Bronchoalveolar Lavage to Diagnose

Respiratory Infections
Paula Ramı́rez, M.D.,1 Mauricio Valencia, M.D.,2 and Antoni Torres, M.D.2

ABSTRACT

Respiratory samples obtained by bronchoalveolar lavage (BAL) in infectious

processes provide important microbiological and cytological information to manage this
type of patient. Most of the clinical and experimental BAL investigations have been done in
ventilator-associated pneumonia (VAP) and in immunosuppressed conditions. The impact
of quantitative BAL bacterial cultures for managing VAP is still controversial. However,

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there is no doubt that this method provides sensitive and specific information on bacterial,
viral, fungal, and noninfectious etiologies. The conclusion is that BAL has to be used in
VAP depending on the clinical situation of the patient and taking into account the local
expertise and laboratory facilities. In immunosuppressed patients with pulmonary infiltrates
its utility has been clearly demonstrated. In this specific population the early use of the
information provided by this method is related to a better outcome. In community-acquired
pneumonia there is no strong information supporting its use. This technique has some side
effects and contraindications that have been weighted individually in each patient.

KEYWORDS: Bronchoalveolar lavage, ventilator-associated pneumonia,

immunosuppressed, pulmonary infiltrates

T he microbiological diagnosis of infection of the
pulmonary parenchyma is fundamentally based on the
analysis of samples from the bronchial tree. Bronchoal-
veolar lavage (BAL) obtained by fiberoptic broncho-
scopy (FOB) is a representative respiratory sample of the
process located in the alveoli, the nature and volume of
which allow correct cytological and microbiological
study. The clinical application of BAL is that of an
invasive diagnostic test with its consequent risks and
must be performed with the appropriate technology and
by trained personnel. The systematic use of this test in
community-acquired pneumonia is not, as yet, justi-
fied,1–3 and nosocomial pneumonia has not been studied
as an independent entity of mechanical ventilator-asso-
ciated pneumonia (VAP). From a health care and
investigational point of view, BAL has been applied in
VAP and in the etiologic diagnosis of pulmonary infil-
trates in immunosuppressed patients. This review ana-
lyzes the diagnostic performance of BAL and the
possible adverse effects, and discusses whether its use is
essential in the diagnosis of these diseases.
BRONCHOALVEOLAR LAVAGE IN THE
DIAGNOSIS OF MECHANICAL
VENTILATOR–ASSOCIATED PNEUMONIA
Several studies have demonstrated that appropriate em-
pirical antibiotic treatment in VAP substantially reduces
the mortality of this disease.4–8 Adjustment of erroneous
initial treatment is not accompanied by a better patient

1
Unidad de Cuidados Intensivos, Hospital La Fe de Valencia, Valencia,
Spain; 2Servei de Pneumologia i Al
lèrgia Respiratòria, Hospital Clı́nic
de Barcelona, Barcelona, Spain.
Address for correspondence and reprint requests: Antoni Torres,
M.D., Servei de Pneumologia i Al
lèrgia Respiratòria, Hospital Clı́nic
de Barcelona, C/ Villarroel, 170, 08036 Barcelona, Spain (e-mail:
atorres@ub.edu).
Bronchoalveolar Lavage; Guest Editors, Robert P. Baughman, M.D.,
Ulrich Costabel, M.D., and Keith C. Meyer, M.D.
Semin Respir Crit Care Med 2007;28:525–533. Copyright # 2007
by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York,
NY 10001, USA. Tel: +1(212) 584-4662.
DOI 10.1055/s-2007-991524. ISSN 1069-3424.
525
 526

Table 1 Evaluation of the Diagnostic Accuracy of TBAS, PSB, and BAL in VAP in Histological Studies
TBAS PSB BAL
Sensitivity Specificity Sensitivity Specificity PPV/NPV Sensitivity Specificity
N VAP gold standard (%) (%) PPV/NPV (%) (%) (%) (%) PPV/NPV

Kirtland et al 17 39 Histology 22 77 22/77 11 80 14/75

Marquette et al18 28 Histology 55 85 57 88 47 100
Torres et al19 30 Histology 36 50 50 45
Torres et al20 25 Histology 31 55 24 54 36 59
Fabregas et al21 25 Histology þ 69 92 90/73 62 75 73/64 77 58 67/70
Bacteriology
Papazian et al22 38 Histology þ 83 80 71/89 42 95 83/73 58 95 88/79
Bacteriology
Chastre et al23 20 Bacteriology 82 89 89 78
SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 28, NUMBER 5

BAL, bronchoalveolar lavage; NPV, negative predictive value; PPV, positive predictive value; TBAS, tracheobronchial aspirate; VAP, ventilator-associated pneumonia.
2007

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outcome, even when the change is determined by a
respiratory sample obtained by quantitatively cultured
invasive methods.7,8 On the other hand, a delay in the
administration of antibiotic treatment, regardless of its
adequacy, is also associated with a greater mortality.4,6
Nonetheless, overdiagnosis of VAP and the consequent
abuse of antibiotics have been associated with the ap-
pearance of multiresistant microorganisms.9,10
Although the data presented seem to indicate that
the evolution of VAP depends on the adequacy of
empirical treatment and not on the adjustment to the
etiologic diagnosis obtained a posteriori, the most appro-
priate type of respiratory sample on which to base the
diagnostic algorithm of VAP remains controversial. Per-
haps the true value of microbiological analysis lies in the
negative result that leads to the identification of unneces-
sary treatments11,12 and points toward other possible foci
of infection.12 Discontinuation of antibiotic treatment
upon the appearance of a negative result of a BAL culture
has shown to be a safe strategy, although further studies
are necessary to corroborate this result.11,13
BAL’s usefulness in the diagnosis of VAP is not
debated.14–17 A review of 23 series analyzing the diag-
nostic utility of BAL in VAP reported mean values of
sensitivity of 73  18% and a specificity of 82  19%.
This variability in the results may be due to the differ-
ences in the type of population studied, previous anti-
biotic treatment, and the reference test used.15
Studies using histological tests as the reference to
evaluate the diagnostic usefulness of quantitative BAL
culture and other types of respiratory samples have
shown low or moderate sensitivity and specificity
(Table 1)17–23 without large differences between the
different types of samples analyzed. Indeed, cultures of
the pulmonary parenchyma seem to have a bad correla-
tion with the histological diagnosis of pneumonia. The
use of both histological and bacteriological criteria to-
gether as the reference tests improves the diagnostic
results,21,22 and the only study in which BAL achieved
optimal qualifications as a diagnostic test was biased by
the choice of the positive pulmonary parenchyma culture
being the only reference test.23 The results of histological
studies are limited by numerous factors, such as their use
in patients without clinical suspicion of VAP, the lim-
itation in VAP in patients in whom the final outcome is
death, the lack of uniformity in the histological diag-
nostic criteria, and the interference of previous antibiotic
treatment.24
The greatest risk in performing BAL is the
deterioration in gas exchange, the intensity and reversi-
bility of which vary greatly among different authors.25–27
Alterations in hemodynamic parameters or the induction
of systemic inflammatory response is much more infre-
quent.28,29 Thus the use of BAL by FOB is a procedure
that carries certain risks whose prediction has not, to
date, been studied.
BAL TO DIAGNOSE RESPIRATORY INFECTIONS/RAMÍREZ ET AL 527
Invasive versus Noninvasive Techniques
The need to undertake invasive techniques for obtaining
respiratory samples was first questioned at the beginning
of the 1990s.30 Numerous studies have compared in-
vasive versus noninvasive methods, and a wide percent-
age of studies did not observe significant differences in
regard to diagnostic capacity.30–33 In a prospective,
multicenter study on the use of sucralfate versus raniti-
dine, Heyland et al performed a subanalysis in a series of
patients with clinical suspicion of VAP. FOB was
performed in 94 cases and in 49 it was not undertaken.
No differences were found in regard to the length of
mechanical ventilation or intensive care unit (ICU) stay,
but in the group undergoing FOB, the number of anti-
biotics used and the percentage of discontinued treat-
ments were greater (18/92 vs 3/49, p ¼ .04). The
mortality was greater in patients in whom FOB was
not performed (34.7% vs 18.5%, p ¼ .03); however, it
should be pointed out that the percentage of patients
with inadequate empirical treatment in each group was
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not specified.34
The importance of the question regarding both
the specific case of each patient as well as in patient
health care management led five different work groups to
undertake prospective, randomized, controlled studies to
compare samples obtained by invasive versus noninvasive
techniques (Table 2).12,35–38 The three Spanish studies
compared quantitative bronchial aspirate (qualitative in
the case of Sole-Violan et al) with quantitative BAL 
protected specimen brush (PSB).35–37 The proportion of
inadequate empirical treatment was similar in the two
study groups of the three research groups. The results
coincide in that there were no differences in mortality,
duration of mechanical ventilation, and ICU stay. In two
studies the percentage of treatments modified according
to the diagnostic results was greater in the patients
undergoing FOB.35,36 The French study included a
much higher number of patients (413) and compared
qualitative cultures of tracheal aspirates with quantitative
cultures of samples obtained by FOB. Although no
differences were observed in the duration of mechanical
ventilation or ICU stay, there were differences in regard
to mortality at 14 days of evolution. Multivariate analysis
identified not undergoing FOB as a risk factor for
mortality at 14 and 21 days. However, the proportion
of patients with inadequate empirical treatment was
much higher in the group not undergoing FOB
(11.4% vs 0.4%; p < .001). The possible causes of this
difference and the adequacy of empirical treatment were
not variables included in the multivariate analysis. The
reduction or discontinuation of antibiotic treatment was
much more frequent in the group receiving invasive
management (number of days without antibiotic at
14 days, 5  5.1 vs 2.2  3.5, p < .001). On the other
hand, negativity of BAL results led to the search for and
the finding of other infectious foci more frequently than
 528

Table 2 Clinical Trials on the Use of Bronchoalveolar Lavage versus Noninvasive Methods in the Diagnosis of Ventilator-Associated Pneumonia
MV Duration ICU Length of % Patients with
N Noninvasive Invasive Inadequate X-ray (%)a Mortality (%) (days) Stay (days) Changed X-rayb

Sole-Violan et al35 91 Qualitative TBAS PSB þ BAL 2 vs 9 p ns 20.9 vs 22.2 p ns 19  3 vs 22  3 vs 12 vs 33 p < .05
43 45 20  3 p ns 24  3 p ns
Sanchez-Nieto et al36 51 Quantitative TBAS PSB þ BAL 16 vs 37 p ns 26 vs 46 p ns 20  17 vs 26  18 vs 16 vs 42 p < .05
27 24 23  12 p ns 28  17 p ns
Ruiz et al37 76 Quantitative TBAS PSB þ BAL 18 vs 28 p ns 46.1 vs 37.8 p ns 20  24 vs 21  18 vs 18 vs 27 p ns
39 37 19  15 p ns 21  15 p ns
Fagon et al12 413 Qualitative TBAS PSB or BAL 11.4 vs 0.4 p < .001 38.8 vs 30.9 p ns 20  10 vs 18  9 vs
209 204 21  9 p ns 19  9 p ns
Heyland34 740 Qualitative TBAS BAL 10 vs 20 p ns 18.4 vs 18.9 p ns 8.8 (7–10.7) vs 12.2 (11–14.2) vs 74.6 vs 74.2 p ns
374 365 8.9 (7.4–10.7) p ns 12.3 (11–13.8) p ns
a
Percentage of patients with inadequate empirical antibiotic treatment.
SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 28, NUMBER 5

b
Changes in the antibiotic treatment because of the result of the microbiological analysis.
BAL, bronchoalveolar lavage; ICU, intensive care unit; MV, mechanical ventilation; ns, not significant; PSB, protected specimen brush; TBAS, tracheobronchial aspirate.
2007

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in tracheobronchial aspirate (TBAS) negative cases
(p < .001); thus the authors underlined the importance
of the negative results of quantitative BAL cultures.12
A meta-analysis of these four studies emphasized
the differences present, particularly with respect to the
type of culture of the noninvasive sample and the bias of
the work by Fagon et al with respect to the percentage of
patients with inadequate empirical treatment. This meta-
analysis concluded that obtaining respiratory samples by
invasive techniques does not achieve a substantial change
in patient outcome but does positively affect the exclusion
of VAP and correct antibiotic management.39
Heyland et al recently presented the results of a
multicenter study in 740 consecutive cases with clinical
suspicion of VAP.34 Unfortunately, this study had two
important limitations: the choice of qualitative cultures
for the noninvasive sample and the exclusion of patients
with a high risk of colonization by Pseudomonas spp. or
methicillin-resistant Staphylococcus aureus. This latter
exclusion criterion led to the elimination of 40% of the
patients evaluated, thereby making it difficult to extrap-
olate the results to a real population.40 The authors did
not find significant differences in regard to mortality,
ICU stay, or duration of mechanical ventilation. The
percentage of patients with inadequate empirical treat-
ment was similar in both groups, but the waiting time
until the initiation of empirical treatment was greater in
the group under invasive management (p < .001).
Direct Vision of Bronchoalveolar Lavage
BAL allows cytological evaluation that identifies the
samples with a high probability of contamination
(> 1% of epithelial cells).41 The diagnostic value of
Gram staining in BAL has been evaluated by several
authors who agree in the observation of a moderate
sensitivity (47 to 54%) and a high specificity (87 to
100%).18,42,43 Other specific stains for microorganisms
less frequently associated with VAP are more useful in
immunosuppressed patients.
The cutoff point in the detection of intracellular
organisms (ICOs) remains to be established, and the
good results found with respect to sensitivity and spe-
cificity (86 to 94% and 79 to 91%, respectively)44–46
should take into account the possible interference of the
use of antibiotics and the previous duration of mechan-
ical ventilation.42
Quantification of the Bronchoalveolar Lavage
Culture
The quantification of the culture of the respiratory
samples is based on the capacity to discriminate between
contamination and infection.47 The cutoff for BAL is
104 or 105 colony-forming units (CFU)/mL with a good
diagnostic performance that has been demonstrated in
BAL TO DIAGNOSE RESPIRATORY INFECTIONS/RAMÍREZ ET AL 529
several studies.15 However, the reproducibility of the
results of quantitative BAL in the same patient is not
always obtained for all bacteria.48 Interpretation of the
results should take the quality of the sample into account
as well as the clinical suspicion and the previous use of
antibiotics.49
Biological Markers
The determination of biological markers in BAL, such as
sTREM-1 (soluble triggering receptor expressed on
myeloid cells), has been found to be useful in the dia-
gnosis of VAP.50 Cytokines have also been under study,
but their diagnostic capacity seems to be less clear.51
Conclusions
The analysis of BAL is a good diagnostic tool in VAP
but it is not essential for correct patient management and
is not risk free. It must first be considered that the use of
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FOB should not represent a delay in the initiation of
antibiotic treatment. Prospective and randomized stud-
ies have not described advantages of FOB over non-
invasive techniques. However, in contrast with other
types of respiratory samples, BAL allows validation of
the samples, includes a greater volume for separate
analyses in different laboratories, and is useful for the
determination of inflammatory markers.
BRONCHOALVEOLAR LAVAGE IN THE
DIAGNOSIS OF THE PULMONARY
INFILTRATES OF IMMUNOCOMPROMISED
PATIENTS
The appearance of pulmonary infiltrates (PIs) in immu-
nocompromised patients is one of the most frequent and
feared complications in these patients (up to 90% mor-
tality in patients undergoing bone marrow transplanta-
tion requiring mechanical ventilation).52 The etiology of
the PIs in these patients varies greatly, with the most
frequent origin being infectious (bacteria, fungi, proto-
zoa, and viruses), although noninfectious causes are also
possible, such as nonobstructive obliterating bronchioli-
tis, toxic drug reactions, idiopathic pneumonia, or dif-
fuse alveolar hemorrhage.53,54 BAL obtained by FOB is
the most widely used diagnostic technique in this type of
patient because of its good performance; the possibility
of obtaining a larger sample volume, which allows
different laboratory techniques to be performed; and
the relatively low risk inherent in its attainment.53,55
Diagnostic Performance of Bronchoalveolar
Lavage
Because the causes of PIs in immunocompromised
patients may be multiple, the establishment of adequate
530 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 28, NUMBER 5 2007

treatment requires that an etiologic diagnosis be
obtained. The absence of an etiologic diagnosis is asso-
ciated with a greater mortality. This association acquires
statistical significance when compared in patients in
whom an etiologic diagnosis has been achieved within
the first 5 days of evolution with those in whom the
etiology was established later (34% vs 53%; p ¼ .017).56
In fact, patients in whom the treatment was modified on
establishment of the etiologic diagnosis within the first
7 days of evolution demonstrated a lower mortality rate
in comparison with patients with later therapeutic
changes (30% vs 70%; p ¼ .007). This relation was
especially reinforced in the subgroup of PIs of infectious
origin (29% vs 71%; p ¼ .001).57
It is difficult to determine the diagnostic qualities
of BAL because of the absence of a gold standard to
measure the sensitivity and specificity of the technique;
thus we can only evaluate the performance observed in
the different series published on the diagnostic results of
BAL (Table 3).57–71
BAL is greater in the PIs of infectious origin except in
diffuse alveolar hemorrhage ( 20% hemosiderin-laden
macrophages in BAL fluid).62
Obtaining an etiologic diagnosis with BAL has a
widely variable impact on the therapeutic management
of patients (41 to 100%),57–59,65,67,68,70 and the influence
that this change may induce in mortality seems to be
based on how early it is established.57,62
The use of a protected specimen brush does not
seem to add great benefits to BAL but does include the
possibility of more complications. Transbronchial biopsy
improves the diagnostic performance of FOB in patients
without severe alterations in hemostasis and platelet
count.57,62
To date no prospective, randomized study has
been performed comparing the performance of the differ-
ent samples and diagnostic techniques in this type of
patient.
BAL should undergo staining, serological tests,
and cultures necessary to cover all the possible infectious

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Diagnostic capacity of BAL seems to be good;
however, definitive conclusions cannot be made due to
the differences in the type of patients studied and the
percentage of PIs of infectious origin. There is no
consensus on the method used to measure the perform-
ance of this test. Although some authors use the number
of BAL achieving diagnosis over the total number of
BAL performed,60,65–69 others use the number of diag-
noses obtained by BAL over the total number of diag-
noses achieved.41,59,62 The diagnostic performance of
etiologies and should be cytologically analyzed for the
diagnosis of noninfectious processes.41,62
Risks Derived from Fibrobronchoscopy and
Bronchoalveolar Lavage
In patients with severe respiratory insufficiency, the first
step to consider is whether the patient is in condition to
undergo such an exploration. Some noninvasive ventila-
tion (NIV) devices allow FOB to be performed, but the

Table 3 Bronchoalveolar Lavage in the Diagnosis of Pulmonary Infiltrates in Immunosuppressed Patients

BAL/ Type of Type of Diagnostic BAL Final Treatment Mortality Adverse
Patients Study Immunosuppression N (%)a Yieldb Change % % Events %

Hohenadel et al58 95/95 R Homogeneous 29 (30%) 29/62 (46%) 41 22 15

von Eiff et al59 90/90 P Hematologic 63 (70%) 78/125 (62%) 38 3
malignancies
Glazer et al60 79/62 R BMT 53 (67%) 49/53 (92%) 53 0
Stover et al61 97/97 P Homogeneous 61(63%) 61/92 (66%) 15c
Jain et al62 99/99 P Homogeneous 48/125 (38%) 13
Kahn and Jones41 100/94 P Homogeneous 67/113 (59%)
Huaringa et al63 124/89 R BMT 52 (42%) 52/81 (64%)
Rañó et al57 135/135 P Homogeneous 68 (51%) 70/157 (44%) 51 40 2
Agusti et al64 18/18 P Steroids 10 (56%) 18/29 (62%) NA 45
Campbell et al65 27/27 P BMT 20 (74%) 20/28 (77%) 85 74 0d
66
White et al 68/52 P BMT 21 (31%) 32 15
Sternberg et al67 58/48 R Renal transplant 32 (66%) 70 16
Gruson et al68 93/93 P Neutropenic 46 (49%) 56 71 17
Weiss et al69 66/47 P BMT 22 (46%) 12
Peikert et al70 35/35 R Neutropenic 17 (49%) 17/35 (49%) 100 26 8
Baughman et al71 894/894 R HIV 530 (60%)
a
Percentage of explorations performed achieving a positive result.
b
Percentage of final diagnoses obtained by BAL.
c
All of them were transient fever without clinical repercussion.
ddThree pneumothorax after a transbronchial biopsy.
BMT, bone marrow transplant; HIV, human immunodeficiency virus; NA, not available; P, prospective; R, retrospective.

efficacy in avoiding respiratory deterioration has only
been shown to be preventive in patients who, despite
respiratory insufficiency, did not require the initiation of
NIV.72,73 Therefore, there are two relatively contra-
dictory trends in the field of PIs in immunosuppressed
patients: the use of NIV74 and the need to obtain
respiratory samples to make an etiologic diagnosis.
The possible complications derived from per-
forming FOB and sample collection are fundamentally
related to the worsening in respiratory insufficiency and
to the appearance of bleeding. In the series analyzed, the
appearance of complications occurred in a wide percent-
age of patients, probably due to the differences in the
type of patient and the severity of the respiratory
insufficiency (Table 3). In the only study reporting the
degree of previous respiratory insufficiency (PaO2), the
need for a greater FiO2 was not statistically related to a
greater probability of complications.62 In a study analyz-
ing a series of immunocompromised patients with PIs
requiring ICU admission, Gruson et al found that the
performance of FOB triggered intubation and mechan-
ical ventilation in two cases (2%).68 Nasal or bron-
chial hemorrhage is a relatively frequent complication,
although it is usually mild58 and is especially related to
the use of transbronchial biopsy.62 Immunosuppressed
patients often present alterations in platelet counts or in
PT-INR (prothrombin time-international normalized
ratio) favoring the appearance of hemorrhages. How-
ever, this association was not demonstrated in the
analysis performed by Jain et al.62
Conclusions
The etiologic diagnosis of PIs in immunosuppressed
patients is a challenge in health care. The diversity of
possible origins requires correct etiologic diagnosis to
manage adequate treatment. However, if the etiology is
not determined early, the potential benefits of this
diagnosis disappear. The type of sample and the volume
obtained on BAL allow cytological and microbiological
analysis. To date, there are no prospective, randomized
studies comparing this diagnostic technique with others.
Despite the hemorrhagic and respiratory risks in this
type of patient, the rates of complications associated with
FOB are relatively low.
FUNDING
Supported by CIBER CB06/06/0028 ‘‘CIBER de en-
fermedades respiratorias.’’
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