Endoscopic biopsy of human olfactory epithelium as a source of progenitor cells

BACKGROUND: The adult central nervous system contains progenitor cells; however, invasive surgery is required for their harvest. Olfactory neuroepithelium (ONe) has attracted attention because it is extracranial and contains progenitor cells that account for its regenerative capacity. Olfactory progenitor cells have been cultured from postmortem ONe. Our aim was to determine if olfactory progenitors could be obtained via biopsy from patients in a feasible, effective, and safe manner. METHODS: Endoscopic biopsy was performed on individuals undergoing sinus surgery (n = 42). Olfactory function was assessed pre- and postoperatively. Specimens were cultured under conditions for olfactory progenitor cell development. RESULTS: Progenitor cells emerged in cultures from 50% of our patients. The superior turbinate, biopsied with cutting punch forceps, gave the highest yield. No adverse impact on olfaction or complications with the biopsy were observed. CONCLUSION: Endoscopic biopsy of ONe for obtaining olfactory progenitor cells from living donors is feasible, effective, and safe.     

Effects of middle turbinate medialization on olfaction.

OBJECTIVE/HYPOTHESIS: Turbinate medialization techniques have gained popularity in an attempt to prevent turbinate lateralization. Theoretically, adhesions between the septum and middle turbinate will prevent lateralization but may compromise airflow to the olfactory neuroepithelium and affect the sense of smell. No studies have addressed this issue. The objective of this study is to evaluate effects of middle turbinate medialization on olfaction. STUDY DESIGN: A prospective controlled study of olfaction before and after middle turbinate medialization using the University of Pennsylvania Smell Identification Test (UP-SIT) and patient questionnaires. METHODS: Fifty patients underwent endoscopic sinus surgery (ESS) with middle turbinate medialization and preservation. The caudal end of the middle turbinate and the opposing septal mucosa were abraded with a microdebrider for iatrogenic synechia formation in an attempt to avoid lateralization of the middle turbinate. Each of the patients underwent preoperative assessment with a questionnaire and UPSIT. All patients were reevaluated approximately 5 weeks after surgery by endoscopic examination, questionnaire, and the UPSIT. The preoperative and postoperative questionnaire responses were compared for subjective analysis. Objectively, the preoperative and postoperative UPSIT scores were compared using the Student t test. RESULTS: The questionnaires showed that the study population's subjective sense of smell either did not change or improved compared with the preoperative state. Objectively, there was a mean increase of UPSIT scores after surgery. This difference was not statistically significant (P = .4). CONCLUSION: Middle turbinate medialization has no detectable adverse effect on olfaction.     

Clinical significance of smell and taste disorders in patients with diabetes mellitus

Chemosensory dysfunction has been reported in patients with diabetes mellitus (DM). However, the clinical significance in relation to the disease stage remains unclear. The aim of this investigation was to assess olfactory and gustatory function with valid clinical tests in patients with DM types 1 and 2 with and without accompanying diseases. Seventy-six patients with DM were divided into three groups according to disease stage. Taste function was tested by means of impregnated paper strips and smell function was screened using a five-item smell identification test. The results of the patients with uncomplicated DM were compared with the results from 29 healthy subjects. The results showed no significant differences in smell and taste function between patients with uncomplicated DM and healthy subjects. However, patients with additional diseases exhibited decreased smell acuity. Moreover, patients with DM type 2 showed impaired smell function compared with patients with DM type 1.     

Effects of systemic or topical administration of corticosteroids and vitamin B in patients with olfactory loss

BACKGROUND: Aim of the present, unblinded, multicentric, open trial was to compare effects of 3 treatments in patients with olfactory dysfunction. METHODS: Treatments included administration of systemic corticosteroids (oral prednisolone), local corticosteroids (mometasone nasal spray), and systemic vitamin B, respectively. A total of 192 patients participated (95 women, 97 men; mean age 56 years). Duration of the smell loss ranged from 1 to 288 months (average 45 months). Olfactory dysfunction was due to infections of the upper respiratory tract (n = 72), sinunasal disease (n = 19), and posttraumatic olfactory loss (n = 10); the largest portion was classified as idiopathic (n = 85); other causes were rare (n = 6). RESULTS: Following systemic administration of corticosteroids improvement of olfactory function was observed (p < 0.001). Similarly, improvement of the sense of smell was found 2 (p = 0.03) and 6 months (p = 0.001) after local administration of mometasone, respectively. In contrast, after administration of vitamin B no significant change of olfactory function was seen after 2 months, while improvement was present after 6 months (p = 0.001). Duration of olfactory dysfunction had no effect on changes of smell function. CONCLUSIONS: These results indicate that improvement of olfactory function is found in olfactory dysfunction of different causes. Adequately controlled, blinded studies are needed to further explore potential effects of the various treatments.     

Does iron deficiency anemia affect olfactory function?

Conclusion This study found a negative effect of IDA on olfactory function. IDA leads to a reduction in olfactory function, and decreases in hemoglobin levels result in further reduction in olfactory function. Objective This study examined the effects of iron-deficiency anemia (IDA) on olfactory function. Method The study enrolled 50 IDA patients and 50 healthy subjects. Olfactory function was evaluated using the Sniffin’ Sticks olfactory test. The diagnosis of IDA was made according to World Health Organization (WHO) criteria. Results Patients with IDA had a significantly lower threshold, discrimination, and identification (TDI) value, and a lower threshold compared with the control group. However, there were no significant differences between the groups in terms of smell selectivity values.     

Office procedures for quantitative assessment of olfactory function

BACKGROUND: Despite the importance of the sense of smell for establishing the flavor of foods and beverages, as well as protecting against environmental dangers, this primary sensory system is commonly ignored by the rhinologist. METHODS: In this article basic issues related to practical measurement of olfactory function in the clinic are described and examples of the application of the two most common paradigms for such measurement--odor identification and detection--are presented. A listing is made of the 27 olfactory tests currently used clinically, along with their strengths and weaknesses. A brief review of common nasosinus-related disorders for which quantitative olfactory testing has been performed is provided. RESULTS: Although many psychophysical tests are available for quantifying olfactory loss, it is apparent that a number are limited in terms of practicality, sensitivity, and reliability. In general, sensitivity and reliability are positively correlated with test length. Given the strengths of the more reliable forced-choice pyschophysical tests and the limitations of electrophysiological tests, the common distinction between "subjective" and "objective" tests is misleading and should not be used. Complete recovery of olfactory function, as measured quantitatively, rarely follows surgical or medical interventions in patients with rhinosinusitis. CONCLUSION: Given the availability of practical clinical olfactory tests, the modern rhinologist can easily quantify cranial nerve (CN) I function. The application of such tests has led to a new understanding of the effects of nasal disease on olfactory function. Except in cases of total or near-total nasal obstruction, olfactory and airway patency measures usually are unrelated, in accord with the concept that rhinosinusitis primarily influences olfactory function by apoptotic pathological changes within the olfactory neuroepithelium.     

A study on the mechanism of phleboid olfactory function

Phleboid olfactory test has wide clinical application for olfactory disturbance. Many unclarified aspects still remain concerning the mechanism of smell after an intravenous infusion of Alinamin. It is believed that when Alinamin is infused intravenously and byproducts are discharged from the blood into the alveoli, odorous substances reach the nasal cavity through exhalation. In order to clarify the mechanism of smell in more detail, we conducted the following experiments: 1) Cases of laryngectomy were examined to determine if intravenous infusion of Alinamin affected the olfactory organ. 2) Saliva specimens in healthy subjects were collected before and after intravenous infusion of Alinamin and examined for the presence of a secreted odorous substance using a functional test. 3) Healthy subjects who were inhibited in their sense of smell were examined for the presence of garlic odor after intravenous infusion of Alinamin. The results were as follows: 1) 80% of subjects of laryngectomy without cotton in the nares and 20% of subjects of laryngectomy with cotton in the nares perceived the garlic odor. 2) Garlic odorous substance was not recognized in saliva specimens collected before and after intravenous infusion of Alinamin. 3) The healthy subjects inhibited in their sense of smell and intravenously infused with Alinamin perceived the odor at the same time as exhalation. The above results indicated that the mechanism of smell after intravenous infusion of Alinamin occurred via exhalation, but not through the other routes.     

Olfactory dysfunction in Parkinson's disease

An olfactory function test in 18 patients with Parkinson's disease (PD) and 10 age-matched control subjects was performed. Both detection and recognition thresholds were measured with five kinds of synthesized odorants (T & T olfactometry). Before each test, rhinoscopic inspections were performed to exclude subjects who could have respiratory hyposmia. Both detection and recognition thresholds in patients with PD were significantly elevated in comparison with those of control subjects. Auditory acuity of PD patients, however, was well preserved and there was no significant correlation between auditory and olfactory threshold. On the basis of the present study, the authors conclude that olfactory dysfunction is one of the characteristic symptoms of PD and it may be attributed to lesions in the olfactory neural pathway including olfactory neuroepithelium.     

Immunohistopathology of human olfactory epithelium, nerve and bulb

The immunohistochemical characteristics of the human olfactory system were (OMP). OMP was detected in the olfactory receptor neurons and processes extending from the olfactory neuroepithelium to the olfactory bulb. The olfactory receptor cells located close to the epithelial surface also contained OMP. In severely degenerate regions, only a few OMP-containing cells were observed. Differences in OMP-staining intensity were noted among the olfactory receptor cells. The thick neuroepithelium. Proliferating olfactory neuroepithelium contained OMP reactive and nonreactive olfactory receptor cells. The presence of OMP reactive and nonreactive olfactory neurons indicates the coexistence of two functionally different phases of olfactory neurons. These findings suggest that continuous cell turnover is occurring in human olfactory neuroepithelium.     

Local and systemic administration of corticosteroids in the treatment of olfactory loss

BACKGROUND: The aim of this study was to evaluate the benefit of patients with olfactory dysfunction from local (group A) or systemic (group B) administration of corticosteroids. METHODS: This unblinded study was conducted at a smell and taste outpatient clinic of an institutional referral center. Patients with olfactory loss after infections of the upper respiratory tract, patients with apparent sinonasal disease, and patients suffering from "idiopathic" smell loss were included. Effects of mometasone nasal spray, administered for 1-3 months, were studied in 37 patients. In addition, effects of oral prednisolone were analyzed in 55 patients who received decreasing doses over 21 days, starting with a dose of 40 mg. Olfactory function before and after treatment was measured. RESULTS: Although odor identification scores tended to increase (p = 0.05), mometasone nasal spray did not significantly improve olfactory function, when looking at the entire group of patients or when analyzing the three diagnostic categories separately. In contrast, after systemic administration of corticosteroids, improvement of olfactory function was seen over all diagnostic categories (p < 0.001). Interestingly, olfactory function also improved in patients diagnosed with olfactory loss after upper respiratory tract infection (p = 0.05) and in patients initially diagnosed with "idiopathic," olfactory dysfunction (p = 0.008). CONCLUSION: In many patients, local application of corticosteroids appears to have little or no positive effect on olfactory dysfunction, especially when considering long-term changes. Duration of disease, the patient's age/sex, or the presence of parosmia does not appear to predict the response to therapy with corticosteroids.     

Individual significance of olfaction: development of a questionnaire

Clinical experience shows that the individual significance of olfactory function varies between subjects. In order to estimate these individual differences we developed a questionnaire to study the subjective importance of the sense of smell. Questions were arranged within three subscales: association with olfactory sensations, application of the sense of smell, and the readiness to draw consequences from the olfactory perception. The questionnaire was shown to be time efficient, suitable for normosmic subjects and patients with hyposmia or anosmia. It exhibited a good internal reliability (Cronbach’s Alpha = 0.77). First results in 123 subjects indicate that the subjective importance of the sense of smell stays at the same level throughout life-span despite of a decreased olfactory sensitivity. Furthermore, women reported a higher importance of olfaction. It is hoped that this questionnaire will contribute to clarify, for example, cross-cultural differences in the perception of odours.     

The impact and prospect of traumatic brain injury on olfactory function: a cross-sectional and prospective study

Traumatic brain injury (TBI) can cause olfactory loss. The aim of this cross-sectional and prospective study was to determine the prevalence of olfactory loss among 110 patients with TBI within 3 months after the trauma. In 81 patients (“cross-sectional”-group), olfactory function could be measured using the validated “Sniffin’ Sticks” test for odor threshold and odor identification. In addition, the prospective change of olfactory function was studied in 36 patients (“follow-up”-group) by means of a validated odor threshold, discrimination and identification test. Olfactory function was significantly better in patients with TBI I° compared to individuals with TBI II° and III°. Clinically significant improvement of olfactory function was found in 36 % of the patients, most frequently during the first 6 months after the injury, in a median follow-up interval of 21 months. TBI I° has in general no major effect on olfaction. In contrast, patients with TBI II° and III° exhibit smell loss in 57 %. Chances for olfactory recovery were highest within the first 6 months after the trauma.     

Potential oscillation elicited by i.v. olfaction and its applicability as an objective clinical olfaction test

OBJECTIVE: Alinamin has long been applied in Japan for testing i.v. olfaction and to diagnose olfactory disorders. The test is subjective, each subject being asked about the presence or absence of olfaction. The credibility of the answers is highly questionable in some cases; as a result, the reliability of the test is poor. Recent studies demonstrated an induced electric potential in the scalp during i.v. olfactory testing. Some patients complain of the pain of the injection during i.v. olfactory testing; therefore, the effect of this pain must be considered with respect to measurement of the i.v. olfaction-elicited potential (IVOP). MATERIAL AND METHODS: This investigation involved 179 subjects with various olfaction levels. Each subject received an Alinamin injection; the elicited potential amplitude was compared before and after the injection and the increasing ratio (IR) was computed. Gender, age, level of olfactory disorder, the presence or absence of olfaction and the presence or absence of the pain of injection were considered as factors affecting IR. RESULTS: IR showed significant increases in groups characterized by the presence of olfaction as well as in groups reporting pain of injection. The test subjects were further divided into four groups based on their olfaction and pain of injection patterns as follows: Group A, no smell and no pain; Group B, smell and no pain; Group C, no smell and pain; and Group D, smell and pain. Subjects exhibiting no recognizable olfaction or pain of injection (Group A) revealed no increase in IVOP following injection. Subjects with either recognizable olfaction or pain of injection (Groups B and C) exhibited a slight increase in IVOP following injection. Subjects with both noticeable olfaction and pain of injection (Group D) demonstrated a significant increase in IVOP following the injection with a very high value of IR (>2). Furthermore, there were significant differences between the four groups in terms of IR level, with the exception of Groups B and C. CONCLUSIONS: Olfaction is largely involved with the generation of IVOP. However, pain resulting from injection of Alinamin is considered to be a significant factor. IVOP showed significant effectiveness for diagnosing olfactory disorders in cases who did not experience pain of injection.     

Olfactory changes at threshold and suprathreshold levels following septoplasty with partial inferior turbinectomy

Partial inferior turbinectomy with septoplasty is routinely carried out for airway obstruction. However, its effects on the sense of smell have not been systematically evaluated. The aim of this prospective study was to evaluate the influence of septoplasty with partial inferior turbinectomy on threshold and suprathreshold olfactory acuity. The subjects were 30 patients undergoing septoplasty including partial inferior turbinectomy. Olfactory function was determined by the "Sniffin' Sticks," which allow the assessment of odor thresholds, odor discrimination, and odor identification. The patients rated both olfactory function and nasal airflow using visual analog scales. Nasal airflow was measured by anterior rhinomanometry. Multivariate analyses of variance for repeated measures were used to analyze the results before and after surgery (mean interval, 9.1 weeks). After operation, 87% of the patients had increased airflow, 80% had improved olfactory function in terms of odor identification, and in 70% odor discrimination was found to be improved - but only 54% had improved olfactory function in terms of odor thresholds. Surgery increased ratings of nasal airflow in 93%, and those of olfactory function in 77% (p < .001). Similarly, bilateral inspiratory nasal flow increased (p < .001) and olfactory function was improved (p < .001) after surgical treatment. However, this increase was most pronounced for suprathreshold tests, while it was moderate for odor thresholds (interaction "surgery" x "olfactory test," p = .001). The present investigation suggests that septoplasty in combination with inferior turbinectomy has a beneficial effect on olfaction, mainly on suprathreshold olfactory functions. This effect may be partly due to interactions between the increased perception of nasal airflow and cognitive factors involved in olfactory sensitivity. According to the present results and data from the literature, a moderate decrease of olfactory function appears to occur in as many as 20% of patients. However, anosmia seems to be an extremely rare complication of septoplasty and partial turbinectomy.     

Congenital lack of olfactory ability.

Twenty-two patients, all of whom reported never having been able to smell anything, were studied to determine the particular features that distinguish individuals with congenital anosmia. The clinical evaluation on these patients included a thorough medical and chemosensory history, physical examination, nasal endoscopy, chemosensory testing, olfactory biopsies, and imaging studies. There was no evidence to indicate that these patients ever had a sense of smell. The results of olfactory testing suggested that these patients had an inability to detect both olfactory and trigeminal odorants; however, many of the patients in the group seemed to have a slight ability to perceive at least some component of trigeminal odorants. The olfactory epithelium, if it was present at all on biopsy, was abnormal in appearance.     

Olfactory mucosa histological findings in laryngectomees

After total laryngectomy, the patients often report immediate and marked olfactory deficit. The aim of this study was to determine whether hyposmia in laryngectomees reflects olfactory epithelial damage. Ten laryngectomized patients and ten rhinologically normal subjects were subjected to olfactory testing, after which histological examination of biopsied olfactory mucosa was performed. Olfactory testing in laryngectomees revealed a marked reduction in odor perception. Histological examination of olfactory mucosa specimens showed that in laryngectomees some neuroepithelial structural features were comparable with those found in normal subjects. However, additional signs of damage were also observed, consisting mainly of various degrees of epithelial degeneration, above and beyond those that are characteristic of physiological epithelium turnover. These different degenerative features consisted of severe damage to the neuroepithelium, culminating in complete topical loss. Bowman's glands were also observed to be involved in the degenerative process. Laryngectomy-induced hyposmia seems to be correlated with the almost complete loss of nasal airflow due to the disconnection between the upper and lower airways, which prevents odor molecules from reaching the olfactory area, together with degenerative phenomena, which affect the neuroepithelium, and consequent failure in neurosensorial performance.     

Olfactory function following nasal surgery

Objective/Hypothesis: This prospective study aimed to investigate predictors of nasal surgery in terms of olfactory function. Study Design: Prospective study. Methods: A total of 775 patients were included in this prospective study (482 men, 293 women; age range 10–81 years, mean age 41 years, standard deviation = 15.3 y). Prior to surgery, patients received a detailed otorhinolaryngologic examination including nasal endoscopy. Olfactory function was assessed with a standardized odor identification test (“Sniffin' Sticks”). In 356 patients, olfactory function was retested 4 months after surgery (63–339 days after surgery; mean 128 days, standard deviation = 29 days); 206 of these patients received sinus surgery, while 150 received surgery involving the septum. Results: Using a conservative definition of change of olfactory function, following sinus surgery, improvement of the sense of smell was found in 23%, no change was seen in 68%, and decreased function was seen in 9% of the patients; in patients with septum surgery, improvement was seen in 13%, no change in 81%, and decreased function in 7%. Patients exhibiting a postoperative decrease of olfactory function had significantly higher preoperative olfactory scores than patients who experienced improvement. In terms of the sense of smell, nasal surgery produced the highest success rates in patients with eosinophilia and a high degree of polyposis. Neither age nor sex had a major impact on the outcome of surgery in terms of olfactory function. Conclusions: These results in a large group of patients confirm previous work. Apart from apparent success in 13 to 23% of patients, there is also a small but significant group of patients (7 to 9%) in whom olfactory function decreases after surgery. Because this decrease was mostly found in patients with relatively good preoperative olfactory function, this group should receive specific attention when counseling patients about the potential risks of nasal surgery.     

Effects of smoking on odour identification in Japanese subjects

OBJECTIVES: Effects of smoking on olfaction appear to be well-known. However, there are not many studies that studied these effects on the basis of olfactory testing, and no studies on this topic have been performed so far in an Asian population. Thus, the aim of this study was to investigate the effects of smoking on odour identification. METHODS: Five hundred fifty seven Japanese subjects (368 men and 189 women) were given the cross-cultural smell identification test (CC-SIT). Their history was taken with special regard to nasal disease and smoking. Urine nicotine level was assessed in 107 subjects. RESULTS: The CC-SIT scores of current and previous smokers were lower than those of nonsmoking subjects (p < 0.05). The Brinkman index (BI) and CC-SIT score were correlated even when controlling for the subjects' age (r = -0.24, p < 0.001). The time since quitting cigarette smoking did not exhibit a relation with the CC-SIT score (r = -0.04, p = 0.76). In addition, urine levels of nicotine and its metabolites exhibited no significant correlation with the CC-SIT score (r = -0.08, p = 0.40). CONCLUSION: Smoking reduces olfactory function. Apparently, recovery of olfactory sensitivity after cessation of smoking appears to be exceptional.     

Anterior Distribution of Human Olfactory Epithelium

Objectives/Hypothesis To functionally investigate the distribution of the olfactory epithelium in humans by means of the electro‐olfactogram (EOG) and anatomically located biopsy specimens. Study Design Prospective, nonrandomized, investigational. Methods Supra‐threshold EOG recordings were made on 12 healthy, trained volunteers (6 women, 6 men; age range, 21–48 y). Vanillin was used as the stimulus, since it exclusively excites olfactory receptor neurons. The EOG was recorded with tubular electrodes that were placed using thin‐fiber endoscopic guidance. Biopsy specimens were obtained of anterosuperior nasal cavity mucosa in the same regions as the positive EOGs in 15 smell‐tested patients (7 women, 8 men; age range, 22–60 y) during routine nasal and sinus surgery. This biopsied tissue was histologically processed and stained for olfactory and neural proteins. Results Viable responses to EOG testing were obtained in 7 of 12 subjects. In these seven subjects it was possible to identify nine sites above or below the anterior middle turbinate insertion where EOGs were obtained. The biopsy results showed mature olfactory receptor neurons in this same area. Conclusions Human olfactory epithelium appears to be distributed more anteriorly than previously assumed.     

Resection of the inferior superior turbinate: does it affect olfactory ability or contain olfactory neuronal tissue?

BACKGROUND: One approach to the sphenoid sinus involves resection of the inferior portion of the superior turbinate. There is general agreement from anatomic investigations that this area contains olfactory mucosa. This study will determine if olfactory tissue can be found in the superior turbinate mucosa of patients with chronic sphenoiditis and what effect its removal has on a patient's olfactory ability. METHODS: The inferior one-third of the superior turbinate removed during endoscopic sphenoidotomy was stained with olfactory marker protein antibody, a marker for mature olfactory tissue. The specimens were graded for content of olfactory neuronal elements. All patients underwent uninasal 12-item smell identification testing before surgery and at least 3 weeks after surgery. RESULTS: Fifty-five superior turbinate samples were taken from 31 patients. Nine (16%) of 55 samples contained olfactory neuronal elements that stained with olfactory marker protein. When comparing the pre- and postoperative smell test results, 52% of the nostrils had no more than a one-item change, 35% of the nostrils had a more than one-item improvement, and only 12% had more than a one-item loss. None of the nostrils with a loss of olfactory ability after the surgery showed olfactory neuronal elements in their superior turbinate specimens. CONCLUSION: There is olfactory mucosa in approximately one-sixth of the superior turbinate specimens removed during the endoscopic transethmoidal sphenoidotomy procedure. Although 12% of the patients had a loss of olfactory ability in this study, none of the loss could be attributed to excision of olfactory tissue.