- Email: [email protected]
Subjective improvement of olfactory function after endoscopic sinus surgery for chronic rhinosinusitis
Subjective Improvement of Olfactory Function After Endoscopic Sinus Surgery for Chronic Rhinosinusitis Brian F. Perry, MD,* and Stilianos E. Kountakis, MD, PhD† Objective: The purpose of this study was to determine the effect of functional endoscopic sinus surgery (FESS) on subjective olfactory dysfunction in patients with chronic rhinosinusitis. Materials and Methods: Prospective collection of data on consecutive patients undergoing FESS after failing prolonged medical therapy for chronic rhinosinusitis at a tertiary institution. Patients were asked to grade their olfactory dysfunction from 0 to 10, with 0 representing normal function and 10 complete anosmia. In addition, data such as computed tomography scores, presence or absence of nasal polyps, and the presence or absence of asthma were recorded and analyzed. Patients were followed up to 1 year after surgery. Results: Data were collected on 178 patients who had sinus surgery over a 2-year period. The average olfactory dysfunction score before surgery was 4.9. This improved to 0.9 at 1 year after surgery (P ⫽ .00). Higher computed tomography scores as per Lund and MacKay correlated with higher olfactory dysfunction scores (r ⫽ 0.62, P ⬍ .01) and greater improvement after surgery (r ⫽ 0.82, P ⬍ .01). Asthmatics and patients with polyps had higher subjective olfactory dysfunction scores than nonasthmatics and patients without polyps (6.8 and 7.2 v 4.4 and 4.1, respectively). All groups had subjective improvement at 1 year (2.3 and 1.5 v 0.6 and 0.7, respectively; P ⫽ .00). Conclusion: Patients with subjective olfactory dysfunction despite appropriate medical management for rhinosinusitis benefit from FESS. (Am J Otolaryngol 2003;24:366-369. © 2003 Elsevier Inc. All rights reserved.)
Olfactory function is a sense that most people take for granted until it is affected in some way by a disease process. Olfaction plays important roles in taste, warning us of danger, and the triggering of emotions and memories.1 Olfaction also plays an important role in sexual attraction in most mammals, although the role in humans is less clear.2 Olfactory dysfunction has been linked to multiple disease processes from Alzheimer’s Disease to depression.3 One of the most common diseases that may present with olfactory dysfunction is rhinosinusitis.4 Some patients
From the *Department of Otolaryngology–Head and Neck Surgery, University of Virginia, and †Otolaryngology–Head and Neck Surgery, Medical College of Georgia, Augusta, GA. Address correspondence to Stilianos E. Kountakis, MD, PhD, Department of Otolaryngology–Head and Neck Surgery, Medical College of Georgia, 1120 Fifteenth Street, Augusta, GA 30912-4060. E-mail: [email protected] © 2003 Elsevier Inc. All rights reserved. 0196-0709/03/2406-0000$30.00/0 doi:10.1053/S0196-0709(03)00067-X 366
will even have this as their chief complaint. For many, there has been a gradual loss of the sense of smell over time, correlating with their course of rhinosinusitis. Chronic rhinosinusitis is a disease of the lining of the upper respiratory tract involving inflammation and thickening of the mucosal surfaces as well as changes in the underlying bone. Classically, olfactory dysfunction in chronic rhinosinusitis was attributed to nasal obstruction and physical blockade of odorant molecules from reaching the olfactory mucosa high in the nasal vault.5 Clinical observations have failed to support this hypothesis, however. Patients may often have severe olfactory deficits without evidence of physical obstruction to airflow across the olfactory epithelium on nasal endoscopy. This has led to other theories of olfactory dysfunction in rhinosinusitis including olfactory mucosal edema and direct attack on olfactory neurons by virus particles and bacterial toxins. The purpose of this report is to further our understanding of the changes associated with
American Journal of Otolaryngology, Vol 24, No 6 (November-December), 2003: pp 366-369
IMPROVEMENT OF OLFACTORY FUNCTION
367
sinus surgery and to be able to better counsel patients as to the likelihood of recovering subjective olfactory function. MATERIALS AND METHODS One hundred seventy-eight patients undergoing endoscopic sinus surgery for chronic rhinosinusitis by a single surgeon were included in our study. All patients were treated with and failed maximal medical therapy (inhaled nasal steroids, guaifenesin, nasal saline douches, and antibiotics if indicated) for at least 1 month before surgery. All surgeries were performed between 1999 and 2001. The senior author and resident physicians under his supervision, using the Messerklinger technique,6-8 performed all surgeries. It is the philosophy of the senior author that the middle turbinate must be preserved whenever possible. If partial resection of the middle turbinate was indicated, only the most anterior-inferior portion of the middle turbinate was resected. No major resection of the middle turbinate was performed in this series. Average patient age was 47, and there were 88 women and 90 men. All patients underwent a standard noncontrast coronal computed tomography (CT) scan before surgery. Patients were excluded from the study if they did not provide an olfactory score or if they did not follow up for 1 full year after surgery. Patients were asked to rate their olfactory (dys)function on a scale from 0 to 10, with 0 being normal sense of smell to 10 being complete anosmia. Data were also compiled on patients as to presence or absence of polyps and other comorbidities such as asthma. Patients were asked to fill out the questionnaire at the initial preoperative visit then at 3 months, 6 months, and 1year postoperatively. CT scans were graded according to the Lund- MacKay9 grading system for each patient. All patients were treated with broad-spectrum antibiotics for 2 weeks after surgery. All patients continued to be treated with their standard medical regimen for rhinosinusitis after surgery (inhaled nasal steroids and guaifenesin 1,200 mg twice daily) for at least 1 year. Patients were instructed in techniques of nasal douching with a saltwater mixture and encouraged to perform this procedure at least twice a day. Patients were seen in routine follow up at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year after surgery. Any observed crusting was removed under direct vision. Statistical analysis was performed using the Student t test to report P values for the average olfactory dysfunction scores before and after surgery. Preoperative CT and olfactory dysfunction scores were correlated by using the Pearson correlation function. Statistical significance is achieved if P ⬍ .05.
Fig 1. Average subjective olfactory dysfunction scores based on a scale from 0-10, with 0 being normal sense of smell and 10 being complete anosmia.
RESULTS One hundred seventy-eight patients met the criteria for entry into the study. The average preoperative subjective olfactory score for all patients was 4.9 ⫾ 1.8. At 3 months postoperatively, 154 of 178 (86%) indicated improvement of their olfactory function, 19 (11%) reported no change, and 5 (3%) reported worsening of their olfactory function. One year after surgery, 173 (97%) patients reported olfactory function improvement, 3 (2%) reported no change, and 2 (1%) reported worsening. The average olfactory function score of the last 2 patients was 1 point higher than before surgery. All 5 patients that reported no change or worsening of olfactory function are asthmatics and with nasal polyps. Looking at the degree of subjective olfactory improvement, the average olfactory score of all patients was 1.8 ⫾ 0.6 3 months after undergoing surgery (P ⫽ .00). Average olfactory score improved to 1.3 ⫾ 0.6 and 0.9 ⫾ 0.4 6 and 12 months after surgery, respectively. There was no statistical significance between the values at 3 months and 6 months (P ⫽ .10) or 6 months and 1 year (P ⫽ .20), but between 3 months and 1 year was found to be significant (P ⫽ .006) (Fig 1). Other data were examined in conjunction. Men had a higher preoperative subjective olfactory scores than women (5.7 ⫾ 1.9 v 4.1 ⫾ 1.7) (P ⫽ .009). Average scores improved to 1.5 ⫾ 0.7 versus 1.1 ⫾ 0.5 at 6 months and 1.0 ⫾ 0.4 versus 0.8 ⫾ 0.4 at 1 year postoperatively (P ⫽ .00).
368
Fig 2. Average subjective olfactory dysfunction scores for asthmatics versus nonasthmatics.
CT scores for all patients were examined. These showed a correlation with olfactory function preoperative score (r ⫽ 0.62, P ⫽ .01). Thirty-eight out of 178 patients were identified with a diagnosis of asthma. Patients with a diagnosis of asthma on average had higher CT scores (17.6 v 11.8) and higher preoperative olfactory dysfunction (6.8 ⫾ 2.0 v 4.4 ⫾ 1.6) than nonasthmatics (Fig 2). Overall, 33 (87%) asthmatics improved, 3 (8%) reported no change, and 2 (5%) reported subjective worsening of their olfactory function by an average of 1 point. Generally, asthmatics improved after surgery; however, the average score at 1 year was still higher compared to nonasthmatics at 1 year. Patients with polyps faired similarly to those with asthma. Fifty of 178 patients were identified with nasal polyps. They had a higher preoperative olfactory dysfunction score than those without polyps (7.2 ⫾ 2.1 v 4.1 ⫾ 1.5). They again improved after surgery but continued to have slightly higher olfactory dysfunction scores at 1 year than nonpolyp patients (1.5 ⫾ 0.5 v 0.7 ⫾ 0.3) (Fig 3).
PERRY AND KOUNTAKIS
signal.10 Several hypotheses have been put forth to explain hyposmia in the setting of chronic rhinosinusitis. Odorants may be physically blockaded by swollen or hypertrophied mucosa and prevented from reaching the olfactory epithelium. Originally, this was thought to be the mechanism for hyposmia in chronic rhinosinusitis. Clinical observations tend to dispute this. Many patients with hyperplastic rhinosinusitis will present with large amounts of polyps in the middle meatus; however, the nasal vault appears free of disease with an unobstructed path to the olfactory epithelium. These patients will often complain of severe disturbances in smell. Another hypothesis is that there is edema of the neuroepithelium preventing neural signal generation.11 As stated earlier, the odorant molecules are generally hydrophobic, and so edema of the neuroepithelium may prevent these molecules from coming into contact with the transduction apparatus. The olfactory epithelium relies on carefully balanced intracellular and extracellular ionic concentrations and osmotic pressures for signal generation and transduction.12 This may be disturbed by a local inflammatory response. After an otherwise full recovery from an upper respiratory tract illness, some patients will continue to complain of hyposmia. Biopsies of olfactory epithelium obtained from
DISCUSSION Olfactory function is a complex process whereby small air-borne hydrophobic molecules are transported to respiratory epithelium where they are converted into a neuronal
Fig 3. Average subjective olfactory dysfunction scores for patients with and without polyps on initial examination.
IMPROVEMENT OF OLFACTORY FUNCTION
these patients show fewer cilia on olfactory dendrites and fewer olfactory neurons and axons.13 This evidence has been used to propose that there may be a direct neurotoxic affect by certain viruses and bacterial toxins. Whatever the reason, patients with chronic rhinosinusitis often complain of a decrease or loss of their sense of smell. This deficit can range from being only a nuisance to causing severe concern and distress in different patients. Patients who rely on their sense of smell/taste for occupational reasons are particularly distressed. Many patients will ask their surgeon what is the likelihood of subjective improvement of their sense of smell after surgery. This is an important question because an individual’s sense of smell is affected not only by cultural and ethnic background but also by individual personal experiences. This study was performed to allow us to be able to more accurately counsel our patients on this question. This study does not attempt to report on objective olfactory outcomes after functional endoscopic sinus surgery. On average, all groups of patients improved their subjective sense of smell after surgery. Those with evidence of nasal polyps and those with a diagnosis of asthma had higher olfactory dysfunction scores before surgery, but these patients also improved about the same degree as those without polyps or asthma. Three patients with asthma and polyps reported no change and 2 worsening of the olfactory function by an average of 1 point. Average improvement in the sense of smell continued up to 1 year after surgery in all groups. Improvements likely represent a combination of the surgery as well as adequate and consistent treatment postoperatively. Men reported worse subjective olfactory function than women, as it has been shown in the literature.14 Both groups improved significantly 1 year after surgery. In summary, olfaction is a complex process affected by chronic rhinosinusitis in ways yet to be shown. Most likely it is a combination of factors including physical blockade to airflow,
369
neuroepithelial edema, and direct neurotoxic affects of viruses and bacterial toxins. An individual’s qualitative sense of smell is also affected by that individual’s personal experience and overall state of physical and mental health. Patients often ask the likelihood of subjective improvement in olfaction after endoscopic sinus surgery. Based on our data, patients can be expected to improve significantly in a period up to 1 year after surgery. This most likely represents a combination of surgery and postoperative medical therapy. REFERENCES 1. Wang L, Walker VE, Sardi H, et al: The correlation between physiological and psychological responses to odour stimulation in human subjects. Clin Neurophysiol 113:542-551, 2002 2. Sobel N, Brown WM: The scented brain: Pheromonal responses in humans. Neuron 31:512-514, 2001 3. Cullen MM, Leopold DA: Disorders of smell and taste. Med Clin North Am 83:57-74, 1999 4. Shin SH, Park JY, Sohn JH: Clinical value of olfactory function tests after endoscopic sinus surgery: A short-term result. Am J Rhinol 13:63-66, 1999 5. Rhee CS, Kim DY, Won TB, et al: Changes of nasal function after temperature-controlled radiofrequency tissue volume reduction for the turbinate. Laryngoscope 111:153-158, 2001 6. Stammberger H: Endoscopic endonasal surgery— Concepts in treatment of recurring rhinosinusitis. Part I. Anatomic and pathophysiologic considerations. Otolaryngol Head Neck Surg 94:143-147, 1986 7. Stammberger H: Endoscopic endonasal surgery— Concepts in treatment of recurring rhinosinusitis. Part II. Surgical technique. Otolaryngol Head Neck Surg 94:147156, 1986 8. Kennedy DW: Functional endoscopic sinus surgery. Technique. Arch Otolaryngol 111:643-649, 1985 9. Lund VJ, Mackay IS: Staging in rhinosinusitis. Rhinology 31:183-184, 1993 10. Sullivan SL: Mammalian chemosensory receptors. NeuroReport 13:A9-17, 2002 11. Apter AJ, Gent JF, Frank ME: Fluctuating olfactory sensitivity and distorted odor perception in allergic rhinitis. Arch Otolaryngol Head Neck Surg 125:1005-1010, 1999 12. Paysan J, Breer H: Molecular physiology of odor detection: Current views. Pflugers Arch Euro J Physiol 441:579-586, 2001 13. Vento SI, Simola M, Ertama LO, et al: Sense of smell in long-standing nasal polyposis. Am J Rhinol 15: 159-163, 2001 14. Callahan CD, Hinkebein JH: Assessment of anosmia after traumatic brain injury: Performance characteristics of the University of Pennsylvania Smell Identification Test. J Head Trauma Rehab 17:251-256, 2002
Olfactory function is a sense that most people take for granted until it is affected in some way by a disease process. Olfaction plays important roles in taste, warning us of danger, and the triggering of emotions and memories.1 Olfaction also plays an important role in sexual attraction in most mammals, although the role in humans is less clear.2 Olfactory dysfunction has been linked to multiple disease processes from Alzheimer’s Disease to depression.3 One of the most common diseases that may present with olfactory dysfunction is rhinosinusitis.4 Some patients
From the *Department of Otolaryngology–Head and Neck Surgery, University of Virginia, and †Otolaryngology–Head and Neck Surgery, Medical College of Georgia, Augusta, GA. Address correspondence to Stilianos E. Kountakis, MD, PhD, Department of Otolaryngology–Head and Neck Surgery, Medical College of Georgia, 1120 Fifteenth Street, Augusta, GA 30912-4060. E-mail: [email protected] © 2003 Elsevier Inc. All rights reserved. 0196-0709/03/2406-0000$30.00/0 doi:10.1053/S0196-0709(03)00067-X 366
will even have this as their chief complaint. For many, there has been a gradual loss of the sense of smell over time, correlating with their course of rhinosinusitis. Chronic rhinosinusitis is a disease of the lining of the upper respiratory tract involving inflammation and thickening of the mucosal surfaces as well as changes in the underlying bone. Classically, olfactory dysfunction in chronic rhinosinusitis was attributed to nasal obstruction and physical blockade of odorant molecules from reaching the olfactory mucosa high in the nasal vault.5 Clinical observations have failed to support this hypothesis, however. Patients may often have severe olfactory deficits without evidence of physical obstruction to airflow across the olfactory epithelium on nasal endoscopy. This has led to other theories of olfactory dysfunction in rhinosinusitis including olfactory mucosal edema and direct attack on olfactory neurons by virus particles and bacterial toxins. The purpose of this report is to further our understanding of the changes associated with
American Journal of Otolaryngology, Vol 24, No 6 (November-December), 2003: pp 366-369
IMPROVEMENT OF OLFACTORY FUNCTION
367
sinus surgery and to be able to better counsel patients as to the likelihood of recovering subjective olfactory function. MATERIALS AND METHODS One hundred seventy-eight patients undergoing endoscopic sinus surgery for chronic rhinosinusitis by a single surgeon were included in our study. All patients were treated with and failed maximal medical therapy (inhaled nasal steroids, guaifenesin, nasal saline douches, and antibiotics if indicated) for at least 1 month before surgery. All surgeries were performed between 1999 and 2001. The senior author and resident physicians under his supervision, using the Messerklinger technique,6-8 performed all surgeries. It is the philosophy of the senior author that the middle turbinate must be preserved whenever possible. If partial resection of the middle turbinate was indicated, only the most anterior-inferior portion of the middle turbinate was resected. No major resection of the middle turbinate was performed in this series. Average patient age was 47, and there were 88 women and 90 men. All patients underwent a standard noncontrast coronal computed tomography (CT) scan before surgery. Patients were excluded from the study if they did not provide an olfactory score or if they did not follow up for 1 full year after surgery. Patients were asked to rate their olfactory (dys)function on a scale from 0 to 10, with 0 being normal sense of smell to 10 being complete anosmia. Data were also compiled on patients as to presence or absence of polyps and other comorbidities such as asthma. Patients were asked to fill out the questionnaire at the initial preoperative visit then at 3 months, 6 months, and 1year postoperatively. CT scans were graded according to the Lund- MacKay9 grading system for each patient. All patients were treated with broad-spectrum antibiotics for 2 weeks after surgery. All patients continued to be treated with their standard medical regimen for rhinosinusitis after surgery (inhaled nasal steroids and guaifenesin 1,200 mg twice daily) for at least 1 year. Patients were instructed in techniques of nasal douching with a saltwater mixture and encouraged to perform this procedure at least twice a day. Patients were seen in routine follow up at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year after surgery. Any observed crusting was removed under direct vision. Statistical analysis was performed using the Student t test to report P values for the average olfactory dysfunction scores before and after surgery. Preoperative CT and olfactory dysfunction scores were correlated by using the Pearson correlation function. Statistical significance is achieved if P ⬍ .05.
Fig 1. Average subjective olfactory dysfunction scores based on a scale from 0-10, with 0 being normal sense of smell and 10 being complete anosmia.
RESULTS One hundred seventy-eight patients met the criteria for entry into the study. The average preoperative subjective olfactory score for all patients was 4.9 ⫾ 1.8. At 3 months postoperatively, 154 of 178 (86%) indicated improvement of their olfactory function, 19 (11%) reported no change, and 5 (3%) reported worsening of their olfactory function. One year after surgery, 173 (97%) patients reported olfactory function improvement, 3 (2%) reported no change, and 2 (1%) reported worsening. The average olfactory function score of the last 2 patients was 1 point higher than before surgery. All 5 patients that reported no change or worsening of olfactory function are asthmatics and with nasal polyps. Looking at the degree of subjective olfactory improvement, the average olfactory score of all patients was 1.8 ⫾ 0.6 3 months after undergoing surgery (P ⫽ .00). Average olfactory score improved to 1.3 ⫾ 0.6 and 0.9 ⫾ 0.4 6 and 12 months after surgery, respectively. There was no statistical significance between the values at 3 months and 6 months (P ⫽ .10) or 6 months and 1 year (P ⫽ .20), but between 3 months and 1 year was found to be significant (P ⫽ .006) (Fig 1). Other data were examined in conjunction. Men had a higher preoperative subjective olfactory scores than women (5.7 ⫾ 1.9 v 4.1 ⫾ 1.7) (P ⫽ .009). Average scores improved to 1.5 ⫾ 0.7 versus 1.1 ⫾ 0.5 at 6 months and 1.0 ⫾ 0.4 versus 0.8 ⫾ 0.4 at 1 year postoperatively (P ⫽ .00).
368
Fig 2. Average subjective olfactory dysfunction scores for asthmatics versus nonasthmatics.
CT scores for all patients were examined. These showed a correlation with olfactory function preoperative score (r ⫽ 0.62, P ⫽ .01). Thirty-eight out of 178 patients were identified with a diagnosis of asthma. Patients with a diagnosis of asthma on average had higher CT scores (17.6 v 11.8) and higher preoperative olfactory dysfunction (6.8 ⫾ 2.0 v 4.4 ⫾ 1.6) than nonasthmatics (Fig 2). Overall, 33 (87%) asthmatics improved, 3 (8%) reported no change, and 2 (5%) reported subjective worsening of their olfactory function by an average of 1 point. Generally, asthmatics improved after surgery; however, the average score at 1 year was still higher compared to nonasthmatics at 1 year. Patients with polyps faired similarly to those with asthma. Fifty of 178 patients were identified with nasal polyps. They had a higher preoperative olfactory dysfunction score than those without polyps (7.2 ⫾ 2.1 v 4.1 ⫾ 1.5). They again improved after surgery but continued to have slightly higher olfactory dysfunction scores at 1 year than nonpolyp patients (1.5 ⫾ 0.5 v 0.7 ⫾ 0.3) (Fig 3).
PERRY AND KOUNTAKIS
signal.10 Several hypotheses have been put forth to explain hyposmia in the setting of chronic rhinosinusitis. Odorants may be physically blockaded by swollen or hypertrophied mucosa and prevented from reaching the olfactory epithelium. Originally, this was thought to be the mechanism for hyposmia in chronic rhinosinusitis. Clinical observations tend to dispute this. Many patients with hyperplastic rhinosinusitis will present with large amounts of polyps in the middle meatus; however, the nasal vault appears free of disease with an unobstructed path to the olfactory epithelium. These patients will often complain of severe disturbances in smell. Another hypothesis is that there is edema of the neuroepithelium preventing neural signal generation.11 As stated earlier, the odorant molecules are generally hydrophobic, and so edema of the neuroepithelium may prevent these molecules from coming into contact with the transduction apparatus. The olfactory epithelium relies on carefully balanced intracellular and extracellular ionic concentrations and osmotic pressures for signal generation and transduction.12 This may be disturbed by a local inflammatory response. After an otherwise full recovery from an upper respiratory tract illness, some patients will continue to complain of hyposmia. Biopsies of olfactory epithelium obtained from
DISCUSSION Olfactory function is a complex process whereby small air-borne hydrophobic molecules are transported to respiratory epithelium where they are converted into a neuronal
Fig 3. Average subjective olfactory dysfunction scores for patients with and without polyps on initial examination.
IMPROVEMENT OF OLFACTORY FUNCTION
these patients show fewer cilia on olfactory dendrites and fewer olfactory neurons and axons.13 This evidence has been used to propose that there may be a direct neurotoxic affect by certain viruses and bacterial toxins. Whatever the reason, patients with chronic rhinosinusitis often complain of a decrease or loss of their sense of smell. This deficit can range from being only a nuisance to causing severe concern and distress in different patients. Patients who rely on their sense of smell/taste for occupational reasons are particularly distressed. Many patients will ask their surgeon what is the likelihood of subjective improvement of their sense of smell after surgery. This is an important question because an individual’s sense of smell is affected not only by cultural and ethnic background but also by individual personal experiences. This study was performed to allow us to be able to more accurately counsel our patients on this question. This study does not attempt to report on objective olfactory outcomes after functional endoscopic sinus surgery. On average, all groups of patients improved their subjective sense of smell after surgery. Those with evidence of nasal polyps and those with a diagnosis of asthma had higher olfactory dysfunction scores before surgery, but these patients also improved about the same degree as those without polyps or asthma. Three patients with asthma and polyps reported no change and 2 worsening of the olfactory function by an average of 1 point. Average improvement in the sense of smell continued up to 1 year after surgery in all groups. Improvements likely represent a combination of the surgery as well as adequate and consistent treatment postoperatively. Men reported worse subjective olfactory function than women, as it has been shown in the literature.14 Both groups improved significantly 1 year after surgery. In summary, olfaction is a complex process affected by chronic rhinosinusitis in ways yet to be shown. Most likely it is a combination of factors including physical blockade to airflow,
369
neuroepithelial edema, and direct neurotoxic affects of viruses and bacterial toxins. An individual’s qualitative sense of smell is also affected by that individual’s personal experience and overall state of physical and mental health. Patients often ask the likelihood of subjective improvement in olfaction after endoscopic sinus surgery. Based on our data, patients can be expected to improve significantly in a period up to 1 year after surgery. This most likely represents a combination of surgery and postoperative medical therapy. REFERENCES 1. Wang L, Walker VE, Sardi H, et al: The correlation between physiological and psychological responses to odour stimulation in human subjects. Clin Neurophysiol 113:542-551, 2002 2. Sobel N, Brown WM: The scented brain: Pheromonal responses in humans. Neuron 31:512-514, 2001 3. Cullen MM, Leopold DA: Disorders of smell and taste. Med Clin North Am 83:57-74, 1999 4. Shin SH, Park JY, Sohn JH: Clinical value of olfactory function tests after endoscopic sinus surgery: A short-term result. Am J Rhinol 13:63-66, 1999 5. Rhee CS, Kim DY, Won TB, et al: Changes of nasal function after temperature-controlled radiofrequency tissue volume reduction for the turbinate. Laryngoscope 111:153-158, 2001 6. Stammberger H: Endoscopic endonasal surgery— Concepts in treatment of recurring rhinosinusitis. Part I. Anatomic and pathophysiologic considerations. Otolaryngol Head Neck Surg 94:143-147, 1986 7. Stammberger H: Endoscopic endonasal surgery— Concepts in treatment of recurring rhinosinusitis. Part II. Surgical technique. Otolaryngol Head Neck Surg 94:147156, 1986 8. Kennedy DW: Functional endoscopic sinus surgery. Technique. Arch Otolaryngol 111:643-649, 1985 9. Lund VJ, Mackay IS: Staging in rhinosinusitis. Rhinology 31:183-184, 1993 10. Sullivan SL: Mammalian chemosensory receptors. NeuroReport 13:A9-17, 2002 11. Apter AJ, Gent JF, Frank ME: Fluctuating olfactory sensitivity and distorted odor perception in allergic rhinitis. Arch Otolaryngol Head Neck Surg 125:1005-1010, 1999 12. Paysan J, Breer H: Molecular physiology of odor detection: Current views. Pflugers Arch Euro J Physiol 441:579-586, 2001 13. Vento SI, Simola M, Ertama LO, et al: Sense of smell in long-standing nasal polyposis. Am J Rhinol 15: 159-163, 2001 14. Callahan CD, Hinkebein JH: Assessment of anosmia after traumatic brain injury: Performance characteristics of the University of Pennsylvania Smell Identification Test. J Head Trauma Rehab 17:251-256, 2002