Clinical Characteristics Of Patients With Olfactory Complaints And Study On Pathogenic Mechanism Of Olfactory Injury By Virus Infections

Disturbances of the sense of smell are frequent.It is estimated to be 19.1% (hyposmia 13.3%,anosmia 5.8%) in adults aged 20 years and older,and 24.5%in adults aged 53 years and older.However,olfaction has traditionally been thought of as a sensory system of minor importance and loss of olfactory function is rarely a life-threatening disability,so many patients postpone medical consultation or assum that their sense of smell will return.In the first part,we evaluated the olfactory function in 146 patients with smell loss by various tests in clinic.These tests or procedures included medical history collection,physical examination of the nose,head and neck,olfactory tests and medical imaging.Olfactory function was assessed by T&T olfactometry and olfactory event-related potentials(OERPs).Our clincial studies suggested that nasal and paranasal sinus disease,upper respiratory infections,head trauma were the most common causes of olfactory dysfunction,and showed the complexity of clinical manifestations of olfactory disorders which included total hyposmia or anosmia of dinasal,partial hyposmia or anosmia of dinasal,uninasal of hyposmia or anosmiam,and an unusual phenomenon was observed that the subjective recognition thresholds was normal,while the expected OERPs was not detectable.The sense of smell is important to survival and quality of life.In the first part study,we knew it was very necessary to increase our awareness of the olfactory sense,and also the results of assessment of olfactory function showed T&T olfactometry was not sufficient,as a objective test,the measurement of OERPs was thus indispensable for investigating the functioning of sensory systems.OERPs could offer a deeper insight into the olfactory system and was an ideal supplementary tool to olfactometry.Upper respiratory tract infection(URTI) or nasal and nasal sinus inflammation diseases might be the two major reasons that cause olfactory disorders.However,there is a major difficulty in the development of therapeutics to treatment such an olfactory dysfunction,because their underlying mechanisms remain unknown.In the second part, we first showed that budesonide nebulization significantly improved olfactory function in patients with dysosmia associated with URTI or nasal and nasal sinus inflammation diseases.These results suggested that local administration of budesonide,a glucocorticoid drug given via nebulization,might be an effective treatment for olfactory dysfunction related to URTI or nasal and nasal sinus inflammation diseases.In the third part,we administered experimental intranasal infection with influenza A/PR/8/34 to make mice models.At 1,3,7,11,21 days postinfection,mice were killed and the skulls including olfactory epithelium and olfactory bulb tissue were removed.For hematoxylin and eosin stain,we observed that the olfactory epithelium and bulb after postinfection all appeared changes,which might indicate virus damage occurred at the level of the epithelium and in central processing pathways such as the olfactory bulb.Based on immunohistochemistry findings of OMP,MMP-9,TIMP-1, OMP staining as control was used to monitor changes in mature olfactory neurons,we discovered that immediately following postinfection OMP levels decreased while MMP-9 and TIMP-1 levels increased in olfactory epithelium.However,following 21 days of virus infection olfactory neurons regeneration OMP levels increased while MMP-9 and TIMP-1 levels turned to control levels.These histopathologic changes represent that MMP-9/TIMP-1 could play a role in olfactory epithelium regeneration and recovery.