Inter-α-Inhibitor Blocks Epithelial Sodium Channel Activation and Decreases Nasal Potential Differences in ΔF508 Mice

Increased activity of lung epithelial sodium channels (ENaCs) contributes to the pathophysiology of cystic fibrosis (CF) by increasing the rate of epithelial lining fluid reabsorption. Inter-α-inhibitor (IαI), a serum protease inhibitor, may decrease ENaC activity by preventing its cleavage by serine proteases. High concentrations of IαI were detected in the bronchoalveolar lavage fluid (BALF) of children with CF and lower airway diseases. IαI decreased amiloride-sensitive (IENaC) but not cAMP-activated Cl− currents across confluent monolayers of rat ATII, and mouse nasal epithelial cells grew in primary culture by 45 and 25%, respectively. Changes in IENaC by IαI in ATII cells were accompanied by increased levels of uncleaved (immature) surface α-ENaC. IαI increased airway surface liquid depth overlying murine nasal epithelial cells to the same extent as amiloride, consistent with ENaC inhibition. Incubation of lung slices from C57BL/6, those lacking phenylalanine at position 508 (∆F508), or CF transmembrane conductance regulator knockout mice with IαI for 3 hours decreased the open probability of their ENaC channels by 50%. ∆F508 mice had considerably higher levels the amiloride-sensitive fractions of ENaC nasal potential difference (ENaC-NPD) than wild-type littermates and only background levels of IαI in their BALF. A single intranasal instillation of IαI decreased their ENaC-NPD 24 hours later by 25%. In conclusion, we show that IαI is present in the BALF of children with CF, is an effective inhibitor of ENaC proteolysis, and decreases ENaC activity in lung epithelial cells of ∆F508 mice

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. Keywords: CFTR, Cystic fibrosis, CFTR deficiency, CFTR dysfunction, Chronic sinusitis, Chronic rhinosinusitis, Chronic obstructive pulmonary disease, Tobacco, Hypoxia, Resveratrol, l-ascorbat

CBCT-Based Image Guidance for Sinus and Skull Base Surgery

The field of otolaryngology—head and neck surgery encompasses the diagnosis and treatment of a wide variety of disease processes involving the ear, nose, and throat (ENT). In particular, surgeries involving the paranasal sinuses and skull base demand a high level of imaging accuracy because of the complexity of the regional anatomy and intimate association with both neurovascular, ocular and cerebral tissues. Improvements in the field of diagnostic imaging have driven a number of technological advancements in operative techniques, especially stereotactic surgical navigation. Image-guided systems (IGS) monitor surgical instruments relative to known patient anatomic landmarks. This chapter will discuss the origins and utility of this modality and highlight the particular use of in-office and intraoperative CBCT imaging for endoscopic paranasal sinus and skull base surgery

Frontal Sinus Cholesterol Granuloma: Case report

A case report of a massive cholesterol granuloma (CG) of the frontal sinus in a 15-year-old male subject treated endoscopically is reported. CGs are slowly expanding, cystic lesions that are rarely observed in the frontal sinus. Frontal sinus CGs characteristically present with proptosis, diplopia, and a unilateral painless expanding mass above the orbit. Patients frequently report a history of chronic nasal obstruction or head trauma. Although the pathogenesis is unclear, it is likely multifactorial in etiology. Surgical resection via endoscopic sinus surgery has been gaining popularity because of the minimally invasive approach and lower rates of recurrence

Intraoperative IGS/CT updates for complex endoscopic frontal sinus surgery.

INTRODUCTION: Computer-aided surgery (CAS) systems integrate endoscopic visualization with real-time localization based on preoperative imaging. One short-coming of the current systems is the lack of real-time, radiographic assessment of surgical changes. We describe the potential applications of xCAT, a new intraoperative mobile volume CT scanner and its utility in providing surgical navigation updates in the operating room. METHODS: A case report is presented describing how intraoperative CT updates were used in a complicated, revision endoscopic frontal sinus surgery. RESULTS: A 53-year-old male with Samter\u27s triad and a history of multiple previous endoscopic sinus surgeries presented with recurrent, symptomatic nasal polyposis and right-sided frontal headaches. Preoperative CT scans showed a large type III frontal recess cell obstructing the frontal sinus. He underwent revision endoscopic surgery with the use of CAS and the xCAT intraoperative CT scanner. Use of the intraoperative CT scanner to update preoperative images was extremely helpful in the endoscopic dissection of the frontal recess cell and in assessing completeness of dissection along the anterior skull base. CONCLUSION: The xCAT intraoperative mobile volume CT scanner shows promise in providing real-time updates to surgical navigation. This may prove to be a valuable tool in endoscopic sinus surgery, especially in complex revision and frontal sinus cases