Objective nasal airflow measures in relation to subjective nasal obstruction, trigeminal function, and olfaction in patients with chronic rhinosinusitis.

BACKGROUND: This study aimed to determine how nasal airflow measures and trigeminal function vary among patients with chronic rhinosinusitis (CRS) versus healthy controls and whether these measures are correlated with subjective nasal obstruction (SNO), olfactory function, and CRS control. METHODOLOGY: Participants included CRS patients and healthy controls. After a structured medical history, nasal airflow (peak nasal inspiratory flow [PNIF]; active anterior rhinomanometry [AAR]), trigeminal function (trigeminal lateralization test, CO2 sensitivity), and olfactory ("Sniffin' Sticks" odor identification test) tests were performed. SNO ratings were also obtained. RESULTS: Sixty-nine participants were included (37 men, 32 women, mean age 51 years). There was no significant difference for objective nasal airflow between patients and controls, but CRS patients had worse SNO, trigeminal function, and olfaction compared to controls. SNO, but not objective nasal airflow tests, was negatively correlated with CO2 sensitivity and odor identification. CONCLUSION: The perception of nasal obstruction does not only depend on nasal airflow, but may also be modulated by trigeminal function and other factors. Thus, the role of objective nasal airflow measures as a sole method of functional nasal obstruction assessment in CRS remains limited.

Taste loss in COVID-19 - psychophysical evidence supporting a low prevalence.

Much - possibly even too much - has been published about chemosensory dysfunction as a consequence of COVID-19. Studies have reported prevalence of taste loss in up to 89.9% (1), which is in a similar range as COVID-19 related smell loss. However, most of these publications rely solely on patients' self-reports. Only few studies used validated psychophysical tests to specifically address olfaction and gustation. Especially for gustation, it is evident that subjective reporting does not correlate well with more objective psychophysical findings, often leading to an overestimation of subjectively impaired taste.

The "Sniffin' Kids-PT" test: A smell test variant for Portuguese children.

OBJECTIVE: Olfactory tests tailored for children are essential, as diagnosing olfactory dysfunction at these ages can be challenging. The 16-item "Sniffin' Sticks" is reliable and easy to perform. To the best of our knowledge, there is currently no validated olfactory test for the Portuguese pediatric population. This study aimed to adapt and validate the "Sniffin' Sticks" olfactory test for the Portuguese pediatric population. METHODS: Between August 2020 and September 2021, 354 children aged between 6 and 17years old enrolled in the study, 336 healthy children with a normal sense of smell, and 18 anosmic children with Kallmann syndrome. The study consisted of two parts. Firstly, the "Sniffin' Sticks" olfactory identification test was applied to healthy children and the odors with statistically significant low identification rates were excluded. A modified version of "Sniffin' Sticks" was defined and named "Sniffin' Kids-PT" test. Secondly, normative data were assessed and test-retest and validation tests were performed. RESULTS: Apple and Cloves odors were identified with a low rate and were excluded from the "Sniffin' Sticks" olfactory test. In the modified 14-item "Sniffin' Kids-PT", scoring <6 (from 6-8years old), <7 (from 9-11years old) or <8 (from 12-14years old and 15-17years old) was indicative of olfactory dysfunction. The test-retest reliability was good (r=0.81; P<0.001) and the differences between scores of healthy children and anosmic children were statistically significant (U213=13.00; P<0.001). CONCLUSION: The modified "Sniffin' Kids-PT" is a reliable test to discriminate between normosmia and olfactory dysfunction in Portuguese children over 5years old.

Underestimated olfactory domains in Huntington's disease: odour discrimination and threshold.

BACKGROUND: Olfaction has recently found clinical value in prediction, discrimination and prognosis of some neurodegenerative disorders. However, data originating from standard tests on olfactory dysfunction in Huntington's disease are limited to odour identification, which is only one domain of olfactory perceptual space. METHOD: Twenty-five patients and 25 age- and gender-matched controls were evaluated by the Sniffin' Sticks test in three domains of odour threshold, odour discrimination, odour identification and the sum score of them. Patients' motor function was assessed based on the Unified Huntington's Disease Rating Scale. RESULTS: Compared with controls, patients' scores of all olfactory domains and their sum were significantly lower. Besides, our patients' odour threshold and odour discrimination impairments were more frequently impaired than odour identification impairment (86 per cent and 81 per cent vs 34 per cent, respectively). CONCLUSION: Olfactory impairment is a common finding in patients with Huntington's disease; it is not limited to odour identification but is more pronounced in odour discrimination and odour threshold.

Olfactory training in normosmic individuals: a randomised controlled trial.

BACKGROUND: Even if olfactory training (OT) is a well-established treatment for individuals with olfactory dysfunction, the effect on individuals with normosmia remains uncertain. In this randomised controlled trial, we explore how OT with different exposure lengths affect olfactory function in individuals with normosmia. METHODOLOGY: Two hundred normosmic individuals were randomly assigned to one of two intervention groups performing OT with different exposure lengths or to a control group. The OT groups did OT twice daily for three months, g four different odours (eucalyptus, lavender, mint, and lemon) for 10 seconds per bottle during either a total of 40 seconds (standard OT) or 4 minutes (extended OT), while the control group did not perform any OT. Olfactory function was assessed using a 48-item Sniffin Sticks test at baseline, after the intervention, and after one year. RESULTS: We found no significant effect of OT in either of the intervention groups on any aspect of olfaction after intervention or at follow-up. There was no association between sex, age, allergic rhinitis, education or olfactory scores at baseline, and changes in olfactory function after OT. The extended OT group performed significantly fewer training sessions compared to those in the standard OT group. CONCLUSIONS: OT had a limited effect on olfactory function in individuals with normosmia. Further, the superiority of a more extended OT is not supported by this study, and shorter training sessions seem to improve compliance with OT.

A Life Without Smell: Olfactory Function in People Working in Odorless Rooms.

OBJECTIVES: Odorous stimulation helps to maintain or to improve olfactory function. In contrast, odor deprivation has been suggested to facilitate olfactory impairment. The aim of this study was to investigate the effects of odor deprivation in people working in an odorless environment. METHODS: Fifty people working in an odorless environment for extended periods of time and 50 people not working in such environments were recruited. The participants were examined for olfactory function (using Sniffin' Sticks), nasal airflow (using peak nasal inspiratory flowmetry), self-rated olfactory function, self-rated nasal airflow, and well-being. Correlation analyses were used to explore the associations between the duration of working in odorless environment and olfaction, nasal airflow, and well-being. RESULTS: The cleanroom workers exhibited slightly, but significantly reduced olfactory scores (sensitivity 7.0 ± 2.5, discrimination 11.4 ± 1.8) compared with controls (sensitivity 8.9 ± 2.5, F = 4.33, p = 0.03; discrimination 12.7 ± 1.6. F = 5.50, p = 0.001), even when controlling for age and rated nasal patency, with their self-rated olfactory function being not affected. The years of working in cleanrooms were negatively associated with olfactory function (r = 0.35, p = 0.013). No significant correlations were observed between scores of olfactory function, nasal patency, and well-being. CONCLUSION: Compared with controls cleanroom workers exhibited slightly, but significantly lower olfactory scores, nasal peak flow, and well-being. Their decreased odor sensitivity was found to be associated with the number of years they had worked in the cleanroom. Overall, these results may suggest that odorous stimulation supports olfactory functioning. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:382-387, 2024.

Trigeminal function in patients with COVID-associated olfactory loss.

PURPOSE: Olfactory dysfunction (OD) can be a long-term consequence of various viral infections, including COVID-19. Dysfunction includes hyposmia/anosmia and parosmia (odor distortions). Interactions of the virus with the olfactory nerve have been extensively researched, but little is known about the interactions of the intranasal trigeminal nerve system in modulating this sensory loss. METHODS: We investigated intranasal trigeminal function across COVID-19 OD patients with and without parosmia compared to normosmic controls, to determine whether (1) post-viral hyposmia and/or (2) post-viral hyposmia with parosmia is associated with altered trigeminal function. OD patients (n = 27) were tested for olfactory function using the extended Sniffin' Sticks olfactory test and for trigeminal function through three methods-odor lateralization, subjective ratings of nasal patency, and ammonium vapor pain intensity ratings. This group was subsequently compared to controls, normosmic subjects (n = 15). RESULTS: Our findings revealed that post-COVID OD patients without parosmia experienced decreased sensitivity in ammonium vapor pain intensity ratings and odor lateralization scores-but similar nasal patency ratings-compared to normosmic controls. There were no significant differences in trigeminal function between OD patients with and without parosmia. CONCLUSIONS: Based on our results, we conclude that the trigeminal nerve dysfunction may partially explain post-viral OD, but does not seem to be a major factor in the generation of parosmia pathophysiology.

Intranasal insulin's effects on the sense of smell.

Intranasal insulin (IN) administration is a promising way to deliver the peptide to the central nervous system (CNS), bypassing the blood-brain-barrier and gastrointestinal absorption inhibition. IN receptors are localized in the olfactory mucosa and the brain, mainly in the olfactory bulb, hypothalamus, hippocampus, amygdala, cerebral cortex, and cerebellum. The pleiotropic mechanism of insulin action is characterized by its anti-inflammatory properties, antithrombotic, vasodilatory, and antiapoptotic effects. It prevents energy failure and has regenerative properties, affects neuro-regeneration and counteracts insulin resistance. Hence, insulin has been suggested for various pathological states including neurocognitive disorders, obesity, and as a therapeutic option for smell loss. A sharply increased prevalence of olfactory dysfunction was observed due to the COVID-19 pandemic. The pandemic also emphasized the lack of therapeutic options for smell loss. Intranasal insulin administration has therefore been suggested to serve as potential treatment, influencing the regenerative capacities of the olfactory mucosa. This narrative review summarizes current knowledge on possible effects of intranasal insulin on the sense of smell.

Variations of olfactory function with circadian timing and chronotype.

BACKGROUND: Cumulative animal studies have suggested that olfaction can be regulated by circadian clock. However, human studies on the topic are relatively limited. The present study thus aimed to investigate diurnal variation in olfaction in healthy adults while examining potential modulating factors. METHODS: We conducted four rounds of testing on 56 healthy adults (32 women) aged 31 ± 12 years, throughout a single day, during morning (8:00-10:00 h), noon (12:00-14:00 h), afternoon (16:00-18:00 h), and evening (20:00-22:00 h). At the first appointment, participants completed full olfactory function testing using the Sniffin’ Sticks, questionnaires on medical history, nasal symptoms, sleep quality, and chronotype, and were assessed for blood pressure, heart rate, peak nasal inspiratory flow (PNIF), attention level, and rated their smell ability, nasal patency, wakefulness, and concentration level using visual analog scale (VAS) ratings. Subsequent appointments measured olfactory threshold, attentional level, PNIF, blood pressure, heart rate and VAS ratings repeatedly. RESULTS: Olfactory threshold (OT) scores varied significantly between different times of the day, with the highest score in the evening and the lowest in the morning. Similar differences were also observed in PNIF, with the highest value in the evening and the lowest in the morning. However, there were no significant correlations between OT score and PNIF across all four-time testing, as well as between differences in [OT evening â€" OT morning] and [PNIF evening â€" PNIF morning]. Furthermore, a generalized linear mixed model indicated that the testing time of the morning, evening chronotype, self-reported body mass index (BMI), rated smell ability, and rated nasal patency significantly predicted the Sniffin' Sticks OT score. CONCLUSIONS: Olfactory function fluctuates throughout the waking hours of the day, with the highest olfactory sensitivity observed in the evening and the lowest in the morning. This pattern is also seen in nasal patency. However, it appears that the circadian changes of nasal airflow may not significantly depend on the circadian changes of the olfactory sensitivity. In addition, chronotype and BMI may regulate such olfactory-circadian variation. These findings provide important insights for future research on the accurate diagnosis and treatment of olfactory dysfunction.

Position paper on olfactory dysfunction: 2023

BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

Patients with olfactory loss exhibit pronounced adaptation to chemosensory stimuli: an electrophysiological study.

BACKGROUND: Pronounced chemosensory adaptation affects many patients with olfactory loss. The study aimed to investigate adaptation to olfactory and trigeminal nasal stimuli in patients with olfactory loss in comparison to controls using electrophysiological measures. METHODOLOGY: Thirty-four patients with olfactory loss (mean age ± SD = 59 ± 16 years) and 17 healthy volunteers (mean age ± SD = 50 ± 14 years) were recruited. Sniffin’ sticks test was used for evaluation of olfactory function and EEG-derived chemosensory event-related potentials were recorded. Intranasal stimuli were presented using high-precision, computer-controlled stimulators based on the principles of air-dilution olfactometry. Data were analyzed in two different approaches according to the relatively short or long inter-stimulus interval. A decreased peak amplitude or a prolonged latency was considered as an expression of adaptation. RESULTS: The majority of participants (88%) responded reliably to chemosensory stimulation. Patients with olfactory loss exhibited pronounced olfactory and trigeminal adaptation within the long-term design, without such effects in healthy controls. Odor sensitivity correlated with both olfactory and trigeminal amplitude changes: the worse the olfactory sensitivity, the more pronounced chemosensory adaptation. CONCLUSIONS: The results help to explain the patients’ complaints in terms of the fast adaptation towards chemosensory stimuli, for example during eating and drinking. The differences in adaptation in patients with olfactory loss and healthy controls could serve as a clinical criterion to gauge olfactory dysfunction.

Optimization of mRNA extraction from human nasal mucosa biopsies for gene expression profile analysis by qRT-PCR.

Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) is the gold-standard method for analyzing modifications in gene expression in cells and tissues. However, large quantities of high-quality RNA samples are needed for analyzing the expression of multiple genes from one human tissue sample. Here, we provide an optimized protocol for extracting large amounts of RNA from human nasal mucosal biopsies. The quality and quantity of samples were sufficient for qRT-PCR analyses of the expressions of various genes, in duplicate. In contrast to other protocols, we optimized RNA isolation to increase the amount from nasal biopsy samples for analyses of multiple genes. In most previous publications, expressions of only one or a few genes, including housekeeping genes, were analyzed because the amount of biological material was small. We were able to improve our protocol with respect to the yield and quality of RNA. This is likely to produce better results from molecular analyses of very small biopsy samples of human nasal mucosa.

Olfactory Function and Olfactory Disorders. / Riechen und Riechstörungen.

The sense of smell is important. This became especially clear to patients with infection-related olfactory loss during the SARS-CoV-2 pandemic. We react, for example, to the body odors of other humans. The sense of smell warns us of danger, and it allows us to perceive flavors when eating and drinking. In essence, this means quality of life. Therefore, anosmia must be taken seriously. Although olfactory receptor neurons are characterized by regenerative capacity, anosmia is relatively common with about 5 % of anosmic people in the general population. Olfactory disorders are classified according to their causes (e. g., infections of the upper respiratory tract, traumatic brain injury, chronic rhinosinusitis, age) with the resulting different therapeutic options and prognoses. Thorough history taking is therefore important. A wide variety of tools are available for diagnosis, ranging from short screening tests and detailed multidimensional test procedures to electrophysiological and imaging methods. Thus, quantitative olfactory disorders are easily assessable and traceable. For qualitative olfactory disorders such as parosmia, however, no objectifying diagnostic procedures are currently available. Therapeutic options for olfactory disorders are limited. Nevertheless, there are effective options consisting of olfactory training as well as various additive drug therapies. The consultation and the competent discussion with the patients are of major importance.

Developing a core outcome set for clinical trials in olfactory disorders: a COMET initiative.

STATEMENT OF PROBLEM: Evaluating the effectiveness of the management of Olfactory Dysfunction (OD) has been limited by a paucity of high-quality randomised and/or controlled trials. A major barrier is heterogeneity of outcomes in such studies. Core outcome sets (COS) - standardized sets of outcomes that should be measured/reported as determined by consensus-would help overcome this problem and facilitate future meta-analyses and/or systematic reviews (SRs). We set out to develop a COS for interventions for patients with OD. METHODS: A long-list of potential outcomes was identified by a steering group utilising a literature review, thematic analysis of a wide range of stakeholders' views and systematic analysis of currently available Patient Reported Outcome Measures (PROMs). A subsequent e-Delphi process allowed patients and healthcare practitioners to individually rate the outcomes in terms of importance on a 9-point Likert scale. RESULTS: After 2 rounds of the iterative eDelphi process, the initial outcomes were distilled down to a final COS including subjective questions (visual analogue scores, quantitative and qualitative), quality of life measures, psychophysical testing of smell, baseline psychophysical testing of taste, and presence of side effects along with the investigational medicine/device and patient's symptom log. CONCLUSIONS: Inclusion of these core outcomes in future trials will increase the value of research on clinical interventions for OD. We include recommendations regarding the outcomes that should be measured, although future work will be required to further develop and revalidate existing outcome measures.

Future therapeutic strategies for olfactory disorders: electrical stimulation, stem cell therapy, and transplantation of olfactory epithelium-an overview.

Olfactory disorders may be temporary or permanent and can have various causes. Currently, many COVID-19 patients report a reduced or complete loss of olfactory function. A wide range of treatment options have been investigated in the past, such as olfactory training, acupuncture, medical therapy, transcranial magnetic stimulation, or surgical excision of olfactory epithelium, e.g., in severe qualitative smell disorders. The development of a bioelectric nose, e.g., in connection with direct electrical stimulation or transplantation of olfactory epithelium or stem cells, represent treatment options of the future. The basis of these developments and the state of knowledge is discussed in the following work.

Olfactory stimulation may modulate the sensation of nasal patency.

BACKGROUND: The sensation of nasal patency can be induced by inhaling menthol, which predominantly produces trigeminal stimulation. It remains unclear whether olfactory stimulation can also induce or modulate the sensation of nasal patency. METHODOLOGY: A total of 118 participants (normosmia: n=67, olfactory dysfunction: n=51) were exposed to four odors in a randomized order: 1) phenylethanol (PEA), 2) menthol, 3) a mixture of PEA and menthol, 4) nearly odorless propylene glycol. The odors were presented by nasal clips. After the nasal clip had been removed, the participants rated relative nasal patency (RNP) from - 50 to +50, and their peak nasal inspiratory flow (PNIF) was measured. Repeated measures analysis of variance was used to examine the difference of RNP and PNIF among the four conditions and the influence of olfactory function. RESULTS: The RNPs, other than PNIFs, differed between the four conditions. Menthol induced the highest RNP, followed by the mixed solution, PEA and the odorless condition. Normosmic participants, but not those with olfactory dysfunction, responded to PEA significantly higher than odorless condition with regard to RNP. The correlation analysis showed that the better the subjective or measured olfactory performance, the greater the PEA-induced sensation of nasal patency. CONCLUSIONS: A specific olfactory stimulant that selectively induces olfactory perception can also evoke and modulate the sensation of nasal patency. Hence, patients might benefit from exposing themselves to odors in order to relieve the annoying nasal obstruction.

Predictors of olfactory improvement after endoscopic sinus surgery in chronic rhinosinusitis with nasal polyps.

OBJECTIVE: This study aimed to determine the predictors of olfactory improvement after endoscopic sinus surgery among patients with chronic rhinosinusitis with nasal polyps. METHOD: This prospective cohort study included patients admitted to a university hospital between 2006 and 2012. Assessment using odour identification testing, a sinonasal symptom questionnaire, the Rhinosinusitis Disability Index and mucus biomarker levels was performed at various time points. Correlation of variables with identification score differences at six post-operative time points and at baseline was performed, followed by multiple linear regression to determine significant predictors at each of the six post-operative time points. RESULTS: Baseline absence of acute sinusitis, elevated serpin F2 and anterior rhinorrhoea predict early olfactory improvement, whereas baseline allergic rhinitis predicts late olfactory improvement. Baseline odour identification score was the strongest predictor across all time points. CONCLUSION: Patients with chronic rhinosinusitis and nasal polyps with worse disease or baseline olfactory function may benefit more from endoscopic sinus surgery in terms of olfactory improvement.

[German S1 Guideline Long-/Post-COVID]. / S1-Leitlinie Long-/Post-COVID.

The German Society of Pneumology initiated 2021 the AWMF S1 guideline Long COVID/Post-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendations describe current Long COVID/Post-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an explicit practical claim and will be developed and adapted by the author team based on the current increase in knowledge.

Real-world-effectiveness of biological treatment for severe chronic rhinosinusitis with nasal polyps.

BACKGROUND: During the last two years, three different monoclonal antibodies have been approved in many countries for the treatment of patients suffering from severe chronic rhinosinusitis with nasal polyps (CRSwNP). Their efficacy has been demonstrated through large double-blind placebo-controlled clinical studies. Until now, only very limited reports on real-world data regarding this therapy have been published. METHODS: This per protocol analysis included patients with an indication for biological treatment because of uncontrolled CRSwNP, despite long-term nasal steroid treatment, systemic steroid use and/ or endonasal sinus surgery. Baseline data on demographics, medical history and comorbidities, polyp score, quality of life and sense of smell (using Sniffin' Sticks) were assessed and a treatment with either dupilumab or omalizumab was started. The patients were followed up after three and six months. The changes in polyp score, quality-of-life measures and olfaction were noted. RESULTS: 70 consecutive patients were evaluated during the study. Of the patients, 49 were treated with dupilumab and 21 with omalizumab. The polyp score decreased significantly after three and six months, and the quality-of-life parameters and olfaction increased. More than 90% of patients showed a moderate to excellent response to the therapy and there was no difference in the overall response between the two treatments. Olfaction improved in two thirds of the patients, but one third was still anosmic after six months treatment. CONCLUSIONS: This real-world study shows the effectiveness of the monoclonal antibodies dupilumab and omalizumab in the treatment of severe CRSwNP. Nasal polyp scores and quality-of-life parameters as well as measured olfactory function were improved after just three months. The response after guideline-based criteria was insufficient only in 5 patients of this cohort.