Potential application of electronic odor diffuser in olfaction testing.

OBJECTIVE: Different olfactory tests have been performed by otorhinolaryngologists in different parts of the world. For example, the University of Pennsylvania Smell Identification Test (UPSIT) has been used in the U.S., whereas the Sniffin' Sticks Test has been used in Europe, and similarly, T&T olfactometry is used in Japan. Although audiometers with electronic oscillators have long been used in hearing tests, electronic odor generators are not typically used in olfaction tests. We attempted an olfactory test using the AROMASTIC® (SONY, Tokyo, Japan), an electronically controlled device that can diffuse five different odors. METHODS: Forty participants who had visited an outpatient olfactory clinic were included in this study. The participants were instructed to answer whether they could smell the five different odors during the AROMASTIC® screening test (AS-test), and the number of odors smelled was summed and scored (AS-score). The patients also underwent T&T olfactometry concurrently. RESULTS: The AS-scores and T&T olfactometry detection and recognition thresholds showed significant correlations, confirming that the AS-test is a valid olfactory test. CONCLUSION: Electronic odor diffusers may be useful for olfaction tests.

Enhancement of olfaction by femtomolar concentrations of zinc ions.

Zinc is recognized as an important element for olfaction. Zinc nanoparticles enhance olfaction in response to odors; however, the mechanisms underlying this action remain unknown. Herein, the effect of zinc on olfactory receptors was deduced using electro-olfactogram (EOG) responses recorded from the isolated olfactory mucosae of bullfrogs (Rana catesbeiana) following the administration or chelation of zinc ions. Menthone and n-amyl acetate were used as odorants, whereas forskolin (an adenylate cyclase activator) and cholera toxin (a Gαolf activator) were used as intracellular signal transduction activators. The EOG responses provoked by the odorants and cholera toxin were suppressed by dithizone-mediated zinc ion chelation, and the EOG responses were recovered by administering non-chelated zinc. However, the EOG response to forskolin was not suppressed by dithizone. In contrast, the addition of femtomolar concentrations of zinc ions enhanced the EOG responses. The above-mentioned effects on EOG responses were examined by changing the concentration of zinc ions but not zinc nanoparticles. The results of this study suggest that Gαolf alone or both olfactory receptors and Gαolf likely require zinc ions for their activation.

Thermography for the Diagnosis of Acute Inflammation in the Paranasal Sinus

Abstract Introduction Although computed tomography scanning is the most common method for the diagnosis of sinusitis today, X-ray imaging is still used in outpatient clinics. Because X-ray imaging is beneficial for patients with severe sinusitis but not for those with mild sinusitis, an alternative method to visualize sinusitis without X-ray imaging is desirable. Objective To study the possibility of using thermography to visualize sinusitis. Methods In the present study, heat distribution on the faces of individuals with and without sinusitis was studied using thermography. Overall, 10 control subjects and 20 patients with sinusitis were included. Original thermography data were cropped, resized, and converted to relative thermography data based on the average temperature for visualization and statistical analysis. Results The shape of the maxillary and/or frontal sinuses was determined based on regions indicating increased temperature in patients with sinusitis. The region with increasing temperature was statistically visualized, and the significant side (t test, p<0.05) coincided with the maxillary shadow on X-ray imaging. Conclusion Thermography demonstrates visually the correlation between the surface temperature of the face and inflammation patterns in the paranasal sinus. Therefore, our comparative study using thermography to visually differentiate individuals with and without sinusitis was effective, indicating that thermography is a possible alternative to X-ray imaging to detect sinusitis.

Thermography for the Diagnosis of Acute Inflammation in the Paranasal Sinus.

Introduction Although computed tomography scanning is the most common method for the diagnosis of sinusitis today, X-ray imaging is still used in outpatient clinics. Because X-ray imaging is beneficial for patients with severe sinusitis but not for those with mild sinusitis, an alternative method to visualize sinusitis without X-ray imaging is desirable. Objective To study the possibility of using thermography to visualize sinusitis. Methods In the present study, heat distribution on the faces of individuals with and without sinusitis was studied using thermography. Overall, 10 control subjects and 20 patients with sinusitis were included. Original thermography data were cropped, resized, and converted to relative thermography data based on the average temperature for visualization and statistical analysis. Results The shape of the maxillary and/or frontal sinuses was determined based on regions indicating increased temperature in patients with sinusitis. The region with increasing temperature was statistically visualized, and the significant side ( t test, p < 0.05) coincided with the maxillary shadow on X-ray imaging. Conclusion Thermography demonstrates visually the correlation between the surface temperature of the face and inflammation patterns in the paranasal sinus. Therefore, our comparative study using thermography to visually differentiate individuals with and without sinusitis was effective, indicating that thermography is a possible alternative to X-ray imaging to detect sinusitis.

Intrinsic chemosensory signal recorded from the human nasal mucosa in patients with smell loss.

Physiological investigation of olfactory receptor function in hyposmic or anosmic patients is rare. Pioneers examined the electro-olfactogram in patients with olfactory disturbance. Although the electro-olfactogram is an established method to record olfactory responses from human olfactory epithelium, the response is only measured at specific sites of the olfactory mucosa. In contrast to that the response of the olfactory epithelium to chemosensory stimuli can be studied in a specific nasal area by means of intrinsic optical signal recording. Five functionally anosmic patients were included in the present study. In all patients, responses could be obtained following trigeminal stimulation with CO2. In some patients, responses could be obtained after olfactory stimulation with H2S and PEA. The present data show that in the studied patients trigeminal function seems to be preserved, while it appears that in some patients olfactory function is preserved to a certain degree.

Topographical differences in the sensitivity of the human nasal mucosa to olfactory and trigeminal stimuli.

The olfactory and trigeminal systems play a role in the sensation of odors. The intrinsic optical signal (IOS) imaging method allows visualization of the neuronal activity. The IOS was measured after the nasal epithelium had been exposed to olfactory (H(2)S) and trigeminal (CO(2)) stimuli. The IOS was measured in the area of the middle turbinate. The response patterns of H(2)S and CO(2) on the middle turbinate were different, and some overlap between regions of activation was also observed. The response to CO(2) (20%) on the medial side of the middle turbinate was significantly higher than the response on the lateral side. In contrast, the response to H(2)S (5.6 ppm) was greater on the lateral side than on the medial side. There were no significant differences in response between the medial and lateral sides of the middle turbinate to stimuli of lower concentration (H(2)S 2.8 ppm, CO(2) 5% and 10%). These data suggest that the middle turbinate has regions which are sensitive to both olfactory and trigeminal stimuli.

Recordings of the optical intrinsic signal from the middle turbinate in response to olfactory and trigeminal stimulation: a pilot study.

Responses from the middle turbinate elicited by olfactory and trigeminal stimuli were studied using the intrinsic optical signal (IOS) recording technique. Nasal cavity was illuminated by 617 nm light. Olfactory (H2S) or trigeminal (CO2) stimuli of 5-s duration were presented using a computer-controlled olfactometer; IOS responses were captured by a special camera. Averages across five individual IOS recordings were analyzed. When the nasal cavity was exposed to H2S, a significant change of the IOS was found; responses to CO2 were even more pronounced. The present results argue for the idea that the IOS is an indicator of intranasal chemosensory activation.

The influence of olfactory loss on dietary behaviors.

OBJECTIVES: To assess dietary behavior and possible changes in food selection in patients with smell loss. PATIENTS AND METHODS: A total of 176 patients (114 women and 62 men) age 17 to 86 years were classified into three diagnostic groups (normosmia, n = 12; hyposmia, n = 75; functional anosmia, n = 89) according to their olfactory test scores obtained with "Sniffin' Sticks." Group differences in food intake and dietary behaviors were investigated with a specifically designed questionnaire providing a dietary alterations score (DAS). RESULTS: Numerous dietary changes were reported, e.g., 29% of all patients reported that they eat less since the onset of olfactory dysfunction, 39% use more spices with their food, 47% go out to eat at restaurants less frequently, 37% eat less sweets, and 48% drink less sweet beverages. Subjects with weight gain or weight loss scored higher on the DAS scale than subjects who did not report changes in weight. Similarly, DAS scale changes were more pronounced in subjects with a gradual onset of olfactory loss compared to subjects with a sudden loss of olfaction. Finally, a change of taste preferences toward savory and salty foods was observed across all patients enrolled in the present study. CONCLUSIONS: Patients with olfactory loss report alterations of dietary behaviors. Numerous factors appear to impact the results of olfactory loss in terms of changes in diet.

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.

Optical recordings from the human nasal mucosa in response to olfactory stimulation.

Using the intrinsic optical signal the present study aimed to investigate changes in blood flow at the nasal epithelium in response to specific olfactory stimulation. Recording equipment included an endoscope, a CCD camera, and a light source of 617 nm. Two concentrations of the specific olfactory stimulant H(2)S (2.8 and 5.6 ppm), generated by a computer-controlled olfactometer, were used for olfactory stimulation. Eight healthy normosmic volunteers participated. Using 5.6 ppm H(2)S stimuli, responses were typically recorded from the olfactory cleft, middle turbinate, and middle meatus while responses were less pronounced for 2.8 ppm H(2)S stimuli. Response areas were significantly larger for the 5.6 ppm H(2)S stimuli. While further experiments are needed, recordings of the intrinsic optical signal may be used to obtain responses from the nasal cavity to specific olfactory stimuli.

Optical recording of the intrinsic signal from the human olfactory cleft.

OBJECTIVES: Endoscopy of the human olfactory cleft is important for both research in human olfaction and clinical examination with regard to olfactory disorders. However, endoscopy only provides information on the morphology and functional status of the epithelium, and it does not allow discrimination between respiratory and olfactory mucosa. To obtain information on the functional status of the olfactory mucosa, I used endoscopy to investigate the optical intrinsic signal recording from the human olfactory cleft. METHODS: A light-emitting diode (617 nm) light source and a cooled charge-coupled device camera were prepared for endoscopy of the olfactory cleft. Subjects were exposed to various odors presented in front of their nostrils. In addition, blanks were used for control. RESULTS: When normosmic subjects sniffed the odors, the intensity of the signal from the olfactory mucosa changed, which was not the case when blank stimuli were presented. Different odors activated different response patterns. A decrease of the oxyhemoglobin level in the activated olfactory epithelium is suspected to be responsible for this observation. CONCLUSIONS: The optical intrinsic signals were recorded from the human olfactory cleft with an endoscope. This technique may be applicable to basic research in olfaction and to a clinical test for the assessment of olfactory disorders.

Lateralized differences in olfactory function.

BACKGROUND: Birhinal testing of odor identification will not allow the detection of unilateral olfactory loss. The aim of the presented study was to evaluate side differences of odor identification in large groups of healthy subjects and in patients with nasal symptoms. PARTICIPANTS AND METHOD: Self-assessment of olfactory function and evaluation of olfactory function by means of a validated test were performed in 479 healthy subjects, in 765 patients with chronic rhinosinusitis (CRS), and in 53 patients with a tumor. A 12-item odor identification test ("Sniffin' Sticks") was used to evaluate olfactory function separately for each nostril. RESULTS: Fifteen percent of the healthy subjects demonstrated side differences in the identification of at least 3 out of 12 odors. Healthy elderly subjects showed larger side differences in identification of odor than younger ones; a general difference between odor identification with the right or left nostril was not found. Both CRS patients and patients with a tumor had larger side differences than healthy subjects. Only 20% of the patients with a tumor complained about impaired olfactory sensitivity, but more than 75% of them showed deficits in olfactory tests. CONCLUSION: Side differences of odor identification of 25% or greater should give reason for further investigation. Future studies are needed to investigate whether side differences in healthy subjects are a predicator of a higher risk for general olfactory loss.

Olfactory and gustatory disturbances caused by digitalism: a case report.

It is known that an overdose of digoxin causes visual disturbance, but the effect on the senses of smell and taste is not known. A case of olfactory and gustatory disturbance caused by digitalism is reported. In a 62-year-old male patient suffering from chronic digitalism, the serum digoxin level rose to 6.0 ng/ml. The patient was diagnosed not only with visual disturbance but also hyposmia and hypogeusia. The patient recovered from visual and chemosensory disturbances after the serum digoxin concentration returned to normal. Because the similarity of intracellular signal transduction between photoreceptor cells and olfactory and/or taste receptor cells is known, it is suspected that the influence of digoxin to chemosensory organs was caused by intermediation of sodium-potassium-adenosine triphosphatase (Na-K-ATPase) of the chemosensory receptor cells.

Superior turbinate osteoma: a case report.

Turbinate osteoma is very rare and only three middle turbinate cases have been previously reported in the literature. A case of superior turbinate osteoma has never been reported before. This is a report of a 61-year-old female presenting superior turbinate osteoma with headaches. The osteoma was resected by endoscopic sinus surgery (ESS) and the patient was relieved of headaches.

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.

Near-infrared spectroscopy of the adult human olfactory cortex.

OBJECTIVE: Near-infrared spectroscopy (NIRS) is a non-invasive method for investigating activation of the human cortex. The applicability of NIRS to the olfactory cortex was investigated. MATERIAL AND METHODS: The relative oxy- and deoxy-hemoglobin levels of the orbito-frontal cortex during olfactory stimulation in healthy subjects were measured using NIRS. RESULTS: When perfumed strips containing the odorants beta-phenyl ethyl alcohol, iso-valeric acid and gamma-undecalactone were presented, the oxy-hemoglobin level increased but the deoxy-hemoglobin level did not change. The increase in the oxy-hemoglobin level was observed bilaterally. A placebo perfumed strip did not elicit a change in the hemoglobin level. It was also observed that the odorant intensity affected the oxy-hemoglobin level. Although the orbito-frontal cortices seemed to be activated bilaterally during olfaction, the right cortex was activated to a greater extent than the left. CONCLUSION: NIRS appears to be an adequate method for investigating the human olfactory cortex.

Hemodynamic response of the frontal cortex elicited by intravenous thiamine propyldisulphide administration.

The intravenous olfaction (IVO) test is a unique type of clinical olfactometry and is widely used in Japan. However, it is difficult to distinguish actual olfactory disturbance from feigned disturbance because the IVO test is a psychophysical test. To resolve this problem, we investigated the possibility of an objective IVO test assisted with near infrared spectroscopy (NIRS). IVO testing was performed according to the usual protocol with thiamine propyldisulphide (alinamin) administration. The relative oxy- and deoxyhemoglobin levels of the orbitofrontal area during olfactory stimulation by IVO test were measured by NIRS. Pairs of NIRS emitters and detectors were positioned on the bilateral frontal scalp. After administration of alinamin, oxyhemoglobin levels increased, though deoxyhemoglobin levels did not change. An increase in oxyhemoglobin levels was observed bilaterally. Administration of saline did not elicit any change in the oxy- or deoxyhemoglobin levels and concentration of the administered alinamin related increasing of the oxyhemoglobin level was observed. Oxyhemoglobin remained unchanged in anosmic subjects despite administration of alinamin. The latency of oxyhemoglobin increase on each side and smelling latency showed significant correlation. Latencies of oxyhemoglobin increases between the right and left sides also showed significant correlation. Oxyhemoglobin response appears to be linked to olfactory related response. NIRS is a useful technique for the development of an objective form of IVO testing.

Potential changes with gamma-band oscillation at the frontal scalp elicited by intravenous olfactory stimulation in humans.

Intravenous olfaction is a unique stimulation method often used in Japan to diagnose olfactory disturbances. Odorant is injected into a vein and transported by blood flow and respiration to the upper air tract. The intravenous olfaction might allow the potential at the frontal scalp to be recorded without contamination from electromyograms, such as those caused by sniffing. We injected Alinamin (thiamine propyldisulphide) into healthy subjects according to a standard protocol for clinical intravenous olfaction testing and we simultaneously recorded potential changes at the frontal scalp. When Alinamin was injected into the right median cubital vein over a 20 s period, the potential changes with gamma-band oscillations were detected 17.6 +/- 6.7 s (mean +/- SD) after the start of the injection. The main frequency component of this gamma-band oscillation is 30-160 Hz. The gamma-band oscillation elicited by intravenous olfactory stimulation (VOP) was similar to the induced wave of the olfactory bulb. Mapping the VOPs on the frontal scalp of a subject with less developed frontal sinuses and the relation between the thickness of the frontal sinuses and VOP amplitude suggest an intracranial source, possibly the olfactory bulb. The gamma-band potential at the frontal scalp is a useful measure of central disturbance.

Role of nerve growth factor in the olfactory system.

Olfactory neurons are unique in the mammalian nervous system because of their capacity to regenerate in adult animals. It has been shown that olfactory receptor cells located in the olfactory epithelium are replaced on a continuous basis and in response to injury throughout the life span of most species. NGF, which is one of the neurotrophic factors, is present in many areas of the central and peripheral nervous system. It has been shown that NGF in the olfactory bulb plays a role in the survival of cholinergic neurons in the horizontal limb of the diagonal band (HDB). Recent studies of NGF in the olfactory bulb suggest that it is involved in the development, maintenance, and regeneration of olfactory receptor cells. In this study, we review reports examining the relationship between NGF in the olfactory bulb and neuronal regeneration and development in the mammalian olfactory systems. Low- and high-affinity NGF receptor immunoreactivity is markedly expressed during regeneration and at different stages of development in the mouse olfactory system. This level of immunoreactivity is no longer present after completion of regeneration and at maturation. Other findings indicate that NGF injected into the olfactory bulb is transported retrogradely to the olfactory epithelium. It has also been shown that continuous anti-NGF antibody injection into the olfactory bulb causes degeneration and olfactory dysfunction. Administration of NGF directory into nasal cavity results in an increase in the expression of olfactory marker protein within the olfactory epithelium in axotomized rats. These findings suggested that the presence of NGF in the olfactory bulb plays an essential role in regeneration, maintenance, and development in the olfactory system of mammals.