Nasal polyps in asthma and rhinitis

A review of 6,037 patients

Guy A. Settipane, M.D., and Francis H. Chafee, M.D. Providence, R. 1.

Data ,from records ef patients with asthma and rhinitis in the Rhode Island Hospital Adult
Allergy Clinic and in an adult allergy private practice were reviewed. The ,frequency of nasal
polyps in the total population qf 4,986 was 4.2%; in the asthmatic portion of the population the
,frequency was 6.770, and in the rhinitis alone group the frequency was 2.2%. Asthmatics with
negative allergy skin tests to inhalant allergers had signijcantly more nasal polyps than
asthmatics with positive skin tests, 12.5% vs 5.0’S, p < 0.01. The frequency of nasal polyps
increased with advancing years. Of the total 21 I cases of nasal polyps, 71 LTOhad asthma and
297~ had rhinitis alone. Also, 147~ of the patients with nasal polyps had aspirin intolerance,
primarily sf the bronchospastic type. In addition, 1,051 patients with asthma and rhinitis ,from
the Pediatric Allergy Clinic with a mean age sf 6 yr were similarly evaluated. Only I (0. I %;)
qf these pediatric patients had nasal polyps.

Nasal polyps have been associated with aspirin in-
tolerancelm4 and cystic fibrosis.5 The frequency of
nasal polyps in aspirin intolerance has been reported
to be between 36% and 6 1%) ‘-’ and in cystic fibrosis,
only 6.7%.5
Adverse reactions to aspirin, known as aspirin intol-
erance, have been subdivided into subtypes, the most
common being the bronchospastic type, followed by
the urticaria/angioedema type, and least, rhinitis type.
The bronchospastic type has a significantly great-
er association with nasal polyps than the urticaria/
angioedema type. In a recent study,6 nasal polyps
were found in the bronchospastic type of aspirin intol-
erance more than four times the frequency found in
the urticaria/angioedema type.
Neither cystic fibrosis nor the bronchospastic type
of aspirin intolerance is thought to be mediated
through an antigen-antibody reaction, e.g., involving
IgE immunoglobulins. The relationship of nasal pol-
yps with IgE-mediated diseases is not known. In this
study, an attempt is made to evaluate a large number
of patients with asthma and rhinitis to determine the
association of nasal polyps with these conditions.
From the Division of Allergy, Department of Medicine,
Island Hospital, and the Division of Biological and Medical Sci-
ences, Brown University.
Received for publication March 10, 1976.
Accepted for publication June 16, 1976.
Reprint requests to: Guy A. Settipane, M.D., 184 Waterman St.,
Providence, R. I. 02906.
MATERIAL AND METHODS
The records of patients with asthma and rhinitis in an
allergy private practice and in Rhode Island Hospital Al-
lergy Clinic were reviewed. This was facilitated by a pro-
gram of coding pertinent details of each record onto McBee
Keysort cards, which had been in use for many years to
provide quick and accurate retrieval of information.
Patients had been tested by the scratch technique to a
battery of inhalant allergens.* When the scratch test was
negative for a particular allergen that was suspected by his-
tory, the intracutaneous test was also done. On a few occa-
sions intracutaneous tests were done without prior scratch
tests. Allergens included trees, grasses, and ragweed pollen
extracts, animal danders, and selected molds. A positive
reaction had to be definitely larger than the control, and all
questionable reactions were considered to be negative tests.
Cards were sorted into those with a diagnosis of asthma
alone, those with rhinitis alone (seasonal or nonseasonal),
and those with both of these conditions. Each diagnosis was
subdivided into those patients who had positive allergy skin
tests to one or more pollens, danders, or molds and those
with negative reactions to those antigens. Cases of acute
infectious rhinitis were excluded from this study. Vaso-
motor rhinitis was classified with those cases of rhinitis
with negative skin tests. A diagnosis of asthma was accepted
if symptoms consisted of clinically reversible signs of
wheezing, shortness of breath, and cough on a recurrent
Rhode basis, not due to any other organic disease. A diagnosis of
rhinitis was accepted if symptoms consisted of repeated
nasal stuffiness, rhinorrhea, and frequent sneezing on a sea-
*Standard scratch test extracts as purchased from Hollister-Stier
and Greer Laboratories.

Vol. 59, No. 1, pp. 17-21

18 Settipane and Chafee J. ALLERGY CLIN. IMMUNOL.
JANUARY 1977

TABLE I. Frequency of nasal polyps in asthma and rhinitis

Positive allergy Negative allergy Total

skin tests skin tests PolYPs
Total
Diagnosis patients Number Polyps % Number Polyps % p value Number % p value

Asthma 2,228 1,717 85 5.0 511 64 12.5 <O.Ol 149 6.7

Rhinitis only 2,758 2,126 32 1.5 632 30 4.7 <O.Ol 62 2.2 <0.01*

Total 4,986 3,843 117 3.0 1,143 94 8.2 211 4.2

*The difference in the frequency of nasal polyps in asthma (6.7%) compared to rhinitis (2.2%) is statistically significant.

sonal or nonseasonal basis. The records were then divided
according to sex and were further arranged by decades ac-
cording to the age when first seen. Those patients 50 yr of
age and over were classified into one group.
A diagnosis of nasal polyps was made by physical
examination, ear, nose, and throat consultation, or by a
definite history of a past diagnosis. The question whether
nasal polyps and aspirin intolerance were present was spe-
cifically included on the Keysort cards. Acute wheezing,
rhinorrhea, urticaria, angioedema, or symptoms of shock
occurring approximately within 3 hr after ingestion were
our criteria for intolerance to aspirin. A diagnosis of aspirin
intolerance was made by history and not by challenge
studies. The charts of those patients whose Keysort cards
demonstrated a diagnosis of nasal polyposis were reviewed
in detail to confirm the diagnosis, and to obtain additional
information.
RESULTS
From our Adult Allergy Clinic at Rhode Island
Hospital and from an allergy private practice, there
were a total of 4,986 patients. The age range was
from 10 to over 50 yr. Of these 4,986 patients, 2,228
had asthma and 2,758 had rhinitis alone. There were
2,817 females and 2,169 males. These 4,986 patients
were further classified into the age when first seen.
The frequency of nasal polyposis in these 4,986
patients was 4.2% (211/4,986). In the asthmatic
group, the frequency was 6.7% (149/2,228), and in
the rhinitis alone group, the frequency was 2.2%
(62/2,758). This difference is statistically significant
(p < 0.01) (Table I).
There was no significant difference in the fre-
quency of nasal polyposis in those patients with
asthma alone and in those with asthma and rhinitis.
Those asthmatics with negative allergy skin tests to
inhalant allergens had significantly more nasal polyps
than those with positive skin tests, 12.5% vs 5.0%
(p < 0.01). In the patients with rhinitis alone, there
was a greater frequency of nasal polyps in those with
negative skin tests than in those with positive skin
tests, 4.7% vs 1.5% (p < 0.01) (Table I). The fre-
quency of nasal polyposis appears to increase with
advancing years, and those asthmatics 40 yr of age or
older had a significantly greater frequency of nasal
polyposis than those asthmatics less than 40 yr of age
(Table II). This increase with advancing age was pres-
ent in all categories of patients, including those with
rhinitis alone.
Of the total 211 patients with nasal polyps, there
were about an equal number of males and females
(Table III). No definite sex difference was found in
any of our categories. Of these 211 cases of nasal
polyps, 70.6% had asthma, 29.4% had rhinitis alone,
and 55.5% had one or more positive allergy skin tests
to inhalant allergens other than housedust.
In the 211 cases of nasal polyps, there were 30
cases of definite aspirin intolerance, 14.2%. Most of
the aspirin intolerance symptoms were solely of the
bronchospastic type (70%), followed by the urticaria
type (13.3%), both the bronchospastic and urticaria
types (6.7%), and the rhinitis type (10%).
In addition to the 4,986 adult allergy patients, we
also evaluated in a similar manner the records of
1,05 1 patients with asthma or rhinitis in the Pediatric
Allergy Clinic at Rhode Island Hospital. The age
range of these pediatric patients was from under 1 yr
to 14 yr. In a typical year, the mean age of these
patients was found to be about 6 yr. Of these 1,05 1
pediatric patients, 689 had asthma and 362 had
rhinitis alone. One of these 1,05 1 pediatric patients
had nasal polyps, and that was a male with rhinitis
alone who was 10 yr of age when first seen at our
clinic.
DISCUSSION
Nasal polyps have ciliated columnar epithelium
and cellular constituents of normal nasal mucosa.
They are thought to release on appropriate stimulation
histamine, slow-reacting substance of anaphylaxis
(SRS-A), and eosinophil chemotactic factor of
anaphylaxis (ECF-A). Kaliner, Wasserman, and Aus-
ten7 have reported that the release of these chemical
mediators in nasal polyps is modulated by agents af-
VOLUME 59 Nasal polyps 19
NUMBER 1

fecting the intracellular concentrations of cyclic nucle- TABLE II. Frequency of nasal polyps in various age
otides. These authors pointed out that quantitatively groups of asthmatic patients
“ . SRS-A released in relation to the amount of
Age when No. with
histamine released from nasal polyps is considerably first seen No. with nasal P
less than that released from human lung . . ..” Re- (vr) asthma PolYPs % value
cently, evidence has been presented that serotonin
may also be found in nasal polyps.’
Whiteside and co-workers9 reported a good correla-
tion between the number of IgE-bearing lymphocytes
40-49
in nasal polyps and serum IgE levels in atopic pa-
tients. They also found that in 5 of 6 cases of nasal 50 and
over
polyps in nonatopic patients, no IgE-bearing lympho-
cytes were detected. They concluded that nasal Total 2228 149 6.1

polyps in atopic patients may have a different etiology *The difference between the lo- to 39-yr-old group (43/1,374),
from those in nonatopic patients. In agreement with 3.1%, compared to the 40-yr-old and over group (106/854),
other authors,10-16 they also felt that IgE is a secretory 12.4%, is statistically significant.
immunoglobulin and is locally produced in the nasal
mucosa. These data are consistent with earlier reports TABLE III. Nasal polyps (211 cases)
that skin-sensitizing antibody, reagin, is found in
Clinical categories No. %
nasal polyps, nasal secretions, and other secretory
fluids of atopic individuals when tested by the Males 106 50.2
Prausnitz-Kiistner procedure.17-20 Females 105 49.8
Similar to another study,21 over 70% of our pa- Asthma 149 70.6
tients with nasal polyps had asthma (Table III). In Rhinitis (alone) 62 29.4
addition, our data demonstrate that nasal polyps are Positive allergy skin tests 117 55.5

most frequently found in asthmatics with negative Total aspirin intolerance 30 14.2

skin tests to inhalant allergens. The frequency of Subtypes qf aspirin intolerance

nasal polyps in those asthmatics with positive allergy Bronchospasm 21 70.0

skin tests is small and probably is not related to the
positive allergy tests (Table I). However, over 55% of
21 1 patients with nasal polyps had positive allergy
skin tests (Table III). Since our cases of nasal polyps
were selected from a biased population, 77%
(3,843/4,986) of whom had positive allergy skin
tests, this high frequency of positive allergy skin tests
in nasal polyps may be misleading and may reflect the
characteristics of our total population. Thus we are
unable to confirm the existence of two mechanisms
for nasal polyps, and we feel that the positive allergy
skin tests in nasal polyps may be a coincidence. The
increased frequency of nasal polyps in those patients
with rhinitis alone and negative skin tests may be an
artifact. Nasal polyps may produce nasal stuffiness,
and, for this reason, a diagnosis of rhinitis may be
made in error.
Our data that nasal polyps are relatively uncommon
in the younger age group agree with past reports.*” ‘*
Most of our patients with nasal polyps were 40 yr of
age or over when first examined. The frequency of
nasal polyps in 742 patients with cystic fibrosis was
reported at 6.7%.5 The mean age of the children with
both nasal polyps and cystic fibrosis was 11.7 yr.
Our frequency of nasal polyps in asthmatics between
Urticaria 4 13.3
Both bronchospasmand urticaria 2 6.1
Rhinitis 3 10.0
10 and 19 yr of age was 1.8%. Thus, nasal polyps in
fibrocystic diseases appear to occur almost 4 times as
frequently as in asthmatics of a similar age group.
Our previous studies on aspirin intolerance dem-
onstrated that at least two mechanisms exist, one
resulting in the symptoms of acute bronchospasm and
the other resulting in urticarialangioedema.‘, *, 6 We
postulated that the bronchospastic type of aspirin in-
tolerance may be related to the prostaglandin system.*
In nonatopic asthmatics with nasal polyps, an abnor-
mal mechanism may exist in which aspirin may affect
the ratio of PGE2, a bronchodilator, to PGF2, a bron-
choconstrictor. A distortion of this ratio may lead to
the dominance of PGF2 and cause a bronchoconstric-
tor effect. This theory is supported by known interac-
tions between aspirin and prostaglandin.23* 26
There is no generally accepted pathogenic
mechanism to explain the urticaria type of aspirin
intolerance. An atopic mechanism has not been ruled
out. In 197 1, DeWeck27 reported reagin induced by
aspirin anhydride, a contaminant of commercial aspi-
20 Settipane and Chafee J. ALLERGY CLIN. IMMUNOL.
JANUARY 1977

rin, to be present in those individuals with the 4. Samter, M.: Intolerance to aspirin, Hosp. Pratt. 8:85, 1973.
urticaria/angioedema type of intolerance, In 1974 5. Shwachman, H., Kulczycki, L. L., Mueller, H. L., and Flake,
C. G.: Nasal polyposis in patients with cystic fibrosis, Pediat-
Phills and PerelmutterZE reported that the broncho-
rics 30:389, 1962.
spastic type of intolerance is not mediated through IgE 6. Settipane, G. A., and Pudupakkam, R. K.: Aspirin intoler-
antibodies and that the urticarialangioedema type is ance. III. Subtypes, familial occurrence, and cross-reactivity
mediated through the IgE immunoglobulins. The with tartrazine, J. ALLERGY CLIN IMMUNOL. 56~215, 1975.
techniques used in this study were the direct skin test 7. Kaliner, M., Wasserman, S. I., and Austen, K. F.: Im-
munologic release of chemical mediators from human nasal
to aspirylpolylysine (ASP-PLL) and rat mast cell test
polyps, N. Engl. J. Med. 289277, 1973.
(RMCT) before and after adsorption of IgE immuno- 8. El-Ackad, T. M., Bumsted, R. M., Smith, J. M., and Brody,
globulin. M. D.: Differential distribution of histamine, serotonin, and
However, in 1974, Schlumberger, Lobbecke, and norepinephrine in nasal polyps, J. ALLERGY CLIN. IMMUNOL.
Kalloszg were unable to confirm positive allergy 55:120, 1975. (Abstr.)
9. Whiteside, T. L., Rabin, B. S., Zetterberg, J., and Criep, L.:
skin tests in those individuals with an urticaria type
The presence of IgE on the surface of lymphocytes in nasal
of aspirin intolerance using N-salicyloyl or N- polyps,J. ALLERGY CLIN. IMMUNOL. 55:186, 1975.
acetylsalicyloyl antigens. Late in 1974, von Maur 10. Ishizaka, K., and Newcomb, R.W.: Presence of gamma E in
and co-workers30 reported a family of which 6 indi- nasal washings and sputum from asthmatic patients, J. AL-
viduals, representing three generations, had aspirin LERGY46:197,1970.
11. Yunginger, J. W., and Gleich, Cl. J.: Seasonal changes in
intolerance. Skin tests to aspiryl-polylysine (ASP-
serum and nasal IgE concentrations, J. ALLERGY CLIN. IM-
PLL) were negative in 4 of these individuals. How- MUNOL. 5k174, 1973.
ever, only 1 of these 4 had the urticaria type of aspirin 12. Tse, K. S., Wither, K., and Arbesman, C. E.: IgE antibodies
intolerance and therefore could have been expected to in nasal secretions of ragweed allergic subjects, J. ALLERGY
have positive reactions to aspiryl-polylysine skin test. 46:352, 1970.
13. Hobday , J. D., Cake, M., and Turner, K. J.: A comparison of
More work is needed in this field. Complicating fac-
the immunoglobulins IgA, IgG, and IgE in nasal secretions
tors appear to be the dose used in skin testing and the from normal and asthmatic children, Clin. Exp. Immunol.
irritative effect of ASP-PLL in high concentration. 9:577, 1971.
Aspirin intolerance, especially the bronchospastic 14. Tada, T., and Ishizaka, K.: Distribution of gamma E-forming
type, most commonly is associated with nasal pol- cells in lymphoid tissues of the human and monkey, J. Im-
munol. 104:377, 1970.
yp~.~ It is most frequently found in those individuals
15. Donovan, R., Johansson, S. G., Bennich, H., and Soothill, J.
who have asthma and negative allergy skin tests. The F.: Immunoglobulins in nasal polyp fluid, Int. Arch. Allergy
clinical triad of asthma, nasal polyposis, and aspirin Appl. Immunol. 37:154, 1970.
intolerance is well established.3, 4, 31* 32 In our 211 16. Huggins, K. G., and Brostoff, J.: Local production of specific
cases of nasal polyps, the frequency of aspirin intol- IgE antibodies in allergic rhinitis patients with negative skin
tests, Lancet 2:148, 1975.
erance was 14.2%, and the predominant type of aspi- 17. Samter, M., and Becker, E. L: Ragweed reagins in nasal secre-
rin intolerance was bronchospasm. The frequency of tions, Proc. Sot. Exp. Biol. Med. 65140, 1947.
coexisting asthma was 70.6% (Table III). Both aspi- 18. Berdal, P.: Serological examination of nasal polyp fluid, Acta
rin intolerance and nasal polyps are most frequently Otolaryngol. (Suppl.) 115: 1, 1954.
19. Remington, J. S., Vosti, K. L., Lietze, A., and Zimmerman,
found in elderly asthmatics with negative skin tests.
A. L.: Serum proteins and antibody activity in human nasal
The coexistence of aspirin intolerance and nasal secretions, J. Clin. Invest. 43:1613, 1964.
polyps in these patients may be related to the 20. Settipane, G. A., Connell, J. T., and Sherman, W. B.: Reagin
pathologic mechanism that produces asthma, rather in tears, J. ALLERGY 3692, 1965.
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We wish to thank Ruth Fish, R.N., and Carol Carlisle, R.N.,
22. Lanoff, G., Daddono, A., and Johnson, E.: Nasal polyps in
for their assistance.
children: a Ten year study, Ann. Allergy 31:551, 1973.
23. Vane, J. R.: Inhibition of prostaglandin synthesis as a
mechanism of action for aspirin-like drugs, Nature [New
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NUMBER 1

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