Olfactory function in patients with chronic rhinosinusitis before and after functional endoscopic sinus surgery

BACKGROUND: The olfactory loss in patients with chronic rhinosinusitis has been measured by different methods. However, the results have been variable and it is not clear whether functional endoscopic sinus surgery (FESS) significantly improves olfactory function. This study was performed to evaluate the influences of FESS on olfactory function in patients with chronic rhinosinusitis using three different types of olfactory tests. METHODS: Seventy patients with chronic rhinosinusitis were administered the University of Pennsylvania Smell Identification Test (UPSIT), a single staircase phenyl ethyl alcohol odor detection threshold test (STT), and a short-term odor memory/discrimination test a day before and 6 months after FESS. A questionnaire inquiring about the patients' self-perception of olfactory function was administered also. Independent ratings of the severity of chronic rhinosinusitis before FESS were established from CT scans. RESULTS: Fifty-two (74.3%) of the patients reported that their olfactory function was impaired before surgery, and 68.6% of the patients reported impaired olfactory function after surgery, a difference that was not significant. No meaningful changes in any of the olfactory test scores were noted 6 or more months after FESS. Preoperatively, small correlations between CT scores and the symptom scores (r = 0.278; p = 0.024), threshold scores (r = -0.27; p = 0.031), and UPSIT scores (r = -0.36; p = 0.003) were observed. CONCLUSION: In patients with severe rhinosinusitis, FESS had little impact on the ability to smell, regardless of the method for assessing smell function. Subtle associations between olfactory function and the severity of chronic rhinosinusitis determined by CT were observed, however, preoperatively. The olfactory test measures were correlated with one another both pre- and postoperatively.     

Predictors of Olfactory Dysfunction in Patients With Chronic Rhinosinusitis

Objectives: To measure the prevalence of and identify clinical characteristics associated with poor olfactory function in a large cohort of patients with chronic rhinosinusitis (CRS). Study Design: Multi‐institutional, cross sectional analysis. Methods: An objective measure of olfactory dysfunction, the Smell Identification Test, demographic data, clinical factors, and comorbidity data were collected from a cohort of 367 patients who presented with CRS at three tertiary care centers. Data were analyzed using univariate and multivariate analyses. Results: Sixty‐four percent of men and women aged 18 to 64 had olfactory dysfunction whereas 95% of patients older than or equal to 65 years had olfactory dysfunction (P < .001); no significant difference was noted by gender. By multivariate logistic regression analysis, patients with nasal polyposis [Odds ratio (OR) 2.4, 95% confidence interval (CI) 1.3–4.2, P = .003] and patients older than or equal to 65 years (OR 10.0, 95% CI 2.3–43.7, P = .002) were at increased risk of hyposmia. Patients with nasal polyposis (OR 13.2, 95% CI 5.7–30.7, P < .001), asthma (OR 4.2, 95% CI 1.8–9.8, P = .001), older than or equal to 65 years (OR 15.6, 95% CI 2.3–104.9, P = .005), and smokers (OR 7.6, 95% CI 1.8–31.6, P = .005) were at increased risk of anosmia. Conclusions: Poor olfactory function is common in patients with CRS. Age, nasal polyposis, smoking, and asthma were significantly associated with olfactory dysfunction in patients with CRS. Neither prior endoscopic sinus surgery nor a history of allergic rhinitis was associated with olfactory dysfunction. Septal deviation and inferior turbinate hypertrophy were associated with normal olfactory function.     

Olfactory function and nasal nitric oxide.

OBJECTIVE: To determine the relationship between nasal nitric oxide (nNO) concentration and its influence on olfactory function. SETTING: Tertiary otolaryngology care centre. PARTICIPANTS: Sixty-four patients suffering from chronic rhinosinusitis and 20 healthy subjects participated. STUDY DESIGN: Prospective study. OUTCOME MEASURES: The nNO concentration was measured by chemiluminescence and olfactory thresholds were measured with the phenyl ethanol threshold of the Sniffin' Sticks. In chronic rhinosinusitis patients this measure was done preoperatively and 3 months after endoscopic sinus surgery. RESULTS: Healthy subjects had significantly higher nNO concentrations and better olfactory thresholds compared to the chronic rhinosinusitis patients, both before and after those had undergone sinus surgery. Olfactory thresholds and nNO concentrations remained unchanged after surgery in the chronic rhinosinusitis group. In the chronic rhinosinusitis group, nNO concentrations correlated positively with the olfactory threshold preoperatively (P < 0.0001) and 3 months after surgery (P < 0.05). In the control group, nNO production did not correlate with the olfactory thresholds (P > 0.05). CONCLUSION: Olfactory function and nNO concentration correlate in chronic rhinosinusitis patients but not in healthy subjects. This suggests that both parameters do rather not directly influence each other but it might be the inflammatory processes found in chronic rhinosinusitis that affects olfaction and nNO. Nasal nitric oxide produced by the paranasal sinuses seems not to directly influence olfactory function.     

Apoptosis in the Aging Olfactory Epithelium

Objectives Olfactory receptor neurons undergo apoptosis at a baseline rate, probably secondary to environmental damage even in the absence of gross disease. The study demonstrates age‐related changes in expression of genes known to regulate apoptosis in the rat olfactory mucosa. These results are compared with gene expression in young rats and rats that have undergone surgical deafferentation of the olfactory receptor neurons. Study Design The olfactory mucosae from three groups of rats were studied: young, normal rats (age, 12 wk); old, normal rats (age, 24 mo); and young rats 9 days after bilateral removal of the olfactory bulb. Bulbectomy is known to produce an initial wave of apoptotic cell death in the population of olfactory neurons. At 9 days after the injury, the olfactory mucosae consist of an enhanced population of regenerating neurons destined to also undergo apoptosis, since their synaptic target (bulb) has been removed. Methods Ribonuclease protection assays and histological analysis of the three groups were performed. Results Ribonuclease protection assay analysis indicates that age induces increases in the expression of pro‐apoptotic genes in the olfactory mucosae similar to the increase seen after deafferentation (bulbectomy). Specifically, the expression of procaspase‐3 and bax was increased in aged animals and bulbectomized animals when compared with young, normal animals. Conclusions Aging induces changes in gene expression in the olfactory mucosae that appear to favor apoptosis, probably associated with increased fragility of olfactory receptor neurons in older animals. These changes may, at least in part, explain the age‐related decline in olfactory sensation and loss of olfactory receptor neurons seen in elderly patients.     

Postoperative evaluation of olfactory dysfunction in eosinophilic chronic rhinosinusitis – comparison of histopathological and clinical findings

Abstract

Background: Olfactory dysfunction in eosinophilic chronic rhinosinusitis (ECRS) is poorly understood.

Objective: To compare olfactory mucosal injury due to eosinophil infiltration in ECRS with postoperative olfactory function.

Methods: Seventeen ECRS patients (ECRS group) and 18 bilateral rhinosinusitis (non-ECRS group) patients were compared. At 3 and 12 months post-endoscopic sinus surgery (ESS), all patients were evaluated for subjective symptoms (nasal obstruction, nasal discharge and olfactory dysfunction), endoscopic nasal findings, CT score and T&T olfactometer recognition threshold test. The eosinophil count, OMP-positive cells and epithelial erosion in olfactory mucosa collected during ESS were compared with the postoperative olfactory function.

Results: The non-ECRS group showed significant improvement in all clinical findings at 3 and 12 months, but the ECRS group showed worsening of the olfactory dysfunction symptoms and T&T olfactometer recognition threshold at 12 months because of recurrence of sinusitis. The groups differed significantly in the ΔT&T value (i.e. pre-ESS T&T recognition threshold – post-ESS T&T recognition threshold) at both 3 and 12 months, and the degree of olfactory improvement differed. Histologically, the ECRS group showed significantly more eosinophils, fewer OMP-positive cells and greater epithelial erosion than the non-ECRS group.

Conclusions: Eosinophilic inflammation was thought to cause olfactory mucosal injury/dysfunction.     

The diagnosis of a conductive olfactory loss

OBJECTIVES/HYPOTHESIS: Two of the most common causes of olfactory loss include upper respiratory infection (URI) and nasal or sinus disease. The etiology of most URI-related losses is thought to be viral and, as yet, there is no available treatment. In contrast, nasal or sinus disease produces an obstructive or conductive loss that often responds dramatically to appropriate therapy. Therefore, the distinction is important but in many cases may be difficult because such patients often present with no other nasal symptoms, and routine physical findings may be nonspecific. The purpose of this report is to characterize those aspects of the history and physical examination that will help to substantiate the diagnosis of a conductive olfactory loss. STUDY DESIGN: A retrospective, nonrandomized study of consecutive patients presenting with a primary complaint of olfactory loss. METHODS: This study reviewed 428 patients seen at a university-based taste and smell clinic from July 1987 through December 1998. Of this total, 60 patients were determined to have a conductive olfactory loss. All patients were referred specifically because of a primary chemosensory complaint. The University of Pennsylvania Smell Identification Test (UPSIT; Sensonics, Inc., Haddon Heights, NJ) was administered in all cases. RESULTS: The most commonly diagnosed etiologies of olfactory loss were head injury (18%), upper respiratory infection (18%), and nasal or sinus disease (14%). Of the 60 patients with a conductive loss, only 30% complained of nasal obstruction, whereas 58% described a history of chronic sinusitis. Only 45% reported that their olfactory loss at times seemed to fluctuate in severity. Anterior rhinoscopy failed to diagnose pathology in 51% of cases, whereas nasal endoscopy missed the diagnosis in 9%. Systemic steroids elicited a temporary reversal of conductive olfactory loss in 83% of patients who received them, offering a useful diagnostic maneuver, whereas topical steroids did so in only 25%. CONCLUSIONS: The etiology for olfactory loss can in many cases be difficult to determine, but it is important to establish prognosis and to predict response to therapy. Diagnosis requires a thorough history, appropriate chemosensory testing, and a physical examination that should include nasal endoscopy. A trial of systemic steroids may serve to verify that the loss is indeed conductive.     

Eosinophilia in the ethmoid mucosa and its relationship to the severity of inflammation in chronic rhinosinusitis

BACKGROUND: The aim of this study was to analyze histopathologically mucosal inflammation in patients with chronic rhinosinusitis. In addition, we assessed tissue eosinophilia in relation to the severity of inflammation and to the computer tomographic (CT) findings. METHODS: Forty-eight pathological sinus mucosa specimens obtained during functional endoscopic sinus surgery were stained by hematoxvlin and eosin. Total inflammatory cells and eosinophils were quantified. The preoperative CT scans were scored by the staging system of Lund-MacKay. RESULTS: The grade of the eosinophilic infiltration in the diseased sinus mucosa correlated significantly with the severity of the mucosal inflammation. Allergy or asthma had no effect on the proportion of the eosinophilic infiltrate. The CT scan scores assessed by the Lund-MacKay system correlated significantly with the severity of the inflammatory cellular infiltrate. The correlation between the CT scan scores and the eosinophilic infiltrate of the mucosa was close to significant. CONCLUSION: Eosinophilic mucosal inflammation represents the most severe inflammatory changes of the mucosa. Twenty to forty percent of the patients with chronic rhinosinusitis had no eosinophilic inflammation of the mucosa. The CT-staging system of Lund-Mackay correlated with the extent of mucosal inflammation.     

Pathology of the olfactory mucosa: implications for the treatment of olfactory dysfunction

Objective: The pathology of the olfactory mucosa is poorly understood; however, most cases of hyposmia and anosmia appear to be associated with a decline in the number of functioning mature olfactory sensory neurons (OSNs). Under normal conditions, OSNs undergo apoptotic cell death at a baseline rate likely secondary to their exposed location in the nose. Regeneration of mature OSNs from precursors in the epithelium allows the animal to maintain an adequate number of neurons necessary for olfactory sensation. In many cases of olfactory dysfunction, this balance is apparently disturbed, with a net loss of OSNs. The current study will examine normal and diseased olfactory tissue for the presence of data demonstrating that the preferred mechanism of OSN cell death is apoptotic in both health and disease. The potential therapeutic implications will be discussed. Study Design: Histologic analysis of human and animal olfactory tissue. Methods: Normal and diseased human and animal olfactory mucosa were assessed for immunohistochemical evidence of apoptosis. Results: Increased activity of the apoptotic effector enzyme caspase‐3 was demonstrated in diseased olfactory mucosa in comparison with normal controls. Conclusion: These results indicate that a common pathway may mediate OSN cell death from a diverse set of pathologic insults including aging, trauma, and sinusitis. Interference with this pathway of cell death is currently the subject of intense pharmacotherapeutic research for the management of stroke and meningitis. These drugs may ultimately prove useful in the treatment of clinical olfactory dysfunction.     

Some risk factors for refractory chronic sinusitis: an immunohistochemical and electron microscopic study

The goal of the present work was to investigate possible risk factors for the poor response of some cases of chronic sinusitis to endoscopic sinus surgery in spite of the precision of the surgical technique. Eleven adult patients who were scheduled for revision endoscopic sinus surgery underwent a complete allergy workup. At the time of surgery, a tiny biopsy was taken from the maxillary sinus mucosa close to the middle turbinate. The specimens were processed for histochemical and transmission electron microscopic examination. Six patients (55 per cent) proved to be allergic. Their sinus mucosa showed eosinophilic infiltration (6.1 cells/mm(2)), and mast cell degranulation. This proves that allergens can reach the sinus mucosa and have a direct impact on it. Another three patients (27 per cent) were non-allergic but exhibited mucosal eosinophilia (5.0 cells/mm(2)), and two of them showed mast cell degranulation. These patients were diagnosed as having nonallergic rhinosinusitis with eosinophilia (NARSE). The nasal mucosa of the remaining two patients did not reveal any characteristic pathological findings, and no pathologic diagnosis could be established for them. None of the patients showed electron microscopic evidence of purulent inflammatory changes, and the bacterial cultures recovered normal respiratory flora in nine patients (82 per cent). The present research spotlights the importance of allergy and nonallergic eosinophilic infiltration of the mucosa as possible risk factors that may degrade the results of endoscopic sinus procedures and discusses some pertinent pathological and clinical aspects.     

Post-traumatic olfactory dysfunction

OBJECTIVES: This study demonstrates histopathologic and immunocytochemical changes in the olfactory bulb of a patient with post-traumatic olfactory dysfunction. These results are analyzed in light of current understanding of the pathophysiology of anosmia and dysosmia following head trauma. Emphasis is placed on potential mechanisms of human regeneration and recovery. STUDY DESIGN: The current study documents the history of a patient with the initial complaint of complete anosmia following minor head trauma. Two months after the injury the patient developed persistent, severe dysosmia with debilitating weight loss. Neurosurgical treatment, including removal of the olfactory bulbs and tracts, resulted in permanent resolution of dysosmia. METHODS: Histopathologic and immunocytochemical analysis of the olfactory bulbs was undertaken and compared with age-matched control tissue. RESULTS: Pathological analysis of the olfactory bulb revealed a marked reduction in the number of nerve processes with few intact olfactory glomeruli compared with an age-matched control. Specific immunohistochemical staining for the olfactory neuron-specific protein OMP, however, demonstrated the presence of intact axonal projections between the olfactory mucosa and the bulb. CONCLUSIONS: These results support the hypothesis that post-traumatic anosmia involves, at least in part, damage to peripheral olfactory nerve fibers with histological changes in the olfactory bulb. Potential mechanisms for the development of post-traumatic dysosmia are also discussed.     

Screening of Olfactory function Using the Biolfa® Olfactory Test: Investigations in Patients with Dysosmia

Objective —To present a statistical evaluation of a new olfactory test, Biolfa^®.

Material and Methods —The olfactory test was carried out in individuals with normal olfactory function (n=67; 31 males; mean age 27.4 years) and in patients with mild, moderate or severe hyposmia (n=155; 61 males; mean age 54.6 years). The main diagnoses of the hyposmic patients were upper respiratory tract infection (32%), nasal polyposis (24%), head trauma (8%), idiopathic (8%), old age (5%) and chronic rhinitis (5%). In the first part of the test, olfactory thresholds were measured for three different substances (eugenol, aldehyde C14 and phenyl ethyl alcohol). The second part comprised an odor identification test for determining olfactory function for a large panel of common odors of Southern European countries.

Results —Mean olfactory thresholds were determined for subjects with normal olfaction and hyposmic patients; there was a statistically significant relationship between olfactory thresholds and degree of olfaction (mild to moderate hyposmia versus severe hyposmia). For the odor identification test, a global score was determined to allow the differentiation of normosmic subjects from patients with mild, moderate or severe hyposmia. The principles of decision theory (i.e. analysis of the receiver operating characteristic curve) were applied to the problem of evaluating the ability of Biolfa to distinguish subnormal subjects from hyposmic subjects.

Conclusion —This study provides a basis for the routine clinical use of Biolfa.     

Circadian anosmia: A rare clinical presentation

We report the case of a 27‐year‐old female who presented with a peculiar story of anosmia fluctuating in a circadian manner. Olfactory function appeared an hour after breakfast, was normal during daytime, and disappeared in the early evening. Imaging confirmed chronic rhinosinusitis (CRS). Initial systemic, followed by topical steroid treatment, rapidly and sustainably reversed this condition. The olfactory fluctuation paralleled the endogenous steroid production. This suggests that slight congestion changes in a chronically inflamed nasal mucosa may have been sufficient to induce this circadian anosmia. The importance of identifying fluctuation of olfactory function as a sign of CRS is emphasized and discussed. Laryngoscope, 128:1537–1539, 2018     

黏蛋白基因MUC2在慢性鼻-鼻窦炎筛窦黏膜中的表达

目的：定量检测慢性鼻-鼻窦炎（CRS）筛窦黏膜中黏蛋白基因MUC2的表达,探讨其在CRS黏液过量分泌中的意义。方法：采用荧光定量RT-PCR检测32例CRS患者（CRS组）和8例正常筛窦黏膜患者（正常对照组）中MUC2 mRNA的表达。结果：MUC2 mRNA在CRS组中的表达[（10．55±3．31）×10^10拷贝／g]较正常对照组[（1．40±0．44）×10^10拷贝／g]增高,两组间差异有统计学意义（P〈0．01）。结论：MUC2 mRNA在CRS筛窦黏膜中表达上调,可能是CRS黏液过度分泌的重要因素之一。     

Abnormalities of axon growth in human olfactory mucosa

OBJECTIVES/HYPOTHESIS: Random biopsies of the human adult olfactory mucosa often demonstrate degenerative changes in the olfactory epithelium (OE) in both dysosmic and normosmic patients and, consequently, have limited diagnostic usefulness. However, detailed analysis of the subepithelial tissue with specific attention to the fascicles of the olfactory nerve and abnormalities of axonal growth may improve the correlation of histopathology with sensory function. STUDY DESIGN: Retrospective review of human OE biopsies. METHODS: Mucosal biopsies from the olfactory area obtained from 27 subjects were examined by light and electron microscopy, with particular attention to the olfactory nerve fascicles; results were correlated with clinical status. Immunohistochemical analysis was used to characterize the extent of axonal depletion, relative maturity of the parent population, and aberrant axonal growth. RESULTS: As expected, there are areas of respiratory metaplasia and neuronal depletion in normosmic as well as dysosmic patients. The degree of axon degeneration within the fascicles correlates better with individual olfactory status. Immature neurons predominate, and re-entrant neuromas develop in patients with olfactory loss caused by disconnection from the olfactory bulb. Individuals with olfactory loss caused by epithelial damage as with chronic rhinosinusitis display evidence of nerve fascicle degeneration and intraepithelial neuromas. CONCLUSION: The status of olfactory axons provides useful information on the overall condition of the olfactory periphery and improves the diagnostic usefulness of mucosal biopsies. In addition to an assessment of the epithelium per se, the fascicles of the olfactory nerve need to be characterized for a complete analysis of the olfactory mucosa.     

Histological evaluation of maxillary sinus mucosa after functional endoscopic sinus surgery

BACKGROUND: This study was performed to evaluate the histological changes of the maxillary sinus mucosa of patients with chronic rhinosinusitis (CRS) after functional endoscopic sinus surgery (FESS). METHODS: In a cohort study, biopsy specimens were collected from the maxillary sinus of patients submitted for FESS. One year after surgery, patients were clinically reassessed. Patients showing recurrence of disease (group 1) required a revision surgery, through which a second biopsy specimen was collected. Patients showing a favorable clinical response (group 2) were submitted to an outpatient maxillary biopsy through the previous opened middle meatus antrostomy. Biopsy material from four cadavers was used as control. The histological and electron microscope findings were analyzed. RESULTS: At the initial surgery, patients presented many histopathological alterations, such as an inflammatory process infiltrating the submucosa, atypical respiratory epithelium with an important increase in goblet cells, metaplasia, or mixed epithelium. Group 1 patients persisted with the same alterations 1 year later, but ciliary dysmorphy was more accentuated. Group 2 patients presented a predominantly pseudostratified epithelium, but some areas contained an increased number of goblet cells and a reduction in the number of ciliated cells. CONCLUSION: Recovery of the maxillary sinus mucosa of patients with CRS, observed by electron and light microscopy, was incomplete 1 year after endoscopic surgery, even in nonsymptomatic patients; nevertheless, these alterations were more important in symptomatic patients than in asymptomatic patients.