Olfactory disorders: Diagnosis, evaluation, and treatment

authors:

avatar Salah Moradi , avatar Seyyed-Kamran Kamrava ORCID , avatar Maryam Jalessi , avatar Fatemeh Yazdian , avatar Sara Simorgh ORCID , avatar Mohammad Farhadi ORCID , avatar Rafieh Alizadeh , *

Koomesh: Vol.24, issue 4; 421-433
published online: September 05, 2022
article type: Research Article
received: April 02, 2021
accepted: February 05, 2022

how to cite: Moradi S, Kamrava S , Jalessi M, Yazdian F, Simorgh S, et al. Olfactory disorders: Diagnosis, evaluation, and treatment. koomesh. 2022;24(4):e152751. 

Abstract

The sense of smell, one of the five basic senses that humans have, helps us detect different types of odors. It also plays an important role in the detection of pollutants, toxic gases, or rotten and hazardous foods. Although olfaction is considered less important than the other senses, smell disorders could cause a variety of problems, including reduced taste detection due to the relationship between taste and smell, depression, and overall loss of quality of life. Olfactory dysfunction is one of the first clinical signs of neurological diseases such as Alzheimer;#39s and Parkinson;#39s disease. The olfactory disorder has many etiologies, some of which are more obvious. Most people with olfactory disorders have experienced a recent illness or trauma. Common causes of olfactory disorders include aging, rhinosinusitis, upper respiratory infections, and cerebral lesion the rest of the cases are less relevant. Since there are limited evidence-based treatments for olfactory disorders, it is necessary to share information about the risks associated with these disorders. This information includes practical and useful screening measures for olfactory dysfunction, appropriate clinical evaluation, patient counseling to prevent injury, health and quality of life management, and the introduction of treatments with higher recovery rates. This review study focuses on the etiology, prevalence, and short-term and long-term consequences of olfactory disorders. Also, diagnostic strategies and new treatment options have been developed and discussed.

References

  • 1.

    Kishida T. Olfaction of aquatic amniotes. Cell Tissue Res 2021; 1-13.https://doi.org/10.1007/s00441-020-03382-8PMid:33409651.

  • 2.

    Sell C. The mechanism of olfaction. chemistry and the sense of smell; sell, CS, Ed; John Wiley & Sons, Inc: Hoboken, NJ, USA. 2014.https://doi.org/10.1002/9781118522981.

  • 3.

    Lyons-Warren AM, Herman I, Hunt PJ, Arenkiel B. A systematic-review of olfactory deficits in neurodevelopmental disorders: from mouse to human. Neurosci Biobehav Rev 2021; 125: 110-121.https://doi.org/10.1016/j.neubiorev.2021.02.024PMid:33610612 PMCid:PMC8142839.

  • 4.

    lek A, Balc MK. Phantosmia with COVID-19 related olfactory dysfunction: report of nine case. Indian J Otolaryngol Head Neck Surg 2021; 1-3.https://doi.org/10.1007/s12070-021-02505-zPMid:33728275 PMCid:PMC7953190.

  • 5.

    Abolmaali ND, Hietschold V, Vogl TJ, Httenbrink KB, Hummel T. MR evaluation in patients with isolated anosmia since birth or early childhood. Am J Neuroradiol 2002; 23: 157-164.

  • 6.

    Pellegrino R, Mainland JD, Kelly CE, Parker JK, Hummel T. Prevalence and correlates of parosmia and phantosmia among smell disorders. Chem Senses 2021; 46.https://doi.org/10.1093/chemse/bjab046PMid:34698820.

  • 7.

    Whitcroft K, Gunder N, Cuevas M, Andrews P, Menzel S, Haehner A, et al. Intranasal sodium citrate in quantitative and qualitative olfactory dysfunction: results from a prospective, controlled trial of prolonged use in 60 patients. Eur Arch Otorhinolaryngol 2021; 278: 2891-2897.https://doi.org/10.1007/s00405-020-06567-7PMid:33471169 PMCid:PMC8266781.

  • 8.

    Leopold D. Distortion of olfactory perception: diagnosis and treatment. Chem Senses 2002; 27: 611-615.https://doi.org/10.1093/chemse/27.7.611PMid:12200340.

  • 9.

    Vennemann MM, Hummel T, Berger K. The association between smoking and smell and taste impairment in the general population. J Neurology 2008; 255: 1121-1126.https://doi.org/10.1007/s00415-008-0807-9PMid:18677645.

  • 10.

    Brmerson A, Johansson L, Ek L, Nordin S, Bende M. Prevalence of olfactory dysfunction: the Skvde populationbased study. Laryngoscope 2004; 114: 733-737.https://doi.org/10.1097/00005537-200404000-00026PMid:15064632.

  • 11.

    Murphy C, Schubert CR, Cruickshanks KJ, Klein BE, Klein R, Nondahl DM. Prevalence of olfactory impairment in older adults. Jama 2002; 288: 2307-2312.https://doi.org/10.1001/jama.288.18.2307PMid:12425708.

  • 12.

    Croy I, Nordin S, Hummel T. Olfactory disorders and quality of life-an updated review. Chem Senses 2014; 39: 185-194.https://doi.org/10.1093/chemse/bjt072PMid:24429163.

  • 13.

    Croy I, Negoias S, Novakova L, Landis BN, Hummel T. Learning about the functions of the olfactory system from people without a sense of smell. PloS One 2012; 7: e33365.https://doi.org/10.1371/journal.pone.0033365PMid:22457756 PMCid:PMC3310072.

  • 14.

    Bojanowski V, Hummel T, Croy I. Isolated congenital anosmia--clinical and daily life aspects of a life without a sense of smell. Laryngorhinootologie 2013; 92: 30-33.##.

  • 15.

    Landis BN, Konnerth CG, Hummel T. A study on the frequency of olfactory dysfunction. Laryngoscope 2004; 114: 1764-1769.https://doi.org/10.1097/00005537-200410000-00017PMid:15454769.

  • 16.

    Nordin S, Brmerson A, Millqvist E, Bende M. Prevalence of parosmia: the Skvde population-based studies. Rhinology 2007; 45: 50-53.

  • 17.

    Zou L, Hummel T, Otte M, Bitter T, Besser G, Mueller C, 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: 164-172.https://doi.org/10.4193/Rhin20.403PMid:33395453.

  • 18.

    Oleszkiewicz A, Park D, Resler K, Draf J, Schulze A, Zang Y, 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: 371-377.https://doi.org/10.1093/chemse/bjz027PMid:31046120.

  • 19.

    Boesveldt S, Parma V. The importance of the olfactory system in human well-being, through nutrition and social behavior. Cell Tissue Res 2021; 1-9.https://doi.org/10.1007/s00441-020-03367-7PMid:33433688 PMCid:PMC7802608.

  • 20.

    Arsalani N, Nobahar M, Ghorbani R, Kia NS, Etemadi M. Nutrition status and its relationship with depression in elderly pepople. Koomesh 2017; 401-411. (Persian).

  • 21.

    Miwa T, Furukawa M, Tsukatani T, Costanzo RM, DiNardo LJ, Reiter ER. Impact of olfactory impairment on quality of life and disability. Arch Otolaryngol Head Neck Surg 2001; 127: 497-503.https://doi.org/10.1001/archotol.127.5.497PMid:11346423.

  • 22.

    Haxel B, Nisius A, Fruth K, Mann W, Muttray A. Deficits in medical counseling in olfactory dysfunction. HNO 2012; 60: 432-438.https://doi.org/10.1007/s00106-011-2448-zPMid:22271138.

  • 23.

    Blomqvist EH, Brmerson A, Stjrne P, Nordin S. Consequences of olfactory loss and adopted coping strategies. Rhinology 2004; 42: 189-194.

  • 24.

    Nordin S, Hedn Blomqvist E, Olsson P, Stjrne P, Ehnhage A, Group NS. Effects of smell loss on daily life and adopted coping strategies in patients with nasal polyposis with asthma. Acta Otolaryngol 2011; 131: 826-832.https://doi.org/10.3109/00016489.2010.539625PMid:21595508.

  • 25.

    Siegel JK, Kung SY, Wroblewski KE, Kern DW, McClintock MK, Pinto JM. Olfaction is associated with sexual motivation and satisfaction in older men and women. J Sexual Med 2021; 18: 295-302.https://doi.org/10.1016/j.jsxm.2020.12.002PMid:33423973 PMCid:PMC8694566.

  • 26.

    Temmel AF, Quint C, Schickinger-Fischer B, Klimek L, Stoller E, Hummel T. Characteristics of olfactory disorders in relation to major causes of olfactory loss. Arch Otolaryngol Head Neck Surg 2002; 128: 635-641.https://doi.org/10.1001/archotol.128.6.635PMid:12049556.

  • 27.

    Chen B, Benzien C, Faria V, Ning Y, Cuevas M, Linke J, et al. Symptoms of Depression in Patients with Chemosensory Disorders. ORL 2021; 83: 135-143.https://doi.org/10.1159/000513751PMid:33756467.

  • 28.

    Getchell TV, Bartoshuk L, Doty RL, Snow JB. Smell and taste in health and disease: Raven Press 1991.

  • 29.

    Ferris AM, Duffy VB. Effect of olfactory deficits on nutritional status: does age predict persons at risk? Ann N Y Acad Sci 1989; 561: 113-123.https://doi.org/10.1111/j.1749-6632.1989.tb20975.xPMid:2735670.

  • 30.

    Brmerson A, Nordin S, Bende M. Clinical experience with patients with olfactory complaints, and their quality of life. Acta OtoLaryngol 2007; 127: 74-167.https://doi.org/10.1080/00016480600801357PMid:17364348.

  • 31.

    Aschenbrenner K, Hummel C, Teszmer K, Krone F, Ishimaru T, Seo HS, et al. The influence of olfactory loss on dietary behaviors. Laryngoscope 2008; 118: 135-144.https://doi.org/10.1097/MLG.0b013e318155a4b9PMid:17975508.

  • 32.

    Jafek BW, Murrow B, Michaels R, Restrepo D, Linschoten M. Biopsies of human olfactory epithelium. Chem Senses 2002; 27: 623-628.https://doi.org/10.1093/chemse/27.7.623PMid:12200342.

  • 33.

    Eccles R. Understanding the symptoms of the common cold and influenza. Lancet Infect Dis 2005; 5: 718-725.https://doi.org/10.1016/S1473-3099(05)70270-X.

  • 34.

    Van Kempen M, Bachert C, Van Cauwenberge P. An update on the pathophysiology of rhinovirus upper respiratory tract infections. Rhinology 1999; 37: 97-103.

  • 35.

    Yamagishi M, Fujiwara M, Nakamura H. Olfactory mucosal findings and clinical course in patients with olfactory disorders following upper respiratory viral infection. Rhinology 1994; 32: 113-118.

  • 36.

    Moran DT, Jafek BW, Eller PM, Rowley III JC. Ultrastructural histopathology of human olfactory dysfunction. Microsc Res Tech 1992; 23: 103-110.https://doi.org/10.1002/jemt.1070230202PMid:1421550.

  • 37.

    Jafek B, Gordon A, Moran D, Eller P. Congenital anosmia. Ear Nose Throat J 1990; 69: 331-337.

  • 38.

    Mueller A, Rodewald A, Reden J, Gerber J, von Kummer R, Hummel T. Reduced olfactory bulb volume in post-traumatic and post-infectious olfactory dysfunction. Neuroreport 2005; 16: 475-478.https://doi.org/10.1097/00001756-200504040-00011PMid:15770154.

  • 39.

    Welge-Lssen A, Wolfensberger M. Olfactory disorders following upper respiratory tract infections. Taste Smell 2006; 63: 125-132.https://doi.org/10.1159/000093758PMid:16733337.

  • 40.

    Wang LS, Wang YR, Ye DW, Liu QQ. A review of the 2019 Novel Coronavirus (COVID-19) based on current evidence. Int J Antimicrob Agents 2020; 105948.https://doi.org/10.1016/j.ijantimicag.2020.105948PMid:32201353 PMCid:PMC7156162##.

  • 41.

    Mirmohammadkhani M, Paknazar F, Rashidy-Pour A. Evaluation of the epidemiological pattern of COVID-19 applying basic reproduction number: an educational review article. Koomesh 2020; 22. (Persian).https://doi.org/10.29252/koomesh.22.3.373.

  • 42.

    Jaberi A. Psychological issues in children and youth during COVID-19 outbreak: A letter to Editor. Koomesh 2021; 23: 317-319. (Persian).https://doi.org/10.52547/koomesh.23.3.317.

  • 43.

    Bagheri SH, Asghari A, Farhadi M, Shamshiri AR, Kabir A, Kamrava SK, et al. Coincidence of COVID-19 epidemic and olfactory dysfunction outbreak in Iran. Med J Islamic Republic Iran 2020; 34: 62. (Persian).https://doi.org/10.47176/mjiri.34.62.

  • 44.

    Bagheri S, Asghari A, Farhadi M, Shamshiri AR, Kabir A, Kamrava S, et al. Coincidence of COVID-19 epidemic and olfactory dysfunction outbreak in Iran. Med J Islam Repub Iran 2020; 34: 62.https://doi.org/10.47176/mjiri.34.62PMid:32974228 PMCid:PMC7500422.

  • 45.

    Parma V, Ohla K, Veldhuizen MG, Niv MY, Kelly CE, Bakke AJ, et al. More than smell-COVID-19 is associated with severe impairment of smell, taste, and chemesthesis. Chem Senses 2020; 45: 609-622.https://doi.org/10.1093/chemse/bjaa041PMid:32564071 PMCid:PMC7337664.

  • 46.

    Palmer K, Monaco A, Kivipelto M, Onder G, Maggi S, Michel J-P, et al. The potential long-term impact of the COVID-19 outbreak on patients with non-communicable diseases in Europe: consequences for healthy ageing. Aging clinical and experimental research. 2020;32(7):1189-94.https://doi.org/10.1007/s40520-020-01601-4PMid:32458356 PMCid:PMC7248450##.

  • 47.

    Jiao L, Yang Y, Yu W, Zhao Y, Long H, Gao J, et al. The olfactory route is a potential way for SARS-CoV-2 to invade the central nervous system of rhesus monkeys. Signal Transduct Target Ther 2021; 6: 1-11.https://doi.org/10.1038/s41392-021-00591-7PMid:33895780 PMCid:PMC8065334.

  • 48.

    Jalessi M, Barati M, Rohani M, Amini E, Ourang A, Azad Z, et al. Frequency and outcome of olfactory impairment and sinonasal involvement in hospitalized patients with COVID-19. Neurol Sci 2020; 41: 2331-2338.https://doi.org/10.1007/s10072-020-04590-4PMid:32656713 PMCid:PMC7354355.

  • 49.

    Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L, et al. Self-reported olfactory and taste disorders in patients with severe acute respiratory coronavirus 2 infection: a cross-sectional study. Clin Infect Dis 2020; 71: 889-890.https://doi.org/10.1093/cid/ciaa330PMid:32215618 PMCid:PMC7184514.

  • 50.

    Vaira LA, Salzano G, Deiana G, De Riu G. Anosmia and ageusia: common findings in COVID19 patients. Laryngoscope 2020.https://doi.org/10.1002/lary.28753.

  • 51.

    Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol 2020; 277: 2251-2261.https://doi.org/10.1007/s00405-020-05965-1PMid:32253535 PMCid:PMC7134551.

  • 52.

    Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020; 77: 683-690.https://doi.org/10.1001/jamaneurol.2020.1127PMid:32275288 PMCid:PMC7149362.

  • 53.

    Yan CH, Faraji F, Prajapati DP, Boone CE, DeConde AS. Association of chemosensory dysfunction and Covid19 in patients presenting with influenzalike symptoms. Int Forum Allergy Rhinol 2020; 10: 806-813.https://doi.org/10.1002/alr.22579PMid:32279441 PMCid:PMC7262089.

  • 54.

    Bnzit F, Le Turnier P, Declerck C, Paill C, Revest M, Dube V, et al. Utility of hyposmia and hypogeusia for the diagnosis of COVID-19. Lancet Infect Dis 2020; 20: 1014-1015.https://doi.org/10.1016/S1473-3099(20)30297-8.

  • 55.

    Klopfenstein T, Kadiane-Oussou N, Toko L, Royer PY, Lepiller Q, Gendrin V, et al. Features of anosmia in COVID-19. Med Mal Infect 2020; 50: 436-439.https://doi.org/10.1016/j.medmal.2020.04.006PMid:32305563 PMCid:PMC7162775.

  • 56.

    Moein ST, Hashemian SM, Mansourafshar B, KhorramTousi A, Tabarsi P, Doty RL. Smell dysfunction: a biomarker for COVID19. Int Forum Allergy Rhinol 2020; 10: 944-950.https://doi.org/10.1002/alr.22587PMid:32301284 PMCid:PMC7262123.

  • 57.

    Kaye R, Chang CD, Kazahaya K, Brereton J, Denneny III JC. COVID-19 anosmia reporting tool: initial findings. Otolaryngol Head Neck Surg 2020; 163: 132-134.https://doi.org/10.1177/0194599820922992PMid:32340555.

  • 58.

    BeltrnCorbellini , ChicoGarca JL, MartnezPoles J, RodrguezJorge F, NateraVillalba E, GmezCorral J, et al. Acuteonset smell and taste disorders in the context of COVID19: a pilot multicentre polymerase chain reaction based case-control study. Eur J Neurol 2020; 27: 1738-1741.https://doi.org/10.1111/ene.14273https://doi.org/10.1111/ene.14359.

  • 59.

    Costanzo RM, DiNardo LJ, Reiter ER. Head injury and olfaction. InHandbook of olfaction and gustation 2003 Mar 27 (pp. 1108-1123). CRC Press.https://doi.org/10.1201/9780203911457-35.

  • 60.

    Kobayashi M, Costanzo RM. Olfactory nerve recovery following mild and severe injury and the efficacy of dexamethasone treatment. Chem Senses 2009; 34: 573-580.https://doi.org/10.1093/chemse/bjp038PMid:19578153 PMCid:PMC2728832.

  • 61.

    Doty RL, Yousem DM, Pham LT, Kreshak AA, Geckle R, Lee WW. Olfactory dysfunction in patients with head trauma. Arch Neurol 1997; 54: 1131-1140.https://doi.org/10.1001/archneur.1997.00550210061014PMid:9311357.

  • 62.

    IKEDA K, SAKURADA T, TAKASAKA T, OKITSU T, YOSHIDA S. Anosmia following head trauma: preliminary study of steroid treatment. The Tohoku Journal of Experimental Medicine. 1995;177(4):343-51.https://doi.org/10.1620/tjem.177.343PMid:8928194.

  • 63.

    Limphaibool N, Iwanowski P, Kozubski W, Swidziski T, Frankowska A, Kamiska I, et al. Subjective and objective assessments of post-traumatic olfactory dysfunction. Front Neurol 2020; 11: 970.https://doi.org/10.3389/fneur.2020.00970PMid:32982956 PMCid:PMC7479332.

  • 64.

    Doty RL, Bromley SM. Effects of drugs on olfaction and taste. Otolaryngol Clin North Am 2004; 37: 1229-1254.https://doi.org/10.1016/j.otc.2004.05.002PMid:15563912.

  • 65.

    Henkin R. Drug effects on smell and taste. Pharmacology in Medicine: Principles and Practice, eds Pradham SN, Maickel RP, Dutta SN Bethesda: SP Press Int. 1986; 748-753.

  • 66.

    Ackerman BH, Kasbekar N. Disturbances of taste and smell induced by drugs. Pharmacotherapy: Pharmacotherapy 1997; 17: 482-496.https://doi.org/10.1002/j.1875-9114.1997.tb03058.x.

  • 67.

    Upadhyay UD, Holbrook EH. Olfactory loss as a result of toxic exposure. Otolaryngol Clin North Am 2004; 37: 1185-1207.https://doi.org/10.1016/j.otc.2004.05.003PMid:15563910.

  • 68.

    Nakamura H, Nonomura N, Fujiwara M, Nakano Y. Olfactory disturbances caused by the anti-cancer drug tegafur. Eur Arch Otorhinolaryngol 1995; 252: 48-52.https://doi.org/10.1007/BF00171440PMid:7718227.

  • 69.

    Lim JH, Davis GE, Wang Z, Li V, Wu Y, Rue TC, et al. Zicam-induced damage to mouse and human nasal tissue. PLoS One 2009; 4: e7647.https://doi.org/10.1371/journal.pone.0007647PMid:19876403 PMCid:PMC2765727.

  • 70.

    Ltsch J, Daiker H, Hhner A, Ultsch A, Hummel T. Drug-target based cross-sectional analysis of olfactory drug effects. Eur J Clin Pharmacol 2015; 71: 461-471.https://doi.org/10.1007/s00228-015-1814-2PMid:25666029.

  • 71.

    Murphy C, Doty R, Duncan H. Clinical disorders of olfaction. Neurol Dis Ther 2003; 57: 461-478.

  • 72.

    Ottaviano G, Cantone E, D'Errico A, Salvalaggio A, Citton V, Scarpa B, et al. Sniffin'Sticks and olfactory system imaging in patients with Kallmann syndrome. Int Forum Allergy Rhinol 2015; 5: 855-861.https://doi.org/10.1002/alr.21550PMid:25951300.

  • 73.

    Murphy C, Cruickshanks KK, Klein R, Nondahl DM. Prevalence of olfactory impairment. J Am Med Assoc 2002; 288: 2307-2312.https://doi.org/10.1001/jama.288.18.2307PMid:12425708.

  • 74.

    Attems J, Walker L, Jellinger KA. Olfaction and aging: a mini-review. Gerontology 2015; 61: 485-490.https://doi.org/10.1159/000381619PMid:25968962.

  • 75.

    Loo AT, Youngentob SL, Kent PF, Schwob JE. The aging olfactory epithelium: Neurogenesis, response to damage, and odorantinduced activity. Int J Dev Neurosci 1996; 14: 881-900.https://doi.org/10.1016/S0736-5748(96)00046-9.

  • 76.

    Schubert CR, Cruickshanks KJ, Fischer ME, Huang G-H, Klein BEK, Klein R, et al. Olfactory impairment in an adult population: the beaver dam offspring study. Chem Senses 2011; 37: 325-334.https://doi.org/10.1093/chemse/bjr102PMid:22045704 PMCid:PMC3325763.

  • 77.

    Saltagi AK, Saltagi MZ, Nag AK, Wu AW, Higgins TS, Knisely A, et al. Diagnosis of anosmia and hyposmia: a systematic review. Allergy Rhinol (Providence) 2021; 12: 21526567211026568.https://doi.org/10.1177/21526567211026568PMid:34285823 PMCid:PMC8264728.

  • 78.

    Bayram A, Cingi C, Rombaux P. Recent advances in olfactory dysfunction treatment and rehabilitation. Chall Rhinol 2021; 387-396.https://doi.org/10.1007/978-3-030-50899-9_38.

  • 79.

    Schfer L, Schriever VA, Croy I. Human olfactory dysfunction: causes and consequences. Cell Tissue Res 2021; 1-11.https://doi.org/10.1007/s00441-020-03381-9PMid:33496882 PMCid:PMC7835667.

  • 80.

    Liu YH, Huang Z, Vaidya A, Li J, Curhan GC, Wu S, et al. A longitudinal study of altered taste and smell perception and change in blood pressure. Nutr Metab Cardiovasc Dis 2018; 28: 877-883.https://doi.org/10.1016/j.numecd.2018.05.002PMid:29858155 PMCid:PMC6428580.

  • 81.

    Blioskas S. Anosmia: Sensorineural. InRhinology and Anterior Skull Base Surgery 2021 (pp. 271-274). Springer, Cham.https://doi.org/10.1007/978-3-030-66865-5_57.

  • 82.

    Kayser J, Tenke CE, Kroppmann CJ, Alschuler DM, Ben-David S, Fekri S, et al. Olfaction in the psychosis prodrome: electrophysiological and behavioral measures of odor detection. Int J Psychophysiol 2013; 90: 190-206.https://doi.org/10.1016/j.ijpsycho.2013.07.003PMid:23856353 PMCid:PMC3962291.

  • 83.

    De Luca C, Cafalli M, Della Vecchia A, Gori S, Tessitore A, Silvestro M, et al. Olfaction in migraine and its psychiatric comorbidities: a narrative review.

  • 84.

    Hlscher T, Seibt A, Appold S, Drr W, Herrmann T, Httenbrink KB, Hummel T. Effects of radiotherapy on olfactory function. Radiother Oncol 2005; 77: 157-163.https://doi.org/10.1016/j.radonc.2005.09.015PMid:16226328.

  • 85.

    Maurage P, Callot C, Philippot P, Rombaux P, De Timary P. Chemosensory event-related potentials in alcoholism: A specific impairment for olfactory function. Biol Psychol 2011; 88: 28-36.https://doi.org/10.1016/j.biopsycho.2011.06.004PMid:21718751.

  • 86.

    Fjaeldstad AW, Ovesen T, Hummel T. The association between smoking on olfactory dysfunction in 3,900 patients with olfactory loss. Laryngoscope 2021; 131: E8-E13.https://doi.org/10.1002/lary.28552PMid:32096874.

  • 87.

    Saramago I, Franceschi AM. Olfactory dysfunction in neurodegenerative disease. Top Magn Reson Imaging 2021; 30: 167-172.https://doi.org/10.1097/RMR.0000000000000271PMid:34096900.

  • 88.

    Rezaee Z, Marandi SM, Alaei H, Esfarjani F. Neuroprotective effects of endurance training in 6-hydroxydopamine rat model of Parkinson's disease. Koomesh 2020; 22: 556-562. (Persian).https://doi.org/10.29252/koomesh.22.3.556.

  • 89.

    Welge-Lssen A. Gestrte riech-und schmeckfunktionTherapieoptionen bei Riech-und Schmeckstrungen. Laryngorhinootologie 2005; 84: 92-105.https://doi.org/10.1055/s-2005-861129PMid:15846544.

  • 90.

    Miwa T, Ikeda K, Ishibashi T, Kobayashi M, Kondo K, Matsuwaki Y, et al. Clinical practice guidelines for the management of olfactory dysfunction-secondary publication. Auris Nasus Larynx 2019; 46: 653-662.https://doi.org/10.1016/j.anl.2019.04.002PMid:31076272.

  • 91.

    Mann NM. Management of smell and taste problems. Cleveland Clinic Journal of Medicine. 2002 Apr 1;69(4):329-36.https://doi.org/10.3949/ccjm.69.4.329PMid:11996203.

  • 92.

    Hummel T, Landis BN, Httenbrink K. Dysfunction of the chemical senses smell and taste. Laryngorhinootologie 2011; 90: S44-55.https://doi.org/10.1055/s-0030-1270445PMid:21523633.

  • 93.

    Oleszkiewicz A, Alizadeh R, Altundag A, Chen B, Corrai A, Fanari R, et al. Global study of variability in olfactory sensitivity. Behav Neurosci 2020; 134: 394.https://doi.org/10.1037/bne0000378PMid:33001681.

  • 94.

    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.https://doi.org/10.1016/0031-9384(84)90269-5.

  • 95.

    Kamrava SK, Farhadi M, Jalessi M, Khosravian B, Pousti B, Hemami MR. University of Pennsylvania smell identification on Iranian population. Iran Red Crescent Med J 2014; 16: e7926.https://doi.org/10.5812/ircmj.7926PMid:24719716 PMCid:PMC3964434.

  • 96.

    Fjaeldstad A, Kjaergaard T, Van Hartevelt T, Moeller A, Kringelbach M, Ovesen T. Olfactory screening: validation of Sniffin'Sticks in Denmark. Clin Otolaryngol 2015; 40: 545-550.https://doi.org/10.1111/coa.12405PMid:25721152.

  • 97.

    Sorokowska A, Albrecht E, Haehner A, Hummel T. Extended version of the "Sniffin'Sticks" identification test: Test-retest reliability and validity. J Neurosci Methods 2015; 243: 111-114.https://doi.org/10.1016/j.jneumeth.2015.01.034PMid:25677404.

  • 98.

    Zou L, Dworschak A, Alizadeh R, Kamrava S, Alwashahi M, Bock M, et al. " U-Sniff"-the international odor identification test for children: an extension of its normative database and study of global reliability. Rhinology 2020; 58: 471-476.https://doi.org/10.4193/Rhin19.355PMid:32333750.

  • 99.

    Jalessi M, Kamrava SK, Amini E, Rafiei F, Nasouti MA, Moosavi N, et al. Is the Persian version of the "Olfactory Disorder Questionnaire" reliable and valid? Iran J Otorhinolaryngol 2017; 29: 209.

  • 100.

    Kamrava SK, Jalessi M, Ghalehbaghi S, Amini E, Alizadeh R, Rafiei F, et al. Validity and reliability of Persian smell identification test. Iran J Otorhinolaryngol 2020; 32: 65.

  • 101.

    Kamrava SK, Hosseini SF, Farhadi M, Jalessi M, Talebi A, Amini E, et al. Cultural adaptation of the Iranian version of the "Sniffin'Sticks" olfactory test. Med J Islam Repub Iran 2021; 35: 1141-1148.https://doi.org/10.47176/mjiri.35.153PMid:35341085 PMCid:PMC8932212.

  • 102.

    Duprez TP, Rombaux P. Imaging the olfactory tract (cranial nerve# 1). Eur J Radiol 2010; 74: 288-298.https://doi.org/10.1016/j.ejrad.2009.05.065PMid:20303227.

  • 103.

    Yousem DM, Oguz KK, Li C. Imaging of the olfactory system. Semin Ultrasound CT MR 2001; 22: 456-472.https://doi.org/10.1016/S0887-2171(01)90001-0.

  • 104.

    Wrobel BB, Leopold DA. Smell and taste disorders. Fac Plast Surg Clin 2004; 12: 459-468.https://doi.org/10.1016/j.fsc.2004.04.006PMid:15337114 PMCid:PMC7129740.

  • 105.

    Doty RL. Treatments for smell and taste disorders: a critical review. Handb Clin Neurol 2019; 164: 455-479.https://doi.org/10.1016/B978-0-444-63855-7.00025-3PMid:31604562.

  • 106.

    Stuck B, Blum A, Hagner A, Hummel T, Klimek L, Hrmann K. ALLERGY Net. Allergy 2003; 58: 1195-1216.https://doi.org/10.1034/j.1398-9995.2003.00162.xPMid:14616133.

  • 107.

    Fong KJ, Kern RC, Foster JD, Zhao JC, Pitovski DZ. Olfactory secretion and sodium, potassium-adenosine triphosphatase: Regulation by corticosteroids. Laryngoscope 1999; 109: 383-388.https://doi.org/10.1097/00005537-199903000-00008PMid:10089962.

  • 108.

    Yuan F, Huang T, Wei Y, Wu D. Steroids and olfactory training for postviral olfactory dysfunction: a systematic review. Front Neurosci 2021; 15.https://doi.org/10.3389/fnins.2021.708510PMid:34456675 PMCid:PMC8387929.

  • 109.

    Stevens MJ, Obrosova I, Cao X, Van Huysen C, Greene DA. Effects of DL-alpha-lipoic acid on peripheral nerve conduction, blood flow, energy metabolism, and oxidative stress in experimental diabetic neuropathy. Diabetes 2000; 49: 1006-1015.https://doi.org/10.2337/diabetes.49.6.1006PMid:10866054.

  • 110.

    Hummel T, Heilmann S, Httenbriuk KB. Lipoic acid in the treatment of smell dysfunction following viral infection of the upper respiratory tract. Laryngoscope 2002; 112: 2076-2080.https://doi.org/10.1097/00005537-200211000-00031PMid:12439184.

  • 111.

    Halyard MY. Taste and smell alterations in cancer patients-real problems with few solutions. J Support Oncol 2009; 7: 68-69.##.

  • 112.

    Henkin RI. Decreased parotid saliva gustin/carbonic anhydrase VI secretion: an enzyme disorder manifested by gustatory and olfactory dysfunction. Am J Med Sci 1999; 318: 380-391.https://doi.org/10.1016/S0002-9629(15)40663-9https://doi.org/10.1097/00000441-199912000-00005PMid:10616163.

  • 113.

    Abdelmaksoud AA, Ghweil AA, Hassan MH, Rashad A, Khodeary A, Aref ZF, et al. Olfactory disturbances as presenting manifestation among egyptian patients with COVID-19: possible role of zinc. Biol Trace Elem Res 2021; 199: 1-8.https://doi.org/10.1007/s12011-020-02546-5PMid:33409924 PMCid:PMC7787876.

  • 114.

    Yee KK, Pribitkin EA, Cowart BJ, Vainius AA, Klock CT, Rosen D, et al. Neuropathology of the olfactory mucosa in chronic rhinosinusitis. Am J Rhinol Allergy 2010; 24: 110-120.https://doi.org/10.2500/ajra.2010.24.3435PMid:20021743 PMCid:PMC5903554.

  • 115.

    Rimmer J, Fokkens W, Chong LY, Hopkins C. Surgical versus medical interventions for chronic rhinosinusitis with nasal polyps. Cochrane Database Syst Rev 2014.https://doi.org/10.1002/14651858.CD006991.pub2.

  • 116.

    Nguyen DT, Bey A, Arous F, NguyenThi PL, FelixRavelo M, Jankowski R. Can surgeons predict the olfactory outcomes after endoscopic surgery for nasal polyposis? Laryngoscope 2015; 125: 1535-1540.https://doi.org/10.1002/lary.25223PMid:25752823.

  • 117.

    Soler ZM, Sauer DA, Mace JC, Smith TL. Ethmoid histopathology does not predict olfactory outcomes after endoscopic sinus surgery. Am J Rhinol Allergy 2010; 24: 281-285.https://doi.org/10.2500/ajra.2010.24.3477PMid:20819467 PMCid:PMC2936485.

  • 118.

    Gktas O, Lau L, Fleiner F. Effect of laser treatment on olfactory dysfunction. Effect of laser treatment on olfactory dysfunction. Indian J Otolaryngol Head Neck Surg 2014; 66: 173-179.https://doi.org/10.1007/s12070-011-0413-5PMid:24533379 PMCid:PMC3918284.

  • 119.

    Alizadeh R, Kamrava SK, Bagher Z, Farhadi M, Falah M, Moradi F, et al. Human olfactory stem cells: As a promising source of dopaminergic neuron-like cells for treatment of Parkinson's disease. Neurosci Lett 2019; 696: 52-59.https://doi.org/10.1016/j.neulet.2018.12.011PMid:30552942.

  • 120.

    Alizadeh R, Bagher Z, Kamrava SK, Falah M, Hamidabadi HG, Boroujeni ME, et al. Differentiation of human mesenchymal stem cells (MSC) to dopaminergic neurons: A comparison between Wharton's Jelly and olfactory mucosa as sources of MSCs. J Chem Neuroanat 2019; 96: 126-133.https://doi.org/10.1016/j.jchemneu.2019.01.003PMid:30639339.

  • 121.

    Alizadeh R, Hassanzadeh G, Joghataei MT, Soleimani M, Moradi F, Mohammadpour S, et al. In vitro differentiation of neural stem cells derived from human olfactory bulb into dopaminergiclike neurons. Eur J Neurosci 2017; 45: 773-784.https://doi.org/10.1111/ejn.13504PMid:27987378.

  • 122.

    Costanzo RM. Regeneration and rewiring the olfactory bulb. Chem Senses 2005; 30: i133-i134.https://doi.org/10.1093/chemse/bjh150PMid:15738076 PMCid:PMC2387238.

  • 123.

    Beites CL, Kawauchi S, Crocker CE, Calof AL. Identification and molecular regulation of neural stem cells in the olfactory epithelium. Exp Cell Res 2005; 306: 309-316.