Eugene H. Chang

Background: Chronic sinusitis is universal in cystic fibrosis (CF) and our current treatments are ineffective in reversing sinus disease. The objective of this work was to determine if increasing CF transmembrane conductance regulator (CFTR) activity by ivacaftor could treat CF sinus disease and assess its effect on primary sinus epithelial cultures.Methods: Case report of 1 patient with long‐standing chronic sinus disease and a new diagnosis of CF with a mild mutation (P205S) and a severe mutation (G551D). We discuss clinical changes in symptoms, radiographic findings, nasal potential difference testing, and nasal pH values before and after treatment with ivacaftor. We then developed primary sinonasal epithelial cell cultures from a biopsy of the patient to determine changes in airway surface liquid (ASL) pH and ASL viscosity after ivacaftor treatment.Results: Ivacaftor treatment reversed CT findings of CF sinus disease, increased nasal voltage and pH, and resolved sinus symptoms after 10 months of therapy. Ivacaftor significantly increased ASL pH and decreased ASL viscosity in primary airway cultures.Conclusion: This report documents the reversal of CF sinus disease. Based on our in vivo and in vitro results, we speculate that ivacaftor may reverse CF sinusitis by increasing ASL pH and decreasing ASL viscosity. These studies suggest that CFTR modulation may be effective in treating CF and perhaps non‐CF sinusitis.

Objective: This study aimed to describe the hybrid lid crease approach in conjunction with functional endoscopic sinus surgery (FESS) for lateral frontal sinus disease with orbital extension. Study Design: Retrospective case review. Methods: Patients undergoing hybrid lid crease approach with FESS for frontal sinus disease were reviewed retrospectively. Surgical indications consisted of inverting papilloma with extension into the frontal sinus (n = 1) and frontal sinus mucocele (n = 2). Inclusion criteria included presence of disease in the lateral frontal sinus with extension into the orbital space and erosion of the superior orbital rim. Preoperative and postoperative parameters included complete ophthalmologic exam, endoscopic exam, and computed tomography scan. Results: We were able to access the frontal sinus and orbit in all 3 cases and address sinus pathology of the lateral frontal sinus and orbit using the lid crease approach with FESS. All patients had improvement in ophthalmologic symptoms and interval disease resolution and were satisfied with their postoperative lid crease incision. Conclusion: The lid crease approach offers direct access to the frontal sinus with minimal dissection through a well-hidden incision. In our case series of lateral frontal sinus pathology with orbital extension, the hybrid lid crease approach with FESS allowed complete eradication of disease without recurrence.

Background: People with cystic fibrosis (CF) sinus disease have developmental sinus abnormalities with airway bacterial infection, inflammation, impaired mucociliary clearance and thick obstructive mucus. The pathophysiology of airway disease in CF is not completely understood, and current treatments in CF sinus disease ameliorate symptoms but do not provide a cure.Methods: This manuscript reviews the history of CF, its manifestations in sinus disease, and the potential impact and relationship of CF on the upper and lower airway.Results: There is increasing evidence that CF sinus disease may affect CF lung disease, the most common cause of mortality in CF. We have been limited in treating the symptoms of advanced CF sinus disease with our current therapies.Conclusions: Recent discoveries in the pathophysiology of CF using the CF porcine animal model and exciting treatments that address the primary gene defect that may translate into improved outcomes in CF and non‐CF sinusitis in humans.

Objectives/Hypothesis: Obstructive sleep apnea (OSA) is a sleep disorder caused by partial or complete collapse of the pharyngeal airway. Genioglossal advancement (GGA) is a well‐tolerated surgical procedure intended to address hypopharyngeal collapse, yet there are few studies that monitor changes in airflow dynamics at this site. Computation fluid dynamics (CFD) utilizes airflow simulation to predict changes in airflow after anatomic manipulation.Study Design: We investigated the change in volume and airflow dynamics of the pharyngeal airway after GGA in a cadaveric model.Methods: We performed serial GGA from 1 mm (control) to 3, 7, and 9 mm on a lightly preserved cadaver. After each intervention, we performed high‐resolution computed tomography scans, reconstructed the pharyngeal airway, and quantified airspace volume and CFD analysis with both laminar and large eddy simulation models.Results: Airway volume increased with linear GGA. In both CFD simulation models, velocity increased and pressure decreased after 9‐mm advancement secondary to increased airway diameter and less abrupt changes in airway geometry.Conclusions: These results suggest that GGA may be effective in increasing airway volume and flow to address hypopharyngeal obstruction in OSA.Level of Evidence: N/A. Laryngoscope, 123:3227–3232, 2013

Objectives/Hypothesis: Chronic sinusitis is nearly universal in humans with cystic fibrosis (CF) and is accompanied by sinus hypoplasia (small sinuses). However, whether impaired sinus development is a primary feature of loss of the cystic fibrosis transmembrane conductance regulator (CFTR) or a secondary consequence of chronic infection remains unknown. Our objective was to study the early pathogenesis of sinus disease in CF.Study Design: Animal/basic science research.Methods: Sinus development was studied in a porcine CF model.Results: Porcine sinus epithelia expressed CFTR and exhibited transepithelial anion transport. Disruption of the CFTR gene eliminated both. Sinuses of newborn CF pigs were not infected and showed no evidence of inflammation, yet were hypoplastic at birth. Older CF pigs spontaneously developed sinus disease similar to that seen in humans with CF.Conclusions: These results define a role for CFTR in sinus development and suggest the potential of the CF pig as a genetic model of CF‐sinus disease in which to test therapeutic strategies to minimize sinus‐related CF morbidity.

Background: Cell tight junction proteins create a barrier between airway epithelial cells to limit paracellular transport from the apical to basolateral surface. This barrier can impede the entry of respiratory pathogens and toxins from the airway lumen into the systemic circulation. Mast cell–mediated inflammation in the human airway can cause a disruption of this barrier. Tryptase is one of the major mediators released by mast cells and has been studied extensively in diseases such as asthma, reflux, and sinusitis. We hypothesize that tryptase may play a role in airway paracellular permeability by disrupting the cell tight junction proteins. Methods: We tested this hypothesis by applying tryptase on the apical and basolateral surface to primary human airway epithelia grown in an air–liquid interface and measured changes in the transepithelial conductance and paracellular permeability of the membrane during short (every minute) and longer (over hours) time courses. We then immunostained the cell membranes for occludins and claudins to observe for changes in the structure of the tight junctions after tryptase application. Results: Our data show that tryptase does not alter paracellular permeability in human airway cells over minutes or hours, and that tryptase does not alter the structure of the cell junction. Conclusion: Tryptase alone does not alter paracellular permeability in human airway cells. Tryptase may be altering the epithelial membrane independent of the cell tight junction pathway or other mast cell mediators may play a role in permeability.