Olfactory dysfunction

Disturbances in olfaction can result from pathologic processes at any level along the olfactory pathway. They can be classified in a way analogous to otologic dysfunction, as conductive or sensorineural defects. In conductive (ie, transport) defects, transmission of an odorant stimulus to the olfactory neuroepithelium is disrupted. Sensorineural defects involve the more central neural structures. Overall, the most common causes of primary olfactory deficits are aging, nasal and/or sinus disease, prior viral upper respiratory tract infections (URTIs), and head trauma. [13]

Conductive defects

Inflammatory processes cause a large portion of olfactory defects. These may include rhinitis of various types, including allergic, acute, or toxic (eg, cocaine use). Chronic rhinosinusitis causes progressive mucosal disease and often leads to decreased olfactory function despite aggressive allergic, medical, and surgical intervention.

Masses may block the nasal cavity, preventing the flow of odorants to the olfactory epithelium. These include nasal polyps (most common), inverting papilloma, or any nasal tumor.

Developmental abnormalities (eg, encephaloceles, dermoid cysts) also may cause obstruction.

Patients with laryngectomies or tracheotomies experience hyposmia because of a reduced or absent nasal airflow. Children with tracheotomies who are cannulated very young and for a long period may have a continued problem with olfaction even after decannulation because of a lack of early stimulation of the olfactory system.

Central/sensorineural defects

Infectious and inflammatory processes contribute to central defects in olfaction and in transmission. A viral URTI may result in smell loss by replacing olfactory neuroepithelium with respiratory epithelium, but studies suggest that stem cells remain, allowing for potential regeneration of the olfactory epithelium. Recovery of smell in these cases can take months to years and, in some instances, may never occur. Sarcoidosis (affecting neural structures), Wegener granulomatosis, and multiple sclerosis are also diseases that can result in smell loss. Once thought to be mostly a conductive defect through mucosal edema and polyp formation, chronic rhinosinusitis also appears to disrupt the neuroepithelium with irreversible loss of olfactory receptors through up-regulated apoptosis.

Head trauma, brain surgery, or subarachnoid hemorrhage may stretch, damage, or transect the delicate fila olfactoria or damage brain parenchyma and result in anosmia. [14] A study by Bratt et al found that out of 182 patients with moderate to severe traumatic brain injury (TBI), olfactory dysfunction was diagnosed in 13.7% of them, with 8.2% of the total group suffering from anosmia. The study found an association between olfactory dysfunction and TBI patients who had sustained a fall, skull base fracture, or cortical contusion. [15]

Employing resting-state functional magnetic resonance imaging (rs-fMRI), a study by Park et al found that compared with healthy controls, individuals with traumatic anosmia demonstrated reduced intranetwork connectivity in the olfactory network. However, the olfactory and whole-brain networks had increased internetwork connectivity. Moreover, patients with traumatic anosmia showed decreased modularity and increased global efficiency in the whole-brain network, with these characteristics correlated with disease severity. [16]

A report by Singh et al of 774 TBI admissions found the overall incidence of anosmia to be 19.7%, with the rate of the condition in mild, moderate, and severe TBI being 9.55%, 20.01%, and 43.5%, respectively. [17]

Sense of smell decreases with age, and it has been shown that the number of fibers in the olfactory bulb decreases throughout one's lifetime. In one study the average loss in human mitral cells was 520 cells per year with a reduction in bulb volume of 0.19 mm3. [18] These olfactory bulb losses may be secondary to sensory cell loss in the olfactory mucosa and/or general decline in the regenerative process from stem cells in the subventricular zone.

Congenital syndromes may be associated with neural losses. Kallmann syndrome is one type of congenital smell loss and is due to failed olfactory structure ontogenesis and hypogonadotropic hypogonadism. One study found the vomeronasal organ to be absent in patients with Kallmann syndrome.

Endocrine disturbances (eg, hypothyroidism, hypoadrenalism, diabetes mellitus) may affect olfactory function.

Toxicity of systemic or inhaled drugs (eg, aminoglycosides, formaldehyde) can contribute to olfactory dysfunction. Many other medications and compounds may alter smell sensitivity, including alcohol, nicotine, organic solvents, and direct application of zinc salts. [19]

Over-the-counter zinc nasal sprays have been implicated in the cause of smell loss. On June 16, 2009, the US Food and Drug Administration (FDA) issued a public health advisory and notified consumers and healthcare providers to discontinue use of intranasal zinc products. The intranasal zinc products (Zicam Nasal Gel/Nasal Swab products by Matrixx Initiatives) are herbal cold remedies that claim to reduce the duration and severity of cold symptoms and are sold without a prescription. The FDA received more than 130 reports of anosmia (inability to detect odors) associated with intranasal zinc. Many of the reports described the loss of smell with the first dose. [20]

The NHANES study determined that smoking can be linked to greater risk of olfactory alteration. [21] Research has identified squamous metaplasia and change in the morphology of the olfactory receptor neurons in smokers, as well as a higher level of apoptosis of these neurons in smokers than in controls. In addition, there is evidence that the volume of the olfactory bulb is reduced in smokers. [22]

Various neuropsychiatric disorders (eg depression, [23] seasonal affective disorder, bipolar disorder [24] ) have been linked to hyposmia. It has also been shown that patients with schizophrenia or acute major depressive disorder have not only decreased olfactory sensitivity but also reduced olfactory bulb volumes. [25, 26] The neurologic explanation for these findings is under active investigation and may lead to new therapies or early detection screening tools.

Degenerative processes of the central nervous system (eg, Parkinson disease [PD], Alzheimer disease) and other neurologic diseases (Huntington disease, multiple sclerosis, motor neuron disease) have been associated with hyposmia. Patients with Alzheimer or Parkinson disease show changes in detection, discrimination, and identification of odors compared with age-matched controls. The severity of dysfunction is correlated to disease progression, although in most cases, olfactory loss is present years before motor or cognitive symptoms; this is usually a gradual loss and often goes unnoticed or unreported by patients.

The presence of olfactory dysfunction at the time of PD diagnosis increases the risk of developing dementia. [27] Indeed, in general, olfactory loss in an individual increases the odds of being diagnosed with dementia within 5 years, [28] but this may be a phenomenon of an overall association of age-related sensory impairment with cognitive impairment. [29]

A study by Roos et al, using the University of Pennsylvania Smell Identification Test, the Unified Parkinson’s Disease Rating Scale motor subscale, and the Mini-Mental State Examination, reported a relationship between hyposomia and motor and nonmotor symptoms of PD, including with regard to cognition, depression, anxiety, autonomic dysfunction, and sleep disturbances. It was also linked to the degree to which nigrostriatal dopaminergic cells are lost. In addition, using single-photon emission computed tomography (SPECT) scanning, the investigators found that olfactory test scores were strongly associated with the binding of dopamine transporter in the putamen and caudate nucleus. [30]

A study by Cecchini et al found severe olfactory impairment in persons with Down syndrome, with these individuals performing worse than euploid controls on tests of odor detection threshold, odor discrimination, and odor identification. Among 56 subjects with Down syndrome, 27 demonstrated functional anosmia. [31]

An association has also been recognized between smell loss and increased risk of mortality. [32] This has been found to be unrelated to dementia and may be an indicator of deteriorating health. [33]

The assessment of olfactory function should become a more standard aspect of patient evaluation. There are numerous functional and structural approaches available to assess the olfactory system, including psychosocial and electrophysiological testing, as well as imaging studies. Objective measures of olfactory function may serve as an early marker for these diseases or as a prognostic indicator. An understanding of the mechanism of the decrease in smell could help to further elucidate the pathophysiology of these disorders or uncover new treatments. [34, 35]

Gustatory dysfunction

Much of what is perceived as a taste defect is truly a primary defect in olfaction resulting in an alteration of flavor. The components that comprise the sensation of flavor include the food's smell, taste, texture, and temperature. Each of these sensory modalities is stimulated independently to produce a distinct flavor when food enters the mouth.

Taste may be enhanced by tongue movements, which increase the distribution of the substance over a greater number of taste buds. Adaptation in taste perception exerts a greater influence than in other sensory modalities.

Other than smell dysfunction, the most frequent causes of taste dysfunction are prior URTI, head injury, and idiopathic causes, but many other causes can be responsible.

Lesions at any site from the mucosa, taste buds, unmyelinated nerves, or cranial nerves to the brain stem may impair gustation.

Oral cavity and mucosal disorders including oral infections, inflammation, and radiation-induced mucositis can impair taste sensation. The site of injury with radiotherapy is probably the microvilli of the taste buds, not the taste buds themselves, since taste buds are thought to be radioresistant.

Poor oral hygiene is a leading cause of hypogeusia and cacogeusia. Viral, bacterial, fungal, and parasitic infections may lead to taste disturbances because of secondary taste bud involvement.

Normal aging produces taste loss due to changes in taste cell membranes involving altered function of ion channels and receptors rather than taste bud loss. [3, 36]

More than 200 medications have been associated with taste disorders. [37] Clinicians need to be aware of this, especially with regard to patients taking numerous drugs.

Malignancies of the head and neck, as well as of other sites, are associated with decreased appetite and inability to appreciate flavors.

Use of dentures or other palatal prostheses may impair sour and bitter perception, and tongue brushing has been shown to decrease taste acuity.

Surgical manipulation may alter taste permanently or temporarily. Resection of the tongue and/or portions of the oral cavity, most commonly for reasons of malignancy, decreases the number of taste buds. Radiation and chemotherapy damage taste receptors and decrease salivary flow, altering taste perception. In otologic surgery, stretching or transection of the chorda tympani nerve may result in temporary dysgeusia. Bilateral injury still may not result in permanent taste dysfunction, because of the alternate innervation through the otic ganglion to the geniculate ganglion via the greater superficial petrosal nerve.

Gastric bypass surgery can also have adverse olfactory and gustatory effects. In a study by Graham et al of 103 patients who underwent Roux-en-Y gastric bypass, sensory changes in taste and smell were reported by 73% and 42% of these individuals, respectively, [38] although patients seem to have less olfactory loss if the bypass is done laparoscopically. [39]

Nutritional deficiencies are involved in taste aberrations. Decreased zinc, copper, and nickel levels can correlate with taste alterations. Nutritional deficiencies may be caused by anorexia, malabsorption, and/or increased urinary losses.

Endocrine disorders also are involved in taste and olfactory disorders. Diabetes mellitus, hypogonadism, Sjögren syndrome, and pseudohypoparathyroidism may decrease taste sensation, while hypothyroidism and adrenal cortical insufficiency may increase taste sensitivity. Hormonal fluctuations in menstruation and pregnancy also influence taste.

AIDS patients often complain of alterations in taste, and detection thresholds of glutamic acid and hydrochloride are higher in patients suffering from AIDS. [40]

Heredity is involved in some aspects of gustation. The ability to taste phenylthiourea (bitter) and other compounds with an –N-C= group is an autosomal dominant trait. Studies have shown that phenylthiourea tasters detect saccharin, potassium chloride (KCl), and caffeine as more bitter. Type I familial dysautonomia (ie, Riley-Day syndrome) causes severe hypogeusia or ageusia because of the absence of taste bud development.

Direct nerve or CNS damage, as in multiple sclerosis, facial paralysis, and thalamic or uncal lesions, can decrease taste perception.

Many other diseases can affect gustation (eg, lichen planus, aglycogeusia, Sjögren syndrome, renal failure with uremia and dialysis, erythema multiforme, geographic tongue, cirrhosis).

COVID-19

According to the American Academy of Otolaryngology - Head and Neck Surgery (AAO-HNS), anecdotal evidence indicates that anosmia and dysgeusia are symptoms of coronavirus disease 2019 (COVID-19). The AAO-HNS recommends that in patients in whom other respiratory diseases, such as allergic rhinitis, acute rhinosinusitis, and chronic rhinosinusitis, are not present, the occurrence of anosmia or hyposmia, as well as dysgeusia, should raise suspicion for COVID-19 infection. [41, 42, 43] The Centers for Disease Control and Prevention (CDC) has added "new loss of taste or smell" to its list of symptoms that may arise 2-14 days after exposure to the COVID-19 virus (ie, severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]). [44] Loss of taste or smell has also been added by the World Health Organization (WHO) to its list of less common COVID-19 symptoms. [45]

A study by Speth et al of 103 patients with COVID-19 found the prevalence of olfactory dysfunction to be 61.2%, with the condition occurring on median infection day 3. A strong correlation was reported between the severity of olfactory dysfunction and the severity of loss of taste. In addition, patients with olfactory dysfunction tended to have more severe shortness of breath. The investigators also found that olfactory dysfunction was less common in older age and more prevalent in females. [46]

Another study, a literature review by Aziz et al, indicated through pooled analysis that taste sensation is altered in almost 50% of patients with COVID-19, although it was suggested that, due to underreporting, the prevalence may be even higher. [47]

A study by Boscolo-Rizzo et al of adult patients with mild COVID-19 reported that within 4 weeks of taste or smell alteration, this symptom partially or completely resolved in 89% of them. [48, 49]