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Figure 1.
The median polyp score for both nostrils combined throughout the treatment period. FPANS indicates fluticasone propionate aqueous nasal spray; BDANS, beclomethasone dipropionate aqueous nasal spray; and asterisk, significant at P=.02.

The median polyp score for both nostrils combined throughout the treatment period. FPANS indicates fluticasone propionate aqueous nasal spray; BDANS, beclomethasone dipropionate aqueous nasal spray; and asterisk, significant at P=.02.

Figure 2.
The total volume (cubic centimeters) measured by acoustic rhinometry before the administration of vasoconstrictor throughout the treatment period. FPANS indicates fluticasone propionate aqueous nasal spray; BDANS, beclomethasone dipropionate aqueous nasal spray; asterisk, P=.03; and dagger, P=.02.

The total volume (cubic centimeters) measured by acoustic rhinometry before the administration of vasoconstrictor throughout the treatment period. FPANS indicates fluticasone propionate aqueous nasal spray; BDANS, beclomethasone dipropionate aqueous nasal spray; asterisk, P=.03; and dagger, P=.02.

Figure 3.
The percentage change in mean morning peak nasal inspiratory flow (PNIF) from baseline throughout the treatment period. FPANS indicates fluticasone propionate aqueous nasal spray; BDANS, beclomethasone dipropionate aqueous nasal spray; asterisk, P=.002; and dagger, P=.02.

The percentage change in mean morning peak nasal inspiratory flow (PNIF) from baseline throughout the treatment period. FPANS indicates fluticasone propionate aqueous nasal spray; BDANS, beclomethasone dipropionate aqueous nasal spray; asterisk, P=.002; and dagger, P=.02.

Table 1. 
Demographic Characteristics of Patients (N = 29)
Demographic Characteristics of Patients (N = 29)
Table 2. 
Clinic Visit Assessments*
Clinic Visit Assessments*
Table 3. 
Results of Acoustic Rhinometry*
Results of Acoustic Rhinometry*
1.
Mygind  N Nasal polyps. Nasal Allergy London, England Blackwell Scientific Publications1979;233- 238
2.
Baumgarten  CKunkel  GRudolph  RStaud  RDSperner  IGelderblom  H  et al.  Histopathologic examinations of nasal polyps of different etiology. Arch Otorhinolaryngol. 1980;226187- 197Article
3.
Mygind  NPedersen  CBPrytz  SSorenson  H Treatment of nasal polyps with intranasal beclomethasone dipropionate aerosol. Clin Allergy. 1975;5159- 164Article
4.
Deuschl  HDrettner  B Nasal polyps treated by beclomethasone nasal aerosol. Rhinology. 1977;1517- 23
5.
Drettner  BEbbesen  ANilsson  M Prophylactic treatment with flunisolide after polypectomy. Rhinology. 1982;20149- 158
6.
Karlsson  GRundcrantz  H A randomized trial of intranasal beclomethasone dipropionate after polypectomy. Rhinology. 1982;20144- 148
7.
Virolainen  EPuhakka  H The effect of intranasal beclomethasone dipropionate on the recurrence of nasal polyps after ethmoidectomy. Rhinology. 1980;189- 18
8.
Hartwig  SLinden  MLaurent  CVargo  AK Budesonide nasal spray as prophylactic treatment after polypectomy. J Laryngol Otol. 1988;102148- 151Article
9.
Rhunno  JAndersson  BDenburg  J  et al.  A double-blind comparison of intranasal budesonide with placebo for nasal polyposis. J Allergy Clin Immunol. 1990;86946- 953Article
10.
Meltzer  EOOrgel  HABronsky  EA  et al.  A dose-ranging study of fluticasone propionate aqueous nasal spray for seasonal allergic rhinitis assessed by symptoms, rhinomanometry, and nasal cytology. J Allergy Clin Immunol. 1990;86221- 230Article
11.
Scadding  GLund  VJHolmstrom  MDarby  YC  et al.  Clinical and physiological effects of fluticasone aqueous nasal spray in the treatment of perennial rhinitis. Rhinol Suppl. 1991;1137- 43
12.
Holmberg  KJuliusson  SSmith  DLRichards  DHKarlsson  GBalder  B  et al.  Fluticasone propionate aqueous nasal spray in the treatment of nasal polyposis. Ann Allergy Asthma Immunol. 1997;78270- 276Article
13.
Lund  VJMackay  IS Staging in rhinosinusitis. Rhinology. 1993;31183- 184
14.
Lund  VJKennedy  DW Quantification for staging sinusitis: the Staging and Therapy Group. Ann Otol Rhinol Laryngol Suppl. 1995;16717- 21
15.
Doty  RLShaman  PDann  M Development of the University of Pennsylvania smell identification test: a standardized microencapsulated test of olfactory function. Physiol Behav. 1984;32489- 502Article
16.
Holmstrom  MLund  VJ Response of olfactory acuity to surgical stress. Am J Rhinol. 1996;101- 4Article
17.
Hilberg  OJackson  ACSwift  DLPedersen  OF Acoustic rhinometry: evaluation of nasal cavity geometry by acoustic reflection. J Appl Physiol. 1989;66295- 303
18.
Youlten  LJF The peak nasal inspiratory flow meter: a new instrument for the assessment of the response to immunotherapy in seasonal allergic rhinitis. Allergol Immunopathol (Madr). 1980;8344- 347
19.
Lund  VJ Surgical management of nasal polyposis.  Paper presented at: European Academy of Allergy and Clinical Immunology 1996 Budapest, Hungary
20.
Lildholdt  TFogstrup  JGammelgaard  N  et al.  Surgical versus medical treatment of nasal polyps. Acta Otolaryngol. 1988;105140- 143Article
21.
Lildholdt  TRundcrantz  HLindquist  N Efficacy of topical corticosteroid powder for nasal polyps: a double-blind, placebo-controlled study of budesonide. Clin Otolaryngol. 1995;2026- 30Article
22.
Holmberg  KKarlsson  G Nasal polyps: surgery or pharmacological intervention? Eur Respir Rev. 1994;4260- 265
23.
Elbrond  OFelding  JUGustavsen  KM Acoustic rhinometry used as a method to monitor the effect of intramuscular injection of steroid on nasal polyps. J Laryngol Otol. 1991;105178- 180Article
24.
Settipane  GA Nasal polyps. RhinitisNew England Regional Allergy Proceedings Providence, RI Oceanside Publications Inc1984;133- 140
Original Article
May 1998

Effect of Fluticasone in Severe Polyposis

Author Affiliations

From the Institute of Laryngology and Otology, Royal National Throat, Nose and Ear Hospital, London (Dr Lund and Ms Flood); Glaxo Wellcome Ltd, Greenford (Mr Sykes); and Glaxo Wellcome Research and Development Public Limited Company, Uxbridge, Middlesex (Mr Richards), England.

Arch Otolaryngol Head Neck Surg. 1998;124(5):513-518. doi:10.1001/archotol.124.5.513
Abstract

Objectives  To investigate the effect of intranasal corticosteroids in the treatment of polyps in patients with severe polyposis listed for surgical treatment and to determine the treatment effect on the progression of the disease.

Design  A double-blind, randomized, parallel-group, placebo-controlled, 12-week study at a single center.

Setting  A tertiary referral center in London, England.

Patients  Thirty-four patients with severe polyposis listed for endoscopic surgical treatment.

Intervention  By random allocation, fluticasone propionate aqueous nasal spray (FPANS), 200 µg twice a day; beclomethasone dipropionate aqueous nasal spray, 200 µg twice a day; or placebo nasal spray twice a day was administered. Patients received 2 actuations to each nostril in the morning and in the evening.

Main Outcome Measures  Efficacy end points were the need for polypectomy at the end of treatment, the results of acoustic rhinometry, the polyp score, the peak nasal inspiratory flow rate, and an assessment of symptoms.

Results  The polyp score was significantly decreased in the FPANS-treated group (P≤.01). The nasal cavity volume was significantly increased in both the FPANS-treated group and the group receiving beclomethasone compared with placebo (P≤.01) at the end of treatment. The percentage change in the mean morning peak nasal inspiratory flow rate was greater in the FPANS-treated group, with a significant effect observed at week 2 (P=.01). Nasal blockage was significantly decreased in both active groups compared with the group receiving placebo. No significant difference was observed between the treatment groups in the number of patients requiring polypectomy.

Conclusions  Fluticasone and beclomethasone aqueous nasal sprays are effective in treating the symptoms of severe nasal polyps. There was some evidence that the group treated with FPANS responded more quickly to intervention and that the magnitude of the response was greater than in the group receiving beclomethasone.

NASAL POLYPOSIS is a common clinical condition that, despite differing hypotheses of its cause, remains a poorly understood disease. Although nasal polyposis is histologically an inflammatory disease,1,2 the preferred treatment is surgical, but the frequent recurrence of polyps after surgical treatment is a problem for many patients. Several studies have demonstrated that topical corticosteroids are effective in reducing the size of polyps, nasal symptoms after surgical treatment, and the recurrence rate of polyps after polypectomy.39

The aim of this study was to investigate the effects of fluticasone propionate aqueous nasal spray (FPANS) in controlling the growth of polyps in patients with severe nasal polyposis who were listed for endoscopic surgical treatment. Fluticasone has already been shown to be an effective and safe treatment in allergic and nonallergic rhinitis,10,11 and results from a preliminary study of patients with moderate to severe polyposis have demonstrated that it is effective in reducing the size of polyps and the associated symptoms of polyposis.12

PATIENTS AND METHODS

This was a randomized, double-blind, placebo-controlled, parallel-group study performed at the Royal National Throat, Nose and Ear Hospital, London, England. This is the first report of a study in this group of patients that we are aware of, and as such, accurate estimations of the parameters required to carry out a meaningful power calculation were not available. The patient group studied was the largest that could be practically assessed in this clinic. Patients were randomly allocated, using a computer-generated random code and a block size of 6, to receive 1 of 3 treatments, if eligible, at clinic visit 2: FPANS, 200 µg twice a day (2 actuations to each nostril in the morning and in the evening); beclomethasone dipropionate aqueous nasal spray (BDANS), 200 µg twice a day (2 actuations to each nostril in the morning and in the evening); and placebo (aqueous nasal spray), twice a day (2 actuations to each nostril in the morning and in the evening). The placebo was identical to the active formulations with the active ingredient omitted and was indistinguishable from the active treatments, which were themselves identical in appearance, taste, and smell.

The study included a 4-week pretreatment period during which no treatment for polyposis, except placebo, could be used by the patient, followed by a 12-week double-blind treatment period and a 2-week follow-up period. Patients attended the clinic for assessment after 4 weeks of pretreatment (visit 2); after 4 weeks (visit 3), 8 weeks (visit 4), and 12 weeks of treatment (visit 5); and after 2 weeks of follow-up (visit 6). All patients were supplied with terfenadine (60 mg) to use as a rescue medication should their symptoms of rhinitis become troublesome. The study was granted approval by the ethics committee, and written informed consent was obtained from each patient before participation in the study.

PATIENTS

Patients older than 16 years with a diagnosis of bilateral nasal polyposis requiring surgical intervention were recruited. Patients with nasal polyps with 1 of the following clinical assessment scores as assessed by a single investigator (V.J.L.) on entry were included13,14:

  • a total polyp score of 4 or higher plus a computed tomographic scan score of greater than 1213;

  • a total polyp score of 3 or higher, a nasal blockage score of 2 or higher, plus a computed tomographic scan score of greater than 12; and

  • a total polyp score of 2 or higher, a nasal blockage score of 2 or higher, a computed tomographic scan score of greater than 12, plus a University of Pennsylvania Smell Identification Test score of greater than 32.15,16 In UPSIT, 0 indicates no polyps; 1, polyps within the middle meatus; 2, polyps outside the middle meatus; and 3, completely obstructive polyps. The polyp scores for both nostrils were added together to give the total polyp score.

Patients were excluded from the study if they had a concurrent purulent nasal infection, a requirement for more than 1000 µg of beclomethasone (or equivalent) per day for the treatment of asthma, an inability to cease treatment with parenteral and intranasal corticosteroids or cromolyn sodium (sodium cromoglycate) at visit 1, used astemizole in the 6 weeks before the study or other antihistamines in the 48 hours before visit 1, or a contraindication to corticosteroid medications.

Before the start of the study, a full ear, nose, and throat examination and skin-prick test were done and a medical history was obtained. At each clinic visit, the investigator (V.J.L.) assessed the degree of nasal blockage, nasal symptoms, and the size of the polyps by endoscopic examination. The grading scale for nasal symptoms was from 0 (no symptoms) to 4 (very severe) for each nostril. At each clinic visit, the nasal volume was assessed by acoustic rhinometry according to the method of Hilberg et al17 and peak nasal inspiratory flow (PNIF) was measured using a peak inspiratory flow meter (Youlten, Clement Clarke International Ltd, Harlow, Essex, England).18

Patients were issued daily record cards (DRCs) for each treatment period, including the 4-week treatment period. Patients recorded an assessment of their nasal blockage, sense of smell, degree of nasal discomfort (facial pain and headache), and overall rhinitis symptoms (sneezing, rhinorrhea, nasal itching) on a 5-point rating scale from 0 (no symptoms) to 4 (very severe). Patients were issued a PNIF meter to record the highest of 3 measurements of PNIF on the DRCs in the morning and evening before taking their study medication.

Safety was assessed by monitoring adverse events reported on the DRC and by specific questioning at each clinic visit. Biochemistry and hematologic values were assessed at baseline, and a physical examination was performed before and at the end of the treatment period.

STATISTICAL ANALYSIS

The median symptom scores for the patients' symptoms of nasal blockage and the degree of polyposis assessed by the physician (V.J.L.) at each clinic visit were analyzed separately using the Wilcoxon rank sum test. Daily symptoms measured on the DRCs were also analyzed using the Wilcoxon rank sum test. The results of acoustic rhinometry and PNIF rates measured at clinic visits and on the DRCs were analyzed using an analysis of covariance. Two-sided tests at the .05 level of significance have been presented for the estimates of the difference for all treatment comparisons.

As with any study of this type involving withdrawals during the treatment phase, the opportunity exists to attribute success inappropriately because the patients with more severe symptoms and those with the lowest probability of treatment response may have withdrawn from the study, leaving the patients with less severe symptoms to be assessed. For this reason, the results expressed in this study involve using the last-value-carried-forward technique to avoid treatment bias.

RESULTS

Of the 34 patients for the study, 29 were randomly assigned to treatment: 9 patients to the group receiving placebo and 10 patients each to the group receiving FPANS and the group receiving BDANS. The demographic details of the patients are listed in Table 1. The patients had a long history of nasal polyposis, with 19 (66%) having had a previous surgical procedure for polyposis and 17 (59%) having had the condition for more than 10 years. Five patients withdrew before randomization because of adverse events (1 patient), a requirement for polypectomy (1 patient), ineffectiveness of the medication during the pretreatment period (1 patient), and failing to return (2 patients). There was evidence, particularly from the acoustic rhinometric and PNIF data, that the patients randomly allocated to receive BDANS had milder symptoms than those randomly allocated to receive FPANS or placebo, even though all patients had been listed for surgical treatment on an equal basis before the study.

EFFICACY

Investigator assessment of the degree of polyposis showed that all 3 treatment groups had the same median polyp score of 4 (total score in both nostrils) at baseline. For both active treatment groups, this score gradually decreased during the treatment period and reached significance for FPANS-treated patients compared with those receiving placebo at week 12 of treatment (Figure 1). The median polyp score in the FPANS-treated group decreased to 2 at week 12 (P=.02). Although BDANS-treated patients also showed a trend for improvement, this did not reach statistical significance when compared with patients receiving placebo.

The number of patients withdrawing during the treatment period was 7–4 patients in the group receiving placebo and 3 in the FPANS-treated group. Of these, 5 patients withdrew because of a perceived lack of efficacy of their medication (3 in the group receiving placebo and 2 in the FPANS-treated group), 1 patient in the placebo group required a polypectomy, and 1 patient in the FPANS-treated group did not follow the protocol.

The total number of patients who required a polypectomy either during treatment or who were assessed as still requiring one at the end of treatment, or who withdrew because of lack of efficacy during the treatment period did not differ significantly between any of the treatment groups. Eight patients in the group receiving placebo, 7 in the FPANS-treated group, and 4 in the BDANS-treated group were deemed to have met these criteria when patients who completed the study were assessed by the physician (V.J.L.) at the end of the study. This assessment was made by the same physician and using the same clinical criteria as had originally resulted in the patients being listed for surgical treatment before entry to the study.

For the assessment of symptoms, in each case a 0- to 3-point scale on the DRC was used, where 0 denoted no symptoms and 3 denoted severe symptoms. Patients assessed each nostril individually, as their polyposis may not have been equally bilateral, and the scores were combined for analysis. The assessment of nasal blockage demonstrated significantly (Table 2) improved (reduced) scores for both FPANS- and BDANS-treated patients when compared with those receiving placebo at week 4. The FPANS-treated group had a median score of 6 at baseline, which decreased to 2 at week 4 (P=.02), whereas the BDANS-treated group had a median score of 4 at baseline, which also decreased to 2 at week 4 (P=.01). The BDANS-treated group remained significantly better than those receiving placebo at all other visits, whereas although the FPANS-treated group showed a trend for improvement, this did not reach significance.

The overall assessment of rhinitis symptoms (Table 2) also showed significant improvement for both FPANS- and BDANS-treated groups at week 4 of treatment but did not reach statistical significance throughout the rest of the treatment period. The median score at baseline for the FPANS- and BDANS-treated groups were 4 and 5, respectively, both of which decreased to 2 at week 4 (P=.02 for both). Again, although the overall score was lower at week 8 and week 12 for both groups, it did not reach statistical significance when compared with those receiving placebo. The placebo-treated group showed a worsening of symptoms during treatment.

Clinic visit measurements of the PNIF (Table 2) showed a difference at baseline between the 2 active treatment groups, with a 73 L/min greater baseline in the BDANS-treated group than in the FPANS-treated group. The baseline for the group receiving placebo was similar to that for the FPANS-treated group. The FPANS-treated group showed an immediate trend for improvement that continued throughout the treatment period but that did not reach statistical significance until week 12 of treatment (mean increase of 76 L/min). The PNIF in the BDANS-treated group also improved throughout the treatment period and reached statistical significance compared with the group receiving placebo at week 8 of treatment (mean increase of 69 L/min).

Acoustic rhinometry results (Table 3 and Figure 2) showed that the total volume of both nostrils combined was significantly improved with both active treatments. The scores before and after vasoconstrictor were significantly improved at all clinic visits for both active treatments compared with placebo. The mean cross-sectional area before and after vasoconstrictor use also showed a trend for improvement in both active groups, reaching significance for the FPANS-treated group before vasoconstrictor use at week 8 of treatment when compared with the group receiving placebo (P=.03).

The PNIF measured on the DRC (Figure 3) also showed a much higher baseline value in the BDANS-treated group when compared with the other 2 groups. The baseline value was 91 L/min in the group receiving placebo, 64 L/min in the FPANS-treated group, and 129 L/min in the BDANS-treated group. The percentage change in mean morning PNIF rates from baseline was significantly increased in both active treatment groups when compared with the group receiving placebo, with a much higher increase observed in the FPANS-treated group. The onset of action for FPANS was faster than that for BDANS, with a significant improvement seen after 2 weeks of treatment (Figure 3). The evening PNIF was also significantly increased in both active treatment groups (P=.002 and P=.02, respectively, at week 12). Assessment of the percentage of days with no nasal blockage during the day showed an improvement throughout the treatment period that was significant for both active treatments from weeks 4 to 12. There was a trend for FPANS to be more effective than BDANS, with more patients in the former group having 100% of days with no nasal blockage. Similarly, both active treatments significantly increased the percentage of days with no nasal blockage during the night, with improvements seen at week 4 and until the end of the treatment period. The percentage of days with no rhinitis symptoms during the day increased for both treatment groups to reach a median value of 89% and 96% for FPANS- and BDANS-treated groups, respectively, at week 12 compared with 0% in the group receiving placebo. This, however, did not reach statistical significance (P=.09 in the FPANS-treated group and P=.06 in the BDANS-treated group compared with the group receiving placebo).

There was no effect on the sense of smell attributable to either active treatment.

SAFETY

All patients randomly allocated to treatment were included in safety evaluations. There were more adverse events (7 [70]) reported in the FPANS-treated group compared with those (3 [33]) in the group receiving placebo and in the BDANS-treated group (3 [30]). Most of the events were associated with asthma, upper respiratory tract infection, and headache. There was only 1 adverse event in the group receiving placebo described as "drug related" and 1 predictable adverse event—throat irritation—in the FPANS-treated group. No serious adverse events were reported.

COMMENT

This study was a pilot study to compare the efficacy and safety of FPANS and BDANS with placebo in the treatment of nasal polyps in adult patients with severe bilateral polyposis who were already listed for surgical treatment.

Most studies have looked at the effect of topical corticosteroids on the recurrence of polyps following polypectomy. Results have shown that topical corticosteroids do not abolish the need for polypectomy, although the frequency of the requirement for repeated polypectomy can be significantly reduced.58 It is generally agreed, therefore, that a combination of both medical and surgical treatment may be required for long-term success.19 This study, however, looked at the effect of fluticasone propionate, a potent topical corticosteroid, to assess whether pharmacological intervention can indeed control the progression of the disease and prevent, or substantially delay, the need for surgical therapy. Previous studies have compared the effect of medical vs surgical treatment of patients with polyps with varying degrees of success.20

Treatment with FPANS resulted in a reduction in the polyp score that was significant at week 12. Treatment with BDANS also showed a trend for improvement, but this did not reach statistical significance. This is in accordance with the results from another study in which a significant reduction in polyp size was seen in patients with moderate to severe polyposis after 14 weeks' treatment with FPANS12 and also other published studies of the use of topical corticosteroids.1,2,5,9,21

One of the main symptoms of polyposis is nasal obstruction with blockage, often increasing during the night.22 Treatment with FPANS and with BDANS significantly decreased nasal blockage assessed by nasal examination and also measured by the patients on the DRC for both daytime and nighttime blockage. In accordance with this, there was a significant increase in nasal airflow assessed by PNIF in the FPANS- and BDANS-treated groups, although it was much greater in the FPANS-treated group, with a significant effect observed within the first 2 weeks of treatment. Acoustic rhinometry, which defines the geometry of the nasal cavity,18 has been used to determine the effect of medical treatment on nasal polyps.23 Results show that the mean cross-sectional area, which is decreased in patients with nasal polyps due to their mass effect, significantly increased with FPANS treatment, whereas BDANS treatment also showed a trend for improvement, although this did not reach significance. The volume (in cubic centimeters) of the nasal cavity was also significantly increased following treatment with FPANS and BDANS when compared with placebo.

Anosmia, the loss of smell, is also a prevalent symptom in patients with polyps, but no significant differences were observed for treatment with either active drug compared with placebo. The symptoms of rhinitis, another common feature of patients with polyps,24 significantly decreased in both active treatment groups compared with the group receiving placebo at week 4 of treatment.

In this study, a deterioration of symptoms was seen in the group receiving placebo, which is contrary to the placebo effect seen in other studies9,21 and which may reflect the more severe nature of the disease in these patients.

Results from this study showed that there was no significant difference in the number of patients who required polypectomy at the end of treatment. A lower number of patients requiring polypectomy in the BDANS-treated group compared with the other 2 groups was observed, but on investigation of the patient groups, there seems to have been an imbalance in the randomization, leading to patients with less severe symptoms being randomly assigned to the BDANS treatment group. Thus, the baseline PNIF was almost twice that seen in the other 2 groups, indicating a milder degree of nasal obstruction on entry into the study. In addition, other baseline variables measured, including nasal blockage, nasal volume measured by acoustic rhinometry, and rhinitis symptoms, were lower on entry for the BDANS treatment group. Two patients withdrew from the FPANS treatment group between weeks 4 and 8 of treatment compared with none in the BDANS treatment group, which also indicates that the patients in the former group perhaps had more severe symptoms.

The results of this pilot study have been encouraging, with significant improvements seen in both treatment groups, although the reduction in the number of patients requiring polypectomy did not reach significance. From these results, further study is warranted to examine a larger patient population, with possibly a longer treatment period, and in particular to determine the cost-effectiveness of medical treatment in delaying or possibly preventing the need for surgical therapy.

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Article Information

Accepted for publication February 4, 1998.

Presented at the European Academy of Allergology and Clinical Immunology, Budapest, Hungary, June 3, 1996.

Reprints: David H. Richards, BSc, Glaxo Wellcome Research and Development Place, Stockley Park West, Uxbridge, Middlesex, England.

References
1.
Mygind  N Nasal polyps. Nasal Allergy London, England Blackwell Scientific Publications1979;233- 238
2.
Baumgarten  CKunkel  GRudolph  RStaud  RDSperner  IGelderblom  H  et al.  Histopathologic examinations of nasal polyps of different etiology. Arch Otorhinolaryngol. 1980;226187- 197Article
3.
Mygind  NPedersen  CBPrytz  SSorenson  H Treatment of nasal polyps with intranasal beclomethasone dipropionate aerosol. Clin Allergy. 1975;5159- 164Article
4.
Deuschl  HDrettner  B Nasal polyps treated by beclomethasone nasal aerosol. Rhinology. 1977;1517- 23
5.
Drettner  BEbbesen  ANilsson  M Prophylactic treatment with flunisolide after polypectomy. Rhinology. 1982;20149- 158
6.
Karlsson  GRundcrantz  H A randomized trial of intranasal beclomethasone dipropionate after polypectomy. Rhinology. 1982;20144- 148
7.
Virolainen  EPuhakka  H The effect of intranasal beclomethasone dipropionate on the recurrence of nasal polyps after ethmoidectomy. Rhinology. 1980;189- 18
8.
Hartwig  SLinden  MLaurent  CVargo  AK Budesonide nasal spray as prophylactic treatment after polypectomy. J Laryngol Otol. 1988;102148- 151Article
9.
Rhunno  JAndersson  BDenburg  J  et al.  A double-blind comparison of intranasal budesonide with placebo for nasal polyposis. J Allergy Clin Immunol. 1990;86946- 953Article
10.
Meltzer  EOOrgel  HABronsky  EA  et al.  A dose-ranging study of fluticasone propionate aqueous nasal spray for seasonal allergic rhinitis assessed by symptoms, rhinomanometry, and nasal cytology. J Allergy Clin Immunol. 1990;86221- 230Article
11.
Scadding  GLund  VJHolmstrom  MDarby  YC  et al.  Clinical and physiological effects of fluticasone aqueous nasal spray in the treatment of perennial rhinitis. Rhinol Suppl. 1991;1137- 43
12.
Holmberg  KJuliusson  SSmith  DLRichards  DHKarlsson  GBalder  B  et al.  Fluticasone propionate aqueous nasal spray in the treatment of nasal polyposis. Ann Allergy Asthma Immunol. 1997;78270- 276Article
13.
Lund  VJMackay  IS Staging in rhinosinusitis. Rhinology. 1993;31183- 184
14.
Lund  VJKennedy  DW Quantification for staging sinusitis: the Staging and Therapy Group. Ann Otol Rhinol Laryngol Suppl. 1995;16717- 21
15.
Doty  RLShaman  PDann  M Development of the University of Pennsylvania smell identification test: a standardized microencapsulated test of olfactory function. Physiol Behav. 1984;32489- 502Article
16.
Holmstrom  MLund  VJ Response of olfactory acuity to surgical stress. Am J Rhinol. 1996;101- 4Article
17.
Hilberg  OJackson  ACSwift  DLPedersen  OF Acoustic rhinometry: evaluation of nasal cavity geometry by acoustic reflection. J Appl Physiol. 1989;66295- 303
18.
Youlten  LJF The peak nasal inspiratory flow meter: a new instrument for the assessment of the response to immunotherapy in seasonal allergic rhinitis. Allergol Immunopathol (Madr). 1980;8344- 347
19.
Lund  VJ Surgical management of nasal polyposis.  Paper presented at: European Academy of Allergy and Clinical Immunology 1996 Budapest, Hungary
20.
Lildholdt  TFogstrup  JGammelgaard  N  et al.  Surgical versus medical treatment of nasal polyps. Acta Otolaryngol. 1988;105140- 143Article
21.
Lildholdt  TRundcrantz  HLindquist  N Efficacy of topical corticosteroid powder for nasal polyps: a double-blind, placebo-controlled study of budesonide. Clin Otolaryngol. 1995;2026- 30Article
22.
Holmberg  KKarlsson  G Nasal polyps: surgery or pharmacological intervention? Eur Respir Rev. 1994;4260- 265
23.
Elbrond  OFelding  JUGustavsen  KM Acoustic rhinometry used as a method to monitor the effect of intramuscular injection of steroid on nasal polyps. J Laryngol Otol. 1991;105178- 180Article
24.
Settipane  GA Nasal polyps. RhinitisNew England Regional Allergy Proceedings Providence, RI Oceanside Publications Inc1984;133- 140
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