Olfactory Dysfunction: Etiology, Diagnosis, and Treatment

Background: Disorders of the sense of smell have received greater attention because of the frequency with which they occur as a symptom of SARS-CoV-2 infection. Olfactory dysfunction can lead to profound reduction in quality of life and may arise from many different causes.

Methods: A selective literature review was conducted with consideration of the current version of the guideline issued by the Association of the Scientific Medical Societies in Germany.

Results: The cornerstones of diagnosis are the relevant medical history and psychophysical testing of olfactory function using standardized validated tests. Modern treatment strategies are oriented on the cause of the dysfunction. While treatment of the underlying inflammation takes precedence in patients with sinunasal dysosmia, olfactory training is the primary treatment option for other forms of the disorder. The prognosis is determined not only by the cause of the olfactory dysfunction and the patient’s age, but also by the olfactory performance as measured at the time of diagnosis.

Conclusion: Options for the treatment of olfactory dysfunction are available but limited, depending on the cause. It is therefore important to carry out a detailed diagnostic work-up and keep the patient informed of the expected course and prognosis.

Despite the widely held assumption that the human sense of smell is relatively poor, humans are actually more sensitive than other mammals to a range of odors (1).

Olfaction is unique among the senses in that the olfactory cells regenerate continuously (e1, 2). Another special feature of the human sense of smell is its duality: odor molecules reach the olfactory mucosa not only orthonasally, on breathing in through the nose, but also retronasally by way of the throat, both on breathing out and when eating and drinking, mainly while swallowing (3, e2, e3). The orthonasal route is important for the perception of ambient odor molecules, the retronasal pathway for the perception of flavor (e4). Besides its function as a warning system for fire or potentially poisonous chemicals, the sense of smell also helps to detect when food has gone off. This explains why patients with olfactory dysfunction report difficulties with eating, when cooking, and in recognition of danger (e5), together with a general sense of insecurity in their daily lives, including the area of personal hygiene (4). Olfaction is also important in social interactions, e.g., in partnership and sexuality, and loss of the sense of smell can lead to social insecurity and, in approximately one third of those affected, to signs of depression (e6, e7). Olfactory dysfunction is thus frequently associated with a distinct deterioration in quality of life (e6).

An important role in perception of odors is played by the chemosensory system of the trigeminal nerve, which is activated by almost all odors in high concentration, triggering sensations such as stinging, pricking, tingling, coolness, warmth, or burning. Persons who lose their sense of smell or were born without it still possess this trigeminal perception.

Learning goals

After completing this article, the reader should be able to answer the following questions:

• What are the principal causes of olfactory dysfunction?
• How can the sense of smell be measured in clinical routine?
• What are the main principles in the treatment of olfactory dysfunction?

Classification of olfactory dysfunction

Olfactory dysfunction is divided into quantitative disorders (readily measurable) and qualitative disorders (much less amenable to measurement) (5). The quantitative disorders can be subdivided by olfactory performance, e.g., according to sensitivity to odors (olfactory threshold), discrimination between odors, or identification of odors. Normal function of the sense of smell is termed normosmia (with the olfactory capacity of young adults often serving as reference value); reduction, hyposmia; and complete loss, anosmia.

Qualitative olfactory dysfunction is separated into two subgroups. The term parosmia describes disorders featuring altered perception of odors from an extant source, while phantosmia is the detection of odors in the absence of a source. As a rule, parosmia involves perception of odors as unpleasant and disgusting, e.g., coffee smells “spoilt” or “fecal.” Phantosmias are often experienced as “smoky” or “burnt.” These erroneous impressions are extremely disconcerting in day-to-day life. The confusing perceptions mean that parosmia and phantosmia both often seriously impair the patients’ quality of life (5, 6).

Quantitative and qualitative olfactory dysfunction may occur in isolation, but are often present in combination. For example, an odor may initially trigger parosmia, followed by persisting phantosmia (e8, 8). Qualitative olfactory dysfunction is found in all causes of loss of the sense of smell and also occurs in persons with demonstrably intact olfactory capacity (normosmia) (e9). Nevertheless, an accumulation of parosmias is found in postinfectious olfactory dysfunction. Phantosmia occurs more frequently with post-traumatic olfactory dysfunction (9).

The causes of olfactory dysfunction

Olfactory disorders are classified according to the underlying cause. In addition to age-related dysfunction, they are divided into conditions of acquired and congenital origin (10). Exclusive categorization of olfactory disorders as conductive or sensorineural should no longer be practiced, because, for example, olfactory dysfunction in chronic sinusitis or following an infection often features both components (11, e10).

In common with hearing and sight, human olfactory function often deteriorates with advancing age (Figure). Reduced olfactory performance is found in up to 75% of persons over the age of 80 years. The underlying causes include decreased regenerative capacity of the olfactory epithelium, increased apoptosis of olfactory cells, and altered central nervous processing (12). In addition to age-related impairment there are many other causes of acquired olfactory dysfunction (Table 1): it can occur after an infection of the upper respiratory tract, for instance COVID-19 (postinfectious); following craniocerebral trauma (post-traumatic); with an underlying sinunasal condition (e.g., chronic rhinosinusitis with or without nasal polyposis); in the presence of an underlying neurological or neurodegenerative disease; in association with medications or other toxic substances; after radiotherapy or surgery; and with a tumor in the frontobasal region. Olfactory dysfunction may also be classified as congenital or—after exclusion of all known causative factors—idiopathic (11).

Figure

Age-dependent change in olfactory function in subjectively normosmic persons (n = 3355), stratified by gender (modified from [23]) TDI, Summed results, olfactory threshold + discrimination test + identification test

Table 1

The most commonly occurring causes of acquired olfactory dysfunction in otorhinolaryngology*

The congenital causes of olfactory dysfunction are divided into isolated and syndromal hyposmia and anosmia (e11). The most widely known examples of syndromal congenital anosmia are Kallmann syndrome (olfactory dysfunction together with hypogonadotropic hypogonadism) (e11) and congenital insensitivity to pain (e12, e13). Genetic variants of both isolated and syndromal congenital anosmia have been described (e14, e15). Congenital olfactory dysfunction is typically first diagnosed at 12 to 14 years of age (e16). A common radiological finding in congenital olfactory dysfunction is hypoplasia or aplasia of the olfactory bulb (e17). Suspicion of congenital olfactory dysfunction on clinical examination or imaging should prompt investigation by an interdisciplinary panel including pediatricians, endocrinologists, and, if possible, geneticists.

With regard to the neurological or neurodegenerative causes of olfactory disorders, over 90% of men and women with idiopathic Parkinson’s disease (IPD) have olfactory dysfunction, which is viewed as a supportive diagnostic criterion in the clinical diagnosis of IPD. Olfactory dysfunction may occur more than 10 years before the onset of the motor symptoms (e19), so early IPD should be borne in mind as a possibility in patients with olfactory impairment of unclear origin, particularly if other non-motor symptoms are present, such as REM sleep disorders, depression, or a family history of IPD (e20, 13).

Olfactory dysfunction is found to a lesser degree in other movement disorders, e.g., multiple system atrophy, supranuclear ophthalmoplegia, and corticobasal degeneration. Only a small number of studies have so far been conducted on olfactory function in familial Parkinson’s disease. Moderate hyposmia has been described in Huntington’s disease (e21) and mild olfactory dysfunction in patients with hereditary ataxia (e22). Mild dysfunction has also been observed in motor neurone disease (e23).

Severe olfactory dysfunction is found in many different forms of dementia (e24, e25). Olfactory dysfunction is an early symptom of Alzheimer’s disease, occurring in patients whose cognitive dysfunction is as yet only mild. Difficulty in identifying odors is a predictor of conversion to dementia (conversion rate 47%, odds ratio [OR] 5.1) (e26). Idiopathic olfactory dysfunction is often diagnosed in the prodromal phase of neurodegenerative diseases.

Olfactory dysfunction is also encountered in inflammatory disorders of the central nervous system: the incidence in multiple sclerosis is reported as 20–45% (e27). Patients with temporal lobe epilepsy tend to be affected by restriction of centrally mediated abilities such as odor identification and discrimination. Those with an acute depressive episode show a distinct reduction in olfactory sensitivity (e28), but after successful drug treatment there is no longer a significant difference from healthy persons. Limitations of the sense of smell are also known to occur in patients with schizophrenia and their first-degree relatives (e29).

Epidemiology

The prevalence of quantitative olfactory dysfunction in the general public is around 20% (7, 14, 15). The reports range widely, however, because of the different methods used to measure olfactory performance (e30). Epidemiological studies estimate a prevalence of about 15% for olfactory dysfunction in the USA (15, e31). European studies in which olfactory performance was assessed state the prevalence of anosmia as around 5%, that of hyposmia as 15% (14, e32, e33).

The prevalence of isolated qualitative olfactory disorders is lower than that of quantitative dysfunction. While the prevalence of isolated phantosmia is assumed to be between 1% and 9%, the rate of parosmia is reported as 2–4% (e9). In contrast, parosmia occurs with much higher frequency in the context of quantitative olfactory dysfunction, depending on the cause of the dysfunction. The rate of parosmia is highest in postinfectious olfactory dysfunction (49–68%), but it is also observed in post-traumatic (14–53%), idiopathic (14–55%), and sinunasal (28–30%) dysfunction (16, 17, 18, 19, e34). A problem with the documentation of qualitative olfactory dysfunction is that so far it has been assessed only by questioning the persons affected.

COVID-19-associated olfactory dysfunction

Around 50% of individuals with SARS-CoV-2-related olfactory dysfunction have loss of the sense of smell (29, e41), a rate higher than found in other viral infections (5). The loss is thought to be caused by damage to the supporting cells in the olfactory mucosa (e37), which leads indirectly to loss of function or death of the olfactory receptor neurons.

In contrast to other virus-related olfactory disorders, in COVID-19, particularly the Delta variant, nasal breathing is rarely impeded. In the Omicron variant olfactory dysfunction occurs less frequently, affecting around 15% of those infected (e40). In about 40–60% of those affected, parosmia arises several weeks or months later, especially in young patients and those with better olfactory performance. Phantosmia occurs less frequently (8).

The outcome of olfactory dysfunction in COVID-19 is thought to be generally favorable: a majority of patients report improvement within 2–3 weeks (29). Systematic investigations with psychophysical testing have shown that the initially impaired olfactory performance was much improved or restored to normal in 80–85% of patients at 6 months and in 95% at 12 months (e40). These patients are frequently regarded as fully recovered on the basis of their subjective assessments, but objective measurement often shows residual deficits (e41). Although overall the prognosis is therefore good, because of the large number of persons infected the SARS-CoV-2 pandemic has led to a significant increase in the prevalence of olfactory dysfunction. Details of the treatment of COVID-19-related olfactory dysfunction can be found in the Box.

Box

Treatment of COVID-19-associated olfactory dysfunction

Measurement of olfaction

The quantitative determination of olfactory performance can be achieved by means of subjective assessment, psychophysical tests, or electrophysiological methods. Structural and functional imaging techniques are also used for evaluation of olfaction.

Subjective assessment is the swiftest and simplest way of estimating olfactory function and is, like the medical history, of great importance. However—probably owing to the variation in both burden of suffering and self-esteem—subjective ratings are imprecise and often do not correspond to the objective olfactory capacity (19, e35).

Psychophysical tests

Psychophysical tests of olfactory performance often evaluate three different olfactory functions (11). Threshold testing enables determination of the lowest concentration at which an odorous substance, e.g., n-butanol or phenethyl alcohol, is detected. The staircase procedure is often used for this purpose: the samples are presented repeatedly in different concentrations until the odor can confidently be distinguished from solvent (20, 21, e36, e38). The discrimination test assesses the ability to tell odors apart: the participants are given various odor triplets to sniff, with two of the samples identical and the third different. In the identification test, various odors are presented and have to be characterized using one of a list of (typically four) terms (e38). These tests are best administered in a forced-choice process, where the study participants have to give a response even if they detect no odor.

In this testing scheme the olfactory threshold tends to describe the function of the periphery of the olfactory system, while odor identification and odor discrimination rather reflect the central nervous processing of odors (5). The identification test can also be administered by the study participants themselves (e38). Numerous versions of the identification test have been developed, varying mainly in the number of different odors used, and the test has to be adapted to avoid odors unfamiliar to the region or cultural group involved (5).

It is important that the diagnostic acuity and the reliability of the tests increase with the number of odors used (22). Screening tests (Table 2) are limited in their ability to assess the course of olfactory function, so additional documentation of the olfactory threshold is advisable (11, 5).

Table 2

Swift tests for assessment of olfaction

The following tests, some of which are commercially available, are used worldwide: the CCCRC test, a combined threshold and identification test; the UPSIT, a single-use disposable odor identification test in different variations with three to 40 odors that can be self-administered and is therefore extremely useful in, for example, patients with acute SARS-CoV-2 infection; and the reusable Sniffin’ Sticks test, which captures the olfactory threshold, odor discrimination, and odor identification (eTable 1). All of these tests are of verified reliability and validity (5); for the Sniffin’ Sticks, for example, there are normative data from over 9000 healthy men and women, enabling age- and gender-dependent classification of olfactory performance into normosmia, hyposmia, and anosmia (23).

eTable 1

Comprehensive tests for assessment of olfaction

It is important to use different olfactory tests in the course of COVID-19 (e40), for example, bearing in mind that odor identification may be largely normal but the olfactory threshold impaired (e41).

The determination of retronasal olfactory function (identification of aromas), however, is not an established element of routine clinical examination, although validated, reliable odor identification tests and tests for determination of the retronasal olfactory threshold are available, e.g., the “tasting powders” (e43) and the Candy Smell Test (24) (eTable 1). In these tests, odorous substances are given by mouth in the form of powders or sorbitol candies and identified, analogous to orthonasal tests, from a list of options in a forced-choice model (e43, e44).

The description of qualitative olfactory dysfunction rests essentially on questioning of those affected (e45). Measurement by the SSParoT method, for example, has been proposed as a means of standardizing the severity of parosmia (e46).

Electrophysiological procedures and functional imaging

While psychophysical testing of olfactory performance plays a major role in daily clinical practice, objective methods are needed whenever the person’s cooperation in psychophysical tests is problematic. This may be the case, for example, in children, in persons with cognitive disorders, or in the context of medicolegal investigations.

Among the electrophysiological techniques, recording of olfactory event-related potentials (OERP) from the EEG has been studied closely (e47). Owing to its technical complexity, however, this method is available at only a small number of centers. Nevertheless, it is currently the only means of assessing olfactory function objectively.

In contrast, magnetic resonance imaging (MRI) is widely available and enables the structural examination of areas of the brain that are intimately involved with the processing of odors, such as the olfactory bulb and the orbitofrontal cortex (25). In these structures, for example, small volumes point to the presence of a reduction in olfactory capacity. With the aid of imaging, a possible prognosis can then be outlined (e48). Cranial MRI naturally also clarifies whether, for instance, an intracranial tumor such as olfactory nerve meningioma is present that could cause olfactory dysfunction (e49). Not only structural MRI but also functional olfactory MRI can be performed (e50); however, the results at individual level are difficult to interpret (e51).

Measurement of the detrimental effect of olfactory dysfunction

Olfactory dysfunction can have a negative impact on the quality of life. This can hardly be assessed by psychophysical tests but is instead ascertained with the aid of questionnaires. One instrument often used to evaluate the olfaction-specific quality of life is the Questionnaire of Olfactory Dysfunction (QOD) with 52 items (26, e52). A short version with seven questions is also available (27).

Retronasal perception of odors has a greater influence on the quality of life than orthonasal detection (e53, 28). Other questionnaires, such as the Importance of Olfaction Questionnaire, measure the individual significance of the sense of smell (e54), which decreases with increasing age and with the increasing duration of olfactory dysfunction (28, e54).

The prognosis of olfactory dysfunction

Olfactory disorders may become less marked (e55) and may, as seen for example in COVID-19-associated dysfunction, disappear entirely (e56, 29).

The prognosis of and spontaneous recovery from olfactory dysfunction depends on, among other factors, the duration of the dysfunction, its cause, the presence/absence of parosmia at initial examination, the patient’s smoking status, and, most important, their age (e57, e58). The prognosis is therefore most favorable in younger non-smokers with a postviral olfactory disorder, relatively good olfactory function, only brief loss of olfactory function, and parosmic changes (17).

Among patients whose loss of the sense of smell persists for a longer period, e,g., 18 months, only around 30% will experience a spontaneous clinically relevant improvement in olfactory performance within 12 months (e59).

Treatment

While for patients with olfactory dysfunction in connection with sinunasal conditions it is recommended that the underlying disease be treated (e60), there are few therapeutic options and recommendations for olfactory disorders of other causes (7, e61).

Although many different kinds of treatment have been tested in clinical studies, apart from management of the inflammatory disease only olfactory training, i.e., the deliberate sniffing of various odors several times each day, possesses proven therapeutic value (5).

Drug treatment of sinunasal olfactory dysfunction

Topical corticosteroids form the basis of treatment (11, e60, e62) (evidence: eTable 2). They not only ameliorate the underlying chronic inflammation, e.g., rhinosinusitis with nasal polyposis, but also have a significant effect on olfactory function (10). Systemic steroids are given only for a short time to confirm the diagnosis of inflammation-related olfactory dysfunction and reduce the inflammation before continuing with topical treatment (e63) (evidence: eTable 3). The review and meta-analysis by Banglawala et al. (e64) included 28 randomized controlled trials (RCT) of topical and systemic corticoid therapy. Meta-analysis of the latter (five studies) showed significant improvement of both subjective (SMD −2.22, 95% confidence interval [−3.94; −0.49]) and objective (SMD 0.65 [0.28; 1.01]) olfactory function compared with placebo. As for topical treatment, 70% of the studies reviewed found improvement. When giving topical therapy, it is advisable to administer the nasal spray using a long applicator (e63, e65). With a normal applicator, the filtering function of the nose practically prevents the spray from reaching the olfactory cleft (e66, e67). The same effect can be achieved by administering the nasal drops in the so-called Kaiteki position (https://goo.gl/ZqxhDN) (e68). Corticosteroids are currently recommended only for sinunasal causes (5, e60).

eTable 2

Evidence for treatment with intranasal topical corticoids in sinunasal olfactory dysfunction caused by chronic rhinosinusitis with polyposis (RCT)

eTable 3

Evidence for treatment with oral corticoids in sinunasal olfactory dysfunction caused by chronic rhinosinusitis with polyposis (RCT)

Various monoclonal antibodies (“biologics”) have recently been approved for the treatment of rhinosinusitis with nasal polyposis. Because of their specific action on the inflammation they also exert a positive effect on the associated olfactory dysfunction (30), but they are not licensed for the treatment of olfactory dysfunction alone.

Olfactory training

Olfactory training has become established as the treatment of choice for non-sinunasal olfactory dysfunction (7, e69) (evidence: eTable 4). A meta-analysis (e70) of 13 RCT featuring very heterogeneous groups revealed a strong association for the improvement of odor identification (g = 0.83), odor discrimination (g = 0.89), and overall olfaction (g = 1.10), together with a mild to moderate effect for the olfactory threshold (g = 0.34). Olfactory training should be carried out carefully and consistently, smelling four different odors for 30 seconds each twice daily over a period of 4–6 months or longer. The effect is even better if the odors are replaced by different ones after 3 months (e71). Studies have shown that the initial olfactory performance and the cause of the olfactory dysfunction are associated with achievement of a relevant improvement in olfactory function after the training (e72, e73, 31). A less pronounced improvement is found for olfactory dysfunction of post-traumatic or idiopathic origin.

eTable 4

Evidence for the efficacy of olfactory training in the treatment of olfactory dysfunction

Further treatment options

Other topical treatments that have been evaluated are

sodium citrate, vitamin A drops, theophylline, palmitoyl ethanolamide/luteolin, and platelet-rich plasma. The systemic treatments that have been investigated include zinc, pentoxifylline, theophylline, cavoverin, α-lipoic acid, and vitamin B (e61, e74). Acupuncture has also been used to treat olfactory dysfunction (e74). Although many of these treatment options showed positive effects in the initial case series, as a rule there is a lack of robust clinical trials, particularly RCT and meta-analyses—although isolated RCT have been carried out for, among others, theophylline, vitamin A, and α-lipoic acid (5, 11).

The general functions of the sense of smell
The human sense of smell is important for the recognition of danger, perception of the flavors of food and drink, and social interaction.

The impact of limited olfactory capacity
Loss of the sense of smell may be associated with distinct deterioration in the quality of life and depressive symptoms.

The classification of olfactory dysfunction
Reduced perception of odors is described as hyposmia, complete loss of the sense of smell as anosmia. In parosmia odors are perceived incorrectly, while in phantosmia odors are perceived in the absence of a source.

The causes of olfactory dysfunction
Age-related decrease in olfactory performance; chronic rhinosinusitis; following upper respiratory tract infection; craniocerebral trauma; medications; underlying neurodegenerative disease; frontobasal tumors; or idiopathic

Epidemiology
Reduced olfactory function is a common occurrence. The prevalence of quantitative olfactory dysfunction in the general population is around 20%, that of anosmia around 5%.

Measurement of olfactory function
Psychophysical assessment of olfactory function with simple screening tests for identification of odors plays a central part in the basic diagnostic work-up for olfactory dysfunction.

Detailed investigation
For more detailed analysis of the progress of olfactory disorders, an odor identification or odor discrimination test can be accompanied by determination of the olfactory threshold. Objective depiction of olfactory function is achieved by documentation of olfactory event-related potentials.

COVID-19-associated olfactory dysfunction
The course of olfactory dysfunction in COVID-19 is viewed as generally favorable: most report improvement within 2–3 weeks.

Measurement of the negative impact of olfactory dysfunction
Validated questionnaires on the impact on the patient’s quality of life are available for documentation of the subjective severity of olfactory dysfunction and of its course.

Smelling tests
Tests widely available across the world are the CCCRC Test, a combined threshold and identification test; the UPSIT, a single-use odor identification test in different variations of three to 40 odors; and the reusable Sniffin’ Sticks test.

Treatment of sinunasal olfactory dysfunction
Treatment of the underlying inflammatory disease is recommended.

Treatment of postviral, post-traumatic, and idiopathic olfactory dysfunction
To date, the only treatment option is olfactory training: sniffing various odors several times each day.

Drug treatment of sinunasal olfactory dysfunction
Topical corticosteroids are the basic treatment. They not only ameliorate the underlying chronic inflammatory condition but also have a significant effect on olfactory function.

Conflict of interest statement
B.S. has received consultancy fees from Pohl-Boskamp, Bristol-Myers-Squibb, and Glaxo-Smith-Kline; lecture fees from Merck und Sanofi; and support for training courses from Bristol-Myers-Squibb, Merck, ALK, Sanofi, Pohl-Boskamp, MSD, and Novartis.

T.H. has received financial support from the Smell and Taste Lab, Geneva, Switzerland and from Takasago. He has received consultancy fees from Primavera, Oy-Mittelberg. T.H. is a committee member of the Olfactology/Gustology Working Group of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery. He has received support in the form of donations in kind from Burghart, Holm, and aspuraclip, Schönefeld.

The remaining authors declare that no conflict of interest exists.

Manuscript received on 3 June 2022, revised version accepted on
21 December 2022.

Translated from the original German by David Roseveare

Corresponding author
Prof. Dr. med. Thomas Hummel
Interdisziplinäres Zentrum für Riechen und Schmecken
Klinik für HNO-Heilkunde, Universitätsklinikum Carl Gustav Carus
TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany

Cite this as:
Hummel T, Lui DT, Müller CA, Stuck, BA, Welge-Lüssen A, Hähner A: Olfactory dysfunction: etiology, diagnosis, and treatment.
Dtsch Arztebl Int 2023; 120: 146–54. DOI: 10.3238/arztebl.m2022.0411

►Supplementary material

eReferences, eTables, eCaseReport:
www.aerzteblatt-international.de/m2022.0411

References

1. McGann JP: Poor human olfaction is a 19th-century myth. Science 2017; 12: 356 (6338)

2. Durante MA, Kurtenbach S, Sargi ZB, et al.: Single-cell analysis of olfactory neurogenesis and differentiation in adult humans. Nat Neurosci 2020; 23: 323–6

3. Rozin P: „Taste-smell confusions“ and the duality of the olfactory sense. Percept Psychophys 1982; 31: 397–401

4. Schäfer L, Schriever VA, Croy I: Human olfactory dysfunction: causes and consequences. Cell Tissue Res 2021; 383: 569–79

5. Hummel T, Whitcroft KL, Andrews P, et al.: Position paper on olfactory dysfunction. Rhinology 2017; Suppl. 25: 1–30

6. Fikentscher R, Rasinski C.: (Parosmias—definition and clinical picture) Parosmien—Begriffsbestimmung und klinisches Bild. Laryngol Rhinol Otol (Stuttg) 1986; 65: 663

7. Patel ZM, Holbrook EH, Turner JH, et al.: International consensus statement on allergy and rhinology. Olfaction. Int Forum Allergy Rhinol 2022;12: 327–680

8. Pellegrino R, Mainland JD, Kelly CE, Parker JK, Hummel T: Prevalence and correlates of parosmia and phantosmia among smell disorders. Chem Senses 2021; 46

9. Mainland JD, Barlow LA, Munger SD, et al.: Identifying treatments for taste and smell disorders: gaps and opportunities. Chem Senses 2020; 45: 493–502

10. Damm M, Schmitl L, Müller CA, Welge-Lüssen A, Hummel T: Diagnostik und Therapie von Riechstörungen. HNO 2019; 67: 274–81

11. Damm M, Hüttenbrink KB, Hummel T, et al.: AWMF Leitlinien Riech- und Schmeckstörungen. www.awmforg/uploads/tx_szleitlinien/017-050l_S2k_Riech-und-Schmeckst%C3%B6rungen_2017-03pdf (last accessed on 3 February 2023).

12. Doty RL, Kamath V: The influences of age on olfaction: a review. Front Psychol 2014; 5: 20

13. Berg D, Godau J, Seppi K, et al.: The PRIPS study: screening battery for subjects at risk for Parkinson‘s disease. Eur J Neurol 2013; 20: 102–8

14. Landis BN, Hummel T: New evidence for high occurrence of olfactory dysfunctions within the population. Am J Med 2006; 119: 91–2

15. Doty RL: Epidemiology of smell and taste dysfunction. Handb Clin Neurol 2019; 164: 3–13

16. Damm M, Pikart LK, Reimann H, et al.: Olfactory training is helpful in postinfectious olfactory loss—a randomized controlled multicenter study. Laryngoscope 2014; 124: 826–31

17. Liu DT, Sabha M, Damm M, et al.: Parosmia is associated with relevant olfactory recovery after olfactory training. Laryngoscope 2021; 131: 618–23

18. Ohla K, Veldhuizen MG, Green T, et al.: A follow-up on quantitative and qualitative olfactory dysfunction and other symptoms in patients recovering from COVID-19 smell loss. Rhinology 2022

19. Landis BN, Hummel T, Hugentobler M, Giger R, Lacroix JS: Ratings of overall olfactory function. Chem Senses 2003; 28: 691–4

20. Doty RL, Wylie C, Potter M, Beston R, Cope B, Majam K: Clinical validation of the olfactory detection threshold module of the Snap & Sniff® olfactory test system. Int Forum Allergy Rhinol 2019; 9: 986–92

21. Cain WS, Gent J, Catalanotto FA, Goodspeed RB: Clinical evaluation of olfaction. Am J Otolaryngol 1983; 4: 252–6

22. Doty RL, McKeown DA, Lee WW, Shaman P: A study of the test-retest reliability of ten olfactory tests. Chem Senses 1995; 20: 645–56

23. Oleszkiewicz A, Schriever VA, Croy I, Hähner A, Hummel T: Updated sniffin‘ sticks normative data based on an extended sample of 9139 subjects. Eur Arch Otorhinolaryngol 2019; 276: 719–28

24. Renner B, Mueller CA, Dreier J, Faulhaber S, Rascher W, Kobal G: The candy smell test: a new test for retronasal olfactory performance. Laryngoscope 2009; 119: 487–95

25. Seubert J, Freiherr J, Frasnelli J, Hummel T, Lundstrom JN: Orbitofrontal cortex and olfactory bulb volume predict distinct aspects of olfactory performance in healthy subjects. Cereb Cortex 2013; 23: 2448–56

26. Frasnelli J, Hummel T: Olfactory dysfunction and daily life. Eur Arch Otorhinolaryngol 2005; 262: 231–5

27. Zou L, Haehner A, Menzel S, Gunder N, Hummel T: Reliability and validity of a brief version of the Questionnaire of Olfactory Disorders (brief QOD) in patients with olfactory dysfunction. Rhinology 2022; 60: 56–62

28. Liu DT, Besser G, Prem B, et al.: Self-perceived taste and flavor perception: associations with quality of life in patients with olfactory loss. Otolaryngol Head Neck Surg 2020; 194599820965242

29. Prajapati DP, Shahrvini B, Said M, Srinivas S, DeConde AS, Yan CH: Assessment of patient recognition of coronavirus disease 2019 (COVID-19)-associated olfactory loss and recovery: a longitudinal study. Int Forum Allergy Rhinol 2021; 11: 1529–37

30. Mullol J, Bachert C, Amin N, et al.: Olfactory outcomes with dupilumab in chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol Pract 2022; 10: 1086–95.e5

31. Konstantinidis I, Tsakiropoulou E, Constantinidis J: Long term effects of olfactory training in patients with post-infectious olfactory loss. Rhinology 2016; 54: 170–5

32. Hintschich CA, Dietz M, Haehner A, Hummel T: Topical administration of mometasone i not helpful in Post-COVID-19 olfactory dysfunction. Life 2022; 12: 1483

e1. Graziadei PP, Karlan MS, Graziadei GA, Bernstein JJ: Neurogenesis of sensory neurons in the primate olfactory system after section of the fila olfactoria. Brain Res 1980; 186: 289-300

e2. Brillat-Savarin JA: La Physiologie du Goût: „Die Physiologie des Geschmacks oder Transcendentalgastronomische Betrachtungen“, German 1865; Leipzig: Philipp Reclam jun. 1826.

e3. Frasnelli J, van Ruth S, Kriukova I, Hummel T: Intranasal concentrations of orally administered flavors. Chem Senses 2005; 30: 575–82

e4. Small DM: Flavor is in the brain. Physiol Behav 2012; 107: 540–52

e5. Nordin S, Blomqvist EH, Olsson P, Stjarne P, Ehnhage A: Effects of smell loss on daily life and adopted coping strategies in patients with nasal polyposis with asthma. Acta Otolaryngol 2011; 131: 826–32

e6. Croy I, Nordin S, Hummel T: Olfactory disorders and quality of life—an updated review. Chem Senses 2014; 39: 185–94

e7. Schäfer L, Mehler L, Hähner A, Walliczek U, Hummel T, Croy I: Sexual desire after olfactory loss: quantitative and qualitative reports of patients with smell disorders. Physiol Behav 2019; 201: 64–9

e8. Frasnelli J, Landis BN, Heilmann S, et al.: Clinical presentation of qualitative olfactory dysfunction. Eur Arch Otorhinolaryngol 2004; 261: 411–5

e9. Nordin S, Brämerson A, Millqvist E, Bende M: Prevalence of parosmia: the Skövde population-based studies. Rhinology 2007; 45: 50–3

e10. Fikentscher R, Fikentscher R, Roseburg B: Systematik und Terminologie der Riech- und Schmeckstörungen. Medizinische Olfaktologie und Gustologie. Halle: KTB, MLU Halle-Wittenberg, Wiss. Beiträge 1988: 100.

e11. Karstensen HG, Tommerup N: Isolated and syndromic forms of congenital anosmia. Clin Genet 2012; 81: 210–5.

e12. Marchi M, Provitera V, Nolano M, et al.: A novel SCN9A splicing mutation in a compound heterozygous girl with congenital insensitivity to pain, hyposmia and hypogeusia. J Peripher Nerv Syst 2018; 23: 202–6.

e13. Mansouri M, Chafai Elalaoui S, Ouled Amar Bencheikh B, et al.: A novel nonsense mutation in SCN9A in a Moroccan child with congenital insensitivity to pain. Pediatr Neurol 2014; 51: 741–4.

e14. Keydar I, Ben-Asher E, Feldmesser E, et al.: General olfactory sensitivity database (GOSdb): candidate genes and their genomic variations. Hum Mutat 2013; 34: 32–41.

e15. Alkelai A, Olender T, Dode C, et al.: Next-generation sequencing of patients with congenital anosmia. Eur J Hum Genet 2017; 25: 1377–87.

e16. Schriever VA, Hummel T: Etiologies of olfactory dysfunction in a pediatric population: based on a retrospective analysis of data from an outpatient clinic. Eur Arch Otorhinolaryngol 2020; 277: 3213–6.

e17. Abolmaali ND, Hietschold V, Vogl TJ, Huttenbrink KB, Hummel T: MR evaluation in patients with isolated anosmia since birth or early childhood. AJNR Am J Neuroradiol 2002; 23: 157–64.

e18. Haehner A, Boesveldt S, Berendse HW, et al.: Prevalence of smell loss in Parkinson‘s disease—a multicenter study. Parkinsonism Relat Disord 2009; 15: 490–4.

e19. Haehner A, Masala C, Walter S, Reichmann H, Hummel T: Incidence of Parkinson‘s disease in a large patient cohort with idiopathic smell and taste loss. J Neurol 2019; 266: 339–45.

e20. Stiasny-Kolster K, Doerr Y, Moller JC, et al.: Combination of ‚idiopathic‘ REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. Brain 2005; 128 (Pt 1): 126–37.

e21. Nordin S, Paulsen JS, Murphy C: Sensory- and memory-mediated olfactory dysfunction in Huntington‘s disease. J Int Neuropsychol Soc 1995; 1: 281–90.

e22. Moscovich M, Munhoz RP, Teive HA, et al.: Olfactory impairment in familial ataxias. J Neurol Neurosurg Psychiatry 2012; 83: 970–4.

e23. Viguera C, Wang J, Mosmiller E, Cerezo A, Maragakis NJ: Olfactory dysfunction in amyotrophic lateral sclerosis. Ann Clin Transl Neurol 2018; 5: 976–81.

e24. Driver-Dunckley E, Adler CH, Hentz JG, et al.: Olfactory dysfunction in incidental Lewy body disease and Parkinson‘s disease. Parkinsonism Relat Disord 2014; 20: 1260–2.

e25. Pardini M, Huey ED, Cavanagh AL, Grafman J: Olfactory function in corticobasal syndrome and frontotemporal dementia. Arch Neurol 2009; 66: 92–6.

e26. Conti MZ, Vicini-Chilovi B, Riva M, et al.: Odor identification deficit predicts clinical conversion from mild cognitive impairment to dementia due to Alzheimer‘s disease. Arch Clin Neuropsychol 2013; 28: 391–9.

e27. Lucassen EB, Turel A, Knehans A, Huang X, Eslinger P: Olfactory dysfunction in Multiple Sclerosis: a scoping review of the literature. Mult Scler Relat Disord 2016; 6: 1–9.

e28. Negoias S, Croy I, Gerber J, et al.: Reduced olfactory bulb volume and olfactory sensitivity in patients with acute major depression. Neuroscience 2010; 169: 415–21.

e29. Moberg PJ, Kamath V, Marchetto DM, et al.: Meta-analysis of olfactory function in schizophrenia, first-degree family members, and youths at-risk for psychosis. Schizophr Bull 2014; 40: 50–9.

e30. Gudziol H, Forster G: Zur Durchführung präoperativer Riechtests aus medicolegaler Sicht. Laryngorhinootologie 2002; 81: 586–90.

e31. „Bhattacharyya N, Kepnes LJ: Contemporary assessment of the prevalence of smell and taste problems in adults. Laryngoscope 2015; 125: 1102–6.“

e32. Vennemann MM, Hummel T, Berger K: The association between smoking and smell and taste impairment in the general population. J Neurol 2008; 255: 1121–6.

e33. Brämerson A, Johansson L, Ek L, Nordin S, Bende M: Prevalence of olfactory dysfunction: the Skövde population-based study. Laryngoscope 2004; 114: 733–7.

e34. Reden J, Maroldt H, Fritz A, Zahnert T, Hummel T: A study on the prognostic significance of qualitative olfactory dysfunction. Eur Arch Otorhinolaryngol 2007; 264: 139–44.

e35. Lötsch J, Hummel T: Clinical usefulness of self-rated olfactory performance—a data science-based assessment of 6000 patients. Chem Senses 2019; 44: 357–64.

e36. Croy I, Lange K, Krone F, Negoias S, Seo HS, Hummel T: Comparison between odor thresholds for phenyl ethyl alcohol and butanol. Chem Senses 2009; 34: 523–7.

e37. Khan M, Yoo SJ, Clijsters M, et al. Visualizing in deceased COVID-19 patients how SARS-CoV-2 attacks the respiratory and olfactory mucosae but spares the olfactory bulb. Cell 2021;184: 5932–49.e15.

e38. Doty RL: Measurement of chemosensory function. World J Otorhinolaryngol Head Neck Surg 2018; 4: 11–28.

e39. Mueller CA, Grassinger E, Naka A, Temmel AF, Hummel T, Kobal G: A self-administered odor identification test procedure using the „Sniffin‘ Sticks“. Chem Senses 2006; 31: 595–8.

e40. Tan BKJ, Han R, Zhao JJ, Tan NKW, et al.: Prognosis and persistence of smell and taste dysfunction in patients with covid-19: meta-analysis with parametric cure modelling of recovery curves. BMJ 2022; 378: e069503.

e41. Mangal V, Murari T, Vashisht R, Iqbal SM, Meghana K, Gujrathi S, et al. Olfactory Dysfunction Among Asymptomatic Patients with SARS CoV2 Infection: A Case-Control Study. Indian J Otolaryngol Head Neck Surg 2021; 73: 1–6.

e42. Whitcroft KL, Cuevas M, Andrews P, Hummel T: Monitoring olfactory function in chronic rhinosinusitis and the effect of disease duration on outcome. Int Forum Allergy Rhinol 2018; 218: 769–76.

e43. Heilmann S, Strehle G, Rosenheim K, Damm M, Hummel T: Clinical assessment of retronasal olfactory function. Arch Otolaryngol Head Neck Surg 2002; 128: 414–8.

e44. Özay H, Çakır A, Ecevit MC: Retronasal olfaction test methods: a systematic review. Balkan Med J 2019; 36: 49–59.

e45. Han P, Su T, Qin M, Chen H, Hummel T: A systematic review of olfactory related questionnaires and scales. Rhinology 2020; 59: 133–43.

e46. Liu DT, Welge-Lüssen A, Besser G, Mueller CA, Renner B: Assessment of odor hedonic perception: the sniffin‘ sticks parosmia test (SSParoT). Sci Rep 2020; 10: 18019.

e47. Stuck BA, Beule A, Damm M, et al.: [Position paper „Chemosensory testing for expert opinion in smell disorders“]. Laryngorhinootologie 2014; 93: 327–9.

e48. Macel D, Huart C, Duprez T, Hummel T, Rombaux P: Prognostic value of olfactory bulb volume measurement for recovery in post-infectious and post-traumic olfactory loss. B-ENT 2012; 8, Suppl. 18: 31.

e49. Rudmik L, Smith KA, Soler ZM, Schlosser RJ, Smith TL: Routine magnetic resonance imaging for idiopathic olfactory loss: a modeling-based economic evaluation. JAMA Otolaryngol Head Neck Surg 2014; 140: 911–7.

e50. Hura N, Yi JS, Lin SY, Roxbury CR: Magnetic resonance imaging as a diagnostic and research tool in patients with olfactory dysfunction: a systematic review. Am J Rhinol Allergy 2022: 36: 668–83.

e51. Han P, Zang Y, Akshita J, Hummel T: Magnetic resonance imaging of human olfactory dysfunction. Brain Topogr 2019; 32: 987–97.

e52. Zou LQ, Hummel T, Otte MS, et al.: Association between olfactory function and quality of life in patients with olfactory disorders: a multicenter study in over 760 participants. Rhinology 2021; 59: 164–72.

e53. Oleszkiewicz A, Park D, Resler K, et al.: Quality of life in patients with olfactory loss is better predicted by flavor identification than by orthonasal olfactory function. Chem Senses 2019; 44: 371–7.

e54. Croy I, Buschhuter D, Seo HS, Negoias S, Hummel T: Individual significance of olfaction: development of a questionnaire. Eur Arch Otorhinolaryngol 2010; 267: 67–71.

e55. Davidson TM, Murphy C, Jalowayski AA: Smell impairment. Can it be reversed? Postgrad Med 1995; 98: 107–9, 12–8.

e56. Loftus PA, Roland LT, Gurrola JG 2nd, Cheung SW, Chang JL: Temporal profile of olfactory dysfunction in COVID-19. OTO Open 2020; 4: 2473974x20978133.

e57. London B, Nabet B, Fisher AR, White B, Sammel MD, Doty RL: Predictors of prognosis in patients with olfactory disturbance. Ann Neurol 2008; 63: 159–66.

e58. Hummel T, Lötsch J: Prognostic factors of olfactory dysfunction. Arch Otolaryngol Head Neck Surg 2010; 136: 347–51.

e59. Reden J, Mueller A, Mueller C, et al.: Recovery of olfactory function following closed head injury or infections of the upper respiratory tract. Arch Otolaryngol Head Neck Surg 2006; 132: 265–9.

e60. Fokkens WJ, Lund VJ, Hopkins C, et al.: European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology 2020; 58 (Suppl S29): 1–464.

e61. Doty RL: Treatments for smell and taste disorders: a critical review. Handb Clin Neurol 2019; 164: 455–79.

e62. Stuck BA, Popert U, Beule A, et al.: Rhinosinusitis. AWMF Leitlinien 2017. www.awmf.org/leitlinien/detail/ll/017–49.html (last accessed on.6 February 2023).

e63. Damm M: Sinunasale Dysosmien. In: Hummel T, Welge-Luessen A (eds.): Riech- und Schmeckstörungen. Stuttgart: Thieme 2009; 61–76.

e64. Banglawala SM, Oyer SL, Lohia S, Psaltis AJ, Soler ZM, Schlosser RJ: Olfactory outcomes in chronic rhinosinusitis with nasal polyposis after medical treatments: a systematic review and meta-analysis. Int Forum Allergy Rhinol 2014; 4: 986–94

e65. Shu CH, Lee PL, Shiao AS, Chen KT, Lan MY: Topical corticosteroid applied with a squirt system being more effective than with nasal spray for steroid-dependent olfactory impairment. Laryngoscope 2012; 122: 747–50.

e66. Scheibe M, Bethge C, Witt M, Hummel T: Intranasal administration of drugs. Arch Otolaryngol Head Neck Surg 2008; 134: 643–6.

e67. Kubba H, Spinou E, Robertson A: The effect of head position on the distribution of drops within the nose. Am J Rhinol 2000; 14: 83–6.

e68. Mori E, Merkonidis C, Cuevas M, Gudziol V, Matsuwaki Y, Hummel T: The administration of nasal drops in the „Kaiteki“ position allows for delivery of the drug to the olfactory cleft: a pilot study in healthy subjects. Eur Arch Otorhinolaryngol 2016; 273: 939–43.

e69. Whitcroft KL, Hummel T: Clinical diagnosis and current management strategies for olfactory dysfunction: a review. JAMA Otolaryngol Head Neck Surg 2019; 145: 846–53..

e70. Sorokowska A, Drechsler E, Karwowski M, Hummel T: Effects of olfactory training: a meta-analysis. Rhinology 2017; 55: 17–26.

e71. Altundag A, Cayonu M, Kayabasoglu G, et al.: Modified olfactory training in patients with postinfectious olfactory loss. Laryngoscope 2015; 125: 1763–6.

e72. Damm M, Pikart LK, Reimann H, et al.: Olfactory training is helpful in postinfectious olfactory loss: a randomized, controlled, multicenter study. Laryngoscope 2014; 124: 826–31.

e73. Konstantinidis I, Tsakiropoulou E, Bekiaridou P, Kazantzidou C, Constantinidis J: Use of olfactory training in post-traumatic and postinfectious olfactory dysfunction. Laryngoscope 2013; 123: 85–90.

e74. Drews T, Hummel T: Treatment strategies for smell loss. Curr Otorhinolaryngol Rep 2016; 4: 122–9.

e75. Doty RL, Marcus A, Lee WW: Development of the 12-item Cross-Cultural Smell Identification Test (CC-SIT). Laryngoscope 1996; 106 (3 Pt 1): 353–6.

e76. Davidson TM, Freed C, Healy MP, Murphy C: Rapid clinical evaluation of anosmia in children: the Alcohol Sniff Test. Ann NY Acad Sci 1998; 855: 787–92.

e77. Hummel T, Konnerth CG, Rosenheim K, Kobal G: Screening of olfactory function with a four-minute odor identification test: reliability, normative data, and investigations in patients with olfactory loss. Ann Otol Rhinol Laryngol 2001; 110: 976–81.

e78. Jackman AH, Doty RL: Utility of a three-item smell identification test in detecting olfactory dysfunction. Laryngoscope 2005; 115: 2209–12.

e79. Mueller C, Renner B: A new procedure for the short screening of olfactory function using five items from the „Sniffin‘ Sticks“ identification test kit. Am J Rhinol 2006; 20: 113–16.

e80. Vodicka J, Pellant A, Chrobok V: Screening of olfactory function using odourized markers. Rhinology 2007; 45: 164–68.

e81. Toledano A, Ruiz C, Navas C, et al.: Development of a short olfactory test based on the Connecticut Test (CCCRC). Rhinology 2009; 47: 465–9.

e82. Hummel T, Pfetzing U, Lötsch J: A short olfactory test based on the identification of three odors. J Neurol 2010; 257: 1316–21.

e83. Mullol J, Alobid I, Marino-Sanchez F, et al.: Furthering the understanding of olfaction, prevalence of loss of smell and risk factors: a population-based survey (OLFACAT study). BMJ Open 2012; 2: e001256.

e84. Doty RL, Shaman P, Dann M: Development of the University of Pennsylvania smell identification test: a standardized microencapsulated test of olfactory function. Physiol Behav 1984; 32: 489–502.

e85. Toyota B, Kitamura T, Takagi SF: Olfactory disorders––olfactometry and therapy. Tokyo: Igaku-Shoin 1978.

e86. Takagi SF: Standardized olfactometries in Japan––a review over ten years. Chem Senses 1989; 14: 5–46.

e87. Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G: ‚Sniffin‘ sticks‘: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses 1997; 22: 39–52.

e88. Thomas-Danguin T, Rouby C, Sicard G, et al.: Development of the ETOC: a European test of olfactory capabilities. Rhinology 2003; 41: 142–51.

e89. Cardesin A, Alobid I, Benitez P, et al.: Barcelona Smell Test—24 (BAST-24): validation and smell characteristics in the healthy Spanish population. Rhinology 2006; 44: 83–9.

e90. Haehner A, Mayer AM, Landis BN, et al.: High test-retest reliability of the extended version of the „Sniffin‘ Sticks“ test. Chem Senses 2009; 34: 705–11.

e91. Croy I, Zehner C, Larsson M, Zucco GM, Hummel T: Test-retest reliability and validity of the Sniffin‘ TOM odor memory test. Chem Senses 2015; 40: 173– 9.

e92. Xu Z, Luo X, Xu L, et al.: Effect of short-course glucocorticoid application on patients with chronic rhinosinusitis with nasal polyps. World Allergy Organ J 2020; 13: 100131.

e93. Zeng M, Wang H, Wang H, et al.: Comparison of efficacy of fluticasone propionate versus clarithromycin for postoperative treatment of different phenotypic chronic rhinosinusitis: a randomized controlled trial. Rhinology 2019; 57: 101–9.

e94. Khan AR, Arif MA: Mometasone furoate intra nasal spray for the treatment of bilateral nasal polyposis. J Med Sci 2019; 27: 203–9.

e95. Zhou B, He G, Liang J, et al: Mometasone furoate nasal spray in the treatment of nasal polyposis in Chinese patients: a double-blind, randomized, placebo-controlled trial. Int Forum Allergy Rhinol 2016; 6: 88–94.

e96. Jankowski R, Klossek JM, Attali V, Coste A, Serrano E: Long-term study of fluticasone propionate aqueous nasal spray in acute and maintenance therapy of nasal polyposis. Allergy 2009; 64: 944–50.

e97. Ehnhage A, Olsson P, Kölbeck KG, et al.: Functional endoscopic sinus surgery improved asthma symptoms as well as PEFR and olfaction in patients with nasal polyposis. Allergy 2009; 64: 762–69.

e98. Small CB, Stryszak P, Danzig M, Damiano A: Onset of symptomatic effect of mometasone furoate nasal spray in the treatment of nasal polyposis. J Allergy Clin Immunol 2008; 121: 928–32.

e99. Papadakis CE, Chimona TS, Chaidas K, Ladias A, Zisoglou M, Proimos EK: Effect of oral steroids on olfactory function in chronic rhinosinusitis with nasal polyps. Eur Ann Otorhinolaryngol Head Neck Dis 2021; 138: 343–8.

e100. Ecevit MC, Erdag TK, Dogan E, Sutay S: Effect of steroids for nasal polyposis surgery: a placebo-controlled, randomized, double-blind study. Laryngoscope 2015; 125: 2041–5.

e101. Alobid I, Benítez P, Cardelús S, et al.: Oral plus nasal corticosteroids improve smell, nasal congestion, and inflammation in sino-nasal polyposis. Laryngoscope 2014; 124: 50–6.

e102. Kirtsreesakul V, Wongsritrang K, Ruttanaphol S: Does oral prednisolone increase the efficacy of subsequent nasal steroids in treating nasal polyposis? Am J Rhinol Allergy 2012; 26: 455–62.

e103. Vaidyanathan S, Barnes M, Williamson P, Hopkinson P, Donnan PT, Lipworth B: Treatment of chronic rhinosinusitis with nasal polyposis with oral steroids followed by topical steroids: a randomized trial. Ann Intern Med 2011; 154: 293–302.

e104. Van Zele T, Gevaert P, Holtappels G, et al.: Oral steroids and doxycycline: Two different approaches to treat nasal polyps. J Allergy Clin Immunol 2010; 125: 1069–76. e4.

e105. Benítez P, Alobid I, De Haro J, et al.: A short course of oral prednisone followed by intranasal budesonide is an effective treatment of severe nasal polyps. Laryngoscope 2006; 116: 770–5.

e106. Wright ED, Agrawal S: Impact of perioperative systemic steroids on surgical outcomes in patients with chronic rhinosinusitis with polyposis: evaluation with the novel Perioperative Sinus Endoscopy (POSE) scoring system. Laryngoscope 2007; 117 (11 pt 2 suppl 115): 1–28.

e107. Hissaria P, Smith W, Wormald PJ, et al.: Short course of systemic corticosteroids in sinonasal polyposis: a double-blind, randomized, placebo-controlled trial with evaluation of outcome measures. J Allergy Clin Immunol 2006; 118: 128–3.

e108. Pieniak M, Oleszkiewicz A, Avaro V, Calegari F, Hummel T: Olfactory training—thirteen years of research reviewed. Neurosci Biobehav Rev 2022; 141: 104853.

e109. Yaylacı A, Azak E, Önal A, Aktürk DR, Karadenizli A: Effects of classical olfactory training in patients with COVID-19-related persistent loss of smell. Eur Arch Otorhinolaryngol 2022; 29: 1–7.

e110. Lechner M, Liu J, Counsell N, et al.: The COVANOS trial—insight into post-COVID olfactory dysfunction and the role of smell training. Rhinology 2022 (Online ahead of print). .

e111. Choi BY, Jeong H, Noh H, Park JY, Cho JH, Kim JK: Effects of olfactory training in patients with postinfectious olfactory dysfunction. Clin Exp Otorhinolaryngol 2021; 14: 88–92.

e112. Qiao XF, Bai YH, Wang GP, Li X, Zheng W: Clinical effects of two combinations of olfactory agents on olfactory dysfunction after upper respiratory tract infection during olfactory training. Rev Assoc Med Bras (1992) 2020; 66: 18–24.

e113. Saatci O, Altundag A, Duz OA, Hummel T: Olfactory training ball improves adherence and olfactory outcomes in post-infectious olfactory dysfunction. Eur Arch Otorhinolaryngol 2020; 277; 2125–32.

e114. Kattar N, Do TM, Unis GD, Migneron MR, Thomas AJ, McCoul ED: Olfactory training for postviral olfactory dysfunction: systematic review and meta-analysis. Otolaryngol Head Neck Surg 2021; 164: 244–54.

e115. Pekala K, Chandra RK, Turner JH: Efficacy of olfactory training in patients with olfactory loss: a systematic review and meta-analysis. Int Forum Allergy Rhinol 2016; 6: 299–307.

e116. Jiang RS, Twu CW, Liang KL: The effect of olfactory training on odor identification in patients with traumatic anosmia. Int Forum Allergy Rhinol 2019; 9: 1244–51.

e117. Langdon C, Lehrer E, Berenguer J, et al.: Olfactory training in post-traumatic smell impairment: mild improvement in threshold performances: results from a randomized controlled trial. J Neurotrauma 2018; 35: 2641–52.

e118. Oleszkiewicz A, Hanf S, Whitcroft KL, Haehner A, Hummel T: Examination of olfactory training effectiveness in relation to its complexity and the cause of olfactory loss. Laryngoscope 2018; 128: 1518–22.

e119. Patel ZM, Wise SK, DelGaudio JM: Randomized controlled trial demonstrating cost-effective method of olfactory training in clinical practice: essential oils at uncontrolled concentration. Laryngoscope Investig Otolaryngol 2017; 2: 53–6.

e120. Poletti SC, Michel E, Hummel T: Olfactory training using heavy and light weight molecule odors. Perception 2017; 46: 343–51.

e121. Konstantinidis I, Tsakiropoulou E, Bekiaridou P, Kazantzidou C, Constantinidis J: Use of olfactory training in post-traumatic and postinfectious olfactory dysfunction. Laryngoscope 2013; 123: E85– 90.

e122. Gellrich J, Han P, Manesse C, Betz A, et al.: Brain volume changes in hyposmic patients before and after olfactory training. Laryngoscope 2018; 128: 1531–6.

e123. Hummel T, Stupka G, Haehner A, Poletti SC: Olfactory training changes electrophysiological responses at the level of the olfactory epithelium. Rhinology 2018; 56: 330–5.

e124. Haehner A, Tosch C, Wolz M: Olfactory training in patients with Parkinson’s disease. PLoS One 2013; 8: e61680.

e125. Hummel T, Rissom K, Reden J, Hahner A, Weidenbecher M, Huttenbrink KB: Effects of olfactory training in patients with olfactory loss. Laryngoscope 2009; 119: 496–9.