STUDY TITLE POPULATION INTERVEN- COMPARISON OUTCOME SENSITIVITY KEY FINDINGS LIMITATIONS

TION SPECIFICITY
The Utility of identified all pa- compared (1) the Comparison of The mean pleural sensitivity of 78% Patients with con- The high local
Pleural Fluid Lac- tients with either LDH/ADA ratios, the pleural fluid LDH/ADA specificity of firmed pleural TB TB burden poten-
tate Dehydroge- a definitive diag- (2) the absolute LDH/ADA ratios, ratio was lower in 90% had significantly tially limits the
nase to Adeno- nosis of pleural ADA levels, (3) ADA levels, and patients with higher pleural applicability of
sine Deaminase TB (with micro- the presence of an lymphocyte pre- pleural TB than ADA levels than our suggested
Ratio in Pleural biological or his- ADA level ≥40 dominance of a alternative diag- those with alter- cutoffs to similar
Tuberculosis tological confir- U/L, (4) the pres- prospectively col- noses. native diagnoses high incidence
mation) or a de- ence of LPEs lected cohort of but comparable populations.
finitive alterna- with an LDH/ patients with The area under LDH levels
tive diagnosis ADA ratio ≤10, proven pleural the receiver oper- Only patients re-
and (5) the pres- TB to those with ating characteris- The pleural fluid ferred to a tertiary
ence of LPEs a definitive alter- tic curve was 0.92 ratio of LDH/ facility were in-
Cases categorized with an ADA native diagnosis for LDH/ADA ra- ADA was signifi- cluded in this
as “nonspecific level ≥40 U/L of tio and 0.88 for cantly lower in study
chronic pleuritis” patients with a an ADA ≥40 U/L patients with
on histology had definitive diagno- alone. pleural TB than Only studies from
been subjected to sis of pleural TB alternative diag- low incidence set-
medical thora- to those with an noses tings would be
coscopy and fol- alternate diagno- able with a high
lowed up for at sis. NPV that might
least 6 months to be used to rule
confirm lack of out pleural TB
clinical and radio-
logical progres-
sion
Diagnostic utility Patients with Adenosine Deam- Serum adenosisne The mean serum Using the lowest Measurement of
of adenosine pleural effusion inase activity was deaminase acitiv- ADAactivity was cut off value for ADA in TB pleu-
deaminase activ- assayed in pleural ity were measures significantly ini- enzyme activity ral effusion has a
ity in pleural fluid fluid and serum in pulmonary tu- creased in pa- in the serum of utility in the diag-
and serum of tu- of subjects with berculosis pa- tients with tuber- patients with TB nosis of TB when
berculous and pleural effusion. tients without cular pleural effu- pleural effusion other clinical lab-
non-tuberculous pleural effusion sion compared to (25 IU/L) oratory test are
respiratory dis- and healthy con- pulmonary tuber- Sensitivity negative
ease patients trols without sys- culosis without 72.41%
temic diseases for pleural effusion, Specificity
comparative anal- those with non- 81.53%
ysis TB respiratory
disease and Using the lowest
healthy control. cut off value for
enzyme activity
in pleural fluid of
patients with TB
pleural effusion
(45 IU/L)
Sensitivity
76.10%
Specificity
1000%
Diagnostic value Nontuberculous All pleural fluid Total ADA was The ADA levels The negative pre- Adenosine deam- In areas where
of adenosine lymphocytic samples were se- determined by in notuberculous dictive value of inase1/adenosine the prevalence of
deaminase in pleural fluid sam- lected from all Blake-Berman lymphocytic ADA for the di- deaminasep cor- disease is low,
nontuberculous ples (malignant, nontuberculous method. pleural effusions agnosis of TB rectly classified there is a higher
lymphocytic idiopathic, parap- lymphocytic seldom exceed was 99% all nontubercu- likelihood of
pleural effusions nerumonic, post pleural fluids col- ADA1 is deter- the cut off set for lous lymphocytic false-positive test
coronary artery lected from pa- mined by Cari- tuberculous effu- The sensitivity pleural effusions results, and this
by pass graft tients who under- laos-Gakis sions. and specificity of with high adeno- can lead to the
surgery, miscella- went thoracente- method ADA depends on sine deaminase unnecessary ad-
neous exudative, sis. Diagnostic The pleural fluid the prevalence of levels. ministration of
rransudative effu- confirmation in The lab cut off ADA levels were tuberculosis in antituberculous
sion TB pleural effu- for TB pleural ef- significantly the population. the measurement therapy or a delay
sion was obtained fusion in >40 and higher in different of the pleural in making an al-
thru ID of MTB cut off for types of exuda- fluid ADA level ternative diagno-
in pleural fluid ADA1/ADAp is tive effusions is an excellent sis such as malig-
and/or bipsy or <0.42 than in transu- test to rule out a nancy.
by the presence dates. tuberculous aeti-
of necrotising ology of lympho-
granulomas An ADA level cytic pleural effu-
<40 virtually ex- sions, irrespective
cluded a diagnop- of the rate of
sis of TB on lym- prevalence of the
phocytic pleural disease.
effusion
Impact of age on Patients with Pleural fluid sam- Comparative Younger age and The predictive The diagnostic Single center
the diagostic proven Transuda- ples for measure- characteristics of high pleural fluid value of pleural yield of pleural study that in-
yield of four dif- tive Pleural effu- ments of patients with dif- ADA level are as- fluid ADA level fluid ADA might cluded moderate
ferent biomakers sion biomarker levels ferent underlying sociated with for TP decreased be affected by pa- number of pa-
of tuberculous 1. Postive cul- during 1st or 2nd causes of pleural very high proba- with patients age tient’s age. This tients
pleural effusion ture for MTB thoracentesis. effusion in term bility of TP. This and the highest pnenomenon is
in pleural ACtivity of ADA sof their age and 39 probability probablity of TP associated with The number of
fluid or pleu- and INF- gamma, the level of four significantly de- was found in pa- the need to appy a patients may have
ral biopsy IP10 and sFasL evaluated pleau- creases not only tients younger hiher ADA ci=ut been too low to
2. Positive concentartion ral fluid biomark- with decreasing than 40 years off values in obtain an ade-
smear of were measured. ers. pleural fluid with ADA levels younger patients. quate statistcal
pleural fluid ADA, but also b/n 75 and 100. power of calcula-
and positive with increasing IN low/intermedi- tions
result of age. ate TB incidence
NAAT for 40 Patient’s age settings, a young
MTB com- does not affect patient’s age and
plex the diagnostic a high pleural
3. Caseating yield of pleural fluid ADA level
granulomas fluid IFN-γ, IP-10 are associated
in pleural and sFas. with very high
biospy or probability of TP.
positive mir-
cobiological
results of res-
piratory sam-
ples
Diagnostic Accu- Assay of total Pleural fluid sam- There was no sig- The results the results must
racy with total ADA in pleural ples were col- nificant differ- demonstrate that be interpreted in
adenosine deami- fluids in a popu- lected from con- ence in the pro- P-ADA is a use- consideration of
nase as a lation based co- tinuous untreated portion of either ful biomarker to the several crite-
biomarker for dis- hort study. Pleu- indi- viduals with sex between the differentiate exu- ria proposed in
criminating pleu- ral fluid samples PES due to vari- transudate and dates from transu- the literature for
ral transudates collected from ous causes. exudate groups. dates. selecting an opti-
and exudates in a untreated individ- mal cut-off point
population based- uals with Pleural Pleural fluid The optimum cut- of a biomarker in
cohort effusion syn- ADA activity was off point in the ROC curve space.
drome due to sev- evaluated ROC curve was
eral causes. determined as the The cut- off value
level that pro- for diagnosis of
vided the maxi- pleural exudate
mum positive and transudate
likelihood ratio must be applied
and was 22.0U/L. to a sample popu-
lation similar in
demographic
characteristics,
prevalence of
PES causes, and
P-ADA assay
method.

no universal cut-
off value exists
for a diagnostic
biomarker
Determination of All patients with Retrospective, The best cut-off In patients under Low test yield,
the ADA value in pleural effusion cross sectional point obtained for 40 years old the prolonged wait-
pleural tuberculo- except those with study ADA was 52 U/l, best cut-off point ing time for crop
sis positive serology They were with a sensitivity was 41 U/l, below results or the use
for HIV and tran- grouped into the of 79% and a that obtained for of invasive tech-
sudates. following diag- specificity of the total study niques.
noses: TB, neo- 90%. population. In our
They were plasm, parapneu- population the
grouped into the monic or other In the subgroup cut-off point for
following diag- with an unclear of patients aged the ADA value in
noses: TB, neo- cause. ADA de- 40 or older, the pleural exudate
plasm, parapneu- termination and best cutoff point for the diagnosis
monic or other culture for my- for the ADA of tuberculosis of
with an unclear cobacteria were value was 53.5 52 U/l presents
cause. performed on all with a sensitivity the highest speci-
samples of pleu- of 79% ans speci- ficity and sensi-
ral fluid ficity of 92% tivity.

Under age of 40,

an ADA value of
41 u/l showed a
sensitivity of 89%
and specidicity of
76%
Optimising the patients with ex- Single center ob- The diagnosis of When analysis We established a Size of the study
utility of pleural udative pleural servational pre- analysed patients was restricted to local pfADA cut-
fluid ADA for the effusion and other sooective study of included TPE, TPE patients, the off of 29.6 U/L Misclassification
diagnosis of tu- causes patients with ex- malignancy, para- local pfADA cut- for TPE. Optimis- bias
berculous pleural udative pleural pneumonic effu- off is 29.6 U/L, ing the utility of
effusion effusion and sion and other with a sensitivity pfADA helps to Information bias
PfADA. causes. of 97.6% and enhance clini-
specificity of cians’ treatment
The mean pfADA 90.4%. confidence of
was 51.15 U/L TPE when initial
among TPE The current work-up is incon-
group and 18.86 pfADA of 40 U/L clusive.
U/L among non- has a sensitivity
TPE. When anal- of 87.8% and
ysis was re- specificity of
stricted to TPE 92.3%.
patients, the local
pfADA cut-off is
29.6 U/L

ADA is a useful diagnostic Investigated the sensitivity and pleural ADA ac-
biomarker to di- utility of pleural diagnostic utility specificity were tivity could be in-
agnose pleural ADA using a ret- of pleural ADA 97.1% and tegrated in the di-
TB in low to rospective analy- using a retrospec- 92.9%, agnostic
medium preva- sis of patients ad- tive analysis of procedures of pT
lence settings mitted with newly patients admitted in low to medium
diagnosed with newly diag- tuberculosis
pleural effusion nosed pleural ef- prevalence set-
without identified fusion without tings.
etiology identiofied etiol-
ogy in paris
Diagnostic value 56 adult patients Prospectie Cross- Primary outcome: Sensitivity: ADA: high sensi- Continuation of
of Adenosine with exudative sectional study to diagnose tuber- 83.30% tivity, high speci- this stidy on a
Deaminase in Tu- pleural effusion Pleural fluid culous pleural ef- Specificity: 94% ficity and high bigger sample to
berculous Pleural admitted in a ter- drainage: thora- fusion using the negative predic- further strengthen
Effusion among tiary hospital centesis or pigtail ADA test as well tive value in diag- the data
adult patients in a from may 2020- cathter insertion as computing for nosis of clinically
tertiary hospital march 2021 Pleural fuid anal- its sensitivity and diagnosed tuber- Further stidues to
in the Philippines ysis: light’s crite- specificity culous pleural ef- evaluate ADA in
ria, microbiologic fusion correlation with
and ADA Secondary out- pleural biopsy for
Sputum TB gene come: to correlate International data the detection of
xpert and TB cul- the significance on pleural fluid MTb
ture of ADA test with (TB pleuritis)
Correlation of other aspects (mi- ADA 40 u/L vs Follow up on the
ADA and clinical crobiologic, radi- Local setting nor- respondents who
signs and symp- ologic, physio- mal value of were clinically di-
toms chemical and ADA in St. Lukes agnosed with TB
clinical presenta- 0-30 U/L pleural effusion
tion) in diagnos- and who are
ing tuberculous Pleural fluid started on TB
pleural effusion ADA values >30 medications (sub-
U/L were signifi- group analysis)
cantly associated
with clinical
symptoms of
cough, dyspnea
and fever
Predictive Role of Retrospective To evaluate cut Pleural fluid was The cut off value Senisitivity: ADA is a very 1. Included only
Adenosine Deam- analysis of 196 off values of exudative with of diagnosing 86.9% useful parameter the patients
inase for differen- patients with de- ADA with sensi- predominantly TPE was >55 u/l Specificity: for the differen- with TPE and
tial diagnosis of finitive diagnosis tivity and speci- mononuclear 86.6% tial diagnosis of MPE in dif-
Tuberculosis and of TPE and MPE ficity resukts for cells TPE and MPE, ferential diag-
Malignant Pleural the differential di- Combined ADA specifically in nosis, probles
Effusion in Tur- agnosis of MPE Conditions of >55 u/l and age Specificity: younger with a occurs in the
key and TPE in a pop- TPE diagnosis: <50 95.7% high incidence of differential
ulation with inter- 1. Necrotixing PPV: 98.8% tuberculosis diagnosis of
mediate incidence granuloma- these two dis-
of TB> tous inflam- eases in the
mation in exudative
pleural sam- lymphocytic
pling via effusion
closed biopy 2. Retrospective
or VATS study, ADA
2. MTB in the was not stud-
pleural fluid ied again in
3. No any rea- the tubercu-
son to explain lous effusions
the pleural with low lev-
fluid,ziel els of ADA
neelsen
stains, lowen-
stein culture
were psoitive
togeteher
with clinical
and radio-
logic apper-
ance suggest-
ing TB
 Diagnosis of
MPE, malignancy
in cytology of the
pleural fluid
and/or histology
of the pleural
fluid

Among patients scheduled for pleural fluid drainage, what is the accuracy of pleural fluid ADA in diagnosisng TB effusion using standard proto-
col as refence?

P: Pleural effusion for pleural fluid drainage via thoracentesis, VATS, Thoracoscopy, CTT, pigtail or pleural catheter at ER/OPD
I: Pleural fluid ADA; Standard TB Gene Xpert, TB CUlture, Cell block and cell cytology; Cinically diagnosed: Lymphocytic predominance
C:Cut off for subgroup
1. Previously treated or recurrent TB
2. Diagnosed Malignancy
3. Cut off per age
O: TB Diagnosis

Pubmed Keywords: Malignant Pleural Effusion, Tuberculous pleural effusion, adenosine deaminanses, Age, sensitivity and specificity