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Purpose: The work aimed to develop a co-loaded loratadine and sulpiride nasal nanoemulsion for allergic rhinitis management., Methods: Compatibility studies were conducted adopting differential scanning calorimetry and Fourier transform infrared spectroscopy. Nanoemulsion formulations were prepared using soybean lecithin, olive oil and tween 80. Sodium cholate and glycerol were employed as co-surfactants. Nanoemulsions were assessed for viscosity, pH, droplet size, polydispersity index, zeta potential, electrical conductivity, entrapment, In vitro drug release and corresponding kinetics. Stability of the selected formulation was investigated. The biological effectiveness was evaluated in rabbit models of ovalbumin-induced allergic rhinitis by measuring TNF-α, TGF-β and IL-1., Results: Compatibility studies revealed absence of drug/drug interactions. Nanoemulsions exhibited > 90% entrapment efficiency. The selected nanoemulsion demonstrated small droplet size (85.2   ±   0.2   nm), low PDI (0.35   ±   0.0) and appropriate Zeta Potential (-23.3   ±   0.2) and stability. It also displayed enhanced in vitro drug release following the Higuashi Diffusion and Baker-Lonsdale models. The mean relative mRNA expression of TNF-α, IL-1 and TGF-β significantly decreased from 9.59   ±   1.06, 4.15   ±   0.02 and 4.15   ±   0.02 to 1.28   ±   0.02, 1.93   ±   0.06 and 1.56   ±   0.02 respectively after treatment with the selected nanoemulsion formulation., Conclusion: The results reflected a promising potent effect of the combined loratadine and sulpiride nasal nanoemulsion in managing the symptoms of allergic rhinitis.

Objective: This study evaluated the post-operative indications for sinonasal topical steroid treatment using a corticosteroid (steroid)-eluting, sinus-bioabsorbable device and its effects in patients with eosinophilic chronic rhinosinusitis., Method: Post-operative courses were investigated in two groups: group A with patients who underwent sinonasal topical steroid treatment, and group B with control patients who did not., Results: Group A was significantly younger than group B (p < 0.01), and the pre-operative computed tomography score was significantly higher in group A than in group B (p < 0.05). In the post-operative stage, the nasal symptoms questionnaire component of olfactory loss and the post-operative endoscopic appearance score were significantly worse in group A than in group B (p < 0.01)., Conclusion: These data suggest that younger age, more severe rhinosinusitis and post-operative olfactory loss led to the need for sinonasal topical steroid treatment to prevent relapsing inflammation after functional endoscopic sinus surgery in patients with eosinophilic chronic rhinosinusitis.

Topical intra-nasal sprays are amongst the most commonly prescribed therapeutic options for sinonasal diseases in humans. However, inconsistency and ambiguity in instructions show a lack of definitive knowledge on best spray use techniques. In this study, we have identified a new usage strategy for nasal sprays available over-the-counter, that registers an average 8-fold improvement in topical delivery of drugs at diseased sites, when compared to prevalent spray techniques. The protocol involves re-orienting the spray axis to harness inertial motion of particulates and has been developed using computational fluid dynamics simulations of respiratory airflow and droplet transport in medical imaging-based digital models. Simulated dose in representative models is validated through in vitro spray measurements in 3D-printed anatomic replicas using the gamma scintigraphy technique. This work breaks new ground in proposing an alternative user-friendly strategy that can significantly enhance topical delivery inside human nose. While these findings can eventually translate into personalized spray usage instructions and hence merit a change in nasal standard-of-care, this study also demonstrates how relatively simple engineering analysis tools can revolutionize everyday healthcare. Finally, with respiratory mucosa as the initial coronavirus infection site, our findings are relevant to intra-nasal vaccines that are in-development, to mitigate the COVID-19 pandemic.

Background: Eosinophilic chronic rhinosinusitis (eCRS) is an inflammatory endotype of CRS. Contemporary treatment includes creation of a "neo-sinus" cavity and postoperative corticosteroid irrigations. Not all patients gain control with local therapy. This study aims to determine, in patients with polyp recurrence, the most common sinuses involved., Methods: A prospective case-series was conducted on consecutive adult (≥18 years) post-FESS eCRS patients followed for a minimum of 12 months. All patients had a neo-sinus cavity created surgically and used corticosteroid irrigations daily for 3-6 months, then tapered to disease control. Sinus cavities were assessed by endoscopy on last follow-up. Polyp recurrence was defined as a score of 5 or 6 in the MLMES in ≥3 sinus cavities. Patient-reported outcomes based on SNOT22 and NSS, frequency of corticosteroid irrigations, and courses of systemic antibiotics and corticosteroid were collected. The pattern of sinus involvement was analyzed., Result: A total of 342 sinus cavities were assessed (mean ± standard deviation, 54.9 ± 13.4 years, 43.2% female). Polyp recurrence occurred in 4.3% (6.4% of patients, n = 7 unilateral) of sinus cavities. Frontal and ethmoid sinus cavities were most affected in those with polyp recurrence, compared to the maxilla and sphenoid (100% vs 100% vs 53% vs 53%, p < 0.01). Although those patients with polyp recurrence utilized more systemic corticosteroids courses per year (0.4 ± 0.4 vs 0.1 ± 0.3, p < 0.01), the use of corticosteroid irrigations was similar (% >4/week; 66.7% vs 48.9%, p = 0.13). Prior surgery was more common in patients with polyp recurrence (86.7% vs 53.5%, p = 0.01)., Conclusion: The frontal and ethmoid sinuses were most affected in those patients with polyp recurrence. Whether the disease is more active in this location or topical therapy has limited access requires further evaluation., (© 2020 ARS-AAOA, LLC.)

Background: A corticosteroid-eluting sinus implant was recently approved by the FDA as a drug to treat adult patients with nasal polyps who have undergone previous endoscopic sinus surgery (ESS) of the ethmoid sinuses. ESS is performed in an operating room under general anesthesia, whereby diseased tissue and bone are removed to provide improved drainage. ESS typically involves dissection of 1 or more of the 4 paired sinus cavities (maxillary, ethmoid, sphenoid, or frontal). The implant, containing 1,350 mcg of mometasone furoate, is inserted by a physician in an office setting and offers controlled localized release of corticosteroid to the polypoid sinus tissue. The implant has demonstrated significant improvements in clinical testing; however, little research has been conducted on its economic impact., Objective: To evaluate and quantify the budget impact to a commercial payer of using this implant instead of ESS in patients with nasal polyps after a previous ESS. Since essentially all patients with recurrent nasal polyps after ESS are patients with chronic sinusitis (CS) diagnosis, this study also identified patients with CS with nasal polyposis (CSwNP) for consistency with the patient population studied in clinical trials evaluating the implant., Methods: A budget impact analysis was conducted from a U.S. commercial payer perspective over a 1-year time horizon with patients who received the implant or revision ESS. Primary outcomes of interest were annual total and per-member per-month (PMPM) direct health care costs. Costs were estimated using a decision analysis model, assuming 50% implant utilization as an alternative to revision ESS in eligible patients, with other levels (25%, 75%) also considered. The model utilized the results of a recently published analysis of 86,052 patients in the Blue Health Intelligence database, results from published clinical trials evaluating the implant, a literature review, and published Medicare national payment amounts., Results: A commercial health plan with 1 million members could anticipate 1,000 CSwNP patients as candidates for receiving the implant or revision ESS. Estimated direct treatment costs for refractory CSwNP using only revision ESS are $11.03 million ($0.92 PMPM). If the implant replaced surgery in 50% of cases and if 63% those patients received a second treatment with the implant during the year, the estimated total cost savings would be $2.56 million ($0.21 PMPM). Cost savings associated with using the implant changed to $0.11 PMPM and $0.32 PMPM with implant adoption of 25% and 75%, respectively., Conclusions: In a large commercially insured U.S. population, annual revision ESS costs are substantial. Using the implant instead of revision ESS could result in considerable cost savings for payers at various levels of adoption., Disclosures: This study was sponsored by Intersect ENT, which was involved in study design and manuscript review. Ernst and Imhoff are employed by CTI Clinical Trial and Consulting Services, which contracted with Intersect ENT to conduct this study. Ernst and Imhoff also report other financial support from Intersect ENT during the conduct of the study. DeConde reports personal fees from Intersect ENT during the conduct of the study, as well as personal fees from Optinose, Stryker Endoscopy, and Olympus, outside the submitted work. Manes reports grants from Intersect ENT during the conduct of the study, as well as grants from Optinose and Sanofi outside the submitted work.

Background: Topical antibiotic therapies have been investigated for their use in chronic rhinosinusitis (CRS). However, society guidelines and evidence-based medicine reviews have recommended against the use of topical antibiotic therapy based on randomized controlled trials (RCTs). The purpose of this article is to review recent clinical research published since the aforementioned guidelines were published., Methods: A structured literature review was performed on clinical studies published in the last 5 years investigating the use of topical antibiotic therapies., Results: One double-blinded, randomized controlled trial (DB-RCT) supported the use of tobramycin using a vibrating aerosolizer; 1 non-blinded non-randomized controlled prospective trial lent support to use of topical ofloxacin for its anti-biofilm properties; and 1 meta-analysis found mupirocin irrigations to be beneficial in the short term. One Cochrane Review was unable to make a recommendation as no trial met the inclusion criteria. An additional systematic review found limited evidence to support the use of topical antibiotics with the exception of mupirocin irrigations that may be considered in Staphylococcus aureus infections. Two retrospective studies found that topical antibiotics change bacterial cultures of the sinuses., Conclusion: There is additional evidence to support continuing investigation of topical antibiotic therapies. Further, larger RCTs are required to establish the efficacy of topical antibiotic therapies., (© 2019 ARS-AAOA, LLC.)

Purpose: Budesonide improves the prognosis of chronic rhinosinusitis (CRS). However, few reports have examined whether its use for nasal irrigation, compared to normal saline, improves the prognosis of patients after endoscopic sinus surgery (ESS). We compared the effects of nasal irrigation with budesonide and normal saline in CRS patients after ESS., Methods: Sixty CRS patients who had undergone ESS were randomly divided into an experimental group (30 patients), which used budesonide nasal irrigation, and a control group (30 patients), which used normal saline nasal irrigation. All patients received regular follow-up evaluations and were assessed via questionnaires, including the Lund-Kennedy endoscopic score (LKES), the symptom visual analog scale (VAS), the 22-item Sino-Nasal Outcome Test (SNOT-22), the Short-Form 36-Item Questionnaire (SF-36), the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS) and a side effects scale., Results: Scores of polyposis, mucosal edema, secretions and total score of LKES; VAS scores of nasal blockage, hyposmia and rhinorrhea; and SNOT-22 results in both groups were significantly improved 3 months after ESS. Scores of polyposis, mucosal edema, secretions and scarring and total score of LKES in experimental group were significantly better than in control group 3 months after ESS. No significant differences were observed in SF-36, SAS or SDS before or 3 months after ESS within or between the two groups. The side effects of the two groups were not significantly different., Conclusions: Nasal irrigation improved the prognosis of CRS patients after ESS. Budesonide nasal irrigation had a better effect than normal saline nasal irrigation.

Background: Based on endoscopic examination, chronic rhinosinusitis (CRS) is divided into chronic inflammation with (CRSwNP) or without nasal polyps (CRSsNP). On the basis of the pathomechanism of inflammation, CRS is divided into endotypes. Eosinophilic CRSwNP with coexisting bronchial asthma and hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) is a real therapeutic challenge., Aim: Comparative analysis of the results of treatment of patients with CRSwNP, bronchial asthma, or hypersensitivity to NSAIDs (NSAID-exacerbated respiratory disease, NERD), using antileukotrienes (leukotriene receptor antagonists, LTRAs) or intranasal glucocorticoids or both drugs together after endoscopic sinus surgery (ESS)., Material and Methods: 33 patients (11 male, 33%) with NERD divided into three groups treated with LTRAs or intranasal glucocorticoids or both drugs together were assessed in terms of general well-being, state of pathological changes, and olfactory disorders using the following tools: Sino-Nasal Outcome Test, Visual Analogue Scale, Brief Identification Smell Test, and Lund-Kennedy score before and at 12 months after surgery. CT assessments were made prior to surgery using the Lund-MacKay scale., Results: Comparable efficacy of treatment with nasal steroids and antileukotrienes was found after 12 months of observation of patients., Conclusions: The results suggest comparable efficacy of treatment with nasal steroids and antileukotrienes in patients with NERD after ESS. Treatment with montelukast and mometasone has not been shown to be superior to both drugs administered separately., (© 2019 S. Karger AG, Basel.)

Introduction : Chronic rhinosinusitis (CRS) is a broad heterogeneous inflammatory disorder of the nose and paranasal sinuses, resulting from the dysfunctional interplay between host immunity, defective epithelial barrier, and environmental factors. CRS with nasal polyps (CRSwNP) is considered a more severe clinical phenotype with greater burden of symptoms and higher relapse rate, especially with comorbid asthma or aspirin sensitivity. Available treatment options after endoscopic sinus surgery (ESS) - systemic corticosteroids or revision surgery - have significant risks and limitations. Areas covered : Bioabsorbable, steroid-eluting implants have been studied extensively for the ability to dilate and re-establish sinus patency by the localized, controlled delivery of topical corticosteroids to diseased sinonasal lining and nasal polyps. This review provides a comprehensive, up to date analysis of the literature regarding a novel, office-based, mometasone furoate (MF) sinus implant that may treat patients with recurrent CRSwNP after ESS. Expert commentary : Clinical evidence has demonstrated the safety and efficacy of steroid-eluting implant in the reduction of polyp size, symptom burden, and the need for revision sinus surgery. MF sinus implants may play an important role in the management of patients with recurrent polyposis after sinus surgery.

Background: Postoperative care is an important factor affecting the outcome of endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). The aim of this study was to test the effect of mometasone furoate (MF)-soaked biodegradable nasal dressings (BNDs) on endoscopic appearance in CRS patients with nasal polyps (CRSwNP) after ESS., Methods: This study was a prospective, randomized, double-blinded, placebo-controlled study. A total of 64 CRSwNP patients with bilateral ESS were enrolled and randomly given 4 mL or 8 mL of MF-soaked BNDs (NasoPore) in 1 nasal cavity and the same amount of normal saline-soaked BNDs in the contralateral side. The BNDs were removed on the 7th or 14th postoperative day. Perioperative sinus endoscopy (POSE) and Lund-Kennedy scores were collected, on the 7th or 14th postoperative days and at 1, 2, and 3 postoperative months., Results: The POSE and Lund-Kennedy scores showed that in the 4-mL, 1-week group, no significant differences between the sides treated with MF-soaked BNDs and the normal saline-soaked control were observed at any postoperative visits. In the 4-mL, 2-week group, significant differences were found at the 2-week and 1-month postoperative visits but not at the 2-month and 3-month visits. In the 8-mL, 1-week group, significant differences were found at the 1-week, 1-month, and 2-month postoperative visits but not at the 3-month visit. In the 8-mL, 2-week group, significant differences were found at all postoperative visits., Conclusion: This study reveals that MF-impregnated BNDs improve the endoscopic appearance in the healing process of CRSwNP after ESS., (© 2018 ARS-AAOA, LLC.)

Background: Topical intranasal corticosteroid sprays (INCSs) are standard treatment for nasal polyps (NPs), but their efficacy is reduced by poor patient compliance and impaired access of drug to the sinus mucosa. A corticosteroid-eluting sinus implant was designed to address these limitations in patients with recurrent polyposis after sinus surgery by delivering 1350 μg of mometasone furoate (MF) directly to the ethmoid sinus mucosa over approximately 90 days., Methods: A randomized, sham-controlled, double-blind trial was undertaken in 300 adults with refractory chronic rhinosinusitis with NPs (CRSwNP), who were candidates for repeat surgery. Eligible patients were randomized (2:1) and underwent in-office bilateral placement of 2 implants or a sham procedure. All patients used the MF INCS 200 μg once daily. Co-primary efficacy endpoints were the change from baseline in nasal obstruction/congestion score and bilateral polyp grade, as determined by an independent panel based on centralized, blinded videoendoscopy review., Results: Patients treated with implants experienced significant reductions in both nasal obstruction/congestion score (p = 0.0074) and bilateral polyp grade (p = 0.0073) compared to controls. At day 90, implants were also associated with significant reductions in 4 of 5 prespecified secondary endpoints compared to control: proportion of patients still indicated for repeat sinus surgery (p = 0.0004), percent ethmoid sinus obstruction (p = 0.0007), nasal obstruction/congestion (p = 0.0248), and decreased sense of smell (p = 0.0470), but not facial pain/pressure (p = 0.9130). One patient experienced an implant-related serious adverse event (epistaxis)., Conclusion: Significant improvements over a range of subjective and objective endpoints, including a reduction in the need for sinus surgery by 61%, suggest that MF sinus implants may play an important role in management of recurrent NP., (© 2018 The Authors International Forum of Allergy & Rhinology, published by ARSAAOA, LLC.)

Background: Eosinophilic chronic rhinosinusitis (ECRS) is a disease characterized by eosinophilic inflammatory infiltrate and a local type 2 cytokine milieu. Current animal models fail to recapitulate many of the innate and adaptive immunologic hallmarks of the disease, thus hindering the development of effective therapeutics. In the present study, mice were exposed intranasally to the cysteine protease papain, which shares functional similarities with parasitic proteases and aeroallergens, to generate a rapidly inducible murine model of eosinophilic rhinosinusitis., Methods: C57BL/6 mice were intranasally instilled with 20 μg papain or heat-inactivated papain (HP) on days 0-2 and days 7-10, and then euthanized on day 11. Nasal lavage fluid (NALF) was analyzed to quantify eosinophils and inflammatory cytokine secretion. Sinonasal tissue was sectioned and stained for goblet cells or homogenized to analyze cytokine levels. Serum samples were assayed for immunoglobulin E (IgE) by enzyme-linked immunoassay. Sinonasal mucosal tissue was dissociated and analyzed by flow cytometry., Results: Compared with HP treatment, papain induced significant eosinophilia in NALF, goblet cell hyperplasia, innate and adaptive immune cell infiltration, type 2 cytokine production, and IgE responses. Flow cytometric analysis of sinonasal tissues revealed significant inflammatory cell infiltration and interleukin-13-producing cell populations., Conclusion: In this study, we demonstrated that the cysteine protease papain induces allergic sinonasal eosinophilic rhinosinusitis and resembles T-helper 2 cell inflammation and innate immune characteristics of ECRS. This model permits further study into the molecular mechanisms underlying ECRS pathology and provides a model system for the evaluation of potential pharmacologic interventions., (© 2018 ARS-AAOA, LLC.)

In the upper respiratory epithelium, bitter and sweet taste receptors present in solitary chemosensory cells influence antimicrobial innate immune defense responses. Whereas activation of bitter taste receptors (T2Rs) stimulates surrounding epithelial cells to release antimicrobial peptides, activation of the sweet taste receptor (T1R) in the same cells inhibits this response. This mechanism is thought to control the magnitude of antimicrobial peptide release based on the sugar content of airway surface liquid. We hypothesized that d-amino acids, which are produced by various bacteria and activate T1R in taste receptor cells in the mouth, may also activate T1R in the airway. We showed that both the T1R2 and T1R3 subunits of the sweet taste receptor (T1R2/3) were present in the same chemosensory cells of primary human sinonasal epithelial cultures. Respiratory isolates of Staphylococcus species, but not Pseudomonas aeruginosa , produced at least two d-amino acids that activate the sweet taste receptor. In addition to inhibiting P. aeruginosa biofilm formation, d-amino acids derived from Staphylococcus inhibited T2R-mediated signaling and defensin secretion in sinonasal cells by activating T1R2/3. d-Amino acid-mediated activation of T1R2/3 also enhanced epithelial cell death during challenge with Staphylococcus aureus in the presence of the bitter receptor-activating compound denatonium benzoate. These data establish a potential mechanism for interkingdom signaling in the airway mediated by bacterial d-amino acids and the mammalian sweet taste receptor in airway chemosensory cells., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Postoperative wound healing after endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS) is an important factor in procedural success. Local steroids and separation of opposing mucosa are commonly implemented to optimize healing. A bioabsorbable, fluticasone propionate (FP)-eluting implant, SinuBand FP, was assessed for its safety and efficacy when used in patients with CRS and nasal polyps, who were indicated for ESS including bilateral anterior and posterior ethmoidectomy., Methods: A first-in-human, randomized, partially double-blind, single-tertiary-referral-center, controlled trial enrolling 30 patients receiving 2 of 3 treatments (1 per sinus, intrapatient control): SinuBand FP, SinuBand (without FP), or standard nasal pack (Merocel®). Primary outcome measures were local safety, ocular safety (intraocular pressure [IOP], lens opacity), and 24-hour urine cortisol. Secondary measures (evaluated by independent review of postoperative video endoscopies) were ethmoid inflammation, polyp score, adhesion formation, and Lund-Kennedy score. Patient-reported outcomes of postoperative pain, nasal congestion, and nasal discharge were collected., Results: Of 30 enrolled patients (used for safety analysis), 27 patients completed the trial. SinuBand FP showed local safety, ocular safety, and no significant change in 24-hour urine cortisol. SinuBand FP showed a trend to do better concerning inflammation. Concerning polyp score SinuBand FP did significantly better compared to Merocel (p = 0.03). No significance compared to SinuBand without corticosteroids (p = 0.97). Adhesions were comparable across treatments. Patient reported pain was nominally lower in the SinuBand group., Conclusion: SinuBand FP was well tolerated and showed evidence of efficacy. A larger study is needed to further evaluate and confirm the benefits of SinuBand FP., (© 2017 ARS-AAOA, LLC.)

Background: Upper airway inflammation is one of the most commonly identified causes of chronic cough, although the underlying mechanism is not clear. This study compared normal saline solution nasal-pharyngeal irrigation (NSNPI) and fluticasone propionate nasal spray (FPNS) treatment for chronic cough associated with allergic rhinitis (AR)., Methods: Patients with suspected AR to house-dust mite were enrolled, and the symptom of cough was assessed by a cough symptom score and the Leicester Cough Questionnaire, and cough response to capsaicin was evaluated. AR was assessed by using the visual analog scale (VAS) and the Mini Juniper Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ). Mediators, including histamine, leukotriene C4, and prostaglandin D2, and the major basic protein from nasal lavage fluid (NLF) were examined. The patients were treated with NSNPI (the NSNPI group) or FPNS (the FPNS group) for 30 days, after which they were reassessed., Results: Forty-five of 50 patients completed this study. The scores of the cough symptom and the Leicester Cough Questionnaire, and the capsaicin cough threshold all improved statistically after NSNPI but did not change after FPNS. There were statistically significant changes in the evaluations of the MiniRQLQ and the mediators, including histamine and leukotriene C4, in the NLF in the NSNPI group. However, significant changes were found in the assessments of VAS, MiniRQLQ, and all above mediators including histamine, leukotriene C4, and prostaglandin D2, and the major basic protein in the NLF of the FPNS group. Furthermore, the assessments of VAS and all the mediators were reduced more in the FPNS group compared with those in the NSNPI group., Conclusion: The patients with suspected AR to house-dust mite reported a better relief of the cough symptom after 30 days of treatment with NSNPI compared with that after nasal corticosteroid.

Mucoadhesive in situ gelling systems (soluble gels) have received considerable attention recently as effective stimuli-transforming vectors for a range of drug delivery applications. Considering this fact, the present work involves systematic formulation development, optimization, functional evaluation and ex vivo performance of thermosensitive soluble gels containing dexamethasone 21-phosphate disodium salt (DXN) as the model therapeutic. A series of in situ gel-forming systems comprising the thermoreversible polymer poloxamer-407 (P407), along with hydroxypropyl methyl cellulose (HPMC) and chitosan were first formulated. The optimized soluble gels were evaluated for their potential to promote greater retention at the mucosal surface, for improved therapeutic efficacy, compared to existing solution/suspension-based steroid formulations used clinically. Optimized soluble gels demonstrated a desirable gelation temperature with Newtonian fluid behaviour observed under storage conditions (4-8°C), and pseudoplastic fluid behaviour recorded at nasal cavity/sinus temperature (≈34°C). The in vitro characterization of formulations including rheological evaluation, textural analysis and mucoadhesion studies of the gel form were investigated. Considerable improvement in mechanical properties and mucoadhesion was observed with incorporation of HPMC and chitosan into the gelling systems. The lead poloxamer-based soluble gels, PGHC4 and PGHC7, which were carried through to ex vivo permeation studies displayed extended drug release profiles in conditions mimicking the human nasal cavity, which indicates their suitability for treating a range of conditions affecting the nasal cavity/sinuses., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Saline irrigation of the nasal cavity is a classic and effective treatment for acute or chronic rhinosinusitis. Topical antibiotics such as mupirocin have been widely used for recalcitrant chronic rhinosinusitis. Therefore, the purpose of this study was to evaluate the effect of saline irrigation using mupirocin., Methods: A systematic literature review and meta-analysis of mupirocin saline irrigation were performed using EMBASE, MEDLINE, and Cochrane library through December 2015. Data were analyzed with R 3.2.2 software. A random effects model was used because of the diversity of included studies. Sensitivity analysis of particular tested groups and single proportion tests were also performed. The main outcome measure was residual staphylococcal infection, as confirmed by culture or PCR., Results: Two RCTs, two prospective studies and two retrospective studies were included. A random effects model meta-analysis of the pooled data identified a relative risk of residual infection of 0.13 (95% CI: 0.06-0.26, p<0.05) with low heterogeneity (I2 = 0%). The proportion of residual staphylococcal infections after 1 month was 0.08 (95% CI: 0.04-0.16). However, this proportion increased to 0.53 at 6 months (95% CI: 0.27-0.78)., Conclusions: The short-term use of mupirocin has a strongly reductive effect on staphylococcal infection in chronic rhinosinusitis. Although there is currently a lack of clear evidence, future studies with well-designed inclusion criteria and randomized controlled trials are needed to examine mupirocin's long-term effect on chronic rhinosinusitis., Competing Interests: The authors have declared that no competing interests exist.

Background: Topical antibiotics, delivered optimally as high-volume culture-directed sinus irrigations, are being increasingly used for recalcitrant chronic rhinosinusitis (CRS). Their impact on subjective and objective outcome measures, however, is still unclear., Objective: To assess if the use of topical antibiotics in recalcitrant CRS is associated with improved 20-Item Sino-Nasal Outcome Test and Lund-Kennedy endoscopic scores, and to determine the negative posttreatment culture "control" rate., Methods: Patients were included in the study if they met diagnostic criteria for CRS, received high-volume topical antibiotic sinus irrigations twice daily for 1 month, between December 2009 and May 2015, and had undergone endoscopic sinus surgery. The primary outcome was the 20-Item Sino-Nasal Outcome Test score. Secondary outcomes were the Lund-Kennedy endoscopic score and a negative posttreatment culture "control" rate. Paired t-tests were used to compare pre- and posttreatment scores. Patients with cystic fibrosis were analyzed separately., Results: Of the 58 patients included, 47% had nasal polyposis, 57% had asthma, 16% had aspirin sensitivity, and 55% had environmental allergies. The median Lund-Mackay computed tomography score was 11 (interquartile range, 6-16), and the median time to follow-up was 8 weeks (interquartile range, 6-10 weeks). The 20-Item Sino-Nasal Outcome Test scores improved from pre- to posttreatment period, although this was not significant mean 1.5 [confidence interval {CI} 1.3, 1.7] to mean 1.3 [CI 1.1, 1.6]; p = 0.16). Lund-Kennedy endoscopic scores, however, significantly improved from pre- to posttreatment (mean 4.9 [CI 4.3, 5.6] to mean 4.1 [CI 3.5, 4.7]; p = 0.05). Of the 47 patients with complete culture data, 72% had negative posttreatment culture results, defined as "controlled." Only one patient discontinued treatment, related to discomfort from irrigations., Conclusion: In patients with recalcitrant CRS, the use of topical antibiotics trended toward improvement in symptom severity and significantly improved endoscopic appearance. Furthermore, 72% had negative posttreatment culture results, meaning microbiological "control." The results of this study support the use of high-volume culture-directed topical antibiotics, and, in the future, more rigorous prospective studies are warranted., Competing Interests: The authors have no conflicts of interest to declare pertaining to this article

Background: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2015 ARS-AAOA, LLC.)

Granulomatosis with polyangiitis (GPA), a disease capable of affecting any organ, most often acts upon the upper respiratory tract. Diagnostic imaging is primarily represented by computed tomography (CT) of paranasal sinuses. The aim of this study was to define the characteristic changes in paranasal CT in patients with GPA and to evaluate diagnostic usefulness of the Lund-Mackey scoring system (L-M System). The study encompassed 43 patients with GPA of the mean age of 47.7 ± 12.8 years who were treated topically with mupirocin. We found that inflammation occurred mainly in the maxillary sinuses (72%). The mean L-M score was 5.8 ± 6.1. The right maxillary sinus had the highest percentage (12.6%) of score hits of 1, i.e., partial opacification and the left ostiomeatal complex had the highest percentage (7.6%) of score of 2, i.e., complete opacification or obstruction. The following changes were the most characteristic for GPA: sinus mucosal thickening, widespread bone damage, and osteogenesis. We conclude that the long-term topical mupirocin treatment of GPA may inhibit nasal bone damage, but also may led to permanent rhinological changes of the rhinosinusitis type. The Lund-Mackey staging system is a useful diagnostic imaging option in GPA patients.

Background: Effective topical decongestion is critical for the safe performance of endoscopic endonasal surgery (EES). Despite the vasoconstriction offered by topical concentrated (1:1000) epinephrine (CE), its use has not gained widespread acceptance because of concerns over systemic absorption and its effect on blood pressure and postoperative rebound epistaxis. The purpose of this study was to examine the physiological changes in blood pressure and rate of epistaxis with use of topical CE in a variety of endoscopic nasal procedures., Methods: EES procedures using inhalational anesthesia and topical CE performed on 1140 consecutive patients (14 patients under 18 years) between 2011 and 2014 were evaluated retrospectively. Demographic data, intraoperative hemodynamic parameters, and postoperative epistaxis rates were recorded., Results: The mean patient age was 45.8 years (range, 5-97 years). No intraoperative cardiovascular complications related to CE use were found. Four patients (0.35%) developed postoperative epistaxis requiring intervention. The mean estimated blood loss among patients undergoing bilateral sinus surgery, skull-base surgery, and orbital decompression was (mean ± SD) 61.7 ± 51.6 mL, 60.1 ± 115 mL, and 67.9 ± 42.2 mL, respectively. The maximum mean systolic blood pressure among these groups was 108.3 ± 28.3 mmHg, 111.9 ± 27.6 mmHg, and 95.1 ± 31.7 mmHg, respectively., Conclusion: The use of topical CE is safe when performing endoscopic endonasal procedures. CE was not associated with any intraoperative complications. The profound intraoperative vasoconstriction does not confer a higher rate of postoperative rebound epistaxis., (© 2015 ARS-AAOA, LLC.)

Background: Endoscopic sinus surgery (ESS) is considered a therapeutic option after failure of maximal medical therapy (MMT) for chronic rhinosinusitis (CRS). There is currently no consensus on the definition of MMT. The objective of this systematic review is to describe the various MMT criteria employed prior to considering ESS., Methods: A systematic review was performed using the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria were adults with CRS based on guideline diagnostic criteria, enrolled to undergo ESS, and study publication within the last 5 years (January 1, 2009, to December 30, 2014). Studies were excluded if the study population included non-CRS indications for ESS. Primary outcome was the MMT criteria employed prior to considering a patient a candidate for ESS. A subgroup analysis was performed based on polyp status., Results: Of 387 reviewed studies, 21% reported MMT criteria. When reported, criteria included topical nasal corticosteroids (91% of studies) for a mean of 8 ± 8 weeks, oral antibiotics (89%) for 23 ± 8 days, systemic corticosteroids (61%) for 18 ± 12 days, saline irrigations (39%), oral antihistamines (11%), oral mucolytics (10%), and topical/oral decongestants (10%)., Conclusion: A minority of studies report MMT criteria used as the indication for ESS. When reported, the majority included an 8-week course of topical intranasal corticosteroids and 3-week course of oral antibiotics. Use of systemic corticosteroids did not differ based on polyp status. Because of variation in current MMT criteria, there is a need to develop standardized indications for ESS that will work to improve the appropriateness of care for patients with., (© 2015 ARS-AAOA, LLC.)

Background and Purpose: The anti-inflammatory and immunomodulatory effects of macrolides include the ability to decrease mucus secretion and inhibit inflammatory mediators in chronic rhinosinusitis. Nevertheless, their mechanisms of action remain to be determined. Here we have investigated the effects of macrolide antibiotics (clarithromycin, azithromycin and josamycin; representating the 14-, 15- and 16-membered macrolides) on endogenous steroids in human sinonasal epithelial cells and mouse nasal mucosa., Experimental Approach: The effects of macrolides on the expression of steroid-converting enzymes [11β-hydroxysteroid dehydrogenase (11β-HSD1 and 11β-HSD2)], steroid-synthesizing enzymes (3β-HSD, CYP21, CYP11B1 and CYP11A1) and cortisol levels were assessed in cultured human epithelial cells. In control and adrenalectomized mice , these enzymes and corticosterone levels were evaluated in nasal mucosa and serum after administration of macrolides., Key Results: The expression levels of 3β-HSD, CYP21, 11β-HSD1 and CYP11B1 increased in human epithelial cells treated with clarithromycin and azithromycin, whereas the expression levels of 11β-HSD2 and CYP11A1 were not affected. Josamycin had no effects on the expression of these enzymes. Cortisol levels increased in epithelial cells treated with clarithromycin or azithromycin. The expression of 3β-HSD, CYP11A1, CYP21, CYP11B1 and 11β-HSD1 was upregulated in nasal mucosa of mice treated with clarithromycin or azithromycin, but not in adrenalectomized mice., Conclusions and Implications: This study provides evidence that 14- and 15-membered macrolide antibiotics may affect the expression of steroid-synthesizing and steroid-converting enzymes in human sinonasal epithelial cells and mouse nasal mucosa, increasing the endogenous cortisol levels in sinonasal mucosa., (© 2015 The British Pharmacological Society.)

Background: Fungus-driven inflammation is proposed to play an important role in the pathogenesis of chronic rhinosinusitis (CRS). Previous studies evaluated the efficacy of intranasal amphotericin B (AMB) in the treatment of patients with CRS, but the results were controversial. The purpose of this study was to evaluate the efficacy of 100 μg/mL of AMB nasal irrigation as postoperative care after functional endoscopic sinus surgery (FESS)., Methods: Patients with CRS who received FESS for treatment were recruited and randomly assigned to two groups at 1 month after surgery. Patients in the AMB group received 100 μg/mL of AMB nasal irrigation daily for 2 months, and those in the normal saline (NS) group received NS solution nasal irrigation daily for 2 months. Pre-FESS, pre-irrigation, and postirrigation sinonasal symptoms were assessed by questionnaires, and the patients received endoscopic examination, acoustic rhinometry, smell test, and saccharine transit test., Results: Seventy-seven patients were enrolled between June 2012 and December 2014. Among the patients who completed the study, 38 received AMB irrigation, and 39 received NS solution irrigation. Although all the patients reported improvement after irrigation, there was no difference in outcome between patients who received AMB and those who received NS solution., Conclusion: Our study showed that nasal irrigation with 100 μg/mL of AMB did not confer a greater benefit than that of NS solution nasal irrigation in post-FESS care.

Introduction: Primary mucosal melanoma of the sinonasal tract is a rare neoplasm, accounting for less than 1% of all melanomas. It has an aggressive and unpredictable biologic behavior characterized by frequent incidence of local recurrence, local and distant metastasis of the disease., Case Report: This report summarizes the results of the previous research concerning sinonasal mucosal melanoma, and by the example of the two patients suffering from mucosal melanoma, we described clinical and histopathological features of this rare neoplasm and our experience in its diagnosis and treatment., Conclusion: Only histopathological analysis complemented by immunobistochemical analysis contributes to early and accurate diagnosis of the disease.

Background: Current treatment of acute exacerbations of chronic rhinosinusitis (CRS) is driven by identification of predominant bacteria using culture-based methods and determination of antibiotic sensitivities. The objective of this study was to evaluate the response of the sinonasal microbiome to antibiotic therapy in the setting of an acute exacerbation of CRS., Methods: Aspirate and swab samples for culture and DNA analysis were collected bilaterally from 8 CRS patients presenting with acute exacerbations. Patients were started on a 2-week course of a culture-directed antibiotic after sensitivities were determined. Repeat samples were taken immediately on the completion of treatment. DNA was extracted from each sample, amplified using bacterial 16S primers and sequenced. Bacterial abundance was determined by quantitative polymerase chain reaction (qPCR). Diversity metrics of the microbiota between pretreatment and posttreatment samples were calculated., Results: There was significantly more bacterial DNA present in the pretreatment group than in the posttreatment group. An increase in α-diversity was found in the posttreatment group relative to the pretreatment group (p < 0.05 in each comparison) with swab sampling, but not by aspirate sampling. The predominant organism identified by 16S sequencing correlated with the culture-identified bacteria genus in each patient., Conclusion: Significant differences exist in the diversity of bacteria populations during acute exacerbations of CRS and after antimicrobial treatment. After therapy, the increase in diversity is accompanied by a decrease in the total of abundance of the bacterial population., (© 2015 ARS-AAOA, LLC.)

Background: Chronic rhinosinusitis (CRS) is a prevalent multifactorial disease process in which bacteria are believed to play a role in the propagation of inflammation. Multiple subtypes of CRS have been described based on clinical and pathologic features, but a detailed examination of the sinus microbiota in patients with CRS and its clinical subtypes has yet to be performed., Objective: We sought to examine the resident microbiota of CRS subtypes and determine whether bacterial diversity is a predictor of disease outcomes., Methods: Sinus swabs from patients with CRS and healthy subjects collected during endoscopic sinus surgery were analyzed by means of molecular phylogenetic analysis of 16S rDNA pyrosequences., Results: Fifty-six patients with CRS and 26 control subjects were studied. Biodiversity was similar between the CRS and control groups. Among the CRS subtypes examined, only 2 conditions (presence of purulence and comorbid condition of asthma) were associated with significant alterations in microbial community composition. In 27 patients with CRS who were followed postoperatively, those with better outcomes had more diverse bacterial communities present at the time of surgery, along with higher relative abundances of Actinobacteria., Conclusion: Analysis of microbiota in a large cohort reveals that particular CRS phenotypes (asthma and purulence) are characterized by distinct compositions of resident bacterial communities. We found that bacterial diversity and composition are predictors of surgical outcome, promoting the concept of community ecology in patients with CRS., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Nuclear factor κB (NF-κB) is a vital transcription factor that is activated by numerous inflammatory stimuli. Its activity is tightly regulated by a family of deubiquitinating enzymes (A20, Cezanne, cylindromatosis [CYLD]) that function in a negative-feedback loop, a process that prevents chronic and systemic inflammation. This study seeks to characterize the expression and functional role of NF-κB-regulating deubiquitinases in the sinonasal epithelium., Methods: Expression of A20, Cezanne, and CYLD was assessed in normal sinonasal tissue using immunohistochemistry. Cultured sinonasal epithelial cells (SNECs) were stimulated with proinflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin 4 [IL]-4, IL-13) or lipopolysaccharide (LPS) and changes in NF-κB activation and deubiquitinase expression were assessed using Western blots and quantitative real-time polymerase chain reaction (qRT-PCR), respectively., Results: NF-κB was activated in response to LPS and TNF-α, but not IL-4 or IL-13. A20, Cezanne, and CYLD were all expressed in sinonasal tissue, primarily along the apical surface of the epithelium. Proinflammatory mediators primarily affected expression of A20, with upregulation by LPS and TNF-α and downregulation by IL-4 and IL-13., Conclusion: The NF-κB-regulating deubiquitinases A20, Cezanne, and CYLD are expressed in sinonasal tissue and are differentially induced by proinflammatory cytokines and the microbial antigen, LPS. These results suggest an important role for NF-κB-regulating deubiquitinases in mucosal immunity and homeostasis., (© 2015 ARS-AAOA, LLC.)

Background: To date, topical therapies guarantee a better delivery of high concentrations of pharmacologic agents to the mucosa of the upper aerodigestive tract (UADT). The use of topical drugs, which are able to reduce mucosal inflammation and to improve healing tissues, can represent a relevant therapeutic advance. Topical sodium hyaluronate (SH) has recently been recognized as adjuvant treatment in the chronic inflammatory disease of the UADT., Aims: The aim of our work was to review the published literature regarding all the potential therapeutic effects of SH in the chronic inflammatory disease of UADT., Methods: Relevant published studies were searched in Pubmed, Google Scholar, Ovid using keywords ("sodium hyaluronate" and "upper airways") or Medical Subject Headings., Results: At the end of our selection process, sixteen publications have been included. Six of them in the post-operative period of nasal-sinus surgery, 2 of them in pediatric patients affected by recurrent upper respiratory tract infections, 4 of them in reducing symptoms and preventing exacerbations of chronic upper airways in adult population, 4 of them in patients with chronic inflammatory disease of UADT, including gastro-esophageal reflux disease (GERD)., Conclusions: Topical administration of SH plays a pivotkey role in the postoperative phase of patients undergoing FESS and nasal surgery, and positive results are generally observed in all the patients suffering from UADT chronic inflammatory disease.

Invasive fungal infection (IFI) is an important cause of mortality in immunocompromised children, particularly after hematopoietic stem cell transplantation. We describe 5 cases of Fusarium IFI in immunocompromised children seen at our institution over a 15-year period. A summary of all published pediatric cases of invasive Fusarium infection is presented. A focus on antifungal management challenges in these patients will be discussed., (© The Author 2013. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Up to now, different surgical techniques and stent systems have already been developed and tested for the continuous and adequate ventilation of the frontal sinuses. However, the results achieved still remain poor. Magnesium-based implants have been successfully used in numerous clinical applications. Offering excellent biocompatibility and biodegradability it may be the ideal material for the development of novel implants of the nasal sinus. Here, we present for the first time results on the behaviour of magnesium alloy in a unique environment, i.e. in contact to the nasal mucosa, air and nasal secretion. In a prospective longitudinal study, magnesium fluoride-coated MgNd2 specimens were implanted in the frontal sinuses of 12 minipigs for the investigation of biocompatibility and of the interface between the implant and the mucosa. Endoscopic examinations, histopathological evaluation and EDX measurements were performed regularly up to 180days. Endoscopic evaluation showed focal mucosal reaction, however, without affecting the patency of the sinus. In addition, no signs of bacterial infections were observed. The EDX analyses showed a marginal but steady increase in the Mg concentration in the mucosa over 180days. Histological analysis revealed a locally confined moderate mucosal hyperplasia and unspecific inflammatory reaction. Furthermore, we did not find any osteoinductive effects of the magnesium alloy. The results indicate the excellent biocompatibility of the MgNd2 alloy in contact with nasal mucosa and provide a novel material compound and solid proof-of-principle for the development of magnesium-based nasal stents., (Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Numerous topical agents have been used intraoperatively to enhance postoperative mucosal healing or reduce scar formation. However, the histological effects of many of these treatments have not been well described. This study investigates the impact of topical mometasone furoate, acitretin, lactoferrin, and Silastic sheet (Medtronic) on sinus mucosal healing in a rabbit model., Methods: Forty-eight New Zealand white rabbits underwent defined, localized stripping of a bilateral region of maxillary sinus mucosa. One of 6 treatments was placed in 1 maxillary sinus, and the treatment carrier was applied contralaterally (0.1% mometasone furoate, 0.25% and 0.5% acitretin, lactoferrin, Silastic, and no treatment; n = 8 each group). Rabbits were euthanized after 2 weeks and histological sections were examined with light microscopy., Results: Treatment with acitretin 0.25% and 0.5% improved cilial recovery by 0.9 ± 0.5 (p = 0.003) and 0.5 ± 0.5 (p < 0.05), respectively. Acitretin 0.25% treatment also significantly reduced collagen in healing mucosa (5.1% ± 4.8%, p = 0.04). Conversely, rabbits treated with mometasone furoate 0.1% were more likely to have reduced cilial and goblet cell recovery. Intergroup comparisons demonstrated a significant improvement in cilial recovery scores with both acitretin doses compared with mometasone furoate (p < 0.05) and less collagen deposition in rabbits treated with placebo gel over Silastic (p < 0.05). Mucosa directly underlying a blood clot had a lower cilia score and impaired epithelial recovery (p < 0.001)., Conclusion: Intraoperatively applied agents have the potential to significantly affect wound healing. Acitretin improved cilial recovery and reduced collagen deposition., (© 2015 ARS-AAOA, LLC.)

Background: Chronic sinonasal disease is common in asthmatic patients and associated with poor asthma control; however, there are no long-term trials addressing whether chronic treatment of sinonasal disease improves asthma control., Objective: We sought to determine whether treatment of chronic sinonasal disease with nasal corticosteroids improves asthma control, as measured by the Childhood Asthma Control Test and Asthma Control Test in children and adults, respectively., Methods: A 24-week multicenter, randomized, placebo-controlled, double-blind trial of placebo versus nasal mometasone in adults and children with inadequately controlled asthma was performed. Treatments were randomly assigned, with concealment of allocation., Results: Two hundred thirty-seven adults and 151 children were randomized to nasal mometasone versus placebo, and 319 participants completed the study. There was no difference in the Childhood Asthma Control Test score (difference in change with mometasone - change with placebo [ΔM - ΔP], -0.38; 95% CI, -2.19 to 1.44; P = .68; age 6-11 years) or the Asthma Control Test score (ΔM - ΔP, 0.51; 95% CI, -0.46 to 1.48; P = .30; age ≥12 years) in those assigned to mometasone versus placebo. In children and adolescents (age 6-17 years) there was no difference in asthma or sinus symptoms but a decrease in episodes of poorly controlled asthma defined by a decrease in peak flow. In adults there was a small difference in asthma symptoms measured by using the Asthma Symptom Utility Index (ΔM - ΔP, 0.06; 95% CI, 0.01 to 0.11; P < .01) and in nasal symptoms (sinus symptom score ΔM - ΔP, -3.82; 95% CI, -7.19 to -0.45; P = .03) but no difference in asthma quality of life, lung function, or episodes of poorly controlled asthma in adults assigned to mometasone versus placebo., Conclusions: Treatment of chronic sinonasal disease with nasal corticosteroids for 24 weeks does not improve asthma control. Treatment of sinonasal disease in asthmatic patients should be determined by the need to treat sinonasal disease rather than to improve asthma control., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Inflammatory myofibroblastic tumour is a rare neoplasm with a potential to behave in a malignant manner. It can occur anywhere in the body, however involvement of the head, especially the para-nasal sinuses is rare., Case Presentation: A 33-year-old South Asian male presented with coryzal symptoms including a persistent cough with an asymmetrical swelling of the left side of the face. Imaging revealed a mass lesion involving the para-nasal sinuses eroding into the orbit. Histology and the clinical picture were compatible with inflammatory myofibroblastic tumour. As curative excision of the tumour was not feasible, medical management was offered. Despite early features of remission to glucocorticoids, tapering resulted in recurrence. Hence combination therapy with glucocorticoids and methotrexate was commenced with dramatic reduction of tumour burden and the patient has been in remission to date., Conclusion: Inflammatory myofibroblastic tumour has the potential to behave in a malignant manner. Medical management with chemotherapy, glucocorticoids and non-steroidal anti-inflammatory drugs though effective, do not have a uniform response pattern. Surgically unresectable inflammatory myofibroblastic tumour above neck should be treated aggressively with combination regimens. Combination of prednisolone with methotrexate has been shown to have good outcome.

Background: Verapamil is an L-type calcium channel blocker (CCB) that has been shown to have immunomodulatory properties in a variety of tissues. The goal of this study was determine whether verapamil is capable of regulating cytokine secretion in sinonasal polyps and to compare this effect to dexamethasone, an established immunosuppressive corticosteroid., Methods: This was an institutional review board (IRB)-approved study in sinonasal polyp explants derived from 8 patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Polyps were incubated with dexamethasone or verapamil for 24 hours followed by an additional 24 hours with Staphylococcal enterotoxin B (SEB). Concentrations of secreted cytokines over each exposure period were determined by enzyme-linked immunosorbent assay (ELISA) and are expressed as a percent. Results were compared using a 2-tailed Student t test., Results: The percent of SEB-stimulated interleukin-5 (IL-5) secretion (mean ± standard deviation [SD], 339.94% ± 315.48%) between the second and first treatment periods was significantly reduced following exposure to dexamethasone (74.08% ± 26.77%, p < 0.05) and verapamil (119.99% ± 69.32%, p < 0.05). The percent of SEB-stimulated IL-6 secretion (217.53% ± 89.51%) was also significantly reduced following exposure to verapamil (148.82% ± 79.15%, p < 0.05) but not dexamethasone (148.86% ± 145.24%). Finally, the percent of SEB-stimulated thymic stromal lymphopoietin (TSLP) secretion (37.86% ± 18.88%) demonstrated a nonsignificant trend toward reduction with both dexamethasone (31.15% ± 35.28%) and verapamil (20.14% ± 12.10%)., Conclusion: Although the mechanism has yet to be fully understood, L-type CCBs are capable of reducing inflammation in multiple tissues. Verapamil was specifically found to reduce airway goblet cell hyperplasia and eosinophilic infiltration in a murine asthma model. Our data support these findings suggesting that verapamil can modulate T-helper cell type 2 (Th2)-associated cytokine secretion in sinonasal polyp explants. This data points to a possible therapeutic role for CCBs in the management of CRSwNP., (© 2014 ARS-AAOA, LLC.)

Objective: Nerve growth factor (NGF) is a neurotrophin which promote and regulate the survival of neurons in the peripheral nervous system. We aimed to evaluate the nasal NGF expressions of mast cells in healthy patients after stimulation with sterilized isotonic solution delivered at high pressure., Patients and Methods: The first part of the study was made with 21 voluntary individuals. The middle third of the inferior turbinate epithelial cells on the right nostril was scraped using a sterile curette and indicated as (pre), than a spray of sterilized isotonic solution at high pressure on the left nostril was delivered and 25 minutes later a similar stimulation was delivered on the same nostril. The stimulation was made with a specific spray. The middle third of the inferior turbinate epithelial cells on the left nostril was scraped using a sterile curette and indicated as (post)., Results: Forced nasal stress induced by local delivery of high pressure physiological solution causes an increase in the number of mast cells and enhances level of NGF in the nasal fluid compared to the control subjects. So based on the first part of our study, since NGF is universally known as effective in protection and repairing of neural cells damage, we started the second part and gave a treatment on the same patients, to increase NGF levels with a six months daily therapy and observed the variations in Sensorineural Hearing Loss (SNHL) and tinnitus intensity from the beginning to the end of the therapy. All patients received sterilized isotonic solution at high pressure (pression emission level: PEL): 7 g/sec for 0.5 sec (emission time: ET) in both nostrils. 25 minutes later a similar stimulation was delivered twice a day. The control group (21 pts) received normal therapy with betahistine dihydrochloride 16 mg twice a day., Conclusions: Upon acuphenometry, there was a lower intensity of tinnitus and the improvement was signaled by the patients. Patients with SNHL treated with conventional therapy had a slight worsening, while the patients treated with our new therapy which increased NGF levels, showed improvement of hearing. This new therapy represents a new therapy of SNHL, tinnitus and hearing disorders.

Background: Adequate surgical field visualization is among the most important factors in preventing complications in functional endoscopic sinus surgery (FESS). The aim of this study was to assess the effect of topical cocaine vs adrenaline on surgical field visualization and intraoperative bleeding during FESS., Methods: A randomized controlled trial was conducted. A total of 37 patients that underwent FESS for chronic rhinosinusitis were randomized to the side of the nose that received adrenaline or cocaine-soaked patties, and the side that was operated first. The surgeon evaluating the bleeding was blinded to the vasoconstrictor allocation. At the commencement of surgery and at regular 15-minute intervals, the operating surgeon evaluated the extent of bleeding in the operative field according to a validated scale. At each assessment, mean arterial pressure (MAP), heart rate, and end tidal CO2 were also recorded. At the end of each side, total blood loss was measured., Results: There was no difference in the mean surgical field scores between the adrenaline and cocaine sides (2.04 ± 0.75 vs 2.17 ± 0.7, p = 0.24), nor the total blood loss (p = 0.43). On the cocaine side, there was a correlation between surgical field grade and duration of surgery (p < 0.05) as well as blood loss (p < 0.05) and MAP (p < 0.05)., Conclusion: There is no difference in the quality of the surgical field achieved through the use of topical cocaine or adrenaline during FESS. Either of these agents can be effectively used for topical decongestion at the onset of surgery., (© 2014 ARS-AAOA, LLC.)

Chronic rhinosinusitis (CRS) is the major disorder of the upper airways, affecting about 10-15% of the total population. Topical treatment regimens show only modest efficacy, because drug delivery to the posterior nose and paranasal sinuses is still a challenge. Therefore, there is a high rate of functional endoscopic sinus surgery in CRS patients. Most nasally administered aerosolized drugs, like nasal pump sprays, are efficiently filtered by the nasal valve and do not reach the posterior nasal cavity and the sinuses, which are poorly ventilated. However, as highlighted in this review, sinus ventilation and paranasal aerosol delivery can be achieved by using pulsating airflow, offering new topical treatment options for nasal disorders. Radioaerosol inhalation and imaging studies in nasal casts and in healthy volunteers have shown 4-6% of the nasally administered dose within the sinuses. In CRS patients, significant aerosol deposition in the sinus cavities was reported before sinus surgery. After surgery, deposition increased to the amount observed in healthy volunteers. In addition, compared with nasal pump sprays, retention kinetics of the radiolabel deposited in the nasal cavity was prolonged, both in healthy volunteers and in CRS patients. These efficiencies may be sufficient for topical aerosol therapies of sinus disorders and, due to the prolonged retention kinetics, may reduce application modes, but have to be proven in future clinical trials. Pulsating aerosols may offer additional new topical treatment options of nasal and sinus disorders before as well as after surgery.

Background: Functional endoscopic sinus surgery (FESS) has become the treatment of choice for patients with medically resistant chronic rhinosinusitis (CRS) and nasal polyps. Despite the consolidated use of different treatments, the postoperative period is often very painful and uncomfortable, especially during the first month. Although evidence on the effectiveness of sodium hyaluronate (SH) on postoperative care following FESS is available, data on the quality of life (QoL) from the patients' perspective are still lacking. This study aimed to evaluate for the first time the effectiveness of nasal douche with SH in reducing patients' discomfort during the first month following FESS., Methods: A double-blind randomized controlled study was carried out on 124 subjects undergoing FESS for CRS with nasal polyposis. They were divided into 2 groups: group I was treated with nasal douche containing 9 mg of high molecular weight SH plus saline solution and group II was treated with saline solution alone. To assess QoL in CRS patients, the Short Form-36 (SF-36) test, the Sino-Nasal Outcome Test-22 (SNOT-22), and the visual analogue scale (VAS) questionnaires were administered., Results: At baseline, there were no statistically significant differences between the 2 groups. However, after 30 days of long postoperative treatments, we found clinically significant improvements in QoL of subjects treated with SH, as evidenced by all QoL scales., Conclusion: Our data indicate that SH significantly improves patients' short-term QoL following FESS in terms of both general health and specific sinonasal status., (© 2014 ARS-AAOA, LLC.)

Background: Despite their widespread use, antibiotics have not been shown to improve chronic rhinosinusitis (CRS) outcomes. We aimed to determine whether culture-inappropriate postoperative antibiotic therapy was associated with less quality-of-life (QOL) improvement following functional endoscopic sinus surgery (FESS)., Methods: This retrospective cohort study recruited 376 adult CRS patients undergoing FESS between October 1, 2007 to December 31, 2011. Patient demographics, comorbidities and medications were collected at baseline. Trimethoprim-sulfamethoxazole and clindamycin were administered for 2 weeks postoperatively. The antibiotic appropriateness was determined based on bacterial resistance profile of organisms identified during intraoperative culture. The QOL outcome was defined as change of 22-item Sinonasal Outcome Test scores from preoperative visit to 1-month, 3-month, and 6-month post-FESS. Clinically significant difference was defined as at least 0.5 standard deviations (SD) of baseline QOL score in the reference group. Mixed-effects regression models were performed., Results: Seven percent of patients (n = 27) had culture-inappropriate antibiotic therapy, and additional 5% (n = 19) had culture-specific antibiotic adjustment. Compared to patients with culture-appropriate antibiotics, patients with culture-inappropriate antibiotics had significantly less improvement of QOL from baseline to postoperative 1-month and 3-month follow-up where the difference became clinically significant; patients with antibiotic adjustment had more QOL improvement from baseline to 1-month follow-up, but their QOL worsened at 3-month follow-up, and these changes were not clinically significant. However, all effects washed out at 6-month follow-up with no significant differences., Conclusion: Culture-inappropriate postoperative antibiotic therapy decreased short-term QOL improvement to a clinically meaningful level after FESS. Culture guided selection of antibiotics may improve short-term FESS outcome., (© 2014 ARS-AAOA, LLC.)

Background: Nasal douching is commonly performed after endoscopic sinus surgery (ESS). There is a lack of studies comparing the clinical effect of various douching solutions after ESS. This study investigated the clinical effects of normal saline, lactated Ringer's, and hypertonic saline nasal douching solutions after ESS., Methods: Adult patients (41.8 ± 12.9 years) undergoing bilateral ESS for chronic rhinosinusitis at a single tertiary referral center were blindly randomized to one of the three study solutions and reviewed on postoperative weeks 1, 3, and 6. The 20-item Sino-Nasal Outcome Test (SNOT-20) scores, visual analog scale (VAS) symptom scores, digital video capture of the sinus cavities, and mucociliary clearance (MCC) times were performed at each visit. The mucosa appearances were scored by a second investigator, blinded to the douching solution., Results: Seventy-four patients were recruited. All groups showed an improvement with treatment in SNOT-20 scores and VAS scores, as well as endoscopic evaluation of mucosa appearance over time. There was no improvement of MCC during the treatment period. Irrigation with lactated Ringer's solution resulted in better symptom scores in SNOT-20 (p < 0.05) and VAS (p < 0.05), compared with irrigation with normal saline or hypertonic saline solutions. Patients receiving hypertonic saline solutions had less polypoidal mucosa at week 6., Conclusion: Douching with lactated Ringer's solution after ESS results in better improvement in sinonasal symptoms, compared with normal saline or hypertonic saline solutions.

Background: Fibroblast migration is crucial for normal wound repair after sinonasal surgery. Prostaglandin E2 (PGE2) is a potent inhibitor of fibroblast functions including chemotaxis, proliferation, and matrix production. The purpose of this study was to determine whether PGE2 affects the migration of nasal fibroblasts and to investigate the mechanism of action of PGE2 on nasal fibroblasts., Methods: Primary cultures of nasal fibroblasts were established from inferior turbinate samples. Fibroblast migration was evaluated with scratch assays. Reverse-transcription polymerase chain reaction was performed for E prostanoid (EP) 1, EP2, EP3, and EP4 receptors. EP receptor-selective agonists and antagonists were used to evaluate receptor functions. Stimulatory G (Gs) proteins were activated to evaluate mechanisms. Intracellular cyclic adenosine monophosphate (cAMP) levels were measured by ELISA, and fibroblast cytoskeletal structures were visualized with immunocytochemistry., Results: PGE2 significantly reduced the migration of nasal fibroblasts. Agonists selective for the EP2 and EP4 receptors significantly reduced the nasal fibroblast migration. Antagonists of the EP2 and EP4 receptors inhibited the effect of PGE2 on nasal fibroblast migration. Activation of Gs protein and adenyl cyclase reduced nasal fibroblast migration., Conclusion: PGE2 inhibited the migration of nasal fibroblasts via the EP2 and EP4 receptors, and this inhibition was mediated by cAMP elevation. Targeting specific EP receptors could offer therapeutic opportunities for conditions such as delayed wound healing after nasal surgery.

Background: Treatment options for chronic rhinosinusitis with recurrent polyposis (CRSwNP) after endoscopic sinus surgery (ESS) are limited, and include frequent use of systemic steroids and revision surgery. A bioabsorbable, steroid-eluting implant was studied for its ability to dilate sinuses obstructed by polyps and provide localized, controlled steroid delivery to reestablish sinus patency. This study assessed the initial feasibility, safety, and efficacy of steroid-eluting implants placed in the office setting in patients who were candidates for revision ESS., Methods: Prospective, multicenter study enrolling 12 patients who had prior ESS but experienced recurrent polyposis refractory to medical therapy. Implants were placed bilaterally under topical anesthesia in-office. Follow-up through 6 months included endoscopic grading, patient-reported outcomes (22-item Sino-Nasal Outcomes Test [SNOT-22]) and need for revision ESS., Results: Implants were successfully inserted in 21 of 24 (88%) ethmoid sinuses, resulting in 11 evaluable patients. No serious adverse events occurred. Within 1 month, mean bilateral polyp grade was reduced from 4.5 at baseline to 2.3 (p = 0.008) and sustained through 6 months (2.33; p = 0.008). Mean SNOT-22 score was significantly improved from 2.19 at baseline to 0.90 within 1 month (p = 0.001) and sustained to 6 months (1.03; p = 0.012). Sixty-four percent of patients were no longer revision ESS candidates at 6 months., Conclusion: The study provided initial clinical evidence of the feasibility, safety, and efficacy of in-office steroid-eluting implant placement in CRS patients with recurrent polyposis after ESS. Although further studies are needed, the results suggest this therapy may provide a safe and effective, office-based option for the treatment of obstructive polyposis., (© 2014 ARS-AAOA, LLC.)

Background: Bacterial biofilms are thought to contribute to recalcitrance in chronic rhinosinusitis (CRS) patients. Manuka honey (MH) and its active component methylglyoxal (MGO) have demonstrated antibiofilm activity in vitro. This study evaluated the safety and efficacy of these agents in an in vivo model., Methods: To assess safety, ovine frontal sinuses were flushed twice daily for 14 days. In each sheep, 1 sinus was flushed with a panel of MGO concentrations ranging from 0.5 to 7.2 mg/mL alone and flushed with a panel of with 16.5% wt/vol MH enriched with MGO at the same range of concentrations (0.5-7.2 mg/mL; designated MH/MGO). Contralateral sinuses were flushed with saline control. Tissue morphology was assessed histologically and with scanning electron microscopy. Efficacy was tested by developing Staphylococcus aureus biofilms in sheep sinuses. Twice-daily irrigation for 5 days was commenced with either saline, MGO (0.5-3.6 mg/mL) alone, or MH/MGO (with 0.5-3.6 mg/mL MGO). Biofilm biomass was compared between the groups (n = 4) using LIVE/DEAD BacLight staining and confocal scanning laser microscopy., Results: The results of the safety assessment, for normal sinuses treated with MGO alone or with MH/MGO (≤1.8 mg/mL) showed normal pseudostratified epithelium and cilia structure; however, higher concentrations caused cilia denudation and squamous metaplasia. As for efficacy, when compared to saline flush, treatment with MH/MGO at 0.9 mg/mL (0.608 ± 0.110 vs 0.316 ± 0.197 μm(3) /μm(2) , respectively; p = 0.015) and 1.8 mg/mL (0.676 ± 0.079 vs 0.114 ± 0.033 μm(3) /μm(2) , respectively; p = 0.001) significantly reduced biofilm biomass., Conclusion: Sinus irrigation with MH/MGO at MGO concentrations between 0.9 and 1.8 mg/mL is both safe to mucosa and efficacious against S. aureus biofilm. MH/MGO irrigation could represent a viable treatment option for recalcitrant CRS., (© 2014 ARS-AAOA, LLC.)

Background: Electrolyzed acid water (EAW) has been recognized to have strong bactericidal activity, and the feasibility and safety of EAW irrigation in body cavities has been reported in the literature. This study was conducted to evaluate the effect of EAW nasal irrigation on the postoperative care of functional endoscopic sinus surgery (FESS)., Methods: Patients with chronic rhinosinusitis who received FESS for treatment were recruited and randomly assigned to three groups at 1 month postoperatively. Patients in group 1 received EAW for nasal irrigation daily for 2 months, those in group 2 received neutral normal saline (NS) daily for 2 months, and those in group 3 did not receive nasal irrigation after surgery. Before and 3 months after FESS, sinonasal symptoms were assessed by questionnaire and patients received endoscopic examination, acoustic rhinometry, smell test, saccharine transit test, and bacterial culture from middle meatus., Results: There were 185 patients enrolled between May 2009 and March 2012. Among the patients who completed the study, 36 received EWA irrigation, 35 received NS irrigation, and 39 (group 3) received no irrigation. Patients with nasal irrigation had a better outcome based on questionnaire score and saccharine transit time. However, there was no difference in outcome between patients who received irrigation with EAW and NS., Conclusion: Our study showed that EWA irrigation did not confer a greater benefit than that of NS irrigation in post-FESS care.