Key points

Introduction

Olfactory dysfunction is a common complaint for patients visiting otolaryngology offices, with chronic rhinosinusitis (CRS) accounting for 14% to 25% of patients. Of patients with CRS, 28% to 84% complain of a decreased sense of smell. Hyposmia decreases a person’s enjoyment of food and can reduce their overall quality of life. Furthermore, the inability to detect spoiled food, fire, toxic fumes, and gas leaks can be dangerous. There are 2 mechanisms by which chronic rhinosinusitis decreases olfaction. First, the obstruction of the olfactory cleft from polyps, nasal discharge, and mucosal edema decreases the ability of the odorant to reach the olfactory receptors. Second, underlying epithelial inflammatory damage from CRS can affect the health of the olfactory neurons or the neurons’ ability to transmit olfaction to the brain. Addressing olfaction with patients who have CRS is important, because a loss of smell is correlated with a lower quality of life.

Discussing olfaction is especially important in patients undergoing endoscopic sinus surgery (ESS) for CRS or endoscopic endonasal surgery for skull base tumors. Without clear and consistent evidence that ESS improves smell, patients’ postoperative expectations need to be addressed, which includes counseling that olfactory loss may persist or even worsen despite surgery and medical therapy. Addressing olfaction is also important before endoscopic endonasal skull base surgery, because smell loss may occur during tumor resection or harvest of a large nasoseptal flap for reconstruction. In a survey of practicing otolaryngologists, roughly 40% routinely discuss the potential for postoperative anosmia with patients. This figure is important because 17% of malpractice litigation cases from ESS pertain to smell loss or complete anosmia. This article reviews the anatomy and physiology of smell, presents options for olfactory testing that can be done in clinic, discusses surgical and medical considerations to optimize olfaction, and emphasizes the importance of including olfaction in the preoperative consent.

Introduction

Olfactory dysfunction is a common complaint for patients visiting otolaryngology offices, with chronic rhinosinusitis (CRS) accounting for 14% to 25% of patients. Of patients with CRS, 28% to 84% complain of a decreased sense of smell. Hyposmia decreases a person’s enjoyment of food and can reduce their overall quality of life. Furthermore, the inability to detect spoiled food, fire, toxic fumes, and gas leaks can be dangerous. There are 2 mechanisms by which chronic rhinosinusitis decreases olfaction. First, the obstruction of the olfactory cleft from polyps, nasal discharge, and mucosal edema decreases the ability of the odorant to reach the olfactory receptors. Second, underlying epithelial inflammatory damage from CRS can affect the health of the olfactory neurons or the neurons’ ability to transmit olfaction to the brain. Addressing olfaction with patients who have CRS is important, because a loss of smell is correlated with a lower quality of life.

Discussing olfaction is especially important in patients undergoing endoscopic sinus surgery (ESS) for CRS or endoscopic endonasal surgery for skull base tumors. Without clear and consistent evidence that ESS improves smell, patients’ postoperative expectations need to be addressed, which includes counseling that olfactory loss may persist or even worsen despite surgery and medical therapy. Addressing olfaction is also important before endoscopic endonasal skull base surgery, because smell loss may occur during tumor resection or harvest of a large nasoseptal flap for reconstruction. In a survey of practicing otolaryngologists, roughly 40% routinely discuss the potential for postoperative anosmia with patients. This figure is important because 17% of malpractice litigation cases from ESS pertain to smell loss or complete anosmia. This article reviews the anatomy and physiology of smell, presents options for olfactory testing that can be done in clinic, discusses surgical and medical considerations to optimize olfaction, and emphasizes the importance of including olfaction in the preoperative consent.

Olfaction anatomy and physiology

The olfactory cleft is composed of pseudostratified columnar epithelium located below the cribriform plate and extending inferiorly along the septum for about 1 cm. Parasagittally, the olfactory epithelium is roughly 2 cm in length along the superoposterior septum and can extend posteriorly to the face of the sphenoid sinus and laterally to the upper portion of the superior and middle turbinates. The olfactory epithelium contains bipolar neurons, which have ciliated dendrites that extend to the epithelial surface. The cilia have G protein–coupled and cyclic AMP–coupled receptors that are triggered by odorants. Once activated, the signal is propagated along the axons of the olfactory sensory neurons, which together form cranial nerve I. The axons pass through the cribriform plate and synapse in the olfactory bulb. Second-order neurons then send the olfactory signals to the amygdala and primary sensory cortex. In addition to olfactory sensory neurons, the olfactory cleft epithelium contains a balance of supporting cells and mucus-secreting glands. Any disruption in the olfaction cascade of events can lead to smell dysfunction. In CRS, either the odorant is unable to reach the receptor or the signal transduction is ineffectively relayed to the brain because of inflammatory changes in the neuroepithelium.

Olfactory testing

Olfactory testing has not been standardized in the literature, but testing measures are useful in documenting olfactory dysfunction in a patient complaining of smell loss. Testing can be subjective or objective. Formal subjective testing includes the 0 to 100-mm visual analog scale (VAS) or any specific item on a sinonasal-specific quality-of-life questionnaire such as item #5 on the Sinonasal Outcomes Test (SNOT)-22. For the VAS, patients rate their sense of smell from anosmia (0 mm) to perfect olfaction (100 mm). On the SNOT-22, smell is graded on a Likert scale from 0 (worst) to 5 (best).

Objective olfactory testing includes threshold tests and identification tests. The most common threshold test is the butanol threshold test (BTT; Sigma-Aldrich, St Louis, MO). This test includes a dilutional series of butanol, with the lowest butanol concentration tested first. The patient is given 2 solution bottles, 1 with diluted butanol and 1 with water or mineral oil, and is forced to choose which bottle has the odorant. The smell threshold is determined when the bottle with the lowest butanol concentration is detected correctly 5 consecutive times.

Smell identification tests use common odorants in order to test how well a person can detect normal environmental odors. There are several smell identification tests, including the most widespread and commercially available University of Pennsylvania Smell Identification Test (UPSIT; Sensonics, Inc, Haddon Heights, NJ). The UPSIT was first described in 1984 and consists of 40 multiple-choice scratch-and-sniff forced-identification questions. There are multiple-choice answers instead of relying on free recall controls for potential failure in word recall. A score of greater than 35 is normal (range, 0–40). There are 4 answers for each question, thus a patient with anosmia should answer about 10 items correctly by chance alone. A score of 5 or less suggests malingering. Other odor identification tests include the Cross-cultural Smell Identification Test (CCSIT; Sensonics, Haddon Heights, NJ), Brief Smell Identification Test (Sensonics, Inc, Haddon Heights, NJ), Smell Diskettes Olfaction Test (Novimed, Dietikon, Switzerland), and Barcelona Smell Test (BAST-24; Barcelona, Spain).

Another olfaction measure used is the Sniffin’ Sticks test (Burghart, Wedel, Germany), which uses a series of pens for threshold testing, discrimination testing, and identification testing. Smell threshold is determined at the lowest butanol concentration at which a patient can correctly detect the butanol pen twice in a row. For discrimination, a patient is presented with 3 pens and asked to identify which one has an odorant. For identification testing, an odorant pen is presented to the patient, and the patient must select the correct odor from a list of 4 choices.

Conductive olfactory loss

Patients are more likely to have smell loss when polyps, nasal discharge, and mucosal edema obstruct odorant molecules from reaching the olfactory cleft. This conductive-type olfactory loss is likely a major reason why patients with CRS with nasal polyps (CRSwNP) have a greater chance of smell loss than patients with CRS without nasal polyps (CRSsNP). Alt and colleagues found that higher scores on both the Lund-McKay Radiologic Score and the Lund-Kennedy Endoscopy Score correlated with smell loss in patients with CRSwNP. In patients with CRSsNP, the Lund-Kennedy score only weakly correlated with smell loss, and there was no correlation with severity of Lund-McKay score.

Besides overall Lund-McKay score, several investigators have shown that increased opacification on computed tomography (CT) specifically within the olfactory cleft correlates with worsening results on olfactory testing. Kim and colleagues graded the olfactory cleft opacification on CT scan as mild (0%–25%), moderate (25%–75%), and severe (>75%). Six months postoperatively the improvement in olfactory scores, on both the odor threshold and identification tests, was significantly better in the mild group than in the moderate or severe groups ( P <.05). The BTT results were improved after surgery in 87% (29 of 33) of the mild group, 45% (16 of 35) of the moderate group, and 50% (18 of 36) of the severe group. A return to normosmia on the BTT was significantly better in the mild group at 76% (25 of 33), compared with 34% in the moderate group, and 13% (5 of 36) in the severe group. There was also a significant difference in the postoperative recovery rate on the CCSIT, in which 85% (12 of 14) of the mild group showed recovery in olfactory identification compared with only 43% (10 of 23) in the moderate group, and 53% (8 of 15) in the severe group. A return to normosmia on the CCSIT was 50% (7 of 14) in the mild group compared with only 17% (4 of 23) in the moderate group, and 6% (1 of 15) in the severe group. Patients with more severe disease seem to have less reversibility in their sense of smell despite surgical removal of the obstructive polyps. This lack of improvement after surgery, especially in severe CRS cases, supports the theory that there may also be an underlying change within the olfactory epithelium from the chronic inflammation that decreases olfaction.

Inflammatory changes to the olfactory epithelium in chronic rhinosinusitis

To determine whether inflammation from CRS damages the olfactory epithelium in patients with CRS, Kern and colleagues analyzed biopsies from the olfactory cleft of patients undergoing either ESS for chronic sinusitis or septoplasty for septal deviation. The inflammatory changes on pathology were then correlated with patient scores on the UPSIT to determine whether there was a correlation with smell dysfunction. Of the 19 biopsy specimens that contained olfactory epithelium, 10 had an influx of lymphocytes, macrophages, and eosinophils. Seven of these 10 patients (70%) had an abnormal UPSIT score (12–31). Of the 12 patients with a normosmia (UPSIT score >35), only 3 (25%) had an inflammatory response.

In addition to an influx of inflammatory cells, there is a loss of normal olfactory epithelial architecture in patients with CRS and hyposmia compared with those patients with CRS and normosmia. Biopsy specimens in patients with CRS and anosmia have revealed an atrophic and thin olfactory epithelium, a decreased ratio of olfactory receptor neurons to supporting cells, and dendrites from olfactory neurons that are tortuous in their course to the surface. These histologic studies suggest that the olfactory dysfunction experienced by patients with CRS also results from the inflammation and damage within the olfactory epithelium in addition to the obstruction from polyps and nasal discharge.

Impact of endoscopic sinus surgery on olfaction in chronic rhinosinusitis

Ensuring that patients understand the goals of ESS during the surgeon’s preoperative discussion is critical, so that reasonable expectations can be achieved. When conservative medical management fails, ESS is an excellent treatment modality to improve sinonasal drainage, remove obstructing polyps and debris, and allow better access for topical medications and irrigations to reach the sinus cavities. Ample evidence in the literature supports ESS, because overall quality of life is better, endoscopic scores are improved, and patients’ symptoms are better controlled. An improvement in sinonasal symptoms, such as thick nasal discharge and nasal obstruction, can reasonably be achieved with appropriate surgery and postoperative care. However, the return of olfaction is difficult to predict. The only significant prognostic factor that seems consistent across several studies is that patients with CRSwNP have a better chance for improvement in smell compared with those patients with CRSsNP. Removing polyps alleviates obstruction, improves nasal airflow, and allows odorant molecules a better chance to reach the olfactory receptors.

There is no gold standard by which olfaction is tested or reported. Testing measures used to assess outcomes after surgery are generally combinations of the previously mentioned subjective questionnaires and objective odor threshold or identification tests. The outcomes vary widely, and olfactory improvement is unpredictable, ranging from roughly 5% to 85%. In a study of 70 patients undergoing ESS, Jiang and colleagues reported no significant differences in UPSIT or BTT scores before or at least 6 months after surgery, because only 6% of patients noted an improvement in their smell. A 1996 study using the UPSIT showed that 52% of patients have an improvement in smell after surgery and 48% do not at an average of 18 months after surgery. Pade and Hummel used Sniffin’ Sticks and found that, 4 months following sinus surgery, smell improved in 23%, did not change in 65%, and decreased in 9% of patients. In a long-term study of smell outcomes 5 years after ESS, Briner and colleagues reported that 27 of 34 (79%) patients improved on the 100-mm VAS from 28.4 mm before surgery to 58.5 mm. On the BTT, 85% of patients improved, 9% had no improvement, and 6% had deterioration of smell. In evaluating patients based on polyp status with the VAS, Oka and colleagues found that those with CRSwNP improved from 14.0 mm before surgery to 57.9 mm at 3 months, 59.1 mm at 6 months, 32.3 mm at 12 months, and 45.3 mm at 24 months. Those patients with CRSsNP had a higher preoperative score of 30.9 mm, which improved to 53.8 mm at 3 months, 54.4 mm at 6 months, 48.9 mm at 12 months, and 54.2 mm at 24 months.

Several studies examined whether the degree of smell loss preoperatively can predict recovery after surgery. Litvack and colleagues compared the improvement in smell for hyposmics and anosmics and found that only anosmics have a significant improvement in olfaction after ESS. The 40-item UPSIT was used as the objective measure; men with scores of 19 to 33 and women with scores of 19 to 34 were considered hyposmics, and anosmics were men and women with scores of 6 to 18. Anosmics significantly improved on the UPSIT from a preoperative mean of 9.7 to 21.3 6 months after surgery, and this improvement was sustained at 12 months after surgery (mean, 21.7). Regarding hyposmics, there was no significant change in the UPSIT scores from before surgery (28.8) to 6 months (30.0) or 12 months (29.5) after surgery. A second study also suggested that patients with anosmia may be more likely to benefit from ESS than those with hyposmia, but the difference in smell recovery between the two groups was not significant. Using the UPSIT, 60.6% of anosmics improved compared with 42.4% of hyposmics.