Quality of life in olfactory dysfunction
Thomas Hummel, M.D.¹, and Steven Nordin, Ph.D.²

¹Smell and Taste Clinic, Department of Otorhinolaryngology, University of Dresden Medical School, Fetscherstrasse 74, 01037 Dresden, Germany; phone 011-49-351-458-4189, fax 011-49-351-4326

²Department of Psychology, Umea University, 90187 Umea, Sweden

Acknowledgments: We greatly appreciate the help of Drs. Johannes Frasnelli and Basile Landis, Smell and Taste Clinic, Department of Otorhinolaryngology, University of Dresden Medical School, Germany, for thoughtful comments.

Disturbances of the chemical senses are frequent. It is estimated that a complete loss of the sense of smell is found in at least 1 % of the US population (⁵; compare ^{6, 7}). In a recent study of individuals aged 53-97 years, 24% were found to have impaired olfactory function ⁸. In addition, each year hundreds of thousands of patients complain to their physician about disturbances of smell or taste ^{9, 10}. This is despite the fact that often olfactory loss appears to go unnoticed ^{10, 11}, even in cases where head trauma caused sudden olfactory loss ¹². Thus, when considering observations in this area of research, the selection bias has to be kept in mind. People with decreased olfactory sensitivity who do not seek counselling are less likely to have a decreased quality of life compared to patients who present themselves actively to specialized centers, where this kind of research is done. Consequently, research in this area will overstate the average impact of olfactory loss.

Major determinants of olfactory sensitivity are gender and age. It is well known that women outperform men in almost all aspects of olfactory sensitivity. Although the exact reason for this difference remains unclear, social, hormonal, or genetic factors are thought to be involved ²⁵. Using different measures, studies have shown a decrease of olfactory sensitivity past the age of 60 ^26-30. In fact, in terms of odor identification more than 50% of 80-year old people exhibit olfactory disturbances ^{8, 31}. Other determinants of olfactory sensitivity include smoking which leads to a mild but significant decrease of olfactory function. This decrease has been shown to be related to the number of cigarettes smoked, but can be reversed after cigarette smoking has terminated ^{32, 33}.

Approximately two thirds of patients with olfactory loss not only complain of decreased olfactory function, but also of taste loss, and approximately 10% of patients with olfactory disorders complain of gustatory loss only ¹⁰. However, a major decrease in gustatory function is only present in less than 5% of patients with chemosensory disorders ¹⁰. More recent data, however, indicate that olfactory loss is also accompanied by a gradual loss of both trigeminal ^{38, 39} and gustatory function ⁴⁰. While the reason for this is unclear, it has been shown that the chemical senses exhibit mutual interactions, both at peripheral and central nervous levels ^41-45.

In both, Alzheimer's and Parkinson's disease, loss of olfactory sensitivity is thought to be among the earliest signs of the disease ^49-51. Considering the relatively high prevalence of both disorders ^{52, 53}, it can be estimated that these neurodegenerative processes significantly contribute to the presence of olfactory dysfunction in the general population

Other frequent causes include congenital anosmia or exposure to toxic substances, each of which has been reported to occur in less than 5% of the cases ^{10, 11, 47}. A wide variety of still other etiologies include, for example, psychiatric causes (e.g., schizophrenia, depression), epilepsy, sarcoidosis, lupus erythematodes, multiple chemical sensitivities, pregnancy, diabetes, hypothyroidism, renal failure, liver disease, olfactory meningeomas, and neoplasms of the brain (for review see ¹⁷). Finally, iatrogenic causes of olfactory disorders include rhinoplasty, neurosurgery, radiation or drug therapy. In an additional 20% of the patients, a cause for the chemosensory disturbance cannot be identified (idiopathic).

It seems reasonable to assume that acute loss of olfactory function following trauma or viral infection is perceived as more severe compared to the gradual loss of olfactory function, e.g., in sino-nasal disease. In fact, signs of higher degree of depression or global psychological distress, respectively, have been reported in patients with a more recent and sudden onset of anosmia ⁵⁴. However, observations have been published indicating that this correlation is weak and difficult to obtain ^{11, 55}. In fact, in patients with post-traumatic olfactory loss it is a characteristic that this deficit is only noted weeks or even months following the actual incident ⁵⁶.

Further difficulties in this area of research become apparent when considering that most, if not all studies, are biased by investigations in subjects who present themselves to specialized centers, or subjects who identify themselves as compromised in terms of olfactory function. Epidemiological research in this area seems to be particularly difficult considering that, within the general population, difficulties to adequately judge olfactory function/dysfunction are frequently found ⁵⁷, and, consequently, many patients would not seek professional advice, even if olfactory function was seriously compromised.

Patient evaluation
The first step in patient evaluation ^46-48 is to take a thorough history. This should include demographics, eating, drinking or smoking habits, listing of major illnesses and injuries, medications taken in relation to symptom onset, history of present illness, endocrine information including questions regarding menstrual status or thyroid function, general nasal health including obstruction, rhinorrhea, and postnasal drip, and finally, changes of the sense of smell. Physical examination typically includes the patient's head and neck; the remainder of the investigation may be directed by the patient's history. Frequently, a detailed neurological examination may become necessary. Specific nasal examination should include at least rhinoscopy, although nasal endoscopy is clearly preferable. Radiological evaluation may be helpful to rule out the presence of olfactory meningeomas, pituitary tumors, frontal lobe gliomas, large aneurysmas, or other cerebral tumors. A CT scan may also be useful in the diagnosis of olfactory loss to be conductive ⁵⁸. Magnetic resonance tomography may be helpful in the diagnosis of congenital olfactory loss ⁵⁹. Additional diagnostic tests may include the search for other underlying causes of the olfactory disorders, e.g., diabetes, hypothyroidism, lupus, zinc deficiency, or deficiency of vitamin A or B12. Finally, biopsies of the olfactory epithelium may become helpful in the diagnosis of olfactory disorders ⁶⁰.

Olfactory testing
Olfactory testing appears to be of particular importance in light of the fact that often olfactory loss appears to go unnoticed ^{10, 11, 61}. During the last decade standardized tests of olfactory function have been developed (e.g., The University of Pennsylvania Smell Identification Test (UPSIT) [a "scratch and sniff" odor identification test] ⁶²; "Sniffin' Sticks" [pen-like odor dispensing devices which include tests for odor identification, discrimination, and thresholds] ⁶³; or the CCCRC test [a combined odor identification and odor threshold test] ⁶⁴). Specialized testing may include EEG-derived measures such as the recording of olfactory event-related potentials. These responses appear to be especially helpful in cases where anosmia needs to be definitively verified, or when it comes to research issues in terms of the processing of odorous information ⁶⁵.

Most people recognize the values of olfactory function only after it has been lost. Although olfactory function is important as a warning system which may alert individuals to poisonous fumes, leaking gases, or spoiled foods, or in interpersonal communication ^1-4, its loss is mostly expressed in terms of a severe decrease of the quality of life.

Temmel and colleagues ¹¹ reported that almost all of the investigated patients (n=278) reported difficulties in daily life due to their olfactory disorder. Specifically, 73% complained of difficulties with cooking, 68% of mood changes, 56% of decreased appetite, 50% eating of rotten food, 41% to little perception of own body odor, 30% of burning food, but only 8% of problems at work. Similar figures were reported by Miwa et al. ⁷⁶ who investigated 345 patients with persisting olfactory dysfunction. The most commonly cited impairments were ability to detect spoiled food (75%), gas leaks (61%), or smoke (50%); eating (53%); and cooking (49%). Thus, problems in quality-of-life issues were reported primarily in the areas of safety and eating. Overall satisfaction with life was reported to be reduced to only 50% of the impaired group. Approximately 25% of their patients indicated that they enjoyed life less. Interestingly, in both studies ^{11, 76} relatively few patients (< 15%) complained of work-related problems due to olfactory loss which maintains the idea that even for anosmic people social functioning is still possible. In fact, in our clinic we have seen chefs who continue their jobs without attracting attention in their professional environments - which is largely due to the fact that most of the cooking is done according to specific recipes or through the processing of pre-prepared foods.

Nevertheless, areas most affected through olfactory loss appear to be eating and safety. This corresponds to observations made by Tennen et al. ⁵⁴, that a "feeling of vulnerability" is the single most stressful aspect of olfactory dysfunction. This complaint was reported by 28% of 66 investigated patients with smell disorders.

Both age and gender seem to have a significant effect on difficulties in daily life due to olfactory dysfunction ¹¹. Specifically, the youngest patients had the highest degree of difficulties (²40 years: 54%; 41-60 years: 53%; >60 years: 38%) (compare ⁷⁷), and women mentioned more complaints than men (women: 53%, men: 42%) (see also ^{78, 79}). Gender effects have also been reported such that olfactory dysfunction appears to be more likely change eating habits in female than in male patients ⁷⁷. This may be interpreted such that olfaction is more important to women than to men. This idea is also supported by the rule that, if gender differences are found, female subjects score higher on olfactory tasks than do men ^80-83. In other words, the world seems to smell different to men and women. In turn, the total or partial loss of this odorous environment is much more meaningful to women than it is for men.

In a study of 72 patients with anosmia (46%) and hyposmia (54%), 77% considered that quality of life in general had deteriorated after the onset of their dysfunction. Based on a retrospective question, olfaction was considered by 90% to be of more importance after than before the dysfunction started. Seventy-five percent experienced risks caused by their dysfunction, 63% found their daily routines to be negatively affected and 34% experienced that their dysfunction affected health. Fifty percent of these latter patients reported depression, and psychological well-being was compromised, which was assessed with the General Well-Being Schedule. Reduced food appreciation and appetite was reported by 53% and 32%, respectively. Physical health, financial security, profession, partnership, friendship, emotional stability and leisure were all rated as important for life quality and rated as negatively affected by their olfactory dysfunction ⁸⁴.

Interestingly, neither duration of disease, nor etiology of the olfactory dysfunction had significant effects on the patients' complaints - other than what has been reported by Tennen et al. ⁵⁴.

Nutritional implications of olfactory dysfunction
An important question in this context in terms of the consequences of olfaction dysfunction relates to the intake of foods. Available data indicates that there is no simple answer. For example, Ferris and Duffy ⁷⁷ report that over 70% of their sample (n=230) indicated that food enjoyment decreased with olfactory loss (see also ^{11, 76}). However, the degree of loss was not directly correlated to loss of food enjoyment. Age appeared to be a factor, as younger subjects with olfactory loss indicated decreased enjoyment of food, which was not seen that often in older subjects, especially when the olfactory loss had been noted for more than three years. However, work by Mattes (for review see ⁸⁵) indicates that anosmic patients do not experience systematic problems in relation to their food intake; both weight loss and gain of weight are reported.

Loss of weight appears to be particularly frequent in patients with qualitative olfactory dysfunction ⁸⁶. These patients have also been shown to exhibit specific dislikes towards certain foods ⁹. In contrast, many anosmic patients may even report an increase in body weight which is often attributed to a "gustatory" reward in the form of a sweet desert following a dull and unexciting meal ⁹. Thus, while olfactory loss severely decreases enjoyment of foods, in general it does not appear to have a major effect on overall food intake, although subtle differences are reported. For example, in elderly women olfactory loss has been reported ⁸⁷ to be associated with a lower preference for certain nutritious foods, while higher amounts of sweets and fats were eaten. This did not translate into a change of body mass index or energy intake. On the other hand, interventions aimed at the amplification and enhancement of foods have been reported to be beneficial in terms of both improvement of nutrient quality ⁸⁸ or increase in caloric consumption ^{89, 90} (for review see ⁹¹).

The odor perception scale ⁹⁷ consists of three questions which allow the patient to indicate the degree of olfactory function. While this scale appears to be easy to use, it may not cover the full range of problems which is reported by patients with olfactory loss. In contrast, the "Questionnaire for Olfactory Dysfunction" (QOD) ⁷⁸ was developed in analogy to questionnaires used to quantify the degree of tinnitus ⁹⁸. The QOD consists of 52 statements, which can be divided into 3 domains: 39 "negative" statements, 5 "positive" statements, and 8 "socially desired" statements. The negative statements give information to which degree the patients suffer from the olfactory impairment. The positive statements indicate how well patients cope with their olfactory impairment; this relates to the fact that many dysosmic patients also report positive effects of their olfactory loss, e.g., they have little trouble changing diapers, sniff at vomit, or clean out unpleasantly smelling foods ⁵⁴. The "socially desired" statements - similar to the "lie scale" of the Eysenck Personality Inventory ⁹⁹ - are used to indicate the extent to which an individual is "honest", or whether he or she is trying to create a certain impression by providing socially desirable responses. In comparison to healthy subjects, based on results from the SD-36, patients suffering from olfactory dysfunction exhibited an impaired quality of life in several domains (e.g., "General Health Perception", and "Vitality"). When assessed with the QOD, hyposmic and anosmic patients' quality of life was found to be significantly impaired compared to patients with normosmia (compare ¹⁰⁰). Further, women seemed to suffer more from olfactory dysfunction than male patients. Additionally, when comparing patients with qualitative and quantitative olfactory dysfunction with those suffering from quantitative olfactory impairment only, the QOD was the only test to differentiate between those groups. In light of the difficulties to reliably quantify the degree of qualitative distortions through tests of olfactory function ³⁷, this seems to be of specific interest as therapeutic effects/changes over time are typically difficult to quantify in this group of patients. Overall, it appears as if the QOD was suited for the specific assessment of patients with olfactory dysfunction.

Another questionnaire has been described by the group around Lehrner ¹⁰⁰. The questionnaire is composed of twelve items. It consists of the 1-item subjective olfactory capability scale, the 5 item self-reported smell related problems scale, and 6-item olfactory related quality of life scale. All three scales significantly discriminate between healthy controls (n=128) and patients with anosmia (n=9). Single item group comparisons revealed that patients with smell loss indicated to be significantly impaired in areas of food, safety, personal hygiene, and additionally, in their sexual life (compare ^{54, 79}).

Varga, Breslin, and Cowart ¹⁰¹ presented a questionnaire to assess the impact of chemosensory dysfunction on every day life which also includes utility-based or time trade-off scales, with a particular focus on the value placed by patients on chemosensory function. In a sample of 105 patients with olfactory loss, increased concern was found regarding the ability to detect smoke, gas leaks, and spoiled food, which was related to measurable smell dysfunction. Up to one third of the patients rated their mood, ability to enjoy food, and social interactions as fair to poor. These ratings were associated with general depression scores. In fact, half of the patients reported to be willing to spend more than 20% of their annual household income to successfully treat chemosensory dysfunction.

Yet another questionnaire is the Multi-Clinic Smell and Taste Questionnaire for Scandinavian Use ¹⁰² which, apart from questions about chemosensory dysfunction and related medical history, includes questions about consequences of olfactory dysfunction. These latter questions refer to interference with daily routines and affected general well-being, life-quality, food appreciation and appetite. The vast majority of the questions have been demonstrated to be comprehensible and to generate responses with good reliability.

Using the Beck Depression Inventory ⁹² Deems and colleagues ¹⁰ reported that signs of depression were found in 29% of patients with chemosensory dysfunction (compare ^{54, 103}). This figure was slightly higher in patients reporting parosmia or parageusia (35%) compared to patients not reporting these symptoms (24%) ⁷⁸. However, remaining olfactory function does not seem to predict the loss of quality of life, as similar changes have been reported for anosmic and hyposmic patients. In addition, not all studies ¹¹ show a correlation between the patients' complaints and the measured ability to smell (but see also ^{55, 104}). In this context it is also interesting to note that persons with congenital anosmia do not indicate a restriction of their quality of life ¹¹. This is also supported by observations indicating that "congenital absence of olfaction does not result in markedly aberrant food preferences" ¹⁰⁵.

The different psychological tests used in the different investigations have been found to exhibit a high degree of correlation ^{78, 100}. The basis for this observation appears to be a state of general depression/impairment of quality of life, which is typcically seen in a large percentage of patients with olfactory dysfunction ^{10, 11, 76}. However, at least in patients with olfactory loss due to sino-nasal disease, a major component of the patients' decreased quality of life is related to the decreased patency of their nasal airways - which in turn will severely affect the results obtained by means of these questionnaires. In other words, at least in this group of patients, analysis of changes of the quality of life appears to be difficult, as olfactory and respiratory functions are so intimately linked to each other.

In closing, it may be allowed to quote a more poetic description of the consequences of taste loss which, in the view of the authors, summarizes many complaints of patients with olfactory dysfunction: "Sense of smell? ... I never gave it a thought. You don't normally give it a thought. But when I lost it - it was like being struck blind. Life lost a lot of its savour - one doesn't realize how much "savour" is smell. You smell people, you smell books, you smell the city, you smell the spring - maybe not consciously, but as a rich unconscious background to everything else. My whole world was suddenly radically poorer..." (from: Sacks O., 1985, The dog beneath the skin. In: The man who mistook his wife for a hat. Summit Books / Schuster & Schuster Inc., New York)

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