493 patients sessed the diagnostic usefulness ofV/Q
was studied prospectively. Nine hundred thirty-one underwent scintigraphy and lung scans in acute pulmonary embo-
755 underwent pulmonary angiography; 251 (33%) of 755 demonstrated pulmo- lism. ~e project protocol and consent
nary embolism. Almost all patients with pulmonary embolism had abnormal forms. were approved by th.e .inst.itutionscans
of high, intermediat8\ or low probability, but so did most without pulmonary al reV1ew b.o~rds.of all partlclpatl."g ce~-
embolism (sensitivity, 98%; specificity, 10%). Of 116 patients with high-probabili- te~. (PartlcIFa;l~g c~nt~rs an~ ln~es~lty
scans an~ definitive angiograms, 102 (88%) had pulmonary embolism, but ~i~~.)are IS eat e en 0 t e
only a minority with pulmonary embolism had high-probability scans (sensitivity,
41 %; specificity, 97%). Of 322 with intermediate-probability scans and definitive METHODS
angiograms, 105 (33%) had pulmonary embolism. Follow-up and angiography Patient Enrollment
together suggest pulmo~~ry embolism occurred amon.g 12% of ~at~ents with From January 1985 through Septemlo~~!-probability
scans. Clinical assessment combined with the ventllatlon/perfu- ber 1986 in each of six clinical centers,
sion scan established the diagnosis or exclusion of pulmonary embolism only for all patients for whom a request for a V/Q
a minority of patients-those with clear and concordant clinical and ventilation! scan or a pulmonary angiogram was
perfusion scan findings. made were considered for study entry.
(lAMA. 1990;263:2753-2759) The eligible study population consisted
, of patients, 18 years or older, inpatients
PERFUSION lung scans have been re- would be abnormal in areas of pneumaand
outpatients, in whom symptoms
that suggested pulmonary embolism
were present within 24 hours of study
ported to be sensitive in detecting pul- nia or local hypoventilation, but that in entry and without contraindications to
monary emboli, but many other condi- pulmonary embolism ventilation would angiography such as pregnancy, serum
F edit t I t 2794
or or 8 com men see p.
be normal.z A number of investigator!
have attempted to make ventilation/
perfusIon .. (V/Q) scans more useful for
creatinine level greater than 260
lJ.JnoUL, or hypersensitivity to contrast
matena. I 0nce approac hed
for the
diagnosing pulmonary embolism by study, patients with recurrences were
tions such as pneumonia or local classifying them not just as normal or not approached for recruitment a secbronchospasm
cause perfusion defects.' abnormal, but if abnormal, as indicating ond time.
Ventilation scans were added to perfusion
scans with the idea that ventilation
high probability, intermediate probability
(indeterminate), or low probability
I
Recru tment
of pulmonary embolism.s Under the aug;. A total of 5587 requests for V/Q scans
Reprint requests to Division of Lung Diseases. Na. pices of the National Heart Lung and
tional Room6A165333WestbardAve.BetheSda.MD20892
Heart. Lung. and BkJOd InstiMe. Westwood Bldg. Blood InstItute, . the Prospectlve '.' Inveswere
recorded in the six PIOPED clini-
c al centers from January 1985t hrough (Carol E Vrelm. PhD) tigation of Pulmonary Embolism Diag- Sel1tember 1986 (Figure). Although
JAMA. May 23/30. 1990-VoI263, No. 20 Ventilation/Perfusion Scan-PIOPED Investigators 2753
,
-

scans were obtained with 1.5 x 10" Bq of
, technetium Tc 99m macroaggregated
albumin that contained 100 000 to
Requests for Lung Scans 700 000 particles using a 20% symmetric
5587 window set over the 140-keV energy
peak. Particles were injected into an
I I antecubital vein over 5 to 10 respiratory
cycles, with the patient supine or at
Scan Requests Cancelled. most semierect. The perfusion images
Scans Requested for Research Purposes. El19lbl~abents consisted of anterior, posterior, both
I Diagnoses Other Than Acute 6 posterior oblique, and both anterior
Pulmonary Embolism, oblique views, with 750 000 counts per
Patients In Whom Angiography ..
Contraindicated. and Other Reasons Consent Consent l~age for each. Fo~ the lateral vIew
, ( for Ineligibility According to Given Refused W1t~ the best perfusIon, 500 000 counts
Study Design 1493 1523 per Image were collected: the other lat-
~ 2571 eral view was obtained for the same
length of time. Scintillation cameras
f Random Sample with a wide field of view (38.1 cm in
; -diameter) were used with parallel-hole,
; I low-energy, all-purpose collimators.
t Not Selected for Selected for Perfus~on scans were sat~sfa~tory or
f Sensitivity and Sensitivity and better In 96% of cas.es, ventilation scans
! Specificity Analyses SpeCIficity Analyses adequate or better In 95%.
( 560 933
(
I Angiography
i I The femoral-vein Seldinger tech-
I Inlerpretable Scan Scan nique with a multiple side-holed, 6F to
Not Compleled Completed 8F pi
gtai l catheter was used Small
2 931 ..
I: amounts of contrast matenal (5 to 8 mI,.)
'; were injected by hand, to check the pa-
I tency of the inferior vena cava by fluo-
! roscopy. The catheter was directed into
Angiogram I Angiogram I the main pulmonary artery of the lung
Completed Not Completed with the greatest V/Q scan abnormali-
755 176 ty. I mtla .. 1 fil mlng .. was In t h e antero-
I posterior projection. Seventy-six per-
I cent iodinated contrast material was
Pulmonary Embolism Pulmonary Embolism Pulmonary ~rnbolism injec~d at a rate of 20 to 35 mL/s for a
Present Absent Uncer1ain total of 40 to 50 mL (2-second injection).
251 480 24 Film ra~s were three per second for 3
seconds, followed by one per second for
4 to 6 seconds. Depending on the size of
i .the lungs, filming was not magnified or
:' Flow char1 illustrating the numbers of r1!Quests for lung scans. recruitment of patients, completion of lung given a low magnification of 1.4. A 12:1
scans. and results of angiography in the Prospectiw InvestigatIOn of Pulmonary Embolism Diagnosis. grid was used and roentgenographic
factors were in the range of 70 to 80
kilovolts (peak) and 0.025 to 0.040 sec-
". onds at 1000 mA (large focal spot of 1.2
...to 1.5 mm in diameter). If emboli were
some patients could not be thoroughly Lung Scan :: not identified, injections were repeated
evaluatedpriortocompletionoftheV/Q and magnification (1.8 to 2.0 times)
scan, clinical investigators made every The protocol directed ventilation and oblique views were obtained of the ar-
effort to record their individual clinical perfusion studies with the subject in the eas suspicious for pulmonary embolism.
impressions as to the likelihood of pul- upright position, but other positions Films were obtained with an air-gap
monary embolism prior to learning the were acceptable. VentilatiOn studies technique (ie, no grid used). Roent-
i results of V/Q scans and angiography. were performed with 5.6 x 10' to genographic factors were in the range of
: Impressions were based on an agreed on 11.1 x 10' Bq of xenon 133 using a 20% 78 to 88 kV(p) and 0.040 to 0.080 seconds
~ set of information-history, results of symmetric window set over the 8O-keV at 160 mA (small focal spot of 0.3 to 0.6
1 physical examination, arterial blood gas energy peak. They started with a mm in diameter). If no emboli were
: analyses, chest roentgenograms, and 100 OOO-count, pos~rior-view, first- found in the first lung, or if bila~ral
electrocardiograms-but without stan- breath image and then pos~rior equi- angiography in the clinical cen~r was
dardized diagnostic algorithms. The librium (wash-in) images for two con- routine, identical techniques were used
medical records of a random sample of secutive 120-second periods. Washout for the second lung. Angiography was
patients who refused or were ineligible consisted of three serial 45-second pos- completed within 24 hours, and usually
for study entry (refuser/ineligible pa- terior views, 45-second left and right within 12 hours of V/Q scans. Pulmo-
'. -tients) were evaluated retrospectively pos~rior oblique views, and a final 45- .nary angiograms were adequate or bet-
,.~ for comparison with study patients. second pos~rior view. Then, perfusion ~r in ~5% of cases.
;~
jf 2754 JAMA. May 23/30. 1990-VoI263, No 20 Ventilation/Perfusion Scan-PIOPED Investigators~

.
'Pq of Central Scan and Table 1-PIOPED Central Scan Interpretation Categories and Criteria'
'gated
)() ~o
Angiogram Interpretations
Two nuclear medicine readers, not
c,,-~ ---~-~,,~ -
High probability
;,,2 Large (> 750/0 of a segment) segmental perf1JSIOn defects WIthout corresponding ~ntilation or roenlgenonetric
from the center that performed the graphIC abnom1alitles or substantially larger than eIther matching ventIlation or chest roentgenogram
nergy
Ito an ~
-atory
or at
llages
..abnom181ltles
scan, mdepe?dently Interpreted the
lung scans WIth chest roentgenograms
accordl 'ng to preestabl ' h d t d .t
IS e S u y cn e-
ria (Table 1). Angiograms were likewise
d I . d ..Bordertlne
ran om y asslgne. .w pairs of angIo-
;,,2 Moderate segmental (;,,25% and ~75% of a segment) perf1JsK)n defects without matching ~ntilation or chest
roentgenogram abnOm1alitles and 1 large mIsmatched segmental defect
;,,4 Moderate segmental perf1JsK)n defects without ventilation or chest roentgenogram abnom1alities
IntermedIate probabIlity (Indetem1inate)
Not lalling into nom1al. ve~low-. low-, or high-probability categories
high or borderlIne low
DIfficult to categonze as low or high
both
terior
ts
per
VIeW
~ounts
er latsame
graphers from clInical centers other
than the ori .nnatin g hos p ital The an-
.e' .'.
gIogram readers Interpreted the angIograms
with lung scans as having acute
uI b I ..Large
p m.onary e~ 0 I.sm present-which
required the IdentIfication of an embo-
I b t t . I th tl ' f
US 0 S ruc mg a vesse or e ou me 0
Low probability
Nonsegmental perf1Jsion defects (~, ~ry small effusion causing blunting of the costophrenic angle. cardiomegaly.
enlarged aorta. hIla. and medIastInum, and elevated dIaphragm)
Single moderate mIsmatched segmental perfuSK)n defect with nom1al chest roentgenogram
Any perf1JSlon defect with a substantially larger chest roentgenogram abnOm1ality
or moderate segmental perf1JSIOn defects InvolvIng no more than 4 segments in 1 lung and no more than
3 segments In 1 lung regIOn with matching ~ntilation defects either equal to or larger In size and chest
roentgenogram eIther nom1al or with abnom1alltles substantially smaller than perf1JSIOn defects
>3 Small segmental perf1JsK)n defects «25% of a segment) with a nom1al chest roentgen.v.ram
Very low probability .._"
me~
cm m
an embolus (filling deti ct) within a vesse
I -a b sent, or uncert . m. If two read-
~3 Small segmental perf1Jsion defects with a nom1al chest roentgenogram
Nom1al No perf1Jsion defects present
l
-hole, ers disagreed, the interpretations'were Perf1J$ion outlines exactly the shape of the lungs as seen on the chest roentgenogram (hilar and aortic impressions
ators. adjudicated by readers who were se- may be si3en. chest roentgenogram and/or ventilation study may be abnom1al)
ry or le~t~d randomly fro~ .the. remaining 'PIOPED indicates Prospectiw Investigation of Pulmonary Embolism Dia nosis
scans clInical centers. If adJudIcatIng readers g
did not agree with either of the first two
readers, scans or angiograms went to
panels of nuclear medicine or angiogra- Table 2 -Recruitment of Patients and Completion of Angiography'
phy readers. The final adjudicated V IQ
tech- scan readings consisted of four catego- 0/. of
6F to . h. h b b ' l ' . d .Eligible No. of PfOPEO P.tlent. With
nes- Ig pro a Ilty, mterme late Patient. Lung Scan. Who Were Seiec1ed for Angiogram.
Small probability (indeterminate), low proba- Clinical Center Recruited Anglographlc Pu..ult Obtained. No. ("!o}
8mL) bility, and low/very low probability ~ukeU~n~~ity 46 --137 1,15-'84)'-'
le pa- through normal (near normal/normal). Henry ~ord Hos~it81 62 228 177 (78)
.~uo- The near-normal/normal category in- ~assachus~~ ~eneral Hospjtal 33 140 120 (86)
d Into cludes readings of very low probability University of Michigan 52 102 65 (64)
~ lun~ by one reader and low probability by the University 01 Pennsylvania 70 168 134 (80)
~all- other, very low probability by both, ~aleuniversity 43 156 144 (92)
1tero- very low probability by one and normal Total 50 931 755 (81)
per- by the other, and normal by both. Re- ,
1 was fu I. I.. bl t ' ts' PIOPED Indicates Prospective Investigation of Pulmonary Embolism Diagnosis
ser me IgI e pa Ien scans were .
~or a read in each clinical center by the clini-
'tlon). cal center's PIOPED nuclear medicine
for 3 reader(s) and not reread.
1d for F II d lants and in whom no outcome event 900 to 1000 patients in the random sam-
:ze of 0 ow-up an ..suggested pulmonary embolism. Pul- pie for PIOPED angiography was
d or Outcome ClassIfication monary embolism status could be deter- planned to obtain estimates of sensitiv-
12:1 Patients were contacted by telephone mined as positive or negative for 902 ityand specificity with 95% CIs no wid-
1hic at I, 3, 6, and 12 months after study patients. A clinical assessment of the er than == 8%. To determine the sensi-
; 80 entry. Deaths, new studies for pulmo- likelihood of pulmonary embolism was tivity and specificity of V IQ lung scans
,ec- nary embolism, and major bleeding available for 887 (98%) of these patients. without the biases associated with hap-
1.2 complications were reviewed by an out- hazard patierlt selection (ie, conveere
come classification committee using all Statistical Methods nience sampling).8.t a 933-patient sam-
lted available information. Only 23 (2.5%) of Probability values for the comparison pie of the 1493 patients who consented
mes) the 931 patients had incomplete (16) or of percentages and proportions and 95% to PIOPED participation was selected
\e ar- no (7) follow-up. Angiograms, follow-up confidence intervals (CIs) were calcu- according to random sampling sched-
\lism, data, and outcome classifications were lated using standard: tests.' A ~ test ules created separately by the data and
r-gap used to determine pulmonary embolism for homogeneity of proportions was coordinating center for each clinical cenoent-
status as positive for patients with an- used to compare distributions.' Sensi- ter, The PIOPED protocol required
1ge of giograms that showed pulmonary em- tivity is defined as the proportion of these 933 patients to undergo angiogra-
:onds boli and for patients for whom outcome cases of pulmonary embolism correctly phy if their scans were abnormal, Of the
:00.6 review established the presence of pul- diagnosed and specificity as the pro- 933 patients selected for angiography, 1
were monary emboli at the time of PIOPED portion of diagnoses that pulmonary patient died before the V/Q scan could
lteral recruitment. Pulmonary embolism sta- embolism is absent for patients without be completed and 1 other patient's V/Q
.was tus was determined as negative for pa- pulmonary embolism. Sensitivity, spe- scan was determined to be uninterpreused
tients with angiograms that did not cificity, and percent agreement have table. These 2 patients are not further
.was show pulmonary emboli and no contrary been calculated according to standard reported herein.
ually outcome review and for patients who methods for proportion8,' Analyses
.lImo- lacked a definitive angiogram reading were performed with the Statistical RESULTS
.bet- who were discharged from the hospital Package for the Social Sciences statisti- Of the 3016 patients eligible for
without a prescription for anticoagu- cal software package.' Recruitment of PIOPED, 1493 (50%) gave consent to
gators JAMA. May 23/30. 1990-VoI263, No 20 Ventilation/Perfusion Scan-PIOPED Investigators 2755
~~- "';::: -I
.

., Table 3-Patienl Characteristics' Table 4-Comparison of Scan Category With Angiogram Findings
Refuser! Pulmonary Pulmonary Pulmonary
Ta
-
PtOPEO
IN = 931l
ineligible
IN = 326) Scan Category
Embolism
Present
Embolism
Ab8ent
Embolism
Uncertain
No
Angiogram
Tota'
No,
Age (mean), y 56.1 564 High probability 102 14 1 7 124
Male. %
Service. %
45 44
Intermediate probability 105 217 9 33 364
Medical/CCU 40
Surgical 18
Emergency depanmenVcllnoc 30
36
21
32
low probability
Near normai/normai
~
39
5
199
50
12
2
62
74
312
131 H;
-
ICU 10 10 Total 251 480 24 178 931 ~
Other
Hospital monaiity. %
1
9
1
10
La
N;
-
'PIOPED Indicates Prospective Investigation at Pul- To
and
monary
ICU,
Embolism
intensive
DiagnosIs'
care unit."
CCU coronary care unit.
,
"
,able 5.-Companson of Scan Category With Angiogram Findings. Sensitivity and SpecifICity
-
Scan Category
High probability
Sen81tlvtty, %
41
Specificit y % .'
97
cli
High or intermediate probability 82 52
participate in PIOPED (Figure). The High. inlermediate. or low probability 98 10
clinical centers varied in the percentage er
of eligible patients for whom consent
could be obtained, from 33% to 70%, and
p,
a
in the percentage of patients for whom of angiograms, respectively. In only 13 sitivity for thromboemboli on angiogra- U
angiograms were obtained among those
selected to determine the sen~tivity
(1.7%) of i55 angiograms was panel adjudication
necessary.
phy increased to 207 (82%) of 251 (95%
CI, 78% to 87%). If the patient had ei-
~
It
and specificity of V /Q lung scans.
(PIOPED angiographic pursuit). from Scan Findings
ther a high-, intermediate-, or lowprobability
V/Q scan, then 246 of 251
a;
P
64% to 92% (Table 2). The PIOPED pa- Most (676) of the 931 patients had had thromboemboli on angiography, a \\
tients resembled refuser/ineligible pa- intermediate- or low-probability V/Q sensitivity of 98% (95% CI, 96% to (~
tients in a variety of clinical characteris- scan readings (39% and 34%, respec- 100%).
tics (Table 3). The PIOPED patients tively) (Table 4). Only 131 (14%) had Only 14 (3%) of 480 patients who did: g
and refuser/ineligible patients were different,
however, in their lung scan abnormalities
(P

~ Table 6 -Pulmonary Embolism (PE) Status'
ul
o.
-~ Clinical Science Prob8bllity, %
.-
24
-"
54
12 Scan Ca1egory
80.100
~ +/No.
of Patient. %
20-79
PE + /No.
of Patient. %
0019
-.
PE + /No
of Patient. Of.
All PTObabllltte.
PE + /No
of Patient. °/.
.11 High probability 28/29 96 70/80 88 -5~ ~ -'1~~;;~'~'. ~~
.11 Intem1ediateprobability 27/41 66 66/236 2~ 1~~ ~~ ;~~ ~
-Low ., probability ,, , 6/15 ~- 40 30/191 ~~ ~ .~ ';~ ~,-~V ~ ,~
Near normal/normal
~
0/5 0 4/62
~-~~-
6 1/61 2
-~"~V
5/128 4
~
Total 61~ 66 170/569 30 21/228 9 252/887 28
-emboll~m status IS based on anglogr~m Interpretation tor 713 patients, on angiogram interpretation and outcome classification commit1ee reassignment tor 4 patients, and on
~ CllnlCallntormation alone (wi1hout definitIVe angIography) tor 170 patients.
-embolism was only 74% (14/19), com- before the scan was performed ("prior COMMENT
pared with 91% (88/97) for those without probability") was compared with pula
history of pulmonary embolism monary embolism status as determined The PIOPED study was conducted as
~- (~% ~Ict:ve valu,es reflects ,a,loss I)f specifi~- tion (T~~le 6) for 887 patients with pri.or mate the sensitivity and specificity of
ei- Ity m the hIgh-probabIlity V/Q scan dI- probabIlIty assessments and defimte the V/Q lung scan for the diagnosis of
,w- agnosis for patie~ts with histories of pulmonary embolism status. A clinical pulmonary embolism. Other retrospec-
:51 pulmonary embolIsm (88%) vs those assessment of 80% to 100% likelihood of tive and prospective studies have fo-
.a with no prior pulmonary embolism pulmonary embolism was made in 00 cused on positive predictive values.
to (98%) (P

,} successfully recruited for PIOPED. If ment with the interpretation of the scan grams. Ninety-five patients (31%) had CI
anything, this selection bias would sug- is supported by the PIOPED study. The pulmonary emboli demonstrated on an- Du
gest that PIOPED tends to overesti- predictive value of the high- and low- giography. The predictive values from I
mate V /Q scans' sensitivities and:under- probability lung scans improved when their study are similar to PIOPED re- ~
estimate specificities. supported by similar clinical assess- suits in the high-probability and inter- .
Clinical decisions are often made on ments. For 90 patients, the negative mediate-probability (indeterrninate) ~
the basis of the predictive values, which predictive value of the low-probability scan categories. The PIOPED study, He!
depend not only on the test's sensitivity scan rose to 96% when accompanied by a likewise, found pulmonary emboli F
and specificity, but also on the preva- clinical assessment of low likelihood. In among patients with scans in the low- ~
lence of disease in the population stud- 29 patients, the positive predictive val- probability category, but fewer than ,4
ied. Based on angiogram resul~~, the ue of a high-probability scan increased the 25% for subsegrnental matched le- M~
prevalence of pulmonary embolIsm in to 96% if supported by a high-likelihood sions and 40% for subsegrnental mis- ~
PIOPED was 33% (251/755) (Table 4); clinical assessment. In the PIOPED ex- matched lesions found by Hull et al. Pa- (
based on pulmonary embolism status- perience, combining a lung scan inter- tient referral patterns or lung scan J.
derived from angiogram evaluation and! pretation with a strong clinical suspi- interpretation criteria may account for ~
or clinical evaluation-the prevalence cion as to whether acute pulmonary the differences between PIOPED re- u~
was 28% (Table 6), similar to the preva- embolism is present is a sound diagnoslences
described in previous reports. '3-21 tic strategy, as previously suggested by
suIts and the Hamilton study results.
Since angiographic studies are not
J
E
In PIOPED, the posi~i.ve predictive val- M~Neil and collea~es, ~,21 but is. suf- available ~nd clinical fol~ow-up has not ~
ue of the high-probabIlIty scan was .8$_%, ficient for only a mmonty of patIents been applIed to determine pulmonary v
whereas the negative predictive v"a1\i'e (Table 6). For a substantial number of embolism status for the 110 patients
of a low-probability scan was 84%. The
negative predictive value of the nearpatients
in the PIOPED study, angiography
was required for a definitive diagwithout
adequate angiography, for the
22 patients without adequate ventila-
.
Re
norrnaVnorrnal scan category was bet- nosis of pulmonary embolism, tion scans, and for the patients with 1.
ter at 91 %. Estimates of negative pre- The PIOPED study employed pulmo- norrnal scans in the Hamilton District Me
dictive values increased when analyses nary angiography, which proved to be a Thromboembolism Programme, com- ~~
took into account patients who did "nOt safe and accurate method of diagnosing parisons of estimates of sensitivity and 2.
undergo angiography, did not receive pulmonary embolism, although it is in- specificity between the two studies are Jos
anticoagulants, and had no evidence of vasive, The four patients (0.5%) for not possible. agr
pulmonary embolism occurring during 1 whom the outcome classification com- The PIOPED results lead to a num- : i~
year of follow-up. Including these pa- mittee disagreed with blinded angio- ber of conclusions that settle controver- BA
tients among those not having pulmo- gram interpretations that showed acute sies about the diagnostic value of the mo
nary embolism in the analysis improved pulmonary embolism to be absent must lung scan in pulmonary embolism.~'" A 100
the negative predictive value of the low- be considered carefully in light of the high-probability scan usually indicates ~
probability scan from 84% to 88% and of angiographic criteria's design for acute pulmonary embolism, but only a minor- 100
the near-norrnaVnorrnal scan from 91% pulmonary embolism, the variable time ity of patients with pulmonary embo- 5. , i
to 96%. Because some instances of acute between angiographic evaluation and lism have a high-probability scan. A his- the I
pulmonary embolism may not have been the patients' deaths, and the variability tory of pulmonary embolism decre~es ~
detected among these patients, the true in pathophysiology and pathological in- the accuracy of diagnoses based on hlgh- Sor,
negative predictive values may be less terpretation ofthromboemboli in evolu- probab~lity scans. A. .low-probabil.ity 7. :
than 88% for low-probability scans and tion. In the PIOPED study, a norrnal scan WIth a strong clInical ImpreSSIon NY
96% for near-norrnaVnorrnal scans, but angiogram almost excluded the possibil- that pulmonary embolism is not likely ~:
still ought to be closer to these latter
values than to the 84% and 91% which
ity of pulmonary embolism, confirming
the results of two previous studies. '4,'0
makes the possibility of lJulmonary embolism
remote. Near-norrnal/norrnal
197
9.
did not account for patients without an- The PIOPED findings extend ob- lung scans make the diagnosis of acute mo;
giography results. servations made by other investi~- pulmonary embolis~ :"ery u~likely. A~ ~::
Although pulmonary emboli did occur tors,l-3,I2-8! from whom the PIOPED m- IntermedIate-probabIlIty (mdeternll-
in patients with scans classified in the vestigators derived stu?y criteria, for n.ate) sc.an is not of help in establishing a
categories between low probability and angiogramand.V/.Q scan mterpreta.tIon. d~agnosl~. In. ~IOPED, the scan c°':l1norrnal,
pulmonary embolism was docu- Although predIctIve values for patIents bmed WI~h clI~lcal.asses~ment pe~Itmented
in only 5 (4%) of 131 of such with high-probability scans and pa- ted a nOninvasIve dlagnosI~ or excluslo~
patients. The true proportion of pa- tients with low-probability scans i~ pre- of a.cute pul':l1°nary embolism for a mItients
with pulmonary embolism must vious series are generally consIstent nontyofpatlents.
be inferred with caution, because large with the PIOPED findings, the underb
f ' . h V t t. f t. t '
norrnal scans were not successfully re- probability scans m preVIous studIes 34010, NO1-HR-34011, NO1-HR-34012. and NO1cruited
for the study. Only 42% of the has in the past led to an exaggerated HR-34013 from the National Heart. Lung. and
131 PIOPED patients in this category
comp Ie ted ang1ograp .h y. 0 n 1 yo. 3 fthe 21
impression of the sensitivity of the high-
Probabilit y lung scan. -111'
Blood Institute: Bethesda, Md.
been The greatly secretarial appreCIated. asSIStance of JoAnne Decker has
patients with lung scans read as norrnal The findings of Hull and colleagues'
by both readers on the final reading
completed anmography' e" all 3 had normal
pulmonary angiograms. None of the
remaining 18 had clinically evident pul-
.. m()nary embolI on follow-up. This findi!1
the Hamilton District ~romboe;mbolIsm
". Programme are partIcularly . mterestmg
m companson W1 th the PIOPED
results. Of the 305 patients with susd
1 b 1. d b
pecte pu ':I1°nary em 0 I~m an, a nor-
Steering Committee
. II
ThePIOP~LJlnvestlgatorsareaslo
-,
ows:
H~rbert A. s~ MD, chairman; Abass
AlaV1, MD, Rlch~reenspan, MD, Charles A.
Hales, MD, Paul 0, ~ MD, Michael Terrin.
ing is consistent with the findings of mal perfusIon lung scans m theIr ~tU?y, MD. MPH, Carol Vreim. PhD, John G. Weg, MD;
Kipper et al.~ 173 (57%) had adequate ventllatl~n alternates: ChristOB Athanasoulis, MD, Alexander
The value of combining clinical judg- scans and adequate pulmonary anglo- Gottschalk,.\iD.
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~ j Clinical Centers University of Pennsylvania " LaFrance. MD, GerardJ. Prnd'homme. MA. Sharn-
Duke University Abass AlaVI. MD. pnnClpallnvestlgator; Marga- on Prnitt. Pauline Raiz. Broce Thompeon. PhD.
Herbert ~tzman. MD. principal investiga- ret Ahearn-Spera. RNC. MSN. Dana R. Burke. Heidi Weissman. MD.
m tJ;r;RU8sell Blinaen1D. R. Edward Coleman. MD. Jeffrey Carson. MD. Mark A. Kelley. MD. .
e- MD, N. Reed Dunnick, MD; William J. Fulker- Gordon K. McLean, MD. Steven G. Meranze. Project Office
r- J MD L Mall tratt RN Carl E R MD. Harold I. Palevsky, MD. Sanford Schwartz.
:ri r. ,ee a " .aVln. MD. Nati?nal Heart. Lung, and Blood TnBtitute: Carol
e) H . F rd H "tal Yale University E. Vrelm. PhD, Margaret Wu. PhD.
V enry 0 OSpl R" hard H G MD al " .
..PaulO Stein MD principal investigator' Debo- IC .reenspan. .pnnclp mvestlga-
)li raiiAriimi:RN .'of tth B k MD J' W tor; Donald F. Denny. Jr. MD. Alexander Gott. Policy and Data Safety
N- Froelic~MD, Ke:net::WV. ~ee~r. MD~r;am: .chalk. MD, Lee H. Greenwood, MD. Jacob S. o. Monitoring Board
Le MD J h Po h J .Loke, MD. RIchard A. Matthay. MD. Steven S.
m A. seer, .0 n poVlC. r. MD. P. C. Morse, MD, H. Dirk Sostman. MD, Felicia Myron Stem. MD, chairman: Daniel M. Biello.
e- Shetty, MD. James Thrall, MD. Tencza, MPH. MD (deceased). Sarah Greene Burger. MPH. Robs-
Massachusetts General HospItal" .ert Henkin, MD, Thomas Hyers. MD, Paul S.
Charles A. Hales. MD. pnnClpal mvestlgator; Data and Coordinating Center Levy. ScD. Franklin Miller. Jr. MD, Robert E.
a- Christos Athanasoulis. MD. Stuart Geller. MD, O'Mara. MD, Morris Simon. MD. Gerard Turino.
in Kenneth McKusick. MD. Deborah Quinn. RN, Maryland Medical Research Institute: Michael MD. George W. Williams. PhD.
Jr MS. B. Taylor Thompson. MD. Arthur C. Walt- L. Terrin. MD, MPH. principal investigator; Wile-
man. MD. ." mot Ball. MD, Mary Burke. Martha Canner. MS, Outcome Classification Committee
UnIversIty of MIchIgan Paul Canner. PhD. Margie Carroll. Martin Gold- "
8. John G. Weg, MD, principal investigator; Grace man. MD. Carol Handy, Elizabeth Heinz. Thomas Mark.~. Kelley. MD. chatnnan; Jeffrey Carson.
ot Ball, RN, KyungJ. Cho. MD. ctlarles A. Easton, E. Hobbins. MD, Frank Hooper. ScD, Steven ~D, Wllltam.J. FUlkerson. MD, Thomas E. Hobot
MD, Andrew Flint. MD. Thomas A. Griggs. MD. Kaufman. MD, Christian R. Klimt. MD. DrPH blnB. MD. RIchard A. M~tthay, MD, Harold Pa-
Jack E. Juni, MD, Jerold Wallis, MD, David (principal investigator. September 1983 through levsky, MD, John PopoVIch. Jr. MD. B. Taylor
7 Williams. MD. September 1984), William F. Krol. PhD, Norman Thompson, MD. John G. Weg. MD.
ts
le Ref8rence8
a-
~h 1. Wagner HN. Sabiston DC. Tio M. McAfee JG. noetic test in unselected populations. N E1I91 I ,'tied. 1983;98:891-899.
ct MeyerJK, Langan JK. Regional pulmonary blood ,'tied. 1006;274:1171-1175. 18. Hull RD, Hirsh J. Carter CJ, et aI. Diagnostic
n- flow in man by radioisotope scanning. lAMA. 11. Li OK. Seltzer SG. McNeil BJ. V/Q mis- value of ventilation-perfusion lung scanning in pad
1004;187:601-603. matches unassociated with pulmonary embolism: tients with suspected pulmonary embolism. Chest.
1 2. Wagner HN Jr. Lopez-Majano V, Langan JK, case report and review of the literature. I Nucl 1985;88:819-828.
re Joshi RC. Radioactive xenon in the differential di- .'tIed. 1978;19:1331-1333. 19. Poulose KP. Reba RC, Gilday DL. Deland FH.
agnosia of pulmonary embolism. Radiology. 12. Biello DR. Kumar B. Symmetrical perfusion Wagner HN. Diagnosis of pulmonary embolism: a
1968;91:1168-1184. defects without pulmonary embolism. EUl" I Nucl correlative study of the clinical. scan, ano angi()n-
3. Biello DR. Mattar AG. McKnight RC. Siegel .'tIed.1982;7:197-199; graphic findings. B.'tII. 1970;3:67-71.
r- BA. Ventilation perfusion studies in suspected pul- 13. Alderson PO. Martin EC. Pulmonary embo- 20. McNeil BJ. Ventilation-perfusion studies and
Ie monary embolism. Am I Radiol. 1979;133:1033- lism: diagnosis with multiple Imaging modalities. the diagnoses of pulmonary embolism: concise com-
A 1037. Radiology. 1987;164:297-312. munication. I Nucl ,'tied. 1980;21:319-323.
, ~. Snedecor JW, Cochran WG. StatiStical Meth- 1~. Cheely R, McCartney WH, Perry JR. et aI. 21. McNeil BJ. Hessel SJ, Branch WT. Bjork L.
-8 odA. 6th ed. Ames: Iowa State University Press; The role of noninvasive tests versus pulmonary Adelstein SJ' Measures of clinical efficacy, III: the
r- 1967. angiography in the diagnosis of pulmonary embo- value of the lung scan in the evaluation of young
()- 5. Cochran WG. Some methods of strengthening li.m. Ami Med. 1981;70:17-22. patients with pleuritic chest pain. I Nucl ,'tied.
s- the common X2te8ts. Biometrics. 1954;10:417-451. 15. Novelline RA, Baitarowich OH. Athanasoulis 1976;17:163-169.
,
_8
6. Fleiss JL. Statistical ,'tIethAJda fOl" Rates and
PropoI"tion.!. 2nd ed. New York, NY: John Wiley &
CA. Waltman AC. Greenfield AJ. Mckusick KA.
The clinical course of patients with suspected pul-
22. Kipper MS. Moser KM. Kortman KE, Ashburn
WL. Long-term follow-up of patients with sus-
1- Sons Inc; 1981. monary embolism and a negative pulmonary arte- pected pulmonary embolism and a normal lung
:y 7. Nie NH, ed. SPSs" USel"~ Gltide. New York. riogram. Radiology. 1978;126:561-567. scan. Chest. 1982:82:411-415.
In NY: McGraw-HilI International Book Co; 1983. 16. Sasahara AA. Stein M, Simon M, Littmann D. 23. Robin ED. Over diagnosis and over treatment
l
y
8. Hill AB. Principles of ,o,{edical Statistics. 9th
ed. New York, NY: Oxford University Press Inc;
Pulmonary angiography in the diagnosis of thromboembolic
disease. N E1I91 J Med. 1004;270:1075of
pulmonary embolism: the emperor may have no
clothes. Ann lntel"n Med. 1977;87:775-781.
1- 1971. 1081. 24. Biello DR. Radiological (scintigraphic) evalua-
Ii 9. Murphy EA. Probability in Medicine. Balti- 17. Hull RD, Hirsh J. Carter CJ, et aI. Pulmonary tion of patients with suspected pulmonary throme
more, Md: The JohnB Hopkin8 University Press; angiography, ventilation lung scanning and venog- boembolism. lAMA. 1987;257:3257-3259.
n
1979.
10. Vecchio JJ. Predictive value of a single diagraphy
for clinically suspected pulmonary emboli8m
with abnormal perfusion lung scan. Ann lntel"n
a .
11
i- '
t.
t- -
l-
Id ~.
18 .
S
'. I;
,r .
s JAMA. May 23/30, 1990-VoI263. No. 20 Ventilation/Perfuslon Scan-PIOPED Investigators 2759
,
..' '- I
.'.:. -j

I
}"
~.. Editorials di
tc
Ie
Ventilation/Perfusion Scan in Pulmonary Embolism : T:
I 'The Emperor Is Incompletely Attired' :
One of the most difficult diagnoses to make in medicine today tive diagnosis of pulmonary embolic disease_2.4 The relatively c~
is that of pulmonary embolic disease, In a study done in the low sensitivity of high-probability scans (41%) means that tl
i I early 1970s, , evidence of pulmonary embolism at autopsy scans, alone, are inadequate to ascertain the presence of
'i correlated poorly to antemortem diagnosis of pulmonary em- pulmonary embolism- On the other hand, only 3% of patients
bolic disease; in only one third of cases were emboli correctly in the Prospective Investigation of Pulmonary Embolism
identified. A batting average

'. t.
'- . ,
I .diagnosing pulmonary embolic disease today, the clinical his- lism, the emperor has a "well-clothed" appearance. When -\
tory, used i~ c~njunction.with evaluation of.arte~al blood gas there is significant doubt, a pulmonary angiogram should be '
levels, ventIlation/perfusion scans, and nOnInvaSive studies of done. . I
the ~e.ep, veins. of the legs, should markedly improve the Roger C. Bone, MD
physIcian s battIng average. If the postmortem studies of the, I
1970 d d . h ., .1. ModanB.SharonE.JelmN.Factorscontributingtotheincon'eCtdiagnosis i
S were repeate to ay, usIng t IS recent InformatIon, the nfpulmonary embolic disease. Che.t. 1972:62:388-393. I
results should be much better. My suggestions for diagnostic 2. The PIOPED l,nvestigators. Value of the ventilation/perfusion scan in acute
~ evaluation are included in an algorithm that uses some of the pulmo~ary e.mbollsm: results of the Prospective Inve.tigation of Pulmonary
most recent
.'
InformatIon from the
..,
article m todays
.Emboll.m
Issue of
Diagno"," (PIOPEDJ.
:I. Robin ED. Overdiagnosis
JA,\f A. 1900:263:2753-2759.
and overtreatment of pulmonary emboli.m: the "
THE JOURNAL, as well as information published on the diag- emperor may h,ave no clothes. Ann Intm! ,\fed. 1977:87:775-781. I
nos tic accuracy of noninvasive studies for dee p venous throm- 4. Hull RD~ HI~hJ. C~rterCJ.etal. Diagnootic VaJueOfventilation.perfu"ion
bosls
..lung
(Flgure)..,..T 1985;88:819-828.
scanning In patients WIth suspected pulmonary embolism. Che../.
'
\
The ventilation/perfusion lung scan, taken in isolation, rep- 5. Hull RD. Hirs.h!. Carter CJ. et al. Diagn~stic efficacy of impedance plethys-
th "th h I th " "th mography for clinIcally suspected deep-vein thrombosIs. Ann In/","" ,~fed.
resen t s nel . er e emperor as no c 0 es nor e emper- 1985:102:21.28.
or I th is fully clothed." b t .. Indeed, the emperor may have some 6. Polak JF. Culler SS. O'Leary DH. Deep veins of the calf: assessment ,,;th \
{ CO es on, u untO rt una tel Y h e . IS, as ye t , . mcomp I e t e I y at- 7Doppler Whl ' te
flow
RH
imaging. McGah a. Radiology. nJP D asc hb
1989:1iI:481-485. ac, h MM .ar H I mg ' RP .lagnoSI" D ' 0 fd eep-
t tired. In the maJonty of cases of suspected pulmonaryembo- vein thrombosis using duplex ultrasound. Ann In/ern ,\fed. 1989:111:29;.304.
r i ,
Methods of Smoking Cessation.-Finally,
Some Answers
Forty million living Americans have quit smoking.' While not are much more likely to participate in an organized cessation
as catchy, perhaps, as "Fifty million Frenchmen can't be program than persons who smoke less. '
"'TOn~' o~ "~illions have rea? t.he book,.now see the movie," These data, and the conclusions derived from them, are a .I
the pnnclple IS the same-this IS a massive number of people movable feast-they provide a wide variety of health profes- ,
focused on one activity. sionals, and smokers themselves, with specific actions each II
can take to help reduce smoking prevalence. Among the
See also p 2760. groups ing: who can benefit from the information are the follow- \
Unfortunately, until now we have known very little, or Physicians. The primary message for physicians is that
have had to surmise, how so many smokers have achieved their advice is a key element in motivating smokers to make
their goal of quitting. The article by Fiore et al' in this issue of quit attempts. Even if smokers do not quit the first or second
THE JOURNAL, however, finally provides some answers and, time they receive their physician's advice to do so-and most
even more important, guidance on this issue. data suggest this is the case-the advice of the physician can
Among the important findings presented by Fiore et al are help move smokers from one stage to another in the quitting
the following: process,3' eventually leading to successful abstinence from
.More than 90% of successful quitters do so on their own, smoking.
without participation in an organized cessation program. In keeping with these data, the National Cancer Institute
.Quit rates (defined as §moking abstinence for ~1 year) recently developed a simple protocol to help physicians pro-
are twice as high for those who quit on their own compared vide advice about smoking cessation.' The National Cancer
with those who participate in a cessation program. However, Institute suggests that the physician's office or clinic be
this finding is not based on randomly allocating smokers to smoke free, that all smokers in the practice be identified, and
one method or the other. Rather, smokers who enter cessa- that the physician (and other office support staff> ask about
tion programs may be those who were unable to quit on their smoking at each patient visit; advise smokers to stop at every
own. opportunity; assist smokers in stopping by helping them set a ;
.Smokers who quit "cold turkey" are more likely to re- quit- date, providing self-help material, and prescribing phar-
main abstinent than those who gradually decrease their daily maci>logical adjuncts as appropriate; and arrange follow-up
consumption of cigarettes, switch to cigarettes with lower tar contact with the patient to prevent relapse.
or nicotine, or use special filters or holders. PtLblic Health Planners/Practitioners. Among the mes-
.Quit attempte are nearly twice as likely to occur among sages for those involved in public health planning or practice
smokers who receive nonsmoking advice from their physi- are the following: (1) Efforts should be directed at motivating
cians compared with those who are not advised to quit. more smokers to make serious quit attempts, rather than
.Heavy (~25 cigarettes a day), more addicted smokers developing new progrartts; (2) existing self-help cessation
materials should be made more widely available; increased
~Iynn IS the Program Director for Smoking Research at the National~ availability will be more successful than developing new ma-
Inst,tu1e. Bethesda, Md terials or "fine tuning" existing materials; and (3) consider-
9(XX) Repnnt Rockvllle reQuests Pike to Bethesda. National MD Cancer 20892-4200 Institute (Dr ExecutIVe Glynn) ~laza North. Room 320.. atIon should.be gIven to ~usmg ' on t h e h eaVler, . more severe-
JAMA. May 23/30. 1990-VoI263, No 20 Editorials 2795
I
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ly addicted smoker in organized cessation programs. Similar (4) advising patients to seek the support, even if quitting "on
" ,. recommendations were made recently by a National Cancer their own," ofaspouse, friend, or someone else in a position to
Institute expert advisory panel, which also encouraged pro- help reinforce their decision to quit. Finally, recent research
! jects that will provide self-help materials to high-risk popula- suggests that, while training physicians to give advice about
..tions, especially blacks, Hispanics, and pregnant women, smoking cessation can increase patient quit attempts, it will
whose particular needs have often been neglected in our take greater effort-perhaps several follow-up visits or consmoking-cessation
efforts." tacts-to reduce the high relapse rates experienced.,..e..l.
Smoking-Cessation Researchers. In addition to finally pro- 8 1b provide those involved in reducing smoking pre'llaviding
evidence for the widespread belief that the majority of leme with the most expedient means of doing so. Too often,
smokers who quit do so on their own, the findings of Fiore et al those charged with reducing smoking prevalence, such as
call our attention to several potential research questions. physicians, nurses, dentists, public health officers, and smok-
What detennines relapse, and how can it be prevented? How ing-cessation program coordinators, are not provided with or
can we motivate more smokers to make Seri01tS quit at- aware of the most appropriate information available to help
tempts? What are the most effective means of dissemination smokers stop, especially on their own. II For physicians, this
and adoption of successful cessation methods? may mean not being aware of effective cessation strategies' or
Smokers. Important messages for smokers in this article the proper use of nicotine gum (or the transcutaneous nicotine
are (1) they can quit; (2) they can successfully stop smoking if patch that may soon be available). It could also mean being
they do so on their own (especially by setting a specific quit unaware of the special help for heavy smokers that organized
date and stopping cold turkey on that date); (3) smoking- cessation programs can provide. For public health officers
cessation programs are helpful for some, especially heavier, and smoking-cessation program directors, it could be not
more addicted smokers: and (4) permanent quitting from a realizing the importance of providing simple self-help materifirst
or second attempt is unusual; the smoker may suffer an al to as many smokers as possible and not limiting their efforts
initial relapse and need to learn from that experience in order to those who have already expressed an interest in giving up
to make another, successful, quit attempt. tobacco. The importance of a variety of providers and a menu
A major conclusion that may be drawn from these data, of methods becomes more important as more smokers are
then, is that we do not need to expand our efforts to involve motivated to make serious quit attempts.
more smokers in formal cessation programs. Nevertheless, With the knowledge that there will be more than 2 million.
I. \ve should not abandon these programs. 7 as some, such as the tobacco-related deaths worldwide from tobacco this year, it is ..
American Lung Association's "Freedom From Smoking" clin- obviously necessary to expand our efforts to reduce smoking
ic program, are successful, and we need to maintain a variety prevalence not only in the United States and other industrialof
approaches to cessation. This is especially true for heavier ized countries but, especially, in the developing world, where
smokers who wish to try to quit \\;th the more formal meth- the tobacco industry is increasing its markets and the rates of
od!l. We do need to focus on the broad pllblic health implica- tobacco-related death are rising. Next week's World Notions
of our !lmoking-cessation efforts, and our agenda should Tobacco Day (May 31), sponsored by the World Health Orgainclude
the following goals: nization, provides an excellent opportunity to embark on a
8 1b motivate more smokers to make serious quit at. renewed effort to help those who want to quit smoking to do
tempts. While physicians are in a unique position to motivate so, and to help those who do not now smoke, especially in
smokers, it is equally important to motivate the smoker on a developing countries, to remain nonsmokers.
society-wide basis, so that nonsmoking
... ki
cues, such as in-
1 d Thomas. J Glynn, PhD
creased tobacco taxes, restnctlve smo ng po ICles, an coun-
teradvertising campaigns, become "persistent and inescap- 1: Pierce JP. Fiore MC, Novotny TE. Hatziandreu EJ, Davis RM. Trends in
bl "
a e.
Th
e
N t . 1 C
a lona ancer
I t ' t t and
ns I u e
the Amen 'can CIgarette smoking In the Umted States: projectIons
1989;261:61-65.
to the year 2000. JAMA.
Cancer Society, through their upcoming American Stop 2. Fiore MC, Novotny TE. Pierce JP, et aI. Methods used to quit smoking in the
Smoking Intervention Study for Cancer Prevention, will pro- United States; do ce!!:88tion programs help? JA,\1 A. 19!MJ;263:2760-2765.
., .." 3. Prochaska JO, DiClemente CC. Stages and processes of self-change of
VIde a major demonstration of this strategy. smoking: towani an integrative model of change. J COn81tlt Clin Psychol.
8 1b increase s1tCCeSS rates amacco and Health In pre..sso
1
(1) motivating smoking patients to make senous, SltStalned
quit attempts; (2) helping patients learn, prior to the quit
. d . f t. 1 0th
attempt, about the seventy and uratlon 0 poten la WI -10.
9. Cohen SJ, Stookey GK. Katz BP. Droo..k CA. Smit..h OM. Encourag1ng
primary ~ physici&ft8 t~ help smokers quIt: a randomized, controlled tnal.
Ann Int~ Med. 1989:110..648-652. '
Cummings SR. Coates TJ, Richard RJ. et aI. Training physicians in counsel-
I i drawal symptoms; (3) prescribing, for heavily addicted smok- ing about smoking cessation: a randomized trial of the 'Quit Cor Life' programo
firs .o th ' 30 ° t f kin g or a Ann Int~ Mad. 1989:110:640-647.
ers (eg, t CIgarette WI m mmu es ~ ~ 11. Glynn TJ, Boyd GM. Gruman JC. Self-Gllided Stmtegies for Smoking
cigarette habit of more than a pack a day), a mcotme replace- Ce3sation: A Program Plan1!$TJ GltiU.. Bethesd..a. ~d: National Cancer Instlment
product, after careful explanation of its proper use; and tute. In preMo National Institutes of Health publicatIon 90-3104.
2796 JAMA. May 23/30. 1990- Vol 263. No 20 Editorials
~III-.
-,