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... The average volume of the human nasal cavity has been measured using magnetic resonance imaging as 16,449.81 mm 3 ± 4288.42 mm 3 with the area of the nostril opening being 357.83 mm 2 ± 108.09 mm 2 (Schriever et al., 2013). Nostril opening correlates positively with nasal cavity volume (Schriever et al., 2013). ...
... mm 3 ± 4288.42 mm 3 with the area of the nostril opening being 357.83 mm 2 ± 108.09 mm 2 (Schriever et al., 2013). Nostril opening correlates positively with nasal cavity volume (Schriever et al., 2013). No difference between the average volume of the nasal cavity was observed between men and women. ...
Article
The global prevalence of neurologic disorders is rising, and yet we are still unable to deliver most drug molecules, in therapeutic quantities, to the brain. The blood brain barrier consists of a tight layer of endothelial cells surrounded by astrocyte foot processes, and these anatomic features constitute a significant barrier to drug transport from the blood to the brain. One way to bypass the blood brain barrier and thus treat diseases of the brain is to use the nasal route of administration and deposit drugs at the olfactory region of the nares, from where they travel to the brain via mechanisms that are still not clearly understood, with travel across nerve fibers and travel via a perivascular pathway both being hypothesized. The nose-to-brain route has been demonstrated repeatedly in preclinical models, with both solution and particulate formulations. The nose-to-brain route has also been demonstrated in human studies with solution and particle formulations. The entry of device manufacturers into the arena will enable the benefits of this delivery route to become translated into approved products. The key factors that determine the efficacy of delivery via this route include the following: delivery to the olfactory area of the nares as opposed to the respiratory region, a longer retention time at the nasal mucosal surface, penetration enhancement of the active through the nasal epithelia, and a reduction in drug metabolism in the nasal cavity. Indications where nose-to-brain products are likely to emerge first include the following: neurodegeneration, post-traumatic stress disorder, pain, and glioblastoma.
... Rearranging Eq. (15) gives ...
... (18) in particular, in its finality in this research) which needs to be tested using data available in the literature. The parameter  is calculated based on the observation that there may be a relationship between anatomical parts of a subject: It is known in the literature that certain respiratory parameter may be dependent on or could be a function of certain anatomical feature [15]. The value of R V used for resting subjects is 12  (750 150) / minute for a male and 12450/ minute for a female having taken into account the fact that whatever volume in a female is about 25% less than the volume in a male. ...
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Background: There had always been a spirited effort in understanding the transport of air or molecular oxygen plus other gases from alveolar air space into the pulmonary capillaries and from the latter back into the former using mathematical models; the determination of the number of alveoli using cadaver and invasive and partially noninvasive methods have been made. There is a need for a noninvasive method of mathematical nature, with evaluative, diagnostic, and prognostic application. Objectives: The objectives of this research were to derive a mathematical equation for the noninvasive determination of the number of alveoli during rest and physical activity and elucidate the usefulness and advantage of the model over known methods. Methods: Theoretical and computational (calculational) methods; data in the literature were substituted into the model mathematical equation for the computation of the number of alveoli in the human lungs. Results and Discussion: The computed number (N alv) of alveoli differed from one country or subcontinental region to another. The N alv for the male were expectedly larger than for the female subjects. Short Research Article Udema; AJOB, 10(1): 38-47, 2020; Article no.AJOB.59914 39 Conclusion: The mathematical equation for totally noninvasive determination by computation is derivable and was derived. The total number (N alv) of alveoli mobilised for function is a function of the width (d) of the nares (d 22/15), rate (R v) of gas flow / , and radius (r alv) of a functional alveolus /. The equation has the potential to be of diagnostic, evaluative and prognostic value in medical practice. This new computational approach could be faster than other known approaches for the determination of the N alv. A noninvasive approach by computation, relying on other noninvasively determined respiratory parameters, can eliminate the possibility of tissue damage.
... The rhinometer was programmed for NCV 0-3 and NCV 3-5.2 , defined Similarly, in our study NC volume did not differ significantly between male and female up to 14 years of age. We thought that numerical differences among our study and others may be derived from the subjects' race, gender, age and methods that were used in researches [35,40]. Only 1 study has investigated the volume of the NC, MNC and INC with CT images using stereological method in healthy people. ...
... They calculated the NCV 0-5,2 ; it was 5.50 ± ± 1.20 cm 3 . Schriever et al.[35] assessed relationship between intranasal volume and the size of the nares in healthy volunteers aged 19-77 years on MR images by software. They determined that average total intranasal volume was 16,449.81 ...
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Background: The anatomy of the human nasal cavity (NC) is complex and its structures are closely related to the functions of the NC. Studies which assessing the mean volumes of NC and conchae are very infrequent. The purpose of current study is to investigate development of NC and conchae according to age and sex by using stereological method. Materials and methods: This retrospective volumetric study was carried out on 342 individuals (166 females and 176 males) between 0-18 years old with no pathological conditions or medical procedures that affected the skeletal morphology of the NC. Volumetric estimations were determined on computed tomography (CT) images using point-counting approach of stereological methods. Results: NC, inferior nasal conchae (INC) and middle nasal conchae (MNC) volume measurements that obtained using point-counting method were increased with age in both sexes until 15 years old. Regardless of gender; no significant difference was determined between the left and right values for NC, conchae volumes and choanae measurements. Generally significant differences were determined in NC and INC volumes according to gender after they reached maximum growth period. According to age the volume ratios of INC to NC, MNC to NC were ranged from 18 to 32% and 9 to15%, respectively. Conclusions: The current study demonstrated that the point counting method is effective in determining volume estimation of NC and is well suited for CT studies. Our results could provide volumetric indexes for the NC and conchae, which could help the physician for both patient selections for surgery, and for the assessment of any surgical technique used to treatment of nasal obstruction.
... A schematic representation of the in vitro system is shown in Figure 1. Based on previous findings on the morphological parameters of the nasal cavity ( Table 2) [30][31][32][33], the experimental conditions were determined such that the volume of nasal mucus relative to the formulation dose applied in vivo was of the same order as that observed under physiological conditions. Specifically, the film was cut into 20 mm square portions, and applied onto the surface of the ANF. ...
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Intranasal drug applications show significant therapeutic potential for diverse pharmaceutical modalities. Because the formulation applied to the nasal cavity is discharged to the pharyngeal side by mucociliary clearance, the formulation should be dissolved effectively in a limited amount of mucus within its retention time in the nasal cavity. In this study, to develop novel formulations with improved dissolution behavior and compatibility with the intranasal environment, a thin-film formulation including drug and polymer was prepared using a vacuum-drying method. The poorly water-soluble drugs ketoprofen, flurbiprofen, ibuprofen, and loxoprofen were dissolved in a solvent comprising water and methanol, and evaporated to obtain a thin film. Physical analyses using differential scanning calorimetry (DSC), powder X-ray diffraction analysis (PXRD), and scanning electron microscopy SEM revealed that the formulations were amorphized in the film. The dissolution behavior of the drugs was investigated using an in vitro evaluation system that mimicked the intranasal physiological environment. The amorphization of drugs formulated with polymers into thin films using the vacuum-drying method improved the dissolution rate in artificial nasal fluid. Therefore, the thin film developed in this study can be safely and effectively used for intranasal drug application.
... Possible explanations for sex differences in olfactory performance were discussed in relation to the female endocrine system and estrogen effects in odor perception [14,16]. Interestingly, no major sex-related differences were reported in the intranasal volume [64] or in the degree of expression of olfactory receptors [65]. ...
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Purpose Loss of smell decreases the quality of life and contributes to the failure in recognizing hazardous substances. Given the relevance of olfaction in daily life, it is important to recognize an undiagnosed olfactory dysfunction to prevent these possible complications. Up to now, the prevalence of smell disorders in Italy is unknown due to a lack of epidemiological studies. Hence, the primary aim of this study was to evaluate the prevalence of olfactory dysfunction in a sample of Italian adults. Methods Six hundred and thirty-three participants (347 woman and 286 men; mean age 44.9 years, SD 17.3, age range 18–86) were recruited from 10 distinct Italian regions. Participants were recruited using a convenience sapling and were divided into six different age groups: 18–29 years (N = 157), 30–39 years (N = 129), 40–49 years (N = 99), 50–59 years (N = 106), > 60 years (N = 142). Olfactory function, cognitive abilities, cognitive reserve, and depression were assessed, respectively, with: Sniffin’ Sticks 16-item Odor Identification Test, Montreal Cognitive Assessment, Cognitive Reserve Index, and the Beck Depression Inventory. Additionally, socio-demographic data, medical history, and health-related lifestyle information were collected. Results About 27% of participants showed an odor identification score < 12 indicating hyposmia. Multiple regression analysis revealed that OI was significantly correlated with age, sex, and cognitive reserve index, and young women with high cognitive reserve index showing the highest olfactory scores. Conclusion This study provides data on the prevalence of olfactory dysfunction in different Italian regions.
... s Popp and Monteiro-Riviere (1985) cited by Gizurarson (1993 Schriever et al. (2013). ...
Article
This advanced review describes the anatomical and physiological barriers and mechanisms impacting nanomedicine translocation from the nasal cavity directly to the brain. There are significant physiological and anatomical differences in the nasal cavity, olfactory area, and airflow reaching the olfactory epithelium between humans and experimentally studied species that should be considered when extrapolating experimental results to humans. Mucus, transporters, and tight junction proteins present barriers to material translocation across the olfactory epithelium. Uptake of nanoparticles through the olfactory mucosa and translocation to the brain can be intracellular via cranial nerves (intraneuronal) or other cells of the olfactory epithelium, or extracellular along cranial nerve pathways (perineural) and surrounding blood vessels (perivascular, the glymphatic system). Transport rates vary greatly among the nose to brain pathways. Nanomedicine physicochemical properties (size, surface charge, surface coating, and particle stability) can affect uptake efficiency, which is usually less than 5%. Incorporation of therapeutic agents in nanoparticles has been shown to produce pharmacokinetic and pharmacodynamic benefits. Assessment of adverse effects has included olfactory mucosa toxicity, ciliotoxicity, and olfactory bulb and brain neurotoxicity. The results have generally suggested the investigated nanomedicines do not present significant toxicity. Research needs to advance the understanding of nanomedicine translocation and its drug cargo after intranasal administration is presented. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.
... Average size of human nasal cavity is 12cm to 14 cm long, and has a surface of around 140cm 2 -150cm 2 and 12-14 ml capacity. 6,7 Both the nasal cavities are divided into three regions each, namely vestibule region at the front side or at opening of nose cavity and just inside the nostrils, respiratory region A c c e p t e d M a n u s c r i p t present at mid of cavity and olfactory region present at backend. The nasal vestibule has no absorption function. ...
Article
Neurological disorders such as Alzheimer’s disease, Parkinson’s Disease, Dementia, Epilepsy, Depression, Migraine etc. are affecting more and more elderly people’s day by day. Conventional route of administration to treat these diseases has to face a major hindrance that is blood brain and Blood-CSF barrier to achieve desired concentration of drug at the site of action for therapeutic effect. Hence, intranasal route of delivery is considered as promising and alternative route to achieve desired goals. In last four decades, brain targeting strategies are widely studied and considered having great potential by researchers; especially intranasal delivery owing to its benefits. Various nano formulations such as nanoemulsions, nanosuspensions, hydrogels, in situ gels, dendrimers and lipidic formulations are studied widely. Lipid nano formulations especially second generation nanostructured lipid carriers offer greater advantages in terms of stability, fabrication techniques, scalability, drug loading and drug targeting. NLC’s constitute of two major components viz solid lipid and liquid lipid in a specific ratio. In this review, authors have discussed about the possible synergistic actions of oils/liquid lipids with synthetic drugs resulting into great therapeutic benefits.
... Elephants have the widest nostrils of any mammal we examined, with a nostril radius ranging from 10 mm at the tip to 30 mm at a distance of 90 cm from the distal tip. An elephant has a nasal radius that 100 times that a of a mouse (0.21 mm nasal radius) [49], and two times that of a human at the distal tip (nasal radius of 5 mm) [50]. Using the approximation [51] that lung pressure applied by animals is constant at −10 kPa, we apply equation (3.8) to estimate the maximum distance for animals to pick up the same tortilla chip in our experiments. ...
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Despite having a trunk that weighs over 100 kg, elephants mainly feed on lightweight vegetation. How do elephants manipulate such small items? In this experimental and theoretical investigation, we filmed elephants at Zoo Atlanta showing that they can use suction to grab food, performing a behaviour that was previously thought to be restricted to fishes. We use a mathematical model to show that an elephant’s nostril size and lung capacity enables them to grab items using comparable pressures as the human lung. Ultrasonographic imaging of the elephant sucking viscous fluids show that the elephant’s nostrils dilate up to 30 % in radius, which increases the nasal volume by 64 % . Based on the pressures applied, we estimate that the elephants can inhale at speeds of over 150 m s ⁻¹ , nearly 30 times the speed of a human sneeze. These high air speeds enable the elephant to vacuum up piles of rutabaga cubes as well as fragile tortilla chips. We hope these findings inspire further work in suction-based manipulation in both animals and robots.
... It is known in the literature that certain respiratory parameter may be dependent on or could be a function of certain anatomical feature. For instance Schriever et al [6] observed that the "relationship between various anatomical measures is, however, well documented. For example, a tall individual with long legs also tends to have long arms". ...
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The flow rate of air has been investigated which showed that rate decreases per tract from one generation to other. However, the physiological implication of the tapering respiratory tract is not adequately elucidated and a noninvasive mathematical model is unknown for the computation of an alveolar radius. The formulation of mathematical models that can account for the effect of tapering airways and calculation of the radius of the alveolus at each generation of respiratory tracts are the objectives of the research. The method of research is theoretical and computational. Known radii of all respiratory tracts except the alveolus were substituted into derived equation for the calculation of alveolar radius. The rate of gas flow, in metres per second, decreases with increasing number of tracts from one generation to another. However, the sum of the distance covered per unit time increases from one generation to another. The alveolar radius for an average adult lung is  1.163  0.080 (SD) exp ( 4) metre (df = 22 and coefficient of variation is  6.879). Older adults have longer alveolar radius in male and female subjects. Although the rate of gas flow in metres per second increases for a while and then decreases, the total distance covered per unit time is increasingly high making the delivery of gas to the alveoli very rapid. The derived equations could be used for the computation of alveolar radius. There are gender, demographically and racially based differences in the radius of alveolus. Keywords: Respiratory tract; Radius of alveolus; Rate of gas flow in volume per cross-sectional area per unit time; Implication of tapering diameter of respiratory tract.
... Possibly, the relatively small sex differences we observed in our research might have anatomical background (Martinez et al., 2017). In this context, differences between men and women are not large; for example, women have smaller nose openings but do not differ from men in intranasal volume (Schriever et al., 2013), and there seems to be no major sex-related difference in olfactory gene receptor expression (Verbeurgt et al., 2014). A few important studies tested sex differences in the olfactory bulb, a part of the brain that influences olfactory function, and that is considered to be the most important relay station in odor processing (Buschhüter et al., 2008). ...
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Although the view that women's olfactory abilities outperform men's is taken for granted, some studies involving large samples suggested that male and female olfactory abilities are actually similar. To address this discrepancy, we conducted a meta-analysis of existing studies on olfaction, targeting possible sex differences. The analyzed sample comprised n = 8 848 (5 065 women and 3 783 men) for olfactory threshold (as measured with the Sniffin Sticks Test; SST), n = 8 067 (4 496 women and 3 571 men) for discrimination (SST), n = 13 670 (7 501 women and 6 169 men) for identification (SST), and a total sample of n = 7 154 (3 866 women and 3 288 men) for works using University of Pennsylvania Smell Identification Test (UPSIT). We conducted separate meta-analyses for each aspect of olfaction: identification, discrimination and threshold. The results of our meta-analysis indicate that women generally outperform men in olfactory abilities. What is more, they do so in every aspect of olfaction analyzed in the current study. However, the effect sizes were weak and ranged between g = 0.08 and g = 0.30. We discuss our findings in the context of factors that potentially shape sex differences in olfaction. Nevertheless, although our findings seem to confirm the “common knowledge” on female olfactory superiority, it needs to be emphasized that the effect sizes we observed were notably small.
... But even if different application methods, as changing of the head position were used, the intranasally applied liquids do hardly reach the olfactory cleft. If the drug is not able to reach the olfactory region efficiently, it has a reduced chance to be transported to the CNS, but cleared by mucociliary clearance or absorbed systemically by blood vessels instead [148][149][150]. ...
Article
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The blood-brain barrier and the blood-cerebrospinal fluid barrier are major obstacles in central nervous system (CNS) drug delivery, since they block most molecules from entering the brain. Alternative drug delivery routes like intraparenchymal or intrathecal are invasive methods with a remaining risk of infections. In contrast, nose-to-brain delivery is a minimally invasive drug administration pathway, which bypasses the blood-brain barrier as the drug is directed from the nasal cavity to the brain. In particular, the skull base located at the roof of the nasal cavity is in close vicinity to the CNS. This area is covered with olfactory mucosa. To design and tailor suitable formulations for nose-to-brain drug delivery, the architecture, structure and physico-chemical characteristics of the mucosa are important criteria. Hence, here we review the state-of-the-art knowledge about the characteristics of the nasal and, in particular, the olfactory mucosa needed for a rational design of intranasal formulations and dosage forms. Also, the information is suitable for the development of systemic or local intranasal drug delivery as well as for intranasal vaccinations.
... The length of the medial side of the maxillary sinus is 38.4 mm in the right, and 39.1 mm on the left [9]. The diameter of the nostril opening can be estimated as 10 to 12 mm, because the average area of the nostril opening of average adults is 357.83 mm2 [10]. Fig. 2 shows the measured distances from nostril to the landmarks of sinuses. ...
Article
RESUMEN Las vías de transmisión de la COVID-19 desde pacientes infectados al personal de la salud son actualmente objeto de debate, pero su consideración resulta fundamental para la selección del equipo de protección personal. El objetivo de este documento es explorar las contribuciones de tres vías de transmisión—contacto, gota e inhalación—al riesgo de infección de COVID-19 adquirida por el personal sanitario en el ámbito laboral. El método consistió en la evaluación cuantitativa de los riesgos microbianos y de un modelo de exposición cuyos posibles parámetros se basaron en datos específicos del virus SARS-CoV-2 cuando se disponía de ellos. El hallazgo clave fue que las vías de transmisión por gotas e inhalación predominan sobre la vía de contacto, contribuyendo en promedio 35%, 57% y 8.2% a la probabilidad de infección cuando no se usa equipo de protección personal. En promedio, 80% de la exposición a la inhalación ocurre cuando el personal sanitario está cerca de los pacientes. La contribución relativa de las gotas y la inhalación depende de la emisión de SARS-CoV-2 en las partículas respirables (<10 μm) a través de la exhalación, y la inhalación se vuelve predominante, en promedio, cuando la emisión supera las cinco copias genéticas por minuto. La concentración prevista del SARS-CoV-2 en el aire de la habitación del paciente es baja (<1 copia del gen por m³ en promedio) y probablemente se encuentre por debajo del límite de cuantificación de muchos métodos de muestreo del aire. Los resultados demuestran el valor que supone la protección respiratoria del personal sanitario y que el muestreo de campo puede no ser lo suficientemente sensible para verificar la contribución que realiza la inhalación del SARS-CoV-2 al riesgo de infección de COVID-19 adquirida por el personal. La emisión e ineficacia del SARS-CoV-2 en gotas respiratorias de diferente tamaño es aún una brecha en el conocimiento, fundamental para comprender y controlar la transmisión de la COVID-19.
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The routes of COVID-19 transmission to healthcare personnel from infected patients is the subject of debate, but is critical to the selection of personal protective equipment. The objective of this paper was to explore the contributions of three transmission routes—contact, droplet, and inhalation—to the risk of occupationally acquired COVID-19 infection among healthcare personnel (HCP). The method was quantitative microbial risk assessment, and an exposure model, where possible model parameters were based on data specific to the SARS-CoV-2 virus when available. The key finding was that droplet and inhalation transmission routes predominate over the contact route, contributing 35%, 57%, and 8.2% of the probability of infection, on average, without use of personal protective equipment. On average, 80% of inhalation exposure occurs when HCP are near patients. The relative contribution of droplet and inhalation depends upon the emission of SARS-CoV-2 in respirable particles (<10 µm) through exhaled breath, and inhalation becomes predominant, on average, when emission exceeds five gene copies per min. The predicted concentration of SARS-CoV-2 in the air of the patient room is low (< 1 gene copy per m³ on average), and likely below the limit of quantification for many air sampling methods. The findings demonstrate the value of respiratory protection for HCP, and that field sampling may not be sensitive enough to verify the contribution of SARS-CoV-2 inhalation to the risk of occupationally acquired COVID-19 infection among healthcare personnel. The emission and infectivity of SARS-CoV-2 in respiratory droplets of different sizes is a critical knowledge gap for understanding and controlling COVID-19 transmission.
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Purpose: To propose a three-dimensional cephalometric analysis of upper airway (UA) related to its functionality, defining normal reference values in healthy individuals and the relationship between nostril, nasal valve, and minimal cross-sectional area (MCS) in functional upper airway. Materials and methods: The UAs of 20 Class I patients were analyzed with CBCT using Nemoceph 3D-OS and HOROS software, determining linear distances, volumes and cross-sectional areas, including MCS. Results: MCS was mostly located in the middle-upper oropharynx and high hypopharynx. MCS showed moderate correlation with the area of both nares (BNA) (r = 0.60, P = 0.004) and high correlation with the area of both internal nasal valves (BNV) (r = 0.66, P = 0.0016). BNA and BNV showed a moderate correlation (r = 0.445, P = 0.049). A total upper airway (TUA) and functional upper airway (FUA) volumes were established. TUA and FUA showed the strongest statistical correlation (r = 0.82, P = 0.00). A paired samples t test compared the measurement as absolute values of MCS with BNA (t = 0.781, P = 0.44), with BNV (t = -0.12, P = 0.90); and BNA with BNV (t = -0.76, P = 0.45), showed no significant differences. Conclusions: A functional cephalometric analysis of the UA with stable parameters in cervical spine and normal reference values has been proposed. BNA and BNV could be used as reference to establish the MCS compatible with respiratory health.
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The pathway to the maxillary sinus is anatomically curved and narrow. Thus, the conventional approach using a straight endoscope and surgical tools is difficult to diagnose and treat some blind regions of the maxillary sinus through the nostrils. Such cases are usually dealt with by an approach with an external incision that causes large invasive surgery. In order to approach the blind regions without any external incision, a new bendable device and an image-guided robotic approach for the maxillary sinus surgery are required. This work reports design, development, and validation of an image-guided dual master–slave robotic system for the maxillary sinus surgery. Initially, specifications of the robotic system for sinus surgery are decided by analysis of the anatomical structure of the sinus. A method for determining the design parameters of continuum type salve robot is also presented. Based on the specifications and the design parameter determining method, a compact design of bendable dual slave robotic system for inspection and biopsy operation of the maxillary sinus area is devised and workspace analysis for verifying the robot design is conducted. The performance of the dual master–slave system equipped with flexible devices is validated through several phantom tests. The results suggest that bendable end-effectors and navigation software are useful to navigate and treat blind regions inside general sinus areas as well as the maxillary sinus.
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Unilateral naris occlusion has long been the method of choice for effecting stimulus deprivation in studies of olfactory plasticity. A significant body of literature speaks to the myriad consequences of this manipulation on the ipsilateral olfactory pathway. Early experiments emphasized naris occlusion's deleterious and age-critical effects. More recent studies have focused on life-long vulnerability, particularly on neurogenesis, and compensatory responses to deprivation. Despite the abundance of empirical data, a theoretical framework in which to understand the many sequelae of naris occlusion on olfaction has been elusive. This paper focuses on recent data, new theories, and underappreciated caveats related to the use of this technique in studies of olfactory plasticity.
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The olfactory bulb (OB) is a remarkably plastic structure with highly active afferent neurons, which is partly reflected by its volume. Although deterioration of olfaction after total laryngectomy is reported by many patients, this problem has not received widespread attention. There has been no study that had addresses this loss olfactory ability as a function of OB volume. The aim of this study was to determine OB volume changes after laryngectomy. Twenty one patients post-total laryngectomy and 17 subjects with normal olfactory function underwent magnetic resonance imaging (MRI) for volumetric measurement of the OB. The history of all participants was taken in detail to exclude other possible causes of smell dysfunction. Volumetric measurement of the OB was performed by manual segmentation of the OB into coronal slices. Olfactory function was assessed with the orthonasal olfaction test. There was no statistically significant difference in volume between the right and left sides of the OB in the study and control groups. However, the study group had smaller OB volumes than the control group. In our assessment of orthonasal olfaction, patients who were post-total laryngectomy had worse orthonasal olfactory function than the control group. There were significant correlations between OB volumes and orthonasal test scores. Our MRI study showed that post-total laryngectomy patients had higher rates of olfactory bulb atrophy than the control subjects. Laryngectomy is associated with measurable decreases in olfactory function and this study hopes to further clarify this association by demonstrating that patients with total laryngectomy have reduced OB volumes when compared to the normal population.
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Closure of the nostril by electrocauterization on postnatal day (PN) 1 or 2 was used to study effects of olfactory deprivation on developing olfactory epithelium (OE) and bulb (OB) in CD-1 mice. No damage was observed in OE sections 1 or 3 days after closure, and at PN 30 no difference was found in the number of OE receptors between closed and open sides. Odor deprivation and a decrease in functional activity in experimental bulbs was evident from deoxyglucose autoradiographs at PN 21 and PN 30. At PN 30 deprived bulbs appeared smaller than nondeprived bulbs. Nissl stains revealed normal cytoarchitecture, but a protargol stain demonstrated fewer intraglomerular dendrites in deprived bulbs. At PN 30, volumes of deprived bulbs were 26% smaller than nondeprived bulbs. The volume of each bulbar lamina was 13 to 35% smaller than the comparable nondeprived lamina except for the ventricular/subependymal zone which was not significantly different between bulbs. Volumes of bulbs contralateral to the closed naris and the volumes of their laminae were not significantly different from control bulbs, suggesting no hypertrophy of nondeprived laminae. Deprivation did not affect the number of mitral cells seen at PN 30, their nuclear size, or their number of nucleoli. Lateral olfactory tract cross-sectional area was also unaffected by deprivation. Mitral cell perikaryal size, however, was smaller in deprived bulbs. Soma surface areal density of deprived mitral-to-granule cell synapses in deprived bulbs was 65% of the nondeprived density, while the density of granule-to-mitral cell synapses was only 46% of the nondeprived density. It is concluded that neonatal naris closure brings about a functional deprivation of the OB without receptor degeneration. Neonatal olfactory deprivation affects the perikaryal surface area but not the number of mitral cells. Also, deprivation markedly affects the reciprocal synapses between mitral and granule cells. Olfactory sensation thus appears necessary for normal development of OB neurons and synapses.
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To evaluate the sites of injury in patients with posttraumatic olfactory deficits and to compare damage with findings on clinical olfactory tests. Twenty-five patients with posttraumatic olfactory dysfunction were examined by means of olfactory testing, endoscopy, and MR imaging. MR surface-coil scans through the olfactory bulbs and tracts and head-coil scans of the temporal lobes were evaluated. Quantitative and qualitative gradings of damage to the olfactory bulbs, tracts, subfrontal region, hippocampus, and temporal lobes were compared with results on tests of odor identification, detection, memory, and discrimination. Twelve patients were anosmic, eight had severe impairment, and five were mildly impaired. Injuries to the olfactory bulbs and tracts (88% of patients), subfrontal region (60%), and temporal lobes (32%) were found, but these did not correlate well with individual olfactory test scores. Volumetric analysis showed that patients without smell function had greater volume loss in olfactory bulbs and tracts than did those posttraumatic patients who retained some sense of smell. Qualitative and quantitative assessments of damage showed few significant correlations with olfactory tests, probably because of multifocal injuries, primary olfactory nerve damage, and the constraints of a small sample size on the detection of clinically significant differences. MR imaging shows abnormalities in patients with posttraumatic olfactory dysfunction at a very high rate (88%), predominantly in the olfactory bulbs and tracts and the inferior frontal lobes.
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Subjects wearing nasal dilators rated olfactory stimuli as being more intense compared with ratings done without nasal expansion. The results support a perceptual constancy model in olfaction.
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This paper describes the effects that nasal dilators have on olfactory ability. Experimental results demonstrate that nasal dilators increase odorant identification, lower odorant threshold, and increase perceptual odorant intensity. In other experiments, magnetic resonance imaging (MRI) data demonstrates that the size of the nasal cavity especially around the region of the nasal valve is increased when nasal dilators are worn. Additionally, pneumotachograph data demonstrates that during a sniff, the peak flow, maximum flow rate, volume, and duration are all increased when nasal dilators are worn. Taken together, the increase in olfactory ability can most easily be explained by an increase in both the amount and the proportion of inspired odorant molecules that are directed to the olfactory mucosa and are, therefore, available for odorant perception.
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Anosmias with chromosomal disorders has been well investigated. However, isolated anosmia (IA) has received less attention, although it occurs more frequently. We compared frontobasal structures in patients with IA since birth or early childhood with those in control subjects. Imaging findings obtained in 16 patients with IA were compared with those obtained in eight control subjects. Imaging was performed with a standard quadrature head coil at 1.5 T. T1-weighted spin-echo (coronal plane perpendicular to frontal skull base; section thickness, 3 mm; pixels, 0.43 x 0.39 mm) and sagittal T1-weighted magnetization-prepared rapid gradient-echo (voxels, 1.0 x 1.0 x 1.0 mm) sequences were performed. We assessed the length and depth of the olfactory sulcus, olfactory bulb volume, and olfactory sulcus depth in the plane of the posterior tangent through the eyeballs (PPTE). Five patients with IA had bilateral hypoplastic olfactory bulbs. Three patients with IA had hypoplastic olfactory bulbs on the right and aplastic olfactory bulbs on the left. Eight patients with IA had bilaterally aplastic olfactory bulbs. The depth of the olfactory sulcus at the level of the PPTE was smaller in patients with IA than in control subjects. The depth of the olfactory sulcus was greater on the right than on the left, and there was no overlap. Among patients with IA, the depth of the olfactory sulcus differed significantly between those with and those without visible olfactory tracts. The depth of the olfactory sulcus at the level of the PPTE reflects the presence of olfactory tracts. The presence or absence of the olfactory tract may therefore have some association with cortical growth of the olfactory sulcus region. The olfactory sulcus is deeper on the right than on the left, particularly in patients with IA. We speculate that olfaction may be processed predominantly in the right hemisphere.
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Adult normative data are presented for unirhinal administration of the University of Pennsylvania Smell Identification Test (UPSIT). Two-hundred and seventy healthy adults, aged 15-64, were administered half of the UPSIT (20 items) to each nostril. The main findings were: (1) unirhinal and birhinal performance are not equivalent necessitating the use of unirhinal norms, rather than prorated birhinal norms, (2) unirhinal performance does not differ according to nostril of presentation, (3) unirhinal performance does not differ according to sex, (4) within the age ranges studied, age accounted for only a minor proportion of the variability, and (5) being a current smoker and having lower levels of formal education contributed to reduced unirhinal UPSIT scores. Correction factors are suggested for the education and smoking variables. Unirhinal evaluation may assist in further delineating the structural integrity of specific ipsilateral brain regions and potentially aid in differential diagnosis for a number of disorders.
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Human sniffing behavior usually involves bouts of short, high flow rate inhalation (>300 ml/s through each nostril) with mostly turbulent airflow. This has often been characterized as a factor enabling higher amounts of odorant to deposit onto olfactory mucosa than for laminar airflow and thereby aid in olfactory detection. Using computational fluid dynamics human nasal cavity models, however, we found essentially no difference in predicted olfactory odorant flux (g/cm2 s) for turbulent versus laminar flow for total nasal flow rates between 300 and 1000 ml/s and for odorants of quite different mucosal solubility. This lack of difference was shown to be due to the much higher resistance to lateral odorant mass transport in the mucosal nasal airway wall than in the air phase. The simulation also revealed that the increase in airflow rate during sniffing can increase odorant uptake flux to the nasal/olfactory mucosa but lower the cumulative total uptake in the olfactory region when the inspired air/odorant volume was held fixed, which is consistent with the observation that sniff duration may be more important than sniff strength for optimizing olfactory detection. In contrast, in rats, sniffing involves high-frequency bouts of both inhalation and exhalation with laminar airflow. In rat nose odorant uptake simulations, it was observed that odorant deposition was highly dependent on solubility and correlated with the locations of different types of receptors.
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Mechanical obstruction of odorant flow to the olfactory neuroepithelium may be a primary cause of olfactory loss in nasal-sinus disease patients. Surgical removal of nasal obstruction may facilitate the recovery of olfactory ability. Unfortunately, quantifying the functional impact of nasal obstruction and subsequent surgical outcomes using acoustic rhinometry, rhinomanometry, or CT scans is inadequate. Using computational fluid dynamics (CFD) techniques, we can convert patient CT scans into anatomically accurate 3D numerical nasal models that can be used to predict nasal airflow and odorant delivery rates. These models also can be rapidly modified to reflect anatomic changes, e.g., surgical removal of polyps. CFD modeling of one patient's nose pre- and postsurgery showed significant improvement in postsurgical ortho- and retronasal airflow and odorant delivery rate to olfactory neuroepithelium (> 1000 times), which correlated well with olfactory recovery. This study has introduced a novel technique (CFD) to calculate nasal airflow dynamics and its effects on olfaction, nasal obstruction, and sinus disease. In the future, such techniques may provide a quantitative evaluation of surgical outcome and an important preoperative guide to optimize nasal airflow and odorant delivery.
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Nasal airflow is important for the many physiological functions of the nose, which include the warming and humidifying of inspired air; the filtration of airborne pollutants; and the sense of smell and nasal pungency. Until recently, airflow properties in the nose could only be understood using qualitative in vitro models of humans or in vivo studies in rodents. Recent advances in constructing three-dimensional geometric models of human nasal passages from CT scans, coupled with computational fluid dynamic modeling, has been a valuable tool for quantifying airflow and transport of gases, heat, particles, and aerosols in the human nose. Additionally, these techniques hold significant promise for evaluating and predicting the impact and successful remediation of a variety of clinical conditions on olfaction and nasal patency and setting guidelines for safe levels of exposure to inhaled materials.
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The aim of this exploratory study was to identify the volume intranasal segments as they relate to parameters of olfactory function. Fifty healthy male volunteers (age range 22–59 years, mean age 28.5 years) were included. Olfactory function was measured by lateralized phenyl ethyl alcohol odor thresholds and odor discrimination, and by bilateral odor identification. Magnetic resonance imaging of the nasal cavity was performed immediately following olfactometry. To correlate the results of olfactometry with intranasal volume, each nasal cavity was divided into 11 segments. Significant correlations were found between the odor thresholds and volumes of the anterior part of the lower and upper meatus of the right nasal cavity. These results reveal that two nasal segments are important for inter-individual differences of odor thresholds in healthy subjects: (i) the segment in the upper meatus below the cribriform plate and (ii) the anterior segment of the inferior meatus. The latter finding is of special interest for nasal surgery, which allows modification of this volume through resection of the inferior turbinate and/or septoplasty.
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The relationship between nasal anatomy and olfactory ability was evaluated by correlating measurements from nasal cavity CT scans with the results of an established clinical measure of olfactory function (Odorant Confusion Matrix, or OCM). The most appropriate mathematical model of this relationship was developed by analyzing the logarithms of 30 anatomical measures and a logistic transform of the OCM percent correct score. Two nasal cavity regions were found to be the most important factors in accounting for the olfactory test results, with a third region modifying the effects of the first two. The results of this study suggest that nasal anatomy may play a role in controlling the access of an odorant to the olfactory receptor area. The conclusions of this study have implications for nasal surgeons who, when possible, should make attempts to repair or preserve these nasal regions which seem to be so important to olfactory function.
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Background: Although widely used in healthy subjects and patients with olfactory loss, the significance of changes of scores from validated olfactory tests is unknown. Aim and methods: The aim of the present study was to relate the self-assigned changes of olfactory function in terms of "better," "unchanged," and "worse" in patients with smell disorders with the results from olfactory testing by means of a validated test set. Olfactory function of 83 anosmic or hyposmic patients (40 women, 43 men; age 12-84 yr) was tested on two occasions (mean interval 136 days, minimum 7 days, maximum 6.7 yr). Olfactory function was assessed using a validated technique ("Sniffin' Sticks"). This test consists of three subtests, one for odor threshold (T), odor discrimination (D), and odor identification (I), with possible results ranging up to 16 points each. From the sum of the results from the three subtests a composite "TDI" score was obtained. Results: Forty-four patients indicated an improvement of olfactory function, whereas 39 patients reported no change. No subject reported deterioration of olfactory sensitivity. Subjects assigned to group BETTER had higher TDI scores in the second olfactory tests than subjects assigned to the group UNCHANGED, both in absolute terms and as compared with the first olfactory test (effect "test occasion" by "self-assessed improvement," P < .001). There was no significant difference between groups with respect to age and sex (P = .99 and .84, respectively). Logistic regression showed that more than 60% of the subjects reported an improvement of olfactory sensitivity when the TDI score increased by 5.5 points. Conclusion: We show that there is a statistically significant relation between measured and perceived improvement of olfactory function in patients who first presented with the diagnosis of anosmia or hyposmia. The results indicate that improved olfactory function in patients with olfactory deficiency is perceived as such in everyday life and is quantitatively related to an improvement in the composite TDI score of the "Sniffin' Sticks" olfactory test battery. This is the basis for the application of a specific therapy for olfactory loss because of a possible gain in quality of life for the patients.
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The development of the first standardized “scratch'n sniff” olfactory test is described. Over 1600 subjects participated in five experiments. In Experiment 1, 50 microencapsulated odorants were rated as to their intensity, pleasantness, irritation, coolness, and familiarity, and two procedures for releasing them were compared. In Experiment 2, the results of the first experiment and familiarity, and two procedures for releasing them were compared. In Experiment 2, the results of the first experiment and other data were used in the development of the test, which was administered to a large number of subjects. Using multiple regression analysis, scores on this test were shown to be significantly related to the subjects' gender, ethnic background, and smoking behavior. Average test scores decreased as a function of age, with the greatest decline occurring between the sixth and tenth decades of life. These age-related changes were not correlated with scores on the Wechsler Memory Scale. Women performed better than men within all age categories. In Experiment 3, the test was shown to differentiate between subjects with known olfactory disorders (e.g., Kallmann's syndrome; Korsakoff s syndrome) and normal controls, and to reliably detect persons instructed to feign total anosmia. In Experiment 4, the test-retest reliability was established (6-month interval; r=0.918, p<0.001), and in Experiment 5 the test was shown to correlate thresholds with odor detection (r=−0.794, p<0.001). This self-administratered test now makes it possible to rapidly and accurately assess general olfactory function in the laboratory, clinic, or through the mail without complex equipment or space-consuming stores of chemicals.
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Rationale and objectives: The purpose of this study was to define the primary sites of injury in patients with posttraumatic anosmia and hyposmia with magnetic resonance (MR) imaging and to determine if these sites correlated with the results of psychophysical olfactory tests. Materials and methods: Thirty-six patients with subjective loss in olfaction after head trauma underwent volumetric MR studies of the olfactory bulbs and tracts and temporal lobes. Pearson correlations were computed between olfactory bulb and tract and temporal lobe volumes and the patients' scores on tests of odor identification (including the University of Pennsylvania Smell Identification Test [UPSIT]), detection, and memory. Analysis of variance was used to compare volumes of the control subjects and the posttraumatic patients. Results: The olfactory bulbs and tracts (32 [89%] of 36 patients), the subfrontal lobes (22 [61%] of 36 patients), and the temporal lobes (11 [31%] of 36 patients) showed the highest incidence of posttraumatic encephalomalacia. Left olfactory bulb and tract volumes showed a statistically significant correlation with left and total UPSIT scores. A statistically significant difference (P < .001) was found in the right and left olfactory bulb and tract volumes between anosmic and hyposmic patients and between posttraumatic patients and control subjects. Conclusion: Olfactory bulb and tract damage may correlate with deficits in odor identification. Olfactory bulb and tract and frontal lobe encephalomalacia coexist in many patients.
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The olfactory bulb (OB) is considered to be the most important relay station in odor processing. The present study aimed to investigate the volumetric development of the human bulb and the olfactory function during childhood and youth. Furthermore, the present study aimed to investigate a possible correlation between OB volume and specific olfactory functions including odor threshold, odor discrimination and odor identification. A total of 87 subjects (46 boys, 41 girls), aged 1-17 years (mean age 8 years), participated in this study. None of them reported olfactory dysfunction or had signs of a dysfunctional sense of smell. Whenever possible, participants received a volumetric scan of the brain and lateralized olfactory tests. Volumetric measurements of the right and left OB were taken by manual segmentation of the coronal slices through the OB. Significant correlations between OB volumes and olfactory function were observed. Both, OB volumes and olfactory function increased with age, although the correlation between structure and function was not mediated by the subjects' age. In conclusion, for the first time, the present study showed a correlation between OB volume and olfactory functions in children.
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Some studies reported olfactory dysfunction in patients with multiple sclerosis (MS). There is no agreement about the most suitable testing method for measuring olfactory function (OF) in MS patients. Recent studies showed that olfactory bulb volume changes with the degree of olfactory dysfunction. We assessed olfactory bulb volume of MS patients with magnetic resonance imaging (MRI) and related it to the OF. Volumetric measurements of the right and left olfactory bulb (OB) were performed by manual segmentation within 36 MS patients. Psychophysical testing of the orthonasal OF was performed using threshold-discrimination-identification (TDI) score in MS patients. Of all MS patients, 44.4% displayed olfactory dysfunction. The TDI score of all 36 MS patients, especially the score of the Identification subtest correlated strongly with neurological scores typical of MS. In patients with a decreased OB volume, there was a positive correlation between volumetry of the OB and OF. OB volumes may provide valuable information about MS patients with olfactory dysfunction. The TDI test and Identification subtest were very sensitive in detecting olfactory dysfunction in MS patients.
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The current report used structural magnetic resonance imaging (MRI) to objectively measure olfactory bulb volume and olfactory sulcal depth in patients diagnosed with chronic schizophrenia and healthy controls. Additional measures were obtained to assess olfactory function. The olfactory bulb and sulcus were manually traced on structural 3T MRIs for 25 right-handed male patients diagnosed with chronic schizophrenia and 25 matched male healthy controls. A sub-set of subjects received the University of Pennsylvania Smell Identification Test (UPSIT). Olfactory bulb volume was significantly decreased in patients with schizophrenia compared to healthy controls, as was their performance on the UPSIT. Additionally, a positive correlation was seen in patients between right bulb volume and UPSIT scores. Overall, our findings support earlier research studies showing morphometric and functional changes in the olfactory system in patients with schizophrenia.
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The nose is the major portal of air exchange between the internal and external environment. The nose participates in the vital functions of conditioning inspired air toward a temperature of 37°C and 100% relative humidity, providing local defense and filtering inhaled particulate matter and gases. It also functions in olfaction, which provides both a defense and pleasure for the individual. Understanding normal physiology provides the basis for recognizing abnormalities.
Article
Olfactory dysfunction is commonly associated with IPD. We here report the association of OB volume and OS depth with olfactory function in patients with PD. Morphometric analyses by using MR imaging and the Japanese T&T olfactometer threshold test were used to evaluate olfactory structure and function in 29 patients with PD and 29 age- and sex-matched healthy controls. The olfactory recognition thresholds were significantly higher in patients with PD than in healthy controls (3.82 ± 1.25 versus 0.45 ± 0.65, P<.001). Olfactory atrophy with reductions in the volume of the OB (37.30 ± 10.23 mm(3) versus 44.87 ± 11.84 mm(3), P<.05) and in the depth of OS (8.90 ± 1.42 mm versus 9.67 ± 1.24 mm, P<.05) was observed in patients with PD but not in controls. Positive correlations between olfactory performance and OB volumes were observed in both patients with PD (r=-0.45, P<.0001) and in controls (r=-0.42, P<.0001). In contrast, there was no significant correlation between the depth of OS and olfactory function in either cohort. The results provide evidence that early olfactory dysfunction in patients with PD may be a primary consequence of damage to the OB. Neuroimaging of olfactory structures together with the assessment of olfactory function may be used to identify patients with PD.
Article
The purpose of this study was to assess olfactory function and olfactory bulb volume in patients with acute major depression in comparison to a normal population. Twenty-one patients diagnosed with acute major depressive disorder and 21 healthy controls matched by age, sex and smoking behavior participated in this study. Olfactory function was assessed in a lateralized fashion using measures of odor threshold, discrimination and identification. Olfactory bulb volumes were calculated by manual segmentation of acquired T2-weighted coronal slices according to a standardized protocol. Patients with acute major depressive disorder showed significantly lower olfactory sensitivity and smaller olfactory bulb volumes. Additionally, a significant negative correlation between olfactory bulb volume and depression scores was detected. Their results provide the first evidence, to our knowledge, of decreased olfactory bulb volume in patients with acute major depression. These results might be related to reduced neurogenesis in major depression that could be reflected also at the level of the olfactory bulb.
The aim of this study was to investigate the relationship between the intranasal airway around the turbinates and olfactory function. In total, 32 nostrils of 16 patients who were awaiting septal surgery were involved in this study. For measurements of the volume of the nasal cavity, paranasal sinus computed tomography scans were performed and reconstructed into three-dimensional images. The Butanol Threshold Test and Cross-Cultural Smell Identification Test were used to evaluate olfactory function. The results were analyzed with Pearson's test. The volume around the turbinates was significantly correlated with the olfactory threshold. However, olfactory identification had no significant correlation with each volume. The airway around the turbinates is very important for nasal airflow and its volume influences olfactory function. Understanding such relationships may help in preserving or improving olfactory function in septal, turbinate or sinus surgery. Further studies are needed regarding the relationships between not only the volume of the nasal cavity and nasal airflow, but also between nasal volume changes and olfactory function.
Article
It is estimated that 15% of normosmic subjects demonstrate lateralized smell loss. The majority of individuals will not notice this difference between nostrils as long as olfactory function of the better nostril remains in the normal range. We were interested in the question whether subjects demonstrating clinically significant side differences of olfactory function are at risk to develop bilateral olfactory loss. Normosmic individuals with such side differences ("difference group", n = 35) were re-tested on average 4.6 years after baseline investigations. Additionally, 58 subjects who did not demonstrate side differences ("control group") were also re-investigated. All participants received detailed olfactory testing using the "Sniffin' Sticks" involving tests for odor threshold, odor discrimination, and odor identification. Olfactory testing at follow-up indicated lower olfactory function (p = 0.005) in the "difference group" than in the "control group". The degree of side difference at baseline correlated negatively with the results from olfactory testing at follow-up (r = -0.29; p = 0.01). These results suggest that individuals with side differences of olfactory function are at risk to develop bilateral olfactory loss within 4.5 years. Thus, the degree of lateralized smell function is an indicator for future smell loss.
Article
Differentiation of progenitor cells into neurons in the olfactory bulb depends on olfactory stimulation that can lead to an increase in olfactory bulb volume. In this study, we investigated whether the human olfactory bulb volume increases with increasing olfactory function due to treatment of chronic rhinosinusitis. Nineteen patients with chronic rhinosinusitis were investigated before and after treatment. For comparison, additional measurements were performed in 18 healthy volunteers. Volumetric measurements of the olfactory bulb were based on planimetric manual contouring of magnetic resonance scans. Olfactory function was evaluated separately for each nostril using tests for odour threshold, odour discrimination and odour identification. Measurements were performed on two occasions, 3 months apart. In healthy controls, the olfactory bulb volume did not change significantly between the two measurements. In contrast, the olfactory bulb volume in patients increased significantly from the initial 64.5 +/- 3.2 to 70.0 +/- 3.5 mm(3) on the left side (P = 0.02) and from 60.9 +/- 3.5 to 72.4 +/- 2.8 mm(3) on the right side (P < 0.001). The increase in olfactory bulb volume correlated significantly with an increase in odour thresholds (r = 0.60, P = 0.006, left side; r = 0.49, P = 0.03, right side), but not with changes in odour discrimination or odour identification. Results of this study support the idea that stimulation of olfactory receptor neurons impacts on the cell death in the olfactory bulb, not only in rodents but also in humans. To our knowledge, this is the first longitudinal study that describes an enlargement of the human olfactory bulb due to improvement of peripheral olfactory function.
Article
Anatomical and physiological investigations in monkeys indicate that olfaction is subserved by several cortical regions. But the areas implicated in the human olfactory system have not been definitively identified by functional criteria. Behavioural evidence has suggested that laterally specialized mechanisms for odour processing may exist, but the neuroanatomical substrate remains unknown. We used positron emission tomography to study the cortical representation of human olfactory processing by comparing cerebral blood flow changes evoked during olfactory stimulation with those of a control task. We report here significant cerebral blood flow increases at the junction of the inferior frontal and temporal lobes bilaterally, corresponding to the piriform cortex, and unilaterally, in the right orbitofrontal cortex. The results complement and extend previous data implicating these regions in olfactory processing, and indicate that a functional asymmetry exists in the human brain favouring the right orbitofrontal area in olfaction.
Article
The present study documents the morphological changes in the aging human olfactory bulb. Eight bulb pairs from white females between the ages of 25 and 102 years were used. The number of mitral cells in layers IV and III was determined for each bulb and corrected for split cell error. Counts were made on 10-micron thick Nissl-stained sections at 250-micron intervals. The mean number of mitral cells per olfactory bulb at age 25 was estimated from linear regression to be 50,935; at age 60, 32,718; and at age 95, 14,501. The average loss over the time interval studied was 520 mitral cells per year. The volume of each bulb layer, except layer IV, was determined. The difference in the volume of each layer within individuals with age and the total volume with age was not significant (P less than 0.11). The estimated mean bulb volume was found to be 50.02, 43.35, and 36.68 mm3 at ages 25, 60, and 95 years, respectively. The estimated reduction in bulb volume per year increase of age was 0.19 mm3. The ratio of mitral cells to bulb volume for layer III decreased by 19.4 units for every year increase in age. No significant difference was found between the left and the right bulbs in regard to the number of mitral cells and the bulb volume. Histologically, the glomerular layer thickness as well as the mitral cell size and concentration per unit area decreased with age. The intrabulbar anterior olfactory nucleus was discontinuous, highly variable in size, and presumably variable even in neuronal numbers.
Article
Because of the wide range of human nasal anatomic configurations, some people sniff odorants against comparatively high resistances. To assess the relationship between sniff resistance and olfaction, ten subjects without nasal pathology or complaint were asked to estimate the perceived magnitude of the odorant, ethyl butyrate, at each of four concentrations and against each of four different resistances. In addition, the airflow profile of the subjects' sniffs was monitored during the performance of the odor task. As expected, perceived intensity increased with concentration, but more noteworthy was the finding that perceived intensity decreased with increasing resistance. Initially, this latter finding, together with the lack of interaction between concentration and resistance, suggested an olfactory analogue to conductive hearing losses. However, the sniffing data suggested that under the conditions of the experiment, the subjects attempted to maintain consistent sniffing behavior across the 16 different treatment combinations of concentration and resistance. These observations, taken together with the finding that subjects could estimate the perceived effort of sniffing, give support to the concept of a perceptual constancy model in olfaction. That is, olfactory magnitude may depend not only on the odorant itself, but also on the perceived effort associated with the sniff.
Article
• Nasal airflow patterns were studied by using xenon 133 gas to image the course taken by air as it flowed through a plastic model of the human nasal cavity. The model was produced from the head of a human cadaver, and was anatomically correct. A needle catheter was used to infuse the radioactive xenon into a continuous flow of room air maintained through the model by a variable vacuum source connected to the nasopharynx. The radioactive gas was infused at one of five release sites in the nostril, and the distribution of the radioactivity was imaged in the sagittal plane with a scintillation camera. The data were organized to show the activity in six contiguous regions of the midnose. For each catheter, release site activity patterns were determined for three flow rates. The results of this experiment showed that both catheter position and flow rate had significant and reproducible effects on the distribution of radioactivity within the model. (Arch Otolaryngol Head Neck Surg 1987;113:169-172)
Article
We investigated chemosensory functions in patients with temporal lobe epilepsy (TLE) to discover whether olfactory and trigeminal stimuli applied either ipsilaterally or contralaterally to the epileptic focus are processed differently. Twenty-two patients were investigated, 12 of whom had epilepsy with a focus located in left temporal lobe (LTL). The remaining 10 patients had a right temporal lobe (RTL) focus. Input from the trigeminal system was examined by use of CO2; input from the olfactory system was evaluated with vanillin and hydrogen sulfide as stimuli. Chemosensory function was assessed by evaluation of chemosensory event-related potentials (CSERP) and the patients' verbal reports in an odor identification test. In both groups of patients, prolonged CSERP latencies were noted after stimulation of the left nostril with CO2 as compared with stimulation of the right nostril. In contrast, a different pattern emerged for olfactory stimuli. After right-sided olfactory stimulation, latencies were prolonged in patients with right-sided epileptical foci. Similarly, when the left nostril was stimulated in patients with a left-sided focus, CSERP latencies were prolonged. Thus, neocortical processing of olfactory, but not trigeminally mediated information evidently is affected by functional lesions of the temporal lobe. After olfactory stimulation in patients with a right-sided focus, the distribution of amplitudes was different from normal. Moreover, analyses showed nonoverlapping 95% confidence intervals (CI) for latency N1 when vanillin was applied to the right nostril. These results indicate that RTL may play a different role in processing of olfactory information as compared with LTL.
Article
Odor memory was studied in 121 patients with unilateral cerebral excision from temporal, frontal, frontotemporal, or centroparietal areas, and 20 control subjects. Odors were presented birhinally, and half were named, to examine the effect of verbal labelling. Testing was by yes-no recognition immediately after presentation, 20 min later, and after 24 hr, using eight different targets and eight new foils each time. The results showed impairment only after excision from the right temporal or right orbitofrontal cortex. All groups showed significant forgetting over time, and verbalized odors were recognized more efficiently than unlabelled ones. The findings, suggesting a right hemisphere predominance in odor memory, support similar results for odor discrimination.
Article
'Sniffin' Sticks' is a new test of nasal chemosensory performance based on pen-like odor dispensing devices. It comprises three tests of olfactory function, namely tests for odor threshold (n-butanol, testing by means of a single staircase), odor discrimination (16 pairs of odorants, triple forced choice) and odor identification (16 common odorants, multiple forced choice from four verbal items per test odorant). After extensive preliminary investigations the tests were applied to a group of 104 healthy volunteers (52 female, 52 male, mean age 49.5 years, range 18-84 years) in order to establish test-retest reliability and to compare them with an established measure of olfactory performance (the Connecticut Chemosensory Clinical Research Center Test, CCCRC). Performance decreased with increasing age of the subjects (P < 0.001). Coefficients of correlation between sessions 1 and 2 were 0.61 for thresholds, 0.54 for discrimination and 0.73 for identification. Butanol thresholds as obtained with the CCCRC increased as a function of age; this relation to the subjects' age was not found for the CCCRC odor identification task. The test-retest reliability for CCCRC thresholds was 0.36, for odor identification it was 0.60. It is concluded that 'Sniffin' Sticks' may be suited for the routine clinical assessment of olfactory performance.
Article
The transport and uptake of inspired odorant molecules in the human nasal cavity were determined using an anatomically correct three-dimensional finite element model. The steady-state equations of motion and continuity were first solved to determine laminar flow patterns of odorous air at quiet breathing flow rates. The air stream entering the ventral tip of the naris traveled to the olfactory slit, and then passed through the slit in nearly a straight path without forming separated recirculating zones. The fraction of volumetric flow passing through the olfactory airway was about 10%, and remained nearly constant with variation in flow rate. The three-dimensional inspiratory velocity field was used in the solution of the uncoupled steady convective-diffusion equation to determine the concentration field in the airways and odorant mass flux at the nasal walls. The mass-transfer boundary condition used at the nasal cavity wall included the effects of solubility and diffusivity of odorants in the mucosal lining, and the thickness of the mucus layer. The total olfactory flux of odorants, that is highly correlated with perceived odor intensity, was determined as a function of all transport parameters in our model. Increase in nasal flow rate at a constant inlet concentration resulted in an increase in total olfactory uptake for all odorants. However, with increase in flow rate, the fractional uptake, i.e., total olfactory flux normalized by convective flux at the inlet, decreased for poorly soluble odorants, while it increased for highly soluble odorants. The pattern of flux (or imposed patterning) across the olfactory mucosa, that carries information concerning odor identity, was also determined as a function of transport parameters. There was an overall decrease in odorant flux as the location on the olfactory surface was varied from the anterior towards the posterior and from the inferior towards the superior ends. The flux pattern became more uniform, i.e., the steepness of the flux gradients across the olfactory surface decreased, as the mucus solubility of the odorants decreased. Different odorants generated discernibly different flux patterns across the olfactory mucosa that may contribute to the encoding of odor quality. Variation of total olfactory flux with time after cessation of airflow was determined by solving the unsteady diffusion equation in the air-phase. The flux decreased approximately exponentially with time. The rate of decay decreased as solubility and diffusivity decreased, but was very rapid over a wide range of the parameters, with time constants of less than 0.5 s for most odorants, implying a rapid decrease in perceived odor intensity with cessation of nasal airflow.
Article
Unilateral naris closure in young rodents leads to striking alterations in the development of the ipsilateral olfactory system. One of the most pronounced effects is a 25% reduction in the size of the experimental olfactory bulb, a change that stems in part from decreased cell survival. Since naris occlusion in rodents alters the system more during development than in adulthood, we investigated the consequences of olfactory deprivation in a species that is born in a very immature state, Monodelphis domestica. In this pouchless marsupial, offspring are born after a short 14-day gestation. In the present study, the thymidine analogue bromodeoxyuridine was used to examine early postnatal neurogenesis in the olfactory bulb. Unlike rats and mice, neurogenesis of the main output neurons (the mitral cells) continues into postnatal life. Unilateral naris closure was begun on postnatal day 4 (P4) or P5 in Monodelphis and continued for 30 or 60 days. Laminar volume measurements revealed a significant reduction in the size of the experimental bulb following 60, but not 30, days of early olfactory deprivation. Mitral cell number estimates indicated a significant reduction after both 30 and 60 days of naris closure. The immaturity of Monodelphis offspring may render the population of mitral cells susceptible to the effects of olfactory deprivation. These findings suggest that afferent activity plays a role in the survival of all bulb neurons, irrespective of cell class.
Article
Interrelations between intranasal detection sensitivity for odor (H2S) and pain (CO2), nasal-airway volume (acoustic rhinometry), and body temperature were studied in young, healthy men across the diurnal cycle. The results showed a weak but statistically significant negative correlation between nasal volume and odor threshold and a weak but positive correlation between body temperature and odor threshold.
Article
The sense of smell shows a diminution with age as measured by the University of Pennsylvania Smell Identification Test (UPSIT). To ascertain whether the volumes of the olfactory bulbs and tracts (OBTs) and the temporal lobes (TL) declined in parallel to smell function, we examined 36 individuals from ages 22 to 78 who did not complain of any loss of the sense of smell using magnetic resonance (MR) imaging. The OBT volumes showed an initial increase to the 4th decade of life and then a decrease with increasing age, while the trend in TL volume was not as dramatic. There was no correlation between OBT or TL volumes with unilateral or total UPSIT scores. The normative data by decades can be used to assess the OBTs of cohorts of patients with neurodegenerative disorders that affect olfaction.
Article
To examine the relationship between uninasal anatomy and olfactory ability. A stepwise analysis of variance was used to regress the logarithm of the percentage of correct responses on the Odorant Confusion Matrix (a measure of olfactory ability) against the logarithm of nasal volume measurements determined from computed tomographic scans. Nineteen patients with hyposmia whose olfactory losses were thought to be related to conductive disorders. After correcting for sex differences, a mathematical model was developed in which the volume of 6 regions of the nasal cavity, 6 first-order interactions, and 3 second-order interactions accounted for 97% of the variation in the measure of olfactory ability. Increases in the size of compartments of the nasal cavity around the olfactory cleft generally increase olfactory ability. Also, anatomical differences in the nasal cavities of men and women may account, in part, for sex differences in olfactory ability.
Article
"Sniffin' Sticks" is a test of nasal chemosensory performance that is based on penlike odor-dispensing devices. It is comprised of three tests of olfactory function: tests for odor threshold, discrimination and identification. Previous work has already established its test-retest reliability and validity in comparison to established measures of olfactory sensitivity. The results of this test are presented as a composite TDI score--i.e., the sum of results obtained for threshold, discrimination and identification measures. The present multicenter investigation aimed at providing normative values in relation to different age groups. To this end, 966 patients were investigated in 11 centers. An additional study tried to establish values for the identification of anosmic patients, with 70 anosmics investigated in five specialized centers where the presence of anosmia was confirmed by means of olfactory evoked potentials. For healthy subjects, the TDI score at the 10th percentile was 24.5 in subjects younger than 15 years, 30.3 for ages from 16 to 35 years, 28.8 for ages from 36 to 55 years and 27.5 for subjects older than 55 years. While these data can be used to estimate individual olfactory abilities in relation to a subject's age, hyposmia was defined as the 10th percentile score of 16- to 35-year-old subjects. Our latter study revealed that none of 70 anosmics reached a TDI score higher than 15. This score of 15 is regarded as the cut-off value for functional anosmia. These results provide the basis for the routine clinical evaluation of patients with olfactory disorders using "Sniffin' Sticks."
Article
The human nasal cavity filters and conditions inspired air while providing olfactory function. Detailed experimental study of nasal airflow patterns has been limited because of the complex geometry of the nasal cavity. In this work, particle image velocimetry was used to determine two-dimensional instantaneous velocity vector fields in parallel planes throughout a model of the nasal cavity that was subjected to a nonoscillatory flow rate of 125 ml/s. The model, which was fabricated from 26 computed tomography scans by using rapid prototyping techniques, is a scaled replica of a human right nasal cavity. The resulting vector plots show that the flow is laminar and regions of highest velocity are in the nasal valve and in the inferior airway. The relatively low flow in the olfactory region appears to protect the olfactory bulb from particulate pollutants. Low flows were also observed in the nasal meatuses, whose primary function has been the subject of debate. Comparison of sequentially recorded data suggests a steady flow.
Article
Olfactory meningiomas are rare benign tumours and represent about 12% of all basal meningiomas. Anosmia is thought to be among the first symptoms, even though patients often present with headaches or visual problems. However, so far no detailed psychophysical tests of olfactory function have been performed in a large number of those patients. Twelve patients (five men, seven women; mean age 52 years) with olfactory meningiomas were examined. In all patients extensive preoperative and postoperative lateralised olfactory testing was performed using the "Sniffin' Sticks" test battery, a psychometric testing tool. In eight cases the meningioma was lateralised (five left, three right), in four patients a bilateral meningioma was found. In addition to a detailed ear, nose, and throat examination MRI was performed in all patients. In preoperative testing six patients were found to be anosmic on the side of the tumour, two were hyposmic. Four patients were normosmic. Postoperative investigations showed lateralised anosmia in four patients on the operated side, three were normosmic on the contralateral side and one hyposmic. The remaining eight patients were completely anosmic postoperatively. (1) Contrary to expectations, olfactory testing seems to be of little help in detecting olfactory meningiomas. (2) The likelihood of normal postoperative olfactory function contralateral to the tumour was high when the tumour was less than 3 cm in diameter and preoperative normosmia had been established. (3) Preservation of olfactory function ipsilateral to the tumour seems to be extremely difficult, irrespective of tumour size or surgical approach.
Article
Nasal congestion is an important symptom in many diseases of the upper airways. Nasal congestion may also affect personal well-being and quality of life. Furthermore, as the nasal mucosa is the first part of the airways in contact with the environment, objective evaluation of nasal congestion or nasal patency is important. Systematic evaluation of nasal patency was described in the last part of the 19th century by Zwaardemaker. Measurement of the pressure drop over the nasal cavity at a passive dow has been described in 1903 by Courtade and is one of first descriptions rhinomanometry. The technique is still in use and computer technology has made the measurements much easier but the method has not yet been accepted for wide clinical use. Acoustic methods have also been used for evaluation of nasal patency. A qualitative method was the hum-test by Spiess (1902), where external occlusion of the nonocciuded side of the nasal cavity is experienced as a change in the timbre of the sound during humming. Acoustic reflections have been used in geophysical investigations especially with regard to search for oil. The use of acoustic reflections from the airways gained special interest in 1960-70 for determining the geometry of the vocal tract shape with regard to speech reconstruction. A method described by A. Jackson (1977) was adopted and for the first time applied to the nasal cavity. The method for determining the cross-sectional area as function of distance in the airways by acoustic reflections is impulse or relatively simple. The incident sound pseudorandom noise in the audible frequency range is compared with the response - the reflections from the airways. Intuitively, if the size of the entrance to the airways is known, the size of the reflections may represent changes of the airway size and the time between reflections may give the distance between the changes, dependent on the speed of sound. In this way it is possible to determine the area as function of distance in the airways. The technique has some assumptions and the major effort has been to validate use in the nose and elucidate aspects with regard to sound loss in the airways and resolution. Therefore, the acoustic reflection technique - named acoustic rhinometry - was compared with other methods like MRI, CT, and rhinomanometry. Allergic and nonallergic subjects were also compared. Acoustic rhinometry showed reasonable correlation with CT in a cadaver and in 10 subjects in comparison with MRI for the first 6 cm of the nasal cavity. Models based on MRI scannings of subjects also showed good correlation for the first 6 cm of the nasal cavity. Posteriorly in the nasal cavity and the epipharynx, differences were found mainly due to 'sound loss' to the paranasal sinuses. Sound loss due to viscous loss or friction at increasing surface/area ratio (the complex geometry in the nose) and loss due to nonrigidity the nasal mucosa were also examined. Neither these factors affected the area-distance function significantly. Acoustic rhinometry seems to reflect the area-distance function in the nose reasonably accurately. In allergic subjects acoustic rhinometry has been used to evaluate hypersensitivity. More pronounced spontaneous variation in nasal mucosa congestion was found in patients suffering from hay fever compared to nonallergic subjects. Furthermore, a tendency to a more swollen mucosa in the allergic subjects compared to the normal state, and increased sensitivity to histamine was found. This and reduction in swelling of the mucosa in allergic subjects during nasal steroid treatment out of the pollen season indicate an ongoing inflammatory process or hypersensitivity in allergic subjects out ot the pollen season. During allergen challenge the change in nasal cavity dimension as well as inflammation may affect olfaction in hay fever patients. Acoustic rhinometry has not only been used to examine hay fever patients but in many different aspects of rhinology. Since the introduction of the acoustic reflection technique in the nose more than papers using the technique have been published. Most of the papers find the technique valuable for evaluation of nasal patency. Fortunately, some critical papers have drawn attention to some practical aspects of the technique. Standard operating procedures, and calibration checks as well as training operators will enhance the accuracy and reproducibility of results. A decade after its introduction acoustic rhinometry is a well-established method for evaluation of nasal patency, but further improvement can be obtained by continued validation and adjustments of the technique.
Article
About 30% of the adult human population does not perceive an odour when sniffing the steroid androstenone (5-alpha-androst-16-en-3-one), but will become sensitive to its smell after repeated exposure to the compound. Here we investigate the origin of the plasticity that governs this acquired ability by repeatedly exposing one nostril of non-detecting subjects to androstenone and then testing the unexposed nostril. We find that the exposed nostril and the naive nostril can both learn to recognize the smell, effectively doubling detection accuracy. As the two olfactory epithelia are not connected at the peripheral level, our results indicate that learning occurs in the brain by a mechanism that shares information from both nostrils.
Article
The aim of this exploratory study was to identify the volume intranasal segments as they relate to parameters of olfactory function. Fifty healthy male volunteers (age range 22-59 years, mean age 28.5 years) were included. Olfactory function was measured by lateralized phenyl ethyl alcohol odor thresholds and odor discrimination, and by bilateral odor identification. Magnetic resonance imaging of the nasal cavity was performed immediately following olfactometry. To correlate the results of olfactometry with intranasal volume, each nasal cavity was divided into 11 segments. Significant correlations were found between the odor thresholds and volumes of the anterior part of the lower and upper meatus of the right nasal cavity. These results reveal that two nasal segments are important for inter-individual differences of odor thresholds in healthy subjects: (i) the segment in the upper meatus below the cribriform plate and (ii) the anterior segment of the inferior meatus. The latter finding is of special interest for nasal surgery, which allows modification of this volume through resection of the inferior turbinate and/or septoplasty.
Article
Olfactory loss is among early signs of idiopathic Parkinson's disease (IPD). The present pilot study aimed to investigate whether this loss would be reflected in a decreased volume of the olfactory bulb (OB) established through magnetic resonance imaging. Eleven consecutive IPD patients were compared to 9 healthy, age-matched controls. Results indicated that there is little or no difference between IPD patients and healthy controls in terms of OB volume. Based upon the relation between loss of olfactory input to the olfactory bulb and consecutive decrease in volume, these data support the idea that olfactory loss in IPD is not a primary consequence of damage to the olfactory epithelium but rather results from central-nervous changes.
Article
The olfactory bulb is a highly plastic structure the volume of which partly reflects the degree of afferent neural activity. In this study, 22 patients with post-infectious olfactory deficit, nine participants with post-traumatic olfactory deficit, and 17 healthy controls underwent magnetic resonance volumetry of the olfactory bulb. Patients presented with significantly smaller olfactory bulb volumes than controls; significant correlations between olfactory function and bulb volume were observed. Patients with parosmia exhibited smaller olfactory bulb volumes than those without parosmia. Findings indicate that smell deficits leading to a reduced sensory input to the olfactory bulb result in structural changes at the level of the bulb. Reduced olfactory bulb volumes may also be considered to be characteristic of parosmia.
As a result of the relative sizes of the various compartments in the nasal cavity, the bulk of the airflow is along the floor of the nasal cavity. The percent of airflow directed to the olfactory region (the superior region of the nasal cavity) is about 10%. Structural changes in the nasal cavity can alter airflow pathways and the characteristics of the airflow (e.g. laminar, mixed or turbulent) within nasal compartments. The relationship between the olfactory response and the stimulus is complex and may vary depending on the physiochemical properties of the odor and the rate at which odorants are delivered to the olfactory receptors. Changes in nasal airflow may impact the various olfactory functions (e.g. identification, differentiation) differently. When there is a nasal obstruction, a decline in olfactory ability may not simply be an access problem, since nasal disease can affect olfactory processing at many levels.
Article
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. 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. 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. 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.
Article
Nasal physiology is dependent on the physical structure of the nose. Individual aspects of the nasal cavity such as the geometry and flow rate collectively affect nasal function such as the filtration of foreign particles by bringing inspired air into contact with mucous-coated walls, humidifying and warming the air before it enters the lungs and the sense of smell. To better understand the physiology of the nose, this study makes use of CFD methods and post-processing techniques to present flow patterns between the left and right nasal cavities and compared the results with experimental and numerical data that are available in literature. The CFD simulation adopted a laminar steady flow for flow rates of 7.5 L/min and 15 L/min. General agreement of gross flow features were found that included high velocities in the constrictive nasal valve area region, high flow close to the septum walls, and vortex formations posterior to the nasal valve and olfactory regions. The differences in the left and right cavities were explored and the effects it had on the flow field were discussed especially in the nasal valve and middle turbinate regions. Geometrical differences were also compared with available models.
Article
The olfactory bulb (OB) is considered to be the most important relay station in odor processing. Involving 125 randomly selected subjects (58 men, 67 women; age range: 19 to 79 years), the present study aimed to investigate a possible correlation between OB volume and specific olfactory functions including odor threshold, odor discrimination, and odor identification. The history of all participants was taken in great detail to exclude possible causes of smell dysfunction. All participants received an otolaryngological investigation including a volumetric scan of the brain (MRI), lateralized olfactory tests and a screen for cognitive impairment. Volumetric measurements of the right and left OB were performed by manual segmentation of the coronal slices through the OB. Significant correlations between OB volumes in relation to olfactory function were observed, independent of the subjects' age. Additionally, OB volumes decreased with age. In agreement with previous research the present study confirmed the correlation between OB volume and specific olfactory functions. Furthermore, the correlation between OB volume and olfactory function was not mediated by the subjects' age. In conclusion, the present data obtained from a relatively large group of subjects forms the basis for age-related normative values of OB volumes.