PULMONARY
FUNCTION
IN
CYSTIC
FIBROSIS
OF
THE
PANCREAS
By JOHN R. WEST, M.D., SHELDON M. LEvIN, M.D., AND PAUL A. DI SANT’AGNESE, M.D.
New York City
C
LINICAL as well as pathologic findingssuggest that the disturbances in lung
function which occur in the course of the
chronic pulmonary disease characteristically
associated with cystic fibrosis of the
pan-creas are largely a result of obstruction of
the smaller air passages by thickened
se-cretions and purulent exudate.’4 The
fre-quent occurrence, furthermore, of signs of
obstructive breathing, cyanosis, and in
Sc-verely ill patients, carbon dioxide retention,
indicates the general nature of this
func-tional impairment; but its further
delinea-tiOIl by specific physiologic measurement
has not heretofore been feasible owing to
the extreme youth of the average patient.
With the advent of intensive use of
anti-biotics in treatment,’ -5 however, increasing
numbers of individuals with recognized
pul-monary disease have become old enough to
cooperate in the performance of physiologic
studies. This report deals with the results
of studies of pulmonary function in six such
patients.
MATERIAL AND METHODS OF STUDY
Six children were studied, 4 males and 2
fe-males, aged 12 to 15 yr. Each had
charactenis-tic gastrointestinal findings of cystic fibrosis of
the pancreas (appendix) (table 1) and one
in-stance, Case 6 (G. D.), the diagnosis was later
confirmed at autopsy. Each, also, had obvious
pulmonary disease, the severity of which varied
widely within the group (appendix).
Pulmonary function tests were carried out
From tile Departments of Medicine and
Pedi-atrics, Columbia University College of Physicians
and Surgeons, New York City.
Supported in part by a grant from the Charles A.
Frueauff Research Gift and in part by the Robert
Bacon \Vhitney Fund for Cystic Fibrosis of the
Pancreas.
Read at the Society for Pediatric Research,
At-lantic City, May 1953.
(Received fr publication July 5, 1953.)
in accordance with methods previously
de-scnibed.’ Studies included determination of the
hung volumes and index of intrapulmonary
mix-ing; measurement of pulmonary ventilation at
rest, during and after a mild standard exercise;
determination of the arterial oxygen saturation
and carbon dioxide tension at rest and
imme-diately after exercise; and estimation of
maxi-mum breathing capacity before and after
in-halation of a vaporized bronchodilator drug.
Predicted normal values for vital capacity and
maximum breathing capacity were calculated
using formulae derived from observations on
normal children of comparable age,’ and the
predicted values for total lung capacity were
based upon the assumption that vital capacity
at this age comprises approximately 80% of
total lung capacity.”#{176} The ratio of dead
space-like ventilation0 to tidal volume was
calcu-lated according to the method of Bohr,”
assum-ing arterial pCO to be equivalent to alveolar
RESULTS AND COMMENT
In order to facilitate comparisons as well
as to delineate best the pattern of
pulmon-ary dysfunction which may be seen in cystic
fibrosis of the pancreas, the cases are
pre-sented in a sequence of increasing severity
of symptoms.
Case 1 (P. D.) who had but minimal
pul-monary disease according to clinical criteria
(appendix) had the least impairment of
function. Essentially normal lung volumes
(table 2), an insignificant reduction in
maxi-mum breathing capacity (table 3) (without
improvement following vaponefrin), and
only mild spirographic obstructive signs
0 The terlll “dead space-like ventilation” is
em-ployed in lieu of “dead space ventilation” in order
to convey the idea that the respiratory dead space
to carbon dioxide as determined by Bohr’s
equa-tion has physiologic rather than anatomic meaning.
The ratio of “dead space-like ventilation” to tidal
Fecal Fatt
gm., 4 % hr. dry
Ssveat) \‘ears on Electrolytes l)ietary
(nEq. I.) Regimen
Cl Na K
0 4 61 89 89 8 4
0 9 49 10 102 0) 9
0 26 30 13 ui 16 H
0 - - 93 97 H I
0 37 38 65 i:i:i 13 8
0 13 :3 109 18(1 2’2 II
156
J.
R. WEST,
S. M.
LEVIN
AND
P.
A. DI SANT’AGNESETABLE 1
PHYSICAL CHARACTERISTICS, LABORATORY FINDINGS AND I)IETARY HISTORY IN 6 PATIENTS WITH CYSTIC FIBROSIS OF PANCREAS
Physical (‘haracteristics
Name Age
Case ‘sex (vr) Height, cm. \\elght, kg.
Ohs. Pred.’ Ohs. Pred.’
Proteolytic
Enzymes
BSA, m2 Duodenum
(viscosi-metric u. ‘cc.)
1 PD. 14 171 165±17 48.0 54±O 1.55 M
V.0. 14 1.5 165±17 41.0 54±20 1.33
M
S C.J. 131 146 161±15 30.0 5l±O 1.13
M
4 RB. i5 149 165±11 37.5 58±17 I.6
.5 MN. 1l 140 157±13 9.5 48±17 1.09
6 G.I). 13 140 158±16 .5..5 48±19 1.O M
* Approximate normal mean ± standard deviations.6
tAverage of 3 day stool collection. Dietary fat intake: 50 to 70 gm/day. Maximum normal fecal fat value: 3 gni. ‘24 hr.. cquivalcnt
to percentage fat al)sorption of 96%.
All values for sweat (‘Iand Na are abnormally high and characteristic of cystic fibrosis of pancreas. Normal values for sweat electrolytes
(mEq./l.): (‘I4-SO (mean 3), Na 10-80 (mean 59), K 6- (mean 1) (di Sant’Agnese et ,il.).
Abbreviations:
lISA, m’-Body surface area in square meters. mEq./l. -Milliequivalents per liter.
M -Male.
F -Fem.ile.
Obs. -()bserved. Pred. -Predicted.
attested to the adequacy of his chest
bel-lows. Although there was dysfunction at the
alveolar level in that distribution of tidal
air to the alveoli was impaired
(
shown bythe increased index of intrapulmonary
mix-ing) there was no arterial hypoxia or carbon
dioxide retention (table 4).
Cases 2 and 3 (V. D. and C.
J.),
withpul-monary disease more advanced according
to clinical findings than in Case 1 (P. D.)
(
appendix), were seen to have greaterim-pairment of pulmonary function. A
some-what greater reduction in maximum
breath-ing capacity (without improvement after
vaponefrin) was noted in both instances
(table 3). In one, Case 3 (C.
J.),
there wasan abnormally high ratio of residual volume
to total lung capacity (table 2), indicating
the presence of diffuse emphysema. In
neither patient, however, was there arterial
unsaturation or carbon dioxide retention
after exercise although one
(
C.J.)
had anabnormal index of intrapulmonar mixing
and both had some increase ill dead
space-like ventilation (table 4).
In Case 4
(
R.
B.), the physiologic as wellas the clinical findings were indicative of
still further advanced disease. The low
maximum breathing capacity, reduced to
about half of that predicted (table 3) and
unaffected by vaponefrin, indicated that
ventilatory function was seriously impaired.
A moderate degree of diffuse emphysema
was present as denoted by an elevation in
the ratio of residual volume to total lung
capacity (table 2), but although
intrapui-monary mixing of air was obviously
im-paired and dead space-like ventilation was
increased, there was no arterial hypoxia or
---, Vital Capacity
Case BTPS Residual Volume
, BPTS
Total Lung
Capacity BTPS
H V
oo Spirographic Findings
Ohs. %
pred.*
Ohs. %
pre(l.*
Ohs. %
pred.*
3710 1’27 177 174 4987 136 26 Very rmiild prolongation of
expiration TABLE
LUNG VOLUMES AND h)lcsCRIp’nIoN OF SPIROGRAPHIC RECORDS IN
PATIENTS WIT!! CYSTIC FIBII0SIS OF PANCREAS
‘2 339() 122 1131 163 45s21 130
3 2575 100 18s5 84 4400 137
4 094 78 1013 152 31(17 93
5 1240 52 1117 189 357 So
6 785 33 1268 14 2053 69
25 Very mild prolongation of
expiration
41 Mil(l prolongation of expi-ration.
33 Mo(lerate prolongation of expiration. M.B.C. executed
iii position of n,aximal
in-fiation.
47 Mildl prolongation of
cx-piration.
6 Severe prolongation of
cx-piration. Air trapping. M.B.C. executed with small tidal voiune in position of
maximal inflation.
* Calculated frommi formulae of ‘I’urner and M(’Lean,’ assuming that the average normal ratio of residual volume
to total lung capacity is 0.0. Al)l)reViIltiOIIs:
R.V. = Residual volume.
T.L.C. = ‘robil lung capacity.
M.B.C. = Maximun breathing capacity. Ohs. = Observed.
1 pred. = Per ccitt of predicted.
BTPS = Body temperature and pressure, saturated with water vapor.
The two remaining patients in this group,
Cases 5 (M. N.) and 6 (C. D.), were victims
of severe chronic pulmonary disease.
Ven-tilatory function was impaired in both.
Maximum breathing capacity was reduced
to, 60% of that predicted in Case 5 (M. N.)
and to 31% in Case 6
(
C. D.), and, as in theother cases, was not aided by use of
vapo-nefrin. Each had severe impairment of
a!-veolar function also as indicated by
mark-edly abnormal distribution of tidal air to
the alveoli (table 4), an increased dead
space-like ventilation (table 4), and,
pos-sibly, by a reduction in the total lung
capacity despite an elevation in the residual
volume6 (table 2). Finally, unlike the
pre-0 Although this finding of a reduced total lung
capacity miay well signify that an eleillent of re-strictive fibrosis is to l)e found in advanced cases of this disease, it seems not unlikely tllat another
factor is responsible for its (levelOpIllent, viz.,
bronchial obstruction per se. Since air contained in
alveoli that are poorly or intermittently ventilated
may be relatively inaccessible to the type of
physi-ologic measurement employed hlere, grave
impair-nient of distribution of tidal air to the alveoli may
be ultimately expressed as a large discrepancy
be-tween the physiologic hung volume and the actual
CaSe
Red. 3
1 57.1 95 .5.() 15.1 13.7 6.1
49.6 84 5.1 13.7 14.0) 6.8
3 53.8 83 6.5 17.5 14.4 8.7
4 31.9 53 5.3 HO 9.s2 8.1
.5 37.7 60 7. 18.2 17.1 S.
6 ‘I.() 31 . 4.8 9.0 8.1 5.7
S Calculated from formulae of Turner and McLean.9
Abbreviations:
L/m/m2 BSA-liters per minute per square meter of I)ody surface area.
Ohs. -observed.
% Pred. -per cent of predicted.
Exer. -during standard exercise.
Rec. I -during first minute of recovery following exercise.
Ree. 5 -during fifth minute of recovery following exercise.
BTPS -body temperature and pressure, saturated with water vapor.
158
J.
R. WEST,
S. M. LEVIN AND P. A. DI SANT’AGNESETABLE 3
MAxIMCM BREAThING CAPACITY AND PULMONARY \ENTILATION mx 6
PATIENTS WITH CYSTIC FIBROSIS OF PANCREAS
Maximum Breathing Capacity
L/mn/m2 BSA& BTPS
Ohs. % Pred.*
Puimlmonary \entilation L’m/II12 BSA; BTPS
Rest Exer. Rec. I
ceding patients, these individuals had
mani-fest abnormalities of the arterial blood
(table 4). Case 5 (M. N.) was found to have
moderate arterial desaturation after
exer-cisc. Case 6 (C. D.) had severe arterial
anoxia at rest as well as after exercise and
also marked carbon dioxide retention.
DIscuSsIoN
In addition to providing information
about the type and degree of pulmonary
dysfunction which may result from cystic
fibrosis of the pancreas, these studies point
out to some extent the mechanisms which
bring about the physiologic disturbances.
One example illustrates the value of the
current intensive use of antibiotics in
ther-apy.
Mechanisms : Since the degree of
hyper-ventilation noted in these patients at any
stage of activity was never strikingly
in-creased (table 3) according to standards for
thorax noted clinically and seen on x-ray (Fig. 1) in
both of these cases suggests that such a discrepancy
may be present here. The reduced physiologic total
lung capacity may thus provide further evidence of
inadequate alveolar ventilation.
young adults8 while reductions in maximum
breathing capacity were in three instances
severe, it would seem that an increased
ventilatory requirement plays a small role
in the development of ventilatory
insuffici-ency in this disease. Of far greater
import-ance are factors which lead to a reduction
in ventilatory capacity. An augmented
re-sistance to air flow in the tracheobronchial
tree occasioned by bronchial obstruction
is probably most important among
altera-tions in breathing mechanics which may be
responsible for impairment of chest bellows
action. The altered chest configuration
see-ondary to emphysema may also be
sig-nificant in some cases since thoracic
hyper-inflation places the muscles of respiration
in a position of relatively poor mechanical
advantage.15 Whether at the same time a
decrease in pulmonary compliance,
occur-ring as a result of fibrosis secondary to
chronic infection or for other reasons,
further reduces ventilatory capacity or
aug-ments the effort of breathing must await
further study.
The almost constant finding of an
ab-normal index of intrapulmonary mixing in
Arterial Blood
----
P D ‘ Index ofSerum Serum ‘‘
intrapul-(‘2 content Serum pH CO’ tension monary
volumes % mm. Hg. mixing %‘
Rest Rec. 1 Rest Rec. 1 Rest Rec. I
58.8 59.7 7.4 7.40 40 4 0.3 4.5
50.4 5.9 7.35 7.34 40 43 0.38 2.1 55.0 51.7 7.40 7.39 39 38 0.34 3.5
55.8 56.6 7.36 7.35 43 45 0.35 3.4
55.4 52.6 7.39 7.35 41 42 0.87 7.1
76.6 78.8 7.30 7.30 67 69 0.36 10.1
a
Concentration of nitrogen in alveolar mmir at end of 7 nun. periO(l of breathing 100% oxygen. Abbreviations:cc. ‘rn-‘m2 lISA- cc. per minute per square meter of body surface area.
S’fpl) -dry gas, 0’ centigrade, 760 mm. barometric pressure. Rec. 1 ---during first minute of recovery following exercise.
P.1)5. ---physiologic dea(l space --respiratory dead space calculated from Bohr equation using arterial carbon dioxide tension,
and corrected for apparatus dead space.
V-r -tidal volume.
TABLE 4
OxYGEN CONSUMPTION, ARTERIAL BLOOm) \ALUES, 1)EAD SPACE-LIKE VENTILATION, AND INDEX OF
INTRAI’ULMONARY MIXING IN 6 PATIENTS WITh CYSTIC FIBROSIS OF PANCREAS
Oxygen Consumption
-
----
---Case .
cc. in m- llA glohin
Hema-S’l’Pl) gm./I00 tocrit
Rest Exer. (.
I 177 70 FL8 40.1
1.5.5 .508 13.7 4.6
3 170 538 H.8 40.3
4 1.55 43 13.6 41.3
.5 180 46 14.4 43.
6 134 54 13.7 43.7
Arterial
Oxygen Saturation
Rest Rec. I
97 93
9 95
99 95 93 96 96 87
76 61
evidence denoting an abnormal
alveolar-capillary membrane and the frequent
find-ing of an illcrease in dead space-like
venti-lation suggest that disturbances in gas
cx-change are largely due to deviations from
normal 111 the distribution of air and blood
to the alveoli, a result of both bronchial
obstruction and local circulatory
disturb-ances. Both arterial hypoxia and carbon
dioxide retention tend to occur when there
is inadequate ventilation of alveoli which
continue to be perfused with the normal
amount of capillary blood. Carbon dioxide
retelltion tends to occur also when large
numbers of alveoli are inadequately
per-fused though normally ventilated because
of the small volume of gas exchange
occur-ring in such alveoli. Hypercapnia will not
develop as long as there exists an adequate
ventilatory stimulus and the ventilatory
capacity necessary to sustain sufficient
corn-pensatory hyperventilation of normally
functioning alveoli, and significant arterial
desaturation will of course be delayed in
appearance by the particular affinity of
hemoglobin for oxygen even at low alveolar
oxygen tensions. Cases 5 and 6 (M. N. and
G.
D.) illustrate the first point. Theproc-esses of gas exchange were impaired in
1)0th, but Ill the former, carbon dioxide
re-tention was not present although there was
arterial anoxia after exercise. This patient
was able to eliminate carbon dioxide by
means of hyperventilation of well perfused
alveoli. In contrast, carbon dioxide retention
did occur in Case 6
(
C.
D.), presumablybecause the disturbance in gas exchange
was too great to be overcome by the
combi-nation of an enfeebled ventilatory apparatus
and a ventilatory stimulus which may have
been somewhat diminished.
Although not clearly apparent from these
studies, chronic carbon dioxide retention
and arterial unsaturation probably have
unfavorable effects in these patients similar
to those seen in chronic pulmonary
em-physema of other etiology. The same
see-ondary deviations from normal in the
nerv-ous regulation of respiration may occur.
The relatively minor increase in ventilation
with exercise
(
table 3) noted in Case 6(
G.
D.) despite marked carbon dioxidere-tention, affords one example of this. Carbon
dioxide narcosis,’7’ 18 occasionally seen in
connection with oxygen therapy in severely
ill patients, provides another.
Finally, although cor pulmonale was not
observed clinically in any of these patients,
the pattern of pulmonary dysfunction in
10
J.
R. WEST, S. M. LEVIN AND P. A. DI SANT5AGNESFFmc. 1. Postero-anterior and lateral view of chest in Case 6 (G. I).) at 13 yr.
of age (for discussion see text).
FIG. 2A. Postero-anterior view of chest in Case 2 FIG. 2B. Postero-anterior view of chest in Case 2
(V. D.) before institution of prolonged antibiotic (V. D.) after 1 yr. of continuous antibiotic
he one conducive to its development.1 Right
ventricular hypertrophy is often found at
necropsy in patients with advanced
pulmon-ary insufficiency2 and was present in Case
6 (G. D.) of this group.
Therapeutic Considerations : Whether the
initial pulmonary abnormality in cystic
fibrosis of the pancreas is the elaboration
of an al)norrnal bronchial secretion as a
primary event, an alteration in the bronchial
mucous membrane secondary to a dietary
defect, or something altogether different is
a matter as yet unsettled. Regardless of its
nature, however, the lesion is one which
predisposes the bronchi and pulmonary
parenchyma to secondary infection,4 which,
114 turn, seems to be the chief cause of the
widespread bronchial and 1)ronchioiar
ob-struction which characterizes this disease.
Although it is not unlikely that a reduction
in caliber of some of the smaller airways
may occur in advanced cases because of
peribronehial fibrotic changes secondary to
chronic inflammation’ or as a result of the
compressive effects upon small bronchi of
raised intrathoraeic and intrapulmonary
pressure during 21. 22 pathologic
findings 111 the lungs indicate that
obstruc-tion is mainly intraluminal in nature, largely
a matter of accumulation of secretions and
purulent exudate.
A major goal of treatment is, therefore,
the reduction of that element of bronchial
obstruction eOntril)uted by respiratory
in-fections. The benefits which may result
from this policy are illustrated by the course
of one of the patients in this group, Case 2
(
V. D.). Since this patient, who was knownto have had an appreciable degree of
pul-monary disease earlier in life, had only
slight impairment of pulmonary function at
the time of study, it is reasonable to hope
that the intensive use of antibiotics in other
patients if started early enough might
favor-ably affect their outlook, not oniy with
re-gard to prolongation of life but with respect
to the filial status of pulmonary function
as well.
SUMMARY
Studies of pulmonary function in patients
with chronic pulmonary disease associated
with cystic fibrosis of the pancreas have
revealed a pattern of dysfunction which
may be said to be characteristic of this
disease, but which is subject to great
varia-tion in severity.
Both ventilatory insufficiency (leading to
dyspnea) and disturbances in gas exchange
(leading to arterial hypoxia and carbon
di-oxide retention) may occur. The former
would seem to be largely the result of
fac-tors which bring about a diminished
venti-latory capacity, among which an increased
resistance to air flow within the
tracheo-bronchial tree, due to obstruction of the
larger and smaller bronchi by accumulated
secretions and purulent exudate, is probably
most important. Defective gas exchange
seems to stem largely from disturbances in
the normal relationships of alveolar
venti-lation to perfusion. This seems in large part
due to uneven distribution of tidal air to
the alveoli as a result of bronchial
obstruc-tion, although concomitant variation in the
distribution of blood probably occurs also.
In general, the severity of the impairment
of pulmonary function closely parallels the
chronicity and severity of the characteristic
secondary bronchial and pulmonary
infec-tiOlis. The treatment of these constitutes,
logically, the major effort in therapy.
APPENDIX
Case 1 (P. D.) was known to have had foul,
bulky, greasy stools since infancy, but had
suffered no dlisturbance in nutrition or growth
and was not placed on an appropriate dietary
regimen’ ulntih the age of 10 yr. Pulmonary
disease was manifest only in 4 to 5 colds per
year with an infrequent though persistent
non-productive cough in intervening periods. He
had no dyspnea, cyanosis or clubbing of the
digits, and no abnormalities of the lungs n
physical examination. Two duodenal assays at
the age of 10 yr. and one at 1 1 yr. of age
162
J.
R.WEST,
S.
M. LEVIN AND P. A. DI SANT’ACNESECase 2 (V. D.) was known to have had
steatorrhca since infancy, and had been
con-siderably helped in this respect by dietary
management which was started at the age of 5
yr. A chronic nonproductive cough was also
noted during infancy and, at the age of 53 yr.
he was seen to have the roentgenologic findings
of a moderate diffuse bronchopneumonic
proc-ess involving both lungs. At this time duodenal
contents were obtained by drainage on 2
occa-sions, and on both, proteolytic activity was
en-tirely lacking. The diffuse bronchopneumonia
associated with persistent cough, some degree
of malnutrition and clubbing of the digits
con-tinucd unabated until, at the age of 1 13 yr., the
patient was started on a program of intensive
antibiotic (aureomycin) therapy. An immediate
decrease in the severity of the cough Was noted
and over the course of the next 13 yr.,
pro-gressive x-ray clearing occurred (Fig. 2). At the
time of study the patient did not complain of
dyspnca, had no cyanosis and although the
digits were clubbed there were no other
physi-cal findings indicative of pulmonary disease.
Nutrition and growth were fair.
Case 3 (C.
J.).
Pancreatic deficiency wasrec-ognized in this child shortly after birth and an
appropriate dietary regimen was started at the
age of 2 yr. At this time, duodenal aspiration
had shown complete absence of proteolytic
en-zymes in the duodenal contents. Respiratory
disease beginning at the age of 2 mo., was
manifest as a persistent nonproductive cough,
a moderate degree of chronic
bronchopneumo-nia with some emphysematous changes on
roentgenographic examination, some limitation
of activity because of dyspnea, and pronounced
digital clubbing. There was no cyanosis, and at
the time of study, the only other physical
find-ings indicative of pulmonary disease were
scat-tered sibilant and sonorous rhonchi over both
lung fields. Some improvement had occurred
under intensive antibiotic (aureomycin)
treat-ment which was started at the age of 12 yr.,
but this was not as striking as- in the preceding
case.
In Case 4 (R. B.), the presence of
pancre-atic deficiency was unrecognized until the age
of 14 yr. despite the fact that the
characteris-tic abnormality of the stools had been present
since infancy. A chronic cough which had been
present since at least the age of 8 yr. was
pro-ductive of moderate amounts of greenish
puru-lent sputum and widespread
bronchopncu-monic changes were seen on the first RG taken
at the age of 14 yr. Growth and development
were considerably impaired. Two duodenal
as-says, one at 14 yr. of age and another at 15 yr.,
were entirely negative for tryptic activity.
Reg-ular doses of terramycin were started soon after
the disease was recognized and, although some
clinical improvement followed, there was no
change in the roentgenographic appearance of
the lungs even after several months of therapy.
At the time of study the patient complained of
exertional dyspnea and was noted to have
marked digital clubbing and persistent basilar
rales bilaterally. There was no cyanosis,
how-ever, and a bronchogram revealed no evidence
of bronchiectasis.
Case 5 (M. N.) was first seen at the age of
4 yr. because of a cough productive of
puru-lent sputum of 8 mo. and cyanosis of 2 mo.’
duration. She was said to have had steatorrhca
for 1 yr. and was found on chest RG to have
extensive bronchopneumonia with some
em-physematous changes. Duodenal contents
ob-tamed at this time showed no protcolytic
ac-tivity. She was treated with penicillin aerosol
with some reduction in cough and sputum and
an improvement in the appearance of the chest
RG. Subsequent years, however, have been
characterized by the presence of chronic
bron-chopncumonia complicated by many acute
cx-acerbations associated with increasing dyspnea
and cyanosis. Penicillin, sulfadiazinc and
strep-tomycin have all been of considerable benefit
during these acute episodes and on a program
of regular doses of terramycin recently
intro-duced, the patient seems to be slowly
improv-ing. Clubbing of digits has been present ever
since she was first examined as has exertional
dyspnea, and growth and development have
been retarded. At the time of study there was
obvious hyperinflation of the thorax with
re-duced expansibility. The lungs were
hyper-resonant and there were sibilant and sonorous
rhonchi and rales scattered about both hung fields.
Case 6 (G. D.) had the onset of stcatorrhca
1 mo. after birth and chronic cough began 5
mo. later. Two duodenal drainages in the first
year of life revealed complete absence of
tryptic activity. At the age of 3 yr. a chest RG
revealed a picture consistent with chronic
bronchopneumonia which, associated with
cyanosis, digital clubbing, and reduction in
cx-ercise tolerance, slowly progressed in severity
until his death at the age of 13 yr.
163
ill1 seemed helpful when an acute respiratory
infection became superimposed on the chronic
process, but nothing halted his steady
down-hill course. Despite a low fat, high protein diet,
growth and nutrition were greatly impaired. At
the time of study the chest was noted to be
hyperinflated and relatively immobile.
Percus-sion note \Va5 hyperresonant and breath sounds
were distant and obscured by adventitious
sounds. The latter included many sibilant and
sonorous rhonchi and rales which were heard
throughout both lung fields.
Approximately 8 mo. after completion of the
pulmonary function studies reported here,
death occurred in association with gradually
worsening bronchial infection. Because of
severe anoxia continuous oxygen therapy was
necessary during the last phases of the illness
and marked carbon dioxide retention was
noted. An attempt was made terminally to
as-sist respirations with a mechanical respirator,
but this was of no benefit.
At autopsy, in addition to the usual findings
in cystic fibrosis of the pancreas,1 there was
hypertrophy and dilatation of the right
ventri-dc. In the absence of other apparent cause this
was thought to be a manifestation of cor
pul-monalc.
REFERENCES
1. Andersen, Dorothy H., Cystic fibrosis of
pancreas and its relation to celiac
dis-ease, Am.
J.
Dis. Child. 56:344, 1938.2. Farber, S., Pancreatic function and disease
Ifl early life. V. Pathologic changes
asso-ciated with pancreatic insufficiency in
early life, Arch. Path. 37:238, 1944.
3. di Sant’Agncsc, P. A., and Andersen,
Dor-othy H., Ccliac syndrome. IV.
Chemo-therapy in infections of respiratory tract
associated with cystic fibrosis of
pan-creas, Am.
J.
Dis. Child. 72:17, 1946.4.
di Sant’Agncse, P. A., Bronchialobstruc-tion with lobar atelectasis and
emphy-sema in cystic fibrosis of pancreas,
PEDIATRICS 12:178, 1953.
5. Shwachman, H., Silverman, B. K.,
Patter-son, P. R., and Zhcuthin, L.
J.,
Antibi-otics in treatment of pancreatic fibrosis,
with emphasis on terramycin, J.A.M.A.
149:1101,
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SPANISH ABSTRACT
Funci#{243}n Pulmonar
en
la
Fibrosis
QuIstica
del
Pancreas
Las alteraciones funcionales dcl pulm#{243}nen
ha enfermedad fibroquIstica dcl pancreas, son
en gran partc resultado dc Ia obstrucci#{243}n por
secreciones espesas y exudado purulento de
has vIas a#{233}rcasinferiores, seg#{252}nse desprende
dc los hahhazgos clInicos y patol#{243}gicos actuales;
sin embargo, hasta la fecha no se tienen
estudios fisiol#{243}gicos adecuados que gradicn
la gravedad de tales altcraciones debido a las
dificultades quc presentan los enfermitos para
reahizarlos a una cdad tan temprana. El
presente artIculo muestra los resultados de los
estudios de la funci#{243}n pulmonar en 6 ninos,
4 hombres y 2 mujeres, de edad variable entre
12 y 15 aflos, y en los que se practicaron las
pruebas pulmonares funcionales descritas por
Baldwin y colaboradores, estudios que a Ia
vez facihitaron en cierto grado Ia investigaci#{243}n
de los mecanismos dctcrminantcs de dichas
alteraciones fisiol#{243}gicas : insuficiente ventilaci#{243}n
y trastornos en los intercambios gaseosos.
El aumento de las necesidades de ventilaci#{243}n
en estos pacientes afecta en poco Ia aparici#{243}n
de Ia insuficiencia ventilatoria; #{233}sta, que
conduce a ha disnea, depende
fundamental-mente de factores que disminuyen Ia capacidad
para Ia ventilaci#{243}n pulmonar, entre los que se
cuentan: Ia mayor resistencia al paso dcl aire
en el #{225}rboltraqueobr#{243}nquico por ha obstrucci#{243}n
de todos los bronquiolos, grandes y pequefios,
debida al ac#{241}mulo de sccrcciones y de exudado
purulento; secundariamente, las anomallas de
ha configuraci#{243}n tor#{225}cica consecutivas al
en-fisema y la disminuci#{243}n de la actividad
pul-monar como resultado de lii fibrosis
deter-minada por infecciones cr#{243}nicas u otras
razones, factor este #{241}ltimo que ann requiere
mayor estudio.
Los trastornos en el intercambio gaseoso,
que conducen a hipoxia arterial y retenci#{243}n
de bi#{243}xidode carbono, parecen deberse
prin-cipalmente a alteraciones en Ia relaci6n normal
entre la ventilaci#{243}n alveolar y la perfusion,
es decir, sc presentan hipoxia arterial y
re-tenci#{243}ndc biOxido de carbono cuando existe
una vcntilaci#{243}n inadecuada en alveOhos quie
continuan perfundi#{233}ndose con Ia cantidad
normal de sangre capilar, o bien, al rev#{233}s,
cuando ventil#{225}ndose adecuadamente tin
nO-mero grande de alv#{233}olos, no
est#{225}nnormal-mentc irrigados. El defecto del intercambio
gascoso depende, pues, fundamentalmente de
una distribuci#{243}n insuficiente de ha corriente de
aire a los alveOlos como resultado de Ia
ob-strucciOn bronquial y secundariamente de una
variaci#{243}n concomitantc en Ia distribuciOn de la
sangre pulmonar; quiz#{225} intervenga un tercer
factor, dependiente de Ia reguhaciOn nerviosa
dc la respiraciOn.
Los autorcs consideran como otra
mani-festaciOn de alteraciOn funcional de los
pull-mones en la enfermedad fibroquIstica del
pancreas, la instalaciOn de cor pulmonale
hipertrofia ventricular derecha.
Dc estos estudios se deduce que si ha
anormalidad depende de alteraciones
intra-bronquiales por obstrucciones diversas que a
su vez predisponen a infecciones sectindarias,
pucde instalarse un cIrculo vicioso. La finalidad
de un tratamicnto adecuado serIa ha reducciOn
de los clemcntos favorecidos por has
infecciones respiratorias, hhevan a ha
obstruc-ci#{243}nbronquial. Es razonable, entonces, esperar
iuc el uso intcnso de alltibioticos iniciado
tempranamente tienda a mejorar eh pronOstico
de estos enfermos no sOlo en relaciOn a
longar su vida sino tambi#{233}n a collservarhes ll
