pulmicort and Nasal-Polyps

Topical therapies play an important role in the management of chronic rhinosinusitis (CRS). A detailed literature review was undertaken to appraise recent evidence surrounding current topical therapies and novel treatments used in the setting of recalcitrant CRS.. Effective sinus surgery aids in the delivery of topical therapies. Budesonide nasal rinses delivered by saline irrigation offer clinical and symptomatic improvements pre and postoperatively with a well-proven safety profile. Topical steroids may additionally offer direct antibacterial effects as per in-vitro testing. Topical antibiotics are not recommended in routine practice; however, they may be of benefit for short-term eradication therapy. Novel treatments are under keen investigation and include bacteriophage, colloidal silver and manuka honey. The evidence base for these treatments is not robust enough to recommend their routine use at present.. Topical steroids delivered in conjunction with saline nasal irrigation offer the best combination of treatments in CRS and should be considered a standard of care. Wide surgical access and aggressive surgical debridement of polyposis facilitates the delivery of steroid irrigations to sinonasal mucosa and is associated with improved long-term outcomes following endoscopic sinus surgery. The use of novel treatments remains within the research setting alone.

Topics: Administration, Intranasal; Administration, Topical; Budesonide; Chronic Disease; Debridement; Glucocorticoids; Humans; Nasal Lavage; Nasal Polyps; Rhinitis; Saline Solution; Sinusitis

This review is one of six looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and is characterised by inflammation of the lining of the nose and paranasal sinuses leading to nasal blockage, rhinorrhoea, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. The use of topical (intranasal) corticosteroids has been widely advocated for the treatment of chronic rhinosinusitis given the belief that inflammation is a major component of this condition.. To assess the effects of intranasal corticosteroids in people with chronic rhinosinusitis.. The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 8); MEDLINE; EMBASE; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 11 August 2015.. Randomised controlled trials (RCTs) with a follow-up period of at least three months comparing intranasal corticosteroids (e.g. beclomethasone dipropionate, triamcinolone acetonide, flunisolide, budesonide) against placebo or no treatment in patients with chronic rhinosinusitis.. We used the standard methodological procedures expected by Cochrane. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity and the commonest adverse event - epistaxis. Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse events of local irritation or other systemic adverse events. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.. We included 18 RCTs with a total of 2738 participants. Fourteen studies had participants with nasal polyps and four studies had participants without nasal polyps. Only one study was conducted in children. Intranasal corticosteroids versus placebo or no intervention Only one study (20 adult participants without polyps) measured our primary outcome disease-specific HRQL using the Rhinosinusitis Outcome Measures-31 (RSOM-31). They reported no significant difference (numerical data not available) (very low quality evidence).Our second primary outcome, disease severity , was measured using the Chronic Sinusitis Survey in a second study (134 participants without polyps), which found no important difference (mean difference (MD) 2.84, 95% confidence interval (CI) -5.02 to 10.70; scale 0 to 100). Another study (chronic rhinosinusitis with nasal polyps) reported an increased chance of improvement in the intranasal corticosteroids group (RR 2.78, 95% CI 1.76 to 4.40; 109 participants). The quality of the evidence was low.Six studies provided data on at least two of the individual symptoms used in the EPOS 2012 criteria to define chronic rhinosinusitis (nasal blockage, rhinorrhoea, loss of sense of smell and facial pain/pressure). When all four symptoms in the EPOS criteria were available on a scale of 0 to 3 (higher = more severe symptoms), the average MD in change from baseline was -0.26 (95% CI -0.37 to -0.15; 243 participants; two studies; low quality evidence). Although there were more studies and participants when only nasal blockage and rhinorrhoea were considered (MD -0.31, 95% CI -0.38 to -0.24; 1702 participants; six studies), the MD was almost identical to when loss of sense of smell was also considered (1345 participants, four studies; moderate quality evidence).When considering the results for the individual symptoms, benefit was shown in the intranasal corticosteroids group. The effect size was larger for nasal blockage (MD -0.40, 95% CI -0.52 to -0.29; 1702 participants; six studies) than for rhinorrhoea (MD -0.25, 95% CI -0.33 to -0.17; 1702 participants; six studies) or loss of sense of smell (MD -0.19, 95% CI -0.28 to -0.11; 1345 participants; four studies). There was heterogeneity in the analysis for facial pain/pressure (MD -0.27, 95% CI -0.56 to 0.02; 243 participants; two studies). The quality of the evidence was moderate for nasal blockage, rhinorrhoea and loss of sense of smell, but low for facial pain/pressure.There was an increased risk of. Most of the evidence available was from studies in patients with chronic rhinosinusitis with nasal polyps. There is little information about quality of life (very low quality evidence). For disease severity, there seems to be improvement for all symptoms (low quality evidence), a moderate-sized benefit for nasal blockage and a small benefit for rhinorrhoea (moderate quality evidence). The risk of epistaxis is increased (high quality evidence), but these data included all levels of severity; small streaks of blood may not be a major concern for patients. It is unclear whether there is a difference in the risk of local irritation (low quality evidence).

Topics: Administration, Intranasal; Adolescent; Adrenal Cortex Hormones; Adult; Beclomethasone; Budesonide; Child; Chronic Disease; Fluticasone; Humans; Mometasone Furoate; Nasal Polyps; Nasal Sprays; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Rhinitis; Severity of Illness Index; Sinusitis; Steroids

The introduction of nasal glucocorticosteroids, 30 years ago, has been the most important therapeutic progress in rhinitis management since the introduction of the first generation of antihistamines. Our knowledge of the mode of action of glucocorticosteroids in the nose has improved as the airway mucous membrane of the nose is easily accessible for investigation. However, the exact mechanism behind the marked clinical effect remains unclear. Topical glucocorticosteroids are highly effective in diseases characterized by eosinophil-dominated inflammation (allergic rhinitis, nasal polyposis), but not in diseases characterized by neutrophil-dominated inflammation (common cold, infectious rhinosinusitis). Experience for 30 years and a long series of controlled studies have shown that the treatment is highly effective and that the side effects are few and benign. Intranasal glucocorticosteroids can therefore be considered as first-line treatment for allergic and non-allergic, non-infectious rhinitis and nasal polyps.

Topics: Administration, Topical; Androstadienes; Animals; Beclomethasone; Budesonide; Dexamethasone; Eosinophils; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Mometasone Furoate; Nasal Mucosa; Nasal Polyps; Pregnadienediols; Randomized Controlled Trials as Topic; Rhinitis; Treatment Outcome; Triamcinolone Acetonide

Topics: Administration, Topical; Anti-Inflammatory Agents; Budesonide; Endoscopy; Glucocorticoids; Humans; Image Processing, Computer-Assisted; Nasal Mucosa; Nasal Obstruction; Nasal Polyps; Paranasal Sinus Diseases; Pregnenediones; Wound Healing

Topics: Adult; Budesonide; Dose-Response Relationship, Drug; Endoscopy; Fatty Acids, Omega-3; Female; Follow-Up Studies; Glucocorticoids; Humans; Male; Nasal Cavity; Nasal Polyps; Nasal Sprays; Recurrence; Retrospective Studies; Single-Blind Method; Treatment Outcome

Allergic fungal rhinosinusitis (AFRS) is a common disorder with a high prevalence and a very high incidence of recurrence. Management includes surgery and medical treatment in the form of local and/or systemic steroids. However, some cases are resistant to the action of steroids and further treatment is warranted. Being an immune-mediated disorder, targeting IgE seems a logical step. Immunotherapy drugs acting on the IgE (e.g. omalizumab) can modify the clinical course of the disease. This study aimed at evaluating the effect of omalizumab on the clinical course of patients undergoing surgery for AFRS.. This is a two-arm prospective, randomized, single blind clinical trial among patients with AFRS. Twenty patients were included and randomly divided into two groups: Group A; 10 patients received a single subcutaneous injection of omalizumab (Xolair ' Novartis) (150 mg) 2 weeks postoperatively. Group B: 10 patients received local steroids nasal sprays (budesonide or mometasone furoate, 100 μg twice daily for 6 months, starting 2 weeks postoperatively. All patients underwent history, examination, CT scan and IgE level estimation and were submitted to endoscopic sinus surgery. They were evaluated at 4 weeks interval for 6 months.. In both groups there were highly significant differences between pre/post-operative SNOT-20 scores, TNSS scores, total IgE level and Philpott-Javer staging scores. Comparison between the two study groups at 24 weeks showed a highly significant difference (p = 0.001) between post-operative SNOT 20 and TNSS scores in favour of group A. There was no statistically significant difference between the two study groups as regarding postoperative total IgE or Philpott-Javer scores. There were two recurrences in both arms, but no significant side effects.. We compared a single post operative injection of omalizumab with twice daily intranasal steroid spray for 6 months. Both treatments were effective, but the omalizumab group showed a more significant clinical and endoscopic response. There were no significant side effects in both arms. This novel approach used a single low dose injection of omalizumab increased the compliance of the patients with minimal complications. Longer follow-up of the patients is ongoing to determine the optimal time for re-injection. The only downside was the higher cost of omalizumab compared to that of local steroids.

Topics: Administration, Intranasal; Adolescent; Adult; Anti-Allergic Agents; Budesonide; Chronic Disease; Endoscopy; Female; Glucocorticoids; Health Status Indicators; Humans; Immunoglobulin E; Injections, Subcutaneous; Male; Mometasone Furoate; Mycoses; Nasal Polyps; Nasal Sprays; Omalizumab; Prospective Studies; Rhinitis, Allergic; Single-Blind Method; Sinusitis; Tomography, X-Ray Computed; Young Adult

Neutrophilic chronic rhinosinusitis with nasal polyps (CRSwNP) occur predominantly in Asian subjects. Appropriate treatments for this endotype have not been elucidated. This study aimed to evaluate the efficacy of budesonide nasal spray on neutrophilic CRSwNP.. Fifteen neutrophilic CRSwNP patients were included, and then they received budesonide nasal spray treatment for 3 months. Biopsies of nasal polyps (NPs) were obtained from these subjects. Their clinical indexes were scored using Visual Analog Scale (VAS), Sino-Nasal Outcome Test (SNOT)-22, and Endoscopic Appearances (EAs). Histological analyses were used to assess numbers of neutrophils, goblet cells, and submucosal gland cells in NPs. Percentages of CD8+ T cells and CD4+CD25+Foxp3+ regulatory T cells (Tregs) were evaluated using flow cytometry. Mucin 5AC (MUC5AC), MUC5B, myeloperoxidase (MPO), interferon (IFN)-γ, and interleukin (IL)-1β and their mRNAs were also examined. After that, we cultured NP tissues in vitro and evaluated the abovementioned inflammatory parameters before and after the administration of budesonide.. Budesonide nasal spray did not improve clinical evaluations including VAS, SNOT-22, and EA scores. Numbers of neutrophils and goblet cells, the score of submucosal gland cells, percentages of CD8+ T cells and Tregs, MUC5AC, MUC5B, MPO, IFN-γ, and IL-1β and their mRNAs were not decreased in NPs after the budesonide treatment. Furthermore, the administration of budesonide into NP cultures also did not reduce their levels in comparison with those before the treatment.. These findings demonstrate that budesonide treatment may not alleviate the inflammatory condition in neutrophilic CRSwNP.

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Chronic Disease; Female; Humans; Male; Middle Aged; Nasal Polyps; Nasal Sprays; Neutrophils; Pilot Projects; Rhinitis; Sinusitis

In China, clarithromycin is considered an effective treatment option for chronic rhinosinusitis (CRS) due to its unique immunopathologic characteristics. Our study's aim was to determine whether a topical steroid and clarithromycin combination is better than a single topical steroid for Chinese patients with CRS.. Patients with CRS with/without nasal polyps were included in this study and randomly assigned to a clarithromycin plus budesonide aqua nasal spray group (CLM + BUD, clarithromycin 0.25 g/d and budesonide 256 μg/d) or a budesonide-alone group (BUD, budesonide 256 μg/d). The treatment period was 3 months. The primary outcome was visual analog scale (VAS) score for 5 major symptoms and a general nasal symptom. Other assessments included the 22-item Sino-Nasal Outcome Test (SNOT-22), computed tomography scan (Lund-Mackay score), and rigid nasal endoscopy (Lund-Kennedy score). Nasal secretion evaluation was the secondary outcome.. Seventy-four patients were included and randomly assigned to the CLM + BUD group (n = 38) or the BUD group (n = 36). VAS scores for nasal obstruction, rhinorrhea, smell reduction, headache, nasal pain, and general nasal symptom were markedly improved in both treatment arms, but the differences between groups were not significant. Furthermore, SNOT-22, Lund-Mackay, and Lund-Kennedy scores improved significantly after treatment in both groups, and were slightly better in the CLM + BUD group. For the responders in the CLM + BUD group, interleukin (IL)-6 and IL-8 were markedly reduced.. The combination of CLM + BUD for the treatment of first-time-diagnosed CRS in this Chinese population cohort did not show a better effect compared with a single BUD regimen, but it may have a better effect in some patients with increased IL-6 or IL-8.

Topics: Administration, Topical; Adult; Anti-Bacterial Agents; Budesonide; China; Chronic Disease; Clarithromycin; Cytokines; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nasal Polyps; Nasal Sprays; Rhinitis; Single-Blind Method; Sinusitis; Treatment Outcome; Young Adult

Cysteinyl leukotriene (LT) has been proposed in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). This study sought to examine the expression of the LT receptor (LTR) in CRSwNP patients and evaluate the potential role of LTR antagonist (LTRA) in the management of eosinophilic CRSwNP (ECRS) patients.. Nasal polyps and uncinate process tissues were collected from 18 ECRS patients, 13 non-eosinophilic CRSwNP (non-ECRS) patients, and 16 control subjects. The messenger RNA (mRNA) and protein expression of LTR (cysteinyl leukotriene receptor 1 [CysLT1R] and cysteinyl leukotriene receptor 2 [CysLT2R]) was examined using quantitative reverse-transcription polymerase chain reaction (qRT-PCR), immunohistochemistry, and Western blot analysis. Moreover, the effects of LTRA and steroids on total nasal symptom scores (TNSS) of uncontrolled ECRS patients were evaluated.. The mRNA and protein expression of CysLT1R and CysLT2R was significantly increased in polyp tissues compared with healthy controls (p < 0.05). Compared with the non-ECRS subset, the ECRS subset showed significantly increased expression of CysLT1R and CysLT2R, as well as leukotriene C4 (LTC4) and leukotriene D4 (LTC4) levels (p < 0.05). Moreover, combined LTRA and steroids significantly decreased TNSS more than steroids alone in uncontrolled ECRS patients (p < 0.01).. Our findings indicate that LTR was differentially expressed between ECRS and non-ECRS patients, and that LTRA may be used as an additional therapy for ECRS patients.

Topics: Acetates; Adult; Anti-Inflammatory Agents; Biomarkers; Blotting, Western; Budesonide; Case-Control Studies; Chronic Disease; Cyclopropanes; Drug Therapy, Combination; Eosinophils; Female; Humans; Leukotriene Antagonists; Leukotrienes; Male; Middle Aged; Nasal Polyps; Prospective Studies; Quinolines; Receptors, Leukotriene; Reverse Transcriptase Polymerase Chain Reaction; Rhinitis; Sinusitis; Sulfides; Treatment Outcome

Nasal steroids are a critical part of the management of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) after endoscopic sinus surgery (ESS). Increasingly, practitioners are using budesonide respules delivered to the sinonasal cavities, which is an off-label use, in lieu of traditional nasal steroids. There has been little research comparing budesonide with traditional nasal steroids and the most effective delivery method of budesonide.. A randomized controlled trial was performed on patients after ESS for CRSwNP in a tertiary care center. Patients were randomized into 1 of 3 groups: group A received fluticasone nasal spray twice daily; group B received budesonide respules via a mucosal atomization device (MAD) twice daily; and group C received budesonide respules instilled via the vertex-to-floor (VF) position twice daily. Primary endpoints were 22-item Sino-Nasal Outcome Test (SNOT-22) and Lund-Kennedy scores at 6 months.. Thirty-two patients were enrolled in the study, 23 of whom completed the 6-month trial. There were no significant differences among groups A, B, and C with respect to age, gender, asthma, aspirin sensitivity, or previous ESS. Group B had a statistically significant greater reduction in SNOT-22 and Lund-Kennedy scores at the primary endpoint of 6 months compared to groups A and C. Group C had the next greatest reduction, which was statistically significant, followed by group A.. Patients treated with budesonide after ESS for CRSwNP had greater improvement in SNOT-22 and Lund-Kennedy scores compared to fluticasone at 6 months. The data supports the use of budesonide respules, particularly with a MAD, over fluticasone for CRSwNP patients after ESS.

Topics: Adult; Budesonide; Chronic Disease; Endoscopy; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Polyps; Nasal Sprays; Nebulizers and Vaporizers; Paranasal Sinuses; Rhinitis; Rhinoplasty; Sinusitis; Treatment Outcome

There is little evidence on the efficacy of glucocorticoid transnasal nebulization therapy in patients with eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP).. We sought to evaluate the immunologic and remodeling effects of budesonide transnasal nebulization in patients with eosinophilic CRSwNP.. Sixty patients with eosinophilic CRSwNP were randomized to receive budesonide or placebo treatment for 14 days by means of transnasal nebulization in a double-blind manner. Endoscopic polyp size scores (maximum = 6 points, Kennedy score) and visual analog scale scores for nasal symptoms were assessed before and after treatment. Similarly, polyp samples were evaluated for inflammatory cytokines, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) by using an immunoassay; collagen by using histochemistry; eosinophils by using hematoxylin and eosin stain; and T-cell subsets by using flow cytometry.. Budesonide transnasal nebulization significantly reduced polyp size compared with placebo (mean difference between groups, -0.73 units; 95% CI, -1.15 to -0.32 units; P = .002) and improved symptoms. Polyp IL-5 and eotaxin expression decreased significantly, whereas TGF-β and IL-10 expression increased. Expression of IFN-γ and IL-17 was not altered. Budesonide transnasal nebulization consistently reduced eosinophil infiltration and TH2 cell frequency and increased natural regulatory T-cell and type 1 regulatory T-cell frequencies. Indices of remodeling, including albumin, MMP-2, MMP-7, MMP-8, and MMP-9, were significantly decreased, whereas collagen deposition and TIMP-1, TIMP-2, and TIMP-4 levels were significantly increased. Budesonide transnasal nebulization did not suppress the hypothalamic-pituitary-adrenal axis or cause any serious side effects.. Short-term budesonide transnasal nebulization is an effective and safe treatment option in patients with eosinophilic CRSwNP, achieving clinical improvement by regulating remodeling, cytokine expression, and T-cell subset distribution.

Topics: Adult; Aged; Bronchodilator Agents; Budesonide; Chronic Disease; Cytokines; Eosinophils; Female; Humans; Inflammation Mediators; Male; Middle Aged; Nasal Polyps; Nebulizers and Vaporizers; Rhinitis; Sinusitis; Treatment Outcome; Young Adult

To evaluate the efficacy and safety of a short course of nebulized budesonide via transnasal inhalation in chronic rhinosinusitis with nasal polyps.. Fifty patients with severe eosinophilic nasal polyps were randomized devided into study group (n = 25) and control group (n = 25). The study group received budesonide inhalation suspension (1 mg twice daily) via transnasal nebulization for one week and the control group received oral prednisone (24 mg QD). Visual analogue scales (VAS) of nasal symptoms, endoscopic polyp scores (kennedy scores) and morning serum cortisol concentrations were assessed in both groups pre- and post-treatment. Operation time and surgical field bleeding were evaluated.. Four subjects dropped out in control group. Budesonide transnasal nebulization caused a significant improvement in all nasal symptoms especially nasal obstruction (baseline: 8.25 ± 0.53; after treatment: 4.97 ± 0.97, P < 0.01) and reduced polyp size significantly (baseline: 4.64 ± 0.63; after treatment: 3.40 ± 0.76, P < 0.01) compared to pre-treatment. The patients treated with oral prednisone, however, showed more obvious improvement in nasal symptoms and polyp size, shorter operation time and better surgical field than budesonide group. Additionally, the morning serum cortisol concentration was mildly decreased after one week treatment in budesonide group [baseline (17.18 ± 2.83) μg/dl, after treatment (16.24 ± 2.93) μg/dl, P > 0.05], but all values were still located in normal range (normal range: 5-25 μg/dl). Conversely, the morning serum cortisol concentration in oral prednisone group was lower than normal limit [baseline (18.19 ± 2.81) μg/dl, after treatment (2.26 ± 0.70) μg/dl, P < 0.01].. Twice daily budesonide transnasal nebulization is an effective and safe treatment as evidenced by significant improvements in nasal symptoms and reduction in polyp size, coupled with an absence of hypothalamic-pituitary-adrenal axis suppression, which is safer than the systemic corticosteroids. Budesonide transnasal nebulization offers a viable treatment option for CRSwNP before operation.

Topics: Administration, Inhalation; Budesonide; Chronic Disease; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Nasal Obstruction; Nasal Polyps; Pituitary-Adrenal System; Prednisone; Rhinitis; Sinusitis; Suspensions

To compare normal saline (NS) vs. NS+budesonide irrigations in post- functional endoscopic sinus surgery (FESS) patients with chronic rhinosinusitis with polyposis (CRSwNP). Currently, no evidence exists for NS+budesonide irrigation over NS irrigation alone.. Prospective, single-blind, randomized controlled trial.. Subjects were prospectively enrolled to NS or NS+budesonide arms. Patients were evaluated at pre-operative and three post-operative visits (POV): POV1 (1-2 weeks post-op), POV2 (3-8 weeks post-op), and POV3 (3-6 months post-op). Patients were evaluated by three quality of life (QOL) questionnaires (SNOT-22, RSOM-31, and RSDI) and two olfaction scores (UPSIT and the PEA test).. Fifty patients were randomized, with 25 patients in the NS arm and 25 patients in the NS+budesonide arm. Two patients had unexpected pathology and were excluded from the study. By POV2 and POV3, patients experienced a significant improvement in all three QOL surveys, although the degree of improvement between arms was not significant up through POV3. Neither arm experienced significant olfactory improvement up through POV3.. While both NS and NS+budesonide treatments improve QOL for post-FESS patients, neither intervention significantly increases QOL as compared to the other. Olfaction was not significantly improved in either treatment group.

Topics: Adult; Budesonide; Chronic Disease; Female; Glucocorticoids; Humans; Male; Middle Aged; Nasal Polyps; Postoperative Care; Prospective Studies; Quality of Life; Recovery of Function; Rhinitis; Single-Blind Method; Sinusitis; Smell; Therapeutic Irrigation; Treatment Outcome

Budesonide is a potent corticosteroid commonly prescribed for management of inflammation in chronic rhinosinusitis (CRS). The standard for prescribing budesonide is via impregnated nasal saline irrigation (INSI), although recently the mucosal atomization device (MAD) has emerged as a theoretically superior method of distributing medication into the sinuses. The MAD atomizes medication into small droplets and this is thought to enhance absorption and improve bioavailability. However, no studies have shown whether enhanced absorption and improved bioavailability of budesonide via MAD causes adrenal suppression. The objective of this study is to determine whether budesonide via MAD affects the hypothalamic-pituitary-adrenal (HPA) axis.. Twenty CRS patients were recruited from a tertiary rhinology clinic and randomized to take budesonide (1 mg) via MAD or via INSI twice a day for 60 days. The adrenocorticotropic hormone (ACTH) stimulation test and 22-item Sinonasal Outcomes Test (SNOT-22) questionnaire were administered on days 1, 30, and 60 of the study. Plasma budesonide and cortisol levels were simultaneously quantified using a high-performance liquid chromatography-tandem mass spectrometry technique.. There was no indication of adrenal suppression in either group (n = 20) based on ACTH stimulation test results nor was there significant plasma budesonide levels detected in either group. Quality of life, as indicated by SNOT-22, did not differ between groups at 60 days (p = 0.404; 95% confidence interval [CI], -37.2 to 15.9), but SNOT-22 scores for patients using MAD did show statistically significant improvement at 60 days compared to baseline (p = 0.02).. The MAD is likely a safe and effective method of delivering budesonide to the sinuses in the short term.

Topics: Administration, Mucosal; Anti-Inflammatory Agents; Budesonide; Canada; Chronic Disease; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Nasal Polyps; Nebulizers and Vaporizers; Pituitary-Adrenal System; Prospective Studies; Quality of Life; Rhinitis; Sinusitis; Time Factors; Treatment Outcome

Recently, we demonstrated that acoustic rhinometry (AR) measurements correlated with nasal cavity volumes in patients with nasal polyposis (NP). The aim of the present study was to evaluate whether AR and nasal nitric oxide (nNO) are useful methods in monitoring and follow-up of medical treatment of NP.. Patients with severe nasal polyps were randomized into two groups after a 4-week steroid washout period (w0): a treatment group received oral prednisone for 2 weeks (w2) and intranasal budesonide for 12 weeks (w12) while the control group received no steroid treatment. Nasal volume (Vol 0-6), minimum cross-sectional area (mCSA), nNO, peak nasal inspiratory flow (PNIF), nasal obstruction, and smell loss were evaluated.. At w2, the treatment group showed a significant increase of vol 0-6 compared to w0 and the control group. The mCSA area also increased compared to w0 and the control group. At w12, the improvement in vol 0-6 and mCSA was maintained after intranasal steroids compared to w0. At w2, the treatment group showed a paradoxical increase of nNO compared to w0 and the control group. At w12, this increase was maintained by intranasal steroids.. Both oral and intranasal steroid treatments improve nasal patency and paradoxically increase nNO, by opening the ostiomeatal complex. This suggests that AR and nNO are useful methods in the monitoring and follow-up of patients with NP.

Topics: Administration, Intranasal; Administration, Oral; Adult; Aged; Aged, 80 and over; Budesonide; Female; Glucocorticoids; Humans; Male; Middle Aged; Nasal Polyps; Nitric Oxide; Nose; Prednisone; Rhinometry, Acoustic; Tomography, X-Ray Computed

To evaluate the efficacy and safety of a short course of nebulized budesonide via transnasal inhalation in chronic rhinosinusitis with nasal polyps.. Thirty patients with severe eosinophilic nasal polyps were randomized into experimental group (n=15) and control group (n=15). The experimental group received nebulised budesonide suspension (1 mg twice daily) via transnasal inhalation for one week and control group-received budesonide nasal spray (256 microg twice daily). Visual analogue scales (VAS)of nasal symptoms (including nasal obstruction, nasal discharge, loss of smell, and headache/facial pain) and endoscopic polyp scores (Kennedy scores) and morning serum cortisol concentration were performed to both groups before and after the treatment.. Nebulized budesonide inhalation caused a significant improvement in all nasal symptoms especially nasal obstruction (baseline: 8.4 +/- 0.7; after treatment: 4.0 +/- 0.8, P<0.01) and reduced polyp size compared with before treatment. Additionally, the patients treated with nebulized budesonide showed more obvious improvement in nasal symptoms and polyp size than control group. The morning serum cortisol concentration was mild decreased after one week treatment in nebulized steroid group [baseline: (17.6 +/- 2.4) microg/dl, after treatment: (14.8 +/- 2.6) microg/dl, P<0.01], but all values still were located in normal range (normal range: 5-25 microg/dl).. A short course of nebulized budesonide transnasal inhalation can rapidly improve nasal symptoms, reduce polyp size, and does not cause obvious HPA axis suppression. Based on these, it is recommend that transnasal inhalation with nebulized budesonide suspension should be performed as a pre-operative routine in patients with nasal polyp.

Topics: Administration, Inhalation; Adult; Budesonide; Female; Humans; Male; Middle Aged; Nasal Polyps; Nebulizers and Vaporizers; Sinusitis; Suspensions; Treatment Outcome; Young Adult

Cell resistance to glucocorticoids is a major problem in the treatment of nasal polyposis (NP).. The objectives of this study were to observe the effect of budesonide on the expression of IL-1beta, TNF-alpha, granulocyte macrophage-colony stimulating factor, intercellular adhesion molecule (ICAM)-1, basic fibroblast growth factor, eotaxin-2, glucocorticoid receptor (GR)-alpha, GR-beta, c-Fos and p65 in nasal polyps and to correlate their expression to clinical response.. Biopsies from nasal polyps were obtained from 20 patients before and after treatment with topical budesonide. Clinical response to treatment was monitored by a questionnaire and nasal endoscopy. The mRNA levels of the studied genes were measured by real-time quantitative (RQ)-PCR.. There was a significant decrease in the expression of TNF-alpha (P<0.05), eotaxin-2 (P<0.05) and p65 (P<0.05) in NP after treatment. Poor responders to glucocorticoids showed higher expression of IL-1beta (3.74 vs. 0.14; P<0.005), ICAM-1 (1.91 vs. 0.29; P<0.05) and p65 (0.70 vs. 0.16; P<0.05) before treatment. Following treatment, IL-1beta (4.18 vs. 0.42; P<0.005) and GR-beta (0.95 vs. 0.28; P<0.05) mRNA expression was higher in this group.. Topical budesonide reduced the expression of TNF-alpha, eotaxin-2 and p65. Poor responders to topical budesonide exhibit higher levels of IL-1beta, ICAM-1 and nuclear factor (NF)-kappaB at diagnosis and higher expression of both IL-1beta and GR-beta after treatment. These results emphasize the anti-inflammatory action of topical budesonide at the molecular level and its importance in the treatment of NP. Nevertheless, IL-1beta, ICAM-1 and NF-kappaB may be associated with primary resistance to glucocorticoids in NP, whereas higher expression of GR-beta in poor responders only after glucocorticoid treatment may represent a secondary drug resistance mechanism in this disease.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Budesonide; Cytokines; Drug Resistance; Endoscopy; Glucocorticoids; Humans; Inflammation; Inflammation Mediators; Middle Aged; Nasal Mucosa; Nasal Polyps; Predictive Value of Tests; Surveys and Questionnaires; Treatment Outcome; Young Adult

Mucus hypersecretion is a hallmark of nasal polyposis (NP). Corticosteroids (CS) are first-line treatment for NP, decreasing their size and inflammatory component. However, their effect on mucin production is not well-understood. The aim of this (pilot) study was to investigate CS effect on mucin expression in NP.. Patients were randomized in control (n = 9) and treatment (oral prednisone for 2 weeks and intranasal budesonide for 12 weeks; n = 23) groups. Nasal polyposis from nonasthmatic (NP; n = 13), aspirin-tolerant (NP-ATA; n = 11) and aspirin-intolerant (NP-AIA; n = 8) asthmatics were studied. Nasal polyposis biopsies were obtained before (w0) and after 2 (w2) and 12 (w12) weeks of CS treatment. Secreted (MUC5AC, MUC5B and MUC8) and membrane-tethered (MUC1, MUC4) mucins (immunohistochemistry) and goblet cells (Alcian blue-periodic acid Schiff) were quantified in both epithelium and glands. Rhinorrea and nasal obstruction were also assessed.. At w2, steroids increased MUC1 (from 70 to 97.5) and MUC4 (from 80 to 100) in NP-ATA patients' epithelium compared with baseline (w0). At w12, steroids decreased MUC5AC (from 40 to 5) and MUC5B (from 45 to 2.5) in NP-ATA patients' epithelium and glands, respectively, compared with baseline. No mucin presented significant changes in NP-AIA patients. MUC5AC and MUC5B expression correlated with goblet and mucous cell numbers, respectively, and MUC5AC also with rhinorrea score.. These results suggest: (i) CS up-regulate membrane (MUC1, MUC4) while down-regulate secreted (MUC5AC, MUC5B) mucins; (ii) there exists a link between secreted mucin expression and goblet cell hyperplasia; and (iii) NP from AIA may develop resistance to CS treatment.

Topics: Adult; Budesonide; Down-Regulation; Female; Gene Expression Profiling; Humans; Male; Middle Aged; Mucins; Nasal Mucosa; Nasal Polyps; Pilot Projects; Prednisone; Prospective Studies; Up-Regulation

Poor response of nasal polyps to glucocorticoids (GCs) may be because of abnormal expression of GC receptors (GR) alpha and beta or to downregulation of GRalpha. We aimed to evaluate the in vivo regulation of GR isoforms in GC-treated nasal polyps and to assess the relationship between clinical response to GCs and GR levels.. Patients with nasal polyps were randomly (3:1) treated (n = 51) or not (n = 14) with oral prednisone and intranasal budesonide for 2 weeks, plus intranasal budesonide for 10 additional weeks. Nasal symptoms were evaluated. Biopsies were obtained before (w0) and after 2 (w2) and 12 (w12) weeks of treatment, and analysed for their inflammatory content and GR mRNA (10(2) cDNA copies/mug total RNA) and protein (% immunoreactive inflammatory cells) expression. Healthy nasal mucosa (n = 11) was also investigated. Data are presented as median and 25-75th percentile.. At w0, nasal polyps expressed less GRalpha mRNA (1343;683-2263; P < 0.05) and GR protein (41;29-54; P < 0.05) than nasal mucosa (2474;1346-2933; 60;51-72, respectively). GRbeta immunoreactivity was higher in nasal polyps (11;4-19; P < 0.05) than in nasal mucosa (5;2-5). At w2, increased GRalpha mRNA (2010;1037-2732; P < 0.01) and GR protein (56;27-71; P = 0.056) were found compared with w0 (1177;759-2058; 37;29-55, respectively). At w12, GRalpha mRNA and GR protein were similar to w0. GRbeta expression was unaltered by treatment. Neither GRalpha nor GRbeta correlated with nasal symptoms. GR immunoreactivity negatively correlated with eosinophils (r = -0.478; P < 0.001).. GRalpha is downregulated in nasal polyps and upregulated by GC treatment. Neither GRalpha nor GRbeta appear to determine the sensitivity to GCs in nasal polyposis.

Topics: Administration, Intranasal; Administration, Oral; Adult; Budesonide; Down-Regulation; Female; Humans; Male; Middle Aged; Nasal Polyps; Prednisone; Protein Isoforms; Receptors, Glucocorticoid; Up-Regulation

To examine the potential of montelukast, a leukotriene receptor antagonist, as an adjunct to oral and inhaled steroid in subjects with chronic nasal polyps.. Prospective, randomized controlled trial.. Thirty-eight consecutive adult patients with bilateral nasal polyps were randomized into two groups. Eighteen subjects were treated with oral prednisolone for 14 days and budenoside nasal spray for 8 weeks. Twenty subjects received similar treatment with additional oral montelukast for 8 weeks. Subjects completed a modified nasal ICSD symptom score at 8 and 12 weeks after beginning treatment and the SF-36 quality of life questionnaire at 12 weeks.. Symptom scores improved in both groups after treatment. Subjects treated with montelukast reported significantly less headache (P = 0.013), facial pain (P = 0.048) and sneezing (P = 0.03) than controls. Four weeks after completing treatment, no significant differences were recorded.. Montelukast therapy may have clinical benefit as an adjunct to oral and inhaled steroid in chronic nasal polyposis, but effects are not maintained after cessation of treatment.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adult; Aged; Aged, 80 and over; Budesonide; Cohort Studies; Cyclopropanes; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Leukotriene Antagonists; Male; Middle Aged; Nasal Polyps; Prednisolone; Quinolines; Sulfides; Treatment Outcome

The objective of the present study was to evaluate the clinical response to topical budesonide in patients with nasal polyposis (NP) and to evaluate if there is any clinical event that may predict the response to treatment. Twenty patients with NP were assessed by a clinical questionnaire, nasal endoscopy and sinusal computed tomography. The patients were then medicated with budesonide, 256 microg/nostril/day, for a 2-month period and afterwards they were submitted to a new clinical questionnaire and a new endoscopy. Post-treatment endoscopy revealed a significant reduction of polyp size's score (4.25 vs. 2.90, p < 0.01), which was associated to improvement of nasal symptoms: posterior rhinorrhea, headache, hyposmia, anterior rhinorrhea, and sneezing (p < 0.05). There was also a significant improvement of the sum of scores (20.10 vs. 10.30, p < 0.0001). Cacosmia and nasal itching did not respond to medical treatment. Patients with a higher tomographic extension of the polyp presented a significantly worse clinical response (p < 0.05). We conclude that there was partial, but significant, improvement of nasal symptoms and polyp size after treatment with nasal budesonide and that this clinical improvement was inversely correlated to the tomographic extension of NP at diagnosis.

Topics: Administration, Topical; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Endoscopy; Female; Glucocorticoids; Headache; Humans; Male; Middle Aged; Nasal Obstruction; Nasal Polyps; Olfaction Disorders; Paranasal Sinuses; Remission Induction; Rhinitis; Sneezing; Surveys and Questionnaires; Tomography, X-Ray Computed; Treatment Outcome

Nasal polyposis is not a life-threatening disorder but has a great impact on the quality of life. Steroids constitute the first line of treatment of nasal polyps. The aims of this study were to evaluate the quality of life in nasal polyp patients after: (1) a short course of oral steroids; and (2) a long-term treatment with intranasal steroids.. Patients with severe nasal polyps received either oral prednisone (n = 60) or no steroid treatment (control group, n = 18) for 2 weeks. Patients treated with steroids were also followed-up and evaluated after 12, 24, and 48 additional weeks with intranasal budesonide treatment.. Patients with nasal polyps showed worse scores on all SF-36 domains, except for physical functioning, compared to the Spanish general population. After two weeks, patients treated with oral prednisone demonstrated a significant improvement (p < 0.05) in all impaired QoL domains compared to both control group and baseline. The mental component summary (51.0 +/- 1.2, p < 0.05) and physical component summary (51.0 +/- 0.9, p < 0.05) were improved compared to both control group and baseline. The improvement of all SF-36 domains was sustained by intranasal budesonida (p < 0.05) after 12, 24, and 48 weeks. Nasal obstruction, sense of smell, and polyp size also improved after both the oral short course and the intranasal long-term steroids treatment (p < 0.05).. These results suggest that the treatment with a short-course of oral steroids improves the quality of life of patients with severe nasal polyps and that this effect is maintained by a long-term treatment with intranasal steroids.

Topics: Administration, Intranasal; Administration, Oral; Aged; Aged, 80 and over; Budesonide; Drug Administration Schedule; Female; Glucocorticoids; Humans; Male; Middle Aged; Nasal Obstruction; Nasal Polyps; Prednisone; Quality of Life; Smell

Nasal polyposis is an inflammatory disease of unknown etiology. This study aimed to evaluate the effect of a short course of oral prednisone followed by intranasal budesonide on nasal symptoms, polyp size, nasal flow, and computed tomography scan.. Eighty-four patients with severe nasal polyps were included. After a steroid washout period, patients were randomized into two groups: group A (n = 63) received oral prednisone for 2 weeks and group B (n = 21) did not receive any steroid treatment. Patients from group A received intranasal budesonide for 12 weeks.. Atopy was positive in 36.8% of patients. Blood eosinophilia was higher in asthmatic (7.2 +/- 0.7%, P < .05) than in nonasthmatic (3.0 +/- 0.4%) patients. Asthmatic patients showed higher scores on nasal obstruction and loss of smell than nonasthmatics. Oral steroids caused a significant improvement in all nasal symptoms and improved polyp size (2.1 +/- 0.1, P < .05) and nasal flow (560 +/- 35 cm/s, P < .05) compared with nontreated patients (2.8 +/- 0.1 and 270 +/- 34 cm/s, respectively). Intranasal budesonide maintained the improvement on nasal symptoms, polyp size, and nasal flow. Steroid treatment reduced the computed tomography scan score (15.4 +/- 1, P < .05) compared with before treatment (18.2 +/- 0.8).. A short course of oral steroids improved all nasal symptoms, polyp size, and nasal flow, whereas intranasal steroid maintain this effect.

Topics: Administration, Intranasal; Administration, Oral; Adult; Aged; Aged, 80 and over; Budesonide; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nasal Polyps; Prednisone; Probability; Prospective Studies; Reference Values; Risk Assessment; Severity of Illness Index; Treatment Outcome

Topics: Anti-Inflammatory Agents; Budesonide; Combined Modality Therapy; Humans; Nasal Obstruction; Nasal Polyps; Olfaction Disorders; Prednisolone; Recovery of Function; Treatment Outcome

We have previously compared different scoring systems for endoscopic staging of nasal polyps. Of the five methods evaluated, we found that two were better than the others with regard to reproducibility and agreement between physicians. One method was lateral imaging, developed by the authors, and the other was a scoring system developed by Lildholdt et al. The main objective of the present study was to compare the sensitivity of these two methods. Another aim was to study the effect on nasal polyposis of topical nasal corticosteroids over a 2-week period. Patients with bilateral nasal polyposis (n = 100) were randomized to a 2-week treatment with a topical corticosteroid (budesonide aqueous nasal spray: 128 microg b.i.d.) or placebo in a double-blind manner. Nasal symptoms were scored before treatment and after 3, 7 and 14 days of treatment, and the patients underwent nasal endoscopy at clinical visits. Patients treated with active substance had an improvement in their symptoms, an effect already detectable after 3 days of treatment, compared with those who received placebo. In addition, a statistically significant decrease in polyp size could be registered after 14 days using lateral imaging but not with the other scoring system. In conclusion, lateral imaging was more sensitive and could detect effects earlier than the other scoring system and can be recommended for the endoscopic staging of nasal polyps in clinical studies.

Topics: Administration, Topical; Anti-Inflammatory Agents; Budesonide; Double-Blind Method; Endoscopy; Female; Glucocorticoids; Humans; Male; Middle Aged; Nasal Polyps; Neoplasm Staging; Reproducibility of Results; Time Factors

Controlled prospective studies are needed to determine whether surgical treatment in fact has an effect additive to that of medical treatment of nasal polyposis.. We sought to compare the effect of medical treatment versus combined surgical and medical treatment on olfaction, polyp score, and symptoms in nasal polyposis.. Thirty-two patients with nasal polyposis and symmetrical nasal airways were randomized to unilateral endoscopic sinus surgery after pretreatment with oral prednisolone for 10 days and local nasal budesonide bilaterally for 1 month. Postoperatively, patients were given local nasal steroids (budesonide). Patients were evaluated with nasal endoscopy, symptom scores, and olfactory thresholds. They were followed for 12 months.. The sense of smell was improved by the combination of local and oral steroids. Surgery had no additional effect. Symptom scores improved significantly with medical treatment alone, but surgery had additional beneficial effects on nasal obstruction and secretion. After surgery, the polyp score decreased significantly on the operated side but remained the same on the unoperated side. Twenty-five percent of the patients were willing to undergo an operation also on the unoperated side at the end of the study.. Medical treatment seems to be sufficient to treat most symptoms of nasal polyposis. When hyposmia is the primary symptom, no additional benefit seems to be gained from surgical treatment. If nasal obstruction is the main problem after steroid treatment, surgical treatment is indicated. Selection of those who will benefit from surgery should be based on the patient's symptoms and not on the examiner's polyp score.

Topics: Budesonide; Combined Modality Therapy; Humans; Nasal Polyps; Prednisolone

To assess the efficacy and tolerability of once-daily treatment with budesonide aqueous nasal spray in patients with nasal polyps.. Randomized, double-blind, placebo-controlled, parallel-group study.. Sixteen hospital clinics.. One hundred eighty-three patients with moderate-sized nasal polyps causing clinically significant symptoms during a 1-week run-in period.. Patients were randomized to receive 1 of the following 4 budesonide aqueous nasal spray treatments: 128 microg once daily in the morning and placebo in the evening, 128 microg twice daily, 256 microg once daily in the morning and placebo in the evening, or placebo 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.. Mean change in nasal polyp size at the end of treatment; mean changes in combined and individual symptom scores.. All doses of budesonide aqueous nasal spray significantly (P<.01) reduced polyp size; no significant differences 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 nasal spray, 128 microg twice daily; 71.6 L/min with budesonide aqueous nasal spray, 256 microg once daily; and 54.6 L/min with budesonide aqueous nasal spray, 128 microg once daily (all P<.001 vs placebo). Combined and individual symptom scores and sense of smell improved significantly in all budesonide-treated groups; the effect on symptoms became apparent within 1 to 2 days of the first dose. Budesonide aqueous nasal spray was well tolerated.. Doses of budesonide aqueous nasal spray, 128 microg once daily, were found to be effective in the treatment of nasal polyps, and doses of budesonide aqueous nasal spray, 256 microg once daily, did not show any significant additional efficacy.

Topics: Administration, Intranasal; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Middle Aged; Nasal Polyps; Treatment Outcome

Nasal polyps are a common disease with in the majority of cases unknown origin. Both the medical and surgical treatment of nasal polyps present a challenge in Otorhinolaryngology.. We developed a four-stage grading system for nasal polyps based on the endoscopic aspect of more than 300 patients. In a study of 37 patients, treated by systemically (Methylprednisolon 64 mg p.o., decreasing amounts for the first 11 days) and locally (Budesonid 400 micrograms intranasal) applied steroids for 90 days, this staging-system was tested.. The mean stage of polyps decreased significantly (p < 0.01) from 2.8 at day 0 to 1.7 at day 7 and further to 1.2 and to 0.7 at day 28 and day 90 respectively. The mean nasal symptom score decreased equally from 1.14 on day 1 to 0.19 and to 0.14 on day 7 and day 28 respectively. To summarize, we observed a significant (p < 0.01) decrease in polyp stages of 75% respectively a significant (p < 0.01) reduction of symptom scores of 93%.. Thus, we present a suitable new grading system for nasal polyps which we applied directly to assess the efficacy of combined local and systemic steroid therapy. It was shown that this treatment can reduce polyps and prevent their recurrence over the observed time.

Topics: Administration, Intranasal; Administration, Oral; Adolescent; Adult; Anti-Inflammatory Agents; Budesonide; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Endoscopy; Ethmoid Sinus; Female; Follow-Up Studies; Humans; Male; Methylprednisolone; Middle Aged; Nasal Polyps; Neoplasm Staging; Paranasal Sinus Neoplasms

A randomized, double-blind, placebo-controlled trial was performed to assess the efficacy of once daily budesonide in patients with nasal polyps. After a 2-week run-in period, 157 patients with symptomatic bilateral nasal polyposis were randomized to receive budesonide, 140 micrograms once or twice daily or 280 micrograms once daily (delivered doses) via Turbuhaler, or placebo for 8 weeks. Polyp size was assessed endoscopically and, in two centres, by magnetic resonance imaging (MRI). Nasal symptoms (blocked nose, runny nose, sneezing) were recorded daily, and patients provided an overall assessment of efficacy at the end of the study. Budesonide, 280 micrograms/day (280 micrograms o.d. and 140 micrograms twice daily), significantly reduced polyp size, compared with placebo, whereas budesonide, 140 micrograms once daily, had no significant effect. Nasal polyp mass score, measured by MRI, was also significantly reduced in patients receiving 280 micrograms/day. All three doses of budesonide significantly reduced symptom scores, and there were no significant differences between the groups. Overall, approximately 70% of patients receiving budesonide, 280 micrograms/day, reported substantial or total control of symptoms, compared with 45% of placebo-treated patients. It is concluded that budesonide, 280 micrograms once daily, reduces polyp size and relieves symptoms in patients with nasal polyposis.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Glucocorticoids; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nasal Polyps; Reference Values; Treatment Outcome

Infiltration of eosinophil granulocytes and endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and P-selectin was investigated in biopsies of polyps and inferior turbinates from 16 patients with nasal polyps, by the use of immunohistochemical staining and stereological quantification before, during and after topical treatment with budesonide (Rhinocort Turbuhaler). Before glucocorticoid treatment a higher density of eosinophil profiles (p < 0.005), making up a larger proportion of the total cellular infiltrate (p < 0.0005), was found in the polyps compared with the inferior turbinates. Endothelial VCAM-1 expression was higher in polyps than in inferior turbinates (p < 0.005), in contrast with the expression of P-selectin, which was more frequently expressed in the inferior turbinates (p < 0.05). Topical glucocorticoid treatment reduced the density of eosinophil profiles (p < 0.05) and the endothelial expression of VCAM-1 (p < 0.007) and P-selectin (p < 0.02) in polyps. Eosinophil counts and VCAM-1 expression returned to pre-treatment levels 8 weeks after discontinuation of budesonide treatment. The observed reduction in endothelial expression of cellular adhesion molecules may interfere with cellular recruitment in nasal polyps and thus contribute to the known anti-inflammatory effect of glucocorticoid in nasal polyposis.

Topics: Administration, Topical; Adult; Aged; Anti-Inflammatory Agents; Biopsy; Budesonide; Endothelium; Eosinophilia; Eosinophils; Female; Glucocorticoids; Humans; Immunoglobulin E; Male; Middle Aged; Nasal Polyps; P-Selectin; Turbinates; Vascular Cell Adhesion Molecule-1

Topical corticosteroids are one of the main pillars in the treatment of nasal polyps. The exact topography of their intranasal deposition has not yet been adequately visualised. The intranasal distribution of a 1% sodium fluorescein solution applied with original Pulmicort Topinasal (budesonide) metered pump bottles was analysed by videoendoscopy. The study group included eight healthy subjects and ten patients who had undergone endonasal sinus surgery. Videoendoscopy was performed in the study group within the first minute after application of the fluorescein solution. Additionally the deposition pattern of Pulmicort Topinasal was analyzed using a nasal model. The examination showed that the majority of the substance is deposited on the anterior portion of the nasal septum and the head of the inferior turbinate. Only a small fraction actually reaches the middle meatus. The distribution is improved by application during the decongested phase of the nasal cycle, after use of vasoconstricting nasal drops and maintaining a spraying angle of 45 degrees upwards. The development of new delivery techniques and systems could improve the efficacy of intranasally administered corticosteroids and reduce the complication rate.

Topics: Administration, Intranasal; Adult; Anti-Inflammatory Agents; Budesonide; Endoscopy; Female; Follow-Up Studies; Glucocorticoids; Humans; Male; Models, Anatomic; Nasal Mucosa; Nasal Polyps; Reference Values; Sensitivity and Specificity; Tissue Distribution; Treatment Outcome; Video Recording

The treatment of nasal polyps is controversial, and medical treatment alone has been little investigated to our knowledge.. To examine the efficacy of therapy using only topical budesonide powder and topical budesonide powder supplemented with surgical removal or intramuscular betamethasone.. Randomized, double-blind comparison of 2 dosages and additional treatment, if therapy failed. After 1 year, treatment with medication was stopped, and the demand for renewed treatment was monitored for another year.. Patients with bilateral nasal polyps who demanded treatment were consecutively enrolled in a hospital outpatient clinic or specialty private practice. During a 15-month period from 1990 to 1992, a total of 126 patients entered the 2-year study.. In phase 1, randomized and double-blind treatment with a topical medication, budesonide powder, 800 micrograms or 400 micrograms daily, or a placebo was given for 1 month. In phase 2, randomized and double-blind treatment with budesonide powder, 800 micrograms or 400 micrograms daily, was given. At the end of phase 1, failed therapy was supplemented by randomly assigned treatment of either surgical removal or a single injection of sustained released betamethasone. In phase 3, treatment with the medication was discontinued, and patients were monitored for another year. The time when treatment was required again was noted. The present article deals with phases 2 and 3.. Patients' scores of treatment efficacy as well as symptoms and signs. Semiquantitative measurement of sense of smell and calculation of peak expiratory flow rate index based on nasal and oral peak expiratory flow.. In all outcome measures, a comparison of the data before treatment with the corresponding figures during phase 2 showed statistically significant efficacy. The clinical course was described at the end of phase 2. About 85% of the patients, including those who received additional therapy because the initial therapy failed, rated total or substantial control over the symptoms. The 2 dosages investigated showed equal results. These findings were consistent with the signs recorded and the peak expiratory flow rate index. The results of phase 3 showed that 50% of patients had demanded treatment after 4 months, while 34% managed without medication after 1 year.. The clinical course in this study showed that most patients with nasal polyps do well with medical treatment. Therefore, surgery was required in few patients. However, the potential of medical treatment should be further explored in future studies.

Topics: Administration, Inhalation; Administration, Topical; Anti-Inflammatory Agents; Betamethasone; Budesonide; Double-Blind Method; Female; Follow-Up Studies; Glucocorticoids; Humans; Injections, Intramuscular; Male; Middle Aged; Nasal Polyps; Peak Expiratory Flow Rate; Powders; Pregnenediones; Time Factors; Treatment Outcome

Budesonide has been used for a number of years as a topical nasal corticosteroid in the treatment of nasal allergy and nasal polyps. Recently, a new device for powder insufflation where no constituents or preservatives are included has been developed (Rhinocort Turbuhaler, Astra Draco AB, Sweden). The present investigation was designed in order to study the efficacy of topical budesonide powder as the only treatment of nasal polyps. A total of 126 patients entered the study. The medical history and clinical recordings included symptoms and signs, a semiquantitative test of smell and measurement of nasal expiratory peak flow index. Medication was either 200 or 400 micrograms of budesonide powder b.i.d. or placebo. After 1 month an overall assessment of treatment efficacy was made to determine whether the treatment had been a success or a failure. The results showed a statistically significant improvement of symptoms and signs in the actively treated groups. The increase in expiratory peak flow index was about 60% in the actively treated groups as opposed to 16% in the placebo group. The overall assessment of treatment efficacy showed success in about 82% of actively treated patients as opposed to about 43% in the placebo group. It is concluded that budesonide powder is useful in the treatment of nasal polyps.

Topics: Administration, Topical; Adrenal Cortex Hormones; Budesonide; Double-Blind Method; Female; Humans; Male; Middle Aged; Nasal Polyps; Placebos; Pregnenediones; Treatment Outcome

The objectives of this study were to determine if the size of nasal polyps could be assessed in a reproducible way and to study the effect of budesonide in patients suffering from eosinophilic nasal polyposis with small and medium sized polyps. Ninety-one patients entered the study. Budesonide 200 micrograms b.i.d. (aerosol or aqua) and placebo (aerosol or aqua) were compared in a 3-month double-blind, multi-centre, randomized study. Efficacy was measured by an assessment of polyp size, nasal peak-flow index and the patient's assessment of nasal symptoms. The conclusions were that the size of polyps could be assessed in a reproducible way, and that budesonide delivered either as a water-based suspension or as an aerosol is effective in the treatment of patients with small and medium sized polyps.

Topics: Administration, Topical; Adolescent; Adult; Aerosols; Aged; Anti-Inflammatory Agents; Budesonide; Double-Blind Method; Glucocorticoids; Humans; Middle Aged; Nasal Polyps; Placebos; Pregnenediones; Treatment Outcome

Intranasal budesonide, 400 micrograms two times a day, was evaluated in 36 patients referred for treatment of nasal polyposis. The age range was 20 to 68 years. Polypectomy was done 5.6 (mean) times previously. After a 5-week, treatment-free, baseline period, patients were treated in a double-blind fashion with either budesonide or placebo during 4 weeks. After this treatment period, placebo-treated patients started receiving budesonide in an open trial for an additional 4 weeks. The patients rated their nasal symptoms daily. Nasal examinations and nasal inspiratory flow rate (IFR) measurements were done at clinic visits. After 3 and 4 weeks of treatment, the response to budesonide was significantly greater than response to placebo. The greater reduction in nasal blockage caused by polyps, observed on physical examination, p = 0.005, was mirrored by an increase in nasal IFR (p = 0.0001). Patient rating of the severity and frequency of nasal blockage were reduced more by budesonide than by placebo (p less than or equal to 0.0005). Switching placebo-treated patients to budesonide treatment resulted in a reduction of nasal blockage (p less than 0.001) and an increase in nasal IFR (p less than 0.001). The results demonstrate that topical nasal budesonide, 400 micrograms two times a day, is an effective treatment of nasal polyps.

Topics: Administration, Intranasal; Budesonide; Double-Blind Method; Glucocorticoids; Humans; Nasal Polyps; Patient Compliance; Placebos; Pregnenediones; Pulmonary Ventilation

This double-blind parallel-group study compared the effect of budesonide with placebo, in the prophylaxis of nasal polyp recurrence after evulsion. Seventy-three patients with first time or recurrent polypectomy were enrolled. At revisits 3 and 6 months after evulsion, the budesonide-treated patients had significantly lower polyp scores than the placebo-treated patients. Only patients with recurrent nasal polyposis benefited from the budesonide treatment, whereas no effect was evident in patients with first time evulsion.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Clinical Trials as Topic; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Middle Aged; Nasal Polyps; Neoplasm Recurrence, Local; Pregnenediones

The etiology of perennial non-allergic rhinitis and nasal polyposis is still not properly understood. Non-specific hyperreactivity forms a major significant symptom. Topical steroids have been used in the treatment of these diseases for about ten years. Their mode of action is still largely unknown. Various test methods in clinical trials can improve our knowledge. The effect of budesonide given intranasally as an aerosol was tested in 22 patients with perennial rhinitis. In another trial the effect of beclomethasone dipropionate (BDP) was compared when given as an aerosol and as a powder. Today we know not only that budesonide and the two forms of BDP are clinically efficacious but also that intranasal steroid treatment can reduce metacholine-induced nasal secretion, reduce the sensitivity of mucosal irritant receptors, and lower the number of basophilic as well as eosinophilic cells in the nasal secretion.

Topics: Administration, Topical; Beclomethasone; Budesonide; Humans; Nasal Polyps; Nose Diseases; Pregnenediones; Respiratory Hypersensitivity; Rhinitis, Allergic, Perennial

A double-blind parallel trial of budesonide versus placebo was carried out in 19 patients suffering from nasal polyposis. The patients were randomly assigned to two groups, one receiving a daily dose of 400 micrograms of budesonide and the other a corresponding dose of placebo intranasally for 4 months. The total mean symptom scores and nasal peak flow values during the trial showed a statistically significant difference in favour of budesonide. On rhinoscopy, a clear decrease in mucosal congestion was noticed in the group receiving the active drug. The polyps diminished in number and size in the budesonide group. Mucociliary function, measured by the saccharin test before and after therapy, did not undergo significant changes in either group. Mean plasma cortisol values were of the same order before and after therapy. Local side-effects were mild in both groups, and there was no indication of mucosal drying or crusting attributable to the test solution. Pre- and post-therapy biopsies revealed a pronounced decrease in tissue eosinophilia following budesonide treatment. Neither nasal smears nor biopsies showed signs of morphological changes in the epithelium.

Topics: Adult; Biopsy; Budesonide; Female; Humans; Male; Middle Aged; Nasal Polyps; Pregnenediones

Pathophysiology-targeting treatments exist for aspirin-exacerbated respiratory disease (AERD) through aspirin desensitization and biologics, such as dupilumab. With increasing attention paid to these treatments, which may be associated with significant side effects and/or cost, there is little description of chronic rhinosinusitis with nasal polyps (CRSwNP) response to treatment with intranasal corticosteroids and saline irrigations in AERD.. To determine the effect of intranasal budesonide irrigations for the treatment of CRSwNP in AERD.. This is an observational study of 14 AERD patients presenting to a rhinology clinic for CRS who were treated with twice daily high volume, low pressure irrigations with 240 mL of saline to which a 0.5 mg/2 mL respule of budesonide was added. All participants completed a 22-item Sinonasal Outcome Test (SNOT-22) at enrollment and at follow up 1 to 6 months later. Polyp scores were also calculated at each time point.. SNOT-22 scores ranged from 26 to 98 (median: 40.5) at enrollment and 3 to 85 (median: 38.5) at follow-up. Polyp scores ranged from 2 to 6 (median: 4) at enrollment at 0 to 6 (median: 2) at follow-up. Over the treatment period, change in SNOT-22 score ranged from -38 to 16 (median: -18) and change in polyp score ranged from -2 to 0 (median: -0.5). Approximately 57% of participants experienced at least 1 minimal clinically important difference in SNOT-22 score and 21% of participants had a SNOT-22 score <20 at follow-up.. Medical management with intranasal corticosteroids and saline irrigations alone leads to significant improvement in sinonasal symptomatology in a subset of AERD.

Topics: Adrenal Cortex Hormones; Aspirin; Asthma, Aspirin-Induced; Budesonide; Chronic Disease; Humans; Nasal Polyps; Rhinitis; Sinusitis

CD8+CD25+Foxp3+ regulatory T cells (Tregs) play an important role in human's immune tolerance. The study was aimed to assess the influence of budesonide nasal spray on CD8+CD25+Foxp3+ Tregs and to evaluate their cellular functions in neutrophilic chronic rhinosinusitis with nasal polyps (CRSwNPs).. Fifteen patients with neutrophilic CRSwNPs were enrolled and received physiological saline or budesonide nasal spray treatment (Saline or Budesonide group) for 3 months. Nasal tissue samples were obtained from normal subjects or those patients and cultured in vitro. CD8+CD25+Foxp3+ Tregs were separated from normal or NP tissues and also cultured in vitro. Then interleukin (IL)-10 and its mRNA were evaluated in the above cell cultures. The cells were applied into NP cultures. Finally, myeloperoxidase (MPO), interferon (IFN)-γ, IL-1β, and tumor necrosis factor (TNF)-α were assessed in the tissue cultures.. CD8+CD25+Foxp3+ Tregs decreased in NP tissues. Budesonide administration did not enhance the percentage of these cells in polypoid tissues. IL-10 and its mRNA were increased in the above cell cultures from NPs. However, there were no statistical differences between the two treatments in the IL-10 expression. Additionally, levels of MPO, IFN-γ, IL-1β, and TNF-α were totally elevated in NP tissue cultures and reduced after the administration of CD8+CD25+Foxp3+ Tregs. However, there were no significant differences in concentrations of these mediators between these two groups of the CD8+CD25+Foxp3+ Tregs treatment in vitro.. The findings indicate that CD8+CD25+Foxp3+ Tregs might regulate the neutrophilic inflammation, and budesonide nasal spray therapy could not ameliorate the inflammation in neutrophilic CRSwNPs.

Topics: Adrenal Cortex Hormones; Budesonide; CD8-Positive T-Lymphocytes; Forkhead Transcription Factors; Humans; Inflammation; Interferons; Interleukin-10; Nasal Polyps; Nasal Sprays; Peroxidase; Rhinitis; RNA, Messenger; Sinusitis; T-Lymphocytes, Regulatory; Tumor Necrosis Factor-alpha

Intranasal corticosteroid drugs are widely used in chronic rhinosinusitis with nasal polyps (CRSwNP). In contrast to classical delivery with nasal pump sprays, pulsating aerosols can deliver significant doses into superior and posterior sinonasal spaces. A case-control study was designed to assess the efficacy of corticosteroid transnasal nebulization on short-term mucosal recovery and quality of life (QoL) following endoscopic sinus surgery in CRSwNP. Thirty patients were prospectively enrolled to receive either 1-month budesonide nasal pump spray or 1-month budesonide 100-Hz acoustic pulsating nebulization at the first postoperative visit (day 8). Patients were evaluated with Lund-Kennedy endoscopic score at day 8 (D8) and 1 month later (M1). CRS-related QoL questionnaires (SNOT22 and RhinoQOL) were fulfilled at M1. The Lund-Kennedy endoscopic scores compared between D8 and M1 were suggestively improved in the group treated with budesonide nebulization (mean difference between groups, - 18.28 units; 95%CI, - 31.29 to - 5.28 units, p = 0.014). QoL measurements were comparable at M1 between the groups of patients. No unexpected adverse event was described with both budesonide delivery protocols. In the early postoperative period, patients with CRswNP may benefit from pulsating nebulization. Large studies should be conducted to confirm the results. Safety profile related to systemic steroid absorption and bioavailability in chronic respiratory diseases also need to be addressed for further use.

Topics: Adrenal Cortex Hormones; Budesonide; Case-Control Studies; Chronic Disease; Humans; Nasal Polyps; Nasal Sprays; Quality of Life; Rhinitis; Sinusitis; Steroids

Eosinophilic chronic rhinosinusitis (eCRS), contemporarily classified as diffuse type 2 dominant chronic rhinosinusitis (CRS), is characterized by eosinophil-dominant mucosal inflammation. Contemporary management of eCRS as an inflammatory airway condition is multimodal with corticosteroid irrigations after the surgical creation of a neosinus cavity.. To assess long-term treatment outcomes in patients with primary diffuse type 2 CRS or eCRS receiving multimodal treatment.. A prospective cohort study of patients seen in a tertiary rhinology practice recruited from May 2010 to November 2018 was conducted. Follow-up duration was 12 months or more following endoscopic sinus surgery (ESS) with a neosinus cavity formed. Data analysis was performed from August to November 2020. Consecutive adult (≥18 years) patients diagnosed with primary diffuse type 2 dominant CRS or eCRS based on the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 criteria were included. Type 2 inflammation was defined as more than 10 eosinophils per high-power field obtained from sinus mucosal biopsy and managed with neosinus cavity ESS and ongoing corticosteroid irrigations. Exclusion criteria were less than 12 months of follow-up and secondary CRS.. Endoscopic sinus surgery with complete removal of intersinus bony partitions to create a neosinus cavity. Nasal irrigation (240 mL) with betamethasone, 1 mg, or budesonide, 1 mg, daily for 3 to 6 months after ESS and tapered to an as-needed basis (minimum, 2-3 per week).. Poor control was defined as polyp recurrence (polyp growth in >1 sinus area on a single side), use of long-term systemic therapy (biologic therapy or ≥3 consecutive months of oral corticosteroids), and revision surgery involving polypectomy. The disease in patients with no poor control criteria was defined as well controlled, and the disease in those with 1 or more criteria was considered poorly controlled. Maintenance medical therapy use and patient-reported outcomes based on the 22-item Sinonasal Outcomes Test for preoperative and last follow-up were collected.. Of the 222 participants recruited with primary diffuse type 2 dominant CRS or eCRS and minimum of year of follow-up, 126 were men (56.8%). Mean (SD) age was 54.8 (13.6) years, and median (SD) follow-up was 2.2 (2.2) years. Of the 222 patients, 195 (87.8%) had well-controlled disease, 16 (7.2%) had polyp recurrence, 7 (3.2%) continued to receive long-term oral corticosteroid therapy, 5 (2.3%) received biologic therapy, and 8 (3.6%) underwent a revision polypectomy. Clinically meaningful change on the 22-item Sinonasal Outcomes Test and the nasal subdomain score was maintained at the last follow-up in 134 patients (67.0%). Poor disease control was not associated with poor adherence to irrigation use.. The findings of this cohort study suggest that long-term disease control and reduction in symptom burden in patients with primary diffuse type 2 CRS or eCRS might be achieved when managed as an inflammatory disorder. Maintenance corticosteroid irrigations in the population examined appeared to be successfully self-tapered to disease activity.

Topics: Betamethasone; Budesonide; Chronic Disease; Cohort Studies; Endoscopy; Eosinophilia; Female; Follow-Up Studies; Glucocorticoids; Humans; Male; Middle Aged; Nasal Lavage; Nasal Mucosa; Nasal Polyps; Paranasal Sinuses; Postoperative Complications; Rhinitis; Sinusitis

Chronic rhinosinusitis and nasal polyps (CRNP) is a common public health concern for general population, and is thought to negatively impact their quality of life. Although previous studies have reported that nasal nebulization inhalation of budesonide (NNIB) can benefit patients with such condition, its conclusions are still inconsistent. Thus, this study will assess the efficacy and safety of NNIB for the treatment of CRNP.. To identify any associated studies, we will comprehensively and systematically search Cochrane Library, PubMed, EMBASE, Web of Science, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. We will search all electronic databases from inception to the present with no limitations of language and publication status. Two independent reviewers will undertake selection of study, data collection, and study quality evaluation, respectively. Another reviewer will help to settle down any different opinions between both of them. Study quality will be checked using Cochrane risk of bias tool, and statistical analysis will be performed using RevMan 5.3 software.. This study will assess the efficacy and safety of NNIB for the treatment of CRNP through assessing primary outcomes of nasal symptoms and polyp sizes, and secondary outcomes of serum cortisol levels, health-related quality of life, and any expected and unexpected adverse events.. The results of this study will summarize the up-to-date evidence on assessing the efficacy and safety of NNIB for the treatment of CRNP.. INPLASY202040108.

Topics: Administration, Intranasal; Anti-Inflammatory Agents; Budesonide; Chronic Disease; Humans; Meta-Analysis as Topic; Nasal Polyps; Nebulizers and Vaporizers; Rhinitis; Sinusitis; Systematic Review as Topic

Topics: Budesonide; CD8-Positive T-Lymphocytes; Chronic Disease; Forkhead Transcription Factors; Humans; Nasal Mucosa; Nasal Polyps; Rhinitis; T-Lymphocytes, Regulatory

A short-course oral corticosteroid taper and topical intranasal corticosteroids may be used to maximize the success of medical management for chronic rhinosinusitis with nasal polyps (CRSwNP). In this study, we sought to identify characteristics that would be predictive of efficacy for this combination regimen.. Sixty-four patients with CRS, bilateral polyps, a polyp score of at least 3, and a 22-item Sino-Nasal Outcome Test (SNOT-22) score ≥20 were prospectively enrolled and uniformly treated with a 15-day prednisone taper and twice daily dilute budesonide irrigations. Participants were assessed at enrollment and at follow up, 2 to 5 months later. Clinical and demographic characteristics were assessed at enrollment. At both time points, CRS symptoms were assessed with SNOT-22, and polyp score (range, 0 to 6) was assessed endoscopically. Associations were determined with regression.. Pretreatment SNOT-22 score (adjusted β = -0.83; 95% CI, -1.08 to -0.58; p < 0.001) and comorbid asthma (adjusted β = 15.75; 95% CI, 4.74 to 26.75; p = 0.007) were associated with a change in SNOT-22 experienced over the study period. Achieving a greater-than-1 minimal clinically important difference (MCID) improvement in SNOT-22 score was also associated with pretreatment SNOT-22 score (adjusted OR = 1.09; 95% CI, 1.04 to 1.14; p < 0.001) and comorbid asthma (adjusted OR = 0.13; 95% CI, 0.03 to 0.72; p = 0.019). SNOT-22 score ≥47 had 81.5% sensitivity and 78.4% specificity to detect patients experiencing 1 MCID improvement. Pretreatment polyp score was not associated with any outcome metric.. In treatment of CRSwNP with prednisone and budesonide irrigations, pretreatment endoscopy was not informative of treatment response. Pretreatment SNOT-22 and comorbid asthma may be more predictive.

Topics: Administration, Intranasal; Administration, Oral; Adrenal Cortex Hormones; Adult; Aged; Budesonide; Chronic Disease; Female; Humans; Male; Middle Aged; Nasal Polyps; Prednisone; Rhinitis; Sino-Nasal Outcome Test; Sinusitis; Treatment Outcome

Although short-term use (≤2 months) of atomized topical nasal steroids has been shown to be safe and effective, the long-term safety has yet to be demonstrated. The aim of this study was to determine the impact of long-term topical budesonide treatment via the mucosal atomization device (MAD) on the hypothalamic-pituitary-adrenal axis (HPAA) and intraocular pressure (IOP).. A cross-sectional study of patients with chronic rhinosinusitis (CRS), with or without nasal polyposis, managed with daily nasal budesonide via MAD was conducted at a tertiary rhinology center. Patients using systemic steroids within 3 months of assessment were excluded. HPAA impact was assessed using the cosyntropin stimulation test for adrenal function and a survey of relevant symptomatology. Patients also underwent tonometry to assess for elevated IOP potentially related to corticosteroid use.. A total of 100 CRS patients were recruited with a mean budesonide treatment duration of 23.5 months (range, 6-37 months). Stimulated cortisol response was diminished in 3 patients (3%). No patients with adrenal suppression had relevant symptomatology. IOP was elevated in 6 patients (6%).. These findings suggest that there is a risk of adrenal suppression and raised IOP associated with the long-term use of topical nasal budesonide via MAD. Otolaryngologists should consider periodic surveillance for these adverse events in this patient cohort.

Topics: Administration, Intranasal; Aged; Anti-Inflammatory Agents; Budesonide; Chronic Disease; Female; Glucocorticoids; Humans; Hypothalamo-Hypophyseal System; Intraocular Pressure; Male; Middle Aged; Nasal Polyps; Nebulizers and Vaporizers; Pituitary-Adrenal System; Rhinitis; Sinusitis

To investigate the effect of oral plus intranasal corticosteroid (CS) treatment on nasal polyp (NP) mucosa remodeling from patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP).. Case series, retrospective study.. Patients (n = 18) with severe CRSwNP were treated with oral prednisone for 2 weeks and intranasal budesonide for 12 weeks. NP biopsies were obtained from patients biopsies before (w0) and after 2 weeks (w2) and 12 weeks (w12) of CS treatment. Matrix metalloprotease 1 (MMP-1), MMP-2, MMP-7, MMP-9, and tissue inhibitor of metalloprotease type 1 (TIMP-1) expression was evaluated by immunohistochemistry in cell and tissue structures. Epithelial damage, eosinophil infiltration, and collagen content were also examined in NP tissues before and after CS treatment.. Compared to w0: 1) oral plus intranasal CS significantly (P < .01) increased presence of submucosal glands at w2, decreased epithelial cell hyperplasia at w12, and decreased tissue eosinophilia at w2 and w12; 2) CS treatment significantly (P < .05) increased immunoreactivity for MMP-1 and MMP-2 in the epithelium at w2, but decreased immunoreactivity for MMP-9 in the epithelium at w2 and w12; 3) at w12, CS significantly (P < .05) reduced MMP-9 immunoreactive positivity and intensity in the extracellular matrix, while increasing total collagen amount in the extracellular matrix; and 4) CS treatment significantly (P < .01) reduced the number of eosinophils and their MMP and TIMP-1 immunoreactive expression.. CS treatment modulates NP mucosa remodeling, particularly by promoting epithelial repair, regulating tissue remodeling markers, increasing total collagen content, and reducing tissue eosinophil infiltration.. 4

Topics: Administration, Intranasal; Administration, Oral; Biopsy; Budesonide; Chronic Disease; Collagenases; Drug Therapy, Combination; Eosinophils; Female; Glucocorticoids; Humans; Immunohistochemistry; Male; Middle Aged; Nasal Mucosa; Nasal Polyps; Prednisone; Retrospective Studies; Rhinitis; Sinusitis; Tissue Inhibitor of Metalloproteinases

Intranasal and oral corticosteroids are widely used in the management of chronic rhinosinusitis with nasal polyps (CRSwNP). Higher-dose topical nasal steroids (HDTNS) such as budesonide irrigations are increasingly used for long-term maintenance in these patients. Oral steroids have the potential to cause increased intraocular pressure (IOP) and glaucoma. It is unclear whether HDTNS have the same potential. The objective of this study was to determine the effect of intranasal budesonide irrigations on IOP.. Two groups of patients with CRSwNP treated with budesonide irrigations were prospectively enrolled. Patients with history of elevated IOP or glaucoma were excluded. Patients in group 1 had been using budesonide for at least 1 month and had IOP measured once at the time of enrollment. Group 2 consisted of patients who were placed on budesonide at the time of enrollment and had IOP measured both before and after at least 4 weeks of therapy.. Ten patients in group 1 and 8 patients in group 2 completed the study. In group 1, the average duration of therapy at enrollment was 6.3 months (1-22 months). Only 1 patient had a single eye pressure above 21 mmHg. None of the patients in group 2 had a significant change in IOP or IOP over 21 mmHg.. Intranasal budesonide irrigations given for a period of at least 1 month do not appear to increase IOP.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Chronic Disease; Female; Follow-Up Studies; Glaucoma; Humans; Male; Middle Aged; Nasal Polyps; Ocular Hypertension; Prospective Studies; Rhinitis; Sinusitis; Therapeutic Irrigation; Young Adult

Eosinophils appear to be central inflammatory cells in the pathogenesis of rhinosinusitis with nasal polyps (NP). One of the most predominantly recognized eosinophil chemoattractants is RANTES. The aim of this study was to assess the influence of vitamin D (VD) derivates on RANTES expression in the culture of nasal polyp fibroblasts.. NP fibroblast cell cultures derived from 16 patients with NP were first stimulated with bacterial LPS and than incubated in increasing concentrations (from 10(-7)M to 10(-4)M) of calcitriol, tacalcitol or budesonide and in combination with one of VD derivate with budesonide in 1:1, 1:3 and 3:1 ratios. Quantitative analysis of RANTES level was conducted in culture supernatants using an ELISA method.. The highest calcitriol concentration (10(-4)M) as well as tacalcitol at 10(-5)M and 10(-4)M reduced RANTES production significantly compared to the control (201.1pg/ml, 338.7pg/ml, 211.3pg/ml v 571.78pg/ml; p<0.05). Budesonide and calcitriol administered in 1:3 ratio and budesonide and tacalcitol in 1:1 and 1:3 reduced RANTES concentration significantly better than each of the drug used in monotherapy (p<0.05). Budesonide and tacalcitol in 1:1 and 1:3 ratios suppressed RANTES production to the lowest level (171.8±97.6pg/ml and 178.7±105.22pg/ml, respectively).. Active VD compounds via downregulation of RANTES production exert a potential role as a complementary element in the therapy of chronic rhinosinusitis with NP. Compounds consisting of budesonide and VD derivate have an advantage over both drugs used in monotherapy.

Topics: Anti-Inflammatory Agents; Budesonide; Calcitriol; Cells, Cultured; Chemokine CCL5; Dihydroxycholecalciferols; Drug Synergism; Fibroblasts; Glucocorticoids; Humans; Nasal Polyps; Rhinitis; Sinusitis; Vitamin D

Nasal polyposis (NP) is treated with topical glucocorticoids (GC). Some patients require endoscopic nasal surgery because GC treatment is ineffective. To exert its function, the GC needs to bind with the GC receptor (GR) and the GC-GR complex moves to the cell nucleus. Our aim was to establish whether the poor response to GC is due to an alteration in the translocation of the GR to the nucleus.. We performed nasal fibroblast cell cultures from seven healthy controls and 12 patients with NP and asthma. Fibroblasts were incubated with budesonide or dexamethasone (10(-7) M) for different times (30 min to 4 h) and GR translocation was analyzed by immunocytochemistry.. Both GC induced GR translocation in every group, doubling its concentration in the cell nucleus (30 min) compared to baseline. There were no differences in GR translocation between controls and patients, nor differences related to the severity of asthma or intolerance to non-steroidal anti-inflammatory drugs (NSAIDs). Atopic subjects showed a decrease in GR translocation with budesonide (1 h, 3 h and 4 h, P<0.05) and dexamethasone (30 min and 2 h, P<.05).. The insensitivity to GC treatment does not appear to be due to an alteration in GR translocation to the nucleus. Neither does the severity of asthma or intolerance to NSAIDs appear to alter GR translocation. The association between atopy and the alteration in GR function deserves further investigation.

Topics: Active Transport, Cell Nucleus; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Asthma, Aspirin-Induced; Budesonide; Cell Nucleus; Cells, Cultured; Dexamethasone; Drug Resistance; Fibroblasts; Glucocorticoids; Humans; Nasal Mucosa; Nasal Polyps; Receptors, Glucocorticoid; Severity of Illness Index

Topics: Active Transport, Cell Nucleus; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Asthma, Aspirin-Induced; Budesonide; Cell Nucleus; Cells, Cultured; Dexamethasone; Drug Discovery; Drug Resistance; Fibroblasts; Glucocorticoids; Humans; Hypersensitivity, Immediate; Nasal Mucosa; Nasal Polyps; Receptors, Glucocorticoid

The aim of the present study was to evaluate the in vivo regulation of cyclooxygenase-2 in nasal polyps. In total, 65 patients with nasal polyps were randomly (3:1) treated with (n = 51; 33 with asthma) or without (n = 14) oral prednisone and intranasal budesonide for 2 weeks plus intranasal budesonide for 10 additional weeks. Biopsies were obtained at baseline and after 2 and 12 weeks of treatment. All samples were analysed for cyclooxygenase-1 and cyclooxygenase-2 mRNA. Attempts were made to detect cyclooxygenase-2 protein. At baseline, cyclooxygenase-1 and cyclooxygenase-2 expression did not differ between polyps from nonasthmatic and asthmatic patients. Cyclooxygenase-1 mRNA was unchanged by glucocorticoid treatment, while cyclooxygenase-2 mRNA increased in glucocorticoid-treated patients at week 2 compared with baseline and then decreased at week 12. Within subgroups, increased cyclooxygenase-2 mRNA was found at week 2 in polyps from nonasthmatic and asthmatic patients compared with baseline. At week 12, cyclooxygenase-2 expression remained high in nonasthmatics while it decreased in asthmatics. Cyclooxygenase-2 protein was not detected under any circumstances. Glucocorticoid therapy enhances cyclooxygenase-2 expression in vivo in nasal polyps, a finding that does not follow the generally accepted assumption that cyclooxygenase-2 expression is suppressed by glucocorticoids.

Topics: Administration, Oral; Adult; Asthma; Biopsy; Budesonide; Cyclooxygenase 1; Cyclooxygenase 2; Female; Gene Expression Regulation; Glucocorticoids; Humans; Male; Middle Aged; Nasal Polyps; Prednisone; RNA, Messenger

Vitamin D (VD) and its different analogues, besides their classic role as regulators of calcium and phosphor homeostasis, have emerged as a large family of antiproliferative agents. Such properties suggested VD potential as a therapy for chronic inflammatory diseases, including nasal polyposis (NP). NP growth involves both an inflammatory process and the proliferation of fibroblast as an important factor inducing aberrations in the phenotype of the epithelium. The aim of this study was to investigate the possible influence of 1alpha,25-dihydroxyvitamin D(3) (calcitriol) and 1alpha,24(R)-dihydroxyvitamin D(3) (tacalcitol) in monotherapy and in combination with budesonid R (BR) on NP fibroblast proliferation.. The study involved 26 samples of NP. NP cells were cultured on 96-well plates beginning with a concentration of 5 x 10(3) cells per well with RPMI 1640 medium supplemented with antibiotics and 10% foetal bovine serum. After the fourth to sixth passage the medium was replaced with a nutrient medium with calcitriol or tacalcitol in a defined concentration (from 10(-9) M to 10(-3) M) alone or in combination with BR in 1:1, 1:3 or 3:1 ratios, each at concentrations from 10(-5) M to 10(-3) M.. Growth inhibition of nasal fibroblasts exposed to calcitriol or tacalcitol was noted. Significant antiproliferating activity was observed at calcitriol concentrations of 10(-4) M and 10(-3) M after 48 h, and at a concentration of 10(-3) M after 72 h with the percentage of proliferating cells reduced to 30% compared to the control samples (P < 0.05). In cells treated with tacalcitol the maximal effect was seen at 10(-4) M after 48 h and at 10(-3)M after 72 h with a 60% inhibition with respect to the control (P < 0.05). The inhibition of fibroblast proliferation reached the maximal level when they were exposed to calcitriol: BR (1 : 1) or tacalcitol: BR (1 : 1), each at a concentration of 10(-4) M, after 72 h (82% and 69%, respectively).. The antiproliferative activity of calcitriol and tacalcitol in NP cultures was confirmed. Because of its lower toxicity and higher activity tacalcitol seems to be the more promising agent in NP therapy, both as a single medication and in treatment protocols with BR.

Topics: Apoptosis; Budesonide; Calcitriol; Cell Proliferation; Cells, Cultured; Cholecalciferol; Dihydroxycholecalciferols; Dose-Response Relationship, Drug; Fibroblasts; Humans; Nasal Mucosa; Nasal Polyps; Rhinitis; Sinusitis

To evaluate the potential for hypothalamic-pituitary-adrenal (HPA) axis suppression by budesonide nasal irrigations in the treatment of refractory chronic rhinosinusitis with polyposis (CRSwP).. Retrospective, descriptive review of patient charts.. Tertiary care rhinology practice in an academic teaching hospital.. Eighteen adult subjects with CRSwP refractory to conservative medical therapy.. The charts of consecutive patients identified as being treated with topical budesonide in saline for nasal irrigation from January to October 2006 were reviewed. In all cases, pre- and posttreatment morning cortisol levels had been measured following at least 8 weeks of uninterrupted therapy. In addition, a subset of patients who continued therapy longer than 8 weeks had undergone the more sensitive adrenocorticotropic hormone (ACTH) stimulation test.. All pre- and posttreatment morning cortisol levels were within the normal range. For an 8-week treatment period, there was no evidence of HPA axis suppression (p=.4171). For patients who continued treatment beyond 8 weeks, ACTH stimulation did not detect HPA axis suppression. Furthermore, there were no issues with compliance or acceptability, nor were any adverse side effects reported.. Budesonide in saline sinonasal irrigation for the treatment of refractory CRSwP does not cause HPA axis suppression. The efficacy of this higher dose of steroid delivered locally would benefit from further study.

Topics: Adult; Budesonide; Chronic Disease; Cohort Studies; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Nasal Lavage; Nasal Polyps; Pituitary-Adrenal System; Retrospective Studies; Rhinitis; Sinusitis; Sodium Chloride; Treatment Outcome

To investigate the effect of intranasal glucocorticoids treatment on the expression of c-fos and c-myc nasal polyps.. Immunohistochemistry method was used to determine c-fos and c-myc expression in nasal polyps from patients with topical steroids treatment for 10-12 weeks and untreated patients.. The rate of c-fos expressing cases was 15% and the rate of c-myc expressing cases was 20% in nasal polyps from topical steroid treated patients, but in untreated patients, the rate of c-fos expressing cases was 80% and the rate of c-myc expressing cases was 85%. There were significant differences between two groups (P < 0.01). The c-fos and c-myc expression was remarkably downregulated in nasal polyps from topical steroid treated patients compared to untreated patients.. The results show that glucocorticoids may induce cell apoptosis in nasal polyps by depressing the c-fos and c-myc expression.

Topics: Adult; Budesonide; Case-Control Studies; Female; Glucocorticoids; Humans; Male; Nasal Polyps; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-myc

Fibroblasts are the main cells of the polyp architecture and play an important role in nasal polyposis through the release of biologically active factors. It has been recently shown that a number of differentiation factors and inflammatory mediators may be involved in nasal polyps growth, but there are not many studies on nasal polyps fibroblast proliferation. In this study, we investigated the influence of Ibuprofen, Nimesulid and Rofecoxib, cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) inhibitors and Budesonide on the nasal polyps fibroblasts proliferation.. Nasal fibroblasts were grown from nasal polyp tissue obtained during usual surgical procedure. Fibroblast proliferation was measured by 3H-thymidine incorporation.. Ibuprofen and Nimesulid showed no influence on fibroblast proliferation. Inhibition of fibroblast proliferation was shown by Rofecoxib at a concentration of 10,000 nM and Budesonide at a concentration of 100 nM.. Proliferation of nasal polyps fibroblasts may be inhibited by Budesonide and a specific COX-2 inhibitor -Rofecoxib.

Topics: Anti-Inflammatory Agents; Budesonide; Cell Proliferation; Cells, Cultured; Fibroblasts; Humans; Ibuprofen; Lactones; Nasal Polyps; Sulfonamides; Sulfones

Nasal polyposis is a model for the study of inflammatory processes. We analyzed the expression of galectin-7, a growth regulator, in surface epithelium, glandular epithelium, and connective tissue in human nasal polyps, and examined the effect of the glucocorticoid budesonide on its expression in human nasal polyps ex vivo.. Using quantitative, computer-assisted microscopy and immunohistochemistry, we measured galectin-7 expression in nine nasal polyps obtained by surgical resection. Five polyps came from allergic patients and four came from non-allergic patients.. Galectin-7 was expressed in all three polyp tissues analyzed. Treatment of polyps from allergic and non-allergic patients with 50 ng/ml budesonide increased the extent of galectin-7 expression in the connective tissue (p = 0.01). Conversely, budesonide at this concentration did not apparently affect galectin-7 expression in glandular epithelium; only a slight decrease in the percentage of the galectin-7-immunopositive cells was observed. In the surface epithelium of nasal polyps from non-allergic patients, the percentage of galectin-7-immunopositive cells was decreased (p = 0.03) by treatment with 250 ng/ml budesonide. In nasal polyps from allergic patients, this percentage was increased by treatment with 50 ng/ml budesonide (p = 0.0001).. These data are consistent with a role for galectin-7 in the regulation of cell growth through a pro-apoptotic effect. Galectin-7 expression coincides with the degree of epithelial stratification, and is subject to upregulation in the connective tissue in response to treatment with 50 ng/ml budesonide. Budesonide modulates galectin-7 expression differently in the surface epithelia of polyps from allergic and non-allergic patients.

Topics: Anti-Inflammatory Agents; Budesonide; Connective Tissue; Galectins; Humans; Hypersensitivity; Nasal Mucosa; Nasal Polyps; Tissue Culture Techniques

Macrophage migration inhibitory factor (MIF) is a counterregulatory lymphokine for glucocorticoid action within the immune system. To provide further insights into the way expression of pleiotropically acting MIF is modulated by glucocorticoids, we investigated the influence of the glucocorticoid budesonide on the level of expression of MIF in a model of human nasal polyposis by quantitative immunohistochemical analysis. Ten nasal polyps obtained from surgical resection were maintained for 24 hours in the presence of 3 budesonide concentrations: 10, 50, and 250 ng/mL. As quantitatively demonstrated by computer-assisted microscopy, 50 ng/mL induced an increase in MIF expression in the surface epithelium and a decrease in MIF expression in the glandular epithelium. At the 250 ng/mL dose, the inverse effect was induced. Evidently, surface and glandular epithelia react nonuniformly to the glucocorticoid regarding MIF presence, adding dependence on the cell type to the regulatory network.

Topics: Anti-Inflammatory Agents; Budesonide; Connective Tissue; Humans; Immunohistochemistry; Macrophage Migration-Inhibitory Factors; Nasal Polyps; Respiratory Mucosa

To explore the follow-up time and the effect of intranasal glucocorticoid for chronic sinusitis and nasal polyps after endoscopic sinus surgery.. After the endoscopic sinus surgery, 30 cases of sinusitis and nasal polyps accepted the postsurgical care for the cavity, sinus washing, and intranasal local glucocorticoid rhinocort, then the clinical effects was follow-up surveyed.. Intranasal local glucocorticoid could evidently reduce the courses of dry and the epithelial metaplasia of nasal cavity and sinus.. After the endoscopic sinus surgery, follow-up of endoscopic sinus, postsurgical care for the cavity and intranasal local glucocorticoid played equally important roles in treating sinusitis and nasal polyps.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Chronic Disease; Endoscopy; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nasal Polyps; Postoperative Care; Sinusitis

To conduct a cost-effectiveness study of nasal budesonide versus surgical treatment in the management of nasal polyps.. A decision-tree model reflecting two different treatment strategies for nasal polyps in Sweden was developed. The first strategy was initial polypectomy, performed under three different sets of circumstances: inpatient functional endoscopic surgery, outpatient evulsion with sedation, or outpatient evulsion with local anaesthesia; all treatments were followed by intranasal treatment with budesonide (Rhinocort) 128 microg twice daily. The second strategy was initial intranasal treatment with budesonide 128 microg twice daily.. Healthcare provider perspective.. After 1 month, treatment with nasal budesonide was classified as a success (82.5%) or a failure (17.5%) based on clinical study data. In cases of success, the treatment was continued, and in cases of failure, polypectomy was undertaken, followed by budesonide 128 microg twice daily. Treatments were evaluated after 4 months using prices from the Central Hospital in Skövde, Sweden. The expected reduction in cost from using initial nasal budesonide treatment compared with the different alternatives of polypectomy were 9760 Swedish kronors (SEK) for inpatient functional endoscopic surgery, SEK2747 for outpatient evulsion with sedation, and SEK672 for outpatient evulsion with anaesthesia (1998 values). Nasal budesonide 128 microg twice daily treatment for nasal polyps revealed a potential reduction in costs of 53% compared with the primary surgery approach.. Initial treatment of nasal polyps with nasal budesonide provides lower costs than treatment with initial polypectomy with maintained effectiveness.

Topics: Administration, Intranasal; Anti-Inflammatory Agents; Budesonide; Clinical Trials as Topic; Cost-Benefit Analysis; Decision Trees; Health Care Costs; Humans; Models, Economic; Nasal Polyps; Treatment Outcome

Histologic and immunohistologic features of nasal polyps (NP) are similar to those observed in asthma, thus suggesting a similar immunopathology.. The primary objective of this study was to further understand the anti-inflammatory and immunoregulatory effects of locally delivered corticosteroids. To this end, the effect of intranasal budesonide on the expression of specific cytokines, lymphocyte subsets, and epithelial remodeling in this model of airway tissue inflammation were studied.. We used immunohistochemical techniques to examine nasal mucosae (NM) from healthy individuals and nasal polyp (NP) tissues from patients with nasal polyposis obtained before and after intranasal budesonide treatment.. First, the density of CD8(+) cells was markedly increased in NP tissues after intranasal budesonide treatment from 16.1 +/- 8.4 (M +/- SEM) per mm(2) to 39.9 +/- 24.1. Second, the density of cells immunoreactive for IL-4, IL-5, IFN-gamma, IL-12, and TGF-beta in NP was significantly greater than in control NM tissues. The density of IL-4(+) and IL-5(+) cells in NP tissues significantly decreased after budesonide treatment from 40 +/- 12 to 17.8 +/- 8 and from 19.3 +/- 11 to 10.4 +/- 7, respectively. In contrast, the density of IFN-gamma(+) and IL-12(+) cells remained unchanged. In addition, we found that the density of TGF-beta(+) cells significantly increased after intranasal budesonide from 18 +/- 5 to 41 +/- 9. Third, damage to the entire length of the NP epithelium was quantified using a grading system. The epithelium of untreated NP was substantially damaged; remarkable epithelial restitution with no apparent changes in stromal collagen deposition was observed after intranasal budesonide treatment.. These findings demonstrate that intranasal budesonide induced an increase in CD8 population and a selective regulatory effect on tissue cytokine expression. Furthermore, intranasal budesonide promoted epithelial remodeling. We hypothesize that these immunoregulatory and remodeling effects elicited by steroids might be, at least in part, mediated by the induction of TGF-beta.

Topics: Administration, Intranasal; Adult; Budesonide; Chronic Disease; Cytokines; Eosinophils; Female; Humans; Immunohistochemistry; Male; Middle Aged; Nasal Mucosa; Nasal Polyps; T-Lymphocyte Subsets; Transforming Growth Factor beta

To study the expression of transforming growth factor alpha, beta 1 in hyperplastic tissue after endoscopic polypectomy and the effect of corticosteroid.. Forty patients with nasal polyps were divided into two groups randomly: corticosteroid group (n = 20) with topical application of Budesonide (BUD, 400 micrograms/d) after endoscopic polypectomy and control group (n = 20) without corticosteroid after surgery. The hyperplastic tissues in operative cavity obtained in the 1st and 8th weeks after operation were studied with HE staining and immunohistochemistry technique respectively.. Morphological changes of hyperplastic tissue after endoscopic polypectomy included pseudostratified epithelium, highly edematous lamina proper and inflammatory cells infiltration, in which the main infiltrative cells were eosinophils (67.5%). Transforming growth factor alpha(TGF alpha) protein was highly expressed in epithelial cells, grand cells and inflammatory cells in the hyperplastic tissue. Transforming growth factor beta 1 (TGF beta 1) protein was highly expressed in inflammatory cells in the hyperplastic tissue. The expression of TGF alpha and beta 1 was significantly decreased after topical BUD spray (P < 0.01, 0.05).. Transforming growth factor alpha and beta 1 may play an important role in the formation and recurrence of nasal polyps.

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Female; Humans; Hyperplasia; Male; Nasal Mucosa; Nasal Polyps; Transforming Growth Factor alpha; Transforming Growth Factor beta

We characterized the anti-inflammatory effects of budesonide on the expression of adhesion molecules involving Lewis(a) (Le(a)) epitope, its sialylated derivative (sLe(a)), and their respective binding sites in human nasal polyposis. By computer-assisted microscopy, we quantitatively characterized the level of histochemical expression of L- and P-selectins, sialylated and nonsialylated Le(a) epitopes, and their respective binding sites in both surface epithelium and glandular epithelium of human nasal polyps obtained from surgical resection, maintained under ex vivo tissue culture conditions for 24 hours, and treated or not with budesonide. Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) were chosen as methodological controls, because data already published in the literature clearly indicated budesonide-mediated effects on ICAM-1 and VCAM-1 levels of expression. The present data show that budesonide significantly modified the levels of expression of ICAM-1 and VCAM-1, and to a lesser extent that of P-selectin, in the surface and glandular epithelia. Budesonide markedly decreased the levels of expression of the binding sites for both Le(a) and sLe(a), while those of Le(a) and sLe(a) remained globally unchanged. In conclusion, the present study documents that glucocorticoid-induced effects can encompass receptors for Le(a) epitopes different from E- and P-selectins on epithelial cells of human nasal polyps.

Topics: Anti-Inflammatory Agents; Binding Sites, Antibody; Budesonide; CA-19-9 Antigen; Culture Techniques; Drug Evaluation, Preclinical; E-Selectin; Eosinophils; Epitopes; Gangliosides; Gene Expression Regulation; Humans; Hypersensitivity; Immunohistochemistry; Intercellular Adhesion Molecule-1; Lewis Blood Group Antigens; Nasal Polyps; P-Selectin; Vascular Cell Adhesion Molecule-1

Topics: Administration, Intranasal; Adult; Aerosols; Androstadienes; Anti-Inflammatory Agents; Budesonide; Child; Female; Fluticasone; Humans; Male; Mometasone Furoate; Nasal Polyps; Pregnadienediols; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Singapore; Sinusitis; Triamcinolone Acetonide

The objective of this study was to determine whether the allergy factor affects therapeutic response of nasal polyps. A total of 68 patients were enrolled between 1 October 1999 and 1 January 2002 at the Allergy and Rhinology Clinic, Faculty of Medicine, Songklanagarind Hospital. Allergy skin prick test was performed in order to divide patients into a positive skin test group and a negative skin test group. Their medical history was recorded including age, sex, nasal symptoms, concomitant diseases and medications. Patients in both groups were treated over a 6 week period with Budesonide nasal spray. Nasal symptoms, polyp size, nasal and oral expiratory peak flow were evaluated at each visit. Overall assessment of treatment efficacy was evaluated by patients at 3 and 6 weeks after treatment. The mean value of these variables during treatment and a baseline period were compared within and between groups. After 3 and 6 weeks of treatment of nasal polyps with topical Budesonide nasal spray, nasal symptoms, polyp size, nasal and oral expiratory peak flow index and overall response to treatment were improved within both groups. Comparing the two groups, there were greater improvements in the negative skin test group compared to the positive skin test group in all variables. These differences in variable scores between groups showed a tendency to increase overtime after treatment was terminated. The results demonstrate that nasal polyps with positive allergen skin test had less improvement compared to nasal polyps with negative allergen skin test in all nasal signs and symptoms and these differences in improvement showed a tendency to increase over time after treatment.

Topics: Administration, Topical; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Cohort Studies; Female; Glucocorticoids; Humans; Male; Middle Aged; Nasal Polyps; Peak Expiratory Flow Rate; Prospective Studies; Respiratory Hypersensitivity; Skin Tests; Thailand; Time Factors; Treatment Outcome

Because of the importance of galectins for various cellular activities, the influence of the glucocorticoid budesonide on the level of expression of galectins-1 and -3 was investigated in human nasal polyposis. Ten nasal polyps obtained from surgical resection were maintained for 24 hours in the presence of various concentrations of budesonide. As quantitatively demonstrated by means of computer-assisted microscopy, 250 ng/ml (the highest dose tested) induced a pronounced increase of galectin-1 expression. This feature was observed in nasal polyps from allergic patients but not in those from nonallergic patients. Since eosinophils represent the main inflammatory cell population in nasal polyps, we investigated the effect of galectin-1 on their migration levels by means of quantitative phase-contrast computer-assisted videomicroscopy. Our results show that galectin-1 (coated on plastic supports) markedly reduced the migration levels of eosinophils in comparison to P-selectin. On the cellular level, marked modifications in the polymerization/depolymerization dynamics of the actin cytoskeleton (as revealed by means of computer-assisted fluorescence microscopy) and, to a much lesser extent, an increase in the adhesiveness of eosinophils to tested substrata were detectable. The present study therefore reveals a new galectin-1-mediated mechanism of action for glucocorticoid-mediated anti-inflammatory effects.

Topics: Administration, Topical; Anti-Inflammatory Agents; Antigens, Differentiation; Binding Sites; Biopolymers; Blotting, Western; Budesonide; Cell Adhesion; Cell Movement; Culture Techniques; Eosinophils; Galectin 1; Galectin 3; Glucocorticoids; Hemagglutinins; Humans; Nasal Polyps; Reverse Transcriptase Polymerase Chain Reaction

We investigated the effect of budesonide and nedocromil sodium on the secretion of IL-6 and IL-8 by cultured epithelial cells from healthy nasal mucosa and nasal polyps. Human epithelial cell conditioned media was generated with fetal calf serum (FCS) in the presence or absence of budesonide and/or nedocromil sodium. Budesonide inhibited FCS-induced IL-6 and IL-8 release in a dose-dependent manner. The IC25 (25% inhibitory concentration) of budesonide on IL-6 release was higher in nasal polyp than in nasal mucosa epithelial cells (34 nM vs. 200 pM). The IC25 of budesonide on IL-8 release was higher in nasal mucosa than in nasal polyps (145 pM vs. 4 pM). Nedocromil sodium caused a dose-related inhibitory effect on IL-8 release from nasal mucosa (IC25, 207 nM), while it only had a significant effect in nasal polyps at 10(-5) M. Nedocromil sodium had no effect on IL-6 release. The inhibitory effect of budesonide was higher than that of nedocromil sodium on both nasal polyps and nasal mucosa. Budesonide and nedocromil sodium may exert their anti-inflammatory action in the respiratory mucosa by modulating the secretion of IL-6 and IL-8. The different effect of budesonide and nedocromil sodium on IL-6 and IL-8 release may be explained by differences in the mechanisms which regulate the upregulation of these cytokines in inflammatory responses.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Cells, Cultured; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-6; Interleukin-8; Male; Microbial Sensitivity Tests; Middle Aged; Nasal Mucosa; Nasal Polyps; Nedocromil; Statistics, Nonparametric

To assess the effects of topical nasal steroid application on the infiltration and activation of eosinophils in nasal polyps.. Nasal polyps from intranasal budesonide treated patients (n = 16) and untreated patients (n = 16) were investigated. The samples were stained with histochemical and ABC immunohistochemical methods.. The majority of eosinophils in nasal polyps were activated eosinophils. Compared with untreated polyps, the proportion of activated eosinophils (EG2+/eosinophil ratio) was significantly less in steroid-treated polyps. Although the numbers of total eosinophils and actived eosinophils were lower in steroid-treated polyps, both of the differences were not statistically significant.. It emphasized that the actived eosinophils play a key role in the pathogenesis of nasal polyps. The effects of intranasal steroid treatment on the number of eosinophils (total and activated) was more profound then on the proportion of activated eosinophils.

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents; Budesonide; Eosinophils; Female; Humans; Male; Nasal Polyps

Nasal epithelial cells maintain eosinophil survival by secreting granulocyte/macrophage colony-stimulating factor (GM-CSF). Corticosteroids antagonize eosinophil viability induced by GM-CSF. We investigated the effect of topical corticosteroids and nedocromil sodium on the release of GM-CSF from nasal polyp epithelial cells. Epithelial cells were obtained from 19 patients undergoing nasal polypectomy and cultured. After reaching confluence, cultured cells were stimulated with 10% foetal calf serum in the absence and presence of four topical corticosteroids and nedocromil sodium for 48 h. GM-CSF was measured by enzyme linked immunosorbent assay (ELISA). Fluticasone propionate was the most potent inhibitor of GM-CSF release (IC25 = 46 pM) closely followed by budesonide (IC25 = 4 nM), beclomethasone dipropionate (IC25 = 40 nM) and triamcinolone acetonide (IC25 = 75 nM). Nedocromil sodium had no effect on GM-CSF release. We conclude that the effect of topical steroids on reducing eosinophil infiltration in nasal polyps may be due in part to downregulation, among other cytokines, of epithelial GM-CSF production which prolongs eosinophil viability. Quantitatively, fluticasone propionate inhibited GM-CSF production more potently than budesonide, beclomethasone dipropionate and triamcinolone acetonide.

Topics: Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Cells, Cultured; Eosinophils; Epithelial Cells; Female; Glucocorticoids; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Nasal Polyps; Nedocromil; Triamcinolone Acetonide

Topics: Aged; Anti-Inflammatory Agents; Budesonide; Humans; Male; Nasal Polyps; Treatment Outcome

Airway inflammation in patients with nasal polyps is characterized by the increased presence of eosinophils, the numbers of which are reduced after treatment with topical corticosteroids. Because eosinophilic responses in the airways are in part due to eosinophil progenitor differentiation, we hypothesized that CD34, a cell surface, sialomucinlike glycoprotein that specifically marks hemopoietic progenitors and endothelium, would be expressed in nasal polyp tissue. We sought to identify CD34(+) leukocytes or endothelial cells in nasal polyps. We also investigated the effect of the topical corticosteroid budesonide on the numbers of CD34(+) cells and vessels in nasal polyps. To accomplish this, we performed immunostaining for CD34 protein in tissue sections of nasal polyps from topical steroid-treated and -untreated groups of patients, as well as from one patient before and after systemic corticosteroid therapy. We also examined myeloid colony formation by isolated polyp mononuclear cells, and performed flow cytometry to detect the presence of CD34(+)/CD45(+) cells within these isolated populations. We also examined the in vitro effects of steroids on human umbilical vein endothelial cell (HUVEC) expression of CD34. We detected CD34-immunoreactive mononuclear cells and blood vessels in the lamina propria of all nasal polyps. CD34(+) mononuclear cells resembled immature hemopoietic cells morphologically. Mononuclear cell fractions from polyps contained myeloid colony-forming cells and cells bearing CD45, a pan-leukocyte marker, as well as CD34, and gated as true hemopoietic blast cells. The numbers of CD34(+) cells and CD34(+) vessels in steroid-treated nasal polyps were significantly higher than in steroid-untreated nasal polyps (15.67 +/- 2.08 cells/10 hpf, versus 5.33 +/- 1.36 cells/10 hpf, P = 0.002; 101.25 +/- 6.24 vessels/0.5 mm2 of lamina propria, versus 57.22 +/- 8.00 vessels/0.5 mm2 of lamina propria, P = 0.0008, respectively). A similar upregulation of CD34 immunostaining, especially for mononuclear cells, was observed in one patient after systemic corticosteroid therapy. Steroid treatment in vitro of HUVECs did not result in enhanced CD34 expression. Both CD34(+)/CD45(+) mononuclear cells and CD34(+) endothelial cells are present within nasal polyps, with higher numbers in patients who have received topical corticosteroid treatment. Because enhancement of CD34 expression was not seen in cultured umbilical vein endothelial cells treated in vitro w

Topics: Administration, Topical; Adrenal Cortex Hormones; Adult; Aged; Anti-Inflammatory Agents; Antigens, CD34; Budesonide; Endothelium, Vascular; Female; Glucocorticoids; Hematopoietic Stem Cells; Humans; Immunohistochemistry; Male; Middle Aged; Nasal Polyps; von Willebrand Factor

We investigated the effect of a potent synthetic steroid, budesonide (BUD), on the survival of nasal polyp (NP) derived eosinophils (EOS). BUD, at the highest dose used, 10(-6) M, decreased this survival but only by approximately one third. We speculated that the relatively small inhibitory effect of budesonide on the survival of NP-EOS could be the result of these EOS being exposed to substantial amounts of GM-CSF, IL-5 or IL-3. In this regard, we detected 148 pg of GM-CSF per 150 mg of tissue, which approximately contained 106 of eosinophils, in the supernatant of NP explants for 24 h without any stimulation. Contents of both IL-5 and IL-3 were much less. We further studied survival of PB-EOS exposed to rhGM-CSF and found that 10(-6) M of BUD could only inhibit by less than one third the survival of PB-EOS exposed to an amount of rhGM-CSF, similar to that detected in the supernatant of NP explants. In addition, we exposed PB-EOS to 200 pg/ml of rhGM-CSF for a relatively long period of time (4 days) in order to mimic chronic exposure in the tissue and found that the survival of these cells was prolonged to the extent similar to that observed in NP-EOS. Our data suggests that the prolonged spontaneous survival of NP-EOS ex vivo is likely the result of sustained in vivo exposure to GM-CSF and budesonide has a smaller inhibitory effect in the survival of these eosinophils as compared to those from peripheral blood.

Topics: Administration, Topical; Anti-Inflammatory Agents; Budesonide; Cell Survival; Cytokines; Drug Interactions; Eosinophils; Glucocorticoids; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; In Vitro Techniques; Nasal Polyps; Recombinant Proteins

Nasal polyposis is a result of a chronic inflammatory disorder in the upper airways. In vitro studies have revealed that extravasation of leucocytes requires interactions between several sets of adhesion molecules expressed on the circulating leucocytes and the vascular endothelium. Therefore, the endothelial expression of intercellular adhesion molecule-1 (ICAM-1) in biopsies from polyps and inferior turbinates was investigated by the use of immunohistochemical staining. Biopsies were obtained from 11 patients suffering from nasal polyposis before, during and after treatment with 100 microg budesonide (Rhinocort Turbuhaler) in each nostril twice daily. Before, during and after treatment, ICAM-1 was expressed in the majority of vessels in polyps and mucosa of inferior turbinates. The intensity of endothelial ICAM-1 expression in polyps was significantly reduced during topical glucocorticoid treatment compared with the pretreatment and posttreatment levels (p < 0.005). In biopsies from the inferior turbinates, the intensity of the endothelial ICAM-1 expression was lower during treatment than after discontinuation of medical treatment (p < 0.005). In conclusion, topical budesonide treatment seems to downregulate ICAM-1 expression on the vascular endothelium in nasal polyps. Such an effect may interfere with leucocyte extravasation and partially account for the anti-inflammatory effect of local glucocorticoid treatment in human nasal polyposis.

Topics: Administration, Topical; Adult; Aged; Anti-Inflammatory Agents; Biopsy; Budesonide; Cell Adhesion Molecules; Endothelium, Vascular; Female; Glucocorticoids; Humans; Immunohistochemistry; Male; Middle Aged; Nasal Polyps; Statistics, Nonparametric

Mast cells are increased in nasal polyp (Np) and allergic rhinitis (AR) tissue and are suppressed by topical corticosteroid treatment. Stem cell factor (SCF), a mast cell growth and survival factor, may explain these phenomena.. We investigated structural cell gene expression and production of SCF in nasal tissues in patients who had received and who had not received in vivo intranasal corticosteroid therapy.. Northern blot analyses for messenger RNA and ELISA for biologically active SCF protein from cultured Np epithelial cells and fibroblasts were performed. Immunostaining for SCF in cultured and tissue nasal structural cells in the presence or absence of steroid treatment was also performed.. We detected significant expression of SCF mRNA and protein by cultured Np epithelial cells and Np fibroblasts; Np fibroblast SCF supported the differentiation of mast cells in vitro. There were more immunoreactive SCF-positive Np epithelial cells in patients with AR than in control subjects (97.2 +/- 2.8 vs 45.6 +/- 22.0%; p < 0.0001). SCF that could be immunostained was significantly diminished overall in Np structural cells in the group given in vivo steroid treatment, with a modest (trend to significant) effect on any given cell type analyzed. In vitro treatment with budesonide of SCF-producing fibroblasts demonstrated inhibition of unstimulated, primary Np fibroblasts but not of IL-1-stimulated fibroblasts or transformed cell lines.. Human Np and AR tissue structural cells express and produce increased SCF. Our in vitro studies suggest that intranasal steroids blunt SCF expression in Nps, an effect that may be responsible for a decrease in mast cells and symptoms.

Topics: Administration, Topical; Adrenal Cortex Hormones; Adult; Anti-Inflammatory Agents; Blotting, Northern; Budesonide; Cells, Cultured; Chymases; Epithelial Cells; Epithelium; Female; Fibroblasts; Gene Expression; Humans; Immunohistochemistry; Interleukin-1; Male; Mast Cells; Middle Aged; Nasal Polyps; Pregnenediones; Rhinitis, Allergic, Seasonal; RNA, Messenger; Serine Endopeptidases; Stem Cell Factor; Tryptases

Topics: Administration, Inhalation; Administration, Intranasal; Aerosols; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Glucocorticoids; Humans; Nasal Polyps; Pregnenediones; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

A follow-up study on 180 patients treated for the first time for nasal polyps was performed. The follow-up period was from 1 to 8 years with a median of 57 months. The majority of patients had postoperative topical steroid treatment. 65.6% of patients had one polypectomy, 17.8% had two polypectomies, 10% had 3, 2.8% had 4, and 3.9% of patients had 5-10 polypectomies performed during the follow-up period. Patients without asthma, acute recurrent or chronic sinusitis, acetylsalicylic acid intolerance, or allergy had fewer polypectomies and less topical steroid treatment than patients with these characteristics. The recurrence profile between the first and second polypectomy described with the life-table method showed a slow decline in the number of patients with only one polypectomy. The time span needed before significant clinical symptoms occurred after the first polypectomy indicates that not all primary polyp patients are prone to recurrence. Nasal polyps is probably a manifestation of different clinical and aetio-pathogenetic entities. Further identification of such entities is needed to improve treatment strategy.

Topics: Adolescent; Adult; Aerosols; Aged; Aged, 80 and over; Beclomethasone; Budesonide; Child; Combined Modality Therapy; Denmark; Female; Fluocinolone Acetonide; Follow-Up Studies; Humans; Male; Middle Aged; Nasal Polyps; Pregnenediones; Recurrence

Topical nasal corticosteroid therapy produces clinical improvement in patients with nasal polyposis. To examine the mechanisms of steroid effect, we quantified the number of inflammatory cell types as well as the expression of relevant cell markers in nasal polyps from steroid treated patients (n = 11) and polyps from untreated patients (n = 10) judged to require polypectomy for symptomatic relief. We found that the majority of eosinophils in these tissues were in the stromal layers, and that the proportion of activated eosinophils (EG2+ versus total eosinophil count) was significantly lower in polyps from patients treated with the topical nasal steroid budesonide, 200 to 400 micrograms/d for 1 mo, than in polyps from untreated patients. We also found that in polyps from treated patients, the superficial stromal layer (SSL) and deep stromal layer (DSL) both contained a significantly lower tissue density of lymphocytes of CD3, CD4, and CD8 subsets. Treatment was also associated with a lower, albeit nonsignificant, expression of ICAM-1 and HLA-DR in the epithelium. The tissue density of CD14+ cells (monocyte/macrophage) and of tryptase+ cells (mast cells) was the same in the two groups. These findings demonstrate tissue effects of topical corticosteroid treatment which may point to the mechanisms of therapeutic benefit. In addition, these observations illustrate the value of markers that indicate cell functional activity rather than just cell numbers.

Topics: Administration, Intranasal; Budesonide; Eosinophils; Female; Glucocorticoids; Histocytochemistry; Humans; Immunohistochemistry; Male; Middle Aged; Nasal Polyps; Pregnenediones; Rhinitis; Statistics, Nonparametric

Clinical parameters of 72 patients who were operated upon for nasal polyps were evaluated as well as biopsy specimens of the mucosa of the middle and inferior turbinates of 41 of these patients. Biopsies were taken at the time of endoscopic sinus surgery (ESS), after 6 months and after 1 year in 23 patients. During the follow-up period the patients were treated with topical corticosteroids (budesonide). At the time of ESS significantly more CD8+ (suppressor/cytotoxic) cells than CD4+ (helper/inducer) cells were found in the middle and inferior turbinates. At 6 months significantly more CD4+ cells were found than at the time of ESS, whereas at 1 year the number of CD4+ cells had decreased and was lower than at 6 months. These data support the theory that the occurrence of nasal polyps is associated with T-cell-dependent disturbances. Clinical evaluation revealed that most of the patients with chronic airway obstruction had better pulmonary functions postoperatively or required less medication for lung disease. These findings show that ESS combined with topical corticosteroids has a positive effect on upper and lower respiratory tract pathology.

Topics: Administration, Topical; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Antigens, CD; Antigens, Differentiation, B-Lymphocyte; Antigens, Differentiation, T-Lymphocyte; Budesonide; CD2 Antigens; CD4-CD8 Ratio; Cell Adhesion Molecules; Combined Modality Therapy; Endoscopy; Glucocorticoids; Humans; Lectins; Lymphocytes; Middle Aged; Nasal Mucosa; Nasal Polyps; Pregnenediones; Receptors, Immunologic; Sialic Acid Binding Ig-like Lectin 2