Pro and Con Session on bronchoscopy for
TB diagnosis
Jean Pierre Zellweger & Christoph Lange
Can we avoid bronchoscopy for
the diagnosis of TB by sputum
induction?
Sputum collection
• Many patients with TB suspicion
– Do not produce sputum
– Produce sputum in inadequate amount or quality
– Have negative smears
• The tendency is to collect sputum from the
site of disease (the lungs) , particularly if the
patient is unable to produce sputum and
bronchoscopy is available
• What can be done apart from or before
bronchoscopy to obtain adequate samples?
Spontaneous vs instructed sputum production
(1494 women and 1561 men)
Khan MS, Lancet 2007;369:1955-60
induced sputum
• Technique
– Inhalation of hypertonic saline (3%) with ultrasonic or air
compressor nebulizer (possible addition of b2 agonist)
– Inhalation of vaporized 15 % aqueous saline
• Yield
– Adequate specimen obtained in 85 to 99 %
• Indications
– Cough without sputum
– Unable to produce sputum
– Negative sputum smear with high clinical suspicion
induced sputum
Yield of induced sputum among 82 patients with
suspected TB unable to produce sputum or with
negative sputum smear
Positive smear SI Positive culture SI
No sputum
13
13
Sputum smear negative
5
17
Parry CM. Tuber Lung Dis 1995;76:72-6
induced sputum
• Among 1648 patients with suspected tuberculosis
with poor or absent sputum submitted to sputum
induction,
– 558 were smear-positive
• 353 previously sputum smear negative
• 97 inadequate sputum
• 108 unproductive cough
Li LM. IJTLD 1999;3:1137-9
induced sputum
Yield of repeated sputum induction among patients
with proven TB but unable to produce sputum
N samples
Smear + (%)
Culture + (%)
1
64
70
2
81
91
3
91
99
4
98
100
Al Zahrani K.IJTLD 2001;5:855-90
induced sputum
• Sputum induction in 30 children with suspect TB (3
to 15 years):
– 29 could bring sputum under induction
• 4 were smear positive
• 4 others were culture positive
– Sputum induction confirmed the presence of
tuberculosis in 28 % of children
Shata AM. Arch Dis Child 1996;74:535-7
TB diagnosis in 140 TB suspects with negative
smear or no sputum production
Morse M, IJTLD 2008;12(11):1279-85
Impact of sputum collection technique on the yield
of smear examination in 78 patients with C+ PTB
%
Chang KC, Eur Respir J 2008;31:1085-90
Impact of adding supervised and/or induced
sputum collection to spontaneous sputum
Chang KC, Eur Respir J 2008;31:1085-90
Sputum induction vs bronchoscopy
• Sputum induction (SI) and bronchoscopy (B) among 101
patients with suspected TB but negative sputum smear
• 26 patients had positive culture for M. tbc (5 by B only, 6
by SI only,14 in both, 1 in sputum)
• B revealed 10 lung cancers
sample
Sensitivity (%)
Neg. Pred value (%)
Bronchoscopy
73
91
Induced sputum
87
96
Anderson C, AJRCCM 1995;152:1570-4
Sputum induction vs bronchoscopy
• Prospective comparison between SI and BAL among 251
patients with suspected TB but no sputum or negative
sputum smears.
• 143 proven TB (94 by SI, 103 by BAL).
• Concordance of bacteriological results from samples
obtained by SI and BAL
concordance
discordance
smears
98 %
2%
cultures
90 %
10 %
Conde MB. AJRCCM 2000;162:2238-40
Cumulative proportion of positive cultures in TB
suspects with 5 induced sputum, 3 gastric washing
and BAL
Brown M, Clin Inf Dis 2007;44:1415-20
Yield of spontaneous and induced sputum
collection and BAL in 101 migrants suspect of PTB
Schoch O, AJRCCM 2007;175:80-6
Schoch O, AJRCCM 2007;175:80-6
Additional yield of increasingly invasive sputum
collection techniques in 150 TB suspects
Bell DJ, IJTLD 2009;13(1):99-104
Immunological diagnosis of TB (IFN- response)
in induced sputum in 42 S- TB suspects
Breen RAM, PLoS One 2007;2:e1335
clinical or radiological suspicion of pulmonary TB
cough and sputum
cough, no sputum
unable to produce sputum
(children)
no cough, no sputum
failure of sputum induction
bronchoscopy available
suspect of other disease
sputum sm ear and culture
induced sputum if sm ear negative
sputum induction
throat swab
gastric lavage
bronchoscopy and BAL
bronchoscopy with BAL
Conclusions:
• The diagnosis of tuberculosis relies on the obtention
of adequate sputum samples for microbiological
(and immunological) examination
• The yield of sputum collection can be greatly
increased by
– Instruction
– Chest physiotherapy
– Sputum induction
• More invasive and/or expensive techniques (gastric
vashings, BAL) add little to the diagnostic yield
Can we avoid bronchoscopy for
the diagnosis of TB by sputum
induction?
Here comes the truth...
• Diagnostic tools for active pTB are sputum
microscopy, -culture, -PCR, TST and IGRA
• In more than half of the patients with active pTB no
AFBs are seen on sputum stains
• The diagnostic sensitivity of rapidly available
techniques like PCR is limited in smear-negative
cases
diagnosis of active tuberculosis
ELISPOT
-
PHA
ESAT-6
CFP-10
Person A
Person B
cut-off:
>5 SFC/250.000 PBMC
sensitivity and specificity of IGRAs for the
diagnosis of active tuberculosis
TST
ELISA
ELISPOT
sensitivity
77 %
74 %
90 %
specificity
69 %
75 %
67 %
TBNET
M. tuberculosis-specific ELISPOT
isolation of mononuclear
cells
BAL-fluid
blood
antigen-specific cells
secrete IFN-
blood
Am J Resp Crit Care Med 2006
blood
BAL-F
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Eur Resp J 2008
blood
Am J Resp Crit Care Med 2009
Am J Resp Crit Care Med 2009
TB suspect
medical history, imaging studies
2 (3) x sputum examinations
microscopy
+
-
+
MTB-NAAT
likely NTMinfection
-
+
MTB-NAAT
-
likely TB
+/+, +/-
NTM specific
NAAT*
IGRA+TST
TB or LTBI
-/-, -/+
TB unlikely
culture (sputum)
Bronchoscopy#
NTMinfection
TB
likely TB, NTM
likely TB
likely TB, NTM, other
likely TB
TB
+ microscopy (BAL, TBB) + NAAT (BAL, TBB)
-
+ histology (TBB)
-
+ IGRA (BAL)
-
+ culture (BAL, TBB)
-
TB unlikely
* NTM NAAT may be helpfull, when available
# in
accordance with WHO recommendations (WHO. Treatment of tuberculosis. Guidelines for national programmes. Geneva; 2003) clinical response to
antibiotic therapy may be considered prior to further investigations, however in countries of low TB-incidence immediate further diagnosis with