351
PEDoAnucs, March 1961
Ped iui rics
VOLUME 27 MARCH 1961 NUMBER 3
COMMENTARY
“BREAK-THROUGH
IN CYSTIC
FIBROSIS”
T
‘F WOULD BE good news indeed if a“break-.1 through in cystic fibrosis” was really
here as has been put forth in the
promo-tional material on Cotazym by Organon,
Inc. in an energetic campaign to sell their
pancreatic preparation. Uncritical
accept-ance of unsupported statements in this
promotional material would actually be a
set-back in the comprehension of present
knowledge of cystic fibrosis and the place
of pancreatic substitution therapy in the
management of patients with this disorder.
False hope may he raised in physicians and
in the parents of the unfortunate victims of
this distressing disease.
Though we (10 not wish to minimize the
importance of the pharmaceutical
develop-ment of an improved pancreatin
prepara-tion, we believe that presenting Cotazym
as a “break-through in cystic fibrosis” is
un-warranted and misleading. Although the
problem of impaired digestion and
absorp-tion in patients with cystic fibrosis is real,
it is their pulmonary lesion which primarily
determines well-being and survival. A
break-through would imply a new
develop-ment that would significantly alter either
our understanding or treatment of the
dis-ease and one which would afford significant
relief of the pulmonary lesion of cystic
fi-brosis.
That the use of a lipolytic agent is not a
new development is evident to anyone
fa-miliar with the literature on cystic
fibro-sis.1-5 In the study by Best
et
al.,6 uponwhich most of the claims in the
advertise-ment of Cotazym are based, absorption of
J’71labeled triolein was determined in nine
patients with cystic fibrosis (not in 24 as
stated in the advertisement) and absorption averaged 35.7%. In these same patients, plus
three others, after Cotazym was
adminis-tered with the test meal, absorption
aver-aged 85.6%. In 1958, employing an I131
labeled fat absorption test, we
demon-strated in 13 patients with cystic fibrosis
that only 44 ± 16% of the I’31-labeled fat
was absorbed. In nine of these patients the
administration of pancreatin resulted in an
increase in absorption to 83 ± 6%. Othersl4
have obtained similar results that show the
effectiveness of pancreatin, using the
bal-ance study method.
Between 1954 and 1961, we studied 82
patients with cystic fibrosis by means of
commercially prepared I‘‘ -labeled triolein.
The effects of two previously available
pan-creatin preparations (Panteric Granules and
Viokase) were studied in 16 patients. The
effects of Cotazym have been studied by us
in 10 patients, and the absorption of J131
labeled oleic acid has been studied in seven
patients who received 1.0 gm of pancreatin
with the test meal and in eight without
pan-creatin. The results (Table I) are not in
agreement with the conclusions drawn by
Best et al. on the evidence from two
studies with Viokase and one with
pancrea-tin. From our data it does not appear that
there is a significant difference in the
effi-cacy of the various pancreatin preparations.
In the dosages used they all improve fat
ab-sorption. It is true that per milligram of the
TABLE I
FAT Aasolip’rIoN IN PATIENTS WITH CYSTIC FIBROSIS
.\‘o. of
Absorbed
Patients
Utilizing J131_ Triolein*
352 CYSTIC FIBROSIS
appears to be two to three times that of the
previously available pancreatin
prepara-tions, but this cannot be construed as a
“break-through in cystic fibrosis.”
Though we do not doubt the validity of
the in-vitro assays indicating that one cap-sule
(
100 milligrams) of Cotazym will digest17 grams of fat, there is no evidence
pre-sented to indicate that this applies in vivo.
In our studies one and one-half times the
“calculated” amount of Cotazym required
to digest all of the fat in the test dose and diet proved inadequate in vivo. An average
of 38 ± 21% of the ingested fat was not
ab-sorbed when a significant amount of fat was
included in the test dose and diet.
Since the degree of gastric acidity, rate of gastric emptying and degree of
alkalini-zation in the duodenum varies markedly
from child to child, a variable degree of
destruction of lipase would be anticipated
with any unprotected pancreatin
prepara-tion like Cotazym. Though food does offer
some protection of lipase from gastric
de-struction, our data indicates this is far from
the complete protection implied in the
ad-vertisement of Cotazym.
The impairment of fat absorption in
pa-tients with cystic fibrosis has not yet been
fully elucidated. That digestion is not the
only problem was first evident from the
studies of Reemtsma et a!.,” in which a
de-fect in the absorption of I131-labeled oleic
acid was demonstrated. Their study lacked
the quantitation of the defect, which is
pos-sible only with stool collections. The
nor-mal individual beyond 2 years of age
ab-sorbs over 95% of the ingested 1131-labeled fat; however, as can be seen in Table I, the child with cystic fibrosis, whether receiving
pancreatin or given no therapy, absorbs
only 84% of a test meal of oleic acid. These
results confirm the findings of Reemtsma et
a!.” and indicate that in addition to the
de-Cystic fibrosis Controls over t yr
8 So
48 ± ‘4%
96± 4%
Pancreatin studies**
Cystic fibrosis without pancreatin
Same with pancreatin
16
16
3.5 ± 16%
69±’20%
Cotazym studies*** Cystic fibrosis without
Cotazym Same with Cotazym
Cystic fibrosis without Cotazym****
Same + 3 with Cotazym****
10 10 9 1h2 45±?3% 61 ±‘21% 36±35% 86±1%
Utilizing 1131 Oleic Acid5
Cystic Fibrosis without
pancreatin
Cystic Fibrosis with pancreatin
6
7
82 ± 6%
85 ± 4%
* The test meals used in our studies contained 5 mi-crocuries of J131 in the labeled triolein or oleic acid plus Iml of nonlabeled corn oil per kilogram of body weight and an estimated 1 gram of dietary fat per kilogram l)ody weight.
** Viokase Powder, \iolun Corporation, Monti(’elIo, Illinois, administered in a dose of 0.4 to 1.6 grams per
feeding. Panteric Granules, Parke, Davis & Company,
Detroit, Michigan, administered in a dose of 0.3 to 1.’2 grams per feeding.
Cotazym, Organon, iiic., West Orange, New
Jersey, administered in a dose of 0.1 to 0.3 grams per feeding.
Results of Best et al.6
the product, namely, better acceptance by
the patient due to the decreased dosage
and less offensive odor of the product and
the marked decrease in the odor of the
COMMENTARY 353 intestinal tract, 20 showed no improvement
and
7 were adversely affected, as compared with their previous pancreatin therapy.With tile present torrent of new, more
potent, and sometimes improved products
and an increasing chance of untoward
reac-tions, it seems ever more desirable to
re-quire adequate documentation of claims in
promotional material. Until this can be
as-sured, it will be safer and wiser for the
phy-sician to depend oii tile information and
guidance in the editorial text of
profes-sional journals that publish articles
scru-tinized by competent reviewers. Effusive
puffery may be innocuous in selling
per-fume and soap, but promotion of health
products calls for honest and dignified pro-cedures if the welfare of the people is to be
safeguarded and confidence of the
profes-sion secured.
LEROY W. MATTHEWS, M.D.
SAMUEL SPECTOR, M.D.
Department of Pediatrics
School of Medicine
Western Reserve University 2103 Adelbert Road
Clceeland 6, Ohio
References
1. Andersen, D. H.: Celiac Syndrome. II. Fecal
excretion in congenital pancreatic deficiency
at various ages and with various diets, with
discussion of the optimal diet. Amer. J. Dis.
Child., 69:221, 1945.
2. Ross, C. A. C.: Fat absorption studies in the diagnosis and treatment of pancreatic fibro-sis. Arch. Dis. Child., 30:316, 1955.
3. Harris, R., Norman, A. P., and Payne, W. W.:
The effect of pancreatin therapy on fat
ab-sorption and nitrogen retention in children
with fibrocystic disease of the pancreas.
Arch. Dis. Child., 30:424, 1955.
4. Kumar, B. B., and Gibbs, C. E.: The effect of
pancreatin on fat digestion in an infant.
Amer. J. Dis. Child., 91:606, 1956.
5. Spector, S., Matthews, L. \V., Lemm, F. J., Van Erp, Y., and Cline, J.: Study of fat
absorption utilizing I”-labeled corn oil in infants and children with and without
steator-rhea. PEDIATRICS, 22:515, 1958.
6. Best, E. B., Hightower, N. C., Jr., \Villiams, B. H., and Carahasi, R.
J.:
Pancreaticre-placement therapy in fibrocystic disease.
Southern Med. J., 53:1091, 1960.
7. Reemtsma, K., diSant’Agnese, P. A., MaIm, J.
R., and Barker, H. G.: Cystic fibrosis of the
pancreas: Intestinal absorption of fat and
fatty acid labeled with I”. PEDIATRICS, 22:
