Intranasal zinc and anosmia: the zinc-induced anosmia syndrome

OBJECTIVE: Commercial preparations of intranasal zinc gluconate gel are marketed as a remedy for the common cold. However, intranasal zinc has been reported as a cause of anosmia in humans and animals. Seventeen patients presenting with anosmia after the use of intranasal zinc gluconate are described. METHODS: The authors conducted a retrospective case series of patients presenting to a nasal dysfunction clinic and conducted complete history and physical examination on all patients, including nasal endoscopy. All patients underwent detailed odor threshold and identification testing. RESULTS: Threshold and identification testing revealed impaired olfaction in all patients. Inflammatory and traumatic causes of anosmia were excluded based on history, physical examination, and imaging. All patients diagnosed with zinc-induced anosmia or hyposmia reported sniffing deeply when applying the gel. This was followed by an immediate sensation of burning lasting minutes to hours. Loss of sense of smell was then perceived within 48 hours. Seven of 17 patients never developed symptoms of an upper respiratory infection. CONCLUSIONS: The zinc-induced anosmia syndrome, characterized by squirt, sniff, burn, and anosmia, occurs after the exposure of olfactory epithelium to zinc cation. It can be distinguished from postviral anosmia based on history.     

Anosmia after intranasal zinc gluconate use

BACKGROUND: Zinc is an essential mineral. Beneficial zinc absorption takes place via enteral, parenteral, or cutaneous routes. However, direct application to the olfactory epithelium has been reported to cause loss of smell. Recently, intranasal zinc gluconate has been recommended as a treatment for the common cold. Severe posttreatment hyposmia and anosmia have been observed. METHODS: The case report of a typical patient is presented and analyzed in detail, followed by a series of patients with severe hyposmia or anosmia after the use of intranasal zinc gluconate. RESULTS: Although interindividual variation in drug response and drug effect is apparent, the severe hyposmia or anosmia appears to be long lasting or permanent in some cases. The mechanism of olfactory loss is thought to be the direct action of the divalent zinc ion on the olfactory receptor cell. CONCLUSIONS: Zinc ions are toxic to olfactory epithelium. Reports of severe hyposmia with parosmia or anosmia have occurred after intranasal use of zinc gluconate.     

Clinical assessment of retronasal olfactory function

OBJECTIVES: To develop a test kit for the simple assessment of retronasal olfactory function and to compare orthonasal and retronasal olfactory function in healthy subjects and patients with olfactory disorders. DESIGN AND PATIENTS: We tested 230 individuals with normosmia, hyposmia, and anosmia using grocery-available powders. Initially, 30 different substances were investigated. Subjects identified each substance using a list with 4 verbal items (forced choice). After preliminary experiments, 20 items were selected according to the degree to which they were identified by normosmic and anosmic subjects. Orthonasal olfactory function was assessed psychophysically using "sniffin' sticks," which includes tests for odor identification, discrimination, and butanol odor thresholds. In addition, anosmia was confirmed electrophysiologically by means of olfactory-evoked potentials. RESULTS: In healthy subjects, there was a test-retest reliability correlation of r(27) = 0.76 for retronasal olfactory function, which is similar to other odor identification tests. Retronasal testing in normosmic subjects allowed for the discrimination of sex-related differences, with women scoring higher than men (P =.007), and the identification of a slight decrease with age (r(120) = -0.20; P =.03). Orthonasal and retronasal identification of odors was found to correlate (r(86) = 0.78; P<.001). Retronasal testing allowed for the discrimination between normosmia, hyposmia, and anosmia (P<.001). In addition, retronasal performance of anosmic patients appeared to improve with duration of anosmia (P =.03). No difference was found between patients with anosmia of different origin. CONCLUSION: Results of the present investigation indicate that the assessment of retronasal olfactory function is possible using oral stimulus presentation.     

Individual significance of olfaction: development of a questionnaire

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

Screening of olfaction with smell diskettes

BACKGROUND: Aim of the study was the development of a new screening test of olfaction with reusable diskettes as odorant applicators. METHODS: A screening test of olfaction was designed using 8 diskettes containing different odorants. The diskettes can be opened to release the odor and are closed after testing. The test was designed as a triple forced multiple choice test using a questionnaire, resulting in a score from 0 to 8 correct answers. Ninety-one volunteers with a normal sense of smell and 13 patients with subjective hyposmia or anosmia were tested to validate the developed test. The same volunteers were also tested with the sniffin' sticks test, another screening test of olfaction that is already validated. After testing, the volunteers were asked to compare the two tests. RESULTS: Among the 91 volunteers with normal sense of smell, 10 achieved a score of 7, and 81 a score of 8 in the smell disk test. The 13 patients with hyposmia or anosmia achieved a score between 0 and 5. Based on the test design, there is a probability of 99.74% that a person who achieves a score of 7 or 8 will have normal olfaction. In the sniffin' sticks test, 85 volunteers with normal sense of smell achieved a score in the normal range for this test (6-8) whereas 6 volunteers were below with a score of 4 or 5. The 13 patients with hyposmia or anosmia scored between 0 and 6. The smell disk test was preferred by 86 persons, the sniffin' sticks test by 5, and 12 assessed both tests as equal. CONCLUSIONS: The developed screening test is reliable for identifying patients with a normal sense of smell, and it can distinguish them from patients with hyposmia and anosmia. The diskettes proved to be reliable and comfortable applicators for odorants in clinical practice.     

Impaired sense of smell in patients with nasal surgery

The aim of the study was to determine the incidence of olfactory disorders before and following nasal and paranasal sinus surgery. It was a prospective observational study. Over a 6-month period, all patients who had been listed for nasal and paranasal sinus surgery underwent preoperative and postoperative evaluation of their sense of smell. A questionnaire and the 'Smell Diskettes Test' were used to assess olfaction. One hundred and eighty-four patients were studied. Preoperatively, 19 patients (10.3%) had an impaired sense of smell (8.1% before septoplasty, 6.1% before rhinoplasty and 17.1% before endoscopic sinus surgery). Only 16 (84%) of these patients were aware of their impaired sense of smell. Following surgery, four patients (2.5%) who were normal preoperatively developed impaired olfaction on questioning, and this was supported by testing it. In the subgroup that had a septoplasty, no patient developed hyposmia compared to one patient (2.6%) after rhinoplasty and one patient (3%) after endoscopic sinus surgery. No patient developed anosmia. Preoperatively, 10.3% of patients had an altered sense of smell, making it desirable that this is documented in order to avoid postoperative claims that this was caused by surgery. It also helps to audit the results of surgery.     

Anosmia caused by inhaled hazardous substances. Significance for expert assessment general practice

BACKGROUND: Both environmental and occupational pollutants can affect the functional integrity of the olfactory epithelium or even destroy olfactory tissue. However, occupational hyposmia and anosmia have not been included into the list of occupational diseases. Therefore, compensation of occupationally induced smell disorders is difficult. OBJECTIVE: To evaluate patients with toxic hyposmia for the pollutants involved and to discuss consequences for occupational and environmental medicine. METHODS: A total of 19 patients were evaluated in our departments between 1993 and 1997 for olfactory disorders related to environmental or occupational pollutants. The charts of these patients were retrospectically analyzed and the causative pollutants compared with the literature. RESULTS: A chronical exposure to mixtures of metal dusts and steam, volatile organic substances, and anorganic gases were the most common pollutants involved in occupational dysosmia. Only one case of acute development of an anosmia due to exposure to CO and combustion gases was documented. CONCLUSIONS: Olfactory disorders are underestimated in occupational and environmental medicine. Relevance of olfactotoxic substances for occupational medicine can be postulated in metal and chemical workers, in welding and disinfection. The list of occupational diseases should be completed by olfactory hyposmia and anosmia.     

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.     

外伤后失嗅患者的嗅觉事件相关电位和MRI评估

目的 探讨嗅觉事件相关电位(olfactory event related potentials,OERP)和嗅觉通路MRI对外伤后失嗅的评估价值.方法 回顾性分析24例外伤后失嗅患者的临床资料.所有患者均行详细的病史采集、全面体检、T&T嗅觉检查、鼻内镜检查、OERP测试、颅脑CT和嗅觉通路MRI检查.结果 主观嗅觉测试:双侧完全失嗅20例;单侧完全失嗅,对侧嗅觉减退2例;单侧完全失嗅,对侧嗅觉正常2例.OERP测试:双侧最大嗅刺激均不能引出OERP者20例,单侧最大嗅刺激不能引出OERP者4例;单侧能引出OERP者4例,其中2例能正常引出,另2例OERP幅值下降且潜伏期延长.氨气刺激均能引出鼻内三叉神经化学感受事件相关电位.嗅路MRI检查:嗅球损伤24例次(100%),额叶直回损伤22例次(91.7%),额叶眶回损伤16例次(67%),远端嗅束和颞叶损伤各2例次(8%).结论 OERP能对外伤后嗅觉进行定性和定量的客观整体评估;嗅路MRI能对外伤后失嗅的损伤部位、程度进行客观、精确的评估.两者结合能对嗅觉功能进行全面、客观评价.     

Comparison of diagnostic findings using different olfactory test methods

OBJECTIVE: To quantify discrepancies in the diagnosis of olfactory function that might exist when comparing results obtained from centers using different methods of olfactory testing. STUDY DESIGN: Prospective study of 50 healthy adult volunteers and 25 adult patients with olfactory complaints. METHODS: Two test methods, the Connecticut Chemosensory Clinical Research Center (CCCRC) test widely used in the United States, and the Jet Stream Olfactometer (JSO) test used in Japan, were used to measure and categorize the diagnostic level of olfactory function (normosmia, mild hyposmia, moderate hyposmia, severe hyposmia, anosmia). Olfactory function was measured separately for each nostril. RESULTS: There was a significant correlation (rs = 0.788, P < .01, n = 150 nostrils) between diagnostic categories assigned by the CCCRC and JSO test methods. Diagnostic categories were identical for 66.7% of the nostrils tested, and in only 7.3% of the cases did the results differ by more than one category. For the anosmic and normosmic categories, test results were in agreement 91.7% of the time, whereas for the hyposmic categories (mild, moderate, and severe) results were in agreement only 22.2% of the time. CONCLUSIONS: Our results demonstrate that when comparing clinical or research data obtained from centers using different olfactory test methods, subjects with diagnoses of anosmia or normosmia may be more reliably compared than those with different levels of hyposmia.     

Screening and rehabilitation of olfaction after total laryngectomy in Swedish patients: results from an intervention study using the Nasal Airflow-Inducing Maneuver

OBJECTIVES: To examine the olfactory function in patients with laryngectomy and to assess the results of the Nasal Airflow-Inducing Maneuver (NAIM) odor-rehabilitation technique. DESIGN: A prospective intervention study. SETTING: University hospital. PATIENTS: Twenty-four patients, 21 men and 3 women, mean age 68 years, who underwent laryngectomy at least 5 months prior to intervention. INTERVENTION: Speech therapists trained patients in the NAIM technique: simultaneous lowering of the jaw, floor of the mouth, tongue, base of the tongue, and soft palate while the lips are closed. Three interventions were given within 6 weeks. MAIN OUTCOME MEASURE: Olfactory testing with semistructured interview, the Questionnaire on Olfaction, Taste, and Appetite (QOTA), and the Scandinavian Odor-Identification Test (SOIT). Quality of life was measured with European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-H&N35 questionnaires. The patients were categorized as smellers or nonsmellers based on the SOIT results. RESULTS: Before the treatment, 10 patients (42%) were smellers (ie, 6 had normosmia and 4 hyposmia), while 14 patients (58%) were nonsmellers (ie, all had anosmia). Thus, 18 patients had impaired olfaction. Using the NAIM technique, 13 (72%) of 18 patients with impaired olfaction showed improvement. Of the 14 nonsmellers, 7 converted to smellers after only 1 intervention session, giving us a success rate of 50% in anosmic patients after 1 session. CONCLUSIONS: Olfactory impairment is common in patients who underwent laryngectomy. The NAIM method is easy to learn and rapidly improves smell and taste. A single intervention session is sometimes sufficient, but many patients benefit from repeated training. The SOIT test is an effective and simple test for the assessment of olfaction acuity after laryngectomy.     

Impact of olfactory impairment on quality of life and disability

OBJECTIVE: To determine whether olfactory loss affects patients' quality of life or level of disability. DESIGN: Retrospective survey using questionnaire data and clinic database review. SETTING: Two university medical center smell and taste clinics. PATIENTS: A total of 1407 patients were tested for smell and taste disturbances from 1984 through 1998. Surveys were mailed to 1093 patients who had abnormal test scores; 420 (38.4%) returned completed surveys. Patients were grouped by self-rated ability to smell as "impaired" (those reporting persisting deficits) or "improved" (those reporting no smell problem when surveyed). MAIN OUTCOME MEASURES: Response frequencies were compared between the 2 groups for questions regarding ability to perform common activities of daily living and quality-of-life issues. RESULTS: Mean (+/-SD) number of activities of daily living affected by olfactory loss was 4.70 +/- 3.56 for the impaired group and 0.61 +/- 1.58 for the improved group (P < .001). Among specific activities, the most common cited impairments were ability to detect spoiled food (impaired vs improved groups, 75% vs 12%; P < .001), gas leaks (61% vs 8%; P < .001), or smoke (50% vs 1%; P < .001); eating (53% vs 12%; P < .001); and cooking (49% vs 12%; P < .001). Differences in quality-of-life issues were reported primarily in the areas of safety and eating. Overall satisfaction with life was reported by 87% of the improved group but only 50% of the impaired group (P < .001). CONCLUSIONS: Patients reporting persistent olfactory impairment after previously documented olfactory loss indicate a higher level of disability and lower quality of life than those with perceived resolution of olfactory compromise.     

Can we smell without an olfactory bulb?

BACKGROUND: Lack of an olfactory bulb (OB) is typically associated with anosmia. METHODS: We present a patient with subnormal olfactory function in whom the OB could not be detected with magnetic resonance imaging (MRI). RESULTS: Olfactory function was evaluated on two occasions. Orthonasal olfactory function was assessed with the "Sniffin' Sticks" test providing a score equivalent to hyposmia. Retronasal olfactory function was studied with "smell powders" indicating a decreased, but not absence of, olfactory function. Importantly, chemosensory event-related potentials were clearly present in response to olfactory and trigeminal stimuli. CONCLUSION: This indicates that olfactory function may be present in some subjects even when an OB can not be detected with MRI.     

Non-sinonasal-related olfactory dysfunction: A cohort of 496 patients

Introduction and aimThere is a high prevalence of olfactory dysfunction in the general population. Several causes of olfactory dysfunction have been reported and this disorder is classically divided into sinonasal and non-sinonasal-related olfactory dysfunction. The aims of this study were firstly, to evaluate the frequency of the various aetiologies of olfactory dysfunction in a population of patients with non-sinonasal-related olfactory dysfunction and secondly, to evaluate the degree of olfactory impairment associated with these various aetiologies.Material and methodsWe retrospectively reviewed a cohort of 496 patients with non-sinonasal-related olfactory dysfunction. The aetiology of the olfactory dysfunction was recorded for each patient. The aetiology was determined by a complete clinical assessment, including medical history, complete otorhinolaryngological examination, psychophysical testing of olfactory function, recording of olfactory event-related potentials and brain magnetic resonance imaging. Six groups of patients were defined on the basis of the aetiology of the disease and orthonasal and retronasal psychophysical olfactory performances were evaluated in each group.ResultsPost-infectious and post-traumatic aetiologies were the most common causes, representing 37.9% and 33.1% of patients, respectively, followed by idiopathic (16.3%), congenital (5.9%), toxic (3.4%) and neurological (3.4%) olfactory dysfunction. Anosmia was significantly more frequent in congenital (93.1%) and post-traumatic (62.8%) olfactory dysfunction, whereas hyposmia was more frequent in the post-infectious group (59.6%). Orthonasal and retronasal olfactory function tests were significantly correlated in all groups except for the congenital group.ConclusionsThe data of this study confirm that the most common causes of non-sinonasal-related olfactory dysfunction are post-infectious and post-traumatic. Post-infectious olfactory dysfunction is mainly observed in middle-aged women and is mainly associated with hyposmia, whereas post-traumatic olfactory dysfunction is mainly observed in young men and is associated with a high rate of anosmia.     

Clinical significance of results from olfactory testing

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.     

Drug-induced olfactory and gustatory dysfunction: Analysis of FDA adverse events reporting system

ObjectivesWith the COVID-19 pandemic, there is growing interest and research in olfactory and gustatory dysfunction (OGD). Drug-induced dysfunction is an often overlooked etiology. While several medications include smell or taste disturbance as a side effect, there are no publications describing which medications are most frequently implicated. We aim to describe the patterns of these adverse drug reactions (ADRs) using the FDA Adverse Events Reporting System (FAERS).MethodsThe FAERS database was queried from 2011 to 2021 for terms describing ADRs related to OGD. Terms included anosmia, hyposmia, olfactory test abnormal, olfactory nerve disorder, hallucination olfactory, parosmia, ageusia, hypogeusia, dysgeusia, and taste disorder. We identified the top reported medications associated with general smell dysfunction, general taste dysfunction, reduced smell, and altered smell.ResultsFrom 2011 to 2021, 16,091 ADRs were reported with OGD, of which13,641 (84.8%) and 2,450 (15.2%) were associated with gustatory and olfactory reactions, respectively. Zinc products (370 reports) and fluticasone propionate (214) were most commonly associated with olfactory dysfunction, specifically reduced olfaction. Varenicline (24) and fluticasone propionate (23) were most commonly associated with altered smell. Lenalidomide (490) and sunitinib (468) were most commonly associated with gustatory dysfunction. Antineoplastic and immunomodulating medications accounted for 21.6% and 36.3% of olfactory and gustatory ADRs, respectively. Among this category, immunoglobulin drugs were the most commonly associated with OGD ADRs.ConclusionGustatory dysfunction is more commonly reported ADR compared with olfactory dysfunction. Immunologic/rheumatologic medications are the leading culprit of reported OGD. With increasing numbers of patients presenting to otolaryngologists for OGD, it is important to consider drug-induced etiology.Level of evidenceIII.     

Chemosensory function assessed with psychophysical testing and event-related potentials in patients with atrophic rhinitis

Atrophic rhinitis (AR) is a chronic inflammation of the nose characterized by an atrophy of the nasal mucosa. This is typically associated with an impaired sense of smell and a subjective sensation of poor nasal breathing. The aim of this study is to assess chemosensory function in patients suffering from AR using psychophysical testings and event-related potentials (ERP) responses. A cohort of nine patients was extensively studied. Eight out of nine had secondary AR sequela of a bilateral total inferior turbinectomy whereas one patient had a primary AR. All the patients had a clinical evaluation using Sniffin’ Sticks test and a retro-olfaction test and an electrophysiological evaluation based upon ERPs obtained after both olfactory and trigeminal stimuli. All the patients complained of a poor nasal breathing and presented a distortion of the chemosensory function. Actually, the orthonasal psychophysical testing showed that four patients out of nine had anosmia, three out of nine had hyposmia and two out of nine were normosmic. All the patients demonstrated retro-olfaction scores inferior to the normal values. The chemosensory ERP showed that seven patients had no olfactory response whereas six had no trigeminal response. Four patients had neither olfactory nor trigeminal ERP response. In conclusion, this study demonstrates that most patients with AR secondary to a total bilateral inferior turbinectomy have a reduction of the chemosensory function measured objectively by psychophysical testings and ERP. Moreover, the trigeminal responses were absent in all the cases.     

先天性失嗅患者的临床研究

目的总结先天性失嗅的分类、临床表现以及影像学特点。方法回顾性分析2004年8月-2006年9月收治的8例先天性失嗅病例的临床资料。4例为伴有其他异常的先天性失嗅患者，其中卡尔曼综合征（Kallmann syndrome）3例，鼻腔鼻窦发育异常1例；另外4例为孤立性失嗅。8例患者均行详细的病史采集、全面体检、T＆T嗅觉检查、嗅觉事件相关电位测试、鼻内镜检查和鼻窦CT检查。7例行嗅觉通路MRI和性激素检测，2例行嗅黏膜活组织检查。结果8例患者自幼均未闻到过任何气味。除1例鼻腔鼻窦发育异常外，其余7例耳鼻咽喉科常规检查以及鼻内镜检查未见异常。主观嗅觉测试均为完全失嗅。嗅觉事件相关电位测试显示最大嗅刺激引不出嗅觉事件相关电位。CT检查显示1例鼻腔鼻窦未发育，其余7例未见异常。MRI检查：6例均为嗅球、嗅束缺失，嗅沟缺失或部分变浅；1例双侧嗅球发育差。内分泌检查：3例青春期后外生殖器以及男性第二性征发育不良，血清睾酮、雌二醇、促黄体生成素以及促卵泡生成素水平低于正常。其余4例性激素检测正常。嗅黏膜活检：1例未见嗅上皮典型结构；另1例为鳞状上皮组织伴慢性炎性病变。结论先天性失嗅诊断应依据病史、专科体检、嗅觉测试、鼻窦cT以及嗅路MRI检查结果。嗅路MRI对诊断有重要价值。