patients. Pneumocystis carinii pneumonia in HIV ...

Prospective evaluation of a prognostic score for Pneumocystis carinii pneumonia in HIV-infected patients. R Speich, M Opravil, R Weber, T Hess, R Luethy and E W Russi Chest 1992;102;1045-1048 DOI 10.1378/chest.102.4.1045 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/102/4/1045

Chest is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright1992by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0012-3692

Downloaded from chestjournal.chestpubs.org by guest on July 10, 2011 © 1992 American College of Chest Physicians

Prospective Evaluation of a Prognostic Score for Pneumocystis carinhl Pneumonia in HIV-lnfected Patients* Rudolf

Speich,

M.D.;

Thomas Hess, Erich WRussi,

Milos

Opravil,

M.D.;

Ruedi Luethy, M.D., F.C.C.P

Rainer

M.D.;

M.D.;

Weber,

for early fatal outcome of a P(A-a)05 >35 mm Hg was 24 percent (6/2,5); the negative predictive value was 98.6 percent (68/69). However, the overall diagnostic accuracy was only 78.7 percent (74/94). The PCP severity score is a valuable tool for clinical decision making, for the early identification of patients with a prognostic unfavorable course, and for the comparison of patient populations in future studies of H1V-associated PCP.

Serum lactate dehydrogenase levels, alveolar-arterial oxygen gradient, and percentage of neutrophils in bronchoalveolar lavage correlate most strongly with early mortality in Pneumocystis carinii pneumonia (PCP) in HIV-infected patients. However, the individual outcome can not be predicted by these parameters due to a considerable overlap between survivors and nonsurvivors. We prospectively investigated a PCP severity score, which has been developed earlier based on a retrospective analysis. Seven of 94 consecutively examined HIV-infected patients died within 14 days after diagnosis of PCP. A PCP severity score greater than 7 had a positive predictive value for early fatal outcome of 66.7 percent (6/9) and a negative predictive value of 98.8 percent (84/85). The overall diagnostic accuracy was 95.7 percent (90/94). The positive predictive value

D

espite

advances

in

prevention,

diagnosis,

(Chest

BAL ciency

immunodeficiency

prognostic

PCP,

factors

serum

arterial

for adverse

lactate

oxygen

(HIV).

and

(LDH),

P(A-a)O2,

strongly

ratory

failure

do

not

allow

to

a considerable

.

with

the

these

prediction

of individual

overlap Based

between

on a retrospective

bining these three parameters, prognostic score (Table 1) that early

fatal

prospective

three

quite

reliably.6

evaluation

ofthis

PCP

Choice

for

drug,

either

and

analysis,

com-

present

score

(P55).

evaluated

1989

94 consecutive

by BAL. The studied mean

men,

age

35

IV

drug

The

sisting

of fever,

*From

the

ofZurich, Manuscript

Reprint University

Four

HIV-infected

36.2 users,

duration

and

one

and

dyspnea,

of Internal

we

PCP

diagnosed

men

and

13 women;

There most

were with

common

the Medicine,

current

58

July

reactions.

with were

severe

PCP

after

Not

for continuous

was

not

in

initial

in about

25

corticosteroids of 5 to 10 days. to ICU

patient’s

(A) survival fatal

the

by pentamidine

admitted

because

refusal.

after

outcome,

bronchoscopy

defined

as death

SD. The significance

±

determined and

indicated

Table

orally

of PCP.

variables

(NS)

first-line

or and

received

or the

as mean

the groups

significant

transfusion-related symptoms smoking University

between

the

patients,

replaced

The

physicians

as

for a period

as follows:

diagnosis

In six

patients

and (B) early

fluid. described.’

patients

was

were

determined

individual used

pentamidine,

syndrome

grouped 14 days,

14 days

the

hospitalized

ventilated

wasting

were of BAL

was

Eight

aspirated

as previously

basis.

using

immediately counts

by

co-trimoxazole

performed

the

with

x’

a p value

1-PCP

test

the

of differ-

Mann-Whitney

for discrete

variables.

0.05.

Severity

Score

homosexual

P(A-a)O,, con-

Points

mm

BAL Neutrophils, LDH,

Hg

U/L

%

status, Hospital

Switzerland. received requests: Hospital,

in

was

gas Chest

bronchoscopy

preparations

determined

mechanically

than

cell

on room

alveolar

admission.

BAL

solution

of intravenous

chronic

Patients

U test

prospectively

with

of8l

patient

three

Department

patients

years.

of the

cough,

1990,

consisted

± 10.5

were

patients

for more

saline

(normal

simplified

scored.

Co-trimoxazole

patients,

LDH

gas samples

by fiberoptic

on an out-patient

ofadverse

of severe

not

intravenously consisted

Serum

1) was calculated

All data are expressed

December

population

was

disease.

and

(Table was

treated

four

Pneumopneumo-

carinii

of hospital

Differential

patient.

because

ences January

score

ofthe

and

were admission

cytocentrifuged

percent

within

Patients

the

a

immunodefiPCP

blood by the

time

a syringe.

the

treatment

noted.

at the

of normal

of therapy

patients

a

METHODS

Between

aliquots with

were

P[A-a]O2

changes

caring

survivors

of the

48 h of hospital

corre-

due

of PCP

obtained

roentgenogram

to respi-

outcome

severity

were

50-ml

human

HIV

at 37#{176}C) and arterial

on Wright-stained,

parameters

We

equation)

PCP severity

we have developed enabled us to predict

outcome

episodes

calculation

manually

alveolar-

due

(with

102:1045-48)

score

previous

four

with

(BAL)

mortality

Unfortunately,

‘-

nonsurvivors.

lavage

early

carinii

460 U!L, measured air

lavage;

1992;

LDH lactate dehydrogenase; pneumonia; PSS Pneumocystis

virus;

within

and the percentage

in bronchoalveolar

most

various

in patients

bronchoalveolar

nia severity

and

Among

outcome

dehydrogenase

gradient

of neutrophils

late

virus

=

cystis

treatment of Pneumocystis carinii pneumonia (PCP), this disease continues to be a major source of morbidity and mortality in patients infected with the human

M.D.;

and

8; revision accepted January 21. Dr. Speich, Department of Internal Medicine, CH-8091 Zurich, Switzerland

1

>20

>460(>normal)

>2

2

>30

>920

>5

3

>40

>1,380(>3xnormal)

4

>50

>15

5

>60

>20

(>

CHEST

2x normal)

I 1 02

>10

I 4 I OCTOBER,


1992

1045

Table

2-Comparison

Survivors (Group (Group B)5

between Nonsurvivors

Group

A

A) and

Group

(p

(Fig

B

(n7)

(n=87)

tively

the

p

Current

38

3

NS

tions

could

14

0

NS

topsy

was

3. 1 ± 2.3

3.4 ± 2.4

NS

revealed

bacterial

5

0

NS

steroids

4

4

.

.

ventilation

1

3

.

.

13f, 74m 52H, 34D,

smokers

RecurrentPCP

of symptoms,

Duration Concomitant

wk

iT

7m

NS

6H,

1D

with

Mechanical

LDH, UIL P(A-a)O,, mm Hg

635±597

Serum

26.4

± 12.6

BALneutrophils,

%

8.9±17.9

BAL eosinophils, BALlymphocytes,

%

1.8 ± 2.6

%

PCPseverityscore

5H

=

homosexual;

D

=

1267±302

0.0002

60. 1 ± 16.3

0.0001

37.1±33.2

0.004

6.7

± 7.8

25.9±20.8

17.0±20.5

3.0±2.4 IV drug use;

9.9±3.1 T

severe

0.02

3.0

NS =

percent) diagnosis

(p

had a score

>7

predictive of patients

caused by respiratory failure in all of them. Age, sex, risk factors for acquired immunodeficiency syndrome (AIDS), current smoking status, duration of symptoms, the number of patients incidence of concomitant significantly

The 302

differ

with recurrent PCP, bacterial infections

between

mean serum LDH U/L in survivors

group

A and

and did

the not

B (Table

2).

was 635 ± 597 U/L and 1,267 and nonsurvivors, respectively

33.2

percent

was

8.9

in survivors

0

± 17.9

and

percent

and

nonsurvivors,

in

It

intersti-

fumigatus. No or infections

severity

score and

66.7

(P55)

was

nonsurvivors,

seven

percent),

nonsurvivors three

of the

value

for early

ie,

87

mortality

percent.

The

(98.8 percent), 7 was 1 .2

a value

of

negative

ie, mortality percent. The

P(A-a)O2

was 24 percent; percent.

98.6

P(A-a)O2 however,

>35 was

The

mm only

35

mm

Hg.

Thus,

fatal outcome the negative predictive

value

for

overall

diagnostic

the of a value

early

accuracy

Hg predicting early 74/94 (78.7 percent).

fatal

of a

outcome,

DISCUSSION

37. 1 ±

Pneumocystis

respec-

carinii

pneumonia

0

80

(PCP)

is still

the

0

0 0

0

70 0

60

60

8

0 50

8 I

E E

0

0 0

0 0

t

40

4

p=0.0002

10

81

of the three

a

20

§ parameters

#{176}

0

II

10

p0.0001

B

A

1 . Overlap

8

40

30 0 C

I

20

0 0

o

.4.

B FIGURE

0.

I I

30

0.

-a

:E

I

#{176}

50 -

C

500

0

1046

with

was

±

8 0

A

to severe

Six ofthe

value was 84/85 with a score

0

1500

z

Au-

nonsurvivors.

survivors

0.0001).

=

predictive

70

-J

PCP

of 6/9 (66.7 a P55 >7 was

patients

80

0

1000

infec-

5500

2n.

0

of seven

moderate

± 3. 1 in

positive

The mean P(A-a)02 was 26.4± 12.6 mm Hg and 60. 1 ± 16.3 mm Hg in survivors and nonsurvivors, respectively (p = 0.0001). The percentage of neutrophils

nonsurvivors.

and

overall diagnostic accuracy was 90/94 (95.7 percent). Mortality of patients with a P(A-a)02 >35 mm Hg was 6/25 (24 percent) compared with 1/69 (1 .4 percent)

(p=O.0002).

BAL

respiratory

in the

(Table 3), whereas only did (p = 0.001). >7 had a positive predictive

fatal outcome patients with

of the 94 patients died within of PCP (group B). Death was

or viral

Aspergillus abnormalities

mean 9.9

respectively

A P55 RESULTS

and

± 2.4

survivors

(7.4 after

with

signifi-

percent

in all of them. One patient showed small pulmonary emboli and a small cavitation

could be found. The calculated

not significant.

Seven 14 days

PCP

differed

B (1 .8 ± 2.6 p = 0.02).

in six

containing noninvasive other additional pulmonary

0.0001 NS

transfusion-related;

=

retrospective

documented

performed

overlapped patient groups analysis, also,

two

eosinophils

bacterial

be

tial fibrosis peripheral

the

group A and respectively;

No concomitant

NS

infection Therapy

to our of BAL

cantly between 6.7 ± 7.8 percent

parameters

between

1). In contrast percentage

36.1±10.7

NS

three

however,

Age, yr Sex Risk category

38.1±7.4

These

0.004).

=

considerably,

between

p=0.004

A

the

two

patient

Prognostic

Score

B

groups.

for PCP in HIV-infected


Patients

(Speich

et a!)

Table

GroupA

3-Distribution

ofPCP

Severity

Score

5

6

7

9

6

3

0

1

2

3

4

8

21

17

10

10

most

common

in patients sive

life-threatening with

opportunistic

AIDS.

Due

and

possibly

treatment,

to early

infection

diagnosis,

the

use

aggres-

of adjunctive

corticosteroids, the mortality ofPCP has been reduced over the last years, but it remains considerable. In our experience, mortality was 50 percent until the end of 1985, 20 percent during the period of 1986 to 1988,6 7.4

percent

accordance

the

toward

and

respiratory

over

time.

(1981 were

in the

with

approach

the

current

survival

for patients

caused

by

the first phase

PCP

ofthe

is in ‘

with

AIDS

has

AIDS

of 0 to 16 percent

clinicians

increasingly

in these

failure

have

been

care

rates of 36 PCP and The

out-

come could not be predicted by clinical factors.9’#{176} Moreover, the APACHE II classification as a measure of severity in PCP

of illness patients

grossly

requiring

underestimates intensive

care

BAL. values

1-7

and

However,

and

concomitant four survivors

than two times mycobacterioses,

non-Hodgkins

than

outcome

factors. with

lymphoma.

neutrophils

concomitant bacterial infections (data not shown). To overcome

The

present

factors, combining

This

may

In our study serum LDH

in the

be

group, levels

prospective

study

BAL

fluid,

could be documented the influence of these

we created these three

the PCP parameters.6 confirms

13 who

survived

This

study

severity the

prog-

nostic value of this score. A PSS >7 had a positive predictive value for early fatal outcome of66.7 percent and a negative predictive value of 98.8 percent. The overall diagnostic accuracy was 95.7 percent. Therefore, a P55 >7 reliably predicts adverse outcome in an individual patient. A drawback of the present study may be the fact

cases

received

mechan-

of advanced

this

approach.

was conducted

with

before

suggesting

that

ever, group

AIDS

or

however, aggressive

the publication mortality

is reduced by adjunctive Therefore, only eight

population

received

How-

a too favorable outcome. 1.2 percent (1/85) in the

Since group of

represent a subset from corticosteroid

The Consensus Conference of the of Health-University of California states

that

patients

with

a P(A-a)02 25

P(A-a)02

side

was

effects

Hg this

should

have

patients

However, using a PSS >7 as therapy, only nine patients The only patient who died

32

corticosteroid treatment remains to be proved.13 deleterious

mm

Applying

and had a PSS s7 would not have been the criteria of the Consensus Conference his

National Expert

>35 16

group,

received corticosteroids. indication for corticosteroid would have been treated.

cause

therapy patients

corticosteroids.

patients with a PSS 7, this may of patients that does not benefit

Panel

of mod-

only four patients in the surviving with steroids reduces the bias of a

predicting was only

therapy. Institute

from

1315

the fact that were treated

P55 7 mortality

short-term

study

the allow

1

therapy with corticosteroids and mechanical ventilation may well improve the prognosis in patients with a high PSS as illustrated by our patient with a PSS of

to our

not

13

12

the patient’s refusal. These circumstances, represent daily clinical practice. Early

cut-off

normal suffeed from extrapulcerebral toxoplasmosis, or In five ofour survivors with

10 percent

concomitant score (P55)

.

PCP

percent

in

11

because

corticosteroid

between

does

severe either

receive

(44.3

overlap

not all of the

B

4

should

of neutrophils

nonsurvivors

of the individual

due to several for instance,

more

percentage

a considerable

in survivors

the prediction

greater monary

the

1 1

1

1

mortality

predicted vs 86.6 percent 12 Thus, a new score system for severity of PCP is urgently needed. As shown by the present study, the most important prognostic factors for PCP are the serum LDH level, P(A-a)O2,

10

ventilation

in our study to

However,

reported.#{176}

9

erate to severe PCP with corticosteroids.

series,

ICU

8

ical

trials

changed

A and

ofGroup

Patients

that

The

epidemic

declined

during the second phase from 1985 to 1987.8 in the past three years, improved survival to 50 percent for AIDS patients with respiratory

This et

all potentially life-extending treatments because of lack of data. In response rates

and

group.

of Brenner

care

failure

to 1984), pursued

study

findings

intensive

During

patients

the

in

1

GroupB

and

(P55)

mm

Hg.

in mild Moreover, such

treated using either beThe

benefit

to moderate steroids may

as an increased

of PCP have

incidence

of herpes simplex 13 disseminated tubercu17 and accelerated clinical progression of Kaposi’s 18 Therefore, a PSS >7 predicting unfavorable outcome of PCP far better (mortality 66.7 percent) than a P(A-a)02 >35 mm Hg (mortality 24 percent) might serve as a cut-off for the indication of corticosteroid therapy. However, this has to be confirmed in a prospective patients had

study, because three a PSS 7 but received

ofa

>35

P(A-a)O2

In conclusion, the severity decision ulations would

mm

surviving because

Hg.

this prospective

score

of our steroids

for PCP

study

is a valuable

confirms tool

that

for clinical

making and the selection of patient subpopwith a prognostic unfavorable course that most probably benefit from innovative thera-

peutic as a method

Moreover, the comparing patient

19

for

CHEST

I 102

PSS might populations

I 4 I OCTOBER,


1992

serve and 1047

assuring

PCP

similar

severity

in HIV-infected

of illness

in future

studies

on

11 Montaner

J, Ruedy

immunodeficiency 12

1 Brenner Lane

M, Ognibene F, Lack E, Simmons T, Suifredini A, H, et al. Prognostic factors and life expectancy of patients

with

acquired

immunodeficiency

pneumonia.

carinii

2 Garay

syndrome

Am Rev Respir

J.

5, Greene

Prognostic

and

Dis 1987;

indicators

immunodeficiency

syndrome.

13

initial

Arch

Intern

quired

Med

G,

Hashimoto

C,

implications

of bronchoalveolar

Dickmann

P. Foutty

C.

pneumonia.

carinii

6 Speich score

Chest

1988;

,

White

Pneumocysti.s

D.

Serum pneumonia.

carinii

dehydrogenase Am

Rev

levels

Respir

Dis

TurnerJ,

Volberding

P, Hopewell

carinii

Respir

1048

respiratory

failure.

Chest

16

R, Russi M, Bloch D, Hopewell pneumonia

and

Dis 1991;

143:251-56

respiratory

P. LuceJ.

the

acquired

failure

Am

Rev

Kemper

C, with

the

in

J Med

EngI

ac1990;

M,

Baier

H,

therapy

Kirskey

for

0,

La Voie

L.

Pneumocystia

severe

immunodeficiency

syndrome.

LM,

Levitt

N,

Belzberg

prevent

severe

early

A, Schechter deterioration

carinii

Pneumocystis syndrome

in

pneumo-

(AIDS).

Ann

113:14-20

Consensus

statement

therapy

for

on

the

Pneurnocystis

immunodeficiency

use

of corticosteroids pneumonia

carinii

syndrome.

N

in the

J Med

EngI

1990;

323:1500-04

N, Hermans

for Pneumocystis

J Med

Engl Gill

AM

PS, .

P. Corticosteroids

carinii

pneumonia

as adjunctive in patients

therapy

with

AIDS.

N

1991; 324:1666-67

Loureiro

Clinical

C, Bernstein

effect

to the acquired

M, Rarick

ofglucocorticoids

MU,

Sattler

on Kaposi

immunodeficiency

F, Levine

sarcoma

syndrome

(AIDS).

of

respiratory

related

Ann

Intern

Med 1989; 110:937-40 19

Miller

R,

patients

Mitchell

with

Pneumocystis

20

in AIDS.

AIDS

treatment

pneumonia N

immunodeficiency

1990;

T

acquired

P Intensive

Pneumocystis

with D,

adjunctive

carinii

Corticosteroids

moderately

Med

National

Lawson

J.

with

Intern

1988;

96:862-66

1989;

ofpatients

syndrome.

in the acquired

JSG,

nia and

and

care of patients with the acquired immunodeficiency syndrome: outcome and changing patterns of utilization. Am Rev Respir Dis 1986; 134:891-96 9 Friedman Y, Franklin C, Rackow E, Weil M. Improved survival in patients with AIDS, Pneumocystis cartnii pneumonia, and 10 Wachter

Montaner patients

18 R, LuceJ,

systemic

J Med 1990; 323:1444-50

as adjunctive

137:796-800

severe

15

93:60-4

lactate

for

96:857-61

A, Gluckstein

early

Pneumocystss

A, Fischl

pneumonia

17 Clumeck M

of

as adjunctive

MT. Ruedy

57:259-63

8 Wachter

5, Boota

carinii

R, Weber R, Kronauer C, Opravil M, Russi E. Prognostic for Pneuinocystis carinii pneumonia. Respiration 1990;

7 Zaman

J, Wu

trial

for

Corticosteroids

neutrophilia

in patients with Pneurnocystis carinii pneumonia and AIDS. Am Rev Respir Dis 1989; 139:1336-42 5 Smith R, El-Sadr W, Lewis M. Correlation of bronchoalveolar lavage cell population with clinical severity of Pneurnocystis

1989;

role

92:1335

323:1451-57 14 Gagnon

1987;

L, Cobb

lavage

Prognosis

immunodeficiency

N Engl

Prognostic

M.

F, Chiu

A controlled

potential

1987;

Chest

care.

5, Sattler

al.

a

Chest

5, Lewis

intensiye

corticosteroids presenta-

147:1413-17

4 Mason

R, Levine

Bozette et

136:1199-206

in the

Smith

[abstract].

requiring

Pneumocystss

tion of Pneurnocystis carznii pneumonia. Chest 1989; 95:769-72 3 Kales C, Murren J, Tones R, Crocco J. Early predictors of inhospital mortality for PneurnocystLc carinii pneumonia in the acquired

syndrome:

corticosteroids

REFERENCES

J, Lawson L. Acute respiratory failure carinii pneumonia in the acquired

to Pneurnocystis

secondary

patients.

the carinii

Siegel

R,

carinii

pneumonia

1988;

Yoo

D.

Management

acquired

immune

pneumonia.

Thorax

0. Therapeutic in patients

deficiency

lavage with

1990; for

AIDS.

failure

in

syndrome 45: 140-46

Pneumocystia

severe Am

and

Rev

Respir

Dis

137:A496

Prognostic

Score

for PCP


in HIV-infected

Patients

(Speich

et a!)

Prospective evaluation of a prognostic score for Pneumocystis carinii pneumonia in HIV-infected patients. R Speich, M Opravil, R Weber, T Hess, R Luethy and E W Russi Chest 1992;102; 1045-1048 DOI 10.1378/chest.102.4.1045 This information is current as of July 10, 2011 Updated Information & Services Updated Information and services can be found at: http://chestjournal.chestpubs.org/content/102/4/1045 Cited Bys This article has been cited by 3 HighWire-hosted articles: http://chestjournal.chestpubs.org/content/102/4/1045#related-urls Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.chestpubs.org/site/misc/reprints.xhtml Reprints Information about ordering reprints can be found online: http://www.chestpubs.org/site/misc/reprints.xhtml Citation Alerts Receive free e-mail alerts when new articles cite this article. To sign up, select the "Services" link to the right of the online article. Images in PowerPoint format Figures that appear in CHEST articles can be downloaded for teaching purposes in PowerPoint slide format. See any online figure for directions.
