xRead - Olfactory Disorders (September 2023)

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PATEL et al.

the piriform cortex, and the projections from function ally disparate glomeruli are largely indistinguishable from each other. 107 An exception is the projection to the corti cal amygdala where the M/T cells of individual glomeruli also project broadly but innervate distinct patches that dif fer from one glomerulus to the next. 108 In terms of odor ant representation in the piriform cortex, spiking activity is sparse and likewise distributed. 108,109 The olfactory tuber cle apparently encodes odorant valency (whether a smell is considered pleasant or unpleasant) and is considered a part of the ventral striatum with a dense innervation by midbrain dopaminergic neurons. 110 At the higher cortical level, the OFC also seems to integrate odorant and reward information to help guide motivated behavior. 111 INCIDENCE AND PREVALENCE The absolute precise incidence and prevalence of olfactory disorders are still unknown. Despite increasing efforts to characterize and diagnose OD and its numerous causes, prevalence rates range widely from ≈ 1.5% to 25% world wide. The wide range of published epidemiologic data is largely secondary to heterogeneity in olfactory testing methodology and study populations. There is at least con cordance that OD increases in prevalence with age and is more common in men relative to women. 14,112 The methods of olfactory assessment used in epidemi ologic studies vary widely. Although a multitude of dedi cated olfactory assessment tools are available worldwide, self-reported OD is a commonly used metric. 14,113 While self-report measures are valuable, these assessments typ ically lack sensitivity and underestimate the degree of OD as compared with psychophysical instruments. 114,115 Nonetheless, the lack of an accepted, universal psy chophysical instrument, coupled with wide variation in patient demographics, exposures, and cultural differences among studies, makes determination of prevalence rates challenging. 112 Self-reported prevalence rates have been explored in sev eral large, population-based studies. A survey of ≈ 80,000 US adults aged > 18 years, utilizing national adjustment estimates, extrapolated that 1.4% of the US adult popu lation experienced olfactory impairment. This prevalence rate markedly increased in older individuals, with 40% of individuals aged > 65 years reporting OD. 116 Meanwhile, olfactory questionnaires from a nationally representative Korean database reported a prevalence rate of OD of 4.5%. 117 Two additional studies in Europe and the United States, using questionnaires aimed primarily at determin ing the prevalence of CRS, reported prevalence rates of OD of 7.6% and 9.4%, respectively. 118,119 Between 2011 and 2014, the US nationally represen tative NHANES database queried participants regarding VI

the presence and frequency of olfactory disturbances. The estimated prevalence of olfactory disturbances was 10.6% ± 1.0% when patients were asked whether they expe rienced a smell disturbance in the preceding 12 months; however, when considering participants with self-reported changes in OF “since age 25,” prevalence rates increased to ≈ 23%. 120,121 Meanwhile, psychophysical assessment using the Pocket Smell Test (PST) demonstrated rates of 12.4% and 13.5% from the 2011 to 2012 and 2013 to 2014 interview cycles, respectively. 122,123 In the same database, 6.5% of par ticipants experienced phantom odor perception. 124 Several additional large population-based studies have included psychophysical measures of OF. Utilizing the SOIT in a nationally representative population from Swe den, the prevalence of OD was 19.1%, with nearly 6% of participants designated as anosmic. 125 Notably, self-reports of “worse-than-normal” olfaction was 15.3% in the same population. 126 An Australian investigation of participants from in and around Sydney, using the SDOIT, identified impaired olfaction in 27% of participants. 127 In a Span ish study, participants were given four microencapsulated odorants and asked to correctly detect, recognize, and iden tify each odorant. Prevalence of impaired detection was 19.4%, with 0.3% of the population reported as anosmic. Meanwhile, 43.5% (0.2% anosmic) and 48.8% (0.8% anos mic) of the population were designated as having impaired olfactory recognition and identification, respectively. 128 Multiple US-based studies have utilized both self reporting and psychophysical testing. In a large cohort of participants from Wisconsin, OD was identified in 24.5% of all participants and 62.5% of participants aged > 80 years, as defined by the SDOIT. 114 Additional US-based studies examining aged populations with various psychometric olfactory instruments have reported rates of OD from 2.7% to 100%, with significant variation regarding the defini tions of dysfunction, study size, participant demographics andage. 129–134,76 Overall, OD is a common condition, with a wide range of prevalence among population-based studies. Accu rate population-level incidence and prevalence rates are challenging to fully elucidate but appear to be higher in more elderly persons and men. PATHOPHYSIOLOGY A Sinonasal Inflammatory Disease 1 Basic underlying mechanisms Sinonasal inflammatory disease is the most common cause of olfactory loss. 135–137 Olfaction relies on conduction of odorants from the air to the OE and subsequent sen sorineural signaling to the brain. Clinical and basic science VII