score of a certified. B reader who was unaware ofthe lavage andbiopsy findings. Data shown are numbers of subjects with each score separated bythe presence.
The relationship between large airway inflammation and airway metaplasia. W W Merrill, D Carter and M R Cullen Chest 1991;100;131-135 DOI 10.1378/chest.100.1.131 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/100/1/131
Chest is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright1991by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0012-3692
Downloaded from chestjournal.chestpubs.org by guest on July 10, 2011 © 1991 American College of Chest Physicians
The Relationship between Large Airway Inflammation and Airway Metaplasia* William Mark
M.D.,
W Merrill, R. Cullen,
F.C.C.R;
Darryl
Cart#{233}rM.D.;
and
M.D.
To assess
significant
airways
the role of acute inflammatory cells in large in the pathogenesis of metaplasia, we performed BAL(&vided into aliquots)and mucosal biopsies on asbestos workers. They had evidence ofasbestos-related lung injury. We found that acute inflammatory cells were signfficantly increased in the first aliquot. Ex-smokers had a greater percentage ofPMN compared with nonsmokers and current smokers. The subjects were subgrouped with respect to
without.
biopsy-detected tween these
metaplasia.
There
was
no
difference
be-
in the first aliquot.
for percentage or total number of PMN However, subjects with metaplasia had
I ndividuals
smoke
have
groups
who
an increased
Metaplasia
is an
airways
and were risk
important
of cigarette
exposed
to asbestos
of pulmonary who
lesion
develop
in the lung
can-
cer.2’3 animal
Moreover, models
it is a common histologic feature of which results ultimately in the devel-
opment to be related
of lung tumors.45 It also has been suggested an important lesion when seen in asbestosdisease.6 The role of inflammatory stimuli in
the
pathogenesis of metaplasia suggested by several observations.
and cancer has been First, inflammatory
lesions in mucosal surfaces often are accompanied by metaplastic change.2’7’8 Second, subjects with chronic inflammatory lung disease may be at an increased risk of lung an
lung
cancer.9”#{176} In fact,
important cancer.”
of releasing simple suggest
this
has been
predisposing factor Finally, inflammatory factors
cause
bacterial assay systems.’’3 that inflammatory stimuli
These may
ofboth cancers.
respiratory
tract
Other rate the
investigators sequential
as
metaplasia
mutations
diffusing
TNC=total
in
and subsequent
School
Pathology
Yale University
ofMedicine, New Haven. These studies were supported in part by NIOSH grant OHO2114, the Adult Clinical Research Center, Yale University School of Medicine (grant No MO1-RR00125) and the Research Service, West Haven VAMC. Manuscript received March 26; revision accepted November 21. Reprint requests: Dr. Merrill, 111-A Medical Service, West Haven DVA Medical Center, West Haven, CT 06516
PMN capacity;
from the large airways are sampling more distal
and lung an in
demonstrated
metaplasia
in airway
biopsies
obtained
from a population of subjects with signfficant past exposure to asbestos. This is a particularly relevant target population because they are known to have an increased risk of cancer and metaplasia in large airways.’8
As noted
observations
of others
the
pooled
peared were
below, these studies confirm prior that the first aliquot is different fluid recovered from subsequent
Moreover, to be unable
these
two
cell
unrelated to one to demonstrate
relationship
between
populations
another. in these
inflammatory
and histologic specimens.
aliquot
biopsy
Care,
monoxide;
the first aliquot.’’6 Because of the prior suggestions that inflammatory cells might be important stimuli for metaplasia, we assessed the relationship between acute inflammatory cells in large airways and histologic
detection
ap-
However, studies
cells
we any
in the
ofmetaplasia
first
in airway
METHODS
Study
Population
Subjects
with
a history
ofoccupational
recruited
from an occupational
screened
and
workers
priorasbestos
exposure.
from
each
prior
cigarette
was
smoked,
since
the
subject average
chest
radiographs
packs
cigarette function tests
per
age
day, duration
was smoked,
was
CHEST / 100
the
of
first cigarette and
obtained.
after
subject
were
approved
I 1 I
obtained
A history
of smoking
was also
pulmonary were performed (Collins DS II, Braintree, MA). All studies Yale Committee on Human Investigation.
Downloaded from chestjournal.chestpubs.org by guest on July 10, 2011 © 1991 American College of Chest Physicians
time
of
of significant
therapist.
at the
were
a subgroup
history
occupational
were
records
indicative
A carefuloccupational including
to asbestos
clinic. Clinic from among
recruited
by a trained
smoking, last
exposure
medicine
were
with abnormal
individuals
0From the Section of Pulmonary and Critical Department and Occupational Medicine Program,
derives aliquots
sepacorn-
posed ofthe first aliquot and a later fraction composed ofa pool ofall the subsequent aliquots.’4’7 Analysis of lavage fluids separated in this fashion suggests that
of carbon
leukocytes; TLCtotal lung cells; VOvalume recovered
Most studies of this type have shown in the number of neutrophils recovered
aliquots.
observations be important
have noted that one may BAL into an early fraction
capacity
nucleated
units.’5 increase
from
in asbestos-related cells are capable
which
in the development
in vitro
suggested
Dco
polymorphonuclear
the first aliquot that subsequent
carcinoma.’
coexisting
smokers
in FEV1IFVC compared with those conclude that there are significant differences in cells between the first and subsequent aliquots. Although inflammatory stimuli may be important in the pathogenesis of metaplasia, PMN present in the first aliquot could not be related to the severity of the metaplastic changes in these workers. (Chest 1991; 100:131-35) reduction
We
JULY,
years
Full
selection
1991
by the
131
Bronchoalveolar
Table
Lavage
Bronchoscopy
was
as described
performed
the nose and upper airways were anesthetic and a fiberoptic bronchoscope The airways were initially inspected
previously.’
was passed carefully
The bronchoscope
chloride
solution.
lvcessitig
A total
gauze
aliquots cellular
three
to
terminated
when
had been
recovered.
into
six
*For
a wedged
due
position
aliquots
were
employed.
was
to remove
filtered
gross
through
a single
mucous
particles,
layer
and
from
recovery
was
aliquots
2 to 5 ofthe
of aliquot
recovered
15.5±17 6.6±11
250 mL
lavage,
Total
cells
0; 3,
of sterile
3).
extremes
were centrifuged at 1,000 g for 10 min at 4#{176}C to pellet Cells from the first aliquot were processed alone, the cells recovered from subsequent aliquots were pooled analysis. Fifty to 100,000 cells from each cell population
Thus,
the
of the
path
sented
in either.
Lavage
Analysis
lost
two
and
two
to coughing or cells in aliquot (score 1, 5; 2, came
and
biopsy
subjects
subjects
scores
lavage.
1. Inadequate
from
1 % PMN
(be)
subjects could not be studied due presyncope. Subjects with inadequate 1 were from most path score categories
individual
the
represent
to poor
material
Fluid
fluid
1, 50 ml instilled.
cells
in Aliquot
0.5±0.7 52±6
112±20
aliquot
tEboled
the
TNC
15±10
Pboledcellst
branch
and PMN
were
from
both
not overrepre-
elements.
whereas for further were
maneuvered
of5
ofRecovered
The recovered surgical
then
remove
Recovery
VO*
Aliquoti
lesions.
BAL was performed by alternately instilling and aliquots of room temperature isotonic sodium
and
50-mi
aspirating
was
via the mouth.
subsegmental
Fluid
BAL Sample
a topical
for abnormal
If none was found, attempts were made to mucosal biopsy specimens at random from points in the right lower lobe. Attempts were operator determined that three visible pieces in the lingula,
Briefly,
with
anesthetized
1-BAL
subsequently
pelleted
subsequent
analysis.
l4vcessitig
of Biopsies
Biopsies
glass slides
onto
and stained with modified
Wright-Giemsa
The
by cytocentrifugation
(Dif-quick,
Harleco)
for 6 h in glutaraldehyde-paraformaldehyde
and 4- sections were cut and stained with hematoxylin and eosin. All biopsies were scored in blinded fashion by one of us (D.C.) who was unaware of the identity or lavage findings of study subjects. The biopsy material was scored with respect to the worst metaplastic lesion present similar to the studies ofAuerbach et al. Biopsies were judged to be adequate if mucosa was seen on cut tissue sections. Statistical continuous
were
screened
variables
were
where appropriate. the Mann-Whitney comprised
a set
study
population
square
test,
for normality
U test.
distributed
The
biopsy
of discontinuous was
analysis
of
results
data,
separated
into
variance
normally
for
smoking this
the
Kruskal-WaIlis
by
the chi
test
as
in the
first
(p
