New insights into the pathogenesis of cystic fibrosis sinusitis

Abstract

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.

Keywords: CFTR; airway biology; electrophysiology; gene therapy; ion transport.

Figure 1

Transcellular ion transport in airway epithelia. Measurements of voltage (Vt), current (i), and conductance (Gt) are drawn in relation to an electric circuit. Vt measures the electric potential difference between the apical and basolateral surface of the cell, i the flow of electrical charge through the cell, and Gt the ease at which the current flows through the cell via ion channels. In this simplified diagram airway epithelia have a sodium–potassium adenosine triphosphatase (Na⁺/K⁺-ATPase) pump and channels/transporters on the basolateral side, and the epithelial Na⁺ (ENaC) and Cl⁻ (CFTR) channels on the apical surface (A). In CF epithelia loss of the CFTR channel reduces Cl transport with increased basal Vt levels.

Figure 2

Piglet anatomy. Sagittal split of piglet head. A. Right hemisagittal section : unc = Uncinate process, mt = Middle turbinate, eth = ethmoid sinus. C, Left hemisagittal section with the uncinate process removed and wire into the middle meatus and in the maxillary sinus (mx). The endoscopic view of the anterior (B) nasal passageway showing the septum (s), inferior turbinate (it), and middle turbinate (mt). Further posterior (D) is the ethmoid sinus (eth).

Figure 3

CF piglet with thick mucus occluding the ethmoid and maxillary sinus (A). Histology of the mucus consistent with cellular debris and gram positive cocci consistent with Staph aureus (B).

Figure 4

Sinus disease without lung disease in a child with CF. Sinus CT scan taken at 4 years of age consistent with chronic sinusitis with thick hyperdense mucus completely occluding the ethmoid and maxillary sinus (A). Lung CT scan taken at the same time without radiologically apparent lung disease (B).