Serum Lactate Dehydrogenase (LDH) in

carinii Pneumonia,
Pneumocystisand
Bacterial Pneumonia*
Tuberculosis,
Joseph Quist, MD; and A. Ross Hill, MD
An increase in serum lactate dehydrogenase (LDH)
activity is commonly taken to support the presumptive

pneumonia (PCP),
diagnosis of Pneumocystis carinii
may also be increased in other
although the LDHandlevel
of extrapulmonary
lung infections itsin a varietyvalue
in patients with
disorders. To assess diagnostic
fever, lung infiltrates, and a high prevalence of HIV
infection, we compared LDH levels in 42 hospitalized
tuberculosis
patients with PCP, 71 with disseminated
bacterial
with
and
37
with
40
TB,
(TB),
pulmonary
in
was
level
LDH
Peak
higher
(p<0.05)
pneumonia.
157 U/L) and disseminated TB
patients with PCP (547
(569 338 U/L) than in patients with pulmonary TB
(25866 U/L) or bacterial pneumonia (331 139 U/L).
However, substantial overlap between groups limited
its diagnostic value for individual patients. Expressing
ratio to simultaneous serum aminotransLDH

as

its

ferases (AST or ALT) did not enhance its discrimina

tory value. Most patients in each group had abnor
malities in other serum enzymes (AST, ALT, alkaline

TTuman immunodeficiency virus (HlV)-induced im--*

to secondary in
munodeficiency typicallyofleads
which
the
fections involving
Pneumocystis
lungs,
carinii pneumonia (PCP), bacterial pneumonia, and
[TB], fungi)
granulomatous infections (tuberculosis
are the foremost examples. Definitive diagnosis of
these infections, which may entail bronchoscopy or
culture results, is often not feasible at presen
delayed
tation. Hence there is considerable interest in nonin
vasive aids to initial presumptive diagnosis and empiric
antimicrobial therapy. PCP has been the main focus of
attention, because it is the most common opportunis
tic pneumonia complicating AIDS and because inva
sive methods are often required for diagnosis.
The serum lactate dehydrogenase (LDH) activity is
increased in more than 90% of AIDS-related cases of
PCP,1"4 but it can also be increased in other pulmo
and numerous extrapulmonary diseases.67 In
nary1,5'6
recent years, we have noted a disconcerting tendency
for physicians to rely on the LDH level to discriminate
PCP from other lung infections, even to the point of
measuring LDH without considering other serum en*From the SUNY Health Science Center and Kings County Hos
pital Center, Brooklyn, NY.

Manuscript received October 25,1994; revision accepted February

27, 1995.
Reprint requests: Dr. Hill, 450 ClarksonAve, Box 19, Brooklyn, NY

making an iso
7-glutamyltransferase),
phosphatase,
uncommon
level
LDH
lated elevation of
(21% of PCP
has
a
LDH
Serum
cases).
high sensitivity for PCP
(100% in this series) but must be interpreted with
caution given its lack of specificity.
(CHEST 1995; 108:415-18)

ALT=alanine aminotransferase; AST=aspartate ami

LDH=lacGGT=Y-glutamyltransferase;
PCP=Pneumocystis carinii pneumo
dehydrogenase;
TB=tuberculosis

notransferase;
tate

nia;

Key words: bacterial pneumonia; enzyme tests; HIV infec

tion; lactate dehydrogenase; Pneumocystis carinii pneumo
nia; tuberculosis

losis)

(pulmonary tuberculosis, miliary tubercu

zyme levels that increase concomitantly in nonpulmonary disorders. To reassess its diagnostic utility in the
infiltrates, we per
setting of a febrile illness withoflung
formed a retrospective study LDH in the three most
common HIV-associated lung infections in our com
munity: PCP, bacterial pneumonia, and TB.
Methods
of patients hospitalized for PCP, focal
samples
were drawn from records
bacterial
and
TB,
pulmonary consultations pneumonia
and from a computerized listing of
of pulmonary
Convenience

cases
diagnoses for 1991 to 1993. Consecutive
hospital discharge
there were
meeting the inclusion criteria were enteredweuntil
studied a previ
40 in each group. Additionally,
approximately
of patients with disseminated TB.8
ously described cohort
Patients were included if their medical record contained at least
two values for LDH during the acute illness as well as simultaneous
values for aspartate aminotransferase (AST) and alanine ami
notransferase (ALT). Patients were excluded if they carried a diag
nosis associated with raised serum LDH level, including erythrocyte
disorders, malignancy, liver disease, shock, rhabdomyolysis, and
renal failure. We report the highest LDH value obtained during the
first week of hospitalization, as well as the ratios of LDH to the si
multaneous AST and ALT. Most patients also had determinations
of alkaline phosphatase and 7-glutamyltransferase (GGT) per
formed within 3 days of the LDH.
The diagnosis of PCP was confirmed bybronchoscopy in all cases.
Pulmonary TB was confirmed by culture of Mycobacterium tuber
culosis from respiratory secretions. Bacterial pneumonia was diag
nosed when the patient presented with fever and focal lung
consolidation and responded to treatment with an antibiotic(s) other

CHEST /108 / 2 / AUGUST, 1995

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415

Table

1.Demographic and Clinical Data

HIV

Group*
PCP
DTB
PTB
BACT

42

71
40
37

Age>

Male,

399
3610
3711
4314

71
82
83
65

Infection, *
100

>73
>40
>41

Tldh,

4 Non-LDH

T LDH, %
(>250 U/L)

AST+ALT, %

Normal,* %

100
93
53
73

21
10
28
22

21
1
25
26

With Normal

Enzymes

DTB=disseminated TB; PTB=pulmonary TB; BACT=bacterial pneumonia.

of HIV status from medical records may be incomplete.
*AST, ALT, alkaline phosphatase, and GGT all within normal range.

* Ascertainment

than trimethoprim/sulfamethoxazole; a bacterial etiology was con

firmed by blood culture in 14 of 37 patients (38%; Streptococcus

pneumoniae in 12, Haemophilus influenzae

in 1).

Staphylococcus
Patients were considered to have HIV disease if they (1) had a
confirmed positive serologic test for HIV, (2) met the 1987 Centers
for Disease Control and Prevention (CDC) case surveillance def
inition for AIDS, or (3) had a risk factor for HIV infection together
with a CD4 count <400 cells
microliter and a CD4/CD8
in

1,

aureus

ratio
per
<1.0.
All data are presented as the meanSD. Intergroup differences
for each enzyme variable were assessed by one-way analysis of

variance followed by the Scheffe

procedure (SPSS). The relation

ship of LDH to the aminotransferases was assessed by analysis of
covariance, using AST and ALT as multiple covariates; the adjusted
LDH means were compared by the Scheffe procedure.
Results

Lactate dehydrogenase level was increased in 100%

of patients with PCP, but it was also increased in most
patients in each of the other groups (Table 1, Fig 1).
The mean values were nearly identical in patients with
PCP and disseminated TB, both groups showing
higher levels than those with bacterial pneumonia or

TB (Table 2).
pulmonary
The chest radiographs of patients with disseminated
TB showed a miliary pattern in 54%, focal lung
lesion(s) in 14%, and clear lungs in 32% at presenta
tion (intrathoracic lymphadenopathy was visible in 9 of
23 with clear lungs). There were no significant differ
ences in LDH levels at the time of the radiographs
among these subgroups (mean LDH=559, 490, and
507 respectively; p=0.71).
Among all patients combined, LDH showed inde
linear correlations with AST and ALT (r=0.66
pendent
and 0.38, respectively; p<0.01). The aminotransferase
levels together accounted for a substantial portion of
the variability in LDH (1^=0.44; multiple regression,
p<0.0001), due largely to its correlation with AST. The
mean LDH values adjusted for AST and ALT (analy
sis of covariance) remained higher in patients with PCP
(579 U/L) and disseminated TB (507 U/L) than in pa
tients with bacterial pneumonia (344 U/L) or pulmo
nary TB (326 U/L) (p<0.05). Thus the high LDH val
ues in disseminated TB were not explained solely by
injury to tissues that also release aminotransferases
proportionately, eg, liver necrosis.
416

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Since the elevation of serum LDH level in patients

with PCP is thought to occur independently from other
commonly measured enzymes, we hypothesized that
the ratio of LDH to AST or ALT would improve dis
crimination of PCP from other causes of increased
LDH. Both ratios tended to be higher in patients with
PCP than in the other groups (Table 2), but the con
siderable overlap made them unreliable for diagnosis
of PCP in individual patients (Fig 2).
Most patients, regardless of group, exhibited mild to
moderate increases of at least one enzyme other than
LDH (AST, ALT, alkaline phosphatase, GGT; Table 1,
Fig 3). In only 21% of patients with PCP was the peak
LDH level accompanied by normal aminotransferase
levels. Levels of GGT and alkaline phosphatase were
both higher in patients with disseminated TB than in
the other three groups (data not shown), probably re
flecting granulomatous lesions of liver and other

extrapulmonary sites.

Discussion
Our main finding is that serum LDH activity is in
creased in most patients requiring hospitalization for
all four conditions studied. Prior reports have sug
gested a diagnostic role for LDH in PCP but included

forms of pneumoni
relatively few patientsWewithhaveother
found LDH levels be

tis for

comparison.14

to

increased in patients with infections that sometimes

mimick PCP (or vice versa) and that frequently enter
its differential diagnosis. Thus, our results confirm the
of the serum LDH level for PCP, but
high sensitivity
its
that
suggest
specificity in this clinical setting is lim
ited.
Pneumocystis carinii pneumonia is considered to
produce an isolated elevation of serum LDH level,
the putative source,3 although
lung parenchyma
beingexamined
studies
have
not
simultaneous values of
prior
other enzymes. Lactate dehydrogenase is a ubiquitous
enzyme, and serum levels increase in a wide variety of
diseases. Some, such as hepatic, hematologic, and
neoplastic disorders, occur frequently in the setting of
AIDS. Isolated elevation of LDH level proved to be
uncommon in our patients with PCP, possibly because
background disorders such as chronic viral hepatitis or
Clinical Investigations

LDH

1750

LDH/AST

35-i

1500 H

30-

1250 H

25

u/l iooo

H
20 H

750

500

/A

10-

250

IK*
..2
DTB

BACT

PCP

PTB

Figure 1. Peak serum LD H level for individual patients in the four

.,.

groups. Horizontal line denotes the upper limit of nor

diagnostic
mal range (250 U/L). DTB=disseminatedTB;
TB;

DTB

PTB=pulmonary

BACT=bacterial pneumonia.

liver often coexist and contribute to enzyme ab

fatty
normalities.
Clinicians are familiar with mild elevations of serum
LDH levels in cases of non-PCP pneumonia. In bac
terial pneumonia the injured lung might be the source,
but the concomitant abnormalities in "liver enzymes"
suggest that alternative mechanisms may often play a
role, such as the hepatic dysfunction associated with
bacterial sepsis9 and/or other coexisting disorders.
To our knowledge, LDH in TB has not received
emphasis in the literature. Tissue necrosis, a charac
teristic feature of tuberculous granulomas, provides a
ready explanation for elevated LDH values. Necrosis
was observed in most tissue samples from disseminated

BACT

PCP

PTB

Figure 2. Ratio of peak LDH level to simultaneous AST in indi

vidual patients. Horizontal lines indicate mean values.

cases8 and was no doubt usually present in pulmonary

well, as evidenced by radiographic cavities in

third of patients. Frank necrosis of lung (or other
organ) parenchyma may not be required to raise the
serum LDH level, however/ as suggested by the ex
amples of PCP and pulmonary alveolar proteinosis,5 in
which lung architecture is often preserved.
Patients with localized pulmonary TB had normal or
increased LDH levels, never exceeding 400
mildly
U/L. Patients with disseminated TB often showed
striking elevations of LDH, exceeding 500 U/L in 41%.
The higher levels in disseminated TB might reflect a
greater total-body burden of tuberculous lesions,
cases as
a

Table 2.Serum Enzyme Activities in Units per Liter (MeanSD)*

PCP (n=42)
DTB (n=71)
PTB (n=40)
BACT (n=37)

LDH

AST

ALT

LDH/AST

LDH/ALT

547157
569338
25866
331 139

6534
118117
4533
7685

4441
6564

10.45.6
6.84.0
7.94.2
8.47.1

21.216.3
13.313.8
11.710.4
15.818.1

3522
4744

* DTB=disseminated
TB; PTB=pulmonary TB; BACT=bacterial pneumonia.
Normal ranges: LDH 80-250, AST 0-40, ALT 0-40.
Statistical differences (ANOVA, Scheffe procedure, p<0.05):

LDH: PCP, DTB>PTB, BACT.

AST: DTB>PCP, PTB.
ALT: DTB>PTB.
LDH/AST: PCP>DTB.
LDH/ALT: PCP>PTB.

CHEST / 108 / 2 / AUGUST, 1995

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417

value in individual patients. While its positive predic

tive accuracy would improve if one took twice the up
per limit of normal (500 U/L) as the diagnostic
threshold, this would greatly reduce its sensitivity (Fig
1), especially for cases that are not full-blown radioA prospective study is needed to deter
graphically.
mine whether knowledge of the serum LDH level
a clinician's
substantially improves the accuracyourof data
caution
Meanwhile,
presumptive diagnosis.
in
level
alone
LDH
on
the
undue
reliance
against
A
serum
normal
a
impression.
forming diagnostic
LDH level may be useful in excluding PCP (at least in
cases with definite lung infiltrates), but elevated values
remain nonspecific and must be interpreted with due
consideration of coexisting diseases and other serum
enzyme abnormalities.

AST

550 i
500
450

400

350-j
U/L

300-1
250

200 H
150

100

50
0

ACKNOWLEDGMENT: The authors gratefuUy acknowledge the

contributions of Drs. Reuben Margolis and Eva Chan to the statis

.ar

A
$ 1-

PTB
DTB
PCP
BACT
Figure 3. Serum AST level simultaneous with peak LDH level for
individual patients in the four diagnostic groups. Horizontal line
denotes the upper limit of normal range (40 U/L).

greater access of LDH to the circulation from small

of certain extra
miliary lesions, a greater propensity bone
liver,
marrow) to
spleen,
pulmonary organs (eg,
release LDH when involved, or other unidentified
factors. LDH values exceeding 1,000 U/L were ob

served only in patients with disseminated TB and were

a sign of poor prognosis: 6 of 11 died. Such extreme
elevations of LDH level probably reflect the wide
spread necrotizing lesions of overwhelming miliary
disease.
In our experience, the initial working diagnosis of
acute lung disease in patients with known or suspected
HIV infection is guided by clinical observations but
rests mainly on the pattern of radiographic abnormal
ity. This study does not permit a formal estimate of the
specificity or positive predictive accuracy of LDH level
in diagnosing PCP, but suggests that LDH, like
hypoxemia, is too nonspecific to hold discriminative

418
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tical analyses.

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Clinical Investigations