CLINICAL NOTE

Efficacy and Tolerability of Budesonide Aqueous

Nasal Spray Treatment in Patients With Nasal Polyps
Roger Jankowski, MD; Camilla Schrewelius, DDS; Pierre Bonfils, MD; Yves Saban, MD;
Laurent Gilain, MD; Jean-Michel Prades, MD; Vladimir Strunski, MD

Objective: To assess the efficacy and tolerability of once- Main Outcome Measures: Mean change in nasal polyp
daily treatment with budesonide aqueous nasal spray in size at the end of treatment; mean changes in combined
patients with nasal polyps. and individual symptom scores.

Design: Randomized, double-blind, placebo-controlled,
parallel-group study.
Setting: Sixteen hospital clinics.
Patients: One hundred eighty-three patients with mod-
erate-sized nasal polyps causing clinically significant
symptoms during a 1-week run-in period.
Interventions: Patients were randomized to receive 1
of the following 4 budesonide aqueous nasal spray
treatments: 128 µg once daily in the morning and pla-
cebo in the evening, 128 µg twice daily, 256 µg once
daily in the morning and placebo in the evening, or pla-
cebo for 8 weeks. Nasal polyp size was scored and peak
nasal inspiratory flow was measured at clinic visits at
the beginning and end of the run-in period and after 4
and 8 weeks’ treatment. Patients recorded daily peak
nasal inspiratory flow, symptom scores (ie, blocked
nose, runny nose, and sneezing) and sense of smell on
diary cards.
Results: All doses of budesonide aqueous nasal spray
significantly (P,.01) reduced polyp size; no significant dif-
ferences were noted between the 4 treatment groups. The
mean improvement in clinic peak nasal inspiratory flow
at 8 weeks was 65.9 L/min with budesonide aqueous na-
sal spray, 128 µg twice daily; 71.6 L/min with budes-
onide aqueous nasal spray, 256 µg once daily; and 54.6
L/min with budesonide aqueous nasal spray, 128 µg once
daily (all P,.001 vs placebo). Combined and individual
symptom scores and sense of smell improved signifi-
cantly in all budesonide-treated groups; the effect on symp-
toms became apparent within 1 to 2 days of the first dose.
Budesonide aqueous nasal spray was well tolerated.
Conclusions: Doses of budesonide aqueous nasal
spray, 128 µg once daily, were found to be effective in
the treatment of nasal polyps, and doses of budesonide
aqueous nasal spray, 256 µg once daily, did not show
any significant additional efficacy.
Arch Otolaryngol Head Neck Surg. 2001;127:447-452

From the Department of
Otorhinolaryngology,
Hôpital Central, Nancy
(Dr Jankowski); Department
of Otorhinolaryngology,
Hôpital Boucicaut, Paris
(Dr Bonfils); Centre
Hospitalier Universitaire,
Clermont-Ferrand
(Dr Gilain); Department of
Otorhinolaryngology, Hôpital
de Bellevue, St-Etienne
(Dr Parades); Department
of Otolaryngology, Centre
Hospitalier du Nord Amiens,
Amiens (Dr Strunski), France;
and Clinical Operations,
AstraZeneca Research and
Development, Lund, Sweden
(Dr Schrewelius). Dr Saban
is in private practice
in Nice, France.
N
ASAL POLYPS are benign
edematous growths that
arise from the lateral mu-
cosa of the middle me-
atus and probably from
the anterior ethmoids.1,2 Although the ori-
gin of nasal polyps is not fully understood,
it is widely accepted that they arise as a
result of a chronic inflammatory process.
Histological examination of polyps shows
extensive infiltration by inflammatory cells,
principally eosinophils,3-5 which is associ-
ated with inflammatory mediator release and
mast cell degranulation.6,7 The process can
lead to progressive growth of polyps with
nasal obstruction and impairment of smell.
Nasal polyposis, thus, is considered a reac-
tion to a chronic inflammatory process and,
hence, most patients with nasal polyps will
have chronic rhinosinusitis.
The aims of medical treatment of na-
sal polyposis are to relieve rhinitis symp-
toms, restore nasal breathing and a sense
of smell, and prevent recurrence.1,8 Anti-
inflammatory treatment with topical or, in
severe cases, systemic glucocorticoste-
roids is increasingly being accepted as first-
line therapy, with surgery being reserved
for cases in which such therapy is insuf-
ficient.1 Intranasal treatment with corti-
costeroids such as budesonide has been
shown to reduce polyp size, relieve symp-
toms, and reduce recurrence rates after sur-
gery.9-15 For budesonide aqueous nasal
spray (Rhinocort Aqua; Astra Draco AB,
Lund, Sweden) once-daily administra-
tion suffices in the treatment of allergy.
Hence, this study was performed to com-
pare the efficacy of 2 once-daily–dose regi-
mens of budesonide aqueous nasal spray

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with that of a twice-daily–dose regi-
men in the treatment of nasal polyps.
PATIENTS AND METHODS
The trial was a randomized, double-
blind, placebo-controlled, parallel-
group study conducted at 16 study
centers in France. It was approved
by local ethics committees at all
study centers.
PATIENTS
Patients were eligible for the clini-
cal trial if they were aged older than
18 years and had bilateral nasal pol-
yps that were causing nasal symp-
toms (ie, blocked nose, runny nose,
and sneezing). Patients were re-
quired to have at least 1 symptom
scoring 2 or higher on a 4-point scale
(0 indicates no symptoms; 1, mild
symptoms that were not trouble-
some; 2, moderate symptoms that
were frequently troublesome but not
sufficiently so as to interfere with
normal daily activities or sleep; and
3, severe symptoms that interfered
with normal activities or sleep) and
a score of 1 or higher for a blocked
nose on at least 4 days during
a 1-week run-in period. Patients
were excluded from the study if they
had received nasal steroid treat-
ment within 4 weeks, or systemic
steroids within 8 weeks, prior to en-
rollment. Other exclusion criteria
included significant medical condi-
tions,previous ethmoidcctomy, acute
and purulent sinusitis, hypersensi-
tivity to budesonide treatment, and
anatomical abnormalities in the nose
that were sufficient to cause obstruc-
tion. Female patients of childbear-
ing potential were required to use ad-
equate contraception. All patients
received full verbal and written
details of the study and provided
informed written consent before
enrollment.
TREATMENT
At the end of the run-in period eli-
gible patients were randomized ac-
cording to a balanced-block design
to receive 1 of the following 4 budes-
onide aqueous nasal spray treat-
ments: 128 µg once daily in the
morning and placebo in the evening,
128 µg twice daily, 256 µg once daily
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in the morning and placebo in the
evening, or placebo twice daily.
Treatment was continued for 8
weeks. The use of topical or oral de-
congestants, topical cromolyn so-
dium or nedocromil sodium, or
ipratropium bromide was not per-
mitted during the study. Compli-
ance with treatment was estimated
from diary card records kept by the
patients.
All study medication was iden-
tical in appearance. Treatment codes
for individual patients were kept in
secure locations at each study cen-
ter; the code was only to be broken
in an emergency, ie, if knowledge of
the study medication was neces-
sary for the management of the pa-
tient’s condition.
ASSESSMENTS
Endoscopic examination for mea-
surement of nasal polyp size was per-
formed at the beginning and end of
the run-in period and after 4 and 8
weeks’ treatment. Nasal polyp size
score was rated on a 4-point scale15
(ie, 0 indicates no polyps; 1, mild
polyps to small polyps not reach-
ing the lower edge of the middle tur-
binate; 2, moderate polyps to me-
dium-sized polyps extending
between the lower edge of the
middle and lower edges of the infe-
rior turbinates; and 3, severe pol-
yps to large polyps extending be-
low the lower edge of the inferior
turbinate).
Peak nasal inspiratory flow
(PNIF) was measured in the clinic
by means of a Youlten PNIF me-
ter16,17 at the beginning and end of
the run-in period and after 4 and 8
weeks’ treatment. In addition, pa-
tients measured PNIF each evening
during treatment and recorded the
results on diary cards. The highest
of 3 readings was recorded on each
occasion.
Symptoms (ie, blocked nose,
runny nose, and sneezing) and
sense of smell were recorded on
diary cards each evening during the
treatment period prior to taking the
PNIF measurements. Symptoms
over the preceding 24 hours were
evaluated according to the 4-point
scale described earlier. Sense of
smell was also recorded on a 4-
point scale (ie, 0 indicates normal
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448
sense of smell; l, slightly impaired
sense of smell; 2, moderately
impaired sense of smell; and 3, no
sense of smell). Patients provided
an overall evaluation of efficacy at
the end of treatment on a 5-point
scale (0 indicates symptoms aggra-
vated; 1, no control of symptoms;
2, minor control of symptoms; 3,
substantial control of symptoms;
and 4, total control of symptoms).
Information about adverse
events was obtained by a standard
question, “Have you had any
health problems since your last
visit?” at randomization and after
4 and 8 weeks’ treatment. In ad-
dition, a full medical examination
was performed on enrollment in
the study and nasal examinations
were performed as described
earlier.
STATISTICAL METHODS
The primary efficacy variable was
the mean change in nasal polyp
size score (sum of scores for both
nostrils) from baseline during the
8-week treatment period. The
study was designed to detect a
treatment difference in polyp size
score of 1.0 with 80% power
(a = .05, one-sided test). Changes
in mean polyp size were analyzed
by analysis of covariance, with
treatment and center as factors, fol-
lowed by pairwise comparisons.
The same approach was used to
analyze changes in combined and
individual symptom scores and
sense of smell from the run-in
period to the last 2 weeks of the
treatment period. The patients’
overall assessment of efficacy was
analyzed by analysis of variance,
with treatment and center as fac-
tors. All statistical tests were
2-tailed and P,.05 was considered
statistically significant.
RESULTS
A total of 183 patients were random-
ized to treatment. Sixteen enrolled pa-
tients were withdrawn prior to ran-
domization because they did not
show the required nasal symptoms
during the run-in period and 2 re-
ceived other medication that ren-
dered them ineligible. Patient dispo-
sition is summarized in Figure 1.
 No. of Patients Enrolled Budesonide, Budesonide,
(N = 201) 128 µg Twice Daily 128 µg Once Daily
Budesonide, Placebo
256 µg Once Daily
No. of Patients Ineligible
(n = 18)
4

Nasal Polyp Size Score

No. of Patients Randomized
(n = 183)
3

No. of Patients Who No. of Patients Who No. of Patients Who No. of Patients Who
Received Budesonide, Received Budesonide, Received Budesonide, Received Placebo
128 µg Twice Daily 256 µg Once Daily 128 µg Once Daily (n = 45)
(n = 48) (n = 42) (n = 48) 2

–1 0 1 2 3 4 5 6 7 8
No. of Patients Who No. of Patients Who No. of Patients Who No. of Patients Who Week
Discontinued Participation Discontinued Participation Discontinued Participation Discontinued Participation
in the Study in the Study in the Study in the Study Figure 2. Mean nasal polyp size scores. All
Adverse Events: n = 1 Adverse Events: n = 2 Adverse Events: n = 2 Other Reasons: n = 3 patients received budesonide aqueous nasal
Other Reasons: n = 6 Other Reasons: n = 3 Other Reasons: n = 1 Deterioration or Not spray treatment (Rhinocort Aqua; Astra Draco
Deterioration or Not Improved: n = 2
Improved: n = 2
AB, Lund, Sweden) or placebo. For an
explanation of the nasal polyp size see the
“Assessments” subsection of the “Patients and
No. of Patients Who No. of Patients Who No. of Patients Who No. of Patients Who Methods” section. No polyps were sized
Completed the Study Completed the Study Completed the Study Completed the Study as 0 or 1.
(n = 41) (n = 37) (n = 43) (n = 40)

Figure 1. Scheme showing the disposition of the patients. All doses of budesonide were administered by
an aqueous nasal spray (Rhinocort Aqua; Astra Draco AB, Lund, Sweden).
Table 1. Demographic Characteristics and Disease History
of 183 Patients With Nasal Polyps*
Budesonide, Budesonide, Budesonide,
128 µg 256 µg 128 µg
Twice Daily Once Daily Once Daily
(n = 48) (n = 42) (n = 48)
M/F 27/21 28/14 31/17
Mean age of patient, y 47.7 (22-76) 45.4 (21-69) 43.4 (23-74)
Mean duration of disease, y 6.2 (0-38) 5.3 (0-29) 5.8 (0-39)
Mean No. of polypectomies performed 1.5 (1-4) 2.6 (1-6) 2.5 (1-15)
Mean time since last polypectomy, mo 80 (5-170) 113 (84-144) 36 (4-96)
*Data are expressed as means (ranges) unless otherwise indicated. All doses of budesonide were
administered by an aqueous nasal spray (Rhinocort Aqua; Astra Draco AB, Lund, Sweden).
The demographic characteristics and 3 regimens were equally effective in
disease history of the randomized this situation. After 8 weeks, the ad-
patients were similar in the 4 groups justed mean change in nasal polyp
(Table 1). size score in patients receiving
budesonide aqueous nasal spray, 128
EFFICACY OF TREATMENT µg once daily, was −1.36 compared
with −1.32 in those receiving budes-
All 3 budesonide aqueous nasal onide aqueous nasal spray, 128 µg
spray regimens produced signifi- twice daily, −1.60 in those receiv-
cant (P,.01) reductions in nasal ing budesonide aqueous nasal spray,
polyp size scores compared with pla- 256 µg once daily, and −0.43 in those
cebo (Figure 2). Adjusted mean receiving placebo. All 3 budes-
changes in nasal polyp size scores at onide aqueous nasal spray regi-
4 and 8 weeks are listed in Table 2. mens were significantly (P,.01)
No significant differences were noted more effective than placebo.
in the change in nasal polyp size be- Mean PNIF, measured in the
tween the 3 budesonide-treated clinic, increased significantly
groups. Moreover, an analysis of the (P,.001) in all 3 budesonide-
effects of budesonide treatment on treated groups, but remained un-
the most severe nasal polyps (nasal changed in patients receiving pla-
polyp size score $4) showed that the cebo (Figure 3). The improvement
was significant at 4 weeks and was
maintained for the duration of the
study. No significant differences were
noted in the change in PNIF be-
tween the 3 budesonide-treated
groups. Patients’ daily measure-
ments of PNIF showed similar trends.
The mean change in PNIF from base-
Placebo line to the end of the treatment pe-
(n = 45) riod was an improvement by 62.1
27/18
L/min in patients receiving budes-
41.0 (18-63) onide aqueous nasal spray, 128 µg
4.9 (0-38) twice daily, 63.0 L/min in those re-
2.8 (1-20) ceiving budesonide aqueous nasal
81 (12-181) spray, 256 µg once daily, and 51.6
L/min in those receiving budesonide
aqueous nasal spray, 128 µg once
daily, compared with 10.6 L/min in
patients receiving placebo.
All 3 doses of budesonide
produced significant (P,.001)
reductions in combined symptom
scores compared with placebo,
but no significant differences
were noted between the active-
treatment groups (Figure 4). The
onset of the effect of budesonide
aqueous nasal spray on symptoms
was assessed by analyzing symp-
tom scores on the first 4 evenings
after starting treatment (ie, ap-
proximately 12, 36, 60, and 84
hours after the first dose). Com-
pared with placebo doses of budes-
onide aqueous nasal spray, 128 µg
twice daily and 128 µg once daily,
both produced significantly greater
reductions in combined symptom
scores than placebo within 36
hours (P<.001 and .04, respec-

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 Table 2. Adjusted Mean Change in Nasal Polyp−Size Score
Budesonide
Doses*
128 µg twice daily
256 µg once daily
128 µg once daily
*All doses of budesonide were administered by an aqueous nasal spray (Rhinocort Aqua; Astra Draco
AB, Lund, Sweden).
Budesonide,
128 µg Twice Daily
Budesonide,
256 µg Once Daily
200 Visits 1-4
190
180
170
160
PNIF, L/min
150
140
130
120
110
100
90
–1 0 1 2 3
Week
Figure 3. Mean peak nasal inspiratory flow
(PNIF). All patients received budesonide
aqueous nasal spray treatment (Rhinocort Aqua;
Astra Draco AB, Lund, Sweden) or placebo.
tively); at subsequent time points,
all active treatments produced
significantly greater reductions
than placebo (Figure 5). The effi-
cacy was separately assessed in the
patients with moderate to severe
nasal polyps, ie, a polyp size score
of 4 or higher.
All 3 budesonide doses pro-
duced significant (P,.01) reduc-
tions in individual symptom scores
and improvements in sense of smell
compared with placebo (with the ex-
ception of sneezing in the group
treated with budesonide aqueous na-
sal spray, 128 µg twice daily); no sig-
nificant differences were noted be-
tween the active-treatment groups
(Figure 6).
At the end of the study, the
proportions of patients reporting sub-
stantial or total control of symptoms
were 73.2% in the group receiving
budesonide aqueous nasal spray, 128
µg twice daily, 68.4% in patients re-
ceiving budesonide aqueous nasal
spray, 256 µg once daily, and 69.6%
in those receiving budesonide aque-
ous nasal spray, 128 µg once daily,
compared with 26.2% in the placebo
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Adjusted Mean Change
(95% Confidence Limits)
4 Weeks
−0.78 (−1.10, −0.47)
−1.14 (−1.48, −0.81)
−0.87 (−1.18, −0.56)
Budesonide, Budesonide,
128 µg Once Daily 128 µg Twice Daily
Placebo Budesonide,
256 µg Once Daily
5 received budesonide aqueous nasal spray
Nasal Symptom Score
4 Lund, Sweden). Single asterisk indicates P,.05;
3
2 µg once daily; 3 receiving doses of
1
0 cebo. Most adverse events were mild
4 5 6 7 8 –7 0 7 14
Time, d
Figure 4. Combined nasal symptoms. All
patients received budesonide aqueous nasal
spray treatment (Rhinocort Aqua; Astra Draco
AB, Lund, Sweden) or placebo.
group. All 3 doses of budesonide
aqueous nasal spray produced sig-
nificantly (P,.001) better results than
placebo; no significant differences
were noted between the groups.
TOLERABILITY OF
TREATMENT
Budesonide aqueous nasal spray
was well tolerated in this study.
Overall, a total of 128 adverse events
were reported by 91 patients. The
principal adverse events reported
more frequently with budesonide
aqueous nasal spray treatment than
with placebo were blood-tinged
nasal secretions, which occurred in
4 patients receiving doses of 128 µg
once daily, 5 patients receiving
doses of 256 µg once daily, 7 pa-
tients receiving doses of 128 µg
twice daily, and 2 patients receiving
placebo. Headache was reported in
1, 1, 6, and 0 patients, respectively.
Bronchospasm occurred in 4 pa-
tients receiving doses of budes-
onide aqueous nasal spray, 128 µg
once daily; 3 receiving doses of
budesonide aqueous nasal spray, 256
450
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Budesonide, Budesonide,
128 µg Twice Daily 128 µg Once Daily
Budesonide,
256 µg Once Daily
Mean Change From Placebo Group
0
8 Weeks –0.2
−1.13 (−1.49, −0.77) –0.4
−1.43 (−1.81, −1.05)
–0.6 ∗
−1.22 (−1.57, −0.86) ∗ ∗
–0.8 ∗ ∗
–1.0
∗∗ ∗ ∗
–1.2
0 12 36 60 84
Budesonide, Time, h
128 µg Once Daily
Placebo Figure 5. Mean reductions in combined
symptom score compared with placebo during
the first 4 days of treatment. All patients
treatment (Rhinocort Aqua; Astra Draco AB,
double asterisk, P,.001.
budesonide aqueous nasal spray, 128
µg twice daily; and 3 receiving pla-
21 28 35 42 49 56 or moderate in intensity. Four seri-
ous adverse events occurred but
none were causally related to budes-
onide aqueous nasal spray treat-
ment, as judged by the investiga-
tors responsible for the concerned
patients.
COMMENT
The results of this study show that
budesonide aqueous nasal spray is ef-
fective in the treatment of nasal pol-
yps, producing significant and sus-
tained improvements in nasal polyp
size, symptoms, and nasal airflow.
The patients recruited in this study
had moderate-sized nasal polyps
(mean score of 3.7 of a maximum
possible score of 6) that were caus-
ing troublesome obstruction (mean
score for nasal blockage of 2). In ad-
dition, most patients had nasal pol-
yps that extended beyond the lower
edge of the concha media on 1 side.
Our patients, thus, had mild to mod-
erate nasal polyposis, and such pa-
tients would normally be consid-
ered for surgery if topical therapy
proved inadequate1,18; hence, the find-
ing that medical therapy can relieve
obstruction and symptoms in these
patients is clinically important.
Previous studies with budes-
onide, administered as a nasal dry
powder or aerosol, have shown that
doses of 400 or 800 µg/d (equiva-
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A Blocked Nose
2.5
Change in Nasal Symptom Score
2.0
1.5
1.0
0.5
0.0
C Sneezing
2.5
Change in Nasal Symptom Score
2.0
1.5
1.0
0.5
0.0
–7
Figure 6. Changes in individual nasal symptom scores and sense of smell for blocked nose (A), runny
nose (B), sneezing (C), and sense of smell (D). All patients received budesonide aqueous nasal spray
treatment (Rhinocort Aqua; Astra Draco AB, Lund, Sweden) or placebo.
lent to supplied doses of up to 280
µg or 560 µg, respectively) are ef-
fective in the treatment of nasal pol-
yps.15,19,20 The results of the present
study show that a dose of 128 µg
given once daily via nasal spray (ie,
supplied dose of 128 µg) is effec-
tive, and that doubling this dose does
not provide any additional statisti-
cally significant improvement in
symptoms or airflow. The severity
of nasal polyps does not seem to be
a major predictor for the efficacy of
budesonide aqueous nasal spray
treatment because patients with
more severe polyps have been found
to respond to treatment.15 This pre-
sumably reflects efficient amounts
of drug supplied with nasal sprays.
The once-daily budesonide aque-
ous nasal spray doses of 128 µg and
256 µg shown to be effective in na-
sal polyposis in this study are iden-
tical to those that are effective in pa-
tients with allergic rhinitis.21 Because
nasal spray treatment has been
shown to be efficacious, it seems un-
necessary to use complicated sup-
ply procedures, eg, using pipettes or
extreme head positions, as has some-
times been advocated for nose drop
formulations.22 Analysis of com-
bined symptom scores during the
Budesonide, Budesonide, Budesonide, Placebo
128 µg Twice Daily 256 µg Once Daily 128 µg Once Daily
B Runny Nose
D Sense of Smell
0 7 14 21 28 35 42 49 56 –7 0 7 14 21 28 35
Time, Day Time, Day
first 4 days of treatment showed that
budesonide aqueous nasal spray has
a rapid onset of action: significant
improvements in symptom scores
were observed within approxi-
mately 1 to 2 days.
In this study, the increase in na-
sal airflow in patients treated with
budesonide aqueous nasal spray was
measured by using the Youlten PNIF
meter.16,17 Results obtained by this
technique have been shown to cor-
relate with those obtained by ante-
rior rhinomanometry and measure-
ment of peak nasal expiratory
flow.16,17,23,24 Nasal airflow did not
change significantly in placebo-
treated patients, whereas some im-
provement in symptom scores was
observed. This might suggest that
any placebo effect resulting from the
use of an aqueous spray, as has been
suggested from some studies in pa-
tients with rhinitis,25 is confined to
subjective symptom assessments.
Our study was designed to
evaluate the effects of short-term
budesonide therapy, but nasal pol-
yps is a chronic condition that of-
ten requires long-term treatment. In
a long-term study, treatment with
budesonide for 1 year produced sig-
nificant and sustained improve-
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©2001 American Medical Association. All rights reserved.
ment in symptoms and objectively
measured nasal peakflow.19,20
This study has also confirmed
the tolerability of budesonide aque-
ous nasal spray treatment seen in
previous studies in patients with na-
sal polyps.15 Blood-tinged nasal se-
cretions tended to be more com-
mon with the higher doses of
budesonide aqueous nasal spray, but
were still infrequent, and the num-
bers were too small to allow any
meaningful interpretation.
In conclusion, this study has
shown that a once-daily dose of 128
µg of budesonide aqueous nasal spray
was effective treatment for mild to
moderate nasal polyps, and a daily
dose of 256 µg of budesonide aque-
ous nasal spray does not exert sig-
nificant additional efficacy.
Accepted for publication August 24,
42 49 56 2000.
We gratefully acknowledge the
contribution of the following French
investigators to this study: Philippe
Bordure, MD, Nantes; Dominique
Chevalier, MD, Lille; Jean M. Klossek,
MD, Poitiers; Claude Conraux, MD,
Strasbourg; Laurence Renaud-
Picard, MD, Besancon; Philippe Ro-
manet, MD, Dijon; Dominique Stoll,
MD, Bordeaux; Alain Londero, MD,
Colombes; Jean P. Fombeur, MD,
Paris; Pierre Kennel, MD, Colmar;
Jean-Claude Merol, MD, Reims.
Corresponding author: Roger
Jankowski, MD, Department of Oto-
rhinolaryngology, Head and Neck Sur-
gery, Central Hospital, H. Poincaré
University, F-54000 Nancy, France.
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