The Effects of Systemic, Topical, and Intralesional Steroid

Otolaryngology http://oto.sagepub.com/
-- Head and Neck Surgery
The Effects of Systemic, Topical, and Intralesional Steroid Treatments on Apoptosis Level of Nasal
Polyps
Burak Kapucu, Engin Cekin, Bulent Evren Erkul, Hakan Cincik, Atila Gungor and Ufuk Berber
Otolaryngology -- Head and Neck Surgery 2012 147: 563 originally published online 2 May 2012
DOI: 10.1177/0194599812446678
The online version of this article can be found at:
http://oto.sagepub.com/content/147/3/563
Published by:
http://www.sagepublications.com
On behalf of:
American Academy of Otolaryngology- Head and Neck Surgery
Additional services and information for Otolaryngology -- Head and Neck Surgery can be found at:
Email Alerts: http://oto.sagepub.com/cgi/alerts
Subscriptions: http://oto.sagepub.com/subscriptions
Reprints: http://www.sagepub.com/journalsReprints.nav
Permissions: http://www.sagepub.com/journalsPermissions.nav
>> Version of Record - Aug 29, 2012
OnlineFirst Version of Record - May 2, 2012
What is This?
Downloaded from oto.sagepub.com at SOCIEDADE BRASILEIRA DE CIRUR on October 29, 2012
Original Research—Sinonasal Disorders
The Effects of Systemic, Topical, and
Intralesional Steroid Treatments on
Apoptosis Level of Nasal Polyps
Otolaryngology–
Head and Neck Surgery
147(3) 563–567
Ó American Academy of
Otolaryngology—Head and Neck
Surgery Foundation 2012
Reprints and permission:
sagepub.com/journalsPermissions.nav
DOI: 10.1177/0194599812446678
http://otojournal.org
Burak Kapucu, MD1, Engin Cekin, MD1, Bulent Evren Erkul, MD1,
Hakan Cincik, MD1, Atila Gungor, MD1, and Ufuk Berber, MD2
No sponsorships or competing interests have been disclosed for this article.
Abstract
Objective. The purpose of this study was to compare the
apoptotic responses to systemic, topical, and intrapolyp injection of glucocorticoid with no treatment in nasal polyps.
Study Design. Prospective, randomized controlled study.
Setting. Tertiary training hospital.
Subjects and Methods. The study was performed on 48
patients with nasal polyposis in the Department of
Otorhinolaryngology between 2008 and 2009. Patients were
assigned to 1 of 4 groups of 12 patients. Group A was treated
with oral methylprednisolone 1 mg/kg/d, and the dose was
tapered gradually. Group B received 0.3 mL triamcinolone
acetonide (40 mg/mL), which was injected into polyp tissue.
Group C was treated with topical 55 mg triamcinolone acetonide 2 times daily for 1 month. Group D received no medication. Samples were collected endoscopically after the seventh
day for groups A and B, the first month for group C, and the
first visit for group D. Apoptotic indexes were determined
using the terminal deoxynucleotidyl transferase-mediated
dUTP nick end labeling method.
Results. Statistically significant differences in apoptotic index
were found between each steroid-medicated group and
the control group (PD-A = .0001; PD-B = .003; PD-C = .026)
and between groups A and C (PA-C = .012). Group B did
not differ significantly from either group A or C (PA-B =
.11; PB-C = .75).
Conclusions. The apoptotic index in nasal polyps treated with
systemic, topical, and intrapolyp injection forms of glucocorticoids was higher than that in the control group. Systemic
steroid treatment induced the most apoptosis.
Keywords
nasal polyp, nasal polyposis, corticosteroid, intralesional,
topical, systemic, apoptosis
Received January 6, 2012; revised March 23, 2012; accepted April 6,
2012.
N
asal polyposis (NP) is defined by an edematous
mass caused by chronic inflammation and is characterized by nasal mucosal metaplasia, secretory
hyperplasia, inflammatory cell infiltration (mostly eosinophils, lymphocytes, and plasmocytes), increased fibroblast
production, extracellular matrix deposition, and fibrosis.1
The prevalence of NP is 1% to 4%,2,3 and it is seen almost
equally in all races and social classes.
Steroids are considered to be the most effective antiinflammatory drugs. The effects of steroids on NP have been
reported, and they are currently the most common drugs used
to treat NP.3 Topical sprays and oral and intrapolyp-injected
forms of glucocorticoids are used in treating NP.
Apoptosis is physiological cell death caused by developmental and environmental stimuli that activate cell suicide
programs in multicellular organisms.4 Apoptosis is an
important process in the reduction of inflammatory cells
and resolution of the inflammatory processes. Induction of
apoptotic cell death has been shown to accompany resolution of the inflammatory process in inflammatory diseases
of the respiratory system such as nasal polyposis. Steroids
are known to induce apoptosis of fibroblasts and inflammatory cells in NP tissue, remove these cells, and resolve
inflammation in nasal polyp tissue.5-11
We compared the different forms of steroid treatments
with each other and with no treatment to demonstrate their
effects on apoptosis in polyp tissue.
Subjects and Methods
This prospective, controlled study was performed on 48
patients (40 men, 8 women) who had NP. The age range
was 20 to 60 years (mean, 32.2 years). The GATA Medical
1
Department of Otorhinolaryngology, GATA Haydarpasa Training Hospital,
Istanbul, Turkey
2
Department of Pathology, GATA Haydarpasa Training Hospital, Istanbul,
Turkey
This study was presented as a poster presentation at the 2010 AAO-HNSF
Annual Meeting & OTO EXPO; September 26-29, 2010; Boston,
Massachusetts.
Corresponding Author:
Bulent Evren Erkul, MD, GATA Haydarpasa Egitim Hastanesi, KBB klinigi
34668 Kadikoy, Istanbul
Email: [email protected]
Downloaded from oto.sagepub.com at SOCIEDADE BRASILEIRA DE CIRUR on October 29, 2012
564
Otolaryngology–Head and Neck Surgery 147(3)
Faculty (Ankara-Turkey) Drug Research Local Ethics
Committee approved the study (12/2008-90), and all
patients gave signed informed consent.
Exclusion criteria were as follows: past surgeries for NP,
any glucocorticoid usage for any reason within 1 month,
nasal polyp that was not eosinophilic NP according to the
pathology study, fungal chronic sinusitis, age younger than
15 years, Churg-Strauss syndrome, immunodeficiency,
Kartagener’s syndrome, Young’s syndrome, cystic fibrosis,
antrochoanal polyp, and unilateral nasal polyp. Additional
exclusion criteria were any contraindications for steroid
treatment (such as glaucoma, peptic ulcer, acute psychosis,
herpetic keratitis, chronic infections, severe osteoporosis,
severe hypertension, uncontrolled diabetes mellitus, thromboembolic predisposition, newly formed bowel anastomosis,
diverticulitis, and Cushing’s syndrome). All patients completed a detailed questionnaire regarding exclusion criteria.
All patients assigned to oral steroid were checked before
starting medication with complete blood testing, including
hemoglobin, hematocrit, leukocyte and thrombocyte counts,
glucose, urea, creatinine, direct and indirect bilirubin, liver
enzymes, total cholesterol, lipid profile, and blood pressure.
Any complications seen during treatment were recorded. All
patients had paranasal computed tomography for diagnosis
before the treatment, but we did not do a radiological evaluation after the treatment.
Treatment Protocols and Material Collection
Patients with NP were randomly assigned to 4 groups of 12
patients.
Group A was treated with oral methylprednisolone
(Prednol 16-mg tablet, Prednol 4-mg tablet; Mustafa Nevzat
Pharmaceutical, Istanbul, Turkey) 1 mg/kg/d. The dose was
applied for 3 days and tapered gradually, with a reduction
rate of 8 mg/3 days, and so duration of drug use varied for
each patient changing according to his or her weight.
Lansoprosol (Lansor 30-mg capsule; Sanovel Pharmaceuticals,
Istanbul, Turkey) 30 mg/d was given to patients in group A
during oral steroid treatment to avoid the possible gastrointestinal side effects of methylprednisolone.
Group B received intrapolyp steroid injections. Two
puffs of xylometazoline hydrochloride (Otrivine Adult
Nasal Spray 0.1%; Novartis Pharmaceuticals, Istanbul,
Turkey) were applied into both nasal cavities once for vasoconstriction. After 5 minutes, 0.3 mL triamcinolone acetonide (Kenacord-A 40-mg/mL ampoule; Bristol-Myers
Squibb, Istanbul, Turkey) was injected into polyp tissue in
both nasal cavities with the help of an endoscope. Injections
were placed in the central area of well-visualized polyps,
and care was taken to avoid injection into vessels. A 27gauge, 50-mm dental needle with a 2-mL syringe was used.
This procedure was recorded endoscopically using a video
recorder to take samples from the same polyps after treatment. Nasal tampons (Sauger surgical patties; Medikokim,
Istanbul, Turkey) were used when bleeding occurred.
Group C was treated topically with 55 mg triamcinolone
acetonide spray (Nasacort AQ Spray; Sanofi-Aventis,
Istanbul, Turkey) 2 times daily with 2 puffs in both nasal
cavities for 1 month.
Group D was the control group, and no medication was
given.
Samples from group A were collected endoscopically on
the seventh day to ensure sampling before possible complete
disappearance of the polyps. Video-guided sample collection
from group B was also performed on the seventh day.
Samples from group C were collected at the end of the first
month from polyps that were located anteriorly in any nasal
cavity. Samples from group D were taken at each patient’s
first visit to the clinic. A piece of each polyp was sent to the
pathology laboratory for study. The rest of the samples were
stored at –80°C prior to immunohistochemical analysis.
Immunohistochemical Preparation of Samples and
Detection of Apoptosis
Paraffin blocks were prepared for each sample. Pathologic
examination confirmed the diagnosis of eosinophilic NP. Threemillimeter-thick paraffin block samples were prepared and
mounted on positively charged microscope slides. Apoptotic
cells were detected by using the terminal deoxynucleotidyl
transferase-mediated dUTP nick end labeling (TUNEL) method
with the ApopTag Plus Peroxidase kit (In Situ Apoptosis
Detection Kit; Chemicon International, Temecula, California).
Approximately 1000 stromal cells were counted in the most
intense TUNEL staining areas using a Nikon light microscope
(Nikon USA, Melville, New York) at 4003. The percentage of
apoptosis-positive cells (brown stained, oval to round in shape,
with narrow/dense cytoplasmic nuclear condensation and fragmentation) was determined, and this result was the apoptotic
index (Figure 1).
Statistical Analysis
Statistical analysis was performed using the Statistical
Package for Social Sciences (SPSS, version 15.0; SPSS, Inc,
an IBM Company, Chicago, Illinois). Means, modes, medians, standard deviations, proportions, and percentages were
determined as applicable. The means and standard deviations were calculated for continuous variables, whereas
ratios and proportions were calculated for categorical variables. Proportions and ratios were compared using 1-way
analysis of variance (ANOVA), post hoc Dunnett’s test, and
Scheffé’s post hoc test. P values less than .05 were taken as
statistically significant.
Results
All participants completed the study. No systemic or local
side effects of steroid treatment were seen in any patients.
We did not detect any complications related to vision in
group B. Anterior nasal packing was not required for epistaxis, which occurred during sampling.
The apoptotic indexes of all groups were normally homogeneously distributed (P = .08) (Table 1).
We compared the apoptotic indexes of groups A, B, and C
with those of the control group (group D) to examine the
effects of steroid treatments. We found statistically significant
Downloaded from oto.sagepub.com at SOCIEDADE BRASILEIRA DE CIRUR on October 29, 2012
Kapucu et al
565
Figure 1. Nasal polyp tissue samples stained with deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). 3#-OH DNA
ends generated by DNA fragmentation apoptotic cells can be seen in black and are marked with arrows. There was intense apoptosis in A
and rare apoptosis in B.
Table 1. Apoptotic Index of Each Group
Groups
No.
Apoptotic Index, Mean 6 SD (Min-Max)
SS
IPI
SPR
Control
SS, IPI, SPR
12
12
12
12
36
32.50 6 9.32 (10-48)
22.50 6 11.21 (7-42)
19 6 13.05 (6-50)
7.92 6 4.74 (0-15)
24.67 6 12.41 (6-50)
Abbreviations: IPI, intrapolyp injection; Min, minumum; Max, maximum; SPR,
spray; SS, systemic steroid.
Figure 3. Error bars of the groups’ apoptosis indexes with the
95% confidence interval. IPI, intrapolyp injection; SPR, spray; SS,
systemic steroid.
Figure 2. Comparison of the distribution of apoptosis indexes
among groups. The x-axis shows the groups and the y-axis shows
the apoptosis index values of the groups. IPI, intrapolyp injection;
SPR, spray; SS, systemic steroid.
differences in apoptotic indexes between groups D and A
(PD-A = .0001), groups D and B (PD-B = .003), and groups
D and C (PD-C = .026) (Figure 2 and Figure 3).
The data from all steroid treatment groups were combined into 1 group (group ABC) (Table 1), and the
resulting apoptosis index was compared with that of the
control group (group D). We found a statistically significant
difference in the apoptotic index between group D and
group ABC (PD-ABC = .0001).
When all steroid treatment groups (A, B, and C) were
compared with each other, we found that group C had the
lowest mean scores (19 6 13.05) (Table 1). We found a statistically significant difference in the apoptosis index between
groups A and C (PA-C = .012). There was no statistically significant difference in the apoptotic index between groups B
and C (PB-C = .75) or between groups B and A (PA-B = .11).
Discussion
Nasal polyposis is the most common cause of mass lesions in
the nasal cavity, and the prevalence of NP is approximately
Downloaded from oto.sagepub.com at SOCIEDADE BRASILEIRA DE CIRUR on October 29, 2012
566
Otolaryngology–Head and Neck Surgery 147(3)
1% to 4%.12 Larsen and Tos3 found that the incidence of NP
increases with age and estimated the overall incidence of
symptomatic nasal polyps as 0.627/1000 per year. The incidence increases after age 20 years and declines after age 60
years, with the disease most commonly diagnosed in patients
42 years of age.12-14 Our study included 40 male and 8
female patients; the mean age was 32.2 years.
Today, medical, surgical, or combination modalities are
used in treating NP. The main objectives are the elimination
of polyps, maintenance of sinus drainage and nasal breathing,
and prevention of recurrence. Corticosteroids are one of the
medical treatment modalities that have a proven effect on the
symptoms and signs of nasal polyps. They can be used topically or systemically or be injected into the polyp tissue.
Intranasal steroid injection was first described in the
1950s. It can be used as an intraturbinal injection for allergic rhinitis or as an intrapolyp injection for NP. The first
reports of visual loss as a complication of nasal steroid
injection followed in the 1960s.15,16 Guidelines included the
choice of a steroid with a small particle size such as triamcinolone acetonide, use of a narrow-gauge needle, and use of
a topical vasoconstrictor to reduce nasal vascular congestion
before injection. Triamcinolone acetonide has the advantage
of being a suspension of small particles with local effects
that last for several weeks.17-20 Topical vasoconstrictor was
applied before triamcinolone acetonide injection, and we
used a narrow-gauge needle to avoid complications in our
study. No visual complications occurred in our patients
treated with 0.3 mL triamcinolone acetonide injected into
the polyp tissue.
Methylprednisolone and dexamethasone are the most commonly used systemic corticosteroids for NP. Van Camp and
Clement21 treated 25 patients with NP with 60 mg oral prednisolone with a progressive reduction of the dose (–5 mg/d)
over 4 days. Seventy-two percent of the patients showed subjective improvement. Tuncer et al22 evaluated the efficacy of
oral methylprednisolone on NP and concluded that steroids
could delay the necessity for surgical intervention. We preferred to use oral methylprednisolone 1 mg/kg/d for systemic
steroid treatment and taper the dose gradually. We did not
encounter any side effects during oral steroid treatment.
Many studies have been conducted on the effects of various nasal steroid sprays in NP treatment, with multiple
placebo-controlled studies demonstrating significant success.23-26 The use of topical corticosteroids in NP was first
reported by Mygind et al.23 In their double-blind study with
beclomethasone dipropionate aerosol, they found the effectiveness of the drug to be 80% vs 13% for the placebo in a
3-week period. Herman25 compared the efficacy, safety,
patient preference, and cost-effectiveness of once-daily
budesonide aqueous nasal spray, fluticasone propionate nasal
spray, mometasone furoate nasal spray, and triamcinolone
aqueous nasal spray for treatment of allergic rhinitis in adult
patients. They have found that these steroid sprays had similar efficacy and safety profiles. We did not find a study
involving apoptosis and triamcinolone acetonide in nasal
polyps. Furthermore, topical triamcinolone acetonide produced
statistically significant reductions in symptoms relative to placebo in a 4-week treatment period in subjects with allergic rhinitis.27 We used 55 mg triamcinolone acetonide topically 2
times daily for 1 month in each nasal cavity in group C. In our
study, we did not encounter any side effects in the triamcinolone acetonide nasal spray group. As the distribution and effectiveness of the spray are not homogeneous, especially in the
rear areas of the nasal cavity in those with common polyps,
the samples were collected from the polyps closest to the
entrance of the nasal cavity to achieve optimum results from
the intranasal steroid spray.
Apoptosis is important in both the topical and the systemic steroid treatment of NP.5-11 However, there are no
prior published comparisons of the apoptotic effects of topical and systemic steroid treatments in vivo. We attempted
to identify the effects of oral, intranasal, and intrapolypinjected steroids in the treatment of patients with nasal
polyps by comparing their apoptotic rates in vivo with each
other and with the control group.
Nittoh et al28 found that dexamethasone, methylprednisolone, and hydrocortisone were similarly effective in inhibiting rat eosinophil survival and enhancing apoptosis in
culture. More recently, Hirano et al8 had incubated polyps
with beclomethasone, dexamethasone, testosterone, and
estradiol in vitro. Using DNA fragmentation to determine
the percentage of apoptotic cells, they observed that 20% of
the cells were apoptotic in the presence of dexamethasone
and beclomethasone, whereas apoptosis was not induced by
testosterone or estradiol. When we combined all our data
from the steroid-treated groups and compared the resulting
apoptotic index with that of the control group, we found a
statistically significant difference between them (PD-ABC =
.0001), showing that steroid treatment increased apoptosis
in polyp tissue.
Saunders et al27 demonstrated increased apoptosis in
inflammatory cells of nasal polyps after steroid application
in vitro. In their double-blind, randomized study, patients
with NP were assigned to 1 of 2 groups: 1 group received
fluticasone propionate spray for 14 days, and the other
group was designated the control group. Specimens were
collected from both groups during nasal polypectomy for
calculating the apoptotic index using the TUNEL method.
No significant difference in the apoptotic index was found.
In the same study, NP samples from 5 patients were cultured in media containing various concentrations of dexamethasone, and the apoptotic indexes of the cells were
assessed by use of the TUNEL method at different times.
The apoptotic index increased with elevated dexamethasone
concentration and time. Watanabe et al10 showed that the
administration of topical steroids in vivo increased the apoptotic index of eosinophils and T lymphocytes in nasal
polyps. Fan et al11 collected samples from patients with
allergic sinusitis before and after oral prednisone 20 mg/d.
Using the TUNEL method, they showed increased eosinophilic apoptosis after treatment. We observed a statistically
significant increase in the apoptotic index in all steroid
treatment groups compared with the control group and
Downloaded from oto.sagepub.com at SOCIEDADE BRASILEIRA DE CIRUR on October 29, 2012
Kapucu et al
567
found that the topical steroid spray induced less apoptosis
than did the systemic or intralesional steroid. The difference
between systemic steroid and steroid spray in the induction
of apoptosis was statistically significant.
We did not compare size of polyps in this study because
of the different anatomic distributions of the different forms
of steroid: systemic steroid treatment affects all polyps, steroid injection affects mostly the area around the injection, and
the steroid spray reaches the most anteriorly located polyps.
Conclusion
Systemic, topical, and intrapolyp injection forms of glucocorticoids induced apoptosis in nasal polyp tissue when
compared with the control group. We found that systemic
steroid treatment induced the most apoptosis. There was no
statistically significant difference in the apoptotic index
between oral and intrapolyp delivery.
Author Contributions
Burak Kapucu, substantial contributions to conception and
design, acquisition of data and analysis, drafting the article, final
approval of the version; Engin Cekin, substantial contributions to
conception and design, drafting the article, final approval of the
version; Bulent Evren Erkul, analysis and interpretation of data,
drafting the article and revising, final approval of the version;
Hakan Cincik, substantial contributions to conception and design,
revising, final approval of the version; Atila Gungor, substantial
contributions to conception and design, revising, final approval of
the version; Ufuk Berber, acquisition of data and analysis, revising, final approval of the version.
Disclosures
Competing interests: None.
Sponsorships: None.
Funding source: None.
References
1. Seethala RR, Pant H. Pathology of nasal polyps. In: Önerci M,
Ferguson BJ, eds. Nasal Polyposis. New York: Springer; 2006:
17-26.
2. Dingsor G, Kramer J, Olsholt R, Soderstrom T. Flunisolide
nasal spray 0.025 % in the prophylactic treatment of nasal
polyposis after polypectomy: a randomized, double blind, parallel, placebo controlled study. Rhinology. 1985;23:49-58.
3. Larsen PL, Tos M. Nasal polyps: epithelium and goblet cell
density. Laryngoscope. 1989;99:1274-1280.
4. Alles A, Alley K, Barrett JC, et al. Apoptosis: A general comment. FASEB J. 1991;5:2127-2128.
5. Meagher LC, Cousin JM, Seckl JR, Haslett C. Opposing effects
of glucocorticoids on the rate of apoptosis in neutrophilic and
eosinophilic granulocytes. J Immunol. 1996;156:4422-4428.
6. Liles WC, Dale DC, Klebanoff SJ. Glucocorticoids inhibit
apoptosis of human neutrophils. Blood. 1995;86:3181-3188.
7. Saunders MW, Wheatley AH, George SJ, Lai T, Birchall MA.
Do corticosteroids induce apoptosis in nasal polyp inflammatory cells? In vivo and in vitro studies. Laryngoscope. 1999;
109:785-790.
8. Hirano S, Asano K, Namba M, Kanai K, Hisamitsu T, Suzaki
H. Induction of apoptosis in nasal polyp fibroblasts by glucocorticoids in vitro. Acta Otolaryngol. 2003;123:1075-1079.
9. Kanai N, Denburg J, Jordana M, Dolovich J. Nasal polyp
inflammation: effect of topical nasal steroid. Am J Respir Crit
Care Med. 1994;150:1094-1100.
10. Watanabe K, Shirasaki H, Kanaizumi E, Himi T. Effects of
glucocorticoids on infiltrating cells and epithelial cells of nasal
polyps. Ann Otol Rhinol Laryngol. 2004;113:465-473.
11. Fan GK, Itoh T, Imanaka M, Fujieda S, Takenaka H.
Eosinophilic apoptosis in sinus mucosa: relationship to tissue
eosinophilia and its resolution in allergic sinusitis. J Allergy
Clin Immunol. 2000;106:551-558.
12. Triglia JM, Nicollas R. Nasal and sinus polyposis in children.
Laryngoscope. 1997;107:963-966.
13. Larsen K, Tos M. The estimated incidence of symptomatic
nasal polyps. Acta Otolaryngol. 2002;122:179-182.
14. Larsen PL, Tos M. Origin of nasal polyps: an endoscopic
autopsy study. Laryngoscope. 2004;114:710-719.
15. Hager G, Heise G. A severe complication with permanent
practical blindness of one eye following intranasal injection.
HNO. 1962;10:325-328.
16. Rowe RJ, Dasler TW, Kinkella AM. Visual changes and triamcinolone. JAMA. 1967;201:117.
17. Kabaker SS. Collected letters of the International Correspondence
Society of Ophthalmologists and Otolaryngologists. Soc
Ophthalmol Otolaryngol. 1975;20:159-160.
18. Baker DC, Strauss RB. The physiologic treatment of nasal
obstruction. Clin Plast Surg.1977;4:121-130.
19. McCleave D, Goldstein J, Silve S. Corticosteroid injections of the
nasal turbinates: past experience and precautions. Otolaryngology.
1978;86:851-857.
20. Mabry RL. Intraturbinal steroid injections: indications, results,
and complications. South Med J. 1978;71:789-791, 794.
21. van Camp C, Clement PA. Result of oral steroid treatment in
nasal polyposis. Rhinology. 1994;32:5-9.
22. Tuncer U, Soylu L, Aydogan B, Karakus F, Akcali C. The
effectiveness of steroid treatment in nasal polyposis. Auris
Nasus Larynx. 2003;30:263-268.
23. Mygind N, Pedersen CB. Treatment of nasal polyps with intranasal
beclomethasone dipropionate aerosol. Clin Allergy. 1975;5:159-164.
24. Waddell AN, Patel SK, Toma AG, Maw AR. Intranasal steroid
sprays in the treatment of rhinitis: is one better than another? J
Laryngol Otol. 2003;117:843-845.
25. Herman H. Once-daily administration of intranasal corticosteroids
for allergic rhinitis: a comparative review of efficacy, safety,
patient preference, and cost. Am J Rhinol. 2007;21:70-79.
26. Skoner D, Rachelefsky GS, Meltezer EO, et al. Detection of
growth suppression in children during treatment with intranasal beclomethasone dipropionate. Pediatrics. 2000;105:23-26.
27. Meltzer EO, Gallet CL, Jalowayski AA, et al. Triamcinolone
acetonide and fluticasone propionate aqueous nasal sprays significantly improve nasal airflow in patients with seasonal allergic rhinitis. Allergy Asthma Proc. 2004;25:53-58.
28. Nittoh T, Fujimori H, Kozumi Y, Ishihara K, Mue S, Ohuchi K.
Effects of glucocorticoids on apoptosis of infiltrated eosinophils
and neutrophils in rats. Eur J Pharmacol. 1998;354:73-81.
Downloaded from oto.sagepub.com at SOCIEDADE BRASILEIRA DE CIRUR on October 29, 2012