Thorax 1981 Rodriguez Roisin 208 12
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8/20/2019 Thorax 1981 Rodriguez Roisin 208 12 http://slidepdf.com/reader/full/thorax-1981-rodriguez-roisin-208-12 1/6 Thorax, 1981, 36, 208-212 Pulmonary involvement in primary biliary cirrhosis R RODRIGUEZ-ROISIN, A PARES, BRUGUERA, J COLL, C PICADO, A AGUSTI-VIDAL, F BURGOS, AND J RODES From the Pneumology and Liver Units, Department of Internal Medicine, Hospital Clinic i Provincial, Facultat de Medicina, Barcelona, Spain ABSTRACT The association of pulmonary fibrosis and primary biliary cirrhosis (PBC) remains controversial. To determine the frequency of pulmonary fibrosis in PBC, a carefully selected series of 14 PBC patients, seven patients with Sicca complex, and 14 control subjects have been studied. Seven of the 14 patients with PBC had Sjogren's syndrome, four of whom had some clinical evidence of pulmonary disease. Evaluation of ventilatory capacity, gas transfer factor, arterial blood gases, and lung mechanics were performed. Gas transfer was reduced in patients with PBC associated with Sj6gren's syndrome and in patients with the Sicca complex. These results suggest that the respiratory, clinical, and functional abnormalities found in PBC are related to the presence of an associated Sjogren's syndrome. The frequency and nature of pleuropulmonary manifestations in primary biliary cirrhosis (PBC) are poorly documented. The finding of both an inter- stitial pattern on chest radiographs and a restrictive ventilatory impairment with a gas transfer defect on routine lung function tests in some cases of chronic active hepatitis and PBC has led some authors to suggest that fibrosing alveolitis could be associated with chronic liver disease,l 2 although others have been unable to find such an association.3 4 Further- more, PBC is frequently associated with Sj6gren's syndrome, an entity in which the interpretation of lung disease remains difficult.5 In the present study we have investigated to what extent PBC is associated with pulmonary signs, symptoms, radiological and functionalabnormalities and have made comparisons with a healthy control population and with a group of patients affected by the so-called Sicca complex, a limited variant of Sjogren's syndrome. Methods The following categories of patients, matched for sex, age, height, and socioeconomic status were studied: seven with PBC and Sj6gren's syndrome, seven with PBC alone, seven with Sicca complex, and 14 normal subjects (table 1 . All were non-smokers who gave no history of alcoholism, occupational Address for reprint requests: Dr Rodriguez-Roisin, Section of Physi- ology M-023,Department of Medicine, Schoolof Medicine, University of California, San Diego, La Jolla, Califomia 92093, USA. Table 1 Physical data in groups investigated Category Sex Age Height (FIM) (years±SD) (cm ± SD ) Healthy control subjects 1 3 1 46-9± 9 4 154-6±4-1 ( n= 14) Primary biliary cirrhosis 13/1 46-3+10-3 154-9±5 8 (PBC) (overall series) PBC without Sj6gren's 7/0 42 9±100 153 1±3 4 Syndrome (n=7) PBC with Sjdgren's 6/1 49-7±10-0 156-5 ±7-4 Syndrome (n=7) Sicca complex (n=7) 7/0 48-7± 7-1 152-4±5 7 exposure to dusts known to cause lung damage, cardiopulmonary or autoimmune diseases, or pre- vious medication with potentially fibrogenic drugs. The diagnosis of PBC was based on clinical and morphological data. All patients had a serum alkaline phosphatase level higher than 300 mU/ml (normal < 85 mU/ml) and a positive antimitochondrial antibody test. Eight of them had a serum bilirubin higher than 34 jpmol/l. According to the liver biopsy three were stage 1, five stage II, five stage III, and one stage IV. The diagnosis of Sicca complex was accepted when both keratoconjunctivitis and xerostomia were present (table 2 . The diagnosis of keratoconjunctivitis was based on the presence of clinical symptoms, an abnormal Schirmer's test (wetting of a paper strip 5 mm or less in 5 min) and Rose bengal ocular staining in the conjunctival sac.6 Xerostomia wa s recognised by clinical history, by abnormal bilateral parotid gland scintigrams after 208 group.bmj.com on February 24, 2016 - Published by http://thorax.bmj.com/ Downloaded from
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T h o r a x , 1 9 8 1 ,
3 6 , 2 0 8 - 2 1 2
P u l m o n a r y
i n v o l v e m e n t i n
p r i m a r y
b i l i a r y
c i r r h o s i s
R
RODRIGUEZ-ROISIN,
A
PARES,
BRUGUERA,
J
COLL,
C
PICADO,
A
AGUSTI-VIDAL,
F BURGOS,
AND
J
R O D E S
F r o m t h e P n e u m o l o g y
a n d
L i v e r
U n i t s ,
D e p a r t m e n t o f
I n t e r n a l
M e d i c i n e ,
H o s p i t a l C l i n i c
i
P r o v i n c i a l ,
F a c u l t a t
d e
M e d i c i n a , B a r c e l o n a ,
S p a i n
ABSTRACT
T h e a s s o c i a t i o n o f
p u l m o n a r y
f i b r o s i s
a n d
p r i m a r y b i l i a r y
c i r r h o s i s
( P B C )
r e m a i n s
c o n t r o v e r s i a l . To
d e t e r m i n e t h e
f r e q u e n c y
o f
p u l m o n a r y
f i b r o s i s i n PBC,
a
c a r e f u l l y s e l e c t e d s e r i e s
o f
1 4 PBC
p a t i e n t s , seven
p a t i e n t s
w i t h
S i c c a
c o m p l e x ,
a n d 1 4
c o n t r o l
s u b j e c t s
h a v e b e e n s t u d i e d .
S e v e n
o f t h e
1 4
p a t i e n t s w i t h
PBC
h a d S j o g r e n ' s
s y n d r o m e , f o u r o f
whom
h a d
some
c l i n i c a l
e v i d e n c e
o f
p u l m o n a r y
d i s e a s e .
E v a l u a t i o n
o f
v e n t i l a t o r y
c a p a c i t y ,
gas t r a n s f e r
f a c t o r ,
a r t e r i a l b l o o d
g a s e s ,
a n d
l u n g
m e c h a n i c s
were
p e r f o r m e d .
G a s
t r a n s f e r
was
r e d u c e d
i n
p a t i e n t s
w i t h
PBC
a s s o c i a t e d w i t h
S j 6 g r e n ' s
s y n d r o m e
a n d i n
p a t i e n t s w i t h
t h e
S i c c a
c o m p l e x .
T h e s e
r e s u l t s
s u g g e s t t h a t
t h e
r e s p i r a t o r y , c l i n i c a l ,
a n d f u n c t i o n a l a b n o r m a l i t i e s
f o u n d i n PBC
are
r e l a t e d
t o
t h e
presence
o f
an
a s s o c i a t e d
S j o g r e n ' s s y n d r o m e .
T h e
f r e q u e n c y a n d
n a t u r e o f
p l e u r o p u l m o n a r y
m a n i f e s t a t i o n s
i n
p r i m a r y
b i l i a r y
c i r r h o s i s
( P B C ) a r e
p o o r l y
d o c u m e n t e d .
T h e
f i n d i n g
o f
b o t h
a n
i n t e r -
s t i t i a l
p a t t e r n
on
c h e s t
r a d i o g r a p h s
a n d
a
r e s t r i c t i v e
v e n t i l a t o r y i m p a i r m e n t
w i t h a
g a s
t r a n s f e r
d e f e c t
o n
r o u t i n e l u n g
f u n c t i o n t e s t s
i n
s o m e
c a s e s
o f
c h r o n i c
a c t i v e h e p a t i t i s
a n d
PBC
h a s
l e d
s o m e
a u t h o r s
t o
s u g g e s t
t h a t
f i b r o s i n g
a l v e o l i t i s
c o u l d
b e
a s s o c i a t e d
w i t h
c h r o n i c l i v e r
d i s e a s e , l
2
a l t h o u g h
o t h e r s h a v e
b e e n u n a bl e t o
f i n d
s u c h a n
a s s o c i a t i o n . 3
4
F u r t h e r -
m o r e , PBC
i s
f r e q u e n t l y
a s s o c i a t e d
w i t h
S j 6 g r e n ' s
s y n d r o m e ,
a n
e n t i t y
i n
w h i c h
t h e
i n t e r p r e t a t i o n
o f
l u n g
d i s e a s e r e m a i n s
d i f f i c u l t . 5
I n
t h e p r e s e n t
s t u d y
we h a v e
i n v e s t i g a t e d
t o w h a t
e x t e n t
PBC i s
a s s o c i a t e d
w i t h
p u l m o n a r y
s i g n s , s y m p t o m s ,
r a d i o l o g i c a l
a n d
f u n c t i o n a l a b n o r m a l i t i e s
a n d h a v e m a d e
c o m p a r i s o n s
w i t h
a
h e a l t h y
c o n t r o l
p o p u l a t i o n
a n d
w i t h
a
g r o u p
o f
p a t i e n t s
a f f e c t e d
b y
t h e
s o - c a l l e d S i c c a
c o m p l e x ,
a
l i m i t e d v a r i a n t
o f
S j o g r e n ' s
s y n d r o m e .
M e t h o d s
T h e
f o l l o w i n g c a t e g o r i e s
o f
p a t i e n t s , m a t c h e d
f o r
s e x ,
a g e ,
h e i g h t ,
a n d
s o c i o e c o n o m i c
s t a t u s
w e r e
s t u d i e d :
s e v e n w i t h
PBC a n d
S j 6 g r e n ' s
s y n d r o m e ,
s e v e n
w i t h
PBC a l o n e ,
s e v e n
w i t h
S i c c a
c o m p l e x ,
a n d
1 4
n o r m a l
s u b j e c t s ( t a b l e
1 .
A l l
w e r e
n o n - s m o k e r s
who
g a v e
no
h i s t o r y
o f
a l c o h o l i s m ,
o c c u p a t i o n a l
A d d r e s s f o r r e p r i n t
r e q u e s t s :
Dr
R o d r i g u e z - R o i s i n , S e c t i o n
o f
P h y s i -
o l o g y
M - 0 2 3 , D e p a r t m e n t
o f
M e d i c i n e ,
S c h o o l o f
M e d i c i n e , U n i v e r s i t y
o f
C a l i f o r n i a ,
S a n
D i e g o ,
La
J o l l a ,
C a l i f o m i a
9 2 0 9 3 ,
USA.
T a b l e
1
P h y s i c a l d a t a i n
g r o u p s i n v e s t i g a t e d
C a t e g o r y S e x
A g e H e i g h t
( F I M )
( y e a r s ± S D )
( c m
±
SD )
H e a l t h y c o n t r o l s u b j e c t s
1 3 1
4 6 - 9 ±
9 4
1 5 4 - 6 ± 4 - 1
(n= 1 4 )
P r i m a r y b i l i a r y c i r r h o s i s
1 3 / 1
4 6 - 3 + 1 0 - 3
1 5 4 - 9 ± 5
8
( P B C )
( o v e r a l l
s e r i e s )
PBC
w i t h o u t
S j 6 g r e n ' s 7 / 0
4 2
9±100
1 5 3
1±3
4
S y n d r o m e
( n = 7 )
PBC
w i t h
S j d g r e n ' s
6 / 1
4 9 - 7 ± 1 0 - 0
1 5 6 - 5
± 7 - 4
S y n d r o m e
( n = 7 )
S i c c a
c o m p l e x ( n = 7 )
7 / 0
4 8 - 7 ±
7 - 1
1 5 2 - 4 ± 5
7
e x p o s u r e
t o
d u s t s
known
t o c a u s e
l u n g
d a m a g e ,
c a r d i o p u l m o n a r y
o r
a u t o i m m u n e
d i s e a s e s ,
o r
p r e -
v i o u s m e d i c a t i o n
w i t h
p o t e n t i a l l y
f i b r o g e n i c d r u g s .
T h e
d i a g n o s i s
o f
PBC
w a s
b a s e d
on
c l i n i c a l a n d
m o r p h o l o g i c a l
d a t a .
A l l
p a t i e n t s
h a d a
s e r u m
a l k a l i n e
p h o s p h a t a s e l e v e l
h i g h e r
t ha n 3 0 0
mU/ml
( n o r m a l
<
8 5
m U / m l )
a n d
a
p o s i t i v e
a n t i m i t o c h o n d r i a l
a n t i b o d y
t e s t .
E i g h t
o f
t h e m
h a d a
s e r u m
b i l i r u b i n
h i g h e r
t h a n
3 4
j p m o l / l .
A c c o r d i n g
t o
t h e l i v e r
b i o p s y
t h r e e
w e r e
s t a g e
1 ,
f i v e
s t a g e I I ,
f i v e
s t a g e I I I ,
a n d
o n e
s t a g e
I V .
T h e
d i a g n o s i s
o f
S i c c a
c o m p l e x
w a s
a c c e p t e d
w h e n b o t h
k e r a t o c o n j u n c t i v i t i s
a n d
x e r o s t o m i a
w e r e
p r e s e n t
( t a b l e 2 .
T h e
d i a g n o s i s
o f
k e r a t o c o n j u n c t i v i t i s
w a s b a s e d on
t h e
p r e s e n c e
o f
c l i n i c a l
s y m p t o m s ,
a n
a b n o r m a l
S c h i r m e r ' s
t e s t
( w e t t i n g
o f a
p a p e r
s t r i p
5 mm
o r
l e s s
i n
5
m i n )
a n d
R o s e
b e n g a l
o c u l a r
s t a i n i n g
i n
t h e
c o n j u n c t i v a l
s a c . 6
X e r o s t o m i a was
r e c o g n i s e d
b y
c l i n i c a l
h i s t o r y ,
b y
a b n o r m a l
b i l a t e r a l
p a r o t i d
g l a n d
s c i n t i g r a m s
a f t e r
2 0 8
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P u l m o n a r y
i n v o l v e m e n t
i n
p r i m a r y b i l i a r y
c i r r h o s i s
T a b l e 2 I n v e s t i g a t i o n
o f k e r t o c o n j u n c t i v i t i s a n d x e r o s t o m i a
C a s e s
L a c r i m a l
S c h i r m e r s
R o s e B e n g a l S a l i v a r y P a r o t i d
g l a n d L i p
g l a n d t e s t
s t a i n g l a n d s
s c i n t i g r a m b i o p s y
s y m p t o m s
s y m p t o m s
P BC
w i t h o u t
S j 6 g r e n ' s
s y n d r o m e
1
N
2
ND
3
_ _
+
ND
4
_ _
+
_
-
-
-
-
-
+
6
- -
- ND
7
- -
-
-
-
ND
PBC
w i t h
S j o g r e n ' s s y n d r o m e
1
2
NR
3
- -
-
4
-
ND ND
S
- -
6
-
7
-
+
+
+
S i c c a
c o m p l e x
1
-
2
-
3
ND
4
-
5
ND
6
-
7
-
-
ND =n ot d o n e ;
NR=not
r e l i a b l e ; ( - ) = a b s e n t ;
( + ) = p r e s e n t .
i n t r a v e n o u s
a d m i n i s t r a t i o n
o f
4 mCu
o f 9 9 m T c
p e r t e c h n e t a t e , 7
a n d
b y
a b n o r m a l
l i p b i o p s y . 8
T h e
d i a g n o s i s
o f
b o t h
k e r a t o c o n j u n c t i v i t i s
a n d x e r o s t o m i a
r e q u i r e d
t h e
p r e s e n c e
o f
a t l e a s t
t w o
o f
t h e i r
r e s p e c t -
i v e d i a g n o s t i c c r i t e r i a .
S j 6 g r e n ' s s y n d r o m e
w a s
c o n s i d e r e d
t o
b e
p r e s e n t
w h e n
k e r a t o c o n j u n c t i v i t i s
o r
x e r o s t o m i a
o r
b o t h
o c c u r r e d
w i t h
P B C . 5
C o n t r o l
s u b j e c t s
w e r e
j u d g e d
t o b e n o r m a l o n
t h e b a s i s o f
n e g a t i v e
h i s t o r i e s
o f
a c u t e
a n d / o r c h r o n i c
d i s e a s e s ,
n o r m a l p h y s i c a l
e x a m i n a t i o n , a n d n o r m a l c h e s t
r o e n t g e n o g r a m s .
On
t h e
d a y
o f
s t u d y
e a c h
p a r t i c i p a n t
w a s s u b m i t t e d
t o a m o d i f i e d
r e s p i r a t o r y
q u e s t i o n n a i r e 9
a n d
w a s
e x a m i n e d
b y
t w o
c h e s t p h y s i c i a n s . P o s t e r o a n t e r i o r
c h e s t
r a d i o g r a p h s
w e r e
p e r f o r m e d ,
a n d
e a c h
e x a m i n e d
a n d
g r a d e d
i n d e p e n d e n t l y b y f i v e
e x p e r i e n c e d
o b s e r v e r s a c c o r d i n g
t o
t h e
1 9 7 1
I L O - U / C s t a n d a r d
c l a s s i f i c a t i o n .
1 0
L u n g
f u n c t i o n
s t u d i e s
w e r e
p e r f o r m e d
a s
f o l l o w s :
( 1 )
a r t e r i a l
P a o 2
a n d
P a c o 2
( 7 2 , R a d i o m e t e r ) ;
( 2 )
t h o r a c i c g a s
v o l u m e
( V t g ) a n d a i r w a y r e s i s t a n c e
( R a w )
u s i n g
a c o n s t a n t - v o l u m e
b o d y
p l e t h y s m o g r a p h
( B o d y - P n e u m o t e s t ,
E
J a e g e r ) , t h e
r e s u l t s
b e i n g
r e p o r t e d
a s
s p e c i f i c
a i r w a y c o n d u c t a n c e
( s G a w ) ; ( 3 )
t o t a l
l u n g c a p a c i t y
( T L C )
a n d
r e s i d u a l
v o l u m e
( R V )
w e r e
c a l c u l a t e d
f r o m V t g ; ( 4 ) s i n g l e - b r e a t h
t r a n s f e r
f a c t o r ( TL C O ) ( R e s p a r a m e t e r
M K - I V , M o r g a n )
w i t h
c o r r e c t i o n f o r a n a e m i a 1 2
a n d
c a l c u l a t i o n
o f t r a n s f e r
c o e f f i c i e n t
( K c o ) ;
( 5 )
F o r c e d
v i t a l
c a p a c i t y
( F V C ) ,
f o r c e d
e x p i r a t o r y
v o l u m e
i n
o n e s e c o n d ( F E V 1 ) ,
p e a k
f l o w
( P E F ) , f o r c e d
m i d - e x p i r a t o r y
f l o w
( V 2 5 - 7 5 ) ,
f o r c e d
e n d - e x p i r a t o r y
f l o w
( V 7 5 - 8 5 ) ,
a n d
m a x i m a l
f l o w
r a t e s a t
50
a n d
75
o f t h e
FVC
( V 5 0
a n d
V 7 5 ,
r e s p e c t i v e l y )
( F l e i s c h p n e u m o -
t a c h o g r a p h ,
HP
4 7 3 0 4
A ) ;
( 6 )
s t a t i c
e x p i r a t o r y
c o m p l i a n c e
o f
t h e
l u n g ( C s t a t )
c l o s e
t o
f u n c t i o n a l
r e s i d u a l
c a p a c i t y
w a s
r e c o r d e d
u s i n g
a n
o e s o p h a g e a l
l a t e x - b a l l o o n
a n d
a s h u t t e r
i n t e r r u p t e r
( E
J a e g e r ) ,
a c c o r d i n g
t o
t h e
m e t h o d
o f . M i l i c
E m i l i
e t
a l . 1 3
T h e
p u l m o n a r y
f u n c t i o n
t e s t s
( s G a w ,
V t g ,
D L C O ,
s t a t i c l u n g
v o l u m e s ,
a n d MEFV
c u r v e s )
w e r e
p e r f o r m e d
o n
t w o
s e p a r a t e
o c c a s i o n s
i n
e a c h
c o n t r o l
s u b j e c t
a n d
o n t h r e e o c c a s i o n s
i n
t h e
g r o u p s
o f
p a t i e n t s .
A r t e r i a l b l o o d g a s e s
a n d
C s t a t
( o n l y
r e l i a b l e
i n 1
1 o u t o f
1 4
c a s e s )
w e r e
m e a s u r e d
o n
t w o
s e p a r a t e
o c c a s i o n s
i n
p a t i e n t s
w i t h
P B C .
T h e
d a t a
a n a l y s e d
f o r
e a c h
p a r t i c i p a n t
w e r e
t h e
a v e r a g e
o f
t w o
o r
t h r e e v a l u e s .
I n
e a c h s u b j e c t
l u n g
f u n c t i o n
s t u d i e s
a n d
c l i n i c a l
a n d
r a d i o l o g i c a l
e x a m i n a t i o n
w e r e
p e r f o r m e d
o n
t h e
s a m e d a y b y s e p a r a t e
o b s e r v e r s
a n d
n o
r e s u l t s
w e r e
r e v e a l e d
u n t i l
t h e
s t u d y
w a s
c o m p l e t e d .
S t a t i s t i c a l
a n a l y s i s
o f t h e r e s u l t s
u s e d
o n e - w a y
a n a l y s i s
o f
v a r i a n c e
w i t h
a
p r i o r i c o n t r a s t ,
a n d
w i t h
P e a r s o n s l i n e a l c o r r e l a t i o n c o e f f i c i e n t s .
W r i t t e n
i n f o r m e d
c o n s e n t
w a s
o b t a i n e d
f r o m
a l l
s u b j e c t s .
R e s u l t s
CLINICAL
AND
RADIOLOGICAL
FEATURES
T h e
p u l m o n a r y
c l i n i c a l a n d
r a d i o l o g i c a l c h a r a c t e r -
i s t i c s
o f t h e p a t i e n t s w i t h PBC
a n d
o f
t h o s e
w i t h
S i c c a
c o m p l e x
a r e
s u m m a r i s e d
i n
t a b l e
3 .
S i g n s
a n d
2 0 9
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R
R o d r i g u e z - R o i s i n e t
a l
T a b l e 3 P r e v a l e n c e
o f
a b n o r m a l r e s p i r a t o r y c l i n i c a l
a n d
r a d i o l o g i c a l f e a t u r e s
i n
p a t i e n t s
w i t h
p r i m a r y
b i l i a r y
c i r r h o s i s a n d S i c c a
c o m p l e x .
P BC PBC
w i t h S i c c a
F e a t u r e s w i t h o u t
S j o g r e n ' s
c o m p l e x
S j 6 g r e n ' s
s y n d r o m e
( n
=
7 )
s y n d r o m e
( n = 7 )
( n = 7 )
Cough
0
1
4
S p u t u m 0 1
2
D y s p n o e a
0
1
0
C l u b b i n g
2 0
W h e e z i n g 0 0 0
C r a c k l e s 0
0 1
A b n o r m a l
c h e s t
r a d i o g r a p h 0
1
*
0
* G r a d e d
l
s y m p t o m s
w e r e
uncommon
among p a t i e n t s
w i t h
l i v e r
d i s e a s e a l o n e b ut
w e r e
p r e s e n t i n
f o u r
o u t o f t h e
s e v e n w i t h a s s o c i a t e d
S j d g r e n ' s s y n d r o m e . One
p a t i e n t
h a d
m i l d
d y s p n o e a , a n o t h e r h a d c o u g h w i t h
s c a n t y
p h l e g m ,
a n d t w o o t h e r s
h a d
f i n g e r
c l u b b i n g ;
o n e
o f
whom
h a d
a n a b n o r m a l
c h e s t
f i l m ,
w h i c h
w a s
g r a d e d 1 / 1 ( I L O - U / C ) ' 6 . O n l y o n e p a t i e n t
w i t h PBC
b u t n o
S j o g r e n ' s s y n d r o m e s h o w e d d i g i t a l
c l u b b i n g .
F i v e
p a t i e n t s w i t h t h e S i c c a c o m p l e x h a d s i g n s
a n d / o r
s y m p t o m s : t w o
h a d
d r y c o u g h ,
t w o h a d
a s l i g h t
p r o d u c t i v e c o u g h , a n d o n e
h a d
u n i l a t e r a l c r a c k l e s .
PULMONARY FUNCTION T E S T I N G
T h e
mean F V C ,
F E V 1 ,
a n d
FEV1/FVC
o f t h e 1 4
h e a l t h y
s u b j e c t s i n v e s t i g a t e d
w e r e 1 0 6 ,
9 5 , a n d
86
o f
t h e i r
p r e d i c t e d
v a l u e s ' 4
r e s p e c t i v e l y ;
V t g ,
T L C ,
V C ,
R V , a n d RV/TLC
w e r e
1 1 9 ,
1 1 1 ,
1 0 9 ,
1 1 9 , a n d 1 0 8
o f
t h e i r
r e s p e c t i v e p r e d i c t e d
v a l u e s 1 5 ;
DLCO
a n d
Kco
w e r e
1 1 4
a n d 1 1 3
o f
t h e i r
r e s p e c t i v e p r e d i c t e d v a l u e s ' 6 1 7 ; a n d P E F ,
V 2 5 - 7 5 ,
V 7 s _ 8 5 , V 5 0 ,
a n d V 7 s w e r e 9 4 ,
6 7 ,
5 2 , 7 2 , a n d 4 0 ,
o f
t h e i r p r e d i c t e d
v a l u e s
r e s p e c t i v e l y . ' 4
1 8
When
t h e s e
d a t a
w e r e c o m p a r e d
b e t w e e n
t h e
g r o u p s s t u d i e d , n o s i g n i f i c a n t d i f f e r e n c e s
w e r e
f o u n d
f o r
m a x i m a l
m i d
a n d e n d - e x p i r a t o r y
f l o w
r a t e s , s t a t i c l u n g v o l u m e s , a n d s G a w . S t a t i c
l u n g
c o m p l i a n c e
a n d
i n
a l l
b u t
t w o
c a s e s
P a o 2
a n d
P a C O 2
w e r e
w i t h i n
p r e d i c t e d
n o r m a l
l i m i t s . ' 6
M i l d
h y p o x -
a e m i a ( l O k P a )
w a s
o b s e r v e d i n t w o
4 5 - y e a r - o l d w o m e n
w i t h
PBC
w i t h
a n d w i t h o u t
S j 6 g r e n ' s
s y n d r o m e
r e s p e c t i v e l y . No
d i f f e r e n c e s
i n a r t e r i a l
b l o o d
g a s e s
a n d
C s t a t
w e r e
o b s e r v e d b e t w e e n
a n y p a t i e n t g r o u p .
Mean
TLCO
w a s
s i g n i f i c a n t l y
l o w e r
b o t h
i n
p a t i e n t s
w i t h
PBC
p l u s S j o g r e n ' s s y n d r o m e ( 2 0 - 5
±1
6 m l
m i n -
mmHg)
a n d
i n
p a t i e n t s
w i t h S i c c a
c o m p l e x
( 2 0 - 4 ± 1
. 1
m l m i n -
m m H g - ) ,
t h a n
i n c o n t r o l s
( 2 5 - 8 ± 1 * 6
m l m i n -
m m H g - ) ( p < 0 - 0 2
a n d
p < 0
0 1 6 ,
r e s p e c t i v e l y ) .
Mean T L C O
i n
PBC p a t i e n t s
w i t h o u t
S j 6 g r e n ' s s y n d r o m e , ( 2 4 - 7 ± 0 - 6
m l
m i n -
m m H g - )
w a s
n o r m a l . Mean Kco
w a s
a l s o s i g n i f i -
c a n t l y
l o w e r
i n
p a t i e n t s
w i t h
PBC
p l u s S j o g r e n ' s
s y n d r o m e ( 5 - 3
±0
4 m i n - mmHg- )
t h a n i n
t h o s e
w i t h o u t i t
( 6 A 4 ± 0 - 3
m i n -
m m H g - ) ,
b u t mean
Kco
d i d n o t d i f f e r
s i g n i f i c a n t l y f r o m
c o n t r o l s
i n e i t h e r o f
t h e s e g r o u p s .
D i s c u s s i o n
T h e
f i r s t
a c c o u n t o f a
c l i n i c a l a s s o c i a t i o n
b e t w e e n
l u n g
f i b r o s i s a n d
PBC w a s g i v e n
b y Mason e t a 1 2 i n
1 9 7 0 , T u r n e r - W a r w i c k h a v i n g
p r e v i o u s l y
d r a w n
a t t e n t i o n
t o
t h e a s s o c i a t i o n o f p u l m o n a r y
f i b r o s i s
w i t h o t h e r c h r o n i c l i v e r d i s e a s e s . L a t e r G o l d i n g e t
a l ' 9
a d d e d f u r t h e r
o b s e r v a t i o n s
a n d r e p o r t e d
t h e
p r e s e n c e
o f
g a s
t r a n s f e r
d e f e c t s , w i t h e i t h e r
a n
a b n o r m a l
c h e s t
f i l m o r
a
r e s t r i c t i v e v e n t i l a t o r y
i m p a i r m e n t ,
i n
s e v e r a l
p a t i e n t s
w i t h
c h r o n i c
l i v e r d i s e a s e
i n c l u d i n g
P B C .
H o w e v e r
i n
t w o
p a t i e n t s
w i t h
PBC
who c a m e
t o
n e c r o p s y
S t a n l e y
e t a 1 3 f o u n d
w i d e s p r e a d i n t r a -
p u l m o n a r y g r a n u l o m a s
w i t h o u t
f i b r o s i s ,
o n e s u b j e c t
h a v i n g a n i n t e r s t i t i a l r a d i o g r a p h i c
p a t t e r n
a n d
a n
i m p a i r m e n t
o f
t h e t r a n s f e r
f a c t o r .
T h e p r e s e n t
s t u d y
s u g g e s t s t h a t
t h e
i n c i d e n c e
o f
c l i n i c a l , r a d i o g r a p h i c
a n d
f u n c t i o n a l a b n o r m a l i t i e s
i s
v e r y l o w a n d t h a t w h e n p r e s e n t i t may
b e r e l a t e d
t o
t h e
e x i s t e n c e
o f
a n
a s s o c i a t e d S j o g r e n ' s s y n d r o m e .
O n l y
f o u r o u t
o f
1 4
p a t i e n t s
w i t h
PBC h a d
o n e
o r
m o r e c l i n i c a l a n d / o r r a d i o l o g i c a l m a n i f e s t a t i o n s
o f
p u l m o n a r y
d i s e a s e
a n d a l l h a d
k e r a t o c o n j u n c t i v i t i s
s i c c a ,
x e r o s t o m i a o r
b o t h .
D i g i t a l
c l u b b i n g
w a s
o b s e r v e d i n
o n e
p a t i e n t
w i t h
PBC
n o t
a s s o c i a t e d
w i t h
S j 6 g r e n ' s
s y n d r o m e
b u t
t h i s f e a t u r e
c a n n o t
b e
r e l a t e d
s p e c i f i c a l l y
t o
p u l m o n a r y
d i s e a s e .
T h e
o n l y c o n s i s t e n t l y
a b n o r m a l l u n g
f u n c t i o n
f i n d i n g
w a s
t h e
r e d u c t i o n
o f
g a s
t r a n s f e r f a c t o r
w h i c h
w a s
o b s e r v e d
i n
p a t i e n t s
w i t h PBC
a s s o c i a t e d
w i t h
S j 6 g r e n ' s
s y n d r o m e
a n d
i n
p a t i e n t s
w i t h
t h e
S i c c a
c o m p l e x .
T h e s e
d a t a
s u g g e s t
t h a t t h e
d e v e l o p -
m e n t
o f
a n
a b n o r m a l
d i f f u s i n g c a p a c i t y
i n
p a t i e n t s
w i t h
P B C ,
i s somehow r e l a t e d
t o
a n a s s o c i a t e d
S j 6 g r e n ' s s y n d r o m e
a n d
n o t t o
l i v e r d i s e a s e
i t s e l f .
C o m p a r i s o n s
o f
t h e r e s u l t s
o f
t h e
p r e s e n t
i n v e s t i -
g a t i o n
w i t h
p r e v i o u s
r e p o r t s
c a n n o t
b e made
b e c a u s e
o f
d i f f e r e n c e s
i n
f o r m a t a n d b e c a u s e i n
p a p e r s
p r e v i o u s l y
r e p o r t i n g
a n
a s s o c i a t i o n
b e t w e e n PBC a n d
l u n g
f i b r o s i s
i t
h a s n o t
b e e n
s t a t e d
t h a t
f a c t o r s n o x i o u s
t o t h e
l u n g
s u c h a s
t o b a c c o ,
a l c o h o l , o c c u p a t i o n a l
o r
n o n o c c u p a t i o n a l e x p o s u r e
t o
d u s t ,
a s s o c i a t e d c l i n i c a l
c o n d i t i o n s ,
a n d
i a t r o g e n i c
f a c t o r s
h a v e
b e e n e x c l u d e d .
F u r t h e r m o r e
t h e
p r e s e n c e
o f an a s s o c i a t e d S i c c a
c o m p l e x ,
t o
w h i c h
p u l m o n a r y i m p a i r m e n t may
b e
r e l a t e d ,
h a s n o t b e e n
i n v e s t i g a t e d p r e v i o u s l y .
R e c e n t l y
C l a r k e
e t a 1 2 0
h a v e
r e p o r t e d
a
h i g h
i n c i d e n c e
o f
m i l d
s c l e r o d e r m a
i n
a s e r i e s
o f
p a t i e n t s
w i t h PBC
i n
s o m e
o f
whom
r e s p i r a t o r y
f u n c t i o n a l
a b n o r m a l i -
t i e s ,
s u c h
a s
g a s
t r a n s f e r
i m p a i r m e n t
a n d
a i r w a y
o b s t r u c t i o n
w e r e
d e t e c t e d .
2 1 0
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P u l m o n a r y
i n v o l v e m e n t i n p r i m a r y
b i l i a r y
c i r r h o s i s
A
w i d e
r a n g e
o f
p u l m o n a r y
a b n o r m a l i t i e s
h a s
b e e n r e p o r t e d
i n
p a t i e n t s
w i t h t h e S i c c a c o m p l e x ,
e i t h e r
i n
i s o l a t i o n
o r i n a s s o c i a t i o n
w i t h a c o n n e c t i v e
t i s s u e
d i s o r d e r - t h a t i s , S j o g r e n ' s
s y n d r o m e . 5 Some
o f t h e s e
a r e p u r e l y m o r p h o l o g i c a l ,
s u c h a s
l y m p h o -
c y t i c
a n d
p l a s m a
c e l l i n f i l t r a t i o n
o f
t h e
t r a c h e a
a n d
t h e l a r g e a n d s m a l l
a i r w a y s . O t h e r s h a v e
c l i n i c a l
r e l e v a n c e - f o r e x a m p l e ,
d i m i n i s h e d m u c o u s s e -
c r e t i o n s
c a u s e d b y b r o n c h i a l
m u c o u s g l a n d
d e s t r u c -
t i o n
i n
l a r g e a i r w a y s ,
b r o n c h o p u l m o n a r y
i n f e c t i o n s
r e l a t e d
t o
d r y n e s s
o f t h e r e s p i r a t o r y t r a c t ,
p l e u r a l
e f f u s i o n s , f i b r o s i n g
a l v e o l i t i s o f b o t h
t h e m u r a l a n d
d e s q u a m a t i v e
t y p e s ,
a n d
l y m p h o c y t i c
i n t e r s t i t i a l
p n e u m o n i t i s .
I n
a
f e w
p u l m o n a r y
f u n c t i o n s t u d i e s
o f p a t i e n t s
s u f f e r i n g
f r o m d i f f e r e n t
c o n n e c t i v e
t i s s u e d i s o r d e r s ,
t h e
e x i s t e n c e
o f
a
g a s
t r a n s f e r
d e f e c t w i t h o r
w i t h o u t
v e n t i l a t o r y
i m p a i r m e n t
h a s
b e e n
n o t e d
i n
s o m e
p a t i e n t s
w i t h S j o g r e n ' s s y n d r o m e . 2 1 - 2 3
I n a s e r i e s
o f
p a t i e n t s
w i t h t h e
S i c c a
c o m p l e x ,
s t u d i e d
b y
N e w b a l l
a n d B r a h i m , 2 4
a l m o s t o n e - h a l f h a d s m a l l a i r w a y s
d y s f u n c t i o n
u n a s s o c i a t e d
w i t h
c h r o n i c
o b s t r u c t i v e
l u n g
d i s e a s e .
H o w e v e r ,
m o s t o f t h e s e s t u d i e s f a i l e d t o e x c l u d e
a
n u m b e r o f
f a c t o r s w h i c h c o u l d
h a v e c o n t r i b u t e d t o
t h e d e v e l o p m e n t
o f
l u n g d i s t u r b a n c e s ,
p a r t i c u l a r l y
t h o s e
c l i n i c a l
c o n d i t i o n s
c h i e f l y
r e l a t e d
t o
c h r o n i c
l i v e r
d i s e a s e s u c h a s r e n a l f a i l u r e ,
f l u i d
r e t e n t i o n ,
o r
h e p a t i c
e n c e p h a l o p a t h y ,
o r
t h o s e c o n n e c t i v e t i s s u e
d i s o r d e r s
w h i c h
a r e
f r e q u e n t l y a s s o c i a t e d
w i t h
S j o g r e n ' s
s y n d r o m e
a n d
h a v e
a
f a i r l y
h i g h p r e v a l e n c e
o f
p l e u r o p u l m o n a r y
m a n i f e s t a t i o n s s u c h a s
r h e u m a -
t o i d a r t h r i t i s
a n d
s y s t e m i c l u p u s e r y t h e m a t o s u s .
I n
o u r
s t u d y
mean
T L C O
w a s
s i g n i f i c a n t l y
l o w e r
o n l y
i n
p a t i e n t s
w i t h
t h e S i c c a c o m p l e x
a n d
i n
t h o s e
w i t h
PBC
a s s o c i a t e d
w i t h
S j o g r e n ' s s y n d r o m e .
No
d i f f e r e n c e s
w e r e
o b s e r v e d
i n
a n y o t h e r
p a r a m e t e r
o f
l u n g
f u n c t i o n , e x c e p t
f o r
h y p o x e m i a i n t w o
n a t i e n t s
a n d
a d i f f e r e n c e i n m e a n
Kco b e t w e e n PBC
p a t i e n t s
w i t h
a n d
w i t h o u t
S j o g r e n ' s
s y n d r o m e ,
t h e
i n t e r p r e t -
a t i o n o f
w h i c h
i s u n c e r t a i n . M a x i m a l
a n d
m i d -
e x p i r a t o r y
f l o w r a t e s ,
c o n s i d e r e d
t o b e
a s e n s i t i v e
t e s t
f o r
e a r l y d e t e c t i o n
o f
s m a l l
a i r w a y
d y s f u n c t i o n ,
w e r e
m o s t l y b e l o w 7 0
o f
t h e i r
r e s p e c t i v e
p r e d i c t e d
v a l u e s
i n a l l
g r o u p s
s t u d i e d ,
i n c l u d i n g
t h e
c o n t r o l
g r o u p . A l t h o u g h
t h e
d i s c r i m i n a n t v a l u e
o f
t h e s e
m e a s u r e m e n t s
i s
s t i l l c o n t r o v e r s i a l , 2 5 i t i s
p o s s i b l e
t h a t e x p o s u r e t o
i n d u s t r i a l
o r u r b a n
p o l l u t a n t s , 2 6 o r
t h e
i n f l u e n c e
o f
h i t h e r t o u n i d e n t i f i e d e n v i r o n m e n t a l
f a c t o r s ,
c o u l d
b e
t h e
c a u s e
o f t h e s e
m i l d
r e s p i r a t o r y
f u n c t i o n a l a b n o r m a l i t i e s .
A l t h o u g h
a n y
c o n c l u s i o n
c o n c e r n i n g
c a u s e
a n d
m e c h a n i s m
i s
p r e m a t u r e ,
t h e
p r e s e n c e
o f a
g a s
t r a n s f e r
d e f e c t
i n
S j o g r e n ' s s y n d r o m e
m i g h t r e p r e s e n t
a
r e s p o n s e
t o
a
v a r i e t y
o f
r e s p i r a t o r y i n j u r i e s .
T h e
a b s e n c e o f
a n y
s i g n i f i c a n t
v e n t i l a t o r y
i m p a i r m e n t
i n
o u r s e r i e s a n d i t s p r e s e n c e i n
p a t i e n t s s t u d i e d b y
o t h e r s
w o u l d s u g g e s t
t h a t
S j b g r e n ' s
s y n d r o m e
i s
a
p r o g r e s s -
i v e
d i s o r d e r
w i t h a w i d e
s p e c t r u m
o f
p u l m o n a r y
f u n c t i o n a l
a b n o r m a l i t i e s .
I n c o n c l u s i o n , i t a p p e a r s
t h a t t h e c l i n i c a l ,
p h y s i o -
l o g i c a l ,
a n d
r a d i o g r a p h i c
m a n i f e s t a t i o n s
o f
p u l m o n -
a r y d i s e a s e
o b s e r v e d i n p a t i e n t s
w i t h
PBC a r e t h e
r e s u l t
o f
a n
a s s o c i a t e d c o n n e c t i v e
t i s s u e
d i s o r d e r ,
s u c h
a s S j 6 g r e n ' s
s y n d r o m e , r a t h e r
t h a n t h e r e s u l t
o f
PBC p e r s e .
W e a r e i n d e b t e d t o
P r o f e s s o r C
R o z m a n ,
Dr J
S a n c h i s - A l d a s , a n d Dr E
R o s , f o r s u g g e s t i o n s
i n
t h e
p r e p a r a t i o n
o f t h e
m a n u s c r i p t ,
a n d t o M r s C
G i s t a u
a n d
G G o d o y ,
r e s p i r a t o r y
p h y s i o l o g y t e c h n i c i a n s ,
f o r
t h e i r a s s i s t a n c e .
R e f e r e n c e s
1
T u r n e r - W a r w i c k M.
F i b r o s i n g a l v e o l i t i s
a n d
c h r o n i c
l i v e r d i s e a s e . Q J Me d
1 9 6 8 ;
3 7 : 1 3 3 - 4 9 .
2
Mason AMS,
M c I l l M u r r a y
MB, G o l d i n g
P L ,
H u g h e s , DTD.
F i b r o s i n g
a l v e o l i t i s
a s s o c i a t e d
w i t h
r e n a l t u b u l a r a c i d o s i s .
B r MedJ 1 9 7 0 ;
4 : 5 9 6 - 9 .
3
S t a n l e y NN, W o o d g a t e D J .
M o t t l e d
c h e s t
r a d i o g r a p h
a n d
g a s t r a n s f e r
d e f e c t
i n
c h r o n i c
l i v e r
d i s e a s e .
T h o r a x
1 9 7 2 ;
2 7 : 3 1 5 - 2 3 .
4
S t a n l e y
NN, W i l l i a m s A J ,
Dewar
C A ,
B l e n d i s , LM,
R e i d
L .
H y p o x i a
a n d
h y d r o t h o r a c e s
i n a
c a s e o f
l i v e r
c i r r h o s i s :
c o r r e l a t i o n
o f p h y s i o l o g i c a l , r a d i o g r a p h i c ,
s c i n t i g r a p h i c , a n d
p a t h o l o g i c a l
f i n d i n g s .
T h o r a x
9 7 7 ;
3 2 : 4 5 7 - 7 1 .
5
S h e a m MA.
S j o g r e n ' s
s y n d r o m e .
P h i l a d e l p h i a :
WB
S a u n d e r s ,
1 9 71 : 9 - 2 3 4 .
6
Holm S . K e r a t o c o n j u n c t i v i t i s
s i c c a
a n d t h e
s i c c a
s y n d r o m e .
A c t a
O p h t h a l m o l 1 9 4 9 ;
S u p p l
n o 3 3 .
7
S c h a l l
G L ,
A n d e r s o n
L G ,
W o l f RO e t a l . X e r o s t o m i a
i n S j o g r e n ' s s y n d r o m e .
E v a l u a t i o n
b y s e q u e n t i a l
s a l i v a r y s c i n t i g r a p h y .
JAMA 1 9 7 1 ; 2 1 6 : 2 1 0 9 - 1 6 .
8
C h i s h o l m
DM, Mason
DK.
L a b i a l
s a l i v a r y g l a n d
b i o p s y i n S o j g r e n ' s
s y n d r o m e . J C l i n
P a t h o l 1 9 6 8 ;
2 1 : 6 5 6 - 6 0 .
9
M e d i c a l R e s e a r c h C o u n c i l . S t a n d a r d i z e d
Q u e s t i o n -
n a i r e o n
R e s p i r a t o r y
S y m p t o m s .
B r
Me d J
1 9 6 0 ;
2 : 1 6 6 5 .
1 0
ILO/UC
I n t e r n a t i o n a l
C l a s s i f i c a t i o n
o f
R a d i o g r a p h s
o f P n e u m o c o n i o s e s , 1 9 7 1 ( n o
2 2
r e v i s e d ) :
O c c u p a -
t i o n a l S a f e t y a n d
H e a l t h
S e r i e s .
G e n e v a :
I n t e r n a -
t i o n a l
L a b o u r
O f f i c e ,
1 9 7 2
1 1
D u b o i s A B , B o t e l h o
S Y , Comroe
JH J r .
A new
m e t h o d
f o r
m e a s u r i n g
a i r w a y
r e s i s t a n c e
i n man u s i n g
a
b o d y
p l e t h y s m o g r a p h :
v a l u e s i n
n o r m a l
s u b j e c t s
a n d i n
p a t i e n t s
w i t h
r e s p i r a t o r y
d i s e a s e s . J
C l i n
I n v e s t
1 9 5 6 ;
3 5 : 3 2 7 - 3 5 .
1 2
C o t e s J E ,
D a b b s
J M , E l w o o d P C ,
H a l l , AM,
M c D o n a l d , A , S a u n d e r s ,
M J . I r o n - d e f i c i e n c y
a n a e m i a :
i t s
e f f e c t o n
t r a n s f e r f a c t o r
f o r
t h e
l u n g
( d i f f u s i n g c a p a c i t y )
a n d
v e n t i l a t i o n
a n d c a r d i a c
f r e q u e n c y
d u r i n g s u b m a x i m a l e x e r c i s e . C l i n
S c i
1 9 7 2 .
4 2 : 3 2 5 - 3 5 .
2 1 1
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R R o d r i g u e z - R o i s i n
e t
a l
1 3
M i l i c - E m i l i J ,
Mead J , T u r n e r
JM,
G l a u s e r ,
EM.
I m p r o v e d t e c h n i q u e f o r
e s t i m a t i n g p l e u r a l
pressure
f r o m
e s o p h a g e a l b a l l o o n s .
J
A p p l
P h y s i o l
1 9 6 4 ; 1 9 :
2 0 7 - 1 1 .
1 4 K n u d s o n
R J ,
S l a t i n RC, L e b o w i t z
MD , B u r r o w s , B .
T h e m a x i m a l
e x p i r a t o r y f l o w - v o l u m e curve. N o r m a l
s t a n d a r d s ,
v a r i a b i l i t y ,
a n d
e f f e c t s
o f
age.
Am
R e v
R e s p i r D i s
1 9 7 6 ; 1 1 3 : 5 8 7 - 6 0 0 .
1 5
Goldman H I ,
B e c k l a k e MR . R e s p i r a t o r y
f u n c t i o n
t e s t s : V a l u e s
a t m e d i a n a l t i t u d e s
a n d t h e p r e d i c t i o n
o f
n o r m a l
r e s u l t s . Am R e v
T u b e r c 1 9 5 9 ; 7 9 : 4 5 7 - 6 7 .
1 6 C o t e s
J E . Lung
f u n c t i o n
a t
d i f f e r e n t
s t a g e s i n l i f e ,
i n c l u d i n g
r e f e r e n c e v a l u e s
i n
l u n g
f u n c t i o n ,
a s s e s s m e n t
a n d
a p p l i c a t i o n
i n
m e d i c i n e .
T h i r d e d i t i o n . O x f o r d :
B l a c k w e l l S c i e n t i f i c ,
1 9 7 5 : 3 4 0 - 3 9 5 .
1 7
B i l l i e t
L ,
B a i s i e r W, N a e d t s J P .
E f f e c t
d e
l a
t a i l l e ,
d u
sexe
e t
d e
l ' a g e sur
l a
c a p a c i t 6 d e d i f f u s i o n p u l m o n -
a i r e
d e l ' a d u l t e
n o r m a l .
J
P h y s i o l
( P a r i s )
1 9 6 3: 5 5:
1 9 9 - 2 0 0 .
1 8 M o r r i s
J F ,
K o s k i
A ,
B r e e s e J D .
N o r m a l v a l u e s a n d
e v a l u a t i o n
o f f or c e d e n d - e x p i r a t o r y
f l o w .
Am
R e v
R e s p i r
D i s 1 9 7 5 ;
1 1 1 : 7 5 5 - 6 2 .
1 9
G o l d i n g
P L , S m i t h
M. W i l l i a m s
R .
M u l t i s y s t e m
i n v o l v e m e n t i n
c h r o n i c l i v e r d i s e a s e s .
Am
JMed
1 9 7 3 ;
5 5 : 7 7 2 - 8 2 .
2 0
C l a r k e
AK,
G a l b r a i t h
RM, H a m i l t o n
EBD, W i l l i a m s
R . R h e u m a t i c
d i s o r d e r s
i n
p r i m a r y b i l i a r y
c i r r h o s i s .
Ann Rheum
D i s 1 9 7 8 ;
3 7 : 4 2 - 7 .
2 1
C a t t e r a l l
M,
R o w e l
NR:
R e sp i r a t o r y f u nc t i o n
s t u d i e s i n
p a t i e n t s
w i t h
c e r t a i n c o n n e c t i v e t i s s u e
d i s e a s e s .
B r J
D e r m a t o l 1 9 6 5 ;
7 7 : 2 2 1 - 5 .
2 2
M a s s a c h u s e t t s
G e n e r a l H o s p i t a l : C a s e
R e c o r d s ,
no . 2 8 - 1 9 7 5 .
N
E n g l J Me d 1 9 7 5 ;
2 9 3 : 1 3 6 - 4 4 .
2 3 S t r i m l a n
C V , Rosenow
E C , D i v e r t i e
MB,
H a r r i s o n ,
E G . P u l m o n a r y
m a n i f e s t a t i o n s
o f
S j o g r e n ' s
s y n d r o m e .
C h e s t 1 9 7 6 ;
7 0 : 3 5 4 - 6 1 .
2 4 N e w b a l l
HH, B r a h i m S A . C h r o n i c
o b s t r u c t i v e a i r w a y
d i s e a s e
i n
p a t i e n t s
w i t h
S j o g r e n ' s s y n d r o m e .
Am R e v
R e s p i r D i s 1 9 7 7 ;
1 1 5 : 2 9 5 - 3 0 4 .
2 5 S o b o l
B J . T h e
e a r l y
d e t e c t i o n
o f a i r w a y o b s t r u c t i o n :
a n o t h e r p e r s p e c t i v e .
Am
J Me d
1 9 7 6 ;
6 0 : 6 1 9 - 2 4 .
2 6 W h i t e J R ,
F r o e b
HF. S m a l l - a i r w a y s d y sf u n c t i o n
i n
n o n - s m o k e r s
c h r o n i c a l l y
e x p o s e d
t o
t o b a c c o s m o k e .
N
E n g l
J
Me d 1 9 8 0 ;
3 0 2 : 7 2 0 - 3 .
2 1 2
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primary biliary cirrhosis.Pulmonary involvement in
Picado, A Agusti-Vidal, F Burgos and J RodesR Rodriguez-Roisin, A Pares, M Bruguera, J Coll, C
doi: 10.1136/thx.36.3.2081981 36: 208-212Thorax
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