Abstract
Purpose
To describe systematic methods developed over 40 years among over 5000 patients at The Taste and Smell Clinic in Washington, DC to evaluate taste and smell dysfunction.
Materials and Methods
A tripartite methodology was developed. First, methods to determine clinical pathology underlying the multiple disease processes responsible for taste and smell dysfunction were developed. Second, methods to determine biochemical parameters responsible for these pathologies were developed. Third, methods to implement these techniques were developed to form a unified basis upon which treatment strategies can be developed to treat these patients.
Results
Studies were performed in 5183 patients. Taste loss was present in 62% of patients, smell loss in 87%. Most patients with taste loss (52%) exhibited Type II hypogeusia; most patients with smell loss (56%) exhibited Type II hyposmia. Sensory distortions were present in 60%. Four common diagnostic entities were found: post influenza-type hyposmia and hypogeusia (27% of patients), idiopathic causes (16%), allergic rhinitis (15%) and post head injury (14%). Regardless of clinical diagnosis the major biochemical abnormality found in most patients (~ 70%) was diminished parotid salivary and nasal mucus secretion of cAMP and cGMP.
Conclusions
Taste and smell dysfunctions are common clinical problems associated with chronic disease processes. These symptoms require a systematic, integrated approach to understand their multiple and complex components. The approach presented here can and has led to effective treatment.
1
Introduction
There are many patients in the United States with taste and smell dysfunction related to chronic disease processes but a systematic, integrated approach to their evaluation has been lacking. To understand these processes an understanding of how these processes occur and how they can be evaluated is necessary prior to application of treatment to correct them.
Taste and smell are chemical senses. Chemosensory activity involving taste and smell function commonly reflects local and systemic changes in bodily function. Many pathologies of bodily function are manifested by these changes in taste and smell function. These changes fall into two classes – loss of sensory acuity and distortions of taste and smell function. These sensory changes usually reflect symptoms of chronic disease processes involving multiple organ systems including endocrine , vitamin , trace metal , metabolic , neurological , neurodegenerative , hematological , immunological and other organ systems . These two classes of dysfunction can also reflect local changes in oral or nasal cavities or in the brain although these changes are not the major pathologies which affect chronic taste or smell dysfunction (v.i.). Descriptions of patients with these sensory dysfunctions have been made by many prior investigators related to both local and systemic pathologies but a report of a systematic approach to evaluation of the multiple chronic pathological and biochemical processes responsible for these dysfunctions has been lacking.
In 1971 we published one of the first systematic studies describing one type of chronic human taste and smell dysfunction and its putative anatomical and biochemical pathology . This publication, with its accompanying editorial , reported on patients at The Taste and Smell Clinic, established at the National Institutes of Health, Bethesda, MD, in 1970, the first clinical program in the United States devoted specifically to evaluate and treat patients with taste and smell dysfunction. Since that time, with the transfer of The Clinic, first to Georgetown University Medical Center in 1975, and then to the private sector in 1981, we evaluated and treated more than 5000 patients with these sensory abnormalities. During these studies we developed systematic methods to determine clinical characteristics of these patients, systematic techniques to describe, measure and classify their taste and smell dysfunction and systematic methods to determine some of the biochemical factors responsible for the pathology which initiated these chronic sensory abnormalities . Based upon these clinical, sensory and biochemical techniques, treatment protocols were developed which were eventually successful in correcting many of the chronic sensory abnormalities responsible for these dysfunctions.
A tripartite methodology was developed to define these symptoms; this involves a detailed description of the clinical history and pathology with quantitative measurements of taste and smell function, biochemical techniques which define the clinical pathology in blood, erythrocytes, urine, saliva and nasal mucus and integration of these two methods to allow development of effective treatment of these patients.
We will not deal in this study in any systematic manner with treatment protocols to correct these chronic dysfunctions. These protocols have been previously published and are referred to primarily in association with the methodological studies described herein.
2
Methods
2.1
Clinical evaluation
2.1.1
History
A comprehensive detailed and specific clinical history technique was developed. In addition to standard, commonly used clinical techniques detailed questions were developed to characterize the complex changes which initiate and perpetuate these sensory dysfunctions.
2.1.1.1
Present illness
History of present illness related to taste and smell dysfunction requires specific detailed questions not usually included in an usual medical history. This is essential to explore the natural history of the disease processes and to accurately describe and characterize them.
- a.
Chief Complaint 1. Do you have a loss of taste and/or smell?
Taste Loss. Can you taste salt, sweet, sour and bitter? What are the characteristics of this loss – its onset (sudden or gradual), its localization, its clinical course, exacerbants, palliatives, its relationship to appetite and its relationship to increased use of salt, sugar or condiments?
Smell Loss. Have you lost ability to smell all odors or are some odors still perceived? What are the characteristics of this loss – its onset (sudden or gradual), its localization, its clinical course, exacerbants and palliatives?
- b.
Chief Complaint 2. Do you have distortions of taste or smell?
Distortions. This history requires systematic characterization of what is termed DYSGEUSIA (for taste) and DYSOSMIA (for smell) . These symptoms usually follow onset of loss of taste and/or smell acuity . To obtain specific information about sensory distortions three basic concepts were developed.
- 1.
If the patient experienced an abnormal or unusual taste in his or her mouth in the absence of any food or drink or an abnormal or unusual smell in his or her nose in the absence of any environmental odor then the patient developed PHANTAGEUSIA (for taste) (see Refs. and Table S1 of the Supplementary Appendix) and/or PHANTOSMIA (for smell) (see Refs. and Table S1 of the Supplementary Appendix). These categories have been subclassified into CACOGEUSIC (fecal, putrid, rotten) for taste, CACOSMIC for smell, TORQUGEUSIC (chemical, metallic, burned, overly salty, overly sweet) for taste, TORQUOSMIC for smell or MIXED (both cacogeusic and torqugeusic for taste or both cacosmic and torquosmic for smell). These changes relate to sensory changes in both receptor and brain and are similar to phantom limb sensations which reflect alterations in brain plasticity . If there are tastes which inappropriately exacerbate phantageusia (e.g., a strong taste or spicy foods) it is termed ALLODYNGEUSIA, similar to allodynia for touch. If there are external odors which inappropriately exacerbate the phantosmia (e.g., strong external odors) it is termed ALLODYNOSMIA, also similar to allodynia for touch.
- 2.
If the patient experienced any distorted taste or smell associated with preparing or eating any food or drinking any beverage or with the smell of any external odor then the patient developed ALIAGEUSIA (for foods) and/or ALIOSMIA (for odors) (see Refs. and Table S1 of the Supplementary Appendix). If patients exhibit distortions to foods or odors of a different character from those of phantom sensations it is termed HETEROGEUSIA for foods and HETEROSMIA for odors.
Distortions have been systematically classified by severity related to degree of inability to eat specific foods, food groups or beverages or smell of specific odors or groups of odors. These are characterized by type as Type I, Type II, Type III or Type IV with severity increasing from I to IV as type increases (see Refs. and Table S6 of the Supplementary Appendix).
- 3.
If the patient misidentified any tastant (e.g., salt tastes sweet) or any odorant (e.g., roses smell like coffee) then the patient developed PARAGEUSIA (for taste) and PAROSMIA (for smell) (see Ref. and Table S1 of the Supplementary Appendix). These responses indicate misidentification (not distortion) of tastants or odorants, e.g., salt tastes sweet, roses smell like coffee.
- c.
Other Distortion Questions relates to symptom onset, course, character, exacerbants and palliatives.
- d.
General Questions. These relate to contact with toxic chemicals, smoking history, alcohol intake, lingual or oral burning and changes in salivary or nasal mucus secretions.
- e.
Symptom Consequences. After symptoms began have you experienced any food or odor accidents related to acuity loss or distortion presence, any gastrointestinal symptoms, any avoidance of food preparation, any avoidance of eating specific food, any appetite change or change in weight?
- f.
Prior Therapeutic Drug Treatment. A complete drug history is critical to evaluate agents which can induce taste/smell dysfunction since many drug classes including antibiotics, antifungals, antihypertensives, antiepileptics, antiglaucoma medications and many others may alter taste or smell function.
- g.
Prior Symptom Evaluation and/or Treatment. Evaluation of prior treatment of acuity loss or distortion presence is necessary to understand extent and character of changes in taste/smell function.
2.1.1.2
Past history
This includes specific history of prior acute/chronic illness (including cancer), drug treatment (including chemotherapy), hospitalization for illness or surgery, radiotherapy, psychiatric treatment, fracture or dislocation of bones/joints, any past history of nasal polyps, acetylsalicylic sensitivity, wheezing or asthma, acute or chronic sinusitis, nasal operations, nasal trauma or head injuries. These events can be associated with chronic taste/smell dysfunction. Anesthesia used for general surgical procedures has been associated with both loss and distortion of taste and smell .
Review of systems complements the present illness and past history. Specific questions relate to contribution of multiple organ systems to onset of taste/smell dysfunction . This includes history of allergies, family and genetic history, social history and work history (including prior exposure to any toxic or noxious substance in work or hobbies), as noted by prior investigators and as discussed previously . Specification of skilled handedness should be included.
- a.
Allergic History. History must include questions not only related to upper airways changes with seasonal or perennial allergies but also to nasal congestion alone or associated with season, weather, temperature, intake of alcohol and/or milk and other dairy products and nasal allergy symptoms. Asthma related to intake of acetylsalicylic acid (aspirin) intake, results of prior eosinophil count, serum IgE and RAST testing can relate to hyposmia presence .
- b.
Other Pathology. History of vision, hearing, neurological, endocrine, skin, cardiac, respiratory, gastrointestinal, hematologic, urologic, genital, muscle-skeletal, joint or bone problems may be relevant since changes in growth factor secretion from these organ systems affect smell and taste function .
- c.
Genetic History must include family history of loss/distortion of smell/taste and its cause. Olfactory receptors constitute the largest gene superfamily in the vertebrate genome with over 1000 associated genes and pseudogenes .
- d.
Work History with respect to major occupation and exposure to any toxic, allergic initiating or sensory distorting odors or substances is relevant .
- e.
Social History with respect to country of origin and past and current living area is relevant.
- f.
Nutritional History is relevant since food and fluid intake influences taste and smell function and vice versa . At The Clinic we initiated a systematic method to relate nutritional intake to loss/distortion of taste/smell function ( , Table S5 of the Supplementary Appendix). Three day food diaries of all foods and beverages taken in over a typical three consecutive day period (two weekdays and one weekend day) were obtained. With the help of a trained technician and use of food models typical dietary intakes were obtained and analyzed in detail for energy intake (protein, fat, carbohydrate, alcohol), major food groups eaten, vitamin, electrolyte and trace metal intake by use of a Nutritionist Pro 4.5 program . Quantity of each nutrient taken in was obtained and related to normal typical intake values related to age, gender, height and weight associated with the U.S. Department of Agriculture recommended daily allowance (RDA). Discrepancies for values considered normal were revealed and related to the patient’s taste and smell acuity/distortion . Results of some of these studies have been previously reported and are not the major subject of this study but the methods for determination of these changes are included (see Refs. ).
Body weight, height and body mass index (BMI) were measured to relate sensory acuity and distortions to body mass and nutritional intake.
2.1.2
Related neurological and head and neck examination
- a.
Neurological Examination. A general, simple but specific neurological examination as outlined by many neurologists is necessary to evaluate local and peripheral sensory function.
- b.
Head and Neck Examination. Clinical evaluation of local head and/or neck pathology, as performed by many otolaryngologists and other physicians needs to be performed.
2.1.3
Sensory measurements of taste and smell function
Measurements of sensory changes in patients with taste and smell dysfunction have been performed by many investigators . However, to evaluate sensory status novel, systematic tests of taste and/or smell function were developed at The Taste and Smell Clinic (A) to measure several basic aspects of taste and smell function quantitatively, (B) to classify these functions on a quantitative scale and (C) to define and quantitate sensory distortions (v.s.). These tests define, on a quantitative basis, taste and smell receptor function and their neural-brain interrelationships. Detection thresholds define receptor presence and function ; recognition thresholds define receptor number and neural-brain relationships to receptor function ; magnitude estimation defines receptor number ; hedonic relationships (hedonics) define neural-brain effects related to sensory pathology .
To obtain this information four concepts were developed and translated into systematic investigative methods.
- 1.
With presentation of three stimuli, two of which are neutral (water for taste, water and/or light mineral oil for smell) and one which contains a tastant or odorant of a given concentration (for taste – NaCl for salt, sucrose for sweet, HCl for sour and urea for bitter; for smell – pyridine for pungent, nitrobenzene for sweet, thiophene for putrid and amyl acetate for fruity), can the patient identify the least concentration of tastant or odorant which is different from the two neutral stimuli? For taste this test is performed as a three stimuli, staircase, forced choice drop technique (see Refs. and Tables S7 and S9 of the Supplementary Appendix); this determines taste detection threshold (DT). For smell this test is performed as a three stimuli, staircase, forced choice sniff technique (see Refs. and Tables S7 and S10 of the Supplementary Appendix); this determines smell detection threshold (DT). Normal detection for tastants is: ≤ 60 mM/L for salt and sweet, ≤ 6 mM/L for HCl and ≤ 150 mM/L for urea (see Refs. ). Normal detection for odorants is ≤ 10 − 5 M/L for each odorant (see Refs. and Table S9 of the Supplementary Appendix). If responses are higher (less sensitive) than normal for any tastant or odorant then this response indicates acuity loss for taste and/or smell (hypogeusia and/or hyposmia).
- 2.
With presentation and responses to the prior tests can the patient describe the character of the correctly identified different stimulus? For taste this is either salty, bitter, sweet or sour (see Refs. and Tables S7, S8 and S9 of the Supplementary Appendix); this determines taste recognition threshold (RT). For smell this is either pungent, putrid, sweet, minty, flowery, fruity, some related descriptive or combination of terms (see Refs. and Tables S7, S8 and S9 of the Supplementary Appendix); this determines smell recognition threshold (RT). Normal recognition for tastants is for salt ≥ 60 mM/L, for sweet ≥ 60 mM/L, for sour ≥ 6 mM/L for HCl and for bitter ≥ 150 mM/L for urea. Normal recognition responses for all odorants are ≥ 10 − 2 M/L. If recognition responses are higher (less sensitive) than normal then these responses can relate both to acuity loss (hypogeusia and/or hyposmia) and distortions (dysgeusia and/or dysosmia). Incorrect recognition responses can indicate presence of dysgeusia and dysosmia and can be considered inappropriate (e.g., amyl acetate characterized as putrid) (see Refs. and Tables S7, S8 and S10 of the Supplementary Appendix).
- 3.
For taste, with correct identification of each tastant at a concentration at or above recognition threshold can the patient judge intensity of the correctly identified tastants using a scale from 1 to 100, one being the least intense, 100 being the greatest (see Refs. )? To perform this test the patient must assign an intensity response to each tastant of the entire tastant range beginning at correct recognition. The mean of these values determines taste magnitude estimation (ME) for each specific tastant (see Refs. and Tables S6 and S8 of the Supplementary Appendix). For smell, with correct identification of the four highest odorant concentrations at or above recognition thresholds for each odorant can the patient judge intensity of the correctly identified odorant using a scale from 1 to 100, one being the least intense, 100 being the greatest? The mean of each set of correct responses determines smell magnitude estimation (ME) for each specific odorant (see Refs. and Tables S6 and S8 of the Supplementary Appendix). Mean values of normal responses are ≥ 50% for each tastant and odorant (see Ref. and Tables S6 and S8 of the Supplementary Appendix).
- 4.
For taste and/or smell, with correct responses associated with question 3, can the patient judge whether the tastant or odorant is pleasant, unpleasant or neutral? For pleasant (e.g., I like the tastant or odorant), the scale extends from 1 to + 100, for unpleasant (e.g., I do not like the tastant or odorant), the scale extends from − 1 to − 100 and for neutral (e.g., I neither like nor dislike the tastant or odorant) the scale is 0. The arithmetic mean of each set of correct responses for question 3 determines hedonic response (H) for each specific tastant and/or odorant (see Ref. and Tables S6 and S8 of the Supplementary Appendix). For tastants Hs for sucrose are usually considered pleasant, ≥+n; for tastants HCl and urea Hs are usually considered unpleasant, ≥−n; Hs for NaCl can vary, ± n. For odorants pyridine and thiophene Hs are usually considered unpleasant, ≥−n; for odorants nitrobenzene and amyl acetate Hs are usually pleasant, ≥+n. If H responses which are usually positive are negative the patient exhibits either dysgeusia and/or dysosmia (see Refs. and Tables S6 and S8 of the Supplementary Appendix).
Answers to these four questions can be formulated into four types of sensory dysfunction. For taste, these are ageusia and hypogeusia Types I, II and III, as defined in Refs. and Table S8 of the Supplementary Appendix. They are defined by degree of taste acuity loss with ageusia (the most severe loss) < Type I hypogeusia < Type II hypogeusia < Type III hypogeusia. For smell, these types are anosmia and hyposmia Types I, II and III. They are defined by degree of smell loss with anosmia (the most severe loss) < Type I hyposmia < Type II hyposmia < Type III hyposmia. These classifications are also defined in Refs. and in Table S8 of the Supplementary Appendix.
These olfactory testing techniques have been evaluated critically and verified in a double blind placebo controlled clinical study and in a controlled, open label clinical trial .
2.1.4
Imaging studies of nasal region, skull, brain and brain function
These studies determine three important manifestations of taste and smell function: 1) anatomical and clinical status of structures of nasal region, skull, head and brain, 2) functional activity of brain related to smell and taste function and 3) functional tractography of brain related to smell and taste function.
- 1.
Anatomical and clinical status of nasal region, head, skull and brain including sinuses have been investigated by many previous clinicians using CT scans of paranasal sinuses and CT scans and/or MRI studies of brain . Repeat studies can confirm and monitor effective treatment .
- 2.
Functional MRI (fMRI) studies are important to understand extent and nature of both taste and smell function among patients with phantageusia , phantosmia or loss of taste and/or smell acuity related to several pathological conditions. Repeat fMRI studies confirm and monitor effective treatment .
- 3.
Diffusion tensor imaging (DTI) tractography of olfactory nerve–brain interrelationships as determined by previous investigators and as applied to olfactory pathways into receptive and integrative regions of brain are critical to determine neuronal functionality of olfaction in patients, particularly in patients with head injury and congenital hyposmia .
2.2
Biochemical evaluations
2.2.1
Blood, urine and red blood cell evaluations
Chronic chemosensory dysfunctions of taste and smell are caused by changes in secretions from multiple body organ systems including hematological, endocrine, renal, liver, pancreas, neurological, immunological and others (v.s., ). Thus, studies of these secretions in blood plasma, erythrocytes, urine, saliva and nasal mucus for those moieties (i.e., growth factors) known to influence taste and smell function were undertaken as discussed previously by ourselves and by other investigators .
To undertake these studies with respect to saliva and nasal mucus we performed one of the first published comprehensive analyses of the major protein components of parotid saliva and nasal mucus .
2.2.2
Parotid saliva evaluations
Changes in many biochemical moieties considered growth factors are responsible for maturation and maintenance of taste buds [ (v.s.)] and thereby responsible for taste function. Saliva contains these moieties and therefore its collection is necessary to understand changes in both taste and smell function .
2.2.2.1
Parotid saliva collection
A modified Lashley cup is applied to Stensen’s duct with 8-10 ml of saliva stimulated by lingual placement of concentrated lemon juice and collected in plastic tubes on ice . Flow rate is calculated by measurement of saliva weight over a specified time period, usually 5-6 min. Samples are transferred to 0.5 ml PCR tubes and stored at − 20 °C until assayed.
2.2.2.2
Parotid saliva analysis
Trace metals (zinc, copper, magnesium) and calcium were measured by atomic absorption spectrophotometry (AAS) . The enzyme carbonic anhydrase VI (gustin) was measured by estimation of its activity . Cyclic AMP and cGMP were measured by a sensitive spectrophotometric ELISA immunoassay (R&D Systems, Minneapolis, MN) . Protein was measured by UV spectrophotometry (the difference between optical absorbance at 215-225 nm multiplied by the extinction coefficient ).
Results of these studies which define impaired secretion of these substances related to chronic disease processes have been previously published ( and see Table S11 of the Supplementary Appendix).
2.2.3
Nasal mucus evaluations
Nasal mucus contains biochemical moieties responsible for maturation and maintenance of olfactory epithelial cells . Therefore, collection of nasal mucus is necessary to understand both smell and taste function .
2.2.3.1
Nasal mucus collection
Spontaneous nasal discharge from the nasal cavity over one to three days was placed in a 50 ml wide-mouth plastic centrifuge tube, kept at 4 °C during any overnight period and weighed upon reaching the laboratory. Mucus was transferred to 12 ml plastic tubes, centrifuged at 17-19 K × g for 45–60 min, supernatant transferred to 0.5 ml PCR tubes and stored at -20 °C until assayed.
2.2.3.2
Nasal mucus analysis
Trace metals (zinc, copper, magnesium) and calcium were measured by AAS . Carbonic anhydrase VI was measured by estimation of its activity . cAMP and cGMP were measured by the same sensitive spectrophotometric ELISA immunoassays used to measure cyclic nucleotides in saliva (R&D Systems, Minneapolis, MN) . Protein was measured by the same technique used for saliva (v.s.).
Results of these studies which define impaired secretion of these substances related to chronic disease processes have been previously published ( and see Table S12 of the Supplementary Appendix).
2.3
Integration of clinical and biochemical pathology to define the major factors responsible for chronic taste and smell dysfunction
Integration of results of these prior methodologies allows the investigator to understand the pathology responsible for taste and smell dysfunction and, based upon these results, to establish protocols to correct these dysfunctions.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
