Acquired cilia dysfunction in chronic rhinosinusitis

Abstract

Background: Cilia are complex and powerful cellular structures of the respiratory mucosa that play a critical role in airway defense. Respiratory epithelium is lined with cilia that perform an integrated and coordinated mechanism called mucociliary clearance. Mucociliary clearance is the process by which cilia transport the mucus blanket overlying respiratory mucosa to the gastrointestinal tract for ingestion. It is the primary means by which the airway clears pathogens, allergens, debris, and toxins. The complex structure and regulatory mechanisms that dictate the form and function of normal cilia are not entirely understood, but it is clear that ciliary dysfunction results in impaired respiratory defense.

Methods: A literature review of the current knowledge of cilia dysfunction in chronic rhinosinsusitis was conducted.

Results: Ciliary dysfunction may be primary, the result of genetic mutations resulting in abnormal cilia structure, or, more commonly, secondary, the result of environmental, infectious, or inflammatory stimuli that disrupt normal motility or coordination. Patients with chronic rhinosinusitis (CRS) have been found to have impaired mucociliary clearance. Many biochemical, environmental, and mechanical stimuli have been shown to influence ciliary beat frequency, and common microbial pathogens of respiratory mucosa such as Pseudomonas aeruginosa and Haemophilus influenzae have developed toxins that appear to interrupt normal mucociliary function. Furthermore, inflammatory mediators known to be present in patients with CRS appear to impair secondarily mucociliary clearance.

Conclusion: The goal of this article is to summarize the recent developments in the understanding of cilia dysfunction and mucociliary clearance in CRS.

Figure 1.

Scanning electron microscopy at nearly 4000× magnification of normal sinonasal epithelium. Cilia are densely packed on the mucosal surface.

Figure 2.

Schematic diagram of the ultrastructure of the axoneme of motile cilia containing two central singlet microtubules surrounded by nine doublet microtubules.

Figure 3.

Dynamic regulation of ciliary beat frequency. Air–liquid interface cultures were established from three different mice (■, ♦, and ▴). Continuous ciliary beat frequency was recorded before and after application of mechanical stimulation (arrow) delivered as an air puff. The panel on the left represents raw data (Hz), and panel on the right normalizes the data to the frequency just before the stimulation.

Figure 4.

Scanning electron microscopy at 1500× magnification of chronic rhinosinusitis sinonasal mucosa showing substantial ciliary loss.