A Case of Pulmonary Alveolar Proteinosis associated with

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Title
A Case of Pulmonary Alveolar Proteinosis associated with Pulmonary
Silicosis
Author(s)
Tashiro, Takayoshi; Goto, Jun; Goto, Ikuo; Akashi, Mitsunobu; Nasu,
Masaru; Itoga, Takashi
Citation
Acta medica Nagasakiensia. 1983, 28(1-4), p.22-34
Issue Date
1983-10-25
URL
http://hdl.handle.net/10069/15638
Right
This document is downloaded at: 2016-10-30T04:52:51Z
http://naosite.lb.nagasaki-u.ac.jp
Acta
Med.
Nagasaki
28; 22-34
A Case
of Pulmonary
associated
Takayoshi
Alveolar
with
Pulmonary
TASHIRO,
Mitsunobu
Silicosis
Jun GOTO,
AKASHI,
Masaru
Takashi
ITOGA
Department
Proteinosis
of Internal
Ikuo GOTO,
NASU,
and
Medicine,
Medical College of Oita
Received
A 53 years
pital
on
lung
fields.
torr
8th
at pH
of which
space
nary
Chest
blood
gas tensions
Transbronchial
proteinosis
were
intraalveolar
and was
alveolar
were
cells
positive
and
mostly
the
and dyspnea
fine
cells.
granular
patient
by bronchoalveolar
that the
from the
lung
through
in the
diagnosed
with
the
observation
materials
86
findings
intraalveolar
as pulmo-
aid
of extra-
and biochemi-
accumulated
secreted
out
AaDO2
microscopic
was
surfactant
to a hos-
and
filled
lavage
microscopic
it was suggested
shadow
and the
materials
The
admitted
PCO2 27 torr
was performed
and electron
originated
5, 1982
PO2 31 torr,
granular
lining
saved
Histochemical
performed,
space
PAS
cough
showed
were
biopsy
of the alveolar
circulation.
cal analysis
X-ray
lung
eosinophilic,
swelling
December
productive
1982.
7.45.
alveolar
complaining
Arterial
showed
corporeal
man
March,
and the
monary
old
for publication,
in the
by the
pul-
type II.
INTRODUCTION
Pulmonary
able granular
alveolar proteinosis
materials
accumulate
is the disease in which eosinophilic
in the alveoli.
ROSEN, CASTLEMAN and LIEBOWI) in 1958.
This disease
In Japan,
and PAS-stain-
was first reported
OKA et al.2) reported
by
the first
case in 1960, and a total of 79 cases have been found out until 19793).
We have experienced
silicosis and pulmonary
a case with pulmonary
tubercurosis.
alveolar
proteinosis
complicated
This patient was saved by bronchoalveolar
with
lavage
(BAL) with the aid of extracorporeal circulation.
During the treatment, we have carried
out histochemical and electron microscopic observations on biopsied lung and the bron田代 隆 良,後 藤 純,後 藤 育 郎,明 石 光 伸,那 須 勝,糸 賀 敬
choalveolar
obtained
lavage fluid (BALF),
are reported
and also analysed
lipids in BALF.
The results
thus
and discussed in this paper.
DESCRIPTION
OF
THE
C SE
Patient : 53 years old man
Chief complaint
: dyspnea
Family history : unremarkable
Past history : The patient worked
Nov.
1979, productive
to tubercle
bacilli,
cough and fever developed.
and he was diagnosed
years treatment with a combination
with INH alone since Nov. 1981.
Present
Aug.
illness : Exertional
1981.
dyspnea,
Since Feb.
thus he was admitted
formed,
dyspnea,
to a hospital
Air bronchogram
and high AaDO2.
ished.
examinations
blood pressure
The respiration
the presence
abdomen
was 124/90 mmHg.
was normal,
Biochemical
96 IU/l.
reports
tests showed an increase
and IgE to 447 IU/ml,
of Internal
Medicine,
increased
1)
marked
was perMedical
on 20th April,
1982.
build and moderately
nour-
was 117 per minute
Heart
and regular.
of the chest revealed
sounds were clear.
were not palpable.
Superficial
Tendon
The
lymph
reflex
showed no abnormality.
number of
to 1,430 IU/1 and GOT to
In lipoprotein
was decreased
of CEA to 8.1 ng/ml,
indicating
(Fig.
indicating
(TBLB)
showed LDH to be increased
to 79.3%, while a-lipoprotein
of
fingers and cyanosis were present.
lung fields.
Serum lipids were within normal limits.
was increased
around
because
(Table 1) : Blood analysis showed slightly increasing
examination
therapy
since
lung biopsy
Physical examination
examinations
2
blood gas analysis
There was no edema in the lower extremities.
and other neurological
Laboratory
RBC.
The pulse
of moist rales over the entire
Arterial
alveolar proteinosis
was flat, and the liver and the spleen
After
Chest X-ray
and AaDO2 86 torr,
but clubbed
was 28 per minute and regular.
nodes were not swollen.
1982.
was also noted.
Transbronchial
were absent,
In
from the hilar region to the middle
: The patient was of averagely
Anemia and jaundice
aggravated
of looking after himself
and the patient was hospitalized to the Department
Physical
tuberculosis.
he has been under
on 8th March,
College of Oita under a diagnosis of pulmonary
The
and RFP,
bilaterally
P02 31 torr, PCO2 27 torr,
hypocapnia
pulmonary
cough and sputum
shadow diffused
and the lower lung fields.
showed pH 7.45,
of EB, INH
from 1949 to 1974.
The sputum was found to be positive
as silicotic
1982, he became incapable
showed the fine granular
hypoxia,
for a tunnel construction
fractions,
to 18.2%.
IgG to 2,919 mg/dl,
~-lipoprotein
Immunoserologicla
IgA to 574 mg/dl
levels of immunoglobulins.
Arterial
blood
gas tensions at the time of admission were P02 44 torr and PCO2 35 torr at pH 7.45
under oxygen inhalation at a rate of 5 1/min.
Radiographic
appearance
silhouettes
reports
spreading
(Fig.
2) : Chest X-ray
over all lung fields.
of the heart and the diaphragm
Clinical course : Bronchoalveolar
uled.
However,
to be inadequate.
bronchopulmonary
because
of advanced
On 27th April
Air
film showed
bronchogram
The
hypoxia,
hemipulmonary
was first sched-
ventilation
was thought
1982, the right lung was lavaged by means of massive
extracorporeal
circulation
vein and
artery and the left subclavicular
infused
artery,
method
the blood
while
the left
with 100% oxygen using a double lumen air duct tube.
The lavage solution used for each lavage was a mixture
saline,
70 ml of distilled
osmotic
pressure
being
was also observed.
lavage under general anesthesia
which removed the blood from the left common ilio-femoral
lung was being ventilated
ground-glass
were ill-defined.
lavage with the aid of the partial
into the left common ilio-femoral
diffuse
water
and
330 mOsm/l.
40 ml of 8.4%
The solution
Meylon,
of 900 ml of physiological
pH being
was introduced
8.0 and the
into the
lung
by
gravity feeding from the level about 30 cm higher than patient's
chest was lightly tapped with hands and vibrated with a vibrator
the solution
was drained
60 cm lower level.
the
by gravity out of the lung into a drain
These procedures
lavage solution
introduced
were repeated
was 9,840 mi,
midchest.
Then,
for about 5 min,
bottle placed
for 10 times.
the
and
at about
The total volume of
and that of the recovered
solution
was
10,090 ml.
As shown in Fig.
lung showed marked
as P02 73 torr,
3, the X-ray picture
improvement.
Arterial
of the chest after the lavage of the right
blood gas tensions
PCO2 40 torr and pH 7.43 under 3 1/min
were also improved
oxygen inhalation.
and right lungs were then lavaged without using extracorporeal
lavagings,
terial
marked
improvement
blood gas tensions
was achieved
were also improved considerably
PCO2 34 torr, AaD02 38 torr under air inhalation.
June,
function
tests
left
After 3 such
(Fig.
to be pH 7.46,
The patient
4). Ar-
P02 71 torr,
was discharged
Table 2. Respiratory
(Table
VC
VC
FEV 1.0
FEV1.0%
TV
FRC
ERV
RV
TLC
RV/TLC
V 75
V 50
V25
DLCO
DLCO
2) : The result of the test performed
before discharge showed % VC of 68.2
%, indicating restraint disorder,
DLCO was decreased to 50.4 %.
Pathohistological
of pulmonary
thickened,
and
findings : The
alveoli was mildly
alveolar lining cells were swo-
llen, and eosinophilic
granular
materials
were packed in the alveoli (Fig. 5).
The large mononuclear cells alike exfoliated alveolar
lining
veolar macrophages
cells type II or alwere also observed in
the intraalveolar
space (Fig. 6). In other
biopsy specimen,
hyalinized
tion of coal powder around
showed the presence
Therefore,
on 30th
collagen fibers were spiralled,
them (Fig.
of considerable
7).
Observation
numbers
function tests
2340 ml
68.2
1990 ml
90.5%
610 ml
1980 ml
1240 ml
740 ml
3080 ml
24
7 1/s
2.6 1/s
1I/s
11.8 m1/min/mmHg
50.4
and there was marked
under
of polarizable
a polarizing
fine
granular
deposi-
microscope
materials.
this was thought to be a silicotic nodule.
Histochemistry
nuclear
pictures
The
1982.
Respiratory
septum
circulation.
in the chest X-ray
such
cell contained
tion exhibited
: As shown in Table 3, the granular
in both biopsy specimen
similar histochemical
reactivities.
material
and the precipitate
The granular
and the large monoof lung lavaged solu-
material
was most strongly
positive to PAS staining, and the mononuclear cell also contained PAS-positive substances. These substances were not digested by a diastase. All lipid stainings tested, i. e. ,
with Oil red 0, Suddan black B and Nile blue, were strongly positive to the large mononuclear
cell, and partly positive to the granular
material
(Fig.
8).
Both granular
mate-
Table 3.
Histochemistry
Biopsy specimen
Granular
HE
PAS
diastase investigation
Oil red O
Sudan black B
Nile blue
LFB
Alcian blue
Toluidin blue
Mucicarmin
PTAH
GMS
material
Lavage fluid
Mononuclear
+
-1-f+
+
+
-F}-
cell
Granular material
+
+
-+
~f-}{+
-
+
-1+
+
+
+
-I-I-!±
-
rial and mononuclear
cell were well stained with LFB staining
the granular
was strongly positive.
material
or Mucicarmin
inii was denied
Electron
elin-like
was negative,
marily around
Staining
and that with PTAH
cell
+
+
-HIf
H
+
±
-
(for phospholipids),
with Alcian blue,
was also negative.
but
Toluidine
blue
Pneumocystis car-
by GMS staining.
microscopic
materials
tron-opaque
Mononuclear
observation
with a concentric
: In the intraalveolar
structure
bodies with various sizes (Fig.
the electron-opaque
them being surrounded
body.
with the myelin-like
space, there were many my-
and various sizes and shapes,
9). The myelin-like
Lamellar
and elec-
material was formed pri-
bodies were also observed,
materials
(Fig.
10). The precipitate
some of
of la-
vaged solution also showed similar images.
Biochemical
analysis of the lavage fluid : A portion of the
from the lst lavage was centrifuged
lavage fluid recovered
at 500 x g for 10 min. The grey
precipitate
with a
yellowishwhite tint thus obtained was largest in amount in the 1st lavage fluid and decreased in subsequent lavage fluids, thus the supernatant became clearer in later lavage
fluids (Fig.
to biochemical
11). The supernatant
analyses.
and the precipitate
Proteins were rich (73.1%)
more abundant (65.1%) in the precipitate.
The proteins consisted of the major proteins of serum such as prealbumin,
min,
al-antitrypsin,
transferrin
abundantly
(Tadle 4),
in the supernatant,
Table 4.
Lipid composition
(weight %)
Supernatant
Precipitate
and IgG
in which
phosphatidylcholin
was the highest
tituent (Table 5).
cons-
while lipids were
Lipid composition of lavage fluid
albu-
(Fig. 12).
Lipids in either the supernatant or the precipitate
contained phospholipids
of the 1st lavage fluid was supplied
Phospholipid
Triacylglycerol
Free fatty acid
Total cholesterol
72.2
0.1
10.1
17.5
80.8
0.8
1.4
17.1
Table 5.
Phospholipid
composition of lavage fluid
Phospholipid
Spot No.
Composition (mole %)
Lipid
Supernatant
I
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Precipitate
Phosphatidylcholine
Phosphatidylethanolamine
Sphingomyelin
Phosphatidylinositol
Phosphatidylserine
Lysophosphatidylcholine
35.7
4.5
28.6
0.9
7.5
6.9
54.9
3.6
11.9
6.4
1.8
6.8
Unknown
Phosphatidylglycerol
Unknown (Glycolipid)
Lyso-bis-phosphatidic
acid
Unknown (Glycolipid)
Unknown (Glycolipid)
Unknown (Glycolipid)
Unknown (Neutral lipid)
Unknown (Neutral lipid)
Origin (Degradated lipid)
2.2
10.8
2.9
3.2
7.6
3.7
DISCUSSION
Pulmonary
alveolar proteinosis
develops regardless
of age,
but it occurs most fre-
quently at the age between 30-50th, and the incidence in man is twice of that in female.
Subjective symptoms are exertional dyspnea, cough and sputum.
The
rise of the
the present
case,
LDH level is frequently
it was also raised
hyperlipemia
have been reported4)5),
be normal.
The
tigators,
lipoprotein
but the
lipoprotein
rise
to 1,430 IU/1.
in biochemical
Although
cases
the serum lipid level has been
fraction
blood test.
complicated
In
with
usually reported
and the
in the present
decrease
case.
of pre-/3-lipoprotein
and
lavage.
decreased
and it was 2.1 ng/ml at the time of discharge.
spread
the CEA value successively,
chest
X-ray
from the hilus.
cloud-like
shadow,
film frequently
to dense and fine granular
Pulmonary
function
analysis reveals hypoxemia
hypoxemia
and
Repetitive
pulmonary
shows fine granular
Such a shadow is sometimes
air bronchogram
is frequently
a-
The serum CEA level in the present
case was as high as 8.1 ng/ml before
The
to
from the serum has been studied by a few inves-
of ji-lipoprotein
were demonstrated
observed
shadow
described
observed,
lavages,
which
as frosted
however,
bilaterally
glass-like
or
which is thought
to be due
lowered DLCO.
Blood gas
alveolar shadow.
tests show restraint
and increased
the increase
of AaDO2.
disorder
AaDO2.
Although
and
The present
case also showed marked
these symptoms
were improved
by
pulmonary lavage, respiratory function tests before discharge indicated the presence of
restraint disorder and lowered DLCO. Since this particular case had pulmonary silicosis
and
tuberculosis
conceivable
as basal
completely
their
material
influence
accumulated
may not be ignored.
in the intraalveolar
the complication
of pulmonary
6 cases have been reported
ROSEN et al.1) also experienced
in Japan,
alveolar
proteinosis
with pulmonary
the inhalation
of silica.
plicated.
Although
The term given by him to these dead cases was `acute
experimental inhalation of silica by animals may produce
fore,
However,
alveolar proteinosis8),
alveolar
the inhalation
that the inhalation
proteinosis
were com-
silico-proteinosis' .
the morbid image
of silica can be one of inducing
many other cases are entirely unrealated
it is unlikely
by
In 1969 BUECHNER et al .7)
4 cases in which acute silicosis and pulmonary
similar to pulmonary
sill-
and one case out of 27 cases reported
described
factors.
It was also
space had not been
eliminated.
Regarding
cosis,
diseases,
that protein-like
to silica
of silica is a direct cause
inhalation.
There-
of pulmonary
alveolar
proteinosis.
Pathohistological
characteristic
of the proteinosis
is the presence
of eosinophilic
granular materials which fill the intraalveolar space.
The existence of the large mononuclear cells appeared to be exfoliated alveolar lining cells type II or alveolar macrophages
are also characteristics.
the
alveolar
lining
The alveolar
cells type
These regions were classified
vation,
septum is mildly thickened.
If is present
Histochemical
findings
10).
and sloughing
in the present
Granular
positive
stainings,
with various
latter.
to lipid stainings
indicating
Electron
sition of alveolar
surfactants
precipitate.
accumulated
the
in the intraalveolar
0.
and decomposed
of the
obser-
with those
reported
by
mononuclear
cells were
black B and
Nile
of electron-opaque
former
being
surrounded
and some of the electron-opaque
space is that formed
Electron
alveolar
to be the origin of the accumulated
analysis
microscopic
blue
bodies
by the
bodies were
ROSEN et al.1) and OKADA et al.9) have stated
lining cells type
degenerated
Biochemical
precipitate
constituent
structures,
lamellar bodies.
other.
lipids.
showed the presence
bodies were also observed,
by such
that the material
suggested
Large
Suddan
sizes and of myelin-like
Lamellar
surrounded
proteins.
such as Oil red 0,
observation
of
in the
were strongly stained with PAS and LFB,
the high content of neutral
microscopic
absent
and the area of accumulation.
case mostly agreed
materials
thus they were thought to be phospholipid-rich
strongly
The proliferation
and
by OKADA et al.9), based on electron
to be the area of desquamation
other investigators')')
in some region
microscopic
by the decompo-
observation
lining cells type
of ours also
If or degenerated
lung
material.
lavage fluid showed the abundancy
of lipids in the
and of proteins in the supernatant.
Although the phospholipid was the major
of the lipid, the supernatant had different phospholipid composition from the
In the supernatant,
phosphatidylcholine
and sphingomyelin
were major, while
phosphatidylcho line was high and sphingomyelin
stated by AKINO et al.11) that the phospholipid
was low in the precipitate.
It has been
in the precipitate is mostly derived from
the lung surfactant
cells type
intraalveolar
free
secrected
cells.
from the alveolar
According
to a study using
f , rather
radioactive
than derived
isotopes,
from
there is no
particular
facilitation
of the synthesis
of phosphatidylcholine,
this phospholipid
de novo and via the lysolecithin
formation
the
lung
cretion
tissue
from
a patient
of phosphatidylcho
Therefore,
it may
accumulation
be
line
thought
with pulmonary
into
the intraalveolar
that
of surfactant-origin
alveolar
disturbed
lipids
proteinosis.
space
removal
though
the synthesis
system is basically
active
Moreover,
is not known
mechanism
in the intraalveolar
the
of
in
se-
to be facilitated.
is responsible
for the
space.
CONCLUSION
A case of pulmonary
silicosis was reported.
extracorporeal
developed
as a complication
The patient was saved by bronchoalveolar
circulation,
cal, histochemical
alveolar proteinosis
because
of advanced
and electron microscopic
was thought that the material accumulated
from the lung surfactant
dyspnea.
observations
lavage with the aid of
On the basis of pathohistologiand of biochemical
in the intraalveolar
secreted by the pulmonary
of pulmonary
analyses,
it
space was mostly originated
alveolar cells type
I .
ACKNOWLEDGMENT
We would
chemical
analysis
like
to thank
of the
Dr.
T.
bronchoalveolar
AKINO,
lavage
Sapporo
fluid
Medical
of the
College,
patient.
for making
a
Fig.
1 Chest roentgenogram
of 8th March,
1982
shows
diffuse
fine granular
shadow
through
out lung fields.
Fig.
2 Chest roentgenogram
shows slight increase
iltrates.
Fig.
3 Chest roentgenogram
of 13th May,
16 days after lavage of the right
Fig.
4 Chest roentgenogram
after three lavages,
shows
considerable
clearing
of that
1982,
lung,
lung.
aring
bilaterally.
of 21th April,
in pulmonary
of 25th May,
shows dramatic
1982
inf-
1982,
cle-
Fig.
5 Biopsy
specimen
obtained
at transbronchial
The alveolar
space are filled
materials typical of pulmonary
Fig.
7 Hyalinized
collagen
fiber
biopsy.
with eosinophilic
granular
alveolar proteinosis.
and anthracosis
are seen.
Fig.
6 High
magnification.
in the intraalveolar
are swollen.
The
space
large
and
mononuclear
the
alveolar
cells
are seen
lining
cells
Fig. 8 Numerous red granules are seen in the alveolar macrophage, (Oil red 0 stain).
Fig.
9
Electron micrograph of bronchoalveolar lavage fluid (13,000x). The electronopaque bodies and the myelin-like materials surrounding them are observed.
Fig. 10 Electron micrograph of bronchoalveolar lavage fluid (10,000x).
The extracellular
lamellar bodies surrounded by myelin-like materials are observed.
Fig.
11
A portion
at 500xg
Normal
patient's
Patient's
of the
lavage
fluid
from
Ist lavage
was
centrifuged
for 10 min.
serum
serum
washing
Light
Chain
L
Light
Chain
K
Fig. 12 Immunoelectrophoresis
revealed the major proteins of serum such
as prealbumin, albumin, al-antitrypsin,
transferrin and IgG.
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