Donald A. Leopold

Anterior distribution of human olfactory epithelium.

Objectives/Hypothesis To functionally investigate the distribution of the olfactory epithelium in humans by means of the electro‐olfactogram (EOG) and anatomically located biopsy specimens.

Disorders in taste and smell.

Although many conditions and medications have been associated with chemosensory disturbances, data from major chemosensory clinical research centers support three major disorders as being causative: nasal and paranasal sinus disease (21%), post-upper respiratory tract viral infection (19%), and head trauma (14%). Despite extensive evaluation, 22% of patients do not demonstrate identifiable causation.

Detection of the chemokine RANTES and endothelial adhesion molecules in nasal polyps

BACKGROUND To better understand the mechanisms of eosinophil recruitment into the upper airways, we examined human nasal polyps for the expression of the chemotactic cytokine RANTES and the endothelial adhesion molecules E-selectin and vascular cell adhesion molecule-1 (VCAM-1). METHODS Routine histologic examination and immunostaining with antibodies to RANTES, E-selectin, and VCAM-1 were performed on three types of tissues: nasal polyps, sinus mucosa, or turbinates from patients undergoing other elective procedures (S/T), and nasal biopsy specimens from nonallergic volunteers (NA). To further quantify the expression of endothelial adhesion molecules, some tissue samples were homogenized, and the resulting supernatants were assayed with sandwich ELISAs for VCAM-1 and E-selectin. RESULTS Polyp eosinophil counts ranged from 19/mm2 to 1818/mm2 (763 +/- 120/mm2, mean +/- SEM) and were significantly higher than those found in the control tissues (5 +/- 2 in S/T samples and 20 +/- 9 in NA samples, p < 0.002). Immunochemical staining for RANTES was observed in 11 of 14 polyps; intense staining for RANTES (grade 3) was observed in six of 14 polyps. None of nine S/T samples or five NA samples demonstrated grade 3 staining. Staining with anti-RANTES was largely localized to airway and glandular epithelium. There was no significant correlation between counts of eosinophils or the combined total of eosinophils plus mononuclear cells and the intensity of epithelial RANTES staining in all nasal tissues. Staining for VCAM-1, as well as for E-selectin, was detected in 11 of 14 polyps and eight of 13 control tissues. VCAM-1 detected by ELISA in polyp tissues (6.8 +/- 1.3 micrograms/gm) was higher than that found in six S/T samples (1.2 +/- 0.3 micrograms/gm, p < 0.005) and in two NA samples (1.8 +/- 0.02 micrograms/gm, p = 0.08). E-selectin values in polyps (1.4 +/- 0.3 micrograms/gm) were not statistically different from those detected in six S/T samples (0.5 +/- 0.2 microgram/gm) or two NA samples (1.6 +/- 0.4 microgram/gm). Counts of eosinophils and eosinophils plus mononuclear cells displayed a strong correlation with VCAM-1 ELISA values (p < 0.005 and p < 0.004, respectively) but not with VCAM-1 staining. VCAM-1 staining correlated with EG2-positive eosinophils in nasal polyp tissues (p < 0.01). E-selectin staining did not correlate with either neutrophil or eosinophil counts. CONCLUSIONS These studies demonstrate that the chemokine RANTES is produced in vivo predominantly to nasal epithelium. Endothelial activation, as indicated by adhesion molecule expression, occurs in human nasal polyp tissues and in control tissues, possibly reflecting the continued antigen exposure of the nasal mucosa. The correlations found in this study suggest that expression of VCAM-1 plays a role in the selective recruitment of eosinophils and mononuclear cells into nasal polyp tissues and that RANTES may be more important in localizing eosinophils to the epithelium.

DISORDERS OF SMELL AND TASTE

As with almost any aspect of medical practice, a thorough history and physical examination coupled with a good understanding of the anatomy and physiology of an organ system are the key factors in reaching a diagnosis. The information in this article is provided to assist the internist with the diagnosis of chemosensory disorders and the differentiation of malingering or other disease process as well as providing insight into the workup, prognosis, and treatment of patients with taste and smell disorders.

Techniques of intranasal steroid use.

OBJECTIVE: The effectiveness of topical intranasal steroids (INS) sprays for the treatment of allergic and nonallergic rhinitis may be limited by lack of instruction in the optimal spray technique. To determine whether the technique used affects the efficacy and safety of the product, this review of evidence had the goal of identifying and establishing a preferred method of applying INS sprays. STUDY DESIGN: A MEDLINE search of pertinent literature on 7 INS and 1 intranasal antihistamine spray preparations conducted with the use of appropriate search terms, yielded an initial 121 articles, 29 of which were identified as appropriate for review and grading for quality of evidence. RESULTS: The analysis provided no definitive evidence regarding how best to instruct patients to use INS or antihistamine spray devices. CONCLUSIONS: On the basis of a lack of clear evidence regarding instructions to maximize efficacy and safety of these drugs, the panel recommended a 7-step standard technique. (Otolaryngol Head Neck Surg 2004;130:5–24.)

An updated review of clinical olfaction.

Purpose of reviewDisorders of the sense of smell can result through hundreds of different processes, but most commonly occur from upper-respiratory-tract infections, trauma, and chronic rhinosinusitis. Recent developmentsResearch in the basic science of olfaction has progressed rapidly with powerful new molecular discoveries; however, our ability to treat these disorders remains limited. In clinical olfaction we are just realizing the broader existence of the sensory dysfunction in our population. We are discovering associations between neurodegenerative disorders and smell function that may allow us to identify these disorders earlier in the disease process. We are also challenging our previous categorization schemes and realizing that many etiologies cross the traditional conductive and neuro-sensory divisions. SummaryCurrently, aside from the possible therapeutic potential of systemic steroids, we have no effective treatment for the most common causes of olfactory loss. Recent advances in the basic science of olfaction provides us with an opportunity to develop new and novel clinical studies in an attempt at improving the quality of life for many of these patients.

Altered Olfactory Acuity in the Morbidly Obese

Background: Obese individuals have been reported to have a heightened desire for and ability to identify sweets when compared with leaner persons. Smell, like taste, may also be altered in obese persons compared with leaner subjects. This study was designed to determine if the sense of smell is different between morbidly obese and moderately obese individuals. Methods: 101 adult volunteers undergoing preoperative evaluation completed the 12-item Cross-Cultural Smell Identification Test (CC-SIT) before surgical intervention. Age, BMI, and smoking history were also obtained. Results: 101 subjects completed the preoperative CC-SIT (87 female, 14 male). Mean age of the subjects was 40 ± 12 years. Mean BMI was 42.5 ± 12.5 kg/m2. 46 subjects (46%) had a BMI >45. 21 were smokers (21%). 9 subjects (9%), all female non-smokers, had a CC-SIT score representing olfactory dysfunction. Subjects with BMI >45 were more likely to have olfactory dysfunction than subjects with BMI <45 (16% vs 4%, P <0.05). Conclusion: Morbidly obese individuals are more likely than moderately obese individuals to demonstrate CC-SIT scores consistent with olfactory dysfunction. The reason for this is unclear but is probably related to metabolic changes occurring in morbidly obese individuals.

Clinical presentation of qualitative olfactory dysfunction

Many patients with olfactory dysfunction not only experience quantitative reduction of olfactory function, but also suffer from distorted olfactory sensations. This qualitative dysfunction is referred to as parosmia (also called “troposmia”) or phantosmia, with the major difference that distorted olfactory sensations are experienced in the presence or absence of an odor, respectively. Our clinical observations corroborate the literature in terms of a general underestimation of the incidence of olfactory distortions. Based on selected cases we try to show that olfactory distortions exhibit a large variance in their clinical appearance. Further, emphasis is placed on the fact that only a detailed and directed history of the patient can provide cues to the correct diagnosis.

Pathology of the olfactory epithelium: Smoking and ethanol exposure

Objective: To investigate the effects of tobacco smoke on the olfactory epithelium. Cigarette smoking has been associated with hyposmia; however, the pathophysiology is poorly understood. The sense of smell is mediated by olfactory sensory neurons (OSNs) exposed to the nasal airway, rendering them vulnerable to environmental injury and death. As a consequence, a baseline level of apoptotic OSN death has been demonstrated even in the absence of obvious disease. Dead OSNs are replaced by the mitosis and maturation of progenitors to maintain sufficient numbers of neurons into adult life. Disruption of this balance has been suggested as a common cause for clinical smell loss. This current study will evaluate the effects of tobacco smoke on the olfactory mucosa, with emphasis on changes in the degree of OSN apoptosis.

Congenital Lack of Olfactory Ability

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