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Acta Biochimica Polonica Sep 2023This study aimed to investigate the efficacy and safety of vitamin D supplementation in the treatment of allergic rhinitis (AR) using mometasone. A total of 140 patients... (Randomized Controlled Trial)
Randomized Controlled Trial
This study aimed to investigate the efficacy and safety of vitamin D supplementation in the treatment of allergic rhinitis (AR) using mometasone. A total of 140 patients with moderate and severe AR treated at our hospital between January 2017 and August 2020 were recruited as subjects for this study. The patients were randomly divided into control and experimental groups, with 70 patients in each group. Mometasone nasal spray was used in both groups, and vitamin D was administered to the experimental group for four weeks. The total nasal symptom scores (TNSS) and rhinoconjunctivitis quality of life questionnaire (RQLQ) were used to assess the efficacy of treatment. T lymphocyte subsets (CD3+, CD4+ and CD8+) and serum anti-inflammatory and proinflammatory cytokines such as interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were analyzed. The incidence of adverse reactions was recorded. Serum vitamin D levels were lower in patients with AR. After 4 weeks of treatment, total TNSS scores, T lymphocyte subsets (CD3+, CD4+), CD4+/CD8+ ratio, TNF-α, and total RQLQ scores were significantly reduced compared to the initial testing (P<0.05) in the two groups; CD8+, IFN-γ, and IL-10 levels as well as serum vitamin D were significantly increased compared to the initial test (P<0.05). The improvement in these parameters in the experimental group was significantly greater than that in the control group (P<0.05), except for sneezing and eye symptoms in the TNSS and RQLQ scores. It was concluded that vitamin D supplementation improves the therapeutic effect of mometasone nasal spray on AR and is thus recommended as an adjuvant therapy for moderate and severe AR.
Topics: Humans; Mometasone Furoate; Interleukin-10; Nasal Sprays; Quality of Life; Tumor Necrosis Factor-alpha; Rhinitis, Allergic; Vitamins; Vitamin D; Interferon-gamma; Dietary Supplements
PubMed: 37716008
DOI: 10.18388/abp.2020_6637 -
Patient Preference and Adherence 2023Combination intranasal corticosteroid and antihistamine sprays are a first-line treatment option for allergic rhinitis (AR), of which Azelastine Hydrochloride and...
Patient Satisfaction and Sensory Attributes of Nasal Spray Treatments of Olopatadine Hydrochloride/Mometasone Furoate Monohydrate and Azelastine Hydrochloride/Fluticasone Propionate for Allergic Rhinitis in Australia - An Observational Real-World Clinical Study.
PURPOSE
Combination intranasal corticosteroid and antihistamine sprays are a first-line treatment option for allergic rhinitis (AR), of which Azelastine Hydrochloride and Fluticasone Propionate nasal spray (AZE/FLU; Dymista), and Olopatadine Hydrochloride and Mometasone Furoate Monohydrate nasal spray (OLO/MOM; Ryaltris) are currently registered in Australia. As it is not known how patients value treatment attributes of current combination nasal sprays, this observational, real-world clinical study aimed to understand patients' satisfaction with, and importance of, treatment attributes of OLO/MOM and AZE/FLU using an Anchored Best-Worst Scaling (ABWS) exercise.
PARTICIPANTS AND METHODS
Four hundred and twenty-six adults in Australia with moderate to severe AR using either OLO/MOM or AZE/FLU completed an online survey incorporating an ABWS with 11 domains: 7 sensory (immediate taste of medication, aftertaste of medication, smell of medication, irritation to your nose, urge to sneeze, dripping out your nose/down your throat, dryness of your nose/throat) and 4 treatment-related (convenience, fast acting, duration of effect, and AR symptom control). The ABWS involved rescaling individual BWS scores using anchored ratings (0-10) for most and least satisfied/important domains to create a total satisfaction index (TSI) (0-100) to be compared across groups. Statistical comparisons were completed using ANOVA (TSI) and MANOVA (individual domains).
RESULTS
Participants using OLO/MOM ( = 68.26, = 1.39) had significantly higher TSI than participants using AZE/FLU (=62.78, = 0.70) ( < 0.001), significantly higher satisfaction on 7 of 11 domains and regarded 8 of 11 domains as significantly more important compared to participants using AZE/FLU (all < 0.05). Preferred domains were predominantly sensory attributes.
CONCLUSION
Current findings showed that participants using OLO/MOM were more satisfied with their overall treatment compared to participants using AZE/FLU, particularly with sensory attributes, thus highlighting the suitability of OLO/MOM for people with AR who value sensory attributes. Prescribers of AR treatments are encouraged to discuss treatment attributes with patients to facilitate shared decision-making.
PubMed: 36687019
DOI: 10.2147/PPA.S389875 -
Healthcare (Basel, Switzerland) Mar 2020Atopic dermatitis is the most common chronic inflammatory skin disease. It is often the first indicator of allergic diseases, and a certain percentage of patients are...
Atopic dermatitis is the most common chronic inflammatory skin disease. It is often the first indicator of allergic diseases, and a certain percentage of patients are affected by allergic rhinitis and/or asthma as a consequence. The study aimed to investigate the link between atopic dermatitis and comorbidity in family medicine. In the specialist family medicine practice Osijek, a retrospective study was conducted in the period from January 1, 2016 to July 1, 2017 on the percentage of patients with atopic dermatitis in the total number of patients, and their comorbid diseases. The data source was the E-chart. The results showed that 195 (10.53%) out of 2056 patients had atopic dermatitis, 80 (41%) patients had atopic dermatitis and allergic rhinitis, 34 (17.4%) asthma, 132 (67.7%) infections, 59 (30.3%) gastrointestinal disturbances, and 68 (34.3%) had mental disorders. Patients up to 18 years old were more likely to have infections, and adult patients were exposed to chronic stress. The most commonly used drug was loratadine (60.5%), while mometasone was the most commonly administered topical drug (40%). The result of this research showed the steps of the ˝atopic march˝. Atopic dermatitis is followed by changes in the skin and its progression to other organ systems in most of the patients.
PubMed: 32218222
DOI: 10.3390/healthcare8020070 -
Annals of Allergy, Asthma & Immunology... Nov 2022GSP301 nasal spray is a fixed-dose combination of the antihistamine olopatadine hydrochloride and the corticosteroid mometasone furoate. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
GSP301 nasal spray is a fixed-dose combination of the antihistamine olopatadine hydrochloride and the corticosteroid mometasone furoate.
OBJECTIVE
To evaluate the efficacy, safety, and tolerability of GSP301 in pediatric patients (aged ≥6 to <12 years) with seasonal allergic rhinitis (SAR).
METHODS
This double-blind, randomized, parallel-group study randomized 446 eligible patients 1:1 (GSP301 [olopatadine hydrochloride 665 μg and mometasone furoate 25 μg] or placebo) as 1 spray/each nostril twice daily for 14 days. The primary end point was change from baseline in average morning and evening subject-reported 12-hour reflective Total Nasal Symptom Score (rTNSS) over a 14-day treatment period analyzed using mixed-effect model repeated measures. Additional assessments included instantaneous Total Nasal Symptom Score, Pediatric Rhinoconjunctivitis Quality of Life Questionnaire, reflective Total Ocular Symptoms Score, instantaneous Total Ocular Symptoms Score, individual symptoms, Physician-assessed Nasal Symptom Score, and adverse events.
RESULTS
GSP301 showed clinically meaningful and statistically significant improvement in rTNSS vs placebo (-0.6; 95% confidence interval, -0.9 to -0.2; P = .001). Statistically significant improvements favoring GSP301 were shown for all individual rTNSS symptoms, instantaneous Total Nasal Symptom Score, and most of its individual symptoms, Physician-assessed Nasal Symptom Score (P = .01), and Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (P < .001). For ocular symptoms, numerical improvements favoring GSP301 were observed, with statistical significance achieved only for reflective "tearing/watering eyes" (P = .04). Treatment-emergent adverse events occurred in 12.0% and 10.4% of patients in the GSP301 and placebo groups, respectively. One subject (0.5%) (placebo group) experienced a serious adverse event (suspected viral meningitis) that was not related to the study treatment and was resolved.
CONCLUSION
GSP301 was well tolerated and efficacious for treating SAR symptoms in pediatric patients and showed a favorable safety profile.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03463031.
Topics: Humans; Child; Olopatadine Hydrochloride; Nasal Sprays; Rhinitis, Allergic, Seasonal; Quality of Life; Treatment Outcome; Mometasone Furoate; Double-Blind Method; Administration, Intranasal; Anti-Allergic Agents
PubMed: 35926824
DOI: 10.1016/j.anai.2022.07.029 -
The Cochrane Database of Systematic... Sep 2014Until recently, phimosis has been treated surgically by circumcision or prepuceplasty; however, recent reports of non-invasive treatment using topical corticosteroids... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Until recently, phimosis has been treated surgically by circumcision or prepuceplasty; however, recent reports of non-invasive treatment using topical corticosteroids applied for four to eight weeks have been favourable. The efficacy and safety of topical corticosteroids for treating phimosis in boys has not been previously systematically reviewed.
OBJECTIVES
We aimed to 1) compare the effectiveness of the use of topical corticosteroid ointment applied to the distal stenotic portion of the prepuce in the resolution of phimosis in boys compared with the use of placebo or no treatment, and 2) determine the rate of partial resolution (improvement) of phimosis, rate of re-stenosis after initial resolution or improvement of phimosis, and the rate of adverse events of topical corticosteroid treatment in boys with phimosis.
SEARCH METHODS
We searched the Cochrane Renal Group's Specialised Register through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Date of last search: 16 June 2014.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) that compared use of any topical corticosteroid ointment with placebo ointment or no treatment for boys with phimosis.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed titles, abstracts and the full-text of eligible studies, extracted data relating to the review's primary and secondary outcomes, and assessed studies' risk of bias. Statistical analyses were performed using the random-effects model and results were expressed as risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI). We contacted authors of primary articles asking for details of study design and specific outcome data.
MAIN RESULTS
We included 12 studies that enrolled 1395 boys in this review. We found that both types of corticosteroids investigated and treatment duration varied among studies.Compared with placebo, corticosteroids significantly increased complete or partial clinical resolution of phimosis (12 studies, 1395 participants: RR 2.45, 95% CI 1.84 to 3.26). Our analysis of studies that compared different types of corticosteroids found that these therapies also significantly increased complete clinical resolution of phimosis (8 studies, 858 participants: RR 3.42, 95% CI 2.08 to 5.62). Although nine studies (978 participants) reported that assessment of adverse effects were planned in the study design, these outcomes were not reported.Overall, we found that inadequate reporting made assessing risk of bias challenging in many of the included studies.Selection bias, performance and detection bias was unclear in the majority of the included studies: two studies had adequate sequence generation, none reported allocation concealment; two studies had adequate blinding of participants and personnel and one had high risk of bias; one study blinded outcome assessors. Attrition bias was low in 8/12 studies and reporting bias was unclear in 11 studies and high in one study.
AUTHORS' CONCLUSIONS
Topical corticosteroids offer an effective alternative for treating phimosis in boys. Although sub optimal reporting among the included studies meant that the size of the effect remains uncertain, corticosteroids appear to be a safe, less invasive first-line treatment option before undertaking surgery to correct phimosis in boys.
Topics: Administration, Topical; Adrenal Cortex Hormones; Beclomethasone; Betamethasone; Clobetasol; Glucocorticoids; Humans; Hydrocortisone; Male; Mometasone Furoate; Ointments; Phimosis; Pregnadienediols; Randomized Controlled Trials as Topic; Triamcinolone
PubMed: 25180668
DOI: 10.1002/14651858.CD008973.pub2 -
The Cochrane Database of Systematic... Feb 2015Vitiligo is a chronic skin disorder characterised by patchy loss of skin colour. Some people experience itching before the appearance of a new patch. It affects people... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vitiligo is a chronic skin disorder characterised by patchy loss of skin colour. Some people experience itching before the appearance of a new patch. It affects people of any age or ethnicity, more than half of whom develop it before the age of 20 years. There are two main types: generalised vitiligo, the common symmetrical form, and segmental, affecting only one side of the body. Around 1% of the world's population has vitiligo, a disease causing white patches on the skin. Several treatments are available. Some can restore pigment but none can cure the disease.
OBJECTIVES
To assess the effects of all therapeutic interventions used in the management of vitiligo.
SEARCH METHODS
We updated our searches of the following databases to October 2013: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2013, Issue 10), MEDLINE, Embase, AMED, PsycINFO, CINAHL and LILACS. We also searched five trials databases, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
Randomised controlled trials (RCTs) assessing the effects of treatments for vitiligo.
DATA COLLECTION AND ANALYSIS
At least two review authors independently assessed study eligibility and methodological quality, and extracted data.
MAIN RESULTS
This update of the 2010 review includes 96 studies, 57 from the previous update and 39 new studies, totalling 4512 participants. Most of the studies, covering a wide range of interventions, had fewer than 50 participants. All of the studies assessed repigmentation, however only five reported on all of our three primary outcomes which were quality of life, > 75% repigmentation and adverse effects. Of our secondary outcomes, six studies measured cessation of spread but none assessed long-term permanence of repigmentation resulting from treatment at two years follow-up.Most of the studies assessed combination therapies which generally reported better results. New interventions include seven new surgical interventions.We analysed the data from 25 studies which assessed our primary outcomes. We used the effect measures risk ratio (RR), and odds ratio (OR) with their 95% confidence intervals (CI) and where N is the number of participants in the study.We were only able to analyse one of nine studies assessing quality of life and this showed no statistically significant improvement between the comparators.Nine analyses from eight studies reported >75% repigmentation. In the following studies the repigmentation was better in the combination therapy group: calcipotriol plus PUVA (psoralen with UVA light) versus PUVA (paired OR 4.25, 95% CI 1.43 to 12.64, one study, N = 27); hydrocortisone-17-butyrate plus excimer laser versus excimer laser alone (RR 2.57, 95% CI 1.20 to 5.50, one study, N = 84); oral minipulse of prednisolone (OMP) plus NB-UVB (narrowband UVB) versus OMP alone (RR 7.41, 95% CI 1.03 to 53.26, one study, N = 47); azathioprine with PUVA versus PUVA alone (RR 17.77, 95% CI 1.08 to 291.82, one study, N = 58) and 8-Methoxypsoralen (8-MOP ) plus sunlight versus psoralen (RR 2.50, 95% CI 1.06 to 5.91, one study, N = 168). In these three studies ginkgo biloba was better than placebo (RR 4.40, 95% CI 1.08 to 17.95, one study, N = 47); clobetasol propionate was better than PUVAsol (PUVA with sunlight) (RR 4.70, 95% CI 1.14 to 19.39, one study, N = 45); split skin grafts with PUVAsol was better than minipunch grafts with PUVAsol (RR 1.89, 95% CI 1.25 to 2.85, one study, N = 64).We performed one meta-analysis of three studies, in which we found a non-significant 60% increase in the proportion of participants achieving >75% repigmentation in favour of NB-UVB compared to PUVA (RR 1.60, 95% CI 0.74 to 3.45; I² = 0%).Studies assessing topical preparations, in particular topical corticosteroids, reported most adverse effects. However, in combination studies it was difficult to ascertain which treatment caused these effects. We performed two analyses from a pooled analysis of three studies on adverse effects. Where NB-UVB was compared to PUVA, the NB-UVB group reported less observations of nausea in three studies (RR 0.13, 95% CI 0.02 to 0.69; I² = 0% three studies, N = 156) and erythema in two studies (RR 0.73, 95% CI 0.55 to 0.98; I² = 0%, two studies, N = 106), but not itching in two studies (RR 0.57, 95% CI 0.20 to 1.60; I² = 0%, two studies, N = 106).Very few studies only assessed children or included segmental vitiligo. We found one study of psychological interventions but we could not include the outcomes in our statistical analyses. We found no studies evaluating micropigmentation, depigmentation, or cosmetic camouflage.
AUTHORS' CONCLUSIONS
This review has found some evidence from individual studies to support existing therapies for vitiligo, but the usefulness of the findings is limited by the different designs and outcome measurements and lack of quality of life measures. There is a need for follow-up studies to assess permanence of repigmentation as well as high- quality randomised trials using standardised measures and which also address quality of life.
Topics: Combined Modality Therapy; Ginkgo biloba; Humans; Lasers, Excimer; PUVA Therapy; Photosensitizing Agents; Phototherapy; Plant Extracts; Quality of Life; Randomized Controlled Trials as Topic; Skin Pigmentation; Skin Transplantation; Steroids; Vitiligo
PubMed: 25710794
DOI: 10.1002/14651858.CD003263.pub5 -
Review of evidence supporting the use of nasal corticosteroid irrigation for chronic rhinosinusitis.Annals of Allergy, Asthma & Immunology... Jan 2023To analyze published reports on the efficacy and safety of CSI in CRS and evaluate the clinical implications of current gaps in evidence. Corticosteroid irrigation (CSI)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To analyze published reports on the efficacy and safety of CSI in CRS and evaluate the clinical implications of current gaps in evidence. Corticosteroid irrigation (CSI) is commonly used for management of chronic rhinosinusitis (CRS) with nasal polyps; however, such use is not approved by the US Food and Drug Administration (FDA).
DATA SOURCES
Publications were obtained through PubMed searches through January 2022.
STUDY SELECTION
Searches were conducted using 2 terms: "chronic rhinosinusitis" or "nasal polyps" as the first term and "corticosteroid irrigation," "steroid nasal lavage," or "sinus rinse" as the second term. We reviewed relevant, peer-reviewed literature (19 original research [9 controlled, 10 uncontrolled trials], 7 reviews, and 1 meta-analysis) reporting safety and efficacy of CSI in patients with CRS.
RESULTS
Studies were difficult to compare because they used a variety of solution volumes (60 mL to 125 mL per nostril), corticosteroid agents (budesonide, betamethasone, mometasone, or fluticasone), corticosteroid doses, preparation protocols (by compounding pharmacy or by patient), and administration (frequency, time of day, body positioning). It is difficult to determine which parameters might substantially influence clinical effects because studies were generally small, showed marginal benefits, and rarely assessed safety. To date, no studies evaluating CSI have shown statistically significant differences in a type-I error-controlled primary end point over any comparator, possibly owing to small sample sizes.
CONCLUSION
Designing more robust clinical trials may help determine whether CSI is a valid treatment option. Until more evidence supporting CSI use exists, health care professionals should strongly consider choosing FDA-approved therapies for the treatment of CRS.
Topics: Humans; Rhinitis; Adrenal Cortex Hormones; Nasal Polyps; Steroids; Nasal Lavage; Sinusitis; Chronic Disease
PubMed: 36116748
DOI: 10.1016/j.anai.2022.09.008 -
Postepy Dermatologii I Alergologii Oct 2021The influence of mometasone furoate for paediatric asthma remains controversial. (Review)
Review
INTRODUCTION
The influence of mometasone furoate for paediatric asthma remains controversial.
AIM
We conducted a systematic review and meta-analysis to explore the efficacy and safety of mometasone furoate for paediatric asthma.
MATERIAL AND METHODS
We have searched PubMed, Embase, Web of science, EBSCO, and Cochrane library databases through October 2019 for randomized controlled trials assessing the effect of mometasone furoate versus placebo for paediatric asthma. This meta-analysis was performed using the random-effects model.
RESULTS
Four RCTs were included in the meta-analysis. Overall, as compared to placebo for paediatric asthma, mometasone furoate is associated with substantially increased predicted forced expiratory volume in 1 s (FEV) (mean difference (MD) = 7.53; 95% CI: 7.02-8.04; < 0.00001), FEV (MD = 0.11; 95% CI: 0.10-0.12; < 0.00001), and morning peak expiratory flow (AM PEF) (MD = 17.70; 95% CI: 9.91-25.49; < 0.00001), but demonstrates no obvious effect on pharyngitis (RR = 0.96; 95% CI: 0.59-1.58; = 0.89), upper respiratory tract infections (RR = 0.73; 95% CI: 0.50-1.05; = 0.09), or adverse events (RR = 1.05; 95% CI: 0.84-1.31; = 0.69).
CONCLUSIONS
Mometasone furoate may be effective and safe for paediatric asthma.
PubMed: 34849118
DOI: 10.5114/ada.2020.93273 -
Current Respiratory Care Reports 2014This literature review updates the reader on the new studies regarding steroid therapy over the last year in stable COPD and in exacerbations. In stable COPD, we... (Review)
Review
This literature review updates the reader on the new studies regarding steroid therapy over the last year in stable COPD and in exacerbations. In stable COPD, we critique the 2011 update and 2013 revision of the GOLD guidelines, discuss why combining inhaled corticosteroids (ICS) with long-acting beta-agonists (LABA) (ICS/LABA) is preferable over LABA alone and review the literature for intraclass differences, finding that the evidence does not clearly support superiority of any particular ICS/LABA. We also address other comparisons against ICS/LABA, including triple therapy. We briefly review which type of inhaler should be chosen. For exacerbations, we report the REDUCE trial findings favouring a 5-day course of systemic steroids, and other trials addressing which steroid and route to use, including in an intensive care setting. Lastly, the future lies in new anti-inflammatories and re-phenotyping the heterogeneous amalgamation of COPD. A Spanish guideline recommends distinguishing steroid-responsive eosinophilic exacerbators from other phenotypes.
PubMed: 25089228
DOI: 10.1007/s13665-014-0084-2 -
Respiratory Research Feb 2011Although antihistamines and topical corticosteroids are used in combination to treat allergic rhinitis, their additive effect has not been yet demonstrated. The aim was...
BACKGROUND
Although antihistamines and topical corticosteroids are used in combination to treat allergic rhinitis, their additive effect has not been yet demonstrated. The aim was investigate the antiinflammatory additive effect of mometasone and desloratadine on cytokine and sICAM-1 secretion by epithelial cells, and on eosinophil survival stimulated by human epithelial cells secretions from nasal mucosa and polyps.
METHODS
Epithelial cells obtained from nasal mucosa or polyps were stimulated with 10% fetal bovine serum in presence of mometasone (10(-11) M-10(-5) M) with/without desloratadine (10(-5) M). Cytokine and sICAM-1 concentrations in supernatants were measured by ELISA. Peripheral blood eosinophils were incubated during 4 days with epithelial cell secretions with (10(-11) M-10(-5) M) and/or desloratadine (10(-5) M) and survival assessed by Trypan blue. Results are expressed as percentage (mean ± SEM) compared to control.
RESULTS
Fetal bovine serum stimulated IL-6, IL-8, GM-CSF and sICAM-1 secretion. In mucosa and polyp epithelial cells, mometasone inhibited this induced secretion while desloratadine inhibited IL-6 and IL-8. The combination of 10(-5) M desloratadine and 10(-9) M mometasone reduced IL-6 secretion (48 ± 11%, p < 0.05) greater extent than mometasone alone (68 ± 10%) compared to control (100%). Epithelial cell secretions induced eosinophil survival from day 1 to 4, this effect being inhibited by mometasone. At day 4, the combination of mometasone (10(-11) M) and desloratadine (10(-5) M) provoked an increased inhibition of eosinophil survival induced by cell secretions (27 ± 5%, p < 0.01) than mometasone (44 ± 7%) or desloratadine (46 ± 7%) alone.
CONCLUSIONS
These results suggest that the combination of desloratadine and mometasone furoate have a greater antinflammatory effect in an in vitro model of eosinophil inflammation than those drugs administered alone.
Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Cell Survival; Cells, Cultured; Cytokines; Dose-Response Relationship, Drug; Eosinophils; Epithelial Cells; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Loratadine; Male; Middle Aged; Mometasone Furoate; Nasal Mucosa; Nasal Polyps; Paracrine Communication; Pregnadienediols; Time Factors
PubMed: 21352574
DOI: 10.1186/1465-9921-12-23