Introduction
About 20% of people in the general population have an impairment of the sense of smell.[1][2][3] Impaired olfaction leads to diminished quality of life. It can be dangerous, as environmental hazards such as the smell of natural gas or smoke may not be appreciated; the sense of taste is intimately connected with the sense of smell, and diminished taste can also result in missed indications of danger, such as spoiled or contaminated food.[4] Furthermore, impaired olfaction may be a warning sign for common neurodegenerative disorders, such as Alzheimer dementia and Parkinson disease.[5][6] The most common causes of olfactory decline are sinonasal disease, viral infection, and nasofacial trauma.[7][8] If there is a clear structural pathology in the nose or brain, treatment may be oriented toward the underlying lesion, such as functional endoscopic nasal surgery for chronic rhinosinusitis with polyposis or neurosurgical interventions for an anterior skull base tumor.[3][8][9] In patients with damage to the olfactory epithelium and olfactory pathways due to inflammation, toxins, trauma, viral infection, or unknown causes, olfactory therapy may be appropriate.[3][8][9]
Medications such as corticosteroids for chronic rhinosinusitis and other inflammatory conditions may provide some relief from olfactory decline.[3][8] Other options include sodium citrate, zinc, and vitamins, but their efficacy has not been definitively proven to date.[3][8] A non-surgical and non-pharmacological approach to improve olfactory function is olfactory training, wherein patients expose themselves twice daily to different odors over the course of several months.[3][8] Several studies have described the efficacy of olfactory training.[10][11][12][13] In many cases, however, the studies' findings are questionable due to the absence of appropriate control groups or the lack of a double-blinded experimental design.[3][13] Moreover, some patients with olfactory dysfunction recover spontaneously. Up to 20% of patients with post-traumatic olfactory dysfunction and up to 60% of patients with post-infectious olfactory dysfunction demonstrate spontaneous resolution of symptoms.[14][15]
Additionally, younger patients, patients with relatively well-preserved olfactory function, women, and non-smokers have a good chance of a spontaneous improvement of olfactory functioning.[14] For patients who smoke, tobacco use should be discouraged because it is associated with diminished olfactory functioning, and continued use may thwart any attempt to improve the sense of smell.[2] Olfactory training is comparatively simple, and so far, serious side effects have not been reported. Although its precise mechanism of action and efficacy are incompletely understood, olfactory training is increasingly applied in routine care for patients with olfactory dysfunction of varying etiologies.[3][8][13]
Anatomy and Physiology
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Anatomy and Physiology
The olfactory system is the most primitive of the human special senses and is very closely connected to the limbic system, the seat of emotion.[16] Airborne particulates are inhaled into the nose and dissolved in the mucinous secretions of the nasal cavity; ciliary action brings them into contact with the olfactory epithelium, where water-soluble molecules from these particulates bind to chemoreceptors that subsequently transduce signals via the unmyelinated axons of the olfactory projections up through the cribriform plate of the ethmoid bone to the olfactory bulbs, and then ultimately to the olfactory cortex of the forebrain.[17]
The olfactory epithelium is located at the apex of the nasal cavity, along both the upper septum and the superior turbinate, as well as the roof of the nose. Olfaction has many roles, including recognition of danger and identification of edible food, and is responsible for a significant proportion of the human sense of taste; taste buds on the tongue can only differentiate among sweet, sour, salty, bitter, and umami (savory) flavors, but the human sense of smell can differentiate as many as 1 trillion odorants.[18] The chorda tympani branch of the facial nerve and the glossopharyngeal nerve provide the oral and pharyngeal portion of the taste pathway, but the major contribution of the sense of smell explains why olfactory decline tends to have a deleterious effect on gustation as well. Of note, the path of the olfactory nerve fibers through the skull base may represent a direct route by which infectious pathogens, such as SARS-CoV-2, may access the central nervous system.[19] The very thin fibers of the olfactory projections that travel through the perforations of the cribriform plate are also highly susceptible to shearing injury, which is why craniofacial trauma may result in hyposmia or anosmia.
Compared to other sensory systems, the olfactory system, including the olfactory epithelium and parts of the olfactory bulb, is unique in that it can adapt and regenerate.[20][21] Exposure to odors enhances this process and leads to improved olfactory functioning.[22][23] This regenerative phenomenon was first discovered in healthy human subjects in the mid-1990s.[24][25] A decade later, repeated exposure to odors was also shown to improve olfactory function for patients with deficiencies due to a broad range of etiologies.[26] Over the last ten years, numerous studies have confirmed the efficacy of olfactory training in humans.[10][11] Additionally, findings from several animal studies and functional imaging studies in humans confirm the effectiveness of olfactory training.[27][28][29][30]
Indications
Recent work suggests that olfactory training is more effective in younger individuals than in the elderly and is more effective in individuals with severe olfactory dysfunction than in individuals who are only mildly affected.[31] However, olfactory training may be employed to treat dysfunction from a broad range of etiologies, irrespective of age and baseline olfactory functioning.[8][11][13][10] The most common indications reported in the literature are:[10][11][12][8][31]
- Post-infectious olfactory dysfunction: This is one of the most common causes of olfactory decline in clinical practice and one of the most common indications for olfactory training.[8][10][11] Following mild to severe upper respiratory tract infection, particularly virally-mediated, post-infectious olfactory dysfunction may occur. Olfactory testing in these patients shows diminished odor threshold and odor discrimination but normal odor identification.[32] Many patients with COVID-19 infection and decline of the chemical senses have this type of olfactory dysfunction.[33] The likelihood of improvement with olfactory training for patients with post-infectious olfactory dysfunction is comparatively good. A study involving more than 100 patients showed that 71% of patients with post-infectious olfactory dysfunction improved with olfactory training over one year, while 37% of patients without olfactory training spontaneously recovered over the same time period.[34] Neither abstinence from alcohol intake nor patient gender appears to affect the chance of improvement with olfactory training in patients with post-infectious olfactory dysfunction.[31] Olfactory training may be used in combination with corticosteroid treatment in selected patients with post-infectious olfactory dysfunction.[35][8][36]
- Post-traumatic olfactory dysfunction: This type of olfactory dysfunction may occur suddenly or with a delay after a brain or nasal injury.[8] Olfactory tests reveal diminished odor threshold and odor discrimination ability, while odor identification is normal.[32] Olfactory training has been reported to work for post-traumatic olfactory dysfunction, but results may be less dramatic than for post-infectious olfactory dysfunction.[37][38][39][26][31] Jiang et al reported that 23% of patients with post-traumatic olfactory dysfunction had improvement in olfactory thresholds when training with phenyl ethyl alcohol, while 5% of patients improved when training with a mineral oil control.[37]
- Parkinson disease: Patients with Parkinson disease have a severe impairment of olfactory functioning, which starts many years before the onset of motor symptoms such as tremors, rigidity, and bradykinesic gait.[40][41][42] Olfactory testing typically reveals impairment of odor discrimination and odor identification abilities, while the odor threshold is relatively normal.[32] Medication prescribed for Parkinson disease does not improve olfactory functioning, and in light of the progressive, neurodegenerative process that underlies Parkinson disease, olfactory training may be an important treatment option for patients who request rehabilitation of sense of smell.[43] The success rate with olfactory training in patients with Parkinson disease is lower than in patients with post-infectious olfactory dysfunction; about 20% of patients with Parkinson disease benefit from olfactory training, while 10% recover olfactory function spontaneously.[44]
Contraindications
There are no described contraindications for olfactory training in terms of past medical or surgical history or medications. However, the value of olfactory training for treating olfactory dysfunction secondary to sinonasal disease remains yet to be determined.[8] Many patients with olfactory dysfunction due to sinonasal disease, especially those with chronic rhinosinusitis (with or without polyposis), may benefit from functional endoscopic surgery, generally with a pre-operative course of nasal topical steroids.[9] Thus, medical and surgical options may be considered first to manage patients with chronic rhinosinusitis.[8] Olfactory training may be considered for olfactory dysfunction secondary to sinonasal disease when surgical treatment options are exhausted, not possible, or after completion of surgical interventions.[9]
Equipment
The set-up for olfactory training includes four sniff bottles or jars (the volume of each container should be approximately 50 mL). Inside each container is 1 mL of an odor solution soaked into cotton pads. The different scents are typically phenylethyl alcohol (rose scent), eucalyptol (eucalyptus scent), citronella (lemon scent), and eugenol (clove scent).[26] Olfactory treatment is an easy-to-use measure to improve olfactory dysfunction; it may be part of the therapeutic repertoire of both the specialized smell and taste clinic and the general ear, nose, and throat practice.[13]
Personnel
Patients need to be instructed on how to perform olfactory training by a physician, a nurse, a nurse practitioner, or other medical professionals with experience in managing olfactory dysfunction.
Preparation
The cause of the olfactory dysfunction needs to be determined using a comprehensive evaluation that follows consensus guidelines.[8] Additionally, patients must be counseled on the planned protocol for their olfactory training.
Technique or Treatment
For standard olfactory training, the patients sniff each of the four scents separately for at least 20 to 30 seconds twice daily (preferably once in the morning before breakfast and once in the evening before going to bed). Patients should constantly sniff for 20 to 30 seconds on each odor without a break. The odors for training are presented in sniff bottles or jars. Typically, patients undergo olfactory training for at least 24 weeks. For patients with post-infectious olfactory dysfunction, olfactory training over the course of one year yielded better results than training for 16 weeks.[34] Results from another study showed that olfactory training with 12 odors was more effective than training with four odors in patients with post-infectious olfactory dysfunction.[45] A third study's results reported that high odor concentrations were more effective than low concentrations of odor for olfactory training in patients with post-infectious olfactory dysfunction.[46] These observations, however, have not been verified in patients with olfactory dysfunction due to other etiologies. For patients with hyposmia or anosmia without a history of sinonasal infection, olfactory training, following the standard protocol (that is, olfactory training with four different odors twice daily for at least 24 weeks), might be a good starting point.
Olfactory training over several months is challenging for both the patients and the healthcare provider. The effects may be less dramatic than expected, and it takes a high degree of discipline to follow the standard protocol of olfactory training.[3][13] An olfactory training ball can be used to improve adherence and outcomes of olfactory training. The olfactory training ball is roughly the size of a baseball, has four tubes containing different odors, and is lightweight and ergonomic.[47] Another approach to improving olfactory training adherence and outcomes is to call or schedule patients for regular office visits (e.g., every six weeks) to monitor their compliance and progress.
Complications
Olfactory training has been assessed in more than 40 clinical studies, and results have been reviewed in several independent meta-analyses.[10][11][12][36] None of the studies found complications arising from olfactory training. However, patients may find olfactory testing tiresome because of the daily nature of the training over several months.
Clinical Significance
Except for post-viral olfactory dysfunction and olfactory dysfunction secondary to chronic rhinosinusitis, there is no established medical or surgical treatment for olfactory dysfunction.[8] Thus, olfactory training is the only treatment option available to patients with olfactory dysfunction due to other etiologies. For this reason, olfactory training is particularly important for the management of patients with olfactory decline.
Enhancing Healthcare Team Outcomes
A multi-professional team is critical for achieving the best possible results of olfactory training. This team should include several members such as medical clerks, nurses, nurse practitioners, and physicians. Medical clerks are responsible for the coordination of patients' appointments and ordering and storing the materials needed for olfactory training. Nurses and nurse practitioners screen patients to determine candidacy for olfactory training. They also instruct patients to ensure the olfactory training protocol is followed correctly and thus facilitate the best possible outcome of the therapy—furthermore, they follow up with patients to ensure adherence to the protocol. Physicians oversee and supervise medical clerks, nurses, and nurse practitioners. Additionally, regular conferences ensure that all team members are apprised of the patient's progress undergoing olfactory training, ensuring all patients' needs are addressed and problems resolved; it is also critical for the team to educate itself regarding current developments in the field of olfaction and olfactory training.
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