The olfactory sense has evolved to provide environmental and physiological cues through the detection of volatile organic compounds. While historically a clinician's sense of smell was used to assist in diagnosing illness, with some notable exceptions, this has fallen out of favour with the advent of analytical tools. Recently, world events have shown that olfactory methodologies can be highly useful for diagnostic purposes. The emergence of the SARS-CoV-2 virus (causing COVID-19) presented a number of logistical issues with regards to establishing fast and accurate diagnosis-while the idea of detection dogs was proposed at the time, little in the way of routine clinical application was accomplished for this disease. The reasons for this are multifactored, but the use of olfaction as a diagnostic tool can be efficacious, provided appropriate methodological considerations are met. Here, the use of olfaction within a medical diagnostic framework is discussed; with olfactory diagnosis having the potential of very high sensitivity and specificity, but with a low diagnostic cost in terms of expense, time, and patient discomfort. This review will also discuss the ways in which olfactory medical diagnosis can be accomplished using humans, dogs, as well as other animals. Finally, this paper will outline recommendations of how future olfactory diagnostic options can be researched and implemented to ensure best practice.

Migraine is a complex disorder characterized by episodes of moderate-to-severe, often unilateral headaches and generally accompanied by nausea, vomiting, and increased sensitivity to light (photophobia), sound (phonophobia), and smell (hyperosmia). Photophobia is considered the most bothersome symptom of migraine attacks. Although the underlying mechanism remains unclear, the intrinsically photosensitive retinal ganglion cells (ipRGCs) are considered to be involved in photophobia associated with migraine. In this study, we investigated the association between the sensitivity of ipRGCs and migraines and cortical spreading depression (CSD), which may trigger migraine attacks. The pupillary responses closely associated with the function of ipRGCs in patients with migraine who were irradiated with lights were evaluated. Blue (486 nm) light irradiation elicited a response from ipRGCs; however, red light (560 nm) had no such effect. Melanopsin, a photosensitive protein, phototransduces in ipRGCs following blue light stimulation. Hypersensitivity of ipRGCs was observed in patients with migraine. CSD was more easily induced with blue light than with incandescent light using a mouse CSD model. Moreover, CSD was suppressed, even in the presence of blue light, after injecting opsinamide, a melanopsin inhibitor. The hypersensitivity of ipRGCs in patients with migraine may induce CSD, resulting in migraine attacks.

Adrenal insufficiency often presents with nonspecific symptoms, physical findings, and laboratory results, leading to diagnostic challenges. However, reports have indicated that specific symptoms such as hypergeusia (hypersensitivity to taste) and hyperosmia (hypersensitivity to smell) can also occur. We report the case of a 60-year-old male with loss of appetite, fatigue, and polyarthralgia, where a detailed medical history revealed the cause of anorexia to be hypergeusia and hyperosmia. These specific symptoms led to the diagnosis of adrenal insufficiency. Treatment with oral steroids for secondary adrenal insufficiency resulted in the improvement of his diverse symptoms. This case illustrates that in patients presenting with chronic nonspecific symptoms, inquiring about heightened taste and smell sensitivity can prompt suspicion of adrenal insufficiency. Moreover, this case serves as a reminder that careful medical history taking in patients with nonspecific symptoms can uncover specific findings that may be diagnostic clues.

Definitions are essential for effective communication and discourse, particularly in science. They allow the shared understanding of a thought or idea, generalization of knowledge, and comparison across scientific investigation. The current terms describing olfactory dysfunction are vague and overlapping.

Sensory perception alterations are common in relation to COVID-19 disease, but less is known about the characteristic of the sensory alterations, and how they associate with alterations in appetite and eating behaviour. The current study aims to investigate the acute and long-term effects of COVID-19 disease on (1) the desire for food, hunger, and satiety sensations; (2) smell, taste, and flavour perception; (3) meals and intake of food types; and (4) the frequency of commonly applied strategies to tackle potential changes in appetite and sensory perception. An online survey was conducted among Danish adults (n = 102) who had experienced changes in appetite, sensory perception, and/or food-related pleasure due to COVID-19 disease. Key results include appetite-altering effects at all times during the day when suffering from COVID-19 and often associated with impaired sensory function. Severe sensory perception alterations were found, namely, for the perception of taste, ageusia > hypogeusia > hypergeusia, and for the perception of smell, anosmia > parosmia > hyposmia > hyperosmia. Eating behavioural changes included alteration in quantitative and qualitative aspects of intake. The effects were, in general, more pronounced during the acute phase of disease than during the post-acute phase. The findings illustrate the complexity by which COVID-19 affects human appetite, sensory perception, and eating behaviour, but also point to strategies to cope with these changes.

Background: Multiple chemical sensitivity (MCS) is a chronic condition with somatic, cognitive and affective symptoms that follow contact with chemical agents at usually non toxic concentrations. We aimed to assess the role of genetic polymorphisms involved in oxidative stress on anxiety and depression in MCS. Materials & methods: Our study investigated the CAT rs1001179, MPO rs2333227, PON1 rs662 and PON1 rs705379 polymorphisms in MCS. Results: The AG genotype of the PON1 rs662 and the TT and CT genotypes of the PON1 rs705379 were involved in anxiety and depression. Discussion: These results are in line with existing evidence of PON1 involvement in MCS and suggest a further role of this gene in the exhibition of anxiety and depression in this disease.

Multiple Chemical Sensitivity (MCS) is a chronic and/or recurrent condition with somatic, cognitive, and affective symptoms following a contact with chemical agents whose concentrations do not correlate with toxicity in the general population. Its prevalence is not well defined; it mainly affects women between 40 and 50 years, without variations in ethnicity, education and economic status. We aimed to assess the core symptoms of this illness in a sample of Italian patients. Two physicians investigated different symptoms with a checklist compilation in 129 patients with MCS (117 women). We conducted a categorical Principal Component Analysis (CATPCA) with Varimax rotation on the checklist dataset. A typical triad was documented: hyperosmia, asthenia, and dyspnoea were the most common symptoms. Patients also frequently showed cough and headache. The CATPCA showed seven main factors: 1, neurocognitive symptoms; 2, physical (objective) symptoms; 3, gastrointestinal symptoms; 4, dermatological symptoms; 5, anxiety-depressive symptoms; 6, respiratory symptoms; 7, hyperosmia and asthenia. Patients showed higher mean prevalence of factors 7 (89.9%), 6 (71.7%), and 1 (62.13%). In conclusion, MCS patients frequently manifest hyperosmia, asthenia, and dyspnoea, which are often concomitant with other respiratory and neurocognitive symptoms. Considering the clinical association that is often made with anxiety, more studies are necessary on the psychosomatic aspects of this syndrome. Further analytical epidemiological studies are needed to support the formulation of aetiological hypotheses of MCS.

Many women report a heightened sense of smell during pregnancy. Accounts of these anecdotes have existed for over 100 years, but scientific evidence has been sparse and inconclusive. In this review, I examine the literature on olfactory perception during pregnancy including measures of self-report, olfactory thresholds, odor identification, intensity and hedonic ratings, and disgust. Support for a general decrease in olfactory thresholds (increase in sensitivity) is generally lacking. There is limited evidence that some suprathreshold measures of olfactory perception, such as hedonic ratings of odors, are affected by pregnancy, but these effects are idiosyncratic. In this review, I explore the hypotheses that have been put forth to explain changes in olfactory perception during pregnancy and provide suggestions for further research.

The genetic basis of odorant-specific variations in human olfactory thresholds, and in particular of enhanced odorant sensitivity (hyperosmia), remains largely unknown. Olfactory receptor (OR) segregating pseudogenes, displaying both functional and nonfunctional alleles in humans, are excellent candidates to underlie these differences in olfactory sensitivity. To explore this hypothesis, we examined the association between olfactory detection threshold phenotypes of four odorants and segregating pseudogene genotypes of 43 ORs genome-wide. A strong association signal was observed between the single nucleotide polymorphism variants in OR11H7P and sensitivity to the odorant isovaleric acid. This association was largely due to the low frequency of homozygous pseudogenized genotype in individuals with specific hyperosmia to this odorant, implying a possible functional role of OR11H7P in isovaleric acid detection. This predicted receptor-ligand functional relationship was further verified using the Xenopus oocyte expression system, whereby the intact allele of OR11H7P exhibited a response to isovaleric acid. Notably, we also uncovered another mechanism affecting general olfactory acuity that manifested as a significant inter-odorant threshold concordance, resulting in an overrepresentation of individuals who were hyperosmic to several odorants. An involvement of polymorphisms in other downstream transduction genes is one possible explanation for this observation. Thus, human hyperosmia to isovaleric acid is a complex trait, contributed to by both receptor and other mechanisms in the olfactory signaling pathway.

The high rate of benzodiazepines (BZD) consumption has been repeatedly confirmed by epidemiological surveys in most major western world countries. In a recent french survey 7% of chronic users of BZD (use in 5/7 days for the last 12 months) were found the general population (17% in the population aged above 65). It has been suggested that the high BZD consumption rate could be related to dependence. The existence of BZD dependence was described in the early sixties with very high dose of chlordiazepoxide but it has become a real concern for the medical community since the late seventies with increasing number of reports of withdrawal symptoms. The extend of the actual rate of withdrawal symptoms at BZD tapering is still very controversial and according to the different studies it varies from 39 to 90%. The between studies difference in parameters such as: the patient populations (psychopathology, treatment duration), the type of tapering employed (duration, nature of the medical and psychological support) and the used operational criteria for withdrawal definition most likely explain this wide variation in the rate of occurrence of withdrawal manifestations. According to the American Psychiatric Association Task Force on Benzodiazepine Dependence, Toxicity and Abuse three type of pathological events can happen after treatment discontinuation: rebound, withdrawal syndrome and recurrence. The rebound consists in the early and transitory reappearance of the anxiety symptoms pre-existing to the treatment but in an exacerbated from; the withdrawal syndrome associates the resurgence of the pre-existing anxiety symptoms and new symptoms as sensory disturbances (metallic taste, hyperosmia, cutaneous exacerbated sensitivity, photophobia...) nausea, headache, motor disturbance in some rare cases depersonalization, paranoid reaction, confusion, convulsion. Rebound or withdrawal syndrome appearance delay varies from hours to few days according mostly to compounds elimination half-life. The relapse develops later with a progressive reapparance of pre-treatment symptoms. In practice recurrence and rebound are often difficult to isolate: recurrence can follow rebound. Different operational criteria of definition for this different entities have been proposed but there is a need for a consensual position. The treatment length, a high daily dose, an alcohol abuse history, a dependent personality and the severity of the psychopathology of the patients have been found to be predictive for the occurrence of withdrawal symptoms. Behavioural therapies (individual or in group) have been proposed with some success for the treatment of benzodiazepine dependence; drug treatment with carbamazepine or imipramine have demonstrated some efficacy. Other drug as buspirone clonidine having anxiolytic properties have not demonstrated efficacy.(ABSTRACT TRUNCATED AT 400 WORDS)

Oral malodor has many etiologies. The use of accurate descriptor terms to describe this condition facilitates its clinical diagnosis and treatment by health care professionals. Oral malodor, a generic descriptor term for foul smells emanating from the mouth, encompasses ozostomia, stromatodysodia, halitosis (both pathological halitosis and physiological halitosis) and fetor oris or fetor ex ore. These latter terms, in turn, denote different sources of oral malodor. The terms ozaena, fetor narium, dysosmia, hyperosmia, cacogeusia, and dysgeusia are also related to oral malodor, and assist in accurately describing a clinical presentation. Systemic pathological states, such as diabetes mellitus, uremia and hepatic diseases, induce metabolic products that are detectable as oral smells. Local oral conditions produce volatile sulphur compounds and other breakdown products that intensify oral malodors. The clinical labelling and interpretation of different oral malodors both contribute to the diagnosis and treatment of underlying disease. This article stresses the relationship between smell and taste, emphasizes specific meanings for related oral malodor terms, reviews smell comprehension and indicates some of those commonly-encountered associated clinical conditions.