xRead - Olfactory Disorders (September 2023)

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confirm the duration, and assess other characteristics of the loss. Olfactory recovery times may be depen dent on the disease that caused the loss of smell. How ever, only a handful of diseases have been studied in isolation for humans, and follow-up times vary widely among studies, leading to many discrepancies in recov ery data. For instance, removing studies with subjective measures, 303,305,1322 smell loss from head injury is related to slower and lower recovery rates (0%–44%) than postvi ral loss (0%–77 %). 135,312,1071,1099,1323–1328 Additionally, medi cal, surgical, and alternative interventions may change the recovery times of smell loss. Without minor interventions, smell may spontaneously recover from diseases that result in nasal congestion or acute inflammation (with mini mal damage to the olfactory epithelium) as these symp tom resolve. 1099,1324,1327,1329,1330 Interestingly, COVID-19, a disease that attacks the underlying structure or support ing cells, 1331 rather than the sensory neurons of the olfac tory epithelium, may show recovery within weeks after symptoms have resolved, but we are now seeing regres sion of symptoms, with the addition of significant paros mias presenting months later. 1332–1335 OSNs do not express the necessary viral entry gene ACE2 for COVID-19 infec tion, unlike supporting cells underlying the OE (eg, sus tentacular or microvillar cells). These cells manage epithe lial maintenance through delivery of glucose to OSNs and local salt/water balance. It may be that only when it comes time for the inherent regenerative process to take place within the neuroepithelium, is when we see the true effect of the damage to these sustentacular cells. However, dis eases that cause direct damage to the OE (either supporting structure, sensory neurons, or both) may require complete neurogenesis for even primary recovery. Within 30 days, several young, mature neurons are grown in the epithe lium (via horizontal basal cells) while another 30 to 60 days are needed for the OE to reacquire a population of neu rons similar to a healthy state. 155 Many individuals with a sensorineural loss show recovery between this time and the first year from loss. While an increased duration of loss has been associated with worse recovery in multi ple studies, 1099,1325,1326,1328,1336 others showed no effect with duration of loss. 252,312,1324 After 3 years of loss, the chance of any recovery is severely reduced, yet, there are cases in which individuals have recovered even up to 9 years after a traumatic incident. 303,305,1337 However, even after recov ery, a portion of patients will still experience parosmia or a distorted sense of smell 23,1327,1338,1339 and phantosmia, 241 presumably caused by altered olfactory receptor neurons and their retargeting of glomeruli in the OB or onward at the level of the cortex. 22,155,1340 Several other factors may affect the natural course of neurogenesis impacting recovery times for smell loss. In general, there is a negative correlation between age and recovery, in that losing smell at an

older age results in slower recovery among multiple studies. 252,1099,1324,1326,1328 However, a lack of correlation has also been reported. 1325,1336,1341,1342 Decreased recovery may be caused by a reduced regenerative capacity of OSNs that comes with advancing age. 1343 In parallel, the size of the OE decreases with age and there may be more respira tory metaplasia over years of insult from diseases in which the damaged OE is replaced by respiratory epithelium and no longer functions as a sensory organ. 1343,522 This can be seen in mice in which telomere shortening (a basic mechanism of cellular aging) impairs OE regeneration, but not homeostatic conditions. 1344 Similarly, the decrease of afferent synaptic input into the brain, decreased neural response, and breakdown of synaptic connectivity and thus limited plasticity with age in the OB and other impor tant processing areas, may lead to less efficient central recovery. 522,1343,1345 There may also be a sex influence, with some reports showing females recovering more often than males 312,1099,1324,1325 ; however, again, many reports have shown no difference 252,1326,1328,1336,1342 (Tables IX.1-X1.2). Last, although most studies show no link between paros mia at initial diagnosis and better olfactory recovery, 1324 this has been postulated as a potential predictive sign. 1327 Recovery rates with limited intervention vary widely based on underlying etiology, age, and duration of loss before any definitive intervention. Aggregate grade of evidence : C (Level 2: three stud ies; Level 3: three studies; Level 4: 11 studies; Level 5: one study). Benefit : Earlier intervention after OD may potentially speed up recovery. Elderly and PTOD are associated with slower and poorer recovery and therefore may benefit most. Harm : None anticipated. Cost : Monetized value for any relevant intervention and follow-up appointments as needed to track recovery Benefits-harm assessment : There is a potential bene fit for follow-up appointments with intervention over nat ural recovery without follow-up Value judgments : It is difficult to conduct well controlled longitudinal studies to measure olfactory recov ery rates as this relies on clinical evaluation in a timely manner and continuous contact during follow-up investi gations. Accurate reporting of onset and recovery rates may enable early intervention while providing data regarding effects of etiology and various demographics on recovery. Additionally, clinicians/researchers should avoid patient populations heterogeneous in respects to etiology and medical, surgical, and alternative interventions when studying recovery from olfactory disorders. Policy level : Follow-up investigation is recommended in individuals with OD.