A New Patient-reported Outcomes Measure for Surgically Treated Epiphora: Tearing Assessment and Rating Scale-12 (TEARS-12).

BACKGROUND: No widely accepted, validated instrument currently exists to measure clinical outcomes in patients who undergo dacryocystorhinostomy (DCR) for treatment of epiphora. OBJECTIVE: To develop a patient-reported outcome measure applicable to this population. METHODS: Psychometric evaluations, consultation with experts, and review of the literature informed item generation of a 12-question questionnaire to incorporate the most relevant symptoms experienced by patients with nasolacrimal duct obstruction. This questionnaire, known as the Tearing Assessment and Rating Scale-12 (TEARS-12), was administered to 32 patients before and after intervention, in the form of endoscopic DCR. Statistical analysis was performed to measure internal consistency, responsiveness, and test-retest reliability. RESULTS: Pre-operative and post-operative TEARS-12 scores (28.2 [standard error (SE) 3.19] vs 11.8 [SE 3.25], respectively, P = 0.001) demonstrated improved patient outcome within 6 weeks following endoscopic DCR. Cronbach's alpha for the questionnaire was 0.90, indicating high overall reliability. Additionally, each question demonstrated internal reliability, with a corrected item-total correlation greater than 0.30. The intraclass correlation between the two pre-operative scores was 0.858 (P < 0.001), indicating high test-retest reliability. CONCLUSION: TEARS-12 is a statistically valid, easy-to-administer instrument to measure clinical outcomes in patients who undergo endoscopic DCR.

A novel technique of otic barotrauma management using modified intravenous cannulae.

This article provides the first detailed description and systematic evaluation of the management of otic barotrauma using modified intravenous cannulae. A 24-gauge IC cannula was modified as a tool for tympanostomy tube placement and middle ear ventilation. The medical records of 271 ears of 156 adult patients (median age 49 years) who underwent this procedure were reviewed retrospectively. Hundred and ninty-one tubes were placed for otalgia because of hyperbaric oxygen therapy, 58 tubes were inserted for air travel prophylaxis and 22 tubes were placed for management of otic barotrauma post-flight. All the patients who had this procedure for prophylaxis experienced regular otic barotrauma symptoms during air travel prior to tube placement. All patients were reviewed 6 weeks (range 2-9 weeks) post-procedure. This technique of otic barotrauma management worked effectively in 99 % of treated patients. On follow-up, 88 % of tubes were found to be extruded and non-extruded tubes were removed in clinic without any anaesthesia. 99.6 % of tympanic membrane had healed completely and spontaneously without sequelae. Given the safety, effectiveness, low risk of complications associated with this novel tympanostomy technique, it provided a simple yet effective therapeutic option for the management of otic barotrauma. Finally, this technique can be easily applied in all health settings as it only requires medical supplies readily available in hospitals, therefore there is no additional cost.

Is allergy related to Meniere's disease?

Meniere's disease (MD) is characterized by episodic rotational vertigo, fluctuating sensorineural hearing loss, aural pressure, and tinnitus. The cause of MD is thought to be multifactorial, with anatomic and genetic contributions. Allergy is thought to be one of the possible extrinsic factors that, when combined with underlying intrinsic factors, may lead to MD. We review the epidemiologic associations of MD and allergy and review the recent literature on the association of allergy and MD.

Ivacaftor restores delayed mucociliary transport caused by Pseudomonas aeruginosa-induced acquired cystic fibrosis transmembrane conductance regulator dysfunction in rabbit nasal epithelia.

BACKGROUND: Abnormal chloride (Cl- ) transport dehydrates airway surface liquid (ASL) in sinonasal epithelium leading to mucus stasis and chronic rhinosinusitis. As an experimental epithelium, rabbit tissue provides an excellent representation of human sinus disease, and the rabbit sinusitis model is both established and well suited for therapeutic interventions in vivo. Our objective in this study was to evaluate whether ivacaftor reverses the consequences of Pseudomonas aeruginosa-induced acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. METHODS: Rabbit nasal cavities were assessed for responsiveness to ivacaftor in vivo (by nasal potential difference [NPD] assay). Rabbit nasal epithelial (RNE) cultures were incubated with an ultrafiltrate of P aeruginosa (PAO1 strain) for 4 hours and tested for acquired CFTR dysfunction. Markers of mucociliary function, including airway surface liquid depth (ASL), periciliary liquid depth (PCL), ciliary beat frequency (CBF), and mucociliary transport (MCT), were measured by micro-optical coherence tomography (µOCT) after PAO1 and/or ivacaftor incubation. RESULTS: Ivacaftor resulted in a significant mean NPD polarization of 21.8 ± 2.1 mV, which was significantly greater than that seen in the low Cl- control (12.9 ± 1.3; p = 0.01). PAO1 exposure induced a state of acquired CFTR dysfunction in rabbit nasal epithelium as measured by forskolin-stimulated short-circuit current (ISC ) (control, 37.0 ± 1.1 µA/cm2 ; PAO1, 24.4 ± 1.1 µA/cm2 ; p < 0.001). RNE cultures exposed to PAO1 had inhibited mucociliary function, whereas coincubation with ivacaftor restored mucociliary clearance, as measured by µOCT. CONCLUSION: In rabbit nasal epithelium, ivacaftor robustly stimulates CFTR-mediated Cl- secretion and normalizes ASL and CBF in PAO1-induced acquired CFTR dysfunction. Preclinical testing of CFTR potentiators as therapy for P aeruginosa rabbit sinusitis is planned.

A Non-inferiority Trial: Safety and Efficacy of Topical 1:1000 versus 1:10 000 Epinephrine in Sino-nasal Surgeries.

OBJECTIVE: This study aimed to test the non-inferiority of topical 1:1000 epinephrine compared to topical 1:10 000 with regard to intraoperative hemodynamic stability, and to determine whether it produced superior visibility conditions. METHODS: A single-blinded, prospective, cross-over non-inferiority trial was performed. Topical 1:1000 or topical 1:10 000 was placed in 1 nasal passage. Hemodynamic parameters (heart rate, systolic and diastolic blood pressures, and mean arterial pressure) were measured prior to insertion then every minute for 10 minutes. This was repeated in the contralateral nasal passage of the same patient with the alternate concentration. The surgeon graded the visualization of each passage using the Boezaart Scale. The medians of the greatest absolute change in parameters were compared using a Wilcoxon Rank-Signed test and confidence intervals were calculated using a Hodges-Lehman test. The non-inferiority margin was pre-determined at 10 bpm for heart rate and 10 mmHg for blood pressures. A Wilcoxon Rank-Signed test was used to assess superiority in visualization. RESULTS: Thirty-two patients were enrolled and after exclusions, nineteen were assessed (mean age = 35.63 ± 12.49). Differences in means of greatest absolute change between the 2 concentrations were calculated (heart rate = 2.49 ± 1.20; systolic = -1.51 ± 2.16; diastolic = 2.47 ± 1.47; mean arterial pressure = 0.07 ± 1.83). In analyses of medians, 1:1000 was non-inferior to the 1:10 000. There was a significant difference (-0.58 ± 0.84; P = .012) in visualization in favor of topical 1:1000. CONCLUSION: Topical 1:1000 epinephrine provides no worse intraoperative hemodynamic stability compared to topical 1:10 000 but affords superior visualization and should be used to optimize surgical conditions.

Infection After Endoscopic Dacryocystorhinostomy: Incidence and Implications.

BACKGROUND: Endoscopic dacryocystorhinostomy (EN-DCR) is an increasingly common procedure performed by otolaryngologists. While EN-DCR has a high rate of success at relieving blockage of the lacrimal system, little is known regarding associated postoperative infection (POI) rates and risk factors. OBJECTIVE: The purpose of this study was to identify factors associated with the occurrence of postoperative orbital and rhinologic infection in a large cohort of patients undergoing EN-DCR. METHODS: A retrospective review of 582 patients who underwent EN-DCR was performed. All patients received antibiotic prophylaxis as a single intraoperative intravenous administration and a ten-day postoperative oral course. Clinical and demographic information was reviewed, including the occurrence of acute orbital or rhinologic infection within 30 days of surgery. Multivariable analysis was performed to identify risk factors associated with POI. RESULTS: Fifteen of 582 patients (2.6%) developed POI following EN-DCR. The most common POI was acute rhinosinusitis (10/15, 66.7%), followed by acute dacryocystitis (2/15, 13.3%), preseptal cellulitis (2/15,13.3%), and acute bacterial conjunctivitis (1/15, 6.7%). The majority of patients (464/582, 79.7%) underwent concurrent endoscopic sinus surgery (ESS). In most cases (302/464, 65.1%), ESS was performed to address comorbid rhinosinusitis, whereas 7.8% (36/464) of patients underwent surgery to enhance surgical access to the lacrimal sac. Patients who underwent concurrent ESS were less likely to develop POI (OR: 0.17, CI: 0.04-0.80, p < 0.05). Evidence of mucopurulence at surgery increased the likelihood of POI (OR: 6.24, CI: 1.51-25.84, p < 0.05). CONCLUSION: Mucopurulence at the time of surgery significantly increased the risk of POI, whereas concurrent ESS, performed most commonly to address comorbid rhinosinusitis, significantly decreased the risk of POI. Awareness of risk factors for POI and appropriate surgical management of concurrent rhinosinusitis can lead to reduced infectious complications after EN-DCR.

Korean Red Ginseng aqueous extract improves markers of mucociliary clearance by stimulating chloride secretion.

BACKGROUND: 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. METHODS: Primary murine nasal septal epithelial (MNSE) [wild-type (WT) and transgenic CFTR-/-], fisher-rat-thyroid (FRT) cells expressing human WT CFTR, and TMEM16A-expressing human embryonic kidney cultures were utilized for the present experiments. Ciliary beat frequency (CBF) and airway surface liquid (ASL) depth measurements were performed using micro-optical coherence tomography (µOCT). Mechanisms underlying transepithelial Cl- transport were determined using pharmacologic manipulation in Ussing chambers and whole-cell patch clamp analysis. RESULTS: RGAE (at 30µg/mL of ginsenosides) significantly increased Cl- transport [measured as change in short-circuit current (ΔISC = µA/cm2)] when compared with control in WT and CFTR-/- MNSE (WT vs control = 49.8±2.6 vs 0.1+/-0.2, CFTR-/- = 33.5±1.5 vs 0.2±0.3, p < 0.0001). In FRT cells, the CFTR-mediated ΔISC attributed to RGAE was small (6.8 ± 2.5 vs control, 0.03 ± 0.01, p < 0.05). In patch clamp, TMEM16A-mediated currents were markedly improved with co-administration of RGAE and uridine 5-triphosphate (8406.3 +/- 807.7 pA) over uridine 5-triphosphate (3524.1 +/- 292.4 pA) or RGAE alone (465.2 +/- 90.7 pA) (p < 0.0001). ASL and CBF were significantly greater with RGAE (6.2+/-0.3 µm vs control, 3.9+/-0.09 µm; 10.4+/-0.3 Hz vs control, 7.3 ± 0.2 Hz; p < 0.0001) in MNSE. CONCLUSION: RGAE augments ASL depth and CBF by stimulating Cl- secretion through CaCC, which suggests therapeutic potential in both CF and non-CF chronic rhinosinusitis.

Lynch vs transcaruncular approach: optimizing access to the lateral frontal sinus.

BACKGROUND: Visualization and instrumentation of the frontal sinus is not always possible with a Draf III or modified endoscopic Lothrop procedure (MELP), and external incisions can help augment exposure. We compare lateral frontal sinus access using only a MELP compared to the adjunctive transcaruncular approach and transcutaneous Lynch incision. METHODS: Twelve cadaveric heads underwent thin-cut computed tomography scanning. Measurement of the frontal beak, anteroposterior depth of the frontal sinus, and interorbital distance was performed. There were 4 specimens with poorly pneumatized frontal sinuses that were excluded from the study. Eight cadaveric heads (16 sides) were dissected and a MELP with bilateral transcaruncular and Lynch incisions for access to the lateral frontal sinus was performed. Under image guidance, measurements extended from the midline crista galli to the most lateral point of the frontal sinus visualized using a 0-degree endoscope with straight suction and a 30-degree endoscope with curved suction. RESULTS: The proportion of the ipsilateral frontal sinus accessed through the contralateral nare with a 0-degree endoscope and straight suction using a MELP only, a MELP with transcaruncular approach, and a MELP with Lynch incision, respectively, averaged 41.6%, 51.6%, and 58.9% on the right, and 48.9%, 47.1%, and 61.2% on the left. Using a 30-degree endoscope and curved suction the proportion accessed using a MELP only, a MELP with transcaruncular approach, and a MELP with Lynch incision, respectively, increased to 76.1%, 62.6%, and 91.8% on the right, and 83.2%, 62.7%, and 88.7% on the left. CONCLUSION: Adjunctive external approaches can improve access and instrumentation of the frontal sinus when combined with a MELP.

Endoscopic endonasal intraconal orbit surgery.

Endoscopic endonasal orbital surgery is evolving. With increasing knowledge, expertise, and technology, the historical limits of the endonasal endoscopic approach to the orbit have been redefined. This review discusses the clinical presentation and etiology, and highlights the pertinent anatomy, and discusses the diagnostic workup and surgical approach to orbital tumors and post-operative care. The role of the multidisciplinary team is not to be underestimated. The introduction of a classification system to ensure standardization of technical difficulty and outcome data will assist with international collaboration and further consolidate our attainment of knowledge in this developing field.

Nonopioid Adjuncts and Alternatives.

Multimodality nonopioid analgesia can be effective for pain control. Balancing risks and benefits of treatment should guide the appropriateness of opioid versus nonopioid pain control.

Frontal sinus fractures and cerebrospinal fluid leaks: a change in surgical paradigm.

PURPOSE OF REVIEW: Traditionally, frontal sinus trauma has been treated using open incisions to access the anterior and/or posterior table. Mounting evidence indicates frontal sinus trauma can be managed using an endoscopic endonasal approach (EEA) with less morbidity. Such an approach permits preservation of a functional sinus and less reliance on computed tomography for postoperative follow up. The goal of this article is to highlight a shift in paradigm away from open approaches using external incisions towards an EEA to repair cerebrospinal fluid (CSF) leaks and fractures of the frontal sinus. RECENT FINDINGS: In a prospective case series of 46 patients undergoing EEA to frontal sinus fractures, 41 patients had active CSF leaks arising from the posterior table of the frontal sinus. A successful endoscopic repair was achieved in 97.6% with only one patient requiring revision Draf IIB surgery. Anterior table fractures were also successfully reduced with excellent cosmesis. SUMMARY: Endoscopic repair of frontal sinus fractures and CSF leaks is effective and well tolerated. In select patients, it is the preferred treatment as it maintains normal sinus structure and function, minimizing both early and late complications.

Lightening in a bottle: comparison of ultraviolet light to traditional sterilization in saline irrigations bottles.

BACKGROUND: Nasal saline irrigations (NSIs) are commonplace in treatment of patients with sinonasal disorders. Contamination of both the water source and delivery bottle remains a challenge with this therapy. The goal of this study was to optimize a disinfection technique with various methods of preparation, disinfection, and delivery of NSIs. METHODS: Distilled and tap water sources in NSI bottles were contaminated by 4 bacterial strains: Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, and Legionella pneumophila. Contaminated bottles were cleaned with tap water, tap water with detergent, or microwave and swabbed for culture. Water-source disinfection was performed with reverse osmosis, distillation, activated carbon filtration, boiling, or ultraviolet (UV) light treatment. Test samples from each experimental group (n = 3/group) were cultivated on the appropriate media with colony-forming units (CFUs) reported. RESULTS: All methods of bottle cleaning with tap water with/without detergent and microwave significantly reduced bacterial load (CFUs) by >99% (p < 0.05). Distillation and boiling of the contaminated water source eliminated 100% of bacteria, whereas reverse osmosis and activated carbon filtration did not. A single UV treatment of contaminated water within a bottle eliminated 99% of bacteria within the water and 100% in the bottle. CONCLUSION: Cleansing of NSI bottles with tap water with/without detergent or microwave produced robust bacterial disinfection. Distillation and boiling of a contaminated water source completely eliminated all bacteria. UV light treatment was capable of simultaneous disinfection of both the water source and bottle, suggesting this may be a convenient, 1-step method of preparing NSIs for patients.

The role of routine nasolacrimal sac biopsy during endoscopic dacryocystorhinostomy.

OBJECTIVES/HYPOTHESIS: Most patients who undergo endoscopic dacryocystorhinostomy (DCR) have a diagnosis of idiopathic nasolacrimal duct obstruction. The purpose of this study was to examine the impact of routine biopsy of the lacrimal sac performed at time of DCR on subsequent patient diagnosis and treatment. STUDY DESIGN: Retrospective review. METHODS: The histopathology of nasolacrimal specimens (n = 769), obtained from 654 consecutive patients undergoing endoscopic DCR by a single surgeon over a 30-year period, were reviewed. Specific focus included the identification of unanticipated pathologic findings as they related to pertinent patient demographics, clinical presentation, radiologic findings, and intraoperative observations. RESULTS: The study population was 69.6% female, with an average age of 56.1 ± 18.2 years. Pathological findings of tissue from the nasolacrimal sac, which was routinely sampled in all cases, showed inflammation (n = 566 [73.6%]), normal histology (n = 147 [19.1%]), granulomas (n = 8 [1.0%]), and neoplastic process (n = 7 [0.9%]). Patient history, preoperative CT scan, and/or intraoperative findings alerted the surgeon to the possibility of an unusual diagnosis in 12 of the 15 patients. An unsuspected neoplastic or granulomatous cause of lacrimal obstruction was identified on intraoperative biopsy in three patients (0.46%). CONCLUSIONS: Although neoplastic and granulomatous diseases are relatively rare causes of lacrimal obstruction necessitating DCR surgery, they may be identified by through patient evaluation in most cases and by routine intraoperative biopsy of the lacrimal sac in all cases. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:584-589, 2020.

Validation of the Maxillary Sinus Roof as a Landmark for Navigating the Pediatric Skull Base.

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.

Antibiotic eluting sinus stents.

OBJECTIVES: Chronic rhinosinusitis (CRS) is a multifactorial disease affecting up to 16% of the United States population and disproportionately affecting the cystic fibrosis (CF) patient population. Despite treating the underlying infection, the use of systemic antibiotics has shown little efficacy in alleviation of symptom burden. This review seeks to discuss recent research on novel antibiotic eluting stent therapy in vitro and within animal models as well as the factors that contribute to its efficacy. DATA SOURCES: PubMed literature review. REVIEW METHODS: A review of all published literature related to antibiotic eluting sinus stents was conducted to integrate and summarize this innovative approach to chronic sinus infections. RESULTS: Placement of the ciprofloxacin sinus stent (CSS) and ciprofloxacin-ivacaftor sinus stent (CISS) exhibited improvement in endoscopic and radiographic findings in rabbit CRS models. While the CSS showed an overall trend toward improvement in microscopic findings and a reduction in biofilm mass, there remained a significant quantity of planktonic bacteria due to antibiotic depletion from an initial burst release in the first 48 hours of stent placement. The CISS and ciprofloxacin-azithromycin sinus stents (CASSs) exhibited controlled antibiotic release over the study period leading to greatly reduced planktonic bacterial load and biofilm mass. In vitro studies indicate that CASS may be just as efficacious at reducing biofilm mass. CONCLUSION: Antibiotic eluting sinus stents show significant promise as a novel therapeutic strategy for CRS. The CISS may have particular promise for the CF patient population by addressing both the infectious and genetic components of disease. Animal studies demonstrate significant promise for translation into human studies. Human clinical trials are warranted to determine the efficacy of antibiotic sinus stents in human patients. LEVEL OF EVIDENCE: NA.

Predictors of long-term success and failure in primary and revision endoscopic dacryocystorhinostomy.

BACKGROUND: Although endoscopic dacryocystorhinostomy (endo-DCR) is a common treatment of nasolacrimal duct obstruction, little is known about the determinants of surgical success and failure. The purpose of this study was to identify patient- and technique-specific factors that may influence surgical outcomes of primary and revision endo-DCR. METHODS: A retrospective review was conducted of 596 patients who underwent endo-DCR over a 30-year period (1989-2018). Patients' demographics and surgical techniques were assessed. RESULTS: Among the cohort of patients (n = 478) who underwent primary endo-DCR, 10% (n = 48) required revision surgery. Patients who failed primary DCR tended to be younger (p = 0.015) and were less likely to have chronic sinonasal inflammation on histopathology (p = 0.047) than the successful surgery group. After adjusting for patient demographics and comorbidities, the occurrence of a postoperative complication was significantly associated with primary DCR failure (odds ratio [OR], 2.2; p = 0.032). Among the cohort of patients (n = 118) who underwent revision endo-DCR, 8.5% (n = 10) required additional revision surgery. Patients who failed revision DCR tended to be younger (p = 0.022), more likely to have had intraoperative laser usage (p = 0.031), and more likely to have had an intraoperative complication (p = 0.013) than the successful revision surgery group. Endo-DCR failure was not associated with smoking status, middle turbinate resection, or intraoperative visualization of the internal common punctum (p > 0.05). CONCLUSION: An understanding of factors associated with primary and revision endo-DCR failure can help to inform preoperative counseling, intraoperative surgical technique, and postoperative care in the treatment of patients with nasolacrimal duct obstruction.

Resveratrol and ivacaftor are additive G551D CFTR-channel potentiators: therapeutic implications for cystic fibrosis sinus disease.

BACKGROUND: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result in defective Cl- transport and cause chronic bacterial infections in the upper and lower airways of cystic fibrosis (CF) patients. Ivacaftor is a CFTR potentiator that improves Cl- transport in CF patients with at least 1 copy of the G551D mutation. Resveratrol is also a potent CFTR potentiator that increases determinants of mucociliary transport. The objective of this study is to determine whether resveratrol and ivacaftor improve Cl- secretion in G551D CFTR over either agent alone. METHODS: Fisher rat thyroid cells (FRT) transfected with G551D CFTR and human sinonasal epithelial cells (HSNE) containing the CFTR G551D mutation were subjected to pharmacologic manipulation of transepithelial ion transport in Ussing chambers. Activity was further evaluated using whole-cell patch clamp methods in G551D FRT cells. RESULTS: In G551D FRT cells, resveratrol (100 µM) and ivacaftor (10 µM) significantly increased Cl- transport (change in short-circuit current, δISC = µA/cm2 ) compared with single-agent and dimethylsulfoxide vehicle controls (resveratrol + ivacaftor 4.97 ± 0.57 vs ivacaftor 0.74 ± 0.12 vs resveratrol 2.96 ± 0.52 vs control 0.74 ± 0.12; p < 0.001). Maximal Cl- secretion (20 µM forskolin) was also significantly enhanced (p < 0.0001). Activity was confirmed in G551D HSNE (resveratrol + ivacaftor 4.48 ± 0.39 vs ivacaftor 1.05 ± 0.11 vs. resveratrol 0.84 ± 0.3 vs control, 0.0 ± 0.02; p < 0.001), and whole-cell patch clamp analysis in G551D FRT cells (resveratrol + ivacaftor -2535 ± 179.3 pA vs ivacaftor -1408.9 ± 101.3 pA vs resveratrol; -766.2 ± 71.2 pA; p < 0.0001). CONCLUSION: Additive improvement in G551D CFTR-mediated Cl- secretion suggests that resveratrol could enhance ivacaftor therapy in these patients and improve CF-related rhinosinusitis.

Acquired cystic fibrosis transmembrane conductance regulator dysfunction.

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.