Bronchoalveolar lavage: a standardized procedure

Eur Reaplr J
1991. 4 , 776-777
EDITORIAL
Bronchoalveolar lavage: a standardized procedure
or a technical dilemma?
U. Costabel*
Bronchoalveolar lavage (BAL) is widely used for
analysis of cells and soluble components of the lower
respiratory tract. In its infancy, this simple and safe
method has been applied as a pure research tool.
Meanwhile, "the child has grown up", and its clinical
usefulness for routine diagnostic purposes has been
recognized worldwide in the various interstitial lung
diseases and particularly in opportunistic infections
of the immunocompromised patient [1). However,
even though this valuable tool has by now "almost
reached adulthood" having been developed by
REYNOLDS and NEWBALL in 1974 [2], there is still considerable criticism of it for not being a standardized
technique. Clearly, the technique of performing BAL
and processing the material in the laboratory is not done
under identical, carefully controlled conditions in the
many centres using this method. But is this really
necessary? Recently the European Society of Pneumology (SEP) task group on BAL published technical
recommendations and guidelines for BAL in this
journal (3]. These guidelines were based on the principle of the so-called smallest common denominator,
hence allowing great technical variations for the different
steps of the BAL procedure. It is not possible in this
short editorial to discuss all of the different steps in
detail, but several aspects are exemplified below
and stand for the whole.
For example, the correct information about cell
differentials is important for clinical purposes. In this
regard, the volume of fluid infused can range from
100-250 ml without affecting the cell differentials.
1;fiis has been shown for normal volunteers [4] and
for patients with interstitial lung diseases [5] . For
routine purposes, therefore, a small 100 ml volume
seems to be sufficient for reliable analysis of cell
differentials. A larger 200-300 ml volume may be a
disadvantage, because of increased patient morbidity
due to the more pronounced drop in oxygen saturation
during the BAL procedure [6), and increased incidence
of post-lavage side-effects such as fever (5, 7).
Another parameter which may influence the BAL
results is the bronchopulmonary segment in which the
lavage is performed. In this context, segments of the
middle lobe or the lingula are recommended as the
standard sites in patients with diffuse shadowings on
• Abt. Pncumologic/Allergologie, Rubrlandklinik, D-4300 Essen 16,
Fed. Rep. of Germany.
the chest roentgenogram for two reasons: 1) their
easy accessibility with the bronchoscope; and 2) the
better recovery of fluid and cells which is 20% greater
than from the lower lobes [8]. Are the results obtained
from BAL at one location representative for the
whole lung? Or should BAL be routinely performed
at several locations in order to minimize the sampling
error? Several studies have addressed the interlobar
variation of BAL cell differentials (9, 10), lymphocyte
subpopulations [11), and asbestos body counts [12)
by performing a BAL on the right side and on the left
side in the same patient and analysing the two sites
independently. In general, these studies have shown
a good interlobar correlation in patients with nonfocal
disease on the chest roentgenogram. Patients with
sarcoidosis and uneven distribution of infiltrates may
have widely varying percentages of cells, however [9],
and one third of patients with idiopathic pulmonary
fibrosis may show discrepancies greater than 10%
regarding the percentage of neutrophils between the
two different sites [10).
In this issue of the Journal, SCHMBKEL et al. [13] shed
further light on the problems related to the interlobar
variability of lavage components. In 12 healthy
subjects, they looked for the interlobar variation of
neutrophils and eosinophils and their secretory
products myeloperoxidase and eosinophil cationic
protein, respectively. They analysed separately the
first 50 ml aliquot (bronchial wash) and the following
two pooled 50 ml aliquots (bronchoalveolar lavage).
In both compartments, they observed a significant
interlobar correlation for the number and concentration
of neutrophils and eosinophils, but not for the solutes.
This inconsistency of solute recoveries between
different lobes has to be considered when investigating
patients with interstitial lung diseases. Up to now,
studies looking for interlobar variations of soluble
components in patients with interstitial lung diseases
are lacking, to my knowledge, and should urgently be
performed.
In contrast to the analyses of the cell profiles in
BAL, which are used for clinical purposes, the
quantitation of soluble components has mainly
remained a research tool. One reason for this may be
that a reliable method to assess the true epithelial
lining fluid (ELF) does not exist. The problem is that
the saline used for lavage significantly dilutes the ELF
that is sampled. Several reference substances have
BAL: STANDARDIZED PROCEDURE OR TECHNICAL DILEMMA
been proposed, such as albumin or potassium, but
both have limitations, albumin because of ils possible
leakage from plasma due to increased permeability
of the epithelial capillary membrane in inflammatory
disease processes, and potassium because of its
potential release from lysed cells in the BAL fluid [3].
Methylene blue has been suggested as an external
marker of dilution (14) and urea as an internal marker
[15). Both markers are not ideal. Methylene blue
may be lost by passing into the circulation or by
binding to cells of the lower respiratory tract, and urea
may diffuse from the plasma during the lavage
procedure, thereby leading to an overestimation
of the ELF volume (16]. A recent study compared
albumin and urea as reference markers in BAL fluid
from patients with interstitial lung diseases [17).
Urea showed less variability between groups than did
albumin, and hence was concluded to be the better
available marker, if dwell time is kept to a minimum.
In this report, the mean dwell time was only 3.2±0.4
min, because the authors excluded all lavages exceeding 4 min in order to reduce passive diffusion of
urea into the BAL. This selection criterion may have
caused a significant bias in favour of urea and against
albumin. Such a bias would make it difficult to extrapolate the results of this study to routine analyses of
soluble components, since in daily routine lavages it
would be impossible to keep the dwell time below 4
min in every patient.
The fluid dynamics during BAL are complex and
not well understood. A recent study demonstrated a
bidirectional flux of water across the alveolar membrane during BAL, the net result being an influx of
fluid from the circulation into the lung [18]. These
fluid kinetics may depend on a number of factors
including BAL volume, site of lung segment, and
suction pressure applied. The fluid movements during
BAL may dilute the solutes which are to be measured
to an unpredictable degree.
Thus, the findings to date indicate that BAL is
sufficiently standardized for clinical routine purposes
with respect to the enumeration of cell differentials
including lymphocyte subpopulations. The quantitation
of soluble components, however, is still hindered by
the variable and unpredictable dilutional effe.cts occurring during the BAL procedure. In this regard, BAL
still represents a technical dilemma. Further work is
needed to develop methods allowing co rrect
determinations of solutes in the fluid of the lower
respiratory tract.
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