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Objectives: Patients with spontaneous cerebrospinal fluid (CSF) rhinorrhea can experience significant sinonasal symptom burden, leading to poor quality of life (QOL). The objective of this study was to investigate sinonasal outcome test-22 (SNOT-22) scores in patients undergoing endoscopic endonasal surgery for spontaneous CSF rhinorrhea and compare them to patients undergoing endoscopic sinus surgery (ESS) for chronic rhinosinusitis without nasal polyps (CRSsNP).Methods: A multi-institutional retrospective review of patients with spontaneous CSF rhinorrhea and CRSsNP was performed. Pre-surgery and post-surgery SNOT-22 scores and domains were compared within each group. Improvements in SNOT-22 scores after surgery were compared between the groups.Results: Ninety-one patients were in the CSF rhinorrhea group and 105 patients were in the CRSsNP group. Within each group, surgery significantly improved total SNOT-22 scores, domain scores, and most of the individual symptoms. Comparing the 2 groups revealed similar improvements in total SNOT-22 scores (P= .244). The CSF rhinorrhea group improved more in runny nose (P< .001), postnasal discharge (P< .001), wake up at night (P= .024), and embarrassed (P= .002). The CRSsNP group improved more in sneezing (P= .027), nasal blockage (P< .001), decreased sense of smell/taste (P= .011), thick nasal discharge (P< .001), facial pain/pressure (P= .008), and the ear/facial domain (P= .010).Conclusions: Patients with spontaneous CSF rhinorrhea experience significant symptom burden. Those who undergo CSF leak repair should experience significant improvement in QOL similar to patients who undergo ESS for CRSsNP as measured by SNOT-22.

Objectives: Spontaneous cerebrospinal fluid (CSF) rhinorrhea is a diagnostic challenge due to its overlapping symptomatology with other sinonasal diseases. The objective of this study was to investigate whether items on the sinonasal outcome test (SNOT)−22 could suggest a diagnosis of spontaneous CSF rhinorrhea versus chronic rhinosinusitis without nasal polyps (CRSsNP).Methods: A multi-institutional retrospective chart review of patients with spontaneous CSF rhinorrhea and a control group of CRSsNP patients was performed. Individual SNOT-22 scores and domain scores were compared.Results: One hundred fifteen patients were included in both cohorts. Of the patients in the CSF rhinorrhea group, 48% were misdiagnosed as chronic rhinosinusitis (CRS) prior to the correct identification of a CSF leak. On bivariate analysis, the CSF rhinorrhea group scored significantly higher on the SNOT-22 for runny nose (P< .001) and was more likely to designate this symptom as most important (P< .001). The CRSsNP group scored significantly higher in nasal blockage (P< .001), thick nasal discharge (P< .001), facial pain/pressure (P< .001), and in the ear/facial (P< .001) and rhinologic (P= .003) domains. Multivariable logistic regression revealed that runny nose (P< .001) was most predictive of spontaneous CSF rhinorrhea while nasal blockage (P< .001), thick nasal discharge (P< .001), and facial pain/pressure (P= .001) were predictive of CRSsNP after adjusting for relevant confounders. No significant difference was observed in total SNOT-22 scores between groups (P= .676).Conclusions: Spontaneous CSF rhinorrhea is commonly misdiagnosed as other sinonasal pathologies. However, individual SNOT-22 items can help aid in suggesting a CSF leak. Spontaneous CSF rhinorrhea should be suspected in patients who have high SNOT-22 scores for runny nose and report this symptom as most important, but have lower scores related to the other cardinal symptoms of CRS.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is comprised of a diverse group of endotypes that cause significant morbidity for afflicted patients. While endoscopic sinus surgery helps ameliorate the disease, polyps frequently recur. Newer strategies are intended to provide access for topical steroid irrigations in attempts to improve the disease process and quality of life, and decrease overall recurrence of polyps.Objective To review the current literature examining the latest surgical approaches for CRSwNP.Methods Review article.Results In dealing with the recalcitrant nature of CRSwNP, surgical techniques have simultaneously become more nuanced and aggressive. Bony resection in anatomically unfavorable areas such as the frontal, maxillary, and sphenoid outflow regions, replacing diseased or denuded mucosa with healthy grafts or flaps at the neo-ostia, and introducing drug-eluting biomaterials to newly opened sinus outflow tracts are highlights in the recent advancements in sinus surgery for CRSwNP. The Draf 3 or modified endoscopic Lothrop procedure has become a standard technique and demonstrated to improve quality of life and decrease polyp recurrence. A number of mucosal grafting or mucosal flap techniques have been described that cover exposed bone of the neo-ostium and evidence shows that this improves healing and diameter of the Draf 3. Partial middle turbinectomy, while controversial, appears to help decrease polyp recurrence in long-term follow-up studies. Modified endoscopic medial maxillectomy improves access to the maxillary sinus mucosa, facilitates debridement and, particularly, in the cystic fibrosis nasal polyp patient, improves overall management of the disease. Sphenoid drill-out procedure provides wider access for topical steroid irrigations and also may improve management of CRSwNP.Conclusion Surgical intervention remains a mainstay of therapy for CRSwNP. Newer techniques revolve around improving access for topical steroid therapy.

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR channel is responsible for the transport of the anions (chloride and bicarbonate) across airway epithelia. Patients with CF have thick mucus, disrupted mucociliary transport, and chronic bacterial infections in the upper and lower airways. In this article, the pathophysiology of CFTR dysfunction and its impact on the united airway are reviewed as well as the treatment strategies for patients with chronic rhinosinusitis–related CF and acquired CFTR dysfunction.

Objective Frontal sinus osteomyelitis is a severe complication which can result from chronic rhinosinusitis, trauma, or as a complication of reconstruction or obliteration of the frontal sinus. The objective of the current study is to evaluate the contemporary management of frontal sinus osteomyelitis in light of recent advancements in endoscopic surgical techniques.Methods Review of a prospectively collected database of patients with frontal sinus pathology was performed from 2008–2020. Data from individuals with frontal sinus osteomyelitis was collected including demographics, etiology, surgical technique, adjunctive medical treatments, complications, and clinical follow up.Results Sixteen patients (average age 48.3, range 8–84) were included in the study. An open approach was utilized in 6 patients (2 osteoplastic flaps, 3 Reidel procedures, 1 cranialization). Seven patients underwent completely endoscopic approaches (3 Draf IIB, 4 Draf III), while 3 individuals had combined procedures (Lynch with Draf III, osteoplastic flap + Draf III, fistula excision + Draf IIb). All patients received 6 weeks of antibiotics. Average clinical follow up was 24.4 months with no patients requiring revision procedures.Conclusion Endoscopic, endoscopic-assisted, and open approaches were utilized successfully in the current series of patients with osteomyelitis of the anterior table of the frontal sinus. While the progression of endoscopic techniques allows an additional surgical treatment option, it is important to select patients appropriately as open procedures continue to have an important role in the treatment algorithm.

Abnormal chloride (Cl−) transport has a detrimental impact on mucociliary clearance in both cystic fibrosis (CF) and non-CF chronic rhinosinusitis. Ginseng is a medicinal plant noted to have anti-inflammatory and antimicrobial properties. The present study aims to assess the capability of red ginseng aqueous extract (RGAE) to promote transepithelial Cl−secretion in nasal epithelium.

Objective: To define a new anatomic relationship in pediatric sinus surgery, assessing the maxillary roof as a constant safe landmark to avoid skull base injury in the pediatric population.Study Design: Retrospective analysis.Setting: Tertiary care children hospital.Subjects and Methods: A retrospective analysis was performed of all computed tomography scans of the sinuses and facial bones at the emergency department of a tertiary children’s hospital over the course of a year. Radiographic measurements included the lowest cribriform plate and planum sphenoidale (PS) heights, or posterior skull base when not yet pneumatized, as well as the highest maxillary roof height. The nasal floor was used for reference. Statistics were performed via Shapiro-Wilks test with a P-value of .05 indicating statistical significance.Results: Three hundred and seven unique scans were reviewed (38.9% female; n = 122; P= .58). Age stratification was based on previously described sinus growth patterns. In all patients, the maximum maxillary height was inferior to the lowest measured cribriform lamella and PS (P< .001; CI, 98.5%-99%). Inter- and intrarater reliability and accuracy were verified through blinded review and re-review (ρ = .99 and .98 respectively, P≤ .001). The validity of sole coronal measurements due to incomplete sagittal reformatting was also confirmed (ρ = 1.00, P≤ .001).Conclusion: Despite variation in sinus growth and development in children, the current study demonstrated the validity of the maxillary sinus roof as a constant safe landmark in the pediatric population, offering a novel anatomic relationship for teaching safety in performing pediatric sinus surgery.Level of Evidence: 4

Background Epithelial ion transport regulates hydration of airway mucosal surfaces, and thus promotes effective mucociliary clearance (MCC). Decreased transepithelial Cl−transport may contribute to epithelial dysfunction by abrogating MCC and increasing mucus viscosity in chronic rhinosinusitis (CRS). The objective of the current study is to evaluate Cl−channel transport properties from cultures of human sinonasal epithelia.Methods Human sinonasal epithelia (HSNE) from patients undergoing sinus surgery were cultured at an air-liquid interface to confluence and full differentiation. The epithelial monolayers were mounted in Ussing Chambers to investigate pharmacological manipulation of ion transport. Epithelial Na+channel (via Amiloride), CFTR (via forskolin), and Ca2+-activated Cl−channel (CaCC, via UTP) transport were investigated among three different patient groups: Control, CRS and CRS with polyposis. CFTR mRNA levels were evaluated with quantitative RT-PCR.Results HSNE cultures from 18 patients (Control = 9, CRS = 6, CRS with polyposis = 3) were evaluated in 142 experiments. Summary data from the 18 patients demonstrated that stimulated CFTR-mediated anion transport (Δ ISC) was significantly lower with CRS (7.58+/−2.24 µA/cm2) compared to control (25.86+/−3.44 µA/cm2) and CRS with polyposis (20.16+/−4.0 µA/cm2) (p = 0.004). No statistically significant difference was found for CaCC anion transport between groups (p = 0.39). Significantly decreased mRNA (relative expression) was noted in CRS cultures (CRS = 40.83+/−1.76 vs. control = 116.2+/−24.27, p = 0.03).Conclusions A substantial decrease in the Cl−secretory capacity of HSNE monolayers was demonstrated in CRS subjects. Data suggest that CFTR may contribute more to abnormal ion transport in CRS than CaCC.

Endoscopic surgery on the maxillary sinus has experienced significant advances in technique and approaches since the maxillary antrostomy was introduced in the 1980s. Disease processes that previously required open surgical approaches to the maxillary sinus can now be treated endoscopically while preserving form and function of the sinus and without injuring the maxillary sinus mucosa or disrupting normal mucociliary clearance. Understanding the techniques described in this article will allow surgeons to appropriately plan treatment strategies for patients with a variety of maxillary sinus diseases from dentoalveolar origin.

Background Methods to improve the clinical efficacy of currently available antibiotics against multidrug resistant bacteria in cystic fibrosis (CF) chronic rhinosinusitis (CRS) are greatly needed. Ivacaftor, a cystic fibrosis transmembrane conductance regulator potentiator, was recently identified as having potentially beneficial off-target effects as a weak inhibitor of bacterial DNA gyrase and topoisomerase IV. The objective of the current study is to evaluate whether ivacaftor enhances the antimicrobial activity of ciprofloxacin against Pseudomonas aeruginosa.Methods The planktonic growth of the PAO-1 strain of P. aeruginosawas studied in the presence of ciprofloxacin and/or ivacaftor. Effects were measured according to optical density of cultured PAO-1 at 600 nm. For a static PAO-1 biofilm assay, the PAO-1 strain was inoculated and cultured for 72 h in the presence of the drugs. Formed PAO-1 biofilms were quantified by crystal violet staining and imaged with confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM).Results PAO-1 growth was significantly reduced in the presence of ivacaftor (8 or 16 µg/mL) and ciprofloxacin (0.02 or 0.05 µg/mL) compared to ciprofloxacin alone (P< .001). Similarly, ivacaftor (8 or 16 µg/mL) showed a significant reduction of PAO-1 biofilms when treated with 0.05 µg/mL of ciprofloxacin. Significant synergism was noted between ciprofloxacin and 16 µg/mL of ivacaftor (P< .0001) in reducing planktonic growth and biofilm formation. Quantitative measurements with crystal violet staining were correlated to CLSM and SEM images.Conclusion Ivacaftor enhanced ciprofloxacin’s antimicrobial activity against P. aeruginosa. Further studies evaluating the efficacy of ivacaftor/ciprofloxacin combination for P. aeruginosafor CF CRS are warranted.

Sinonasal respiratory epithelium is a highly regulated barrier that employs mucociliary clearance (MCC) as the airways first line of defense. The biological properties of the airway surface liquid (ASL), combined with coordinated ciliary beating, are critical components of the mucociliary apparatus. The ASL volume and viscosity is modulated, in part, by the cystic fibrosis transmembrane conductance regulator (CFTR). The CFTR is an anion transporter of chloride (Cl−) and bicarbonate (HCO3−) that is located on the apical surface of respiratory epithelium and exocrine glandular epithelium. Improved understanding of how dysfunction or deficiency of CFTR influences the disease process in both genetically defined cystic fibrosis (CF) and acquired conditions has provided further insight into potential avenues of treatment. This review discusses the latest data regarding acquired CFTR deficiency and use of CFTR specific treatment strategies for CRS and other chronic airway diseases.

Background The osteoplastic flap provides access to pathology of the frontal sinus and is often performed with obliteration, which can result in significant long-term complications.Objective To describe the authors’ approach to osteoplastic flap without obliteration.Methods Descriptive analysis.Results Osteoplastic flap without obliteration preserves frontal sinus function while permitting direct access to the frontal sinus. In this study, we demonstrate a combined nonobliterated approach, accessing the frontal sinus with a Draf III approach to remove a large frontal sinus osteoma.Conclusion The approach provides excellent exposure for large tumors not otherwise accessible via purely endoscopic procedures, permits improved surveillance, and minimizes long-term complications of obliterated sinuses.

Calcifying cystic odontogenic tumor (CCOT) is a rare histologic subtype of odontogenic tumor. Treatment requires complete enucleation. We report what we believe is the first case of CCOT to be [...]

Amphotericin B (AMB), a potent antifungal agent, has been employed as topical and systemic therapy for sinonasal fungal infections. A novel formulation of nanodisc (ND) containing super aggregated AMB (ND-AMB) for the treatment of fungal infections has been recently developed to provide greater protection from AMB toxicity than current, clinically approved lipid-based formulations. The objective of the current study was to evaluate the safety and potency of ND-AMB for sinonasal delivery using an in vitromodel.

Primary spontaneous cerebrospinal fluid (CSF) rhinorrhea is an unusual phenomenon that may occur anywhere along the skull base. However, CSF leaks originating from clival defects are rarely reported in the literature. The majority of reported cases were managed with microscopic techniques, using free grafts. The present study discusses a case of spontaneous CSF rhinorrhea from a clival defect closed with our transnasal operative approach using endoscopic techniques. The skull base defect was successfully managed with an endoscopic binostril approach to create a nasal septal flap pedicled at the sphenopalatine artery, while also preserving the integrity of the nasal septum.

Encephaloceles and cerebrospinal fluid (CSF) leaks of the frontal sinus may result from congenital, traumatic, spontaneous, or neoplastic causes. Paramount to success is adequate preoperative planning with accurate history, physical exam, endoscopy, imaging, and testing to confirm location of the leak and origin of the disease. Generally, frontal sinus CSF leaks may be addressed endoscopically with favorable anatomy, proper surgical technique, and appropriate equipment. Open surgical approaches (eg, osteoplastic flap) are often required for superior/lateral defects or if the surgeon is not experienced with endoscopic frontal sinus techniques.

Background Transnasal endoscopic pituitary surgery has proven to be a safe and effective method for removing pituitary tumors. Direct and angled endoscopy at the site of dissection provides excellent visualization without external incisions. However, olfactory loss has been documented after surgical approaches to the pituitary and is accompanied by a significant detriment to quality of life.Study Design A prospective cohort study.Methods Subjects 19 years and older who were undergoing transnasal endoscopic pituitary surgery were recruited for this study. The University of Pennsylvania Smell Identification Test (UPSIT) was administered preoperatively and then at 3–4 months. Data regarding demographics, reconstructive technique, and complications were recorded. The patients had skull-base reconstruction with a Medpore implant or a vascularized nasoseptal flap.Results and Discussion A total of 33 subjects were recruited, with 18 completing the study. The mean (SEM) age was 58.2 ± 2.4 years, with 12 females and 6 males. The majority of patients (89%) had nonfunctioning macroadenomas, and six individuals had reconstruction by using a vascularized nasoseptal flap. Matched mean (SEM) preoperative and postoperative UPSIT scores for this cohort were not significantly different (31.3 ± 0.4 versus 30.5 ± 0.5, respectively; p = 0.54). In addition, there was no significant difference between the mean preoperative and postoperative UPSIT scores of the patients who had nasoseptal flaps (29.4 ± 1.1 vs. 28.6 ± 1.3 respectively; p = 0.87).Conclusions In the current study, pre- and postoperative UPSIT scores were not significantly different in patients who underwent endoscopic transnasal pituitary surgery. The use of a nasoseptal flap also did not adversely affect postoperative UPSIT scores.

Background Intraoperative image guidance is a useful modality for transsphenoidal pituitary surgery. However, the outcomes associated with this technology have not been systematically evaluated.Objective The purpose of the study was to quantify complication rates with and without the use of image guidance during transsphenoidal pituitary surgery using a nationwide database with broadly applicable results.Methods A retrospective analysis of the Nationwide Inpatient Sample was performed from 2007 to 2011. Transsphenoidal pituitary resections for adenomas were identified by International Classification of Diseases-9th Revision, Clinical Modification code. The effect of image guidance on cerebrospinal fluid (CSF) leak complications and cost-benefit was analyzed.Results A total of 48,848 transsphenoidal pituitary resections were identified, of which 77.5% were partial resections and 22.5% were complete. Pathologic indications included benign (89.3%), malignant primary (0.6%), and malignant secondary (0.4%). Complications included same-stay death (0.4%), CSF leak (8.8%), postoperative CSF rhinorrhea (1.9%), diabetes insipidus (12.4%), and meningitis (0.4%). Image guidance was employed in 7% (n = 3401) of all cases. When analyzed by modality, computed tomography (CT)-assisted procedures had lower CSF rhinorrhea rates (1.1%) compared with cases with no image guidance (1.9%), whereas magnetic resonance (MR)-assisted procedures had the highest rates (2.7%, χ2p < 0.001). Rates of CSF leak demonstrated a similar pattern (CT 6.4%, no image guidance 8.9%, MR 9.2%, χ2p < 0.001). CT-assisted surgery had significantly shorter length of stay (2.9 days) versus no image guidance (3.7 days, p < 0.001), lower total charges ($47,589 versus $62,629, p < 0.001), and lower total cost ($16,748 versus $20,530, p < 0.001).Conclusions CT-assisted surgery is associated with a lower rate of CSF leak, shorter length of stay, and lower cost compared with patients without image guidance. Further studies that control for severity and extent of disease are warranted to confirm this finding.

Upper airway disease engenders significant morbidity for patients with cystic fibrosis and is increasingly recognized as having a much greater role in pulmonary outcomes and quality of life than originally believed. Widespread disparate therapeutic strategies for cystic fibrosis chronic rhinosinusitis underscore the absence of a standardized treatment paradigm. This review outlines the most recent evidence-based trends in the management of upper airway disease in cystic fibrosis.

Background Chronic rhinosinusitis with nasal polyposis (CRS/NP) is a medical disease that is managed more effectively after endoscopic sinus surgery (ESS). Despite topical treatment with intranasal steroids, acute inflammatory exacerbations (AEs) are common and are typically treated with oral prednisone, which has significant and well-documented side effects. The objective of the current study was to critically evaluate the topical application of triamcinolone acetonide (80) in carboxymethylcellulose (TA/CMC) foam for AEs in CRS/NP patients after ESS.Methods CRS/NP patients managed with ESS by a single rhinologist over a 5-year period were included in the study. Data were reviewed regarding demographics, number of AEs, revision surgery, 22-item Sino-Nasal Outcomes Test (SNOT-22) scores, frequency of oral prednisone and/or TA/CMC, and notable side effects.Results A total of 371 CRS/NP patients were treated with ESS over a 5-year period. Mean follow-up was 49.3 weeks (range, 2–249 weeks). During this time period, 130 patients (46 years; range, 28–48 years) developed a cumulative 267 AEs. Before initiating use of TA/CMC in 2010, 66 AEs were treated with prednisone. Subsequently, 116 of 201 AEs were managed with TA/CMC with a sequential decrease in prednisone use over the last 3 years (77, 39, and 32%). SNOT-22 scores (n = 33) decreased significantly after TA/CMC instillation (preinstillation, 1.69 ± 0.86, versus postinstillation, 1.23 ± 0.8; p < 0.01).Conclusion Management of AEs with TA/CMC decreased overall prednisone use in a large population of CRS/NP patients in this retrospective evaluation. TA/CMC appears well tolerated and is a useful treatment option for AEs in postoperative CRS/NP patients.

Introduction Inverted papillomas of the middle ear are extremely rare tumors that carry an increased risk of recurrence and malignant transformation. There are currently 59 cases of middle ear inverted papillomas reported in the literature. The objective in this study was to systematically evaluate outcomes regarding middle ear inverted papillomas with respect to demographics, anatomical tumor sites, malignant transformation status, recurrence rate and HPV status.Study Design Retrospective case series and systematic review.Methods A systematic review was completed on June 25, 2020 with a search strategy including PubMed, Embase, Scopus and Google Scholar. This revealed 181 articles. Full-text review was completed, and 66 articles were included. 115 articles were eliminated due to duplication of articles from databases, article titles not applicable to the aims of the systematic review and articles describing inverted papilloma of body sites other than middle ear.Discussion Thirty-one cases of primary inverted papillomas of the middle ear were found in the literature with an additional 26 cases of secondary tumors. Four case reports did not specify primary versus secondary. The malignant transformation rate was 34.4% with a 53.6% recurrence rate. Treatment of middle ear inverted papillomas is primarily surgical with adjuvant radiation therapy considered for patients with recurrence or malignant transformation. Frequent clinical follow up of these patients is critical due to the increased rate of recurrence and malignant transformation.Conclusion Inverted papillomas of the middle ear are rare tumors that carry a high risk of recurrence and malignant transformation necessitating complete resection and frequent clinical follow up.

Background Chronic rhinosinusitis (CRS) is one of the most common chronic medical conditions, with a significant impact on patient quality of life. CRS is broadly classified into two groups: CRS with nasal polyposis (CRSwNP) and CRS without NP (CRSsNP). Clinically, the major subtypes of CRSwNP may be divided into eosinophilic chronic rhinosinusitis (e.g., allergic fungal rhinosinusitis and aspirin-exacerbated respiratory disease [AERD]) and nasal polyps associated with neutrophilic inflammation (e.g., cystic fibrosis [CF]). CF is characterized by mutation of the gene encoding the CF transmembrane conductance regulator. Functional endoscopic sinus surgery is usually required for most NP patients with increased frequency in patients with AERD. This study provides a review of the epidemiology and major classification of CRSwNP.Methods A review was performed of the literature regarding different subtypes of CRSwNP.Results Many definitions of CRSwNP exist and estimates of prevalence vary.Conclusion CRSwNP is a clinical syndrome with a heterogeneous inflammatory profile. Of the subtypes associated with eosinophilic inflammation, AERD remains the most recalcitrant to medical and surgical therapeutic interventions.

Background Advances in the care of patients with cystic fibrosis (CF) have improved pulmonary outcomes and survival. In addition, rapid developments regarding the underlying genetic and molecular basis of the disease have led to numerous novel targets for treatment. However, clinical and basic scientific research focusing on therapeutic strategies for CF-associated chronic rhinosinusitis (CRS) lags behind the evidence-based approaches currently used for pulmonary disease.Methods This review evaluates the available literature and provides an update concerning the pathophysiology, current treatment approaches, and future pharmaceutical tactics in the management of CRS in patients with CF.Results Optimal medical and surgical strategies for CF CRS are lacking because of a dearth of well-performed clinical trials. Medical and surgical interventions are supported primarily by level 2 or 3 evidence and are aimed at improving clearance of mucus, infection, and inflammation. A number of novel therapeutics that target the basic defect in the cystic fibrosis transmembrane conductance regulator channel are currently under investigation. Ivacaftor, a corrector of the G551D mutation, was recently approved by the Food and Drug Administration. However, sinonasal outcomes using this and other novel drugs are pending.Conclusion CRS is a lifelong disease in CF patients that can lead to substantial morbidity and decreased quality of life. A multidisciplinary approach will be necessary to develop consistent and evidence-based treatment paradigms.

IMPORTANCE Pharmacologic activation of mucociliary clearance (MCC) represents an emerging therapeutic strategy for patients with chronic rhinosinusitis, even in the absence of congenital mutations of the CFTR gene. Drug discovery efforts have identified small molecules that activate the cystic fibrosis transmembrane conductance regulator (CFTR), including potentiators under development for treatment of cystic fibrosis. OBJECTIVE To evaluate the properties of CFTR modulators and their effects on ciliary beat frequency (CBF) in human sinonasal epithelium (HSNE). DESIGN Primary HSNE cultures (wild type and F508del/F508del) were used to compare stimulation of CFTR-mediated Cl− conductance and CBF by the CFTR modulators genistein, VRT-532, and UCCF-152. MAIN OUTCOMES AND MEASURES Increase in CFTR-dependent anion transport and CBF. RESULTS HSNE cultures were analyzed using pharmacologic manipulation of ion transport (change in short-circuit current [∆ISC]) and high-speed digital imaging (CBF). Activation of CFTR-dependent anion transport was significantly different among agonists (P &lt; .001), with genistein exerting the greatest effect (mean [SD] ∆ISC, genistein, 23.1 [1.8] μA/cm2 > VRT-532, 8.1 [1.0] μA/cm2 > UCCF-152, 3.4 [1.4] μA/cm2 > control, 0.7 [0.2] μA/cm2; Tukey-Kramer P &lt; .05) in the absence of forskolin. Genistein and UCCF-152 augmented CBF (under submerged conditions) significantly better (Tukey-Kramer P &lt; .05) than cells treated with VRT-532 or dimethyl sulfoxide vehicle control (mean [SD] fold change over baseline, genistein, 1.63 [0.06]; UCCF-152, 1.56 [0.06]; VRT-532, 1.38 [0.08]; control, 1.27 [0.02]). Activation of CBF was blunted in F508del/F508del HSNE cultures. CONCLUSIONS AND RELEVANCE The degree of CBF stimulation was not dependent on the magnitude of Cl− secretion, suggesting that different mechanisms of action may underlie MCC activation by these small molecule potentiators. Agents that activate both CFTR-dependent ISC and CBF are particularly attractive as therapeutics because they may address 2 independent pathways that contribute to deficient MCC in chronic rhinosinusitis.

OBJECTIVE To highlight concepts critical to achieving successful repair and avoiding intracranial complications in the treatment of cerebrospinal fluid (CSF) leaks from the lateral recess of the sphenoid sinus (LRS). DESIGN Outcomes study. SETTING Tertiary referral university hospital. PATIENTS Eleven patients with LRS CSF leaks from June 2008 to June 2010. INTERVENTIONS Endoscopic transpterygoid approach and multilayer repair of skull base defect in the LRS. MAIN OUTCOME MEASURES Recurrence, graft techniques, postoperative intracranial pressure (ICP), and use of ventriculoperitoneal (VP) shunt. RESULTS Thirteen CSF leaks originating in the LRS were surgically repaired in 11 patients; 2 patients required bilateral leak repair. The endoscopic transpterygoid approach was used in 12 of 13 repairs. Eight patients had failed attempts at repair prior to presentation (4 endoscopic sphenoidotomies and 4 middle cranial fossa [MCF] approaches). One patient presented with a temporal lobe abscess following hydroxyapatite “obliteration” to seal off the LRS. This required a combined MCF/transpterygoid approach to drain the abscess, remove the encephalocele and hydroxyapatite, and seal the skull base defect. In 2 cases, the LRS was left patent owing to concerns of inadequate mucosal extirpation. The median duration of follow-up was 10.8 months (range, 2-29 months). One patient experienced a failure (2 months after repair), which was successfully sealed on the second attempt. Postoperatively, 5 patients required VP shunts, and 5 were maintained on acetazolamide for elevated ICP (average, 26.7 cm H2O in 8 patients; presumed elevated in 2 patients). CONCLUSIONS The current study demonstrated a 92% success rate using the endoscopic transpterygoid approach for LRS skull base defects providing support for routine use in the treatment algorithm. Poor outcomes were observed with previous surgical attempts to obstruct the LRS without repairing the skull base defect.

Background Chronic rhinosinusitis has a major impact on the quality of life of patients with cystic fibrosis (CF) and may contribute to progression of chronic lung disease. Despite multiple sinus surgeries, maxillary sinus involvement is a recurrent problem. The modified endoscopic medial maxillectomy (MEMM) permits debridement in the clinic, improves mucus clearance with nasal irrigations, and increases access for topical delivery of therapeutics. However, clinical outcomes of aggressive sinus surgery with regimented postoperative medical treatment have not been systematically evaluated.Methods CF patients completed the 22-Item Sinonasal Outcome Test questionnaires before sinus surgery (and bilateral MEMM) and at sequential postoperative visits. Objective measures included Lund-Kennedy endoscopic score and pulmonary function tests (forced expiratory volume at 1 second percent [FEV1%] predicted). Culture-directed antibiotic therapy, prednisone, and topical irrigations were initiated postoperatively.Results Twenty-two patients (mean age, 26.5 years; 4.9 prior sinus operations) underwent MEMM and sinus surgery. Symptom scores were significantly reduced at 60 days (primary outcome, 64.7 ± 18.4 presurgery versus 27.5 ± 15.3 postsurgery; p < 0.0001) and up to a year postoperatively (27.6 ± 12.6; p < 0.0001). Endoscopic scores were also reduced after surgery (10.4 ± 1.1 presurgery versus 5.7 ± 2.4 [30 days], 5.7 ± 1.4 [60 days], 5.8 ± 1.3 [120 days], and 6.0 ± 1.1 [1 year]; p < 0.0001)]. There were no differences in FEV1% predicted up to 1 year postoperatively, but hospital admissions secondary to pulmonary exacerbations significantly decreased (2.0 ± 1.4 versus 3.2 ± 2.4, respectively; p < 0.05).Conclusion Prospective evaluation indicates sinus surgery with MEMM is associated with marked improvement in sinus disease outcomes. Additional studies are necessary to confirm whether this treatment paradigm is associated with improved CF pulmonary disease.

Background Increasing epithelial chloride (Cl−) secretion in the upper airways represents a putative method for promoting mucociliary clearance through augmentation of airway surface liquid depth. Several naturally occurring flavonoid compounds, including quercetin, have shown the capacity to increase transepithelial Cl−transport. Quercetin exhibits well-known antioxidant and anti-inflammatory activity and is now recognized as a potent activator of the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel activity in a fashion largely independent of cyclic adenosine monophosphate signaling. The present study investigates whether this compound activates Cl−secretion and ciliary beat frequency (CBF) in well-characterized culture models of sinonasal epithelium.Methods Cystic fibrosis and non-cystic fibrosis primary human sinonasal epithelial (HSNE) and murine nasal septal epithelial (MNSE) cultures were studied for transepithelial ion transport in Ussing chambers under voltage clamp conditions and CBF was performed using pharmacologic manipulation.Results Change in short circuit current (DeltaISC, expressed as microamperes per squared centimeter) in response to quercetin were significantly greater than controls in both MNSE (23.23± 5.44 versus 2.47± 1.62; p< 0.0001) and HSNE (-8.72± 1.88 versus -1.88± 0.66; p< 0.01) cultures. CBF was significantly increased in quercetin-treated cells (expressed as fold change over baseline) in wild type (1.65± 0.13 versus 1.23± 0.05 [control]; p< 0.01), but not CFTR−/-(1.65± 0.29 versus 1.48± 0.38; p = 0.23).Conclusion Quercetin significantly increased transepithelial Cl−transport and CBF in MNSE and HSNE cultures. Future studies investigating quercetin as a means to promote mucociliary transport in individuals with rhinosinusitis are warranted.

Background Dynamic regulation of respiratory ciliary beat frequency (CBF) is regulated by fluxes in intracellular calcium (Ca2+). P2X receptors (P2XR) are extracellular ATP-gated, Ca2+-permeable, nonselective cation channels. Zinc increases intracellular Ca2+in a sodium (Na+)-free environment through activation of P2XR channels. We hypothesize that topical zinc increases CBF in a Ca2+-dependent fashion as a result of this mechanism.Methods The apical surface of mouse sinonasal air–liquid interface cultures were bathed in zinc in a Na+-free solution with or without Ca2+. High-speed digital video imaging captured and analyzed CBF at a sampling rate of 100 frames/s.Results CBF significantly increased fourfold over baseline from 5.99 ± 3.16 Hz to 22.4 ± 4.33 Hz in the presence of zinc chloride (50 micromoles) and calcium chloride (3 mM). This effect is abolished in the presence of extracellular Na+and was pH dependent.Conclusions Zinc stimulates CBF in the presence of Ca2+likely through activation of P2X receptors. Thus, zinc represents a promising agent for stimulation of mucociliary clearance.

Background Sternberg's (lateral craniopharyngeal) canal was originally described in anatomic studies as a membranous space in the lateral wall of the sphenoid sinus. The canal has been etiologically associated with lateral sphenoid sinus “spontaneous” cerebrospinal fluid (CSF) leaks. A patent Sternberg's canal has been reported in up to 4% of adults, and persistent vestiges have been reported in up to 30%. However, no modern studies analyzing high-resolution CT scans have been published.Methods A consecutive analysis of 1000 high-resolution CT scans of sphenoid bones was performed. Scans were analyzed for a lateral recess, bony defects, arachnoid pits, and holes possibly representing Sternberg's canal. Data were compared with a case series of lateral sphenoid CSF leaks.Results Average patient age was 38.7 years (10-92 years). A sphenoid lateral recess was present in 35.3% (17.4% bilateral) of cases. Arachnoid pits were present on the floor of the middle cranial fossa in 23.4% of cases. Seven skull base defects were identified. Only one traveling medial to V2 resembled the description of Sternberg's canal. In contrast, a case series of 25 patients with lateral sphenoid sinus CSF leaks all had a lateral recess, defects, and arachnoid pits lateral to V2 (p < 0.00001).Conclusion Sternberg's canal as historically defined is not nearly as prevalent as previously reported. Furthermore, the presence of arachnoid pits in all sphenoid CSF leaks and the predominant leak location lateral to the sites of fusion of ossification centers suggests that the leaks are acquired. Contributing factors may include arachnoid pits/weaknesses in the skull base and intracranial hypertension.

Background The purpose of this study was to compare vectorial ion transport within murine trachea, murine nasal septa, and human sinonasal cultured epithelium. Our hypothesis is that murine septal epithelium, rather than trachea, will more closely mimic the electrophysiology properties of human sinonasal epithelium.Methods Epithelium from murine trachea, murine septa, and human sinonasal tissue were cultured at an air-liquid interface to confluence and full differentiation. A limited number of homozygous dF508 epithelia were also cultured. Monolayers were mounted in modified Ussing chambers to investigate pharmacologic manipulation of ion transport.Results The change in forskolin-stimulated current (delta-ISC, expressed as micro-A/cm2) in murine septal (n = 19; 16.84 ± 2.09) and human sinonasal (n = 18; 12.15 ± 1.93) cultures was significantly increased over murine tracheal cultures (n = 15; 6.75 ± 1.35; p = 0.035 and 0.0005, respectively). Forskolin-stimulated ISCwas inhibited by the specific cystic fibrosis transmembrane regulator (CFTR) inhibitor INH-172 (5 μM). No forskolin-stimulated ISCwas shown in cultures of dF508 homozygous murine septal epithelium (n = 3). Murine septal ISCwas largely inhibited by amiloride (12.03 ± 0.66), whereas human sinonasal cultures had a very limited response (0.70 ± 0.47; p < 0.0001). The contribution of CFTR to stimulated chloride current as measured by INH-172 was highly significantly different between all groups (murine septa, 19.51 ± 1.28; human sinonasal, 11.12 ± 1.58; murine trachea, 4.85 ± 0.49; p < 0.0001).Conclusion Human sinonasal and murine septal epithelial cultures represent a useful model for studying CFTR activity and may provide significant advantages over lower airway tissues for investigating upper and lower respiratory pathophysiology.

Cerebrospinal fluid leaks that occur spontaneously are challenging to manage clinically owing to frequent recurrences following attempted surgical closure. Understanding of the underlying pathophysiology has increased in recent years as we now recognize that the vast majority of these patients demonstrate clinical symptoms and radiographic signs of elevated intracranial pressure. Individuals with this disorder also arise from a distinct demographic group. Increased knowledge of the characteristics of this patient population along with updated medical and surgical management will provide increased success rates in the management of this clinical entity.

Background Chronic rhinosinusitis (CRS) that is refractory to medical or surgical intervention may involve a particularly resistant form of infection known as a bacterial biofilm. Bacterial biofilms are three-dimensional aggregates of bacteria that often are recalcitrant to antibiotics secondary to physical barrier characteristics. To date, all studies investigating biofilms in CRS have been descriptive in either human or animal tissue. To better understand the interactions of bacterial biofilms with respiratory epithelium, we describe an in vitro model of biofilm sinusitis by establishing mature biofilms on airway epithelial air-liquid interface cultures.Methods Airway epithelial cell cultures were grown on collagen-coated semipermeable support membranes as an air-liquid interface on tissue culture inserts. Confluent air-liquid interface cultures were inoculated with the biofilm-forming PAO-1 strain of Pseudomonas aeruginosa and compared with cultures inoculated with two mutant strains (sad-31 and sad-36) unable to form biofilms. Inoculated tissue transwells were incubated for 20 hours, allowing for biofilm growth. The semipermeable membranes were then harvested and imaged with confocal laser scanning microscopy and scanning electron microscopy.Results Microscopic analysis revealed the formation of biofilm-forming towers in the PAO-1 inoculated wells. The bacterial biofilms were supported by a viable airway epithelial cell surface monolayer.Conclusion This study shows a reliable method for analysis of in vitro interactions of bacterial biofilms and airway epithelium. The experimental manipulation of this air-liquid interface model will help explore novel treatment approaches for bacterial biofilm-associated CRS.

Background Symptoms of postnasal drainage and thickened mucus are commonly seen in patients with chronic rhinosinusitis (CRS) recalcitrant to sinus surgery and conventional medical therapies. Chemical surfactants can act as a mucolytic by reducing water surface tension and have the potential to serve as an antimicrobial agent. Baby shampoo is an inexpensive, commercially available solution containing multiple chemical surfactants. This is an in vitro study of its antimicrobial effects on Pseudomonas biofilms with translation to a clinical study for use as an adjuvant nasal wash in patients with CRS who remain symptomatic despite adequate sinus surgery and conventional medical therapies.Methods In vitro testing was performed to determine the optimal concentration of baby shampoo that disrupted preformed bacterial biofilms and inhibited biofilm formation. This concentration was then used in a prospective study of symptomatic post–functional endoscopic sinus surgery (FESS) patients who irrigated twice a day for 4 weeks. Validated outcome forms and objective smell testing was performed before and after therapy.Results One percent baby shampoo in normal saline was the optimal concentration for inhibition of Pseudomonas biofilm formation. Baby shampoo had no effect on the eradication of preformed Pseudomonas biofilms. Eighteen patients with CRS with an average of 2.8 surgeries were studied after irrigating with 1% baby shampoo solution. Two patients discontinued use because of minor nasal and skin irritations; 46.6% of patients experienced an overall improvement in their subjective symptoms, and 60% of patients noted improvement in specific symptoms of thickened mucus and postnasal drainage.Conclusion Baby shampoo nasal irrigation has promise as an inexpensive, tolerable adjuvant to conventional medical therapies for symptomatic patients after FESS. Its greatest benefit may be in improving symptoms of thickened nasal discharge and postnasal drainage.

Background Transient receptor potential (TRP) channels are a novel class of nonvoltage gated membrane cation channels that can be activated by mechanical stimulation and temperature change. Recently, TRP vanilloid type 4 (TRPV4) has been implicated in detecting viscosity changes in fallopian tube epithelial cells and inducing a compensatory response in ciliary activity and, as such, represents a possible molecular trigger for modulating respiratory ciliary activity. Thus, the goal of this study was to establish the expression pattern of TRPV4 in human sinonasal mucosa and determine whether expression is altered in chronic rhinosinusitis (CRS).Methods Sinus mucosal biopsy specimens were obtained from patients with CRS, CRS with nasal polyps (NPs), and healthy controls. TRPV4 mRNA and protein expression were confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) and immunoblot analysis, respectively. TRPV4 gene expression was measured next using quantitative RT-PCR. Immunofluorescence was performed on sinus mucosal explants and respiratory epithelial air–liquid interface cultures to localize cellular expression.Results TRPV4 mRNA and protein were expressed in all samples. There was a statistically significant increase (p <0.05) in TRPV4 gene expression in nonpolypoid CRS patients, but no difference in CRS with NP. Dual label immunofluorescence showed TRPV4 expression to be mutually exclusive of ciliated cells.Conclusion Although TRPV4 represents an ideal molecular trigger for ciliary modulation, absent expression of the channel in ciliated cells precludes this function. However, altered expression of the channel in CRS and presumed expression of TRPV4 in secretory cells of the mucosa indicate a potential role in mucus homeostasis and CRS pathogenesis.

Background The endoscopic resection of sinonasal inverted papillomas (IPs) has been well described. However, the majority of published reports in the literature are small case series with limited clinical follow-up. The aim of this retrospective study was to review the experience with the endoscopic and endoscopic-assisted resection of IPs at a major academic tertiary care facility and assess long-term outcomes.Methods A retrospective review of endoscopic and endoscopic-assisted resections of IP was performed. Charts were reviewed for standard demographic data, operative technique, adjuvant approaches, complications, and postoperative follow-up times.Results One hundred fourteen patients (average age, 56 years) underwent endoscopic or endoscopic-assisted resection for IPs with a mean disease-free follow-up of 40 months (7–135 months). Seventeen patients developed disease after endoscopic or endoscopic-assisted resection for a recurrence rate of 15%. Average time to recurrence was 23 months. Combined approaches were used when indicated in 34% (39/114) of patients, including adjuvant osteoplastic flap, midface degloving, trephine, or Caldwell-Luc approaches. Four patients (4%) had cerebrospinal fluid leaks that were successfully repaired endoscopically.Conclusion In this large series of endoscopically resected IPs with extensive clinical follow-up, recurrences occurred an average of 23 months after the procedure. This emphasizes the importance of long-term endoscopic follow-up to detect recurrences in all patients. Endoscopic or endoscopic-assisted resection of IPs is a valid technique in this series with recurrence rates comparable with open approaches.

Background Air–liquid interface cultures using murine tracheal respiratory epithelium have revolutionized the in vitro study of airway diseases. However, these cultures often are impractical because of the small number of respiratory epithelial cells that can be isolated from the mouse trachea. The ability to study ciliary physiology in vitro is of utmost importance in the research of chronic rhinosinusitis (CRS). Our hypothesis is that the murine nasal septum is a better source of ciliated respiratory epithelium to develop respiratory epithelial air–liquid interface models.Methods Nasal septa and tracheas were harvested from 10 BALB/c mice. The nasal septa were harvested by using a simple and straightforward novel technique. Scanning electron microscopy was performed on all specimens. Cell counts of ciliated respiratory epithelial cells were performed at one standard magnification (1535×). Comparative analysis of proximal and distal trachea, midanterior and midposterior nasal septal epithelium, was performed.Results Independent cell counts revealed highly significant differences in the proportion of cell populations (p < 0.00001). Ciliated cell counts for the trachea (106.9 ± 28) were an average of 38.7% of the total cell population. Nasal septal ciliated epithelial cells (277.5 ± 16) comprised 90.1% of the total cell population.Conclusion To increase the yield of respiratory epithelial cells harvested from mice, we have found that the nasal septum is a far superior source when compared with the trachea. The greater surface area and increased concentration of ciliated epithelial cells has the potential to provide an eightfold increase in epithelial cells for the development of air–liquid interface cultures.

Background Surfactant-associated proteins (SP) A and D are both innate immunity mediators and produced in normal and diseased sinus mucosa. Cystic fibrosis (CF) is associated with Th1 adaptive inflammation whereas allergic fungal rhinosinusitis (AFRS) is associated with Th2 adaptive inflammation. The purpose of this study is to show and quantify the presence of SP A, SP D, tumor necrosis factor (TNF) alpha, (a Th1 marker), and eotaxin (a Th2 marker) in normal and diseased sinus mucosa.Methods Intraoperative sinus mucosal biopsy specimens from human volunteers were obtained during endoscopic sinus surgery for CF (n = 4), AFRS (n = 10), and normal controls (CTLs; n = 4). Specimens were evaluated for presence and quantity of SP A, SP D, and TNF-alpha using Western blot with semiquantitative immunoblot analysis. Eotaxin was quantified using ELISA immunoassay. Results were standardized and reported as picograms of mediator per microgram of total protein.Results SP A, SP D, and TNF-alpha levels in CF tissue extracts were 2–10 times higher than levels in AFRS tissue (with SP D and TNF-alpha reaching statistical significance) but CF tissue was not significantly higher than CTL tissue. SP A, SP D, and TNF-alpha were not significantly elevated in AFRS. Eotaxin showed elevated levels in CF and AFRS when compared with CTLs (p = 0.03 and 0.003, respectively).Conclusion SP D and TNF-alpha are significantly increased in CF compared with AFRS, suggesting activation of both innate immunity and Th1-mediated inflammation and potential correlation between SPs and downstream adaptive immune responses.

Air-liquid interface models using murine tracheal respiratory epithelium have revolutionized the in vitro study of pulmonary diseases. This model is often impractical because of the small number of respiratory epithelial cells that can be isolated from the mouse trachea. We describe a simple technique to harvest the murine nasal septum and grow the epithelial cells in an air-liquid interface. The degree of ciliation of mouse trachea, nasal septum, and their respective cultured epithelium at an air-liquid interface were compared by scanning electron microscopy (SEM). Immunocytochemistry for type IV β-tubulin and zona occludens-1 (Zo-1) are performed to determine differentiation and confluence, respectively. To rule out contamination with olfactory epithelium (OE), immunocytochemistry for olfactory marker protein (OMP) was performed. Transepithelial resistance and potential measurements were determined using a modified vertical Ussing chamber. SEM reveals approximately 90% ciliated respiratory epithelium in the nasal septum as compared with 35% in the mouse trachea. The septal air-liquid interface culture demonstrates comparable ciliated respiratory epithelium to the nasal septum. Immunocytochemistry demonstrates an intact monolayer and diffuse differentiated ciliated epithelium. These cultures exhibit a transepithelial resistance and potential confirming a confluent monolayer with electrically active airway epithelium containing both a sodium-absorptive pathway and a chloride-secretory pathway. To increase the yield of respiratory epithelial cells harvested from mice, we have found the nasal septum is a superior source when compared with the trachea. The nasal septum increases the yield of respiratory epithelial cells up to 8-fold.

Introduction:Surfactant protein (SP)‐B is a hydrophobic protein secreted within pulmonary surfactant that facilitates the adsorption of surface‐active lipids to the air‐liquid interface of the alveoli and increases alveolar stability. SP‐B may also have anti‐inflammatory properties. It is implicated in decreasing the pulmonary inflammatory response to bacterial lipopolysaccharide. However, the expression and function of SP‐B in the sinonasal cavities has not been elucidated. Our objective was to detect the presence of SP‐B, measure alterations in several forms of chronic rhinosinusitis (CRS), and localize cellular protein expression.

Background Cystic fibrosis (CF) patients often have widespread inflammatory paranasal sinus disease with an increased incidence of frontal, maxillary, and sphenoid hypoplasia. The most common genetic defect in CF is the delta F508 mutation. The effect of specific CF genotypes on phenotypic sinus development and infections is not well understood. The purpose of this study was to determine whether the homozygous delta F508 mutation is associated with an increased incidence of sinus hypoplasia when compared with other mutations.Methods This study is a retrospective review of all adult patients seen at our CF center from 1996 to 2005. Patients ≥18 years old with a CF diagnosis using genetic and sweat chloride testing and sinus CT scans were included. Frontal sinus aplasia/hypoplasia and maxillary and sphenoid sinus hypoplasia were documented using published criteria. Data collected included patient demographics, genetic mutations, and prior sinus surgeries.Results Forty-five patients were identified with an average age of 32 years (range, 18–48 years). Thirty-one patients had prior sinus surgeries. Delta F508 homozygotes (n = 25) had a significantly increased frequency of underdeveloped frontal (98%), maxillary (70%), and sphenoid (100%) sinuses (p < 0.001) when compared with other mutations (69, 8, and 50%, respectively).Conclusion CF patients homozygous for the delta F508 mutation have a greater incidence of hypoplastic or underdeveloped sinuses. Whether this is secondary to an increased frequency of sinus infections or a phenotypic expression of the genetic mutation itself remains an area for further investigation.

Background Dendritic cell (DC) activation and antigen presentation to T cells are critical to innate and adaptive immunity. Toll-like receptors (TLRs) are known to bind pathogen-associated molecular patterns in addition to sinonasally secreted surfactant proteins (SP) such as SP-A and SP-D. TLR binding is known to activate DCs. Based on these observations, we sought to establish the presence, in sinonasal mucosa, of DC and the pattern recognition receptors (PRRs), CD14, TLR2, and TLR4.Methods Sinonasal biopsy specimens were taken from patients with eosinophilic nonatopic nasal polyposis (n = 4), allergic fungal sinusitis (n = 1), and nondiseased patients undergoing cerebrospinal fluid leak repair or pituitary tumor resection (n = 2). Tissue samples were stained immunohistochemically for PRR (CD14, TLR2, and TLR4), mature DC marker (CD208), iDC marker (CD209), or isotype controls.Results Immature and mature DC were immunolocalized to the subepithelial stroma and ciliated epithelial surface, respectively. Diffuse staining of CD14 was observed throughout the stroma with additional staining in the ciliated epithelium. The TLR markers showed no staining in the ciliated epithelium. TLR2 primarily localized in stroma immediately deep to the ciliated epithelial surface. TLR4 immunolocalized to submucosal seromucinous gland ductal epithelium. Data from nondiseased patients were mixed, with one patient showing minimal staining of any of the tested cellular markers.Conclusion This study indicates progressive DC activation and emigration of mature antigen-presenting cells from the epithelial surfaces of sinonasal mucosa. The presence of TLR known to bind SP-A and SP-D suggests a link between SP expression and immune response in sinonasal mucosa.

AbstractIntroduction: Surfactant-associated proteins (SPs) play a crucial role in the innate defense system and serve as the initial step in the immune response to inhaled pathogens. SP-A and SP-D expression and function are altered in a variety of inflammatory and infectious diseases of the lungs, such as asthma, allergies, and cystic fibrosis, but their presence and function in the sinonasal cavity has not been investigated. The objective of this study was to test our hypothesis that SP-A and SP-D are present in the human sinus. Materials and Methods: Sinus mucosal biopsies were performed in 8 patients undergoing endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis, pituitary tumors, and cerebrospinal fluid leak repairs. Expression of SP mRNA and protein by the sinus mucosa was detected by RT-PCR and immunoblot analysis, respectively. Results: Analyses of mucosal biopsies from these patients revealed the presence of SP-A and SP-D mRNA and protein in all specimens. Conclusion: SP-A and SP-D are expressed in both normal and diseased human sinus tissue. Understanding the role of SPs in diseased and healthy states may elucidate their possible roles in innate immunity in the upper airway and allow us to develop novel treatments for sinonasal pathologies.Copyright © 2007 S. Karger AG, Basel

Objectives:Previous reports indicate that elevated intracranial pressure (ICP) may cause spontaneous cerebrospinal fluid (CSF) leaks. In this study we examined the clinical diagnosis of benign intracranial hypertension (BIH) in this population using the modified Dandy criteria.Methods:We performed a retrospective review of clinical data and measurements of ICPs after surgical repair.Results:Sixteen patients with spontaneous CSF leaks were surgically treated from 1996 to 2002. In 11 patients with CSF pressure measurements, strict adherence to the modified Dandy criteria definitively confirmed a diagnosis of BIH in 8 patients (72%) and a likely diagnosis in the 3 remaining patients. The mean ICP was 31.1 cm H2O (range, 17.3 to 52 cm H2O), and 81% of the patients were obese middle-aged women. Clinically, all patients had signs and/or symptoms of elevated ICP, such as headache (91%), pulsatile tinnitus (45%), hypertension (45%), balance problems (27%), and visual complaints (18%). Surgical repair was 100% successful in leak cessation over a mean follow-up of 14.1 months.Conclusions:Most patients with spontaneous CSF leaks fulfill the modified Dandy criteria; thus, this disorder appears to be a variant of BIH. Further investigation is needed to determine the exact cause of elevated CSF pressures in this group and whether medical or surgical treatments to correct the intracranial hypertension are warranted.

Background Surfactant-associated proteins (SP) A and D are in the family of collectin proteins that play an integral part in the innate defense system. SP-A and SP-D expression and function are altered in a variety of inflammatory and infectious diseases of the lungs, such as asthma, allergies, and cystic fibrosis. Our prior studies are the first to identify the presence of these proteins in the human sinonasal cavity. The objective of this study was to immunolocalize SP-A and SP-D in human sinonasal tissue.Methods Sinonasal mucosal biopsies were performed in patients with various forms of chronic hyperplastic rhinosinusitis with nasal polyposis and nondiseased mucosa from patients undergoing transsphenoidal hypophysectomy. (n = 10) Immunolocalization of surfactant proteins was performed with antibodies to SP-A and SP-D using immunoperoxidase staining technique. Isotype-negative controls were performed on all specimens.Results Analyses of mucosal biopsy specimens from human sinonasal tissue reveals staining within respiratory and intermediate (metaplastic)-type surface epithelium. In addition, staining was intense in the submucosal ductal epithelium of the seromucinous glands. These properties appear to be consistent regardless of disease state and location within the sinuses.Conclusion This is the first study to immunolocalize SP-A and SP-D in sinonasal human mucosa. These are secreted proteins that are intricately involved in innate immunity in the lungs. Their secretion in the upper airway indicates that future studies may allow manipulation of these proteins and development of novel treatments for sinonasal pathology.

The diverse etiologies of cerebrospinal fluid leaks and encephaloceles make it essential to have a thorough understanding of the underlying pathophysiology, principles of treatment, and treatment options to achieve an excellent outcome. Our current diagnostic studies and preoperative imaging for localization of skull base defects permit accurate identification with minimal operative morbidity. The site of the skull base defect ultimately determines the specific surgical approach. Almost all skull base defects in the anterior skull base are amenable to endoscopic repair. However, external approaches are still mandatory for posterior table defects in the frontal sinus located beyond the reach of frontal sinus instruments. Reconstruction of the skull base defect is dependent on the etiology of the leak and other factors, including the underlying intracranial pressure. This article will highlight the surgical techniques and perioperative care relevant to sinonasal cerebrospinal fluid leaks and encephaloceles. [Copyright &y& Elsevier]