Jeremiah A. Alt, MD, PhD
Figure 1: Representation of cilia in the upper respiratory system.
In order for the mucus produced in the sinuses to reach the throat, the cilia throughout the sinonasal cavity are “programmed” to beat in a very specific direction. Each sinus has an ostium (opening) that the cilia carry the mucus towards and through into defined anatomical areas within the sinonasal cavity (see sinus anatomy). The middle meatus is located lateral to the middle turbinate and accepts drainage from the frontal, maxillary, and the anterior ethmoid sinuses. Posteriorly, the superior meatus is below the superior turbinate, which accepts drainage from the posterior ethmoid sinuses. The drainage continues medially into the sphenoethmoidal recess, which also accepts drainage from the sphenoid sinus and ends up in the nasopharynx or the upper part of the throat and subsequently swallowed.
Cilia continuously beat to drive the debris-laden mucus from the airways. Ciliated cells have multiple sensors that allow the cell to respond to locally produced mediators and/or certain cues, such as changes in mucus thickness and mucus loads to make their cilia increase the speed at which they beat. By increasing the speed at which they beat, the cilia can generate more force and thus continue to clear the heavier mucus, or clear normal mucus at a faster rate. Conversely, when mucociliary clearance is inhibited or slowed there may be an increased incidence of rhinosinusitis, as seen in patients with cystic fibrosis (see cystic fibrosis).
While the ciliated cells respond to environmental cues, environmental insults can also affect cilia function in a detrimental manner. Many microbes that attack the airways produce toxins that rapidly alter cilia movement. Paralyzing the cilia stops the movement of mucus and optimizes the conditions for infection. Infection perpetuates a local inflammatory response and it is becoming clear that even the inflammatory molecules our bodies produce to fight infection also have detrimental effects on cilia function thereby worsening the insult and further hindering mucus clearance. The combination of microbes and inflammation over a relatively short period can lead to loss of cilia (Figure 2).
Figure 2: Note the extensive loss of cilia.
The upper respiratory system needs a mechanism by which it can detect and initiate an appropriate response to microbes. Bitter taste receptors (T2Rs), identified in the cilia of sinonasal epithelial cells, are an emerging receptor class that may be contributing to this mechanism via recognition and removal of microbes. For example activation of one specific T2R, T2R38, by molecules secreted by gram-negative (a particular type of) bacteria, stimulates the ciliated cells to produce nitric oxide, which in turn increases mucociliary clearance and directly diffuses into the mucus where it kills bacteria. Furthermore, genetic variability of T2R38 may explain why certain individuals are more susceptible to developing gram-negative infections and inflammation. Additional T2Rs are expressed throughout the respiratory epithelium but the role of these T2Rs have yet to be identified.
This combination of microbial and inflammatory products is often found in the upper airway of patients with chronic rhinosinusitis. The good news is that if the microbes can be removed and the inflammation controlled, the cilia can regrow and resume proper movement of mucus.
Why certain individuals can easily recover from an upper respiratory infection without developing chronic rhinosinusitis while others seem to always progress to a lengthy course is not completely understood. What we do know is this: when it comes to the development of chronic rhinosinusitis many factors including anatomic variations, microbial exposure, as well as an individual’s inflammatory response play a role. Novel approaches are being developed to help combat sinonasal infection, improve removal of mucus, accelerate sinus healing, and control the inflammation.
An understanding of the physiology of the nose is critical to understand nasal symptoms and diseases that can develop in the nose and sinuses, which are described further under the tabs conditions and treatments.
©American Rhinologic Society